Electrochemical Halogenation of Organic Compounds - Springer Link

ISSN 10231935, Russian Journal of Electrochemistry, 2013, Vol. 49, No. 6, pp. 497–529. © Pleiades Publishing, Ltd., 2013. Original Russian Text © B.V. Lyalin, V.A. Petrosyan, 2013, published in Elektrokhimiya, 2013, Vol. 49, No. 6, pp. 563–596.

Electrochemical Halogenation of Organic Compounds B. V. Lyalin and V. A. Petrosyanz Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia Received April 24, 2012

Abstract—Data on the electrochemical chlorination, bromination, and iodination of organic compounds from various classes were summarized and systematized. The influence of the nature of the halogen and organic substrate on these processes was discussed. Data on the effects of the solvent, anode material, current density, and temperature on electrohalogenation were analyzed. The main tendencies of these reactions and their peculiarities as reactions of hydrogen substitution in the substrate were considered. Keywords: halogenation, organic compounds, electrochemical synthesis DOI: 10.1134/S1023193513060098

CONTENTS I. Introduction II. Electrochemical chlorination of organic com pounds from various classes III. Electrochemical bromination and iodination of organic compounds from various classes IV. Factors governing the electrohalogenation V. Electrochemical halogenation as substitution of the hydrogen atom in the organic substrate: main tendencies I. INTRODUCTION Halogenated organic substances are widely used in the chemical, electronic, metalworking, pharmaceu tical, and some other industries and agriculture [1]. These substances are generally obtained by halogena tion of substrates with highly toxic chlorine, bromine, and iodine. The desired products are formed from only half of the whole amount of halogens, the other half spent on the formation of HCl, HBr, or HI as nonuti lizable waste. This complicates largescale chlorina tion; bromine and especially iodinesubstituted organic products are not produced on a large scale either because the processes involve expensive and deficient Br2 and I2. Electrochemical halogenation is devoid of the shortcomings of the chemical process owing to the replacement of halogen by nontoxic solutions of halides. Moreover, electrochemical halogenation does not require the transportation and storage of toxic compounds such as chlorine. It offers wide opportuni ties for control over halogenation and for investigating its subtle mechanism by varying the current density, z

Corresponding author: [email protected] (V.A. Petrosyan).

the charge passed, and the electrode material and by using a diaphragm or diaphragmless electrolyzer. Electrochemical chlorination (EC) is occasionally energetically favorable. For example, the electric power consumption for the chemical chlorination of hydrocarbons is 2500 kW h per 1 t of the chlorine product (its drying, compression, etc. included). The electrochemical chlorination of hydrocarbons in aqueous media, giving the same amount of the desired product (per 1 t of free chlorine), however, allows a reduction of consumption to 1800 kW h [2]. EC is generally characterized by higher selectivity [3]. The same is true of electrochemical bromination (EB) and iodination (EI), combining the possibilities of high selectivity of reaction and pure target products, which is especially important in syntheses of biologi cally active substances. Finally, using electrochemical methods opens up prospects for comprehensive use of halogens in syn theses of organohalogen compounds, which create a number of advantages over traditional technologies from the viewpoint of environmental protection for electrochemical chlorination and are important for electrochemical bromination and iodination [4]. All this has stimulated studies of electrochemical halogenation of organic compounds from various classes. Data on electrohalogenation were widely reviewed in the literature. Some of these publications, however, were part of review [5], while others were chapters in monographs on wide topics, e.g., [3, 6–9]. The cover age, therefore, was incomplete. An exception was the monograph [10] (1987) devoted to the electrosynthe ses of chloroorganic compounds, but it omitted a lot of useful information presented in the original publica tions. The same holds for the review [11] on EC, EB,

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Table 1. Chlorination of PNCA (c = 0.01 M) in a MeCN solution of Et4NCl (c = 0.2 M) (potentiostatic mode*, Ea = 1.0 V relative to Ag/Ag+, T = 25°C) No.

E1ox2, V rel. to Ag/Ag+ (Pt anode)

Anion –

Product yield on different anodes, %

Chlorination product

Pt

RTOA

graphite

–

–

–

–

0.8

1

Cl

2

PhC(NO2)2

0.61

PhC(NO2)2Cl

50

85

74

3

0.82

MeC(NO2)2Cl

50

85

66

4

MeC(NO2)2− − HC(NO2)2

1.03

HC(NO2)2Cl C(NO2)2Cl2

99 0

95 0

80 10

5**

HC(NO2)2

1.03

HC(NO2)2Cl C(NO2)2Cl2

0 93

0 92

10 85

−

−

6

CNC(NO2)2−

1.50

CNC(NO2)2Cl

92

94

94

7

C(NO2 )3−

1.52

C(NO2)3Cl

99

94

91

Notes: * Q = 2 F per mol of PNCA. ** Q = 5 F per mol of PNCA.

and EI published in 1991 and mainly presented as ref erence tables. The goal of this review, therefore, was to highlight the main results on electrohalogenation of some classes of organic compounds, including the results of studies cited in [10] but deserving more comprehen sive coverage, and to discuss recent results in more detail. In addition, the widespread electrochemical halogenation of aromatic compounds, which is basi cally hydrogen substitution by halogen in the sub strate, in our opinion, deserves a special discussion. II. ELECTROCHEMICAL CHLORINATION OF ORGANIC COMPOUNDS FROM VARIOUS CLASSES 1. Saturated Hydrocarbons Studies in this field were mainly performed in the 1960–1970s. To summarize the main results of these studies cited in [10], the EC of saturated hydrocarbons was generally conducted with concentrated aqueous HCl as a supporting electrolyte. The EC of methane on porous carbon impregnated with Pt (1–30% of the mass of the anode) led to methyl chloride without forming the products of deeper chlorination under these conditions; for ethane (graphite anode), how ever, a mixture of 1,2dichloroethane (75%) and ethyl chloride (25%) formed. Mono and dichloro deriva tives were also found in the EC of hydrocarbons С10–15 on a carbon anode. The EC of cyclohexane and its homologs (methyl, 1,2dimethyl, 1,3dimethyl, 1,4dimethyl, and isopropylcyclohexane) in a hydro carbon–conc. HCl (or 20% aqueous NaCl) twophase system on a Pt (graphite) anode in a diaphragmless electrolyzer led to the corresponding monochloro

derivatives (yields 50–80% based on the changed hydrocarbon, 30–35% conversion of hydrocarbon). The peculiarities of the EC of carbanions and their effects on the ease of oxidation and pK of the conju gate acid can be assessed from the data of [12]. Tables 1 and 2 summarize the results of the EC of polynitrocar banions (PNCAs) of the general formula – RC(NO2 ) 2 M+ (R = Me, Ph, H, NO2, CN; M+ = Na+, Alk4N+) in a potentiostatic mode on Pt or graphite anodes, or on a ruthenium–titanium oxide anode (RTOA) in H2O or MeCN. According to Table 1, the yields of CNC(NO2)2Cl and C(NO2)3Cl in MeCN are nearly quantitative. The lower yields of PhC(NO2)2Сl and MeC(NO2)2Cl are explained by the oxidation of PhC(NO 2 )2− and – MeC(NO2 ) 2 anions at electrolysis potentials and fur ther destruction processes. Of interest are the data on the EC of the HC(NO 2 )2−, anion, whose chemical chlorination gave C(NO2)2Cl2 as the sole product (70% yield), which was dechlorinated to НC(NO2)2Cl (80% and the same current efficiency [35, 37]. Using lower concen trations of HCl had an adverse effect on the yield of chloro derivatives and anode stability [37]. The EC of anisole, toluene, and chlorobenzene in aqueous HCl (c = 0.1–0.5 M) under diaphragm elec trolysis conditions at a potential Еа= 1.2–1.25 V (rel ative to s.c.e.) on a graphite or carbon anode modified with αcyclodextrin gave predominantly parachloro derivatives in >90% yield [38–42]. This is explained by the fact that cyclodextrin molecules are cyclic oligo mers of 1,4bonded Dglucopyranoses containing six (α), seven (β), and eight (γ) glucose fragments, the αcyclodextrin unit having a cavity in the form of a RUSSIAN JOURNAL OF ELECTROCHEMISTRY

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truncated cone comparable in size to the benzene molecule [38, 39]. When in a cavity, the functional group of the monosubstituted benzene molecule is ori entated outside, thus blocking all positions except the paraposition at which chlorine attacks. At the same time, the selectivity of EC on a graphite anode treated with αcyclodextrin depends strongly on the nature of the arene [38]. Thus the ratio of para/ortho isomers among the reaction products is >20 in the EC of ani sole and up to 4.6 in the EC of toluene. This is explained by the fact that MeO is a stronger paraori entating group than Me [38]. Note that the practical utility of these results is decreased by the dependence of the para/ortho ratio on the conversion of the starting arene. Thus in the EC of anisole, the para/ortho ratio of chloroanisole isomers among the reaction products is 18 (anisole conversion 2.2%) and 2.7 (61%) [39]. This can be explained by the decomposition of cyclo dextrin during prolonged electrolysis. EC in the arene ring of benzene, toluene, alkoxy benzenes, and naphthalene in MeOH (DMF, MeCN) on Pt, graphite, and RTOA anodes was studied in [43⎯46]. Tables 3 and 4 summarize the data of [43] on the EC of benzene and toluene on Pt in MeCN con taining LiCl or Et4NCl and АlCl3, respectively. The EC of benzene (Table 3) occurred with diffi culty; for the theoretically required charge (Q = 2 F per mole of benzene), the yield of chlorobenzene and the benzene conversion were up to 55%, the yield of chlorobenzene reaching 90% only at Q = 4 F/mol. The EC of chlorobenzene was still slower because at Q = 2 F per mole of chlorobenzene, its conversion was up to 5%. In contrast, the EC of toluene (Q = 2 F/mol) gave 90% yield of monochloro derivatives and the orthoisomer as the main product (the ratio of para/ortho isomers was 0.64) owing to the activating effect of the methyl group. In this case, chlorination in the ring occurred more readily than chlorination at the methyl group. At Q > 2 F/mol, dichloroarenes formed with poor (up to 10%) yield. On the basis of voltammetric measurements, the mechanism of the EC of arenes was described by the following scheme [43]: No. 6

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Table 3. EC of arenes during electrolysis in a potentiostatic or galvanostatic mode (Pt anode, S = 12 cm2, 0.5 M LiClO4 in MeCN, Ag/Ag+ reference electrode) Arene (c, M)

Chloride, (m)*

Composition of the mixture of electrolysis products, %

E, (E1 – E2)a, V** Q, F/mol

Benzene (0.13)

LiCl (m = 0.5)

(1.5–2.5)

2

Benzene (50), chlorobenzene (50)

Benzene (0.13)

LiCl (m = 0.5)

2.2

2

Benzene (50), chlorobenzene (50)

Benzene (0.13)

LiCl (m = 0.25)

(1.5–2.3)

4

Chlorobenzene (90), dichlorobenzenes (10)

Chlorobenzene (0.09) Et4NCl (m = 1)

(1.5–2.5)

2

Chlorobenzene (95), dichlorobenzenes (5)

Chlorobenzene (0.09) Et4NCl (m = 1)

2.4

2

Chlorobenzene (95), dichlorobenzenes (5)

Toluene (0.10)

Et4NCl (m = 0.25)

(1.5–2.5)

2

Toluene (10), parachlorotoluene (35), orthochlorotoluene (55)

Toluene (0.10)

Et4NCl (m = 0.25)

2.3

2

Toluene (10), parachlorotoluene (35), orthochlorotoluene (55)

Toluene (0.10)

LiCl (m = 0.25)

(1.5–2.3)

4

Parachlorotoluene (45), Orthochlorotoluene (45), 2,4dichlorotoluene (10)

* m is the ratio of the mole concentrations of arene/chloride. ** E is the potential of potentiostatic electrolysis; (E1 – E2)a are potentials of the beginning and end of galvanostatic electrolysis with ja = 25 mA cm–2.

Table 4. EC of arenes during electrolysis in a potentiostatic or galvanostatic mode in the presence of AlCl3 additions (Pt anode, Sa = 12 cm2, supporting electrolyte 0.5 M LiClO4) A, V* (I, mA)

Q, F/mol

Benzene

2.3

2

1

Benzene (10), chlorobenzene (80), dichlorobenzenes (9)

Benzene

2.3

4

1

Chlorobenzene (21), dichlorobenzenes (79)

Benzene

2.3

6

0.5

Dichlorobenzenes (60), trichlorobenzenes (40)

Chlorobenzene

2.4

2

1

Chlorobenzene (33), dichlorobenzenes (66)

Toluene

(320)

2

1

Toluene (5), parachlorotoluene (53), orthochlorotolu ene (42)

Toluene

(320)

3

1

Parachlorotoluene (28), orthochlorotoluene (22), 2,4 dichlorotoluene (50)

Orthochlorotoluene

(320)

2

0.5

Orthochlorotoluene (20), 2,4dichlorotoluene (80)

Arene

m**

Composition of the mixture of electrolysis products, %

Notes: * Relative to Ag/Ag+. ** m is the ratio of the mole concentrations of arene/AlCl3.

–e

(a) Cl–

Cl•

• rapidly

(b) 2Cl

(c) Cl2 + ArH

(d) ArH…Cl2

Cl2 ArH…Cl2

The authors supposed that the formation and transformation of the charge transfer complex (stages с and d) were slow. With excess Cl2, a new complex can

slowly

ArHCl+ + Cl–

(e) ArHCl+

ArCl + H+

(f) ArCl + Cl2

ArCl…Cl2.

be formed (stage f), but the equilibrium constant for it is still lower than for stage с. This explains both the low yield of the products of benzene EC and the insignifi

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cant (∼10%) amount of dichloro derivatives in ben zene and toluene chlorinations. Of interest are the data on the effect of the catalytic АlCl3 additions on the EC of arenes [43] (Table 4). According to Table 4, the EC of benzene and toluene in MeCN with АlCl3 additions led to the formation of the corresponding monochloro derivatives with yields of 80–90%. At Q > 2 F per mole of arene, the dichloro derivatives of arenes formed (50–80% yield), but the trichloro derivatives (at Q = 6 F/mol) formed in lower yields because of the insufficient amount of АlCl3 used for catalyzing the EC [43]. CH3

503

It was also noted that the EC of toluene in the pres ence of АlCl3 led to a larger amount of the paraisomer (the para/ortho ratio was 1.26, but not 0.64, as above). This is caused by the fact that the dissociation of АlCl3 in MeCN occurred by the scheme [43] +

AlCl 2 + Cl

АlCl3

–

Cl– + AlCl3

–

AlCl 4 ,

and that the para complex involving the AlCl 4− ion formed more readily than that of the ortho complex (because of steric hindrances):

CH3

CH3

•

•

+

–e

H

+

H

kp AlCl4–

ko AlCl4–

CH3

CH3

•

•

kp > ko

H

Cl AlCl3 H ,

Cl AlCl3

where kp and ko are the rate constants of the formation of the para and orthoisomers.

(which is highly active in electrophilic chlorination) in dry MeCN (≤0.03% Н2О). The following scheme shows that these processes form different products:

The EC of arenes was further studied in [44]; the authors compared the data on the chemical chlorina tion and EC of 1,4dimethoxy2tertbutylbenzene Chemical chlorination:

OMe

OMe

OMe

Cl Cl2 –HCl

OMe 1

OMe

+ Cl

OMe

OMe 4

OMe Cl Cl + Cl

+

Cl OMe 5

OMe

OMe –e

Cl + Cl

OMe OMe 2 3 Electrochemical chlorination:

OMe

OMe

Cl +

OMe 6

OMe Cl + Cl Cl

OMe 7

Cl OMe 8

OMe

Cl + •

+Cl, –e –H

+

.

Cl

OMe 1

OMe

OMe 2

OMe 3

Even in the absence of a catalyst (FeCl3), the chemical chlorination of 1 led to the formation of 1,4 dimethoxy2tertbutyl5chlorobenzene (3) and a small amount of 1,4dimethoxy2tertbutyl6chlo robenzene (2) as the primary products. Further reac RUSSIAN JOURNAL OF ELECTROCHEMISTRY

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tions formed 1,4dimethoxy2,5dichlorobenzene (4), 1,4dimethoxy2tertbutyldichlorobenzene (5), 1,4dimethoxy2chlorobenzene (6), 1,4dimethox ytrichlorobenzene (7) (the tertbutyl group was replaced by the electrophilic mechanism [44]), and a No. 6

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small amount of 1,4dimethoxy2tertbutyltrichlo robenzene (8). In contrast, the EC of 1 yielded only monochloro derivatives 2 and 3, which were not chlorinated fur ther (and the tertbutyl group was not replaced). The EC was conducted under diaphragmless potentio static electrolysis conditions of a MeCN solution of 1 containing Et4NCl on a Pt anode and a Pt or steel cathode. In a system with a Pt cathode and Pt anode, the ratio of 2 to 3 in the reaction system depends on the anode potential. At Еа = 0.55 V (the Cl– oxidation potential relative to Ag/AgBF4), the total current effi ciency of 2 and 3 was 38% and their ratio was 1 : 6. The latter was explained by the electrophilic interaction of Cl2 formed on the anode and substrate 1, the electro philic attack preferably occurring at the 5 position in the benzene ring of 1 [44]. In the electrolysis at Еа = 0.98 V (the oxidation potential of 1 relative to Ag/AgBF4 was 0.95 V), the total yield of 2 and 3 was 83% and the ratio was 1.2 : 1, respectively. In this case, the process could occur by the reaction of radical cat ion 1+• with the nucleophile (Cl–) or radical (Cl•), the preferable site for the nucleophilic attack being the 6 position of radical cation 1+• [44]. Despite the forma tion of HCl in the course of electrolysis, pH of the electrolyte remained neutral due to the reduction of Н+ on the cathode, which is important because the acid medium catalyzes deeper chlorination. It is interesting that at the oxidation potential of 1 under similar conditions but with the Pt cathode replaced by a steel one, the EC led to the acidification of the electrolyte to pH 2 and to deeper chlorination, giving products 4, 5, 6, and 7 and only insignificant amounts of monochloro derivatives 2 and 3. This is probably due to the formation of a catalyst (evidently, FeCl3) in dry MeCN during the interaction of traces of iron oxides (which are present on the steel cathode) with HCl isolated in EC [44]. The chlorination is thus autocatalyzed. At the same time, the autocatalysis is blocked by small additions of Н2О to the electrolyte (0.1 mL per 50 mL of MeCN), which terminate the reaction at the stage of the formation of monochrolo derivatives, the medium pH remaining neutral [44]. These results vividly demonstrate that EC can easily be controlled using small additions of Н2О. When comparing the chemical chlorination and the EC involving reactive arenes, the authors of [44] noted that the chemical reaction required more care ful control over addition of Cl2 to the reaction mixture to ensure low reaction rate. However, here again the reaction is difficult to be stopped at the monochlorina tion stage even when terminating it early or on cool ing. In contrast, during EC the Cl2 release rate can readily be controlled by the passed current, keeping pH of the reaction mixture neutral, which conse quently leads to arene monochlorination products as the sole products.

The possibility of preferably obtaining one isomer (para or ortho) in the EC of arenes was examined in [45, 46]. Thus the EC of methoxy and ethoxyben zenes in DMF or acetamide on a Pt anode under dia phragm potentiostatic (Еа = 1.3 V relative to s.c.e.) electrolysis conditions in a LiCl supporting solution predominantly led to the formation of the paraisomer (the para/ortho ratio was 12–17) in 88–99% yield [45]. The isomer ratio was decreased by replacing the Pt anode by a graphite anode or RTOA, replacing LiCl by NH4Cl, and increasing the H2O content in the sup porting electrolyte; the replacement of formamide by MeOH drastically decreased (to ∼3) both the para/ortho ratio and the yield of the desired product (43–49%). This agrees with the data of [46], which revealed that the logarithmic dependence of para ClC6H4OMe/orthoClC6H4OMe decreased linearly as the acceptor ability of the solvent increased in the EC of anisole under the diaphragm potentiostatic elec trolysis conditions in different media (THF, DMF, AcOH, Ме2СО, MeNO2, and С5Н5N). Let us consider the possibility of EC into the side chain of the aromatic substrate. It was suggested that EC should be conducted in a twophase system (the electrolyte and the substrate lying in different phases) under diaphragmless galvanostatic electrolysis condi tions [47]. Thus the EC of toluene in a mixture of CHCl3 with saturated aqueous NaCl (Pt anode and cathode, ja = 30 mA cm–2, aqueous phase : CHCl3 = 2.4 : 1, Т = 30°С, Q = 3.5 F per mol of toluene) led to the formation of benzyl chloride in 81% yield based on the loaded toluene (91% conversion) and a small amount (9% yield) of chlorotoluenes. A CHCl3 solu tion of toluene and a saturated aqueous solution of NaCl were poured in the electrolyzer during the pro cess. The electrodes were placed in the aqueous (upper) phase close to the interface, but not touching it. The organic phase was stirred with a magnetic stir rer at a low rate of ∼40 rpm in such a way that it did not touch the electrode and the interface remained intact. Small portions of H2SO4 were added to the electrolyte in the course of electrolysis to avoid alkalinization. The formation of benzyl chloride was attributed to the generation of Cl• radicals (formed in the aqueous phase during the oxidation of Cl– ions) and their inter action with toluene at the interface [47]. This is con firmed by the fact that the EC of toluene in a two phase system of this kind (toluene–10% aqueous HCl) but with vigorous stirring (electrolysis in emulsion) led only to a mixture of ortho and parachlorotoluenes, while benzyl chloride did not form [47]. Note that this method of EC of toluene into the side chain is an effective alternative to the conventional chemical pro cedures. The process occurs under mild conditions and is characterized by high yield of the desired prod uct and high conversion of toluene. The EC of naphthalene was described in [48]. It was shown that in the electrolysis (Pt anode, MeCN) of a mixture containing naphthalene and the Cl– anion at an oxidation potential of the latter of Еа =

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1.5 V (relative to Ag/AgCl), naphthalene did not change, while at Еа = 2.1 V (the oxidation potential of naphthalene) 1chloronaphthalene formed (∼33% yield based on the changed substrate). A cyclic volta mmetry study showed that the process occurred by oxidation of naphthalene to the radical cation fol lowed by its interaction with the Cl– anion. It was assumed that the yield of the desired product was low because of the side reactions of the radical cation with the nucleophiles (H2O, MeCN) present in the solu tion [48]. The EC of naphthalene under galvanostatic elec trolysis conditions of an emulsion of aqueous NaCl with CH2Cl2 using the Bu4N+ cation (Bu4NHSO4) for Cl– transfer from aqueous to organic phase was inves tigated in continuation of these studies [48, 49]. The authors of [48] considered that here, as in the case of EC in MeCN, the process occurred via the formation of the naphthalene radical cation and its subsequent interaction with Cl– in the organic phase. The condi tions were found that provided satisfactory yield of 1chloronaphthalene (60% based on the changed sub strate, 70% conversion): diaphragmless electrolysis, Pt anode, aqueous saturated solution of NaCl/CH2Cl2 = 1 : 1, 0.1 M naphthalene, 0.05 M Bu4NHSO4, jа = 49 mA cm–2, and Q = 2.33 F per mole of naphthalene [48]. According to [48], the higher yield of 1chlo ronaphthalene in a CH2Cl2–Н2О emulsion (com pared with the yield in MeCN) is explained by the lower nucleophilicity of CH2Cl2 relative to that of MeCN, the shortliving radical cation completely reacting in the CH2Cl2 phase. The yield of 1chloronaphthalene increased when ZnCl2 (Lewis acid) was added to the electrolyte [48, 49]. The Cl– anion is then transferred from aque ous to organic phase in the form of the compound (Bu4N)2ZnCl4 [49]. The influence of the electrolysis conditions (concentration of Bu4NHSO4, NaCl, ZnCl2, and naphthalene; current density; and anode material) on the yield of 1chloronaphthalene under diaphragmless conditions was studied in [49]. The optimum conditions were found (Pt anode, Ni cath ode; the NaCl, Bu4NHSO4, ZnCl2, and naphthalene concentrations are 3.0, 0.05–0.15, 0.75, and 0.1– 1.0 M, respectively; janode = 50–130 mA cm–2; Q = 2.33 F per mole of naphthalene) that provide good yield of 1chloronapthalene (65–75% based on the changed substrate at 65–70% conversion of the latter). It was found that replacement of the Pt anode by RTOA decreased the yield of 1chloronaphthalene by ∼13%; the conversion of naphthalene decreased more than twofold [49]. In addition, it was found that a tran sition from diaphragmless to diaphragm electrolysis

increased the yield of the desired product and the naphthalene conversion by 15 and 20%, respectively [49]. The method for the EC of napthalene in a two phase medium (emulsion) suggested in [48, 49] is quite convenient and effective because it affords 1chloronaphthalene with high yield (∼90%) and cur rent efficiency (∼80%). Note, however, that the pro cess leads to dichloronaphthalene in 10% yield along with the desired product. The EC of 9,10diphenylanthracene to 9,10 dichloro9,10diphenyl9,10dihydroanthracene (68% yield) in MeCN containing Bu4NCl on a Pt anode under diaphragm potentiostatic electrolysis condi tions (Еа = 1.4 V relative to s.c.e.) was investigated [50]. The process occurred via the initial formation of the 9,10diphenylanthracene radical cation. 4. Alcohols, Carbonyl Compounds, Acids, and Their Derivatives An attempt to perform the EC of MeOH gave only the product of its oxidation СН2О [26]. The EC of EtOH solutions led to CHCl3 when performed in aqueous alka lies and to chloral hydrate in acid media. The conditions that led to high yields (>95%) of both products were found [51–53]. The electrosynthesis of organic hypochlorites (see the scheme) as the key products of the synthesis of olefin oxides was studied in [54, 55]: NaCl + H2O el. current NaOCl + H2; NaOCl + ROH ROCl + NaOH. The EC of secondary and tertiary alcohols on RTOA in aqueous NaCl under diaphragm or dia phragmless galvanostatic electrolysis conditions (jа = 160–200 mA cm–2) was studied in [55]. In diaphragm electrolysis, the current efficiency of the desired prod ucts under optimum conditions (cNaCl = 250– 320 g L ⎯1, pH of anolyte 6.5–8.5, Т = 5–40°С) reached 90%. In diaphragmless electrolysis, high (∼90%) yield of the product was provided by additions of CCl4 extractant to the electrolyte to prevent possible reduction of alkyl hypochlorites on the cathode. The EC of anhydrous primary alcohols ROH (R = Et, Bu, and isoBu) saturated with HCl under dia phragmless galvanostatic electrolysis conditions on graphite electrodes at room temperature led to the for mation of 1chloraldehyde acetals with high current efficiency (80% in the case of EtOH) [56]. The process is described by a scheme that involves the electrogen eration of Cl2, oxidation of alcohol with Cl2 to alde hyde, and the formation and subsequent chlorination of acetal:

–4e

4Cl– 2Cl2, RCH2CHO + 2H+ + 2Cl–, RCH2CH2OH + Cl2 2RCH2CH2OH + RCH2CHO RCH2CH(OCH2CH2R)2 + H2O, RCH2CH(OCH2CH2R)2 + Cl2 RCHClCH(OCH2CH2R)2 + H+ + Cl–. RUSSIAN JOURNAL OF ELECTROCHEMISTRY

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Electrolysis in anhydrous isoPrOH saturated with HCl under similar conditions led only to the forma tion of acetone as the main product, while allyl alcohol was electrochemically chlorinated to 2,3dichloro propanol (current efficiency 25–30%) [26]. Note, however, that the first stage of the EC of alcohols mostly involves their oxidation to the corresponding aldehydes or ketones and only then these substances or the products of their coupling with the starting com pound are chlorinated. The EC of butyric aldehyde (diaphragmless elec trolysis, graphite anode, jа = 500–750 mA cm–2, aqueous CaCl2 acidified with HCl, Т = 30–45°С) gave 2chlorobutyric aldehyde with 90–95% current effi ciency and 85–90% yield; the enol form of aldehyde was involved in chlorination [57].

The EC of acetone under diaphragmless electroly sis conditions on a Pt anode in aqueous HCl led to a mixture of monochloro, 1,1dichloro, and 1,3dichloroacetones (the total current efficiency was ∼78%), the ratio of which depended on the charge passed through the solution [58]. During EC in alka line (pH > 7) media, CHCl3 formed by haloformic cleavage [58]. The EC of monochloro or 1,1dichlo roacetone (RTOA, carbonate buffer solution) under diaphragm electrolysis conditions led to selective for mation of 1,1,1trichloroacetone (82% yield). The potentiostatic electrolysis of barbituric (Ia), 1methyl (Ib), and 1,3dimethylbarbituric (Ic) acids in a diaphragm cell with a pyrographite anode in acid (pH 1) chloride (aqueous KCl acidified with HCl) solutions proceeded according to the scheme [59]: O

O

O H

R1N

+

O

H H

R1N O

N R2

O

O

O

–e –H+

H

R1N O

Ia R1 = R2 = H Ib R1 = Me, R2 = H Ic R1 = R2 = Me

•

N R2 a

N R2 b

O

O

H

H

O

OO +2Сl–

N R2

O

Cl

OO IV

It formed 5,5dichlorobarbituric acids (II) (20–30% yield), alloxanes (substituted mesoxylureas) (V) (14– 20%), 5,5'dichlorohydurylic acids (IV) (30–40%), and dialuric acids (III) in small amounts. It was assumed that at the electrolysis potential (Еа = 1.0 V relative to s.c.e.), there was no pronounced discharge of Cl– ions and the first stage (see the scheme) corresponded to the oxidation of acid I to radical а [59]. The latter was either dimerized and then chlorinated, leading to compound IV, or oxidized to carbocation b. This cation interacted with the Cl– anion to give 5chlorobarbituric acid с, which was transformed by a similar mechanism into 5,5dichlo robarbituric acid II or dimerization product IV. Some carbocations b reacted with Н2О molecules, forming compound III, which was oxidized to alloxanes V.

c

O

O

N R2

–H+ +Сl–, –2e

O NR1

N R2

N R2 V

O

N R2

–e –H+

R1N O

O

–4e

O Cl

O

H Cl

R1N

NR1 N R2

O

R1N

O

R1N O

–2e –H+

III

–e

O

O

N R2

+Cl–

O

H OH

R1N

H2O –H+

R1N

O O

O Cl •

N R2

Cl Cl

R1N

O O

N R2

O II

The EC of carboxylic acid derivatives was described. The EC of malonodinitrile in aqueous NaCl in a diaphragm cell (RTOA, jа = 70 mA cm–2, cNaCl = 90–100 g L–1, Т = 20–25°С) gave dichloro malonodinitrile (the product yield based on loaded malononitrile was 78%, process selectivity 90%) [60]. Under the conditions of EC (diaphragm elec trolysis, aqueous NaCl, RTOA, jа = 70 mA cm–2, cNaCl = 3.33 M, Q = 4 F per mole of substrate), ace tacetic ether formed 2,2dichloroacetoacetate (92% yield based on the isolated product) and a small amount (∼3%) of 2,2,4trichloroacetoacetate [61]. The latter product formed by competitive chlorina tion; the EC could not be stopped at the stage of the formation of monochloroacetoacetate. The EC of higher aliphatic acids leads to various chlorinecon taining compounds [5].

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The EC of 2,2,6,6tetramethylpiperidine hydrochlo ride, having a similar structure, in a neutral medium (saturated aqueous NaCl–organic (CCl4) solvent het erophase system in a ratio of 1 : 1.2; jа = 75 mA cm–2 , Q = 2 F per mole of amine hydrochloride) gave Nchloro2,2,6,6tetramethylpiperidine in 72% yield. Note, however, that the diaphragmless electrolysis of the indicated amine hydrochloride under slightly dif ferent conditions (jа = 75 mA cm–2, Q = 6.7 F per mole of amine hydrochloride, aqueous NaCl (с = 0.14 M) and Na2SO4 (с = 0.7 М)–CH2Cl2 heterophase system in a ratio of 2.33 : 1.0) led [63] to the formation of 2,2,6,6tetramethylpiperidine1oxyl nitroxide (35% yield) along with Nchloramine because of the partial oxidation of Nchloramine [64]:

5. Amines, Amides, and Imines The EC of 4oxo2,2,6,6tetramethylpiperidine on Pt and graphite anodes under diaphragmless galvano static electrolysis conditions (jа = 30 mA cm–2) in an acid aqueous medium (12 M HCl solution) led to 4oxo3,3,5,5tetrachloro2,2,6,6tetramethylpiperi dine hydrochloride (34–80% yield) [62]: O

O 4Cl–, –8e

Cl Cl

Cl Cl

N H

⋅ HCl.

N H

Cl–, –2e

–e

+ •

N

N

–0.5Cl2

+

+

Cl– + H 3 O + t BuNH2 t BuNH3Cl + H2O. The possibility of selective synthesis of t BuNCl2 was considered because at least half of all amine trans formed into hydrochloride during EC [65]. To avoid this, the process was conducted in the presence of a base (NaHCO3) that binds H3+O [66]: t BuNH2 + 2NaHCO3 + 4Cl– –4e

t BuNCl2+ 2Na+ + 2H2O + 2CO2+ 2Cl–. Though t BuNCl2 was obtained in ≥90% yield under these conditions, this required already 4 F per mole of amine. Note that the yield of the desired prod uct decreased at lower concentrations of NaCl and smaller NaHCO3 : t BuNH2 ratios. RUSSIAN JOURNAL OF ELECTROCHEMISTRY

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.

N OH

Cl

H2O + t BuNH2 + Cl– t BuNHCl + H 3 O, t BuNHCl 0.5BuNCl2 + 0.5BuNH2,

–e –H+

N

N

The Nchloro derivative of 2,2,6,6tetramethylpi peridine is thus an intermediate in the synthesis of a nitroxide [63]. The EC of primary and secondary aliphatic amines to the corresponding Nchloro derivatives on RTOA under the conditions of galvanostatic diaphragm elec trolysis of aqueous NaCl was described in [65]. The EC of primary amines was investigated using t BuNH2, which is not so readily oxidized as the Cl– anion. When Q = 1 F per mole of the starting amine was passed, a mixture of mono and dichloramine formed (current efficiency ∼80% based on active chlo rine) instead of the expected monochloramine. The dominance of t BuNCl2 in the mixture was explained by the disproportionation of the initially formed t BuNHСl because the equilibrium shifted toward t BuNCl2, which is less readily soluble [65]: –2e

H2O –H+

+

N Cl

H

507

O•

The EC of secondary amines, which are oxidized more readily than the Cl– ion, was studied using Et2NH as an example [65]. As in the EC of t BuNCl2, the process was conducted in the presence of NaHCO3, while passing 2 F of electrical charge per mole of amine: Et2NH + NaHCO3 + 2Cl– –2e

Et2NCl + Na+ + Cl– + CO2 + H2O.

The yield of Et2NCl was lower than that of t BuNCl2 and decreased as the amine concentration increased and the current density decreased because of the electrooxidation of Et2NH, which complicates its EC. Nevertheless, conditions were found that pro vided a good (∼73%) yield of the desired product. The yield of Et2NCl could be increased by using Et2NH2Cl instead of Et2NH as a substrate [65]. The increase in the yield is evidently explained by the equilibrium Et2NH2Cl + NaHCO3 NaCl + [Et2NH2HCO3]

H2O

Et2NH + H2CO3.

The intermediate amine carbonate was partially hydrolyzed, providing low amine concentrations, which are favorable for EC. The above regularities were used to obtain chloramines MeNCl2, EtNCl2, nPrNCl2, nBuNCl2, and Me2NCl in 91, 93, 91, 92, and 74% yield, respec tively [66]. The above process can therefore be regarded as the general procedure for the preparation of Nchloroalkylamines from the corresponding alky lamines. In continuation of these studies, the possibility of preparing monochloro derivatives of alkylamines (MeNH2, isoBuNH2, piperidine) under galvanostatic No. 6

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(ja = 200 mA cm–2) diaphragm electrolysis conditions using RTOA was investigated [67]. The EC of MeNH2 in concentrated solutions of amine (с = 2 M) at a given current density led to MeNHCl with ∼70% yield (the ratio of MeNHCl and MeNCl2 in the reaction mixture was 6 : 1). The EC of more readily oxidizable BuNH2 gave chloramine in a yield that was ∼30% lower but increased when the amine concentration was decreased from 2.0 to 0.17 M [67]. Taking into account these data, the EC of isoBuNH2 was con ducted at its low current concentration (0.17 M), dos ing it during the process; the yield of isoBuNHCl was 81%. This technique was ineffective in the EC of readily oxidizable amines of piperidine type. Electrochemical chlorination was performed for piperidine hydrochlo ride in the presence of NaHCO3 (as in the above exam ple of the preparation of Et2NH2Cl). This afforded the desired Nchloropiperidine in a satisfactory yield (∼60%). The abovedescribed method for the prepara tion of Nchloroalkylamines was later improved by performing it as a diaphragmless procedure [68]; this allowed the base additions (required for full conver sion of the starting amine to the desired product) to be replaced by the alkali formed on the cathode during electrolysis: ⊕

–

2OH

Cl2 2Cl–

CCl4

⊕

N2H4 + 2NH2Cl

0.5RNCl2 + 0.5RNH2 .

+6e

3Cl2

NH4Cl + N2H4, N2 + 2NH4Cl.

䊞

6NH+4

–6e

NH2Cl + NH4Cl,

This problem can be solved by using indirect two stage synthesis of NH2Cl suggested in [72]. The first stage (a) is the formation of NCl3 (80% yield) in the electrolysis of NH4Cl in a СCl4–Н2О heterophase sys tem:

RNHCl + Cl– + H2O

6Cl–

–2e

2NH3 + NH2Cl

OCl– + Cl– 2H2O

RNH3Cl

(a)

2NH3 + 2Cl–

䊞

+2e

–2e

The electrolysis was conducted in a water–CCl4 heterophase system to prevent the reduction of chloramine on the cathode; the role of СCl4 was reduced to effective extraction of chloramine from the aqueous phase [69]. The EC of primary amine hydro chlorides under the conditions of galvanostatic elec trolysis of aqueous NaCl (RTOA, Ti cathode) was optimized in the case of MeNH3Cl. The influence of different factors on the process was studied and the effective parameters were determined: ja = 170 mA cm–2, 1 and 4 M MeNH3Cl and NaCl, Т = 10°С, the ratio of the volumes of the aqueous and organic phase is 3 : 1). A number of Nchloro deriva tives of alkylamines (MeNCl2, EtNCl2, nPrNCl2, nBuNCl2, t BuNCl2, Me2NCl, and Et2NCl) were obtained under these conditions in high (>90%) yields [70]. This process can be regarded as an effective gen eral procedure for the preparation of Nchloramines from the corresponding amine hydrochlorides. Chloramine NH2Cl is an important intermediate in organic and inorganic synthesis. For its preparation, however, the abovedescribed methods for the EC of chloramines are unsuitable because NH2Cl quickly reacts with the starting NH3, forming NH4Cl with N2 evolution [71]:

(b) NCl3 (in CCl4) + 2NH3 (in H2O)

6NH3

HCl CCl4

. 3NH2Cl. 50%

NCl3 + 5NH4Cl

The excess of NH3 formed during the electrolysis was neutralized with calculated HCl additions. At the second stage (b), the organic phase containing NCl3 was vigorously stirred with aqueous NH3. The desired product formed in moderate 50% yield because of the low rate of the heterophase reaction, which initiates the side process of N2 and NH4Cl formation in the presence of excess NH3 (see above) [71]. The EC of aromatic amines was discussed in [73, 74]. The EC of diphenylamine and its derivatives (methyl, 4formyl, 2acetyl, etc.) in aqueous solutions

of alkali metal chlorides containing AcOH or MeCN additions gave 4chlorodiphenylamine derivatives [73]. It was shown that aniline can be subjected to EC on a carbon anode in concentrated HCl (12 M), giving a mixture of trichloroquinone and 2,4,6trichloroa niline; the low yield of the latter is explained by the ability of aniline to be readily oxidized [74]. The EC of benzoic and stearic acids, paraami nobenzenesulfamide, benzenesulfamide, and para toluenesulfamide under diaphragm electrolysis condi tions on a platinized Ti anode in aqueous solutions of

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metal chloride (NaCl, MgCl2) gave the corresponding N,Ndichloramides with yields of 55–92% [75, 76]. The EC of phthalimides and succinimides under sim ilar conditions led to Nchlorimides (50–70% yield) [75–78].

509

It is interesting to note that the EC of acetanilide under these conditions gave a mixture of ortho and parachloroacetanilides (total yield ∼60%) instead of the expected Nchloramide because of the rearrange ment of the initially generated Nchloramide [79]:

Cl –

NHCOMe

Cl , –2e –H+

NHCOMe + Cl

NClCOMe

The sodium salts of Nchlorosubstituted arylsul famides (benzenesulfamide, paratoluenesulfamide, and parachlorobenzenesulfamide) are among the most important products of chloroorganic synthesis. Therefore, the syntheses of these products with almost quantitative yields under diaphragmless electrolysis conditions are of interest [80]:

䊞

⊕

2NaOH

⊕

2NaOH +

2NaCl–

2OH–

–2e

+2e, –H2

2H2O HCl

NaCl + H2O 䊞

NHCOMe .

NaOH

Cl2 NaOCl

䊞

+

2NaCl–

2OH–

O

+2e, –Cl–

–2e

+2e, –H2

2H2O

N –

O O

Cl2 NaOCl

liquid

.

N OO Cl 75–90%

O.

N H

Earlier, we have already summarized some of the results described in this subsection [83, 84].

solid

RSO2NH2 –

RSO2NClNa+

6. Heterocyclic Compounds The Na salts of Nchloroarylsulfamides, as well as the starting arylsulfamides, are almost insoluble in a saturated aqueous solution of NaCl and thus not liable to cathode decomposition. As a result, the EC of aryl sulfamides that occurs at the interface leads to the desired products in high yields (97–99%). The chem ical method of synthesis gives ∼20% lower yields, pro ceeding with the formation of large amounts of sewage water. Therefore, the possibility of EC with recycling of disposal solutions was studied; it was shown that six recyclings did not lead to any pronounced decrease in the yield of the desired products [81]. This allowed experimental justification of the basic principles of the organization of the lowwaste synthesis of arylsul foacid Nchloramide sodium salts [81]. The electrosynthesis of Nchlorosuccinimide was performed under similar conditions [82]. It required HCl additions to neutralize the excess of alkali (see the scheme). It was noted that the current efficiency of the desired product could be lower because of the partial electroreduction of Nchlorosuccinimide when it accumulated in solution. RUSSIAN JOURNAL OF ELECTROCHEMISTRY

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A method for the EC of 3substituted sydnones to the corresponding 4chlorosydnones (see the scheme) under diaphragm potentiostatic electrolysis condi tions (Pt anode, Еа = 1.15 V relative to s.c.e., 0.3 M solution of Me4NCl in MeOH) was described in [85]. The yields of the desired products (87–100%) were considerably higher than the yields obtained using the chemical procedures. R N N

CH ±

O

O

Cl–, –2e MeOH

R N N

CCl ±

O

O

R = C6H5, 4 MeC6H4, 2 MeC6H4, C6H5CH2 .

The EC of indigo dye on a graphite anode in 34.4% aqueous HCl under galvanostatic (ja = 30 mA cm–2) diaphragmless electrolysis conditions formed 5,5'dichloroindigo (51.5% yield) [5]. The EC of dihy dropyrane was performed in MeCN and Et4NCl sup porting solution in the presence of pyridine on a glassy carbon anode (Е = 0.75 V relative to Ag/Ag+) and gave 3chloro2oxytetrahydropyrane (50% yield) [86]: No. 6

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LYALIN, PETROSYAN

Cl

Cl–, –2e MeCN, C6H5N

O

.

O

OH

5Chlorouracil (~100% yield) was the sole product of the EC of uracil under diaphragm potentiostatic (Еа = 1.14 V relative to s.c.e.) electrolysis conditions on a Pt anode in nonaqueous media (MeOH, DMF, THF, and MeCN) [87]. The EC of 1substituted azu lenes with electronacceptor groups (NO2, COOMe, and PhN=N) in a MeCN solution of triethylbenzy lammonium chloride on Pt and glassy carbon anodes led to the formation of 3chloroazulenes in 58–100% yields [88]. The EC of pyrazole, its alkylsubstituted deriva tives, and 3nitropyrazole on a Pt anode in het erophase media (aqueous NaCl–CHCl3) under dia phragm galvanostatic electrolysis conditions was stud ied in [89]. It was shown that the EC was promoted if the pyrazole ring contained donor substituents but +

hindered if it contained acceptor substituents. The yield of 4chlorosubstituted derivatives in the chlori nation of pyrazole, 3,5dimethylpyrazole, and 3nitropyrazole was 51, 59, and 41%, respectively. For 1,5dimethylpyrazole, electrochemical chlorination in the side chain of pyrazoles was possible [90]. The EC of pyrazoles (see the scheme) proceeded via the formation of Nchloro derivative 1a followed by its N–C rearrangement into Chalo derivative 1b, as shown for unsubstituted pyrazole used as an exam ple. Along with the expected 4chloropyrazole, the reaction gave a small amount of 4,4'dichloro1,3'(5') bipyrazole 1d in yield of up to 14% [89]. The forma tion of this compound was explained by the low rate of the N–C rearrangement of intermediate Nchloropy razoles; as a consequence, 1,4dichloropyrazole 1с more quickly interacted with 4chloropyrazole by the kinesubstitution mechanism, forming “dipyrazole” 1d [91]:

2Cl–

Cl

–2e

Cl2 +

N N 1 H

–HCl

N

N 1a Cl

N

Cl Cl2

N H 1b

N

Cl

Cl N

N Cl 1c

N H

–HCl

Cl

The same tendencies are typical for the EC of pyra zole3 and pyrazole5carboxylic acids performed on a Pt anode under conditions of diaphragm electrolysis in aqueous NaCl [92]. The efficiency of the process depends on the donor–acceptor properties of substit uents and their position in the pyrazole ring. Thus the yield of 4chloropyrazoles in the EC of pyrazole3(5) carboxylic acid, 1methylpyrazole3carboxylic acid, 1methylpyrazole5carboxylic acid, 1ethylpyra zole3carboxylic acid, and 1methyl3nitropyra zole5carboxylic acid was 92, 93, 69, 80, and 4%, respectively. III. ELECTROCHEMICAL BROMINATION AND IODINATION OF ORGANIC SUBSTANCES FROM VARIOUS CLASSES

N H N N

N N

Cl N

Cl

Cl N

1d

N H

.

The halo derivatives of saturated hydrocarbons, which exhibit acid properties, are electrochemically brominated in the presence of bases. Thus CHBr3 (methane derivative) was brominated to CBr4 under galvanostatic (ja = 450 mA cm–2) diaphragmless elec trolysis conditions on a graphite anode with 71% yield and 99% current efficiency. The reaction was con ducted in a CHBr3 emulsion with an aqueous solution containing NaBr and NaOH [93]. Cyclohexane and methylcyclohexane were electro chemically brominated (40% aqueous solution of HBr) to the corresponding monobromo derivatives with 16–20% yields based on the charged hydrocar bon under similar conditions (ja = 400 mA cm–2) in a heterophase medium on a Pt anode [94]. In contrast to the EC of these hydrocarbons [10], their EB occurred only in a diaphragm electrolyzer.

1. Saturated Hydrocarbons The chemical reactions involving bromine and iodine occur less readily than reactions with chlorine because the activity of these halogens is lower than that of chlorine. The same holds for EB and EI [11].

2. Unsaturated Hydrocarbons The EB of olefins in aqueous solutions does not radically differ from their EC. In neutral solutions, bromohydrins formed along with the dibromo

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derivatives of hydrocarbons [95]; in alkaline solu tions, bromohydrins were the sole products. Of interest is selective functionalization of dimethyl

4cyclohexene1,2dicarboxylic ether (1) to the corresponding epoxide (2), bromohydrin (3), or 1,2dibromide (4) [96]: CO2Me

MeCN–H2O (1/4); NaBr

+

O CO2Me 97%

2

2Br– –2e

CO2Me

1

Br

CO2Me

HO

CO2Me 3 72%

MeCN–H2O (1/19); NaBr; H2SO4

Br2 +

511

CO2Me

Br

CO2Me

MeCN–H2O (4/1); NaBr; H2SO4

Br

The process was conducted under galvanostatic (ja = 3.3 mA cm–2) diaphragmless electrolysis condi tions on a Pt anode in a MeCN–Н2О system contain ing NaBr. At сNaBr < 0.1 M, the electrolyte was a homo geneous solution; at higher concentrations, it existed as two phases. At сNaBr < 0.1 M, the EB led to product 2 in a neutral medium and 3 in an acid medium, while at сNaBr > 1.5 M, the sole product in an acid medium was dibromo derivative 4. As a matter of fact (see the scheme), in a system with high сNaBr and low content of Н2О, Br2 generated in the aqueous phase passes to MeCN and reacts with the olefin, giving dibromide 4 [96]. At low сNaBr, the system was monophase and fast hydrolysis of Br2 led to HOBr, which reacted with 1 to form bromohydrin 3 in an acid medium and epoxide 2 in a neutral medium. A study of the EB of isosafrole 1 (aqueous–aceto nitrile (MeCN : Н2О = 7 : 3) solution of NaBr, Pt anode, galvanostatic diaphragmless electrolysis condi tions (ja = 6.60 mA cm–2, Q = 2.83 F per mole of sub strate, Т = 20–25°С)) was reported in [97]. The reac tion gave a mixture of epoxide 2 (71% yield) and diol 3 (23%):

(CH2)10

Br–, electrolysis

OAc 1

O

O O Br–, –2e

Br

1

HO

O 2

.

3

The EB of enolacetate 1 in an aqueous–acetoni trile (MeCN/Н2О = 3 : 1) solution of NH4Br on a Pt anode under galvanostatic diaphragmless electrolysis conditions (ja = 6.7 mA cm–2, Q = 2.3 F per mole of substrate) gave αbromoketone 2 (95% yield) [21]:

I , electrolysis

(CH2)10

O (CH2)10

OSiMe3 3

Vol. 49

OH H

H

Treatment of this mixture with 1% aqueous H2SO4 led to a complete conversion of epoxide into diol (94% yield). Product 3 is of practical value: it is used for the synthesis of the DOPA neuromediator [97]. Note that a replacement of NaBr by NaI for EI of isosafrole decreased the yield of 3 more than twofold.

Br

The EI of enol derivative 3 under similar condi tions (NH4I, ja = 2–2.7 mA cm–2, Q = 2.4 F per mole of substrate) gave αiodoketone 4 (97% yield) [21]. The EB of enol 5 (NH4Br, ja = 6.7 mA cm–2, Q = 2.9 F

O +

–

;

O

O

H Br

H+, H2O

H2O –2Br–

H

2

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O

O

O (CH2)10

CO2Me . 4 92%

.

I 4

per mole of substrate) formed αbromoketone 6 and the EI of enol 7 (NH4I, ja = 2.1–2.3 mA cm–2, Q = 5.9 F per mole of substrate) gave αiodoketone 8 (71% yield) [21]: No. 6

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LYALIN, PETROSYAN Br–, electrolysis

; Br нC5H11

нC5H11

O

OAc 5

6

Like EC (Section II), the EB and EI of unsaturated compounds in nonaqueous media (MeCN, MeOH, DMF, AcOH) yielded not only haloolefins, but also the products of their interaction with the solvent in large amounts. Thus the EB of vinylacetylene on a graphite anode in anhydrous MeOH gave a mixture of 1,1,3trimethoxy2,2,4tribromobutane and 1,1,8,8 tetramethoxy2,2,3,6,7,7hexabromooctane (their total yield was 82%) [98]. The EB of cinnamic acid under similar conditions gave αbromoβmethox yphenylpropionic acid (current efficiency ∼40%) [25]; the EB of cyclohexene in DMF formed a mixture of 1,2dibromocyclohexane and 1formyloxy2bro mocyclohexane with a total yield of 80% [99]. The electrolysis of a solution of AcOK in glacial AcOH containing I2 and cyclohexene (Т = 20–25°С) gave 1iodo2acetoxycyclohexane (85% yield) [99]. Under similar conditions but at Т = 50°С, the elec trolysis of cyclopentene gave 1iodo2acetoxycyclo pentane as the main product, while the EI of 1phe nyl2butene in MeCN in the presence of iodides led to 1phenyl2iodo3acetamidobutane [99]. The EB of 1acetylcyclohexene1 (concentrated aqueous HBr–nheptane heterophase system, graph ite anode, diaphragmless electrolysis) formed

I+

MeOH

–2e

I–, electrolysis

нC5H11 OSiMe3 7

.

нC5H11

I O 8

1,2dibromo1acetylhexane in 90–95% yield [100]. Regioselective EB of α , βunsaturated ketones (2cyclohexenone and 2cyclopentenone) was per formed under galvanostatic (ja = 15–30 mA cm–2) dia phragmless electrolysis conditions on a graphite anode using the CF3COOH–CuBr–Et4NOTs–MeCN sup porting electrolyte [101]. The EB of 2cyclopentenone can be described as O

O –2e, Br–

Br

.

The EI of terminal acetylenes in a methanol solu tion of NaI on a Pt anode under galvanostatic (ja = 7.5 mA cm–2) diaphragm electrolysis conditions was reported in [33]. In contrast to EC (Section II), this process formed 1iodoacetylenes (78–88% yield) without halogen addition at the multiple bond. The reaction mechanism involves the stage of the genera tion of the I+ cation, which reacted with the starting acetylene, forming an intermediate complex readily hydrolyzed into 1iodoacetylene according to the scheme

I–

[MeO–I+]

R C

CH

intermediate complex

3. Aromatic Hydrocarbons Aromatic compounds are not readily brominated. The EB of benzene in an emulsion with 48% aqueous HBr was studied in [102]. The slow chemical stage was dominant in the electrosynthesis of bromobenzene. The EB did not occur below 30°С; at 60°С, the cur rent efficiency of the desired product was only 11%. The EB into the benzene ring on a Pt anode in non aqueous (AcOH, MeCN) media was investigated in [103–105]. The voltammetric curves of benzene [103], toluene, and paraxylene [104] in an AcOH solution containing the Br– anion contain two waves. The first wave (Е1/2 = 0.78–0.79 V relative to s.c.e.) corresponds to the oxidation of Br– to Br2 (in contrast

H2O

R C

CI .

to MeCN (see below), in AcOH solution only one wave corresponds to this process). The second wave (Е1/2 = 1.15–1.40 V) corresponds to the electrooxida tion of the complex involving arene, Br2, and AcOH. The electrolysis at a potential (plateau) of the first wave (Е = 1.0 V) did not form bromoarenes (benzene) [103] or formed toluene or paraxylene in 10–20% yields because of the low (see above) rate of Br2 and arene interaction [104]. The EB at a potential of the second wave (Е = 1.2–1.4 V) led to increased yields of the desired products (35–50%); in AcOH, bromoace tic acid formed (in addition to bromoarenes) in 50– 60% yields (based on the starting Br– anion) [103, 104]. The voltammetric curve of anisole in

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Table 5. Yields of products formed during the coelectrolysis of a mixture of arene and I2 (A) in MeCN and with arene ad ditions to the MeCN solution of I2 subjected to electrolysis (B) A

B

Substance yields of products of iodination in the ring, %

yields of products of substitution yields of products of iodination in the side chain, % in the ring, %

Benzene

11

Toluene

16 (ortho); 2 (meta); 16 (para)

0

47 (ortho); 47 (para)

50

12 (Nparaxylylacetamide)

100

6 (ortho); 1 (meta); 13 (para)

Tar products

24 (ortho); 56 (para)

Paraxylene Anisole Nitrobenzene

96

0

0

Mesitylene

73

0

No data

Triphenylmethane

15

36 (triphenylmethanol)

No data

MeCN contains three waves: the first (Е1/2 = 0.43 V relative to Ag/Ag+) and second (Е1/2 = 0.79 V) waves correspond to the oxidation of Br– to Br3− and of Br3− to Br2, respectively; the third wave (Е1/2 = 1.30 V) corre sponds to the oxidation of the intermediate including anisole and Br2 [105]. The EB of anisole in MeCN, as well as in AcOH, occurred via the formation of an intermediate, which was oxidized less readily than the Br– anion. Importantly, bromoanisole formed (with 90% current efficiency) only under the electrolysis conditions at the potentials of the oxidation wave of this intermediate (Е = 1.5 V). Note that the possibility of the formation of bromoarenes by interaction of the arene radical cation with the Br– anion that comes from the bulk of the solution was not taken into account in [103–105] (Section V). In studies of the EC of benzenes, methods for increasing the yields of the isomers were examined (Section I). Thus anodes impregnated with cyclodex trin were used to increase the yield of parachloroben zenes [38–41]. For EB of arenes, this was not studied in detail but it was noted that the ratio of para to orthoisomers was changed by varying the electrolysis potential [106]. Thus the EB of phenol on a Pt anode in concentrated aqueous HBr at Е = 0.56 V (relative to s.c.e.) led to a mixture of para and orthobromophe nols with a molar ratio of 3.56, which decreased to 1.8 when the electrolysis potential increased to Е = 0.83 V. RUSSIAN JOURNAL OF ELECTROCHEMISTRY

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Another problem concerning the EB of arenes is selective synthesis of mono or dibromoarenes. For EB of thymol, which occurs by the scheme [107] Me

Me Br–, –2e

HO Me

Br

Me Br–, –2e

HO Me

Me

Me

Br

Br

HO

,

Me

Me

this problem was solved by varying the nature of the solvent. The process was performed using various bro mides (LiBr, Et4NBr, NaBr, NH4Br) in MeCN or MeOH under diaphragm electrolysis conditions on a Pt anode at Br– discharge potentials (Е = 0.85–1.0 V relative to Ag/Ag+ in MeCN or Е = 0.35–0.75 V in MeOH). In MeCN, only 6bromothymol formed irrespective of the charge passed (65–97% yield); in MeOH, the main product was 6bromothymol (69– 97% yield) at Q = 2 F/mol and 2,6bromothymol (77– 94% yield) at Q = 4 F/mol. This effect was explained by the fact that electrogenerated Br2 is polarized more strongly in MeOH [Brδ+–Brδ– → S (where S is the sol vent)] than in MeCN, where Br2 molecules are less active [107]. The EI of benzenes (benzene, toluene, para xylene, mesitylene, anisole, and triphenylmethane) in a MeCN solution of LiClO4 containing I2 under potentiostatic (Е = 1.6–1.7 relative to Ag/Ag+) dia No. 6

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LYALIN, PETROSYAN

phragm electrolysis conditions on a Pt anode was studied in [108]. The coelectrolysis of I2 and arene led (Table 5) to the formation of monoiodo derivatives; for paraxylene and triphenylmethane, the solvent partic ipation in the oxidation of arene led to the products of substitution in the side chain containing no iodine. Note that the yields of the iodo derivatives (Table 5) were much higher when arene was added to the MeCN solution of I2 preliminarily subjected to electrolysis. This was explained by the formation of a highly reac tive iodinating agent, namely, Niodoacetonitrilium cation, during the oxidation of I2 (for details, see Sec tion V) [108]. Arene was not oxidized under the exper imental conditions and the products of substitution into the side chain did not form. It follows from the data of [108] that high yields of EI products were observed only for electronenriched arenes, while, e.g., PhNO2 did not undergo electro chemical iodination. A solution to this problem was sug gested by the authors of [109] who showed that in 1,2 dichloroethane or CH2Cl2 containing 10% CF3COOH, EI with I2 (amperostatic (ja = 3.1 mA cm⎯2) diaphragm electrolysis with a Pt anode) led to iodoarenes with elec tronaccepting substituents (I, CHO, CF3, CN, and NO2) with 46–97% yields. The use of 1,2dichloroet hane gave better yields than CH2Cl2. As in [108], the process occurred via the oxidation of I2, possibly form ing iodine trifluoroacetate as an iodinating agent [109]. For EI of arenes (as well as their EB, see above), it was shown that one isomer can be obtained as a dom inant isomer by varying the solvent. Thus the EI of tol uene in MeCN led to approximately equal amounts of para and orthoiodotoluenes, but when MeCN was replaced by trimethylorthoformate, the ratio of para to orthoisomers became 2.33; after the EI of tert

butylbenzene in MeCN, this ratio was 2.96, but the same process in trimethylorthoformate led only to the paraiododerivative of tertbutylbenzene [110]. Section II described the possibility of EC of arenes (toluene) into the side chain by electrolysis in het erophase media [47]. In recent years, this principle was developed in [111–113], which reported the EB of arenes in twophase media (CHCl3, 40–60% aqueous NaBr with a catalytic amount of HBr). The process was conducted under galvanostatic (ja = 30 mA cm–2) diaphragmless electrolysis conditions on Pt electrodes at moderate (0–2°С) temperatures. The EB of toluene and its derivatives (4chloro, 4bromo, 2,4 dichloro, 4methyltoluene, and ethylbenzene) led to αmonobromo derivatives with yields of 50–95% and regioselectively of over 95% [111]. The yields of αmonobromo derivatives decreased as the donor properties of substituents increased in tol uene, and the yields of the products of bromination into the ring simultaneously increased. Thus after the EB of 4methyltoluene, the yield of the αmono bromo derivative was 50%; for 4methoxytoluene, however, the product was a mixture of its αmono bromo derivative (12% yield), 3bromo4methoxy toluene (39%), and 2bromo4methoxytoluene (37%). Under the same conditions, methoxybenzene, 1,2dimethoxybenzene, methoxynaphthalene, 1,2 dimethoxynaphthalene, aniline, dimethylaniline, 2methylnaphthalene, 3methoxy4hydroxybenzal dehyde, and 2hydroxytoluene formed the derivatives bromosubstituted in the ring with nearly quantitative yields (92–98%) despite the benzyl position in the starting arenes (2methylnaphthalene, 2hydroxytol uene) [112]. The abovementioned products formed according to the scheme [111]

Aqueous phase:

Organic phase: •

–2e

2Br– Br2 (a) Br2 + H2O (b) 2HOBr

HBr + HOBr Br2O + H2O

(c) Br2O Br•+ OBr CH3 • (d) + OBr

•

CH2

•

CH2Br

Br

–HOBr

Br+ + H2O

OCH3

OCH3 (e)

+ Br+

.

–H +

Br

According to this scheme, the electrolysis of aque ous NaBr leads to the generation of Br2, which reacts with Н2О to form HOBr (stage a). This acid (in the presence of the catalytic amounts of HBr) can form two brominating agents: Br2O (brominates by the rad ical mechanism, stages c and d) and Br+ (attacks the aromatic ring having high electron density, stage e). These brominating agents then pass to the organic

phase, where radical bromination (nonactivated aro matic compounds) and electrophilic substitution (activated aromatic compounds) occur. The suggested procedure for the synthesis of αbrominated aromatic compounds has a number of advantages over the chemical procedure, which requires the use of a reaction initiator (azobisisobu tyronitrile, benzoyl peroxide, or irradiation with light)

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and high (100–170°С) temperatures. The electro chemical method allows easy isolation of the desired product from the organic phase after the distillation of CHCl3 and promises to become a wasteless procedure. According to [112], the required amounts of NaBr and HBr can be added to the aqueous phase remaining after the separation of CHCl3, a new portion of the CHCl3 solution of arene can be introduced, and the electrosynthesis can be continued. The EB of naphthalene in AcOH [103] and MeCN [114] and of anthracene in MeCN [114] on a Pt anode under potentiostatic electrolysis conditions was described. The electrolysis at Е = 1.0 V relative to s.c.e. (the oxidation potential of Br–) in AcOH formed bro monaphthalene (65% yield) [103]. In contrast to the EB of toluene, benzene, and paraxylene (cf. above), bromoacetic acid did not form because of the high reaction rate of Br2 with naphthalene. The EB of anthracene and naphthalene in MeCN at the Br– oxi dation potential (E = 0.80 V relative to Ag/Ag+) did not form bromoarenes [114]. The EB of anthracene at Е = 1.2 V exceeding the anthracene oxidation poten tial, however, gave 9bromoanthracene (current effi ciency 48%); at Е = 1.6 V exceeding the oxidation potential of 9bromoanthracene, both 9bromoan thracene (current efficiency 26%) and 9,10dibro moanthracene (current efficiency 19%) formed. For

Anode: 8X–

–8e

Cathode: 8H2O

X = Br, I

4X2 +8e

Solution: X2 + 2OH– 8OH– + 4H2

515

naphthalene, the EB at Е = 1.35 V (naphthalene oxi dation) led to the formation of 1bromonaphthalene (current efficiency 70%), while at Е = 2.0 V the main product was 1.4dibromonaphthalene (current effi ciency 71%). The authors of [114] believed that the EB of both naphthalene and anthracene occurred via the stage of the interaction of the arene radical cation with the Br– ion. The EI of diphenyl and diphenyl ether was studied in [115]; arene was added to the preliminarily electro lyzed MeCN solution of I2 (the conditions were simi lar to those described in [108], see above). As a result, the corresponding iodoarenes were obtained with 95% (diphenyl) and 75% (diphenyl ether) yields. 4. OxygenContaining Compounds The EB and EI of oxygencontaining compounds were similar to the chlorination of these compounds (Section I). Thus ethanol [116, 117] and isopropanol [118] were transformed during EI into CHI3 with cur rent efficiency 90–97%. The conditions of EI: gal vanostatic (ja = 100–200 mA cm–2) diaphragmless electrolysis; Т = 60°С; Pt, graphite, or graphitesup ported PbO2 anodes; slightly alkaline (Na2CO3 addi tion) aqueous NaI or KI solutions. The formation of СHI3 can be explained by the following processes:

–H2O

OX– + X–

CH3CH2OH

OX– –X–

CH3CHO

CH3CHCH3

OX– –X–

CH3CCH3

OH

3X2 –3X–

3X2 –3X–

O

The EB of acetone occurred by a similar mecha nism (aqueous NaBr, pH 9.5–10.5, galvanostatic (ja = 100 mA cm–2) diaphragmless electrolysis, graphite or graphitesupported PbO2 anodes, Т = 20–22°С) and gave CHBr3 with a yield of 94% and current efficiency 91% [119]. The EB of cinnamic acid in MeOH satu rated with HBr led (under diaphragmless electrolysis conditions) to αbromoβmethoxyphenylpropionic acid (current efficiency 40%) [25].

CX3CHO

OH–

CX3CCH3

CHX3 + HCOO–

OH–

CHX3 + CH3COO–.

O

The EB of BuOH was described in [56] (galvano static diaphragmless electrolysis of a solution of HBr in the starting alcohol, graphite anode). The product was a mixture of acetals of 2bromopropionic (current efficiency 23%) and 2,2dibromopropionic (current efficiency 8%) aldehydes. The process involves the oxidation of the alcohol with anodegenerated bro mine followed by the formation and bromination of acetal:

6Br– 3Br2, CH3CH2CH2CHO + 2H+ + 2Br–, Br2 + CH3CH2CH2CH2OH CH3CH2CH2CHO + CH3CH2CH2CH2OH CH3CH2CH2CH(OCH2CH2CH2CH3)2 + H2O, CH3CH2CH2CH(OCH2CH2CH2CH3)2 + Br2 CH3CH2CHBrCH(OCH2CH2CH2CH3)2 + H+ + Br–, CH3CH2CHBrCH(OCH2CH2CH2CH3)2 + Br2 CH3CH2CBr2CH(OCH2CH2CH2CH3)2 + H+ + Br–. It was noted that EB required the use of higher temperature (Т = 60°С) than EC (Т = 30°С) because RUSSIAN JOURNAL OF ELECTROCHEMISTRY

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The synthesis of hypobromites occurred by the scheme [54] Br– + ROH + OH–

–2e

ROBr + H2O.

The secondary or tertiary alcohols were electro chemically brominated in aqueous NaBr at pH 6.5– 8.5 (diaphragm galvanostatic electrolysis with Pt, Ti platinized, or graphite anodes). The yield of hypobro mites was ∼100%; the current efficiency was 65–90%. The EB at the αposition (see the scheme below) of αsubstituted methyl ethers with malonic R1CH(CO2Me)CO2Me (R1 = H, n Bu, PhCH2, Me2C=CH–CH2) and acetoacetic R1CH(CO2Me)COMe (R1 = n Bu, PhCH2) acids was studied in [120]. The process was conducted in CH2Cl2 containing Et4NBr (electrolyte) and MeONa (enolizing agent) on a Pt anode under diaphragmless electrolysis conditions and occurred according to the scheme CO2Me R1CH CR2 1 O

CO2Me

CO2Me MeONa

R1C CR2 2 − O

–2e

Br–

R1CBr CR2 . 3 O

R2 = Me, OMe

Conditions were found (ja= 87–133 mA cm–2, molar ratio Et4NBr/substrate = 20–35) that prevented the oxidation of enolates 2 (which led to dimerization) and provided high (64–84%) yields of the desired products 3. In the EB of dimethyl malonate, chloro derivatives formed (in yields of 50–60%) along with the dimerization products at a low molar ratio of Et4NBr/substrate = 1–2. The formation of the chloro derivatives may be explained by the cathode reduction of CH2Cl2, generating Cl– ions, and participation of these ions in the competitive EC of the substrate on the anode, though this aspect was not considered in [120]. The EB and EI of dibenzoylmethane in aqueous AcOH under diaphragmless galvanostatic electrolysis conditions were described; these reactions led to dibenzoylbromo and dibenzoyliodomethanes in good yields [121]. The EB of dimethylsulfoxide on RTOA in aqueous KBr with Na2CO3 (NaHCO3) additions under gal vanostatic (ja= 60 mA cm–2) diaphragmless electroly

sis conditions was studied [122]. When performed in the presence of Na2CO3, EB led to the formation of (CBr3)2SO2 (50% yield); with NaHCO3, the product was CBr3SO2CH3 (36% yield). (CBr3)2SO2 was assumed to result from volume bromination with the oxidation of DMSO by the mechanism of basic catal ysis, while the electrosynthesis of CBr3SO2CH3 occurred via the stage of the formation of the adsorbed DMSO–Br2 complex followed by its electrooxidation. 5. Amines, Amides, and Imines A number of patents are available on the electro chemical synthesis of bromo and iodoanilines [123⎯125]. In an aqueous alkaline (NaOH addition) solution of NaI, aniline was readily electrochemically iodinated into paraiodoaniline with a nearly quanti tative yield. Attempts to obtain bromoaniline by replacing iodide by bromide under similar conditions failed. At the same time, the EB of Nacetylaniline (ja = 11.5–14.5 mA cm–2, Т = 22–25°С) in aqueous AcOH containing NH4Br gave Nacetyl4bromoa niline in 96.6% yield [124]. The EI of 3,5disubsti tuted anilines or 3,3'disubstituted5,5'fused bis anilines in aqueous acid media led to the formation of 2,4,6,2',4',6'hexaiodo3,3'disubstituted5,5'bonded bisanilines. For example, the EI of 3,5bis(2,3dihy droxypropylaminocarbonyl)aniline (0.15 M NaBF4, Т = 20°С, Pt anode, pH 1.5, J = 200 mA) in aqueous MeOH containing I2 in a diaphragm cell formed 3,5 bis(2,3dihydroxypropylaminocarbonyl)2,4,6tri iodoaniline with a quantitative yield; to complete the reaction after the electrolysis, the anolyte was main tained for 24 h at Т = 60°С [125]. The EB and EI of 4oxo2,2,6,6tetramethylpipe ridine (triacetoneamine, TAA) gave 3,5dibromo4 oxo2,2,6,6tetramethylpiperidine and 3carboxam ido2,2,5,5tetramethylpyrrolidine hydrobromides, which are substrates in the syntheses of 2,2,5,5tet ramethylpyrrolidine nitroxides [62, 126, 127]. Thus the EB of TAA in 30% aqueous HBr under galvano static (ja = 30–100 mA cm–2) diaphragm electrolysis conditions on a Pt anode led to 3,5dibromo4oxo 2,2,6,6tetramethylpiperidine hydrobromide with a yield of over 90% [62]:

O Me Me

O Me Me

N

HBr electrolysis

H

When HBr was replaced by more readily accessible KBr (aqueous solution with an H2SO4 addition), the yield of the desired product decreased by 10–20%

Br Me Me

N H

Br Me ⋅ HBr. Me

[126]. In a neutral medium, the EB of TAA led to the formation of Nbromotriacetoneamine with a moder ate (∼30%) yield [62].

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The EI of TAA on a Pt anode in an aqueous solu tion containing KOH, KI, and NH3 under galvano static (ja = 100–500 mA cm–2) electrolysis conditions was studied in [127]. It formed 3carboxamido

Anode: 2I–

–2e

+2e

2KOH + H2

I2 + 2KOH

KOI + KI

KOI

Me Me

N

Me Me

A replacement of KOH by К2СО3 led to the forma tion of only Niodotriacetoneamine [127]. The EB of ethyl and isopropylcarbamates in aque ous NaBr on a Pt/Ti anode formed ethylN,Ndibro mocarbamate and isopropylN,Ndibromocarbamate (galvanostatic (ja = 600 mA cm–2) diaphragmless elec trolysis) in 98–99% yield [128]. The EB of phthalim ide and succinimide under the same conditions, gave the corresponding Nbromoimides (~98% yield) [75]. Studies not directly related to the synthesis of Nbromoamides are also of interest because EB is the key stage in the synthesis of useful products [129–131]. For example (see also Section V), the electrolysis of amides RCONH2 (R = Ph, PhCH2, C3H7) [127–129] or formamides R1NHCHO (R1 = nalkyl, cycloalkyl, aralkyl) in the presence of alcohols R2OH (R2 = Me, lower alkyl) and the catalytic amounts of alkali bro mides on graphite or Pt anodes under diaphragmless electrolysis conditions gave carbaminic acid ethers (intermediates in the synthesis of pesticides) in ~80% yield [130]. The process involves the electrochemi cally generated Hofmann rearrangement and is described by the scheme (for amides) 0.5Br2 –e

Br–

RCONH2

–

MeO–

RCONHBr –

RCONBr

–0.5H2, +e

MeOH

–Br–

••

••

[RCON ]

RNCO

MeOH

C I Me

N H

H

+

O NH2 Me . Me

O

O Me Me

2,2,5,5tetramethylpyrrolidine in yields of 65–78%. The iodo derivative of TAA, which formed as an inter mediate in this process, underwent the Favorskii rear rangement, leading to the desired product:

I2

Cathode: 2K+ + 2H2O

Solution:

517

NH3

Me Me

Me

N H

6. Heterocyclic Compounds The EB of 3substituted sydnones to the corre sponding 4bromosydnones was described in [85]: R N N

CH ±

O

O

Br–, –2e MeOH

R N N

CCl ±

O

O

R = C6H5, 4 MeC6H4, 2 MeC6H4, C6H5CH2 .

Under potentiostatic diaphragm electrolysis con ditions (Е = 0.75 V relative to s.c.e., Pt anode, MeOH solution of NaBr), the yields of the desired products (93–99%) were much higher than those in chemical procedures. Several attempts to obtain 4iodosyd nones by a similar procedure failed because direct chemical iodination of sydnones is impossible [85]; thus 3phenyl4iodosydnone was obtained only by exchange of halogen in 3phenyl4bromosydnone. The EB and EI of uracyl under diaphragm potentio static electrolysis conditions (Е = 0.996 V relative to s.c.e. for bromination and Е = 0.412 V for iodination) on a Pt anode in nonaqueous (MeOH, DMF, THF) solvents gave 5bromo and 5iodouracyls, respec tively, with nearly quantitative yields [87]. The EB of 2 and 3methylthiophenes on a graph ite anode in a methanol solution of NH4Br under dia phragmless galvanostatic electrolysis conditions led to a mixture of mono (86–97% in a mixture) and dibro mothiophenes with a total yield of 54–60% [132]. The structure of the desired products depends on the posi tion of the Me substituent:

RNHCO2Me.

Synthesis of NacetylNmethylurea (70–80% yield) was reported in [131]. It involved EB of aceta mide in an aqueous slightly alkaline solution of NaBr under diaphragmless electrolysis conditions. As in [129], the process occurred via the intermediate for mation of isocyanate (methylisocyanate), whose reac tion with acetamide led to the desired product. RUSSIAN JOURNAL OF ELECTROCHEMISTRY

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Br Br–, –2e

S

Me

Br–, –2e

Br

S

Me

Me

No. 6

Me

Me Br–, –2e

S 2013

S

Me

Br–, –2e

S

Br

Br

.

Br

S

Br

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LYALIN, PETROSYAN

Thus the products of the reaction of 2methylth iophene were 5bromo2methylthiophene and 3,5 dibromo2methylthiophene, while 3methylth iophene led to 2bromo3methylthiophene and 2,5 dibromo3methylthiophene. After the EB of 3meth ylthiophene, the yield of the dibromo derivative was four times higher than in the case of 2methylth iophene because of the presence of two unoccupied αpositions for electrophilic bromination in the 3methylthiophene molecule [132]. Under similar conditions, thiophene formed a mixture of 2bro mothiophene (24% yield) and 2,5dibromothiophene ⊕

(6.4%), while 2acetylthiophene gave only 5bromo 2acetylthiophene (12%) [133]. The EB of furan in a methanol solution of NH4Br (under the same conditions as in the EB of thiophene) proceeded in a different way [134]. The product was 2,5dimethoxy2,5dihydrofuran (73% yield) instead of the expected bromo derivatives of furan. This was explained by the 1,4addition of anodegenerated bro mine to the furan ring (with a loss of aromaticity) fol lowed by methanolysis [133, 134]:

Br2

2NH3

䊞

O 2NH+ 4

2Br–

2MeOH Br

O

Br

+

–2Br–, –2NH4

MeO

OMe .

O

1Acetyl5bromoindoline (95–99% yield) (inter mediate in the synthesis of bromoindigo) was synthe sized by EB of 1acetylindoline [135, 136]. The pro cess was conducted on a Pt anode at Т = 22–25°С in 50% aqueous AcOH containing metal bromides (LiBr, NaBr, KBr, MgBr2), while keeping voltage on the cell constant (V = 3 V). The anode potential was Еа = 0.8– 0.9 V relative to s.c.e.; ja = 3–5 mA cm–2. The EB of benzofuran in aqueous AcOH solutions containing NH4Br and aqueous NaBr–CH2Cl2 het erophase system was studied in detail [137]. The pro cess was conducted in a galvanostatic mode (ja = Br

Br

Br –e

–e

O 50–80% 4

10 mA cm–2) on a Pt anode under diaphragmless elec trolysis conditions. According to the scheme pre sented below, the electrolysis of benzofuran in the AcOH–H2O system (AcOH : H2O = 100 : 1) occurred smoothly via substitution, which led to 5bromoben zofuran (Q = 2.2. F per mole of benzofuran) or 5,7 bromobenzofuran (Q = 4 F per mole of benzofuran). In contrast, electrolysis in the CH2Cl2/H2O (1 : 1) or АсОН/H2O (10 : 1) systems in the presence of NaBr (NH4Br) led to the addition product 2,3dibromo 2,3dihydrobenzofuran as the sole product:

O

Br

NaBr CH2Cl2/H2O (1/1)

2

–e

NH4Br AcOH/H2O (100/1)

O

O 1

48%

Br 3 47%

or NH4Br AcOH/H2O (10/1)

The difference in the pathways of these processes was explained by the difference in the concentrations of the Br– anion in the reaction mixture, which depend on the solubility of the salts (NaBr, NH4Br) in

.

the solvents used [137]. The NH4Br–АсОН–H2O system with a ratio of АсОН/H2O = 10 : 1 contained Br– in a high concentration; Br2 formed by oxidation of the anion effectively reacted at the C(2)=C(3) dou

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ble bond, giving addition product 4. The same is char acteristic of the NaBr–CH2Cl2–H2O system with a ratio of CH2Cl2/H2O = 1 : 1. When the process was conducted in the system with a ratio of AcOH/H2O = 100 : 1, the Br– concentration in the reaction mixture was low and small amounts of electrogenerated Br2 were quickly hydrolyzed to HOBr (or AcOBr), which, in turn, reacted with benzofuran, leading to products 1 and 3. The EB of pyrazole and its derivatives in aqueous NaBr under galvanostatic diaphragm electrolysis con ditions on a Pt anode led to the formation of the cor responding 4bromosubstituted derivatives [138]. The process occurred favorably if the pyrazole ring contained donor substituents (Me, Et); acceptor sub stituents (NO2, COOH) had no pronounced effect on the reaction. After the EB of pyrazole, 3,5dimeth ylpyrazole, 1,5dimethylpyrazole, 3nitropyrazole, pyrazole3(5)carboxylic acid, 1methylpyrazole3 carboxylic acid, 1methylpyrazole5carboxylic acid, 1ethylpyrazole3carboxylic acid, and 1meth ylpyrazole3,5dicarboxylic acid, the yield of the cor responding 4bromosubstituted derivatives was 70, 94, 88, 89, 84, 78, 84, 89, and 84%, respectively. The EI of pyrazole and its derivatives in aqueous KI under similar conditions was studied in [139]. The rate both EI and EC [89] increased when pyrazoles con tained donor substituents (Me) but decreased in the case of acceptor substituents (NO2, COOH). Iodina tion was generally slow and promoted only by base (NaHCO3) additions to the reaction mixture to bind the liberated HI. Under optimum conditions, the yields of 4iodopyrazoles were 60–90% for donor sub stituents and up to 30% for acceptor ones. It is inter esting to note that iodination was promoted when the Me group was at the carbon atom of the pyrazole ring but decelerated when the group was at the nitrogen atom. This was explained by the fact that iodination (in the presence of bases) involves the more reactive pyrazole Nanion if pyrazole does not contain substit uents at the nitrogen atom, but this is impossible in the presence of substituents [140]. Of interest are the results of [141, 142]. The gal vanostatic (j = 125 mA cm–2) diaphragmless electrol ysis of a solution of trialkylboranes R3B (R = C3H7, C6H13, C8H17) on Pt anode and cathode in MeNO2 containing Et4NI led to the formation of alkylation products (16–92% yield) involving the solvent [141]: Anode:

–2e

– –e

I3 3I– R3B + I•

I2 + I• RI + R2B•

+e–

Cathode:

H3CNO2

Solution:

RI + CH2NO2

CH2NO2 + 0.5H2 –I

RCH2NO2.

Alkylation (and hydrogenation) of ethyl acrylate under galvanostatic (j = 500 mA cm–2) diaphragmless electrolysis conditions of an acetonitrile solution con taining an ester, R3B (R = C3H7, C4H9 and C5H11), RUSSIAN JOURNAL OF ELECTROCHEMISTRY

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and Bu4NI using Pt anode and cathode was performed and gave good yields (51–86%) [142]. The scheme of the process is [142] Anode: Cathode:

–2e

I3– 3I– R3B + I• RI

+2e

–e

I2 + I • RI + R2B•

R– + I–

–

CH2=CHCO2Et

R

.

–

RCH2CHCO2Et

H+

RCH2CH2CO2Et

+e

– +e, RI

[CH2CHCO2Et]•

The anodic generation of combined Br–Cl haloge nating reagents and their excell use in the synthesis of halo derivatives were described in [143]. Reagents of this type are polybromine chloride BrxCl −y , anions, existing in solution as salts of Et4NBr3, Et4NBr2Cl, and Et4NBrCl2 type. These salts were obtained by gal vanostatic (ja = 5.0–8.0 mA cm–2) diaphragm elec trolysis (Pt anode) of a СH2Cl2 solution of a mixture of Et4NCl and Et4NBr (with Bu4NClO4 used as a sup porting electrolyte). Based on the data of [144, 145], the electrosynthesis of polybromine chloride anions is described by the scheme 2Br–

–2e

2Cl–

–2e

Br– + Br2 Cl– + Br2 2Cl– + Br2 + Cl2

Br2, Cl2, Br–3 , Br2Cl–, 2BrCl2– .

The major products were salts containing one of the aboveindicated anions (see the scheme) depend ing on the Et4NCl/Et4NBr molar ratio in the reaction mixture and the charge passed (based on the charged Br– anion). For example, at a molar ratio of Et4NCl/Et4NBr = 1, the Br3− anion formed at Q < 0.6 F per mole of Br–, Br2Cl– formed at Q ~ 1.09 F, and BrCl 2− at Q ~ 1.90 F. Thus various products from weak est (Br3−) to strongest (BrCl 2− ) brominating agents can be obtained by varying the charge passed and the Et4NCl/Et4NBr molar ratio. The solutions of the aboveindicated anions were tested in brominations of methoxybenzene and 1,2 dimethoxybenzene. The reactivity of the electrogen erated brominating reagents was evaluated from the yields of brominesubstituted arenes. In continuation of these studies, it was found that the interactions of the brominating reagents (obtained by the above described procedure) with styrene and cyclohexene led to the formation of the corresponding dibromo and bromochloro derivatives. The formation of the latter can be described by the scheme based on the data of [144, 145] No. 6

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C C + Br2Cl– BrCl2–

C C + Br Br

–Br–(Cl–)

C C Cl Br

Cl– + BrCl

– C C + BrCl2

C

Cl–

C Br δ+ Cl δ–

The selectivity of the process (dibromo/bromo chloro derivative molar ratio) can readily be controlled by varying the Et4NCl/Et4NBr molar ratio and the charge passed [143]. IV. FACTORS GOVERNING THE ELECTROHALOGENATION An analysis of the data considered in the previous sections reveals the factors governing the electrochem ical halogenation. 1. Solvent The electrochemical halogenation of organic sub stances is generally performed in aqueous solutions of alkali or alkali earth halides, HCl, or HBr. To improve the solubility of the organic substance, a solvent (e.g., AcOH [37, 137] or MeCN [96, 146]) is added to the aqueous electrolyte, or nonaqueous solvents (e.g., MeCN [27–29], DMF [22, 99], MeOH [26, 107], EtOH [56], DMSO [23], CH2Cl2 [109, 143], etc.) are used with lithium, sodium, ammonium, or tetraalky lammonium halide supporting electrolytes. Heterophase mixtures of an aqueous electrolyte with an inert component (CCl4, CHCl3, CH2Cl2, etc., in which the product is readily soluble) are widely employed to prevent further transformations of the desired products [30, 48, 55, 111–113]. The solvent occasionally interacts with the inter mediates of electrochemical halogenation (see, e.g., [22–26, 96–99]), thus participating in the formation of the end product, which is most typical for halogena tion of unsaturated compounds. Lewis acids are often added to the supporting elec trolyte to increase the process efficiency; they polarize the Hal2 molecule and enhance its electrophilic prop erties (Section II). For example, FeCl3 (2–3%) addi tions to the electrolyte increase the yield and purity (99.5% main substance) of dichloroethane during the electrochlorination of ethylene and promote [15] the process due to an increase in the current density (to 1100 mA cm–2). 2. Anode Material The choice of anode material depends on the nature of the starting and end products and halogenat ing agent. The anode materials generally include Pt,

C C + Cl– . Cl Br

graphite, magnetite, glassy carbon, RTOA (e.g., [10, 11]), etc. Platinum and graphite are most widely used for anodes, platinum being preferable because of lower overvoltage and good catalytic properties. To reduce the consumption of Pt during anode prepara tion, a platinum–titanium anode (PTA) is obtained by plating or welding Pt foil onto a Ti support [10]. In the former case, there is a danger of breakdown of the Ti support at the electrode–gas interface. The break down stability of PTA can be improved by applying a thin layer of Ru oxides to the Ti support before platini zation [10]. When preparing PTAs for use in halogena tion of organic compounds, it is recommended to use thick Pt coatings because the organic substances can promote the erosion of the Ti support while penetrat ing into the pores of the coating [10]. A Pt–Ir alloy is recommended; the (Pt + 40% Ir) alloy has higher (than Pt) corrosion resistance under the stringent con ditions of the preparation of persulfates and perchlor ates [147]. However, occasionally graphite is preferable to Pt. The yields of mono and polychlorinesubstituted cyclohexanes were 42.2 and 8.5% on Pt anode and 54.4 and 10.9% on graphite anode at 58.8 and 68% conversion of the starting compound, respectively [10]. The use of graphite chemically modified with αcyclodextrin is justified (Section I) when selectively chlorinating arenes at the paraposition [38–42]. Though RTOAs are widely used in electrohalogena tion, the presence of organic substances in solution can increase the wear of anodes. The peculiarities of the process should therefore be taken into account when using these electrodes [10]. PbO2 anodes were successfully used in the EC of hexene and styrene [18]. The catalytic properties of modified graphite anodes with high (up to 70%) porosity and high (up to 140 m2 g–1) specific surface areas were occasionally used [148]. The pores were filled with a noble metal (e.g., Pt) salt solution and the anode was heated in a hydrogen atmosphere to reduce the salt to the metal [3]. Hollow anodes were prepared from porous graph ite mass; the substance (generally hydrocarbon) to be chlorinated was fed to the electrolyzer through the anode pores [3]. A porous hydrophobicallymodified electrode with a welldeveloped surface proved highly effective in the EC of paraffins (nbutane, npentane, and nhexane); this was a fused mixture of finely dis perse graphite and waterproofing agent (ftoroplast 4D) particles deposited on a Ti gauze current lead. The

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substance to be chlorinated was fed to the electrolyzer through the anode pores [149]. 3. Current Density EC can be promoted by conducting it at high cur rent densities. The rate of the proper chlorination stage can be low. To avoid the evolution of Cl2 into the atmosphere, it is necessary to take into account the amounts of Cl2 generated and consumed in the chem ical reaction. For these reasons, the anode current density is related to the nature of the starting sub stances and generally varies from 100 to 600 mA cm–2. The process can be conducted at high current densities (400–600 mA cm–2) if the rate of the reaction of Cl2 with the substrate is increased. For this purpose, Lewis acids or radical reaction initiators (benzoyl peroxide or azobisisobutyronitrile) are added to the reaction mixture [14] or the reaction zone is irradiated with a strong source of visible light for generating Cl• radicals [150]. For example, light illumination that initiated a radical process allowed the selective chlorination of toluene and diphenylmethane into the side chain [150]. It should be emphasized, however, that varying the current density can change the halogenation mechanism and hence the composition of the prod ucts (see, e.g., [22]). EB and EI are generally performed at lower anode current densities (10–100 mA cm–2 for EB and 3.1– 7.5 mA cm–2 for EI) than EC because of the lowering of reactivity in the series Cl > Br > I and, as a conse quence, accumulation of considerable amounts of unchanged halogens in the reaction medium. How ever, Br2 and I2 have much lower volatility than Cl2 and it is recommended to allow the reaction mixture to stay after electrolysis for the electrogenerated halogen to react with the substrate. For example, storage of the reaction mixture for ~20 h after electrolysis during the EB of benzene in 48% aqueous HBr led to an enor mous (from 11 to 83%) increase in the yield of bro mobenzene [102]. Storage at elevated temperatures is recommended.

5. Electrolysis in Divided and Undivided Cells; Anode Potential; Charge Passed Let us consider another three factors governing the route of electrohalogenation. Halogen derivatives are usually obtained under diaphragm electrolysis condi tions. The use of an undivided cell, however, some times changes the reaction route. For example, the EC of arylsulfamides under diaphragm electrolysis condi tions led to the formation of N,Ndichloramides [75, 76], while the diaphragmless process gave monochloro derivatives [80, 81]. The EB of acid amides in the presence of alcohols under diaphragm less electrolysis conditions led to carbaminic acid ethers [129, 130]; i.e., the reaction was more profound than diaphragm electrolysis, which formed only Nbromamides. Variation of the charge passed allows selective preparation of mono and dihalo derivatives of organic compounds (e.g., in the EC of phenylolefins [30], iso prene [31], and benzene [43] and in the EB of thymol [107]). Variation of the electrode potential can change the route of halogenation (e.g., 1,2dichlorocyclohexane formed in the EC of cyclohexene at low electrolysis potentials, while 3chlorocyclohexene formed at high potentials [22]) and obtain agents with different haloge nating properties (e.g., at low potentials, the oxidation of I– in nonaqueous (MeOH and MeCN) media led to I2, while at higher potentials I2 can transform into a more reactive complex containing I+ [33, 108, 109]). V. ELECTROCHEMICAL HALOGENATION AS SUBSTITUTION OF THE HYDROGEN ATOM IN THE ORGANIC SUBSTRATE: MAIN TENDENCIES The above treatment of electrochemical halogena tions did not accentuate that their result (except the halogenation of unsaturated compounds) was the replacement of the hydrogen atom in the organic sub strate. From this viewpoint, electrochemical haloge nation can be regarded as electroinduced nucleophilic substitution of the hydrogen atom by the halide ion: 2Hal–

4. Temperature The rate of electrochemical halogenation generally increases with temperature, but each type of com pound has its optimum mode. Electrolysis is often performed at Т = 20–40°С. Elevated temperatures (80–100°С) are used for EC of saturated hydrocar bons [3] and preparation of CHCl3 by chorination of EtOH [51, 52]. Lower temperatures (5–10°С) are used for EC and EB of amines, amides, and imides [75–82] to prevent or retard undesirable side reac tions. RUSSIAN JOURNAL OF ELECTROCHEMISTRY

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–2e

Hal2 + RH

–HalH

RHal.

Here, the electrochemical inversion of the polarity (umpolung) of the starting Hal– leads to the product of hydrogen substitution by Hal at subsequent stages. The electrochemical halogenation is thus a variety of SHN reactions [151, 152] called SHN (An) reactions (An is the anode) [153]. The I–, Br–, and Cl– anions are oxidized at anode potentials (0.5–1.2 V relative to s.c.e.) much lower than the oxidation potentials of the majority of aro matic and especially olefin systems and hydrocarbons. The main types of interaction during electrochemical halogenation can be described by a scheme similar to No. 6

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LYALIN, PETROSYAN

the one given [153] for the case when the nucleophile is oxidized more readily than the organic substrate: RH

– –e

Hal RH

–e

Hal• RH

×2

HalH + R•; Hal• + R•

RHal 1

RH –HalH

Hal2

interest, however, are reactions involving radical cat ion intermediates. Thus the Cl– anion is absent at the electrode sur face during EC, but it is present in the nearelectrode layer of the solution, to which the relatively stable RH+• radical cation can migrate during desorption. The interaction of these species by route 2.3.a is another mechanism of the formation of RCl realized, e.g., during the EC of 1,4dimethoxy2tertbutylben zene [44] or naphthalene [48]. Route 2.3.b is realized during the interaction of radical (Сl•) and radical cation (RH+•) species. This reaction was considered in detail in [44]. A similar mechanism called EECPCR was studied in the case of methoxylation of naphthalenes [154]; it was noted that it was difficult to choose between routes 2.3.a and 2.3.b. The possibility of RH+• interaction with nucleophilic or radical species was analyzed in detail in [155]. Finally, the RH+• radical cation can act as an oxi dant (this process is not reflected in the scheme above) if the RH/RH+• stage is reversible and close to the Cl ⎯ /Сl•/Cl2 stage in its potential [44]. Also note that the redox mechanism, which involves stable RH+• and is based on the ability of the radical adduct (route 2.3.a) to reduce the starting RH+•, was called the halfregeneration mechanism and was discussed in detail in monograph [9]. A number of factors play an important role in these reactions: the nature, struc ture, and adsorption properties of the RH substrate; the potential and reversibility of its oxidation; the nature of the solvent, etc. It follows from the above treatment that the Сl– anion, the Сl• radical, and the Сl2 molecule can act as chlorinating agents during EC, but the choice between them is not always evident from a description of the reaction mechanism. Moreover, even description of the mechanism of Сl– discharge at the stage preceding halogenation is still difficult [11, 44]. The aboveconsidered tendencies are mainly inherent in EC of aromatic systems, while the EC of unsaturated hydrocarbons has its own peculiarities. Like chemical chlorination, this process generally occurs by the mechanism of the electrophilic addition of chlorine via the formation of a chloronium com plex, and the reaction is accelerated in the presence of Lewis acids:

RHal 2 .

• +

RHal 3

–H+

Two main types of reaction that occur during elec trohalogenation are distinguished. Reactions of the first type occur at the oxidation potential of the halide ion and form halogen, which further interacts with the organic substance (this type is similar to chemical halogenation); reactions of the second type occur at the oxidation potential of the organic substrate and form positive species (radical cations or cations), which further interact with Наl• or Наl–. Data on the EC of organic compounds were cov ered most comprehensively in the literature; therefore, it is most convenient to discuss the main tendencies of electrohalogenation on these processes. Thus EC at the oxidation potentials of the chloride ion, for exam ple, the EC of saturated hydrocarbons inactivated to the electrophilic attack occurs by route 1 involving the Сl• radical [3]. The EC under these conditions is mostly described by route 2 (see the scheme above), by which the reaction occurs readily when the electro philic properties of Сl2 are enhanced by Lewis acid addition or when the organic substrate (RH) is acti vated with respect to the electrophilic attack. The mechanism of the process is more complex when it occurs by both routes 2 and 3 (see again the scheme above), i.e., during the cooxidation of Сl– and RH. Possible interactions in this case are presented in detail below: 2 Cl–

–e

2.3.a

RCl

+

–H+

RHCl

Cl•

1/2Cl2

2.3.b

+

–e •

RHCl

RHCl

3 RH

–e

–H+

RCl .

•

RH+

Here, the desired RCl product can form by several routes at once. One of these is route 1 (if RH is suffi ciently activated to the electrophilic attack). Of greater +δ –δ

Cl2 + FeCl3

Cl–Cl

FeCl3

Cl–

C

H2O

–2e

2Cl–

C C FeCl4–

C +

Cl ROH

C C Cl Cl C C Cl OH C C . Cl OR

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realized at Cl– discharge potentials. The same process per formed at olefin oxidation potentials, however, follows a different mechanism. For example, the allyl chlorination of cyclohexene at its oxidation potentials in MeCN con taining LiCl proceeds by route (a) [22]:

In addition, the EC of olefins in aqueous or alcoholic media, like the chemical chlorination of these substances, is accompanied by the addition of not only Cl– anions, but also fragments of water, forming chlorohydrins or alcohol, leading to chloroethers. Scheme below describes the EC

(a)

523

Cl +

–2e –H+

(b)

Cl– MeCN

+Cl2

Cl

Cl H2O

+ Cl CH3CN

.

+

N C CH3

At Cl2 isolation potentials, however, this process (MeCN, Et4NCl) follows route (b), leading to the chloroacetamidation product [22, 23]. The mechanism of EB and EI was not studied in detail in the cited references. An analysis of the litera ture data, however, suggests that these processes (espe cially iodination) mostly follow the mechanism that involves halogen electrogeneration and its subsequent chemical reaction with the organic substrate (route 2, the first scheme at the page 522). The reactions involv ing unsaturated compounds and leading to bromo [25, 98] and iodo [99] olefins led to the products of interaction with the solvent (as in EC, see above). At the same time, several examples of EB occurring via the oxidation of the substrate, forming a radical cat ion (carbenium ion), are known [156, 157]. A similar mechanism was considered in a study that dealt with the EB of anthracene and naphthalene in MeCN [114]. Of interest are the data of [105] according to which the EB of anisole in MeCN occurs by the scheme +

2Br– –2e

Br2 δ–

OMe

δ+

Br Br –e, –0.5Br2

H Br

OMe

H

1

+

OMe

–H+

Br

OMe.

2

The suggested reaction mechanism involves the stages of electrogeneration of Br2, its interaction with RUSSIAN JOURNAL OF ELECTROCHEMISTRY

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anisole to form complex a, and the oxidation of the latter to σ+ complex 2. The latter is stabilized, elimi nating a proton and leading to the desired product. This mechanism is based on voltammetry data: the addition of anisole to a solution containing the bro mide anion leads to the appearance of the oxidation wave of complex 1 at anode potentials higher than the Br2 generation potential but lower than the anisole oxidation potential. Importantly, electrolysis at poten tials of this wave (actually the oxidation wave of the πcomplex) leads to the formation of the desired prod uct, while the increase in the electrolysis potential to the oxidation wave of anisole is accompanied by a complete passivation of the anode. Though the rea soning given in [103] is quite convincing, the very fact of voltammetric fixation of the πcomplex is doubtful. Anyhow, these interesting results stimulate further studies especially because the data of [105] have a cer tain analogy to the data on the EB of benzene, tolu ene, paraxylene, and naphthalene in AcOH [103, 104]. Two publications played an important role in the development of the concept about the mechanism of iodination of aromatic systems [108, 158]. Analyzing the results of the electrolysis of solutions containing arene (benzene, toluene, paraxylene, and triphenyl methane) and I2 in MeCN, the authors concluded that EI occurred via the generation of the derivatives of positive iodine formed in the electroiodination of I2 because iodine atoms or molecules cannot be active halogenating agents. The iodoacetonitrilium cation 1 or (in acid media) Niodoacetamide 2 were consid ered to be active iodinating species formed by the scheme [108] No. 6

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LYALIN, PETROSYAN I2 + CH3CN

–2e

+

CH3 C NI 1

+

CH3 C NI + H2O

–H+

+

CH3

H+

I2

2I+

nI2

O C NH2 .

ArI + CH3

The nI2 ⋅ I+ complex formed by reactions –2e

O CH3 C NHI 2

ArI + CH3CN + H+

CH3 C NI + ArH O C NHI + ArI

OH CH3 C NI

zole molecule, leading, via the stage of the formation of the σ+ adduct, to the intermediate Nhalo derivative. The efficiency of halogenation of pyrazoles is deter mined by the rate of the intramolecular N–C rear rangement of halogen into the 4halo derivative. The low rate of this rearrangement in the EC of pyrazoles 1 led to the accumulation of 1,4dichloropyrazole and its interaction with 4chloropyrazole, forming bipyrazole, which lowered the yield of the desired 4chloropyra zole. The EB of pyrazoles 2 occurred more effectively due to the high rate of the N–C rearrangement [138]. The same was characteristic of the iodination of pyra zoles 3 , but the process efficiency decreased because of the low rate of σH+ adduct formation [88–92, 138, 139].

nI2 ⋅ I+

was also considered to be an iodinating agent [108, 158]. The mechanism of iodination was later refined in studies performed by the competitive reactions method [159]. The participation of nI2 ⋅ I+ complexes in EI was denied, while the participation of Niodoac etonitrilium cation 1 (Niodoacetamide 2 under pro longed exposure) was confirmed. The mechanism of electrochemical halogenation of pyrazoles is rather specific. According to the scheme depicted below, the halogen generated by electrooxida tion of the halide ion interacts reversibly with the pyra

Cl

Cl

Cl

Cl

Cl2

N

N Cl

slow

N

1

N

N H

N H N N

2Hal– –2e

N

Hal2

Cl N – N Hal Hal H + σ adduct

(I2, slow)

3

I

+

N H

N I

N H

N N

Cl

N

Cl

N

Cl N H

2

–HBr(I)

Br

Br

I I2

N

N

–HCl

–HCl

+

slow

N Cl

Br

Br

Br2

N

quick

N H

N

quick

N Br(I)

N

The EC and EB of acetanilide [79, 124] and EI of aromatic amines [123, 125] were considered to follow a similar mechanism. Finally, we consider electrochemical processes involving Cl–, Br–, and I– anions, in which these anions are used as mediators that form haloorganic

N H

N

quick

N Br

N

N H

.

compounds at intermediate stages. These reactions have recently been developed and led to the synthesis of a wide range of valuable products, demonstrating the possibility of performing multicomponent (including cascade) processes in the synthesis of com plex organic systems [160].

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525

An example is the multicomponent electrosynthesis of cyclopropane 1 using Br– and I– salts as mediators [161]:

R

R

CH C(CN)2

CH O + CH2(CN)2 R

R

NC NC

–Hal–

–

NC CO2Me; MeO CO2Me MeO

1

C(Hal)(CO2Me)2 CH(Hal)(CO2Me)2

CO2Me N H 2

O

Hal = Br, I 䊞

MeO–

–

CH(CO2Me)2

⊕

1/2Hal2

+e, –1/2H2

–e

MeOH

.

–

Hal

CH2(CO2Me)2

scheme at the page 522) and leads to the product of hydrogen substitution by Hal. A similar principle underlies the chain processes that form cyclopropanes 3 [163], 4 [164], and cyclobutane 5 [165]:

Under conditions of more prolonged electrolysis, product 1 is converted into bicyclic product 2 [162]. One of the key stages of this process is the SHN (Аn) reaction, which occurs by mechanism 2 (the first

CN

CO2Me CO2Me CO2Me CO2Me(CN)

electrolysis

CO2Me

NaI, MeCN

MeO2C electrolysis LiCl, MeOH

MeO2C (NC)MeO 2C

R R

CO2Me CO2Me

electrolysis NaBr, MeOH

R 5

Details of these reactions are found in reviews [160, 166, 167]. ACKNOWLEDGMENTS This work was financially supported by the Russian Foundation for Basic Research (project no. 1203 00517a) and the Department Branch of Chemistry and Materials Sciences, Russian Academy of Sciences (fundamental research program no. 01). REFERENCES 1. Promyshlennye khlororganicheskie produkty: Spravoch nik (Industrial Chloroorganic Products: Handbook), Oshin, L.A., Ed., Moscow: Khimiya, 1978. 2. Tedoradze, G.A., Paprotskaya, V.A., and Tomilov, A.P., Abstracts of Papers, Novosti elektrokhimii organ icheskikh soedinenii. VIII Vsesoyuz. soveshch. po elek RUSSIAN JOURNAL OF ELECTROCHEMISTRY

CO2Me 3

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4

CO2Me(CN) CO2Me

CO2Me CO2Me CO2Me . CO2Me

trokhimii organicheskikh soedinenii (Organic Electro chemistry News. 8th AllUnion Conf. on Organic Electrochemistry), Riga: Zinante, 1973, p. 196. 3. Tomilov, A.P., Fioshin, M.Ya., and Smirnov, V.A., Ele ktrokhimicheskii sintez organicheskikh veshchestv (Elec trochemical Synthesis of Organic Substances), Lenin grad: Khimiya, 1976. 4. Khusainova, R.M., Dorozhkin, V.P., Shiypov, R.T., Khairallin, R.V., and Maksimov, D.A., RF Patent 2217440, Chem. Abstr., 2004, vol. 141, p. 72799. 5. Tomilov, A.P., Usp. Khim., 1961, vol. 30, no. 12, p. 1462. 6. Organic Electrochemistry, Lund, H. and Hammerich, O., Eds., New York: Marcel Dekker, 2001, 1393 p. 7. Shono, T., Electroorganic Chemistry as a New Tool in Organic Synthesis, Berlin: SpringerVerlag, 1984. 8. Torii, S., Electroorganic syntheses. Method and applica tion, part 1, Tokyo: Kodansha VCH. No. 6

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