catalysts Article
YCl3-Catalyzed Highly Selective Ring Opening of Epoxides by Amines at Room Temperature and under Solvent-Free Conditions Wuttichai Natongchai 1 , Rais Ahmad Khan 2 , Ali Alsalme 2 and Rafik Rajjak Shaikh 1, * 1 2
*
ID
School of Molecular Science and Engineering, Vidyasirimedhi Institute of Science and Technology (VISTEC), 555 Moo 1, Payupnai, Wangchan, Rayong 21210, Thailand;
[email protected] Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia;
[email protected] (R.A.K.);
[email protected] (A.A.) Correspondence:
[email protected]; Tel.: +66-33-014-164
Received: 16 October 2017; Accepted: 6 November 2017; Published: 10 November 2017
Abstract: A simple, efficient, and environmentally benign approach for the synthesis of β-amino alcohols is herein described. YCl3 efficiently carried out the ring opening of epoxides by amines to produce β-amino alcohols under solvent-free conditions at room temperature. This catalytic approach is very effective, with several aromatic and aliphatic oxiranes and amines. A mere 1 mol % concentration of YCl3 is enough to deliver β-amino alcohols in good to excellent yields with high regioselectivity. Keywords: epoxides; β-amino alcohols; rare-earth metal catalysis; green chemistry
1. Introduction The β-amino alcohols are categorized as very useful chemical compounds due to their presence in numerous natural products, medicinally important molecules and ligands or chiral auxiliaries [1–3]. Other applications of these versatile compounds include their use as intermediates/precursors in the synthesis of cosmetics and daily-use products such as perfumes, hair dyes, and photo developers [4]. Moreover, β-amino alcohols are very useful precursors towards structurally complex and intriguing chemical compounds such as (multi-)cyclic organic compounds which can be obtained through rather facile chemical transformations or through synthesizing metalloorganic compounds via complexation with a metal center [5,6]. The simplest approach to the β-amino alcohols is the ring opening of epoxides with amines (Scheme 1) [7]. This approach is usually met with some limitations such as kinetically slow reactions that may be due to inefficient activation of epoxides and low regioselectivity. To overcome these issues, many new catalytic methods have been introduced using various catalysts, with aims to enhance the electrophilicity of epoxides through metallic coordination or H-bonding [8–26]. The N-alkylation of amines using cyclic carbonates is also an attractive approach to molecules under discussion [27,28]. Many methods for the synthesis of β-amino alcohols from epoxides or cyclic carbonates require a high reaction temperature, dry reaction conditions, and high catalyst loadings. The preparation of β-amino alcohols under solvent-free conditions and at room temperature is desirable and important due to environmental considerations.
Catalysts 2017, 7, 340; doi:10.3390/catal7110340
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Scheme 1. Aminolysis of epoxides for the synthesis of β‐amino alcohols. Scheme 1. Aminolysis of epoxides for the synthesis of β-amino alcohols. Rare-earth metals including lanthanides, scandium, and yttrium are being increasingly exploited Rare‐earth metals including lanthanides, scandium, and yttrium are being increasingly in organic synthesis because of their unique reactivity and selectivity [29–37]. Rare-earth metals exploited in organic synthesis because of their unique reactivity and selectivity [29–37]. Rare‐earth tend to tend be oxyphilic, in general, exhibit a exhibit highly Lewis-acidic character. character. One workOne involving metals to be oxyphilic, in and general, and a highly Lewis‐acidic work rare-earth acid catalysts suchcatalysts as YCl3 demonstrated highly efficient strategy catalytic towards involving Lewis rare‐earth Lewis acid such as YCl33 ademonstrated a catalytic highly efficient the synthesis of cyclic activation [38]. we envisaged theSimilarly, Lewis-acidic strategy towards the carbonates synthesis via of epoxide cyclic carbonates via Similarly, epoxide activation [38]. we activation of epoxide by Sc- and Y-based catalysts, thus making epoxide susceptible to nucleophilic envisaged the Lewis‐acidic activation of epoxide by Sc‐ and Y‐based catalysts, thus making epoxide attack by amines to produce β-amino alcohols (Scheme 2). susceptible to nucleophilic attack by amines to produce β‐amino alcohols (Scheme 2).
Scheme 2. Lewis-acidic activation of epoxide by YCl3 . 33. Scheme 2. Lewis‐acidic activation of epoxide by YCl
In this work, we report a simple, efficient, and environmentally friendly method using a rare-earth In this work, we report a simple, efficient, and environmentally friendly method using a rare‐ metal-based catalyst, YCl3 , for33, for the ring opening of a library of epoxides by various amines under the ring opening of a library of epoxides by various amines under earth metal‐based catalyst, YCl solvent-free conditions at room temperature. To the best of our knowledge, the ring-opening reaction solvent‐free conditions at room temperature. To the best of our knowledge, the ring‐opening reaction of epoxide with amines catalyzed by YCl333 has not been reported before. has not been reported before. of epoxide with amines catalyzed by YCl 2. Results and Discussion 2. Results and Discussion Initially, we screened the ring-opening reaction of styrene oxide (1a) as the model substrate with Initially, we screened the ring‐opening reaction of styrene oxide (1a) as the model substrate with aniline (2a) as the model nucleophile at room temperature. The conversion and regioselectivity were aniline (2a) as the model nucleophile at room temperature. The conversion and regioselectivity were calculated based on 111H‐NMR of crude reaction mixture, and the results are summarized in Table 1. H-NMR of crude reaction mixture, and the results are summarized in Table 1. calculated based on In the absence of a catalyst, In the the In the absence of a catalyst, only only traces traces of of corresponding corresponding β-amino β‐amino alcohol alcohol were were observed. observed. In presence of 1 mol % YCl as a catalyst, we were delighted to see a more than 90% conversion of presence of 1 mol % YCl333 as a catalyst, we were delighted to see a more than 90% conversion of 1a, 1a, producing both possible regioisomers, 3aa and 4aa (Table 1, entry 2). The result indicates that producing both possible regioisomers, 3aa and 4aa (Table 1, entry 2). The result indicates that the the reaction proceeded smoothly with high regioselectivity (3aa:4aa, 93:7). After 3 h of reaction, reaction proceeded smoothly with high regioselectivity (3aa:4aa, 93:7). After 3 h of reaction, 1 mol % 1loading of YCl mol % loading of YCl3 gave a 100% conversion of 1a under solvent-free conditions (Table 1, entry 6). 33 gave a 100% conversion of 1a under solvent‐free conditions (Table 1, entry 6). Under Under identical reaction conditions, ScCl333 gave an 82% conversion of 1a with 92% regioselectivity gave an 82% conversion of 1a with 92% regioselectivity identical reaction conditions, ScCl towards 3a (Table 1, entry 3). towards 3a (Table 1, entry 3). We tried a higher catalyst loading (5 mol %) for both YCl333 and ScCl and ScCl333 and found no noticeable and found no noticeable We tried a higher catalyst loading (5 mol %) for both YCl effect on regioselectivity of the reaction; however, an increase in rate of substrate conversion was noted effect on regioselectivity of the reaction; however, an increase in rate of substrate conversion was (Table 1, entries 4 and 5). Adding the solvent to the reaction had a negative effect on the catalytic noted (Table 1, entries 4 and 5). Adding the solvent to the reaction had a negative effect on the activity of Lewis acids. When CHCl3 was used as the reaction solvent with 1 mol % YCl3 and at room catalytic activity of Lewis acids. When CHCl 33 was used as the reaction solvent with 1 mol % YCl 33 and temperature, only a 50% conversion of 1a was noted after a 1 h reaction time (Table 1, entry 7), and it at room temperature, only a 50% conversion of 1a was noted after a 1 h reaction time (Table 1, entry took more than 12 h to achieve full conversion of the epoxide under these conditions. It is worth noting 7), and it took more than 12 h to achieve full conversion of the epoxide under these conditions. It is that, when 5 mol % YCl3 was used with and without the solvent (CHCl3 ), the aminolysis of 1a was worth noting that, when 5 mol % YCl 33 was used with and without the solvent (CHCl 33), the aminolysis slightly slower in the presence of a solvent, further confirming that the highest efficiency of YCl3 can of 1a was slightly slower in the presence of a solvent, further confirming that the highest efficiency be achieved under solvent-free conditions (Table 1, entry 8). Full conversion of 1a was noticed after 2 h of YCl 33 can be achieved under solvent‐free conditions (Table 1, entry 8). Full conversion of 1a was using 5 mol % YCl3 in CHCl3 , while33 in CHCl under a 33solvent-free condition, 100% conversion was noted after , while under a solvent‐free condition, 100% conversion noticed after 2 h using 5 mol % YCl
was noted after 1 h. Similarly, a 5 mol % loading of ScCl33 also gave a lower conversion of 1a (88%) in
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1 h. Similarly, a 5 mol % loading of ScCl3 also gave a lower conversion of 1a (88%) in the presence of the presence of CHCl 3 (Table 1, entry 9) compared to solvent‐free conditions (100%) (Table 1, entry CHCl5). (Table 1, entry 9) compared to solvent-free conditions (100%) (Table 1, entry 5). 3 Table 1. Optimization studies for the aminolysis of styrene oxide (1a). Table 1. Optimization studies for the aminolysis of styrene oxide (1a).
Sr. No. 1Sr. No. 2 3 4a 5b 6c 7d 8e 9f 10 11 12 13
Catalyst Catalyst None
Conversion (%) Conversion NR (%) 90 NR 82 90 100 82 100 100 100 100 50 100 87 50 88 87 82 75 88 traces 82 85 75 traces e
3aa:4aa Ratio (%) 3aa:4aa Ratio (%) ‐ 93:7 92:8 93:7 93:7 92:8 92:8 93:7 93:7 92:8 94:6 93:7 94:6 94:6 93:7 94:6 87:13 87:13 93:7 87:13 nd 82:18 87:13
YClNone 3 1 ScCl 3 3 2 YCl YCl3 3 ScCl3 ScCl3 4 a YCl3 YCl3 5 b ScCl YCl3 3 6 c 3 YClYCl 3 7 d 3 ScClYCl 3 8 e YCl NbCl 5 3 ZrCl ScCl 9 f 4 3 ZnCl 2 5 10 NbCl Nb(OEt) 5 4 11 ZrCl 12 ZnCl a 5 mol % YCl ; b 5 mol % ScCl ; c 3 h; d CHCl as2 reaction solvent; 5 mol % YCl andnd CHCl3 as reaction solvent; 3 3 3 3 f 5 mol % ScCl and CHCl13 Nb(OEt) 5 No Reaction; 85 82:18 NR = nd = not determined. 3 3 as reaction solvent. a 5 mol % YCl3; b 5 mol % ScCl3; c 3 h; d CHCl3 as reaction solvent; e 5 mol % YCl3 and CHCl3 f 5 mol % ScCl We also compared the catalytic activity of four 3transition metal-based Lewis acid catalysts NbCl5 , as reaction solvent; 3 and CHCl as reaction solvent. NR = No Reaction; nd = not determined. ZrCl4 , ZnCl 2 , and Nb(OEt)5 (Table 1, entries 10–13). When used under solvent-free conditions at
room temperature, 1 mol % NbCl5 , Nb(OEt)5 , and ZrCl4 gave conversions of 82%, 85%, and 75%, We after also compared the catalytic activity of four transition metal‐based Lewis acid catalysts respectively, a 1 h reaction time with a decrease in regioselectivity when compared to tested NbCl5, ZrCl4, ZnCl2, and Nb(OEt)5 (Table 1, entries 10–13). When used under solvent‐free conditions rare-earth based catalysts. The change in counter anion in the case of Nb(OEt)5 did not result in at room temperature, 1 mol % NbCl5, Nb(OEt)5, and ZrCl4 gave conversions of 82%, 85%, and 75%, any considerable change or enhancement in catalytic activity towards aminolysis. Moreover, to our respectively, after a 1 h reaction time with a decrease in regioselectivity when compared to tested surprise, ZnCl2 gave almost no conversion under identical reaction conditions, even when reaction rare‐earth based catalysts. The change in counter anion in the case of Nb(OEt) 5 did not result in any time was prolonged to 5 h. Figure 1 shows the proton nuclear magnetic resonance (1 H-NMR) spectra considerable change or enhancement in catalytic activity towards aminolysis. Moreover, to our for the aminolysis2 gave almost no conversion under identical reaction conditions, even when reaction reaction of 1a with 2a for all tested catalysts under identical reaction conditions. surprise, ZnCl 1H‐NMR) spectra time was prolonged to 5 h. Figure 1 shows the proton nuclear magnetic resonance ( Comparatively, YCl3 as a catalyst seemed to be the best choice amongst the tested series of catalysts for the aminolysis reaction of 1a with 2a for all tested catalysts under identical reaction conditions. considering the higher conversion of epoxide and higher regioselectivity (Figure 1 and Table 1). Comparatively, YCl3 as a catalyst seemed to be the best choice amongst the tested series of catalysts considering the higher conversion of epoxide and higher regioselectivity (Figure 1 and Table 1).
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1H‐NMR spectra of crude mixtures of regioselective ring‐opening Figure 1. Comparative analysis of Figure 1. Comparative analysis of 1 H-NMR spectra of crude mixtures of regioselective ring-opening
reaction of styrene oxide (1a) with aniline (2a) using different metal catalysts to give (3aa) and (4aa). reaction of styrene oxide (1a) with aniline (2a) using different metal catalysts to give (3aa) and (4aa). The regioisomer (3aa) forms predominantly, as can be observed from spectra. The letters a, b, c, and The regioisomer (3aa) forms predominantly, as can be observed from spectra. The letters a, b, c, and d d indicate the peaks or peak region corresponding to protons on carbons indicated by a, b, c and d in indicate the peaks or peak region corresponding to protons on carbons indicated by a, b, c and d in chemical structures of 3aa and 4aa. Reaction conditions: 1a (1 equiv.), 2a (1 equiv.), catalyst (1 mol %), chemical structures of 3aa and 4aa. Reaction conditions: 1a (1 equiv.), 2a (1 equiv.), catalyst (1 mol %), RT, 1 h. RT, 1 h.
The most convenient and economically friendly reaction conditions—1 mol % YCl3 3, , no solvent, no solvent, The most convenient and economically friendly reaction conditions—1 mol % YCl and room temperature—were then applied to overnight reactions of structurally diverse epoxides and room temperature—were then applied to overnight reactions of structurally diverse epoxides and various amines as nucleophiles. The results are summarized in Table 2. The results showed that and various amines as nucleophiles. The results are summarized in Table 2. The results showed that the aminolysis of 1a proceeds efficiently with aromatic amines such as aniline (2a), 3-methoxyaniline the aminolysis of 1a proceeds efficiently with aromatic amines such as aniline (2a), 3‐methoxyaniline (2b), (2b), and and 4-chloroaniline 4‐chloroaniline (2c) (2c) (Table (Table 2,2, entries entries 1–3), 1–3), giving giving aa 100% 100% conversion conversion ofof 1a 1a with with excellent excellent regioselectivity, while thethe presence presence of aof a strong electron-withdrawing nitronitro group in 4-nitroaniline (2d) regioselectivity, while strong electron‐withdrawing group in 4‐nitroaniline showed a negating effect on the reaction, giving only a 13% conversion of 1a in an almost equimolar (2d) showed a negating effect on the reaction, giving only a 13% conversion of 1a in an almost mixture of 3ad and 4ad regioisomers (Table 2, entry 4). equimolar mixture of 3ad and 4ad regioisomers (Table 2, entry 4).
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Table 2. Ring‐opening of epoxides with amines catalyzed by YCl Table 2. Ring‐opening of epoxides with amines catalyzed by YCl Table 2. Ring‐opening of epoxides with amines catalyzed by YCl Table 2. Ring-opening of epoxides with amines catalyzed by YCl3.3.3.3.3.3.3. . 3. Table 2. Ring‐opening of epoxides with amines catalyzed by YCl Table 2. Ring‐opening of epoxides with amines catalyzed by YCl Table 2. Ring‐opening of epoxides with amines catalyzed by YCl
O
R11111 R R R R1 R R R11
1
Table 2. Ring‐opening of epoxides with amines catalyzed by YCl Table 2. Ring‐opening of epoxides with amines catalyzed by YCl3.3. R333333 R R44444 4 R R OH R R44444 4 R OH R R33NN R R R R R O O OH OH R R R OH R OH R R R44 N 4 3 YCl (1mol%) 4 3 O YCl (1mol%) N N N O 3 O 3 OH R OH R44 R R R R 4 3 + YCl (1mol%) NN OH O 3 333 44 N YCl (1mol%) N YCl YCl (1mol%) O +22 ++ R R ++R4R 33333 (1mol%) OH 1 1 3 44N R R R YCl (1mol%) R N N 3 YCl (1mol%) + + 1 1 OH N 1 33 N 3 R11 1 NN R RN R RR N R222 ++ RR R OH OH 33 R111 1 R R R OH++++ +R N NN H H R R R OH 11R 33 R3 R OH R N R RT, solvent-free N RT, solvent-free solvent-free R 11 H + R R2R 2 R R 2 R R R R H H R22 RT, 2 R 2 H HH R R R 2 RT, solvent-free RT, solvent-free 2 2 R 2 R22 RT, R RT, solvent-free 2 RT,solvent-free solvent-free R R R R R 22 R R22 R R R2R 2 2 1 1 2 44 11 11 33 1 2 2222 3 44 44 33 4 333 4
2a: R 2a: =Ph, R R44444=H =H R33333=Ph, 1a: =Ph, R =H R =Ph, R =H R 1a: R =Ph, R R22222=H =H R11111=Ph, 2a: 1a: 33 44 2a: 2a: =Ph, R =H R =Ph, R =H R 11 22 1a: 1a: 3 =Ph, R =H R =Ph, R =H R 1 3 2a: =Ph, R =H R 2 1a: 1 2 =Ph, R =H R 2a: =Ph, R =H66H R 3 4 1a: =Ph, R =H R 1 2 2b: 3 =3-OMe-C R =H R 2b: =3-OMe-C H55,,, R R44444=H =H R33=Ph, 1b:=Ph, 1b: =CH Cl, R R222=H =H R111=CH Cl, R 2a: R =H RR 1a: 1b: R 222=H R 1b: 2b: =CH Cl, R =H R =3-OMe-C H R 333 44 2b: 2b: =3-OMe-C =H =3-OMe-C H ,4,R R =H R 1b: =CH Cl, R =H R 111 22 =CH R =H R 6H 5,4 66 55 22Cl, 2b: 3 =3-OMe-C H , R =H R 2 1b: 1 2 2b: =CH Cl, R =H R =3-OMe-C H R R 1b: =CH Cl, R =H R 6 5 3 4=H 22R 6 5 1 R 2 2c: 2c: =4-Cl-C H , R =H R =4-Cl-C H , R =H R 3 4 1c: 1c: =Me, R =H R =Me, =H 1 2 6 5 3 4 6 5 3 4 1 2 2b: 2c: =3-OMe-C H , R =H R 1 2 =4-Cl-C H , R =H R 1b: 1c: =CH R22=H =H R 1c: =Me, R =H R 6 2c: =4-Cl-C H ,, R R544=H =H R 33 2c: 2Cl,R =4-Cl-C 1c: R =Me, R =H R 6H 66 2c: 33 44 =4-Cl-C HH55555,H =H R 22 1c: 2c:R =Me, R =H R =4-Cl-C , R5R =H R 1c: =Me, R =H R111111=Me, 6-C 6 2d: 2d: =4-NO H , R =H R =4-NO -C , R =H R 3 4 3 4 1e: , 1e: , =CH =CH =H R R =CH =CH =H R R 2 1 2 2 6 3 4 2 6 5 2 2 3 4 2, R22=H 2c: 1 =CH 2d: =4-NO -C H ,R =H 1e: H666H ,R =H RR =CH R 1c: 1e: =Me, R 2=CH =H R 3=4-Cl-C 2d: 2d: =4-NO =4-NO -C H R =H R 1=CH 1e: 6-C 5 3 R =CH =CH =H R R 2,,,2,2R 22 =4-NO -C R =H R 1e: 111 =CH =CH =H R R 2d:R =4-NO22222-C H55555,,,,R R44=H =H R 1e:R =CH222222Me, =CHR =H 2d: R R22=H 66H 222 =Me 1f: 1f: =CO Me, R =Me R =CO 3 4 1R 1=CO 2 11 222=Me 1f: Me, R 2 2d: =4-NO -C H , R =H R 1e: 1f: , 11 22 1f: =CH =CH =H R R =CO Me, R =Me R =CO Me, R =Me R 2 6 5 2 2 2 2 1f: 1f: RR =CO =CO22Me, Me, RR =Me =Me 1 2 2e= 2e= 2f= 2f= 1f: R1d= =CO Me, R =Me 2e= 2f= 2e= 2e= 2f= 2f= 1d= 2 O O N 2e= N 2f= 2e= 1d= O 2f= 1d= 1d= N O O N N 1d= H 1d= H O O N N H 2e= 2f= H H HH 1d= O N Epoxide Amine Epoxide Amine Epoxide Amine Epoxide Amine Epoxide Amine H Epoxide Amine Epoxide Amine Sr. Sr. Sr. Sr. Sr. Epoxide Amine Sr. Sr.
Epoxide Amine Sr. No. 1 2 No. 1 2 Sr. No. No. 1 2 No. 1 1 2 2 No. No. No.
No.
1 1 1
1 1 1 1 1 1 1 1 1
1
2 22
2 1a 1a 1a 1a 1a 1a 1a 1a
1a
3 3 3 3 3 3 33
N N N N N H H N N H H H H H
Epoxide Epoxide Epoxide Epoxide Epoxide Epoxide Epoxide Conversio Conversio Conversio Conversio Conversio Epoxide Conversio aa and 3:4 Conversio n and 3:4 n Epoxide a aaaa and 3:4 n and 3:4 n n and 3:4 Conversion aa and 3:4 n bb n Ratio and 3:4 Ratio b b Conversio b b b and 3:4 Ratio Ratio Ratio Ratio b b Ratio Ratio (%) (%) (%) a (%) n and 3:4 (%) (%) (%) (%)
N H
4 4 4 4 4 4 44
3
Ratio b (%)
4
100 100 100 100 100 100 100 100 93:7 93:7 93:7 93:7 93:7 93:7 93:7 93:7
2a 2a 2a 2a 2a 2a 2a 2a
2a
100 93:7
1a 1a 1a 1a 1a 1a 1a 1a
2 2 2 2 2 2 2 2
1a
2
2b 1a 1a 1a 1a 1a 1a 1a 1a
3 3 3 3 3 3 3 3
2b 2b 2b 2b 2b 2b 2b 2b
2c 2c 2c 2c 2c 2c 2c 2c
100 >99:99:99:99:99:99:99:99:99: