Cryptands and bismacrocycles with cyanuric and

Tetrahedron 68 (2012) 8581e8588

Contents lists available at SciVerse ScienceDirect

Tetrahedron journal homepage: www.elsevier.com/locate/tet

Cryptands and bismacrocycles with cyanuric and isocyanuric units: synthesis and structural investigations Flavia Pop a, b, Crina Socaci a, Anamaria Terec a, *, Eric Condamine c, y, Richard Attila Varga d, Ciprian I. Rat¸ d, Jean Roncali b, Ion Grosu a, * a

Babes-Bolyai University, Organic Chemistry Department, Supramolecular Organic and Organometallic Chemistry Center (SOOMCC), Cluj-Napoca, 11 Arany Janos str., 400028 Cluj-Napoca, Romania University of Angers, CNRS, MOLTECH-Anjou, Group Linear Conjugated Systems, 2 Bd Lavoisier, 49045 Angers, France c University of Rouen, Laboratory of Organic Chemistry and Structural Biology, CNRS, UMR 6014, 76821 Mont-Saint-Aignan, France d Babes-Bolyai University, Inorganic Chemistry Department, Supramolecular Organic and Organometallic Chemistry Center (SOOMCC), Cluj-Napoca, 11 Arany Janos str., 400028 Cluj-Napoca, Romania b

a r t i c l e i n f o

a b s t r a c t

Article history: Received 14 April 2012 Received in revised form 11 July 2012 Accepted 31 July 2012 Available online 7 August 2012

Hay synthesis of cryptands and bismacrocycles starting from tripodands with cyanuric and isocyanuric cores is reported. The structure of the compounds is revealed by X-ray diffraction, NMR spectrometry and MS investigations. DNMR experiments carried out with bismacrocycles indicated the flipping of the rings and the free-energy barrier for the conformational process could be determined in one case. Ó 2012 Elsevier Ltd. All rights reserved.

Keywords: Cryptands Bismacrocycles Triazines Dynamic NMR Diynes

1. Introduction Cryptands with C3 based symmetry are attractive targets for building host molecules and a plethora of compounds with 1,3,5trisubstituted benzene,1 tertiary amines2 or phosphines,3 cyclotriveratrylene,4 and 1,3,5-triazine5 units have been investigated. Acetylenic homocoupling represents a versatile tool for molecular construction and has been extensively used and diversified since Glaser’s discovery of oxidative coupling of copper alkynylbenzene.6 The most important modifications of the initial Glaser coupling technique were reported by Eglinton7 [the EglintoneGalbraith method: excess Cu(OAc)2 in pyridine, 20e40% yield] and Hay8 [the GlasereHay coupling: CuCl, N,N,N0 ,N0 -tetramethylethylenediamine (TMEDA), solvent, up to 97% yield]. The mechanism of this reaction has not yet been completely elucidated, despite the wide range of

* Corresponding authors. Tel.: þ40 264 59 3833; fax: þ40 264 59 0818; e-mail addresses: [email protected] (A. Terec), [email protected] (I. Grosu). y sonance Magne tique Nucle aire, Institut de Present address: Laboratoire de Re Biologie Structurale CEA-CNRS-UJF “J.-P. Ebel” (UMR CNRS 5075), 41 rue Jules Horowitz, 38027 Grenoble Cedex 1, France. 0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tet.2012.07.100

applications of alkyne couplings,9 from natural products chemistry to pharmaceuticals and macrocyclic derivatives.10 In parallel with advances in acetylenic coupling, the chemistry of the derivatives with cyanuric and isocyanuric units is developing very fast. The increasing interest in the derivatives of triazine is due to the accessibility and reactivity of the basic starting materials (cyanuric acid, melamine and cyanuryl chloride) and to the large number of applications of these compounds in materials science.11 In a previous work12 we reported the synthesis of tripodands with C3 symmetry, which are derivatives of cyanuric (I) and isocyanuric (II) acids (Chart 1). These tripodands have pendant arms of different lengths (bearing one or more ethyleneoxide units) which exhibit terminal propargyl groups (the triple bonds are at the ends of the chains). We considered to be of interest to investigate the acetylene homocoupling of tripodands I and II (Chart 1) and to obtain new cryptands (Chart 1, targets III and IV; only intermolecular coupling reactions) and bismacrocycles (Chart 1, V and VI; intramolecular and intermolecular coupling reactions) with diyne moieties in the chains and 1,3,5-triazine or 1,3,5-triazine-2,4,6-trione as central units (Chart 1). We planned to investigate the competition between

8582

F. Pop et al. / Tetrahedron 68 (2012) 8581e8588

Scheme 2. Chart 1. General formula for podands (I and II), target cryptands (III and IV) and bismacrocycles (V and VI).

the intermolecular and intramolecular coupling reactions and to correlate the results with the lengths of the chains in the starting podands.

2. Results and discussions The reaction of trialkyne tripodands with a cyanuric (2e4) or isocyanuric (8 and 9) core, under Hay coupling conditions (CuI, TMEDA, O2/CH2Cl2), afforded cryptands 5a and 10a (compounds obtained only by intermolecular couplings) or/and bismacrocycles 5b, 6b, 7b and 11b (compounds obtained by both intramolecular and intermolecular coupling reactions) in fair to good yields (Schemes 1 and 2). The short arms of podand 8 favor the intermolecular coupling reactions and the formation of cryptand 10a as unique product.

Scheme 1.

The bismacrocycles are obtained by two intramolecular (enclosure of macrocycles) and one intermolecular (formation of the linkage between the macrocycles) coupling reactions. This reaction pattern is possible if the pendant arms are long enough and this process can remain in competition with obtaining cryptands (in the case of podand 2), but for the podands with longer branches (3, 4 and 9) it leads exclusively to the formation of bismacrocycles. Failure of 1 to form the target macrocycles and the lower yields in cryptands and bismacrocycles in the case of podands with triazine core, as compared to the behavior of the similar isocyanuric type podands, suggests a lower reactivity for the cyanuric type derivatives, probably due to the competition of the N atoms (with complexation abilities) of the triazine unit on the catalytic process. 2.1. Solid state structural investigations Suitable crystals for X-ray diffraction investigations were obtained for cryptand 5a and bismacrocycle 11b (slow diffusion in chloroform/hexane). The solid state molecular structure of 5a reveals a surprising architecture (Fig. 1A) in which the aromatic heterocyclic units are almost perpendicular (the dihedral angle between the planes of the heterocycles is a¼84.38 ). The solid state molecular structure of 5a does not exhibit C3 or Cs symmetry and the three chains are all different. The distances between the centroids of the diyne units (d¼9.465, 10.579 and 10.651 A) and between these centroids and the centroids of the closest heterocycles (d¼3.649; 5.322 and 5.484 A) exhibit different values. The peculiar arrangement of the chains and the collapse of the cavity are probably due to CHen interactions13 involving the hydrogen and the heteroatoms of the fragments eN] CeOeCH2(a)eCH2(b)e of different chains. Short CHeN (d¼2.654 and 2.882 A) and CHeO (d¼2.601 A) contacts between these units were observed (Fig. 1B). The pep stacking14 of the triple bonds of

Fig. 1. Single-crystal X-ray diffraction molecular structure (Ortep diagram) of 5a (A) and representation of the relevant intramolecular contacts (B).


one chain and the neighboring heterocycle (distance between the centroids of the diyne unit and of the heterocycle d¼3.641 A) could be also revealed. Contacts involving the hydrogen atoms of propargyl positions or of a and b positions of eOCH2CH2e units on one side and the N (d¼2.708 and 2.733 A) or O (d¼2.454, 2.542 and 2.649 A) atoms of neighboring molecules on the other side were noticed in the lattice (Fig. 2 and SI). The view of the lattice along the b crystallographic axis reveals a layered structure with CHeO contacts (d¼2.542 A) between the molecules of the same layer and CHeN contacts (d¼2.733 A) between layers (Fig. 2).

8583

structures VII with a disubstituted triazaheterocycle and the substitution of a methylene group of the eCH2eCH2e units with oxygen atoms. The macrocycles of 11b, similarly to structure VIII, exhibit heteroatoms in the cycle and prefer the chair conformation. In the lattice, the bismacrocycles form catemers built up by contacts between the triazacyclohexan-trione units (Fig. 5). The catemers are either parallel or tilted. At their turn, the triazatrione type heterocycles are located in two sets of parallel planes. The angle between the heterocycles belonging to different sets is a¼76.10 .

Fig. 2. View (along the b axis) of the lattice of the crystal of 5a with emphasis on the CHeN (yellow) and CHeO (blue) contacts.

The single-crystal X-ray investigation of 11b shows a centrosymmetrical structure (Fig. 3A) with the synesyn arrangement of the chains of the macrocycles and the connection between the macrocycles. The three substituents of each triazine are oriented on the same side of the heterocycle and generate the synesyn isomer, while the macrocyclic units exhibit the anti conformer when the torsion around the central diyne part is considered. The diyne moieties of both macrocycles are close to the diyne unit that connects the two macrocycles. In this structure, contacts between the electrondrich triple bonds and the electrondpoor heterocycle can be achieved (interactions of electron rich guests with isocyanuric units as hosts already reported)15 and the distance between the centroid of diyne part and the centroid of the N-containing heterocycle is d¼3.88 A (Fig. 3B). This peculiar structure of the macrocycles is also stabilized by intramolecular CHep contacts13g,14a,16 involving the propargyl type H atoms of the central bridge and the diyne units of the macrocycles (the distances between the considered hydrogen atoms and the centroids of the triple bonds of the macrocycles are 3.111 and 3.257 A; Fig. 3B). The macrocycles exhibit a chair conformation and their structure can be compared to that of some cyclic tetraynes investigated by Gleiter.17 In Gleiter’s tetraynes (Fig. 4), two rigid units (eZeC^CeC^CeZe; Z¼CH2, Se) are connected to each other by two eCH2eCH2e bridges and form medium size cycles (Fig. 4; structures VII and VIII). The conformation of carbocycles [VII (Z¼CH2)] is a twisted one, while the heterocycles [e.g., VIII (Z¼Se)] prefer their usual chair conformations. Compound 11b can be compared to these cyclic tetraynes and it can be formally obtained by simultaneous replacement of a diyne moiety in

The heterocycles exhibit an offset face-to-face arrangement, the distance between the centroids of the rings being d¼3.504 A, while the distance between the planes of the heterocycles is 3.322 A and the offset is 1.114 A. The heterocycles in contact are rotated relative to each other so that the N atoms of one heterocycle are directly above the C atoms of the C]O groups of the other heterocycle. The catemers cross each other and the most important contacts are located in the diyne moieties. The C]O groups of the isoA) with cyanuric unit of one chain exhibit H bonds (dOeH¼2.717 propargyl type H atoms of the crossing chain (Fig. 5) and these contacts may be responsible for this architecture of the lattice. Other CHeO contacts involving the C]O groups and the H atoms of A) or of the propargylic posithe eCH2CH2Oe units (dOeH¼2.664 A) were also observed (see SI). tions (dOeH¼2.613

2.2. Structural investigations in solution While the solid state molecular structure of 5a revealed different arrangements of the chains, the room temperature NMR spectra of cryptands 5a and 10a are simple and exhibit unique signals for similar protons or carbon atoms of the chains suggesting chain flexibility in solution and NMR signals corresponding to an average of the possible individual magnetic environments. As an example, the 1H NMR spectrum of cryptand 5a (Fig. 6A) exhibits two multiplets (d¼3.89 and 4.61 ppm, respectively) for the protons of the ethyleneoxide units and one singlet (d¼4.29 ppm) for the protons of the propargyl positions.

8584


Fig. 3. Single-crystal X-ray diffraction molecular structure of 11b (ORTEP diagram, A; ball and sticks representation showing intramolecular contacts, B).

Fig. 4. Single-crystal X-ray diffraction molecular structures (ball and sticks representations) of VII (A) and VIII (B).17

The spectra of bismacrocycles 5b, 6b, 7b and 11b show two sets of signals corresponding to the macrocycles and to the connection between the macrocycles, respectively (in 1H NMR spectra a 2/1 ratio of the intensities of the signals could be noted; Fig. 6). The 1H NMR spectrum of 5b (Fig. 6B) exhibits the same signals as that recorded for 5a, but in the case of the bismacrocycle they are doubled. The 1H NMR spectrum of 11b recorded at 298 K (Fig. 7a) suggests a conformational equilibrium (Scheme 3) and the shape of some of the signals indicates that they are close to coalescence. Relevant variable temperature NMR experiments (5 K steps from 238 to 298 K) were carried out with 11b (Fig. 7). The shape and the positions of the signals [two multiplets (d1,12¼3.80; d2,11¼4.19 ppm) and a singlet (d4,9¼4.26 ppm)] belonging to protons of the chain which connect the two macrocycles remain unchanged during the DNMR experiment and these signals are not affected by the conformational equilibrium of compound 11b. The other signals, pertaining to the protons of the macrocycles, are

dramatically modified in the spectra recorded at low temperatures. These results suggest as a possible conformational equilibrium the flipping of the macrocycles (Scheme 3). This equilibrium would convert diastereoisomeric structures (syn,syn$syn, anti$anti, anti) generated by the different relative orientations of the chain (that connects the macrocycles) and of the macrocycles (the three substituents of the N atoms reported to the plane of the isocyanuric unit). The changes observed in the 1H NMR spectra at low temperatures are generated by the differences between the magnetic environments of the equatorial and axial protons of the macrocycles, while the differences between the magnetic environments of similar protons of the diastereoisomeric structures are too small to be observed in the low temperature NMR spectra. As a result of the fast conformational exchange, the spectra at 298 K exhibit unique signals at mean d values for the equatorial or axial positions of the protons of the macrocycles (Table 1; SI), while at low temperature, when the equilibrium is slow on the NMR time scale, the 1H NMR spectrum reveals different signals for the axial and equatorial orientations of the protons of the macrocycles (Table 1; SI). The coalescence of the signals was estimated at 265 K (Tc). The values of the chemical shifts for the rigid structure were collected from the spectrum recorded at 238 K (Table 1) and the free-energy barrier for the flipping of the macrocycles was calculated (using Eyring equations)18 to be DG# ¼55.20.4 kJ/mol (13.20.1 kcal/ mol; see SI). DNMR experiments were tried with the other bismacrocycles too, but in these cases it was not possible to obtain the frozen structures (down to 215 K, using CD2Cl2) and it was concluded that the flipping of the macrocycles can be easily frozen only for 11b, which exhibits the shortest chains among the investigated bismacrocycles.


Fig. 5. Representations (11b) of the crossing chains along the b axis (A) and along the c axis (B) highlighting the most relevant intermolecular contacts.

Fig. 6. 1H NMR spectra (rt, fragments) of cryptand 5a (A) and bismacrocycle 5b (B).

8585

8586


Fig. 7. 1H NMR (600 MHz) of compound 11b in CDCl3 at 298 K (a), 268 K (b), 263 K (c), 238 K (d).

involving the diyne units, the N atoms or CO groups of the triazaheterocycles are responsible for the collapse of the cavity as revealed by the crystal structure of 5a and by the spectacular arrangement of the molecules in the lattices of 5a and 11b. DNMR experiments on bismacrocycle derivatives revealed the flipping of the macrocycles and for compound 11b the barrier for this process was measured (DG# ¼13.2 kcal/mol). Scheme 3.

4. Experimental part 4.1. General experimental data

Table 1 Results of DNMR investigations (CDCl3) of 11b Temp K

Positions 10 , 120 ax

298 238

3.96 4.02

20 , 110 eq

ax

3.90

4.12 4.37

40 , 90 eq

ax

eq

3.84

4.12 4.29

3.95

3. Conclusions Alkyne coupling reactions of tripodands with cyanuric and isocyanuric cores led to the formation of cryptands and/or bismacrocycles. The reactions are shifted toward the formation of cryptands if the pendant arms of the tripodand are short and the preference for bismacrocycles increases with the length of pendant arms independent of the nature of the central core. Interactions

1 H NMR (300 MHz) and 13C NMR (75 MHz) spectra, COSY, HSQC and HMBC were recorded in C6D6 and CDCl3 at room temperature on a 300 MHz spectrometer using the solvent line as reference. The DNMR experiments were performed on a 600 MHz spectrometer. Thin layer chromatography (TLC) was conducted on silica gel 60 F254 TLC plates and preparative column chromatography was performed using 40e63 mm silica gel. Solvents were dried and distilled under argon using standard procedures. Chemicals of commercial grade were used without further purification. MSs were recorded using an ion-trap MS equipped with a standard ESI/APCI source. Crystallographic data were collected at room temperature and the crystals were mounted on a cryo loop with Paraton oil. The structures were solved by direct methods (SHELXS-97)19 and refined by full matrix least-squares procedures based on F2 with all measured reflections (SHELXL-97).19 All non-hydrogen atoms were refined anisotropically. The drawings were created with ORTEP20 and Diamond program.21 Further details on the data collection


and refinement methods can be found in SI. These data can be also obtained free of charge from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; (fax: (þ44) 1223336-033; or e-mail: [email protected]). The deposition numbers are: CCDC-856167 (5a) and CCDC-856168 (11b). 4.2. General procedure for the acetylenic coupling reaction To a 5 mM solution obtained using 1 mmol of podand in 200 ml dry CH2Cl2 and containing dry TMEDA (40 mmol), dry CuI (or dry CuCl) (20 mmol) was added and the resulting mixture was stirred for 2 h at room temperature under oxygen atmosphere. After solvent evaporation, extraction with dichloromethane and washing several times with water (for complete removal of the copper salts), the organic layer was purified by chromatography on silica gel. 4.3. New compounds 5a, 10a, 5be7b and 11b 4,7,14,17,23,26,33,36,39,42,49,52-Dodecaoxa-2,19,21,38,53,54hexaazatetracyclo[18.18.14.13,37.118,22]tetrapentaconta-1,3(53),18(54), 19,21,37-hexaene-9,11,28,30,44,46-hexayne (5a). Yield: 10% (37 mg), colorless liquid, Rf¼0.44 (eluent: toluene/acetone¼4/1). Calculated for C36H36N6O12; C, 58.06; H, 4.87; N, 11.29; found: C, 57.88; H, 4.69; N, 11.21. 1H NMR (300 MHz, CDCl3) d¼3.88e3.90 (m, 12H, 6-H, 15-H, 25H, 34-H, 41-H, 50-H), 4.29 (s, 12H, 8-H, 13-H, 27-H, 32-H, 43-H, 48-H), 4.59e4.62 (m, 12H, 5-H, 16-H, 24-H, 35-H, 40-H, 51-H). 13C NMR (75 MHz, CDCl3) d¼59.0 (8-C, 13-C, 27-C, 32-C, 43-C, 48-C), 67.1 (5-C, 16-C, 24-C, 35-C, 40-C, 51-C), 67.6 (6-C, 15-C, 25-C, 34-C, 41-C, 50-C), 70.5, 75.2 (9-C, 10-C, 11-C, 12-C, 28-C, 29-C, 30-C, 31-C, 44-C, 45-C, 46C, 47-C) 172.9 ppm (1-C, 3-C, 18-C, 20-C, 22-C, 37-C). ESI-MS m/ z¼745.2 [MþHþ], 767.2 [MþNaþ]. 1,14-Bis(20 ,50 ,120 ,150 -tetraoxa-170,190 ,200 -triaza-bicyclo[14.3.1] icosa-160 ,180 ,200 (10 )-triene-70,90 -diyne-180 -yl)-1,4,11,14-tetraoxate tradeca-6,8-diyne (5b). Yield: 25% (93 mg), white solid, mp¼175 C (decomp.), Rf¼0.39 (eluent: toluene/acetone¼4/1). Calculated for C36H36N6O12; C, 58.06; H, 4.87; N, 11.29; found: C, 58.21; H, 4.99; N, 11.11. 1H NMR (300 MHz, CDCl3) d¼3.88e3.90 (m, 4H, 3-H, 12-H), 3.97e4.00 (m, 8H, 40 -H, 130 -H), 4.23 (s, 8H, 60 -H, 110 -H), 4.31 (s, 4H, 5-H, 10-H), 4.56e4.59 (m, 4H, 2-H, 13H), 4.65e4.67 (m, 8H, 30 -H, 140 -H). 13C NMR (75 MHz, CDCl3) d¼58.9 (5-C, 10-C); 59.4 (60 -C, 110 -C), 67.0 (2-C, 13-C), 67.3 (30 -C, 140 -C), 67.6 (3-C, 12-C), 68.2 (40 -C, 130 -C), 70.4, 76.2 (6-C, 7-C, 8C, 9-C), 70.9, 75.1 (70 -C, 80 -C, 90 -C, 100 -C), 172.7 (180 -C) 173.0 ppm (10 -C, 160 -C, 180 -C). ESI-MS m/z¼745.2 [MþHþ], 767.2 [MþNaþ]. 1,20-Bis(20 ,50 ,80 ,150 ,180 ,210 -hexaoxa-230 ,250 ,260 -triazabicyclo [20.3.1]hexacosa-220 ,240 ,260 (10 )-triene-100 ,120 -diyne-240 -yl)1,4,7,14,17,20-hexaoxaicosa-9,11-diyne (6b). Yield: 58% (292 mg), yellow liquid, Rf¼0.34 (eluent: toluene/acetone¼4/1). Calculated for C48H60N6O18; C, 57.14; H, 5.99; N, 8.33; found: C, 57.38; H, 5.82; N, 8.51. 1H NMR (300 MHz, CDCl3) d¼3.69 (s, 24H, 5-H, 6-H, 15-H, 16-H, 60 -H, 70 -H, 160 -H, 170 -H), 3.82e3.85 (m, 12H, 3-H, 18-H, 40 -H, 190 -H), 4.24 (s, 8H, 90 -H, 140 -H), 4.27 (s, 4H, 8-H, 13-H), 4.53e4.56 (m, 4H, 2-H, 19-H), 4.59e4.62 (m, 8H, 30 -H, 200 -H). 13C NMR (75 MHz, CDCl3) d¼58.9 (8-C, 13-C), 59.0 (90 -C, 140 -C), 67.2 (30 -C, 200 -C); 67.4 (2-C, 19-C), 68.8 (40 -C, 190 -C); 68.9 (3-C, 18-C), 69.3, 69.4, 70.4, 70.6 (5-C, 6-C, 15-C, 16-C, 60 -C, 70 -C, 160 -C, 170 -C), 70.5, 70.7, 75.3, 75.5 (9-C, 10-C, 11-C, 12-C, 100 -C, 110 -C, 120 -C, 130 -C) 173.0, 173.1 ppm (10 -C, 220 -C, 240 -C). ESI-MS m/z¼1009.4 [MþHþ], 1031.3 [MþNaþ]. 1,26-Bis(20 ,50 ,80 ,110,180 ,210,240 ,270 -octaoxa-290 ,310,320 -triazabicyclo[26.3.1]dotriaconta-280 ,300 ,320 (10 )-triene-130 ,150 -diyne-300 yl)-1,4,7,10,17,20,23,26-octaoxahexacosa-12,14-diyne (7b). Yield: 20% (127 mg), yellow liquid, Rf¼0.39 (eluent: toluene/acetone¼1/ 1). Calculated for C60H84N6O24; C, 56.59; H, 6.65; N, 6.60. Found: C, 56.83; H, 6.39; Cl, N, 6.43.1H NMR (300 MHz, CDCl3) d¼3.60e3.70

8587

(overlapped peaks, 48H, 5-H, 6-H, 8-H, 9-H, 18-H, 19-H, 21-H, 22-H, 60 -H, 70 -H, 90 -H, 100 -H, 190 -H, 200 -H, 220 -H, 230 -H), 3.80e3.85 (m, 12H, 3-H, 24-H, 40 -H, 250 -H), 4.25e4.27 (overlapped peaks, 12H, 11H, 16-H, 120 -H, 170 -H), 4.49e4.54 (m, 12H, 2-H, 25-H, 30 -H, 260 -H). 13 C NMR (75 MHz, CDCl3) d¼58.9 (11-C, 16-C, 120 -C, 170 -C), 67.4, 67.6, 68.8, 69.1, 69.3, 70.3, 70.4, 70.5, 70.6, 70.7, 70.9, 75.40, 75.41 (2-C, 3-C, 5-C, 6-C, 8-C, 9-C, 12-C, 13-C, 14-C, 15-C, 18-C, 19-C, 21-C, 22-C, 24-C, 25-C, 30 -C, 40 -C, 60 -C, 70 -C, 90 -C, 100 -C, 130 -C, 140 -C, 150 -C, 160 -C, 190 -C, 200 -C, 220 -C, 230 -C, 250 -C, 260 -C), 172.9 ppm (10 -C, 280 -C, 300 -C). ESI-MS m/z¼1273.6 [MþHþ], 1295.6 [MþNaþ]. 1,3,10,12,14,21-Hexaazatetracyclo[10.10.6.13,21.110,14]triaconta5,7,16,18,24,26-hexayne-2,11,13,22,29,30-hexaone (10a). Yield: 33% (79.2 mg), beige solid, mp¼207 C (decomp.), Rf¼0.62 (eluent: dichloromethane/diethylether¼3/7). Calculated for C24H12N6O6; C, 60.00; H, 2.52; N, 17.49. Found: C, 60.16; H, 2.68; N, 17.33. 1H NMR (300 MHz, CDCl3) d¼4.66 (s, 12H, 4-H, 9-H, 15-H, 20-H, 23-H, 28-H). 13 C NMR (75 MHz, CDCl3) d¼53.4 (4-C, 9-C, 15-C, 20-C, 23-C, 28-C), 89.6 (5-C, 8-C, 16-C, 19-C, 24-C, 27-C), 131.0 (6-C, 7-C, 17-C, 18-C, 25C, 26-C), 161.2 ppm (2-C, 11-C, 13-C, 22-C, 29-C, 30-C). ESI-MS m/ z¼481.1 [MþH]þ. 1,12-Bis(30 ,100 -dioxa-130 ,150 ,170 -triaza-bicyclo[12.3.1]octadeca0 14 ,160 ,180 -trioxo-50 ,70 -diyne-150 -yl)-3,10-dioxadodeca-5,7-diyne (11b). Yield: 64% (238 mg), white solid, mp >300 C, Rf¼0.5 (eluent: toluene/acetone¼4/1). Calculated for C36H36N6O12; C, 58.06; H, 4.87; N, 11.29. Found: C, 57.90; H, 4.92; N, 11.39. 1H NMR (300 MHz, CDCl3) d¼3.78e3.81 (m, 4H, 1-H, 12-H), 3.96e3.98 (m, 8H, 10 -H, 120 H), 4.12 (broad signal, 12H, 20 -H, 40 -H, 90 -H, 110 -H), 4.17e4.21 (m, 4H, 2-H, 11-H), 4.26 (s, 4H, 4-H, 9-H). 13C NMR (75 MHz, CDCl3) d¼41.9 (1-C, 12-C), 43.9 (10 -C, 120 -C), 53.4 (6-C, 7-C), 58.4 (4-C, 9-C), 58.7 (40 -C, 90 -C), 66.3 (2-C, 11-C), 67.0 (20 -C, 110 -C), 70.5 (60 -C, 70 -C), 75.2 (5-C, 8-C), 78.5 (50 -C, 80 -C), 149.2 (140 -C, 160 -C), 149.7 ppm (180 -C). APCI-MS m/z¼745.3 [MþH]þ, 767.3 [MþNa]þ. Acknowledgements We are grateful to CNCSISeUEFISCDI for the financial support of this work, projects PN IIeIDEI 515 and 570/2007. Supplementary data Supplementary data associated with this article can be found in the online version, at http://dx.doi.org/10.1016/j.tet.2012.07.100. These data include MOL files and InChiKeys of the most important compounds described in this article. References and notes € gtle, F. Angew. Chem., Int. Ed. Engl. 1992, 31, 528e549; (b) Mas1. (a) Seel, C.; Vo talerz, M. Angew. Chem., Int. Ed. 2010, 49, 5042e5053; (c) Sambasivan, S.; Kim, S. G.; Choi, S. M.; Rhee, Y. M.; Ahn, K. H. Org. Lett. 2010, 12, 4228e4231; (d) Gomez-Lor, B.; Hennrich, G.; Alonso, B.; Monge, A.; Gutierrez-Puebla, E.; Echavarren, A. M. Angew. Chem., Int. Ed. 2006, 45, 4491e4494; (e) Kumazawa, K.; Yamanoi, Y.; Yoshizawa, M.; Kusukawa, T.; Fujita, M. Angew. Chem., Int. Ed. 2004, 43, 5936e5940; (f) MacGillivray, L. R.; Atwood, J. L. Angew. Chem., Int. Ed. 1999, 38, 1018e1033; (g) Higler, I.; Timmerman, P.; Verboom, W.; Reinhoudt, D. N. Eur. J. Org. Chem. 1998, 2689e2702. 2. (a) Ballester, P. Chem. Soc. Rev. 2010, 39, 3810e3830; (b) Kang, S. O.; Llinares, J. M.; Day, V. W.; Bowman-James, K. Chem. Soc. Rev. 2010, 39, 3980e4003. 3. (a) Stollenz, M.; Barbasiewicz, M.; Nawara-Hultzsch, A. J.; Fiedler, T.; Laddusaw, R. M.; Bhuvanesh, N.; Gladysz, J. A. Angew. Chem., Int. Ed. 2011, 50, 6647e6651; (b) Bauer, I.; Habicher, W. D. Collect. Czech. Chem. Commun. 2004, 69, 1195e1230. 4. (a) Perraud, O.; Robert, V.; Martinez, A.; Dutasta, J. P. Chem.dEur. J. 2011, 17, 4177e4182; (b) Sanseverino, J.; Chambron, J. C.; Aubert, E.; Espinosa, E. J. Org. Chem. 2011, 76, 1914e1917; (c) Khan, N. S.; Perez-Aguilar, J. M.; Kaufmann, T.; Hill, P. A.; Taratula, O.; Lee, O. S.; Carroll, P. J.; Saven, J. G.; Dmochowski, I. J. J. J. Org. Chem. 2011, 76, 1418e1424; (d) Brotin, T.; Dutasta, J. P. Chem. Rev. 2009, 109, 88e130; (e) Holman, K. T.; Drake, S. D.; Steed, J. W.; Orr, G. W.; Atwood, J. L. Supramol. Chem. 2010, 22, 870e890; (f) Li, M. J.; Lai, C. C.; Liu, Y. H.; Peng, S. M.; Chiu, S. H. Chem. Commun. 2009, 5814e5816; (g) Bouchet, A.; Brotin, T.; Linares, M.; Agren, H.; Cavagnat, D.; Buffeteau, T. J. Org. Chem. 2011, 76, 1372e1383.

8588


5. (a) Naseer, M. M.; Wang, D. X.; Zhao, L.; Huang, Z. T.; Wang, M. X. J. Org. Chem. 2011, 76, 1804e1813; (b) Morales-Sanfrutos, J.; Ortega-Munoz, M.; Lopez-Jaramillo, J.; Hernandez-Mateo, F.; Santoyo-Gonzalez, F. J. Org. Chem. 2008, 73, 7772e7774. 6. Glaser, C. Ber. Dtsch. Chem. Ges. 1869, 2, 422e424. 7. Eglinton, G.; Galbraith, A. R. Chem. Ind. (London) 1956, 737e738. 8. Hay, A. S. J. Org. Chem. 1962, 27, 3320e3321. 9. Siemsen, P.; Livingston, R. C.; Diedrich, F. Angew. Chem., Int. Ed. 2000, 39, 2632e2657. €gtle, F. In Comprehensive Supramolecular Chem10. (a) Breitenbach, J.; Boosfeld, J.; Vo €gtle, F., Ed.; Pergamon: Oxford, 1996; Vol. 2, pp 29e67; (b) Whitlock, B. J.; istry; Vo € gtle, F., Ed.; PerWhitlock, H. W. In Comprehensive Supramolecular Chemistry; Vo gamon: Oxford, 1996; Vol. 2, pp 309e324; (c) Frank, B. B.; Laporta, P. R.; Breiten, B.; Kuzyk, M. C.; Jarowski, P. D.; Schweizer, W. B.; Seiler, P.; Biaggio, I.; Boudon, C.; Gisselbrecht, J. P.; Diederich, F. Eur. J. Org. Chem. 2011, 4307e4317; (d) Jarowski, P. D.; Diederich, F.; Houk, K. N. J. Org. Chem. 2005, 70, 1671e1678; (e) Manini, P.; Amrein, W.; Gramlich, V.; Diederich, F. Angew. Chem., Int. Ed. 2002, 41, 4339e4343; (f) Rubin, Y.; Parker, T. C.; Khan, S. I.; Holliman, C. L.; McElvany, S. W. J. Am. Chem. Soc.1996,118, 5308e5309; (g) Rubin, Y.; Parker, T. C.; Pastor, S. J.; Jalisatgi, S.; Boulle, C.; Wilkins, C. L. Angew. Chem., Int. Ed. 1998, 37, 1226e1229. 11. (a) Soler-Illia, G. J. A. A.; Azzaroni, O. Chem. Soc. Rev. 2011, 40, 1107e1150; (b) Mintzer, M. A.; Grinstaff, M. W. Chem. Soc. Rev. 2011, 40, 173e190; (c) Carofiglio, T.; Lubian, E.; Varotto, A. J. Porphyrins Phthalocyanines 2010, 14, 701e707; (d) Lim, J.; Mintzer, M. A.; Perez, L. M.; Simanek, E. E. Org. Lett. 2010, 12, 1148e1151; (e) Lai, L. L.; Hsu, H. C.; Hsu, S. J.; Cheng, K. L. Synthesis-Stuttgart 2010, 20, 3576e3582; (f) Choi, S.; Drese, J. H.; Jones, C. W. ChemSusChem 2009, 2, 796e854; (g) Percec, V.; Imam, M. R.; Peterca, M.; Cho, W. D.; Heiney, P. A. Isr. J. Chem. 2009, 49, 55e70; (h) Singh, M.; Gupta, S. Synth. Commun. 2008, 38, 2898e2907. 12. Piron, F.; Oprea, C.; Cismas¸, C.; Terec, A.; Roncali, J.; Grosu, I. Synthesis 2010, 1639e1644. 13. (a) Vibhute, A. M.; Gonnade, R. G.; Swathi, R. S.; Sureshan, K. M. Chem. Commun. 2012, 717e719; (b) Shivakumar, K.; Vidyasagar, A.; Naidu, A.; Gonnade, R. G.; Sureshan, K. M. CrystEngComm 2012, 14, 519e524; (c) Salonen, L. M.; Ellermann, M.; Diederich, F. Angew. Chem., Int. Ed. 2011, 50, 4808e4842; (d) Scheiner, S. Phys. Chem. Chem. Phys. 2011, 13, 13860e13872; (e) Melandri, S. Phys. Chem.

14.

15. 16.

17.

18.

19. 20. 21.

Chem. Phys. 2011, 13, 13901e13911; (f) Parthasarathi, R.; Bellesia, G.; Chundawat, S. P. S.; Dale, B. E.; Langan, P.; Gnanakaran, S. J. Phys. Chem. A 2011, 115, 14191e14202; (g) Takahashi, O.; Kohno, Y.; Nishio, M. Chem. Rev. 2010, 110, 6049e6076; (h) Schneider, H. J. Angew. Chem., Int. Ed. 2009, 48, 3924e3977; (i) € y, C. B.; Champness, N. R.; Janiak, C. CrystEngComm 2010, 12, 22e43; (j) Aakero Hua, Y.; Flood, A. H. Chem. Soc. Rev. 2010, 39, 1262e1271; (k) Gale, P. A. Chem. Soc. Rev. 2010, 39, 3746e3771; (l) Kovacs, A.; Varga, Z. Coord. Chem. Rev. 2006, 250, 710e727. (a) Jennings, W. B.; Farrell, B. M.; Malone, J. F. Acc. Chem. Res. 2001, 34, 885e894; (b) Klosterman, J. K.; Yamauchi, Y.; Fujita, M. Chem. Soc. Rev. 2009, €ller, C. R.; Wu € rthner, F. Chem. 38, 1714e1725; (c) Chen, Z.; Lohr, A.; Saha-Mo Soc. Rev. 2009, 38, 564e584; (d) Bellachioma, G.; Ciancaleoni, G.; Zuccaccia, C.; Zuccaccia, D.; Macchioni, A. Coord. Chem. Rev. 2008, 252, 2224e2238; (e) Tewari, A. K.; Dubey, R. Bioorg. Med. Chem. 2008, 16, 126e143; (f) Grimme, € ck-Lichtenfeld, C. Org. Biomol. Chem. 2007, 5, S.; Antony, J.; Schwabe, T.; Mu 741e758. Frontera, A.; Saczewski, F.; Gdaniec, M.; Dziemidowicz-Borys, E.; Kurland, A.; , P. M.; Quin ~ onero, D.; Garau, C. Chem.dEur. J. 2005, 11, 6560e6567. Deya (a) Nishio, M. Phys. Chem. Chem. Phys. 2011, 13, 13873e13900; (b) Nishio, M.; Umezawa, Y.; Honda, K.; Tsuboyama, S.; Suezawa, H. CrystEngComm 2009, 11, 1757e1788; (c) Tsuzuki, S.; Fujii, A. Phys. Chem. Chem. Phys. 2008, 10, 2584e2594; (d) Nishio, M. Tetrahedron 2005, 61, 6923e6950; (e) Lucas, R.; ~ o, A.; Reina, J. J.; Eritja, R.; Gonzalez, C.; Morales, J. C. J. Am. Gomez-Pinto, I.; Avin Chem. Soc. 2011, 133, 1909e1916; (f) Fujii, A.; Hayashi, H.; Park, J. W.; Kazama, T.; Mikami, N.; Tsuzuki, S. Phys. Chem. Chem. Phys. 2011, 13, 14131e14141. (a) Werz, D. B.; Gleiter, R.; Rominger, F. J. Org. Chem. 2004, 69, 2945e2952; (b) Gleiter, R.; Merger, R.; Chavez, J.; Oeser, T.; Irngartinger, H.; Pritzkow, H.; Nuber, B. Eur. J. Org. Chem. 1999, 2841e2843. (a) Kurland, R. J.; Rubin, M. B.; Wise, W. B. J. Chem. Phys. 1964, 40, 2426e2427; (b) Eliel, E. L.; Wilen, S. H. Stereochemistry of Organic Compounds; Wiley: Chichester, UK, 1994; p 504; (c) Eliel, E. L.; Wilen, S. H.; Doyle, M. P. Basic Organic Stereochemistry; Wiley Interscience: New York, NY, 2001; p 327. Sheldrick, G. M. Acta Crystallogr., Sect. A 2008, A64, 112e122. Farrugia, L. J. J. Appl. Crystallogr. 1997, 30, 565. Brandenburg, K. DIAMOND, Crystal Impact GbR; Germany: Bonn, 2006.