Heterocyclic betaines. 13. Synthesis and electronic and molecular

Ermitas Alcalde, Carlos Ayala, Immaculada Dinarès, Neus Mesquida, and Francisco Sánchez-Ferrando. The Journal of Organic Chemistry 2001 66 (7), 2281...
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4829

J. Org. Chem. 1992,57,4829-4834

Heterocyclic Betaines. 13.' Synthesis and Electronic and Molecular Structures of Methylenepyridinium and Methyleneimidazolium Azolate Inner Salts Ermitas Alcalde,*" Lluha P&ez-Garda,t Carlos Miravitlles; Jordi Rius,t and Eduard Valent!# Laboratorio de Q u h i c a Orgcinica, Facultad de Farmacia, Universidad de Barcelona, E-08028-Barc$ona, Spain, Znstituto de Ciencias de Materiales, C.S.Z.C.,E-08193-BeElaterra, Spain, and Departamento de Quimica Mgdica, Laboratorios Dr. Esteve, E-08026-Barcelona, Spain Received December 2,1991

A convenient synthesis of several examples of betaines 3 and 4 is reported. The electronicand molecular structure of the title betaines 3 and 4 is investigated in terms of a single-crystal diffraction X-ray analysis of compound 7, spectroscopic methods, and experimental dipole moment values (12.34-15.34 D). Semiempirical molecular orbital calculations (MNDOand AM1 methods) provide a useful complementary information to the experimental resulte.

Heterocyclic betaines have been the subject of extensive investigation, mainly because their dipolar character has a dominant influence upon their chemistry. In the context of a current search for organic substrates with high dipole momenta, and our interest in the chemistry of the azinium azolate 1 and azolium azolate inner salts 2,'-3 we have now inveatigated a new type of heterocyclic betaine homologues of the N-ylides 1 and 2, the methylenepyridinium and methyleneimidazolium azolate inner salts 3 and 4. Owing to their structure, they can be incorporated as subunit(s) in host molecules and could confer unusual properties to the cavities-either cavitates or clathrates.

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Results and Discussion Synthesis. A facile entry into the unknown inner salts of methylenepyridinium benzimidazolate 5-8, triazolate 9 and 10 and methyleneimidazolium benzimidazolate 11-14, triazolate 15 and 16 is described: as well as their precursors, the (azolylmethy1)pyridiniumand -imidazolium salta 17-28 according to a general procedure shown in Scheme I. In this connection, other l-(lH-benzimidazol-2-ylmethy1)pyridiniumsalts have been so far reported by Dorofeenko et al.bband by Alvarez-Builla et al.k

Firstly, 2-(chloromethyl)benzimidazole (29),2-(chloromethyl)-5,6-dimethylbenzimidazole(30),and 3(5)-(chloromethyl)-1,2,4-triazole(31) were prepared by standard methods? Then, the (azolylmethy1)pyridiniumsalts 17-22 and the (azolylmethy1)imidazolium salts 23-28 were obtained by reaction of a pyridine or an 1-alkylimidazoleand the accessible 2-(chloromethy1)azoles 29-31, following a general method for preparation of quaternary heteroaromatic compounds (Menachutkin reaction). Transformation of compounds 17-28 into the title betaines 5-16 was achieved using an anion-exchange Amberlite IRA-401 regin (OH- form)' (Scheme I). The physical data of all new Universidad de Barcelona.

* Instituto de Ciencias de Materiales, C.S.I.C.,

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compounds described in this work (5-28) are listed in Tables I and 11. (1)(a) Part XI1 Alcalde, E.; PCrez-Garcia,Ll.; Dinar& I.; Frigola, J.; Coombs, G. H. Eur. J. Med. Chem. 1992,27, 171. (b) Abstracted from the Ph.D. Thesis of Ll& Plrez-Garda, Facultad de Farmacia, Universidad de Barcelona, 1991 (microfilmno. OOO, Univeraidad de Barcelona). (2) (a) Alcalde, E.; Dinarb, I.; Elguero, J.; Fayet, J.-P.; Vertut, M.-C.; Miravitlles, C.; Molins, E. J. Org. Chem. 1987,52,5009. (b) Alcalde, E.; DinarCs,I.; Elguero, J.; Frigola, J.; Osuna A.; Castanys, S. Eur. J. Med.

Chem. 1990,25,309.

(3) (a) Alcalde, E.; DinarBs, I.; Frigola, J.; Jaime, C.; Fayet, J.-P.; Vertut, M.-C.; Riua, J.; Miravitlles, C. J. Org. Chem. 1991,56,4223, and references quoted therein. (b) Alcalde, E.; Dinar6s, I. J. Org. Chem. 1991,

56,4233. (4) For an earlierreport see: Alcalde, E.; PBrez, L.; Fayet, J.-P.; Vertut, M.4. Chem. Lett. 1991, 845. (5) (a) Dorofeenko, G.N.; Narkevich, A. N.; Zhdanov,Yu. A.; Soroka, T. G. Khim. Geterosilk. Soedin. 1970, 315. (b) Dorofeenko, G. N.;

Zvezdina, E. A.; Zhdanova, M. P.; Barchan, I. A. Khim. Geterosikl. Soedin. 1973, 1682. (c) Cuadro, A. M.; Novella, J. L.; Molina, A.; Alvarez-Builla, J.; Vaquero, J. J. Tetrahedron 1990,46,6033 and references quoted therein.

0 1992 American Chemical Society

4830 J. Org. Chem., Vol.57,No.18,1992

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Table I. Physical Data of Methylenepyridinium Azolate Inner Salts 6-10 and Their Corresponding N-(Azolylmethy1)pyridinium Salts 17-22 azolyl or azolate R' methodb (yield, %) reaction time, h mp, O C (solvent)c lH-i-benzimidazol-2-yl H A (83) 0.25 221-2 (A) BI6-dimethyl-1H-benzimidazol-2-yl H A (61) 1 224-5 (B) lH-benzimidazol-2-yl NMe2 B (80) 1 263-4 (C) 5,6-dimethyl-lH-benzimidazo1-2-y1 NMe2 B (92) 0.80 215-6 (D) 1H-l,2,4-triazol-3(5)-yl H c (79) 0.75 162-3 (D) lH-1,2,4-triaz01-3(5)-yl NMe2 B (46) 0.25 253-5d 2-benzimidazolate H D (76) 78-808 (A) 5,6-dimethyl-2-benzimidazolate H D (86) 208-106 (D) 2-benzimidazolate NMe2 D (95) 199 (C) 5,6-dimethyl-2-benzimidazolate NMe2 D (94) 182 (C) 3(5)-lI2,4-triazolate H D (33) 160-1 (A) 3(5)-1,2,4-triazolate NMe2 D (98) 202 (E)

"Satisfactory analytical data (10.4% for C, H, N)were obtained for all new compounds. bYieldswere not optimized. 'A, acetonitrile; B ethyl acetate; C, ethanol; D, 2-propanol; E, 85% ethanol. See Experimental Section. e Not analytically pure. Table 11. Physical Data of Methyleneimidazolium Azolate Inner Salts 11-16 and Their Corresponding N-(Azoly1methyl)imidazolium Salts 23-28 azolyl or azolate R' reaction time, h compd" mp, O C (so1vent)e 1H-benzimidazol-2-yl Me 0.50 254 (A) 23 238-9 (B) 2 24 5,6-dimethyl-lH-benzimidazo1-2-y1 Me Bu 1.5 173 (C) 26 1H-benzimidazol-2-yl Bu 1.50 183-4 (C) 5,6-dimethyl-lH-benzimidazol-2-yl 26 Me lH-1,2,4-triaz01-3(5)-yl 1 163 (D) 27 Bu lH-1,2,4-triaz01-3(5)-yl 0.50 130-2d 28 Me 2-benzimidazolate 164 dec 11 Me 5,6-dimethyl-2-benzimidazolate 12 190 (A) Bu 140 dec 2-benzimidazolate 13 Bu 214 dec 5,6-dimethyl-2-benzimidazolate 14 Me e 3(5)-1,2,4-triazolate 16 Bu e 3(5)-1,2,4-triazolate 16 'Satisfactory analytical data (10.4% for C, H, N) were obtained for all new compounds. bYields were not optimized. cA, ethanol; B, acetonitrile; C, acetone; D, 2-propanol. See Experimental SEction. e Hydroscopic oily compound. Scheme I'

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"Reagents and conditions: (i), pyridine or N-alkylimidazole as reagent and solvent, or 4-(dimethy1amino)pyridine in dimethylformamide, at 130 OC under an atmosphere of nitrogen; (ii) anionexchange resin IRA-401 (OH- form). Overall yields: 6-8 and 11-14 > 61%; 9, 10, 15, 16 > 25%.

Spectroscopic Methods. The IR spectra of the compounds 17-28 showed absorptions in the range of 3Nk3200 cm-'(m) and 2775-2600 cm-' (hydrochlorides) (compounds 17-27) or 1200-1000 cm-'(tetrafluoroborates) (compound 28), while these bands were absent for the methylenepyridinium and methyleneimidazolium azolate inner salts 5-10 and 11-16. 'H and 13C NMR data for betaines 5-16 proved very important for structural proof of their highly dipolar structure, aa they were for the previously reported N-ylides 1 and 2. Selected 'H and 13C NMR chemical shifts of betaines 5-16 and their precursors 17-28 are shown in Table Ill and IV (see Tables V-VIII in the supplementary material). The chemical shifts of the CH protons in the azolate moiety move upfield with respect to their precursors 17-28,

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