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.
@,lo
-(laR -
W -CH,
pv'
R
CI'
NCN H
21,22
R H
A H Me H H NMe;l
Ma
qN 3
cr
H 17-20 5,17 6,16 7,lO 6,20
CH,
0,21
lo,=
A H NMe;l
NMe;l
I
1
I
I
~
+
CR
-
H
l~m + -~C H z~q N 3~
11-14
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.,
Campus de la U.
A.B., Bellaterra. Laboratorios Dr. Esteve Barcelona.
0022-3263/92/1957-4829$03.00/0
I
R
I
+
CI'
~
N"
-
15,16
C
H
, R~
~
I~m +~ - c H z q N 3 A'
H
N" H
23-26
R 11,a 12,24 lS,2S 14,B
A
Me Me Me H
H
RBU
Me RBU
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
compd" 17 18 19 20 21 22 5 6 7 8 9 10
Alcalde et al.
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'
mi
Table 111. Selected 'Hand lF NMR Spectra Data of Methylenepyridinium Azolate Inner Salts 5-10 and Their Corresponding N-(Azoly1methyl)pyridinium Salts 17-22'
w - c " z 4 ; a RR
17-21
516
"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,
54
17-20
compd 17
H-2',6' 9.18 9.29
Ab
-0.11
6b 18
96 21
9.16 9.26 -0.10 8.38 8.45 -0.07 8.36 8.46 -0.10 H-2',6' 9.11 9.29
Ab
-0.18
10 22
8.29 8.36 -0.07
5b
A6 7 19
Ab 8
20
Ab
compd
A6
(6) (a) Lettr6, H.;Fritach, W.; Porath, J. Chem. Ber. 1951, 719. (b) IUamab, P.; Petrow, V.;Sturgeon,B.J. Chem. Soc. 19M),1600. (c) Jones, R. G.; Ainsworth, C. J. Am. Chem. SOC. 1955, 77,1538. (7) The use of an anion-exchange AmberliteIRA-401reain (OH- form) or compounds with had been convenientlyapplied to other a betaine character.%
w-cHz
