4- Alkenyl imidazoles

Mit Carbonyl-Verbindungen werden l-(l-Alkenyl)-imidazole Oder an der Methylen-Grup-pe substituierte Diimidazolo-methane gebildet (vgl. S. 167, 168)689. Thiokohlensaure-688,689 und Oxalsaure-diimidazolid995 reagieren analog Kohlensaure-diimid-azol. 

Using the Stille reaction similar to the one described immediately above, a new synthetic route to imidazo[4,5-c]pyridines has been delineated [46]. Following the coupling reaction to provide alkenyl imidazole 79b, an electrocyclic reaction was employed to provide 80 after aromaticity was attained by the elimination of methanol. The flexibility of this process is demonstrated by the fact that nearly identical yields are possible regardless of whether the Stille coupling reaction is done on compound 79a or the aldehyde compound that immediately precedes it in the synthetic sequence. 

Keywords 1-Substituted imidazoles, isothiocyanates, cyanophenylacetylene, catalyst-free, solvent-free, room temperature, multi-component reaction, N-(Z-alkenyl)imidazole-2-car-bothioamides, stereoselectivity... 

To a mixture of isothiocyanate (2 1 mmol) and cyanophenylacetylene (3 1 mmol) was added 1 -substituted imidazole (1 1 mmol). The mixture was stirred at room temperature for 24 h (stirring for 48 h is required when arylisothiocyanates are used). After then the reaction mixture was washed with Et20 (1x3 mL) to afford Al-(Z-alkenyl)imidazole-2-carbothioamide 4 in moderate to good yields (62-91%). All the products were characterized by means of elemental analyses and spectral studies including IR, H-NMR, and C-NMR. 

Trofimov, B. A., Andriyankova, L. V., Nikitina, L. P., Belyaeva, K. V., Mai kina, A. G., Afonin, A. V., and Ushakov, I. A. (2012). Stereoselective metal-fiee reaction of imidazoles with isothiocyanates involving cyanophenylacetylraie A shortcut to iV-(Z-alkenyl)imidazole-2-carbothioamides. Synlett, 23, 2069-2072. 

Imidazole, 4-acetyl-5-methyl-2-phenyl-synthesis, 5, 475 Imidazole, 1-acyl-reactions, 5, 452 rearrangement, 5, 379 Imidazole, 2-acyl-synthesis, 5, 392, 402, 408 Imidazole, 4-acyl-synthesis, 5, 468 Imidazole, C-acyl-UV spectra, 5, 356 Imidazole, N-acyl-hydrolysis rate constant, 5, 350 reactions, 5, 451-453 synthesis, 5, 54, 390-393 Imidazole, alkenyl-oxidation, 5, 437 polymerization, 5, 437 Imidazole, 1-alkoxycarbonyl-decarboxylation, 5, 453 Imidazole, 2-alkoxy-l-methyl-reactions, 5, 102 thermal rearrangement, 5, 443 Imidazole, 4-alkoxymethyl-synthesis, 5, 480 Imidazole, alkyl-oxidation, 5, 430 synthesis, 5, 484 UV spectra, 5, 355 Imidazole, 1-alkyl-alkylation, 5, 73 bromination, 5, 398, 399 HNMR, 5, 353 synthesis, 5, 383 thermal rearrangement, 5, 363 Imidazole, 2-alkyl-reactions, 5, 88 synthesis, 5, 469... 

Alkenyl groups in A-alkenylazoles act as weak or moderate -electron acceptors. Thus, the basic pKa of 1-vinylimi-dazole (5.14) is nearly 2 pK units lower than that of imidazole. Examination of 1SN NMR spectra of 1-vinylimidazoles and -benzimidazoles shows that the nitrogen attached to the vinyl group resonates in at a higher field than N(3). In accord with these results 1-vinylimidazoles form less stable complexes with transition metals than 1-alkylimidazoles. 

There are numerous examples of quaternizing alkylations of imidazoles using such diverse reagents as alkyl, alkenyl or aralkyl halides, ethyl chloroacetate, phenacyl bromide or dimethyl sulfate. Since water is frequently held very tenaciously by imidazole quaternary salts the compounds are often best prepared in anhydrous conditions (e.g. dry benzene solvent in a dry nitrogen atmosphere) even though the reaction is commonly slower in non-polar solvents. 

Studies of alkenyl- and alkynyl-imidazoles in recent years have increased because of the interest in the polymerization of these compounds under the influence of free radical initiators. 

From the interaction at low temperatures in basic medium of an aldehyde or ketone and tosylmethyl isocyanide ( tosmic ), iV-(l-tosyl-l-alkenyl)formamides are formed. When these are dehydrated they produce 1-isocyano-l-tosylalkenes (66) which react with primary amines to form imidazoles in high yields (Scheme 35) (79RTC258). 

Table 9 N-arylation/alkenylation of imidazole and benzimidazole via improved Ullmann-type ooupling reaotions... 

Imidazole zinc reagent 372 was made from 2-iodoimidazole 371 with activated zinc dust. The organozinc reagent was cross-coupled with aryl iodides and alkenyl iodides, in good yields (Scheme 88), <1997T7237>. 

Alkenyl) substituted arylimidazoles 776 ( = 1,2) undergo iodocyclization to form fused imidazoles 775, 777 (Scheme 190). The extent of iodination on the imidazole core depends on the nature of the reagents used... 

Unactivated imidazoles and benzimidazoles are seldom sufficiently electron deficient for nucleophilic substitution, but electron-withdrawing substituents or quatemization can facilitate reaction. For example, 1,3-bis(alkoxycarbonyl)imidazolium salts, formed in situ, react with organotin reagents to form 2-alkenyl products (Scheme 31) <92TL5399>. 

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