Imidazoles reaction with dimethyl acetylenedicarboxylate

N-silylated imines 509 react with the Li salts of tosylmethylisonitriles to give 4,5-disubstituted imidazoles in moderate yields [93]. Acetylation of N-trimethylsilyl imines 509 with acetyl chloride and triethylamine affords 72-80% of the aza-dienes 510 these undergo readily Diels-Alder reactions, e.g. with maleic anhydride at 24 °C to give 511 [94] or with dimethyl acetylenedicarboxylate to give dimethyl pyridine-3,4-dicarboxylates [94] (Scheme 5.29). 

The reaction of iV-acylimidazole with dimethyl acetylenedicarboxylate in acetonitrile at 25 °C provided (2-imidazolyl)maleates and, as by-product, dimethyl(imidazol-l-yl)-fumarate tl57]... 

Reaction of 108 with dimethyl acetylenedicarboxylate gave pyrrolo[2,3-4] imidazole 111 in poor yield (Equation 11) <2001JHC205>. 

Imidazole nitrones 127 reacted with dimethyl acetylenedicarboxylate to yield imidazo[l,5-fc]isoxazoles 128, which in the presence of base afforded imidazoles 129 <00TL5407>. Chiral imidazoline nitrone 130 participated in a [3+2] cycloaddition reaction with various dienophiles to furnish imidazoisoxazoles 131 <00SL967>. A convenient synthesis of AyvyV -trisubstituted ethylenediamine derivatives from 2-methyl-2-imidazoline has been reported <00SC3307>. Dehydrogenation of 1,3-di- and 1,2,3-trisubstituted imidazolidines afforded l//-4,5-dihydroimidazolium salts <00SC3369>... 

The reaction of nitrone 99 with dimethyl acetylenedicarboxylate (DMAD) at room temperature in CH2CI2 gave a colorless crystalline product that has been identified as trimethyl 3,3-dimethyl-l-phenyl-377-pyrrolo[l,2-f]imidazole-5,6,7-tricarboxylate 100. A mechanism explaining this transformation has been reported (Equation 13) <2001RCB882>. 

This classification is illustrated in Scheme 317. Imidazole synthesis under this category is uncommon, as noted in CHEC(1984) and CHEC-II(1996). One example, in which secondary amino-AT-carbothioic acid (phenyl- -tolylimino-methyl)amides 1258 react with dimethyl acetylenedicarboxylate to form 4-aminoimidazoles 1259, has been reported. A reaction mechanism including the formation of a seven-membered cyclic intermediate followed by the extmsion of thioglyoxylic ester has been proposed (Scheme 318) <2004TL8945>. 

Cyclic nitrones 1490 (A -imidazoline 3-oxides) react regioselectively with alkyl phenylpropiolates 1491 (or with dimethyl acetylenedicarboxylate) to give the corresponding 2-phenyl-3a,4,5,6-tetrahydroimidazo[l,5- ]isoxazole-3-carboxylic acid alkyl esters 1492. Subsequent thermal, base (piperidine, triethylamine, or alkoxide) induced ringopening reactions led to imidazoles 1493 (Scheme 385) <2004SC1617, 2000TL5407>. 

---