Alkoxycarbonyl imidazoles

A few hydrazides and thiohydrazides prepared with the aid of alkoxycarbonyl-imidazoles or thiocarbonylimidazoles are shown below 12261,12271... 

As alternatives to 4-nitrophenyl chloroformate, carbonyl diimidazole [100-102] or di-A-succinimidyl carbonate [103,104] can be used to convert polymeric alcohols into alkoxycarbonylating reagents suitable for the preparation of support-bound carbamates. Polystyrene-bound alkoxycarbonyl imidazole is less reactive than the corresponding 4-nitrophenyl carbonate, and sometimes requires heating to undergo reaction with amines. Additional activation of these imidazolides can be achieved by N-methylation (Entry 9, Table 14.7). 

Rearrangement of alkoxycarbonyl imidazole acryl azides in diphenyl ether at high temperatures afforded imidazo[l,5-c]pyrimidinone or imidazo[4,5-c]pyridinone derivatives <02TL5879>. Efficient synthesis of imidazopyridodiazepines from peri annulation in imidazo[l,2-a]pyridine has been described <02TL9119>. A convenient synthesis of 3,6-disubstituted-2-aminoimidazo[l, 2-a]pyridines has been published <02TL9051>. Novel 2,3-dihydroimidazo[2,l-h][l,3]oxazoles were prepared from intramolecular nucleophilic i/wo-substitution of 2-alkylsulfonylimidazoles <02S2691>. 4,4 -Bi-l//-imidazol-2-ones were efficiently synthesized from 5-amino-ot-imino-1 //-imidazole-4-acetonitriles and isocyanates <02JOC5546>. 

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... 

The parent 2(3/i/)-oxazolone moiety functions as a bifunctional leaving group when carboxyl groups are activated for acylations and condensations, similar to other five- and six-membered heterocycles such as imidazole, triazole, and 2-pyridinethiol. The excellent leaving ability of a 2(3//)-oxazolone moiety has led to the development of versatile reagents. Thus, 3-acyl- and 3-alkoxycarbonyl-2(3//)-oxazolones serve as ready-to-use -type agents for the regioselective and chemoselective N-protection of amino alcohols, amino phenols and polyamines. 

Als a-Amino-carbonsaure-nitrile werden oft Amino-malonsaure-ester-nitrile, -amid-nitrile bzw. -dinitrile eingesetzt195,198 202. Die so erhaltenen 4(5)-Alkoxycarbonyl-5(4)-amino-, 5(4)-Amino-4(5)-aminocarbonyl- bzw. 5(4)-Amino-4(5)-cyan-imidazole sind wich-tige Bausteine fur zahlreiche Purin-Synthesen203. 

Mit Alkoholen oder Aminen wird nur ein Aquivalent Imidazol abgespalten und man erhalt unter Erhalt der CO-Gruppe 1-Alkoxycarbonyl- bzw. 1-Aminocarbonyl-imidazole (Bd. E4, S. 180), in denen auch der zweite Imidazol-Rest durch ein weiteres Nukleophil substituiert werden kann688. Analog fiihrt die Umsetzung mit Hydroperoxiden zu 1-Alkylperoxycar-bonyl-imidazolen994. 

Electrocyclization is the key step in a route to 4//-imidazoles 1187 and imidazoles 1188. Thus, activation of AT-acylamidines 1183 with trifluoromethanesulfonic anhydride and subsequent condensation with amino compounds 1185 produces l-amino-2,4-diazapenta-l,3-dienes 1186. Deprotonation of 1186 by the use of strong organic bases yields the corresponding 4//-imidazoles 1187 or imidazoles 1188 after amine elimination through an anionic 1,5-electrocyclization reaction. For the cyclization to occur, the amino compound 1185 needs to possess electron-withdrawing substituents such as alkoxycarbonyl or fluorenyl groups (Scheme 290) <2004EJO2567>. 

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>. 

N-Alkoxycarbonyl)- and (N-aryloxycarbonyl)imidazoles (carbamates) were unambiguously proven to be the products of the reaction of JV,JV -carbonyldiimidazole (CDI) with alcohols [448]. Reaction of CDI with 2,6-dimethylphenol or 1-indanol gave (on the basis of IR and NMR evidence) the corresponding carbamate in yields of 91% and 42%, respectively. 

Anisimova VA, Kuz menko TA, Spasov AAet al (1999) Synthesis and study of the hypotensive and antiarrhythmic activity of 2,9-disubstitued 3-alkoxycarbonyl-imidazo[l,2-a]benz-imidazoles. Pharm Chem J 33(7) 361-365... 

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