A-Acetylimidazoles

When 2-lithio-2-(trimethylsilyl)-l,3-dithiane,9 formed by deprotonation of 9 with an alkyllithium base, is combined with iodide 8, the desired carbon-carbon bond forming reaction takes place smoothly and gives intermediate 7 in 70-80% yield (Scheme 2). Treatment of 7 with lithium diisopropylamide (LDA) results in the formation of a lactam enolate which is subsequently employed in an intermolecular aldol condensation with acetaldehyde (6). The union of intermediates 6 and 7 in this manner provides a 1 1 mixture of diastereomeric trans aldol adducts 16 and 17, epimeric at C-8, in 97 % total yield. Although stereochemical assignments could be made for both aldol isomers, the development of an alternative, more stereoselective route for the synthesis of the desired aldol adduct (16) was pursued. Thus, enolization of /Mactam 7 with LDA, as before, followed by acylation of the lactam enolate carbon atom with A-acetylimidazole, provides intermediate 18 in 82% yield. Alternatively, intermediate 18 could be prepared in 88% yield, through oxidation of the 1 1 mixture of diastereomeric aldol adducts 16 and 17 with trifluoroacetic anhydride (TFAA) in... 

Whereas under the conditions specified above JV-acetylpyrrole, like a typical acetamide, is not detectably hydrolyzed in neutral aqueous medium, the half-life of N-acetylpyrazole is 908 min, and that of A-acetylimidazole is reduced to 41 min for 1-acetyl-1,2,4-triazole and for the isomeric 1-acetyl-1,2,3-triazole, half-lives of 6.4 and 26.6 min, respectively, were observed (for an explanation of the different reactivities of the two pairs of isomers see above). Hydrolysis of TV-acetyltetrazole under the same conditions occurs too rapidly to be measured with conventional spectroscopic techniques. The reaction enthalpy AH was determined for A-acetylimidazole to be — 4.83 kcal/mol for the corresponding 1,2,4-triazolide the value was — 7.29, and for the tetra-zolide — 10.31 kcal/mol. 111... 

The same order of reactivity observed for the hydrolysis of A-acetylazoles (Table 1-1) is also found for azolides with other N-acyl groups. Exceptional, however, are the Af-formylazoles A-formylimidazole in neutral water is hydrolyzed immeasurably rapidly even in a 1 1 mixture of water/tetrahydrofuran at 20.6 °C the half-life is in the order of only 3.7 min, approximately a factor of 100 faster than that for A-acetylimidazole under the same conditions. 131... 

The acetylation of methyl-a-D-glucopyranoside with A-acetylimidazole (DMF, room temp., 48 h) affords no significant selectivity, and leads to partial substitution at all four hydroxyl groups (2-OAc 3-OAc 4-OAc 6-OAc = 35 15 20 35). 19 1... 

A-Acetylimidazole was found to be a very efficient terminating (capping) agent in the solid-phase synthesis of peptides.t40],[41] A terminating agent is used to block any N-terminal amino groups that have not reacted in the coupling steps.[40]... 

A Lewis acid is also necessary for the acetylation of tetracarbonylferrate using N-acetylimidazole. In the absence of a Lewis acid, a Claisen-type condensation product was formed, which has been synthesized independently from 2 moles of A-acetylimidazole with sodium terf-butanolate in tert-butyl alcohol (55% yield) or with imidazole sodium in THF (95% yield) ... 

Pyrrole and alkylpyrroles can be acylated by heating with acid anhydrides at temperatures above 100 °C. Pyrrole itself gives a mixture of 2-acetyl- and 2,5-diacetyl-pyrrole on heating with acetic anhydride at 150-200 °C. N-Acylpyrroles are obtained by reaction of the alkali-metal salts of pyrrole with an acyl halide. A-Acetylimidazole efficiently acetylates pyrrole on nitrogen (65CI(L)1426). Pyrrole-2-carbaldehyde is acetylated on nitrogen in 80% yield by reaction with acetic anhydride in methylene chloride and in the presence of triethylamine and 4-dimethylaminopyridine (80CB2036). 

The mechanism of CDI-mediated acylation of amines is well understood. The first step involves a partial protonation of the basic imidazole-nitrogen, protonated A-acetylimidazole has a p a of 3.6,f l leading to an activated species which is then attacked by the carboxylate. The resulting mixed anhydride extrudes carbon dioxide giving rise to A-acylimidazole which on treatment with an amine compound leads to the desired anoide (Scheme 1). An important advantage of this method over the carbodiimide method is that the byproducts carbon dioxide and imidazole are readily and quantitatively separated from the reaction product by simple washing procedures. 

An interesting mechanistic application of free energy relationships in calculating rate constants concerns the reactivity of the putative intermediate in the reaction of imidazole with 4-nitrophenyl acetate. The putative stepwise process (Scheme 15) involves a zwitterionic tetrahedral intermediate which would decompose to the product A-acetylimidazole, subsequently hydrolysing to acetate ion and imidazole. 

Acylation of aquatic humic substances with acetic anhydride in a variety of solvents was found to be unsatisfactory because of dehydration and 7r-bond formation. The mild acylating reagent, A-acetylimidazole, did not give complete acylations of hindered hydroxyl groups. Acetyl chloride was tested under a variety of conditions and gave complete derivatization of primary and secondary hydroxyls under the conditions shown in reaction (3) ... 

Some protocols recommend a capping reaction for unreacted chains following each coupling. The capping step is usually carried out by acetylation with AcaO-DDEA (1 1, 30 equiv.) in DMF. In some automated instruments AcaO is replaced by a 0.3 M solution of A-acetylimidazole in DMF [21]. 

Some properties of purified endo-(l- -4)- 3-D-xylanase from the ligniperdous fungus Trametes hirsuta have been investigated. The enzyme was stable between pH 4.0 and 8.0 with optimum activity at pH 5.0-5.5. The temperature optimum was 50 C and the enzyme was stable for up to 30 min at 45 C however, it was denatured at higher temperatures. The for 4-0-methyl-D-glucurono-D-xylan was 6.36 X10" equivalents of D-xylose per litre, the activation energy was 28 kj moF The enzyme (mol. wt. 2.2-2.4X 10 by gel chromatography) was activated by Ca " and inhibited by Ag and Hg. On the basis of the effects of 2-hydroxy-5-nitrobenzyl bromide, iV-bromosuccinimide, and A-acetylimidazole it was assumed that L-tryptophan and possibly L-tyrosine residues influence the enzyme catalysts. 

Phytohaemagglutinins.—Abrin, ricin, and their isolated A and B chains have been subjected to various chemical treatments and the effect of these on the biological activity of the lectins assessed. Reductive methylation, periodate oxidation, or succinylation of abrin or ricin reduced the toxicity and haemagglutinating ability of the former but not the latter. Treatment with A-acetylimidazole or A-bromosuccinimide resulted in strongly reduced toxicity of abrin and ricin, while 2-hydroxy-5-nitrobenzyl bromide had much less effect. 

Acetyl-l-hydroxynaphthalene,. see A-00026 A-Acetylimidazole, in I-OOOOl A-Acetylmercaptosuccinic anhydride, in... 

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