1- Acetylimidazole

4-Amino-5-methylisoxazole hydrochloride (1.35 g, 10 mmol) is treated with sodium acetate (0.820 g, 10 mmol) and excess acetic anhydride (5 ml) at room temperature (2h). The mixture is then concentrated under reduced pressure, and the residue is taken up in diethyl ether, dried (MgS04), filtered, and the filtrate concentrated in vacuo before removal of traces of acetic anhydride under high vacuum. The product is isolated as a white solid (1.38 g, 98%), m.p. 94-97 C. 

This is made by the general procedure above in 37% yield, m.p, 128-130°C, recrystallized from ethyl acetate-isopropyl ether. 

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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. iV-Acylpyrroles are obtained by reaction of the alkali-metal salts of pyrrole with an acyl halide. AC-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). 

This catalysis follows Scheme II that catalysis occurs means that N-acetylimidazole is more susceptible to hydrolysis than is the ester. (This does not explain why the N-acetylimidazole is formed, however.)... 

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... 

Sanders and his co-workers reported two enzymatic reactions using CPO 3 described above (Fig. 9). In the reactions, three zinc metals are incorporated into each porphyrin. The first reaction is the acylation reaction of pyridyl alcohol 18 using AT-acetylimidazole (19) [35] to afford 20. In the presence of 3, the reaction is accelerated 16 times compared to the reaction without 3. The replacement of 3 with 4 (M=Zn) gave no significant acceleration of the reaction therefore, the enzymatic reaction proceeds through a supramolecular... 

Catalysis by flavoenzymes has been reviewed and various analogues of FAD have been prepared e.g. P -adenosine-P -riboflavin triphosphate and flavin-nicotinamide dinucleotide ) which show little enzymic activity. The kinetic constants of the interaction between nicotinamide-4-methyl-5-acetylimidazole dinucleotide (39) and lactic dehydrogenase suggest the presence of an anionic group near the adenine residue at the coenzyme binding site of the enzyme. ... 

This mechanistic interpretation is supported by the isolation of N-acetylimidazole as a major product and the observation of only first order catalysis by N-methylimidazole irrespective of the pH... 

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... 

Direct acylation of imidazole can also be achieved with carboxylic acid anhydrides. For example, if imidazole is dissolved at room temperature in acetic anhydride, crystals of iV-acetylimidazole begin to separate out after removal of excess anhydride and the resulting acetic acid under vacuum at 60 °C, nearly pure iV-acetylimidazole (m.p. 100-102 °C) is obtained in almost quantitative yield.[4]... 

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... 

For the aminolysis of TV-acylimidazoles in dry tetrahydrofuran a bimolecular reaction is suggested. The rate constant for conversion of AT-acetylimidazole with an ammonia-saturated solution in tetrahydrofuran at 25 °C was found to be 0.01 min-1, with t1/2 = 69.3 min.[3]... 

While with AT-acetylimidazole (A) only primary amines are generally converted to amides in high yields, and secondary amines are formed in moderate or low yields, both primary and secondary amines can be acetylated in high yield using l-acetyl-3-benzylimidazo-lium bromide (B) at room temperature [140]... 

A polyimide film was made by heating a polyamide carboxylic acid at 300 °C for 30 min with azolides such as iV-acetylimidazole, iV-trifluoroacetylimidazole, or N-benzoy limidazole.[ 1633... 

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]... 

Proteins/enzymes that have been modified with TV-acetylimidazole include ... 

In ref. [74] it is emphasized that N-acetylimidazole reacts with all tyrosyl residues in copolymers and denatured proteins but only with free tyrosyl residues in native proteins. In ref. [75] it is noted that Af-acetylimidazole reacts extensively with both lysine and tyrosine chains. 

The synthesis of isoxazoles by use of azolides is illustrated by the following example of 3,4-diphenyl-5-methylisoxazoles, prepared by conversion of the deoxybenzoin oximes with JV-acetylimidazole with the aid of butyllithium 1381... 

By condensation of 1-acetylimidazole or l-(l-pentin-4-oyl)imidazole with dimethyla-cetyl-enedicarboxylate at higher temperature, 7/f-pyrrolo[l, 2-a]imidazoles are formed along with dimethyl(imidazol-l-yl)fumarate tl58],[157]... 

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) ... 

Several different aqueous acid media can be used for the reaction. Figure 14 refers to acetylimidazole in sulfuric acid log H2o is subtracted from the... 

Fig. 14 Plot of logk, — logaH,o against X for the hydrolysis of acetylimidazole in aqueous sulfuric acid at 25°C. Data from refs 251 and 252. Reprinted with permission from ref. 254, 1997 NRC Canada.

In the reaction with PNPA, myristoylhistidine [29] in a cationic micelle rapidly forms acetylimidazole as a fairly stable intermediate which is readily observable at 245 nm. On the other hand, a mixed micelle of [29] and N,N-dimethyl-N-2-hydroxyethylstearylammonium bromide [30] leads to the formation and decay of the intermediate, indicating that the acetyl group is transferred from imidazole to hydroxyl groups (Tagaki et al., 1977 Tagaki et al., 1979). This can be a model of cr-chymotrypsin which catalyses hydrolysis of PNPA (non-specific substrate) by initial acylation of the histidyl imidazole followed by acyl transfer to the seryl hydroxyl group (Kirsh and Hubbard, 1972), as indicated schematically in (12). 

Bifunctional micellar catalysis has also been reported by Moss and coworkers (Moss et al., 1975, 1977) and Tonellato (1977). In contrast to the situation of the mixed micelle, the acetylimidazole intermediate was not observable in the reaction using the bifunctional catalyst [31]. In a preparative... 

Dimethylisoxazole, 2,4-Dimethylthiazole, and 1-Acetylimidazole. Org. Mass Spec-trom. 1981,16,55-61. 

Dimethylamino)propanol (201 R = H) is known to be acetylated by N-acetylimidazole (206) by a mechanism that involves intramolecular general base... 

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