Acyl imidazoles, acylation

In general, acylation reactions for chromatography are carried out with three main types of acylating reagent acid anhydrides, acid halides and reactive acyl derivatives such as acylated imidazoles, acylated amides or acylated phenols, and the different types are chosen for different reasons. Acyl halides are highly reactive, which may be important with compounds that are difficult to acylate, because of steric factors for instance. A drawback to acyl halides is that a basic acceptor for the halogen acid produced in the reaction is usually required (equation (8)),... 

These compounds are easily prepared from the appropriate 2-aminothiazole and acyl chloride (see Section III.2.D) or by general heterocydization methods. Acyl chlorides may be replaced by the corresponding anhydrides (471). Acids themselves may be used as acylating agents provided that the imidazole-triphenyl phosphine mixture is used as a catalyst (472). The Curtius degradation of 247 yields 2-acetamido-4-phenylthiazole (248) (Scheme 149) (473). 

Data taken from <71pmhi3i297), which contains references to the original literature. Simple alkyl- and aryl-imidazoles. iV-Unsubstituted compounds are IV-acylated prior to injection. 

Azoles containing a free NH group react comparatively readily with acyl halides. N-Acyl-pyrazoles, -imidazoles, etc. can be prepared by reaction sequences of either type (66) -> (67) or type (70)->(71) or (72). Such reactions have been carried out with benzoyl halides, sulfonyl halides, isocyanates, isothiocyanates and chloroformates. Reactions occur under Schotten-Baumann conditions or in inert solvents. When two isomeric products could result, only the thermodynamically stable one is usually obtained because the acylation reactions are reversible and the products interconvert readily. Thus benzotriazole forms 1-acyl derivatives (99) which preserve the Kekule resonance of the benzene ring and are therefore more stable than the isomeric 2-acyl derivatives. Acylation of pyrazoles also usually gives the more stable isomer as the sole product (66AHCi6)347). The imidazole-catalyzed hydrolysis of esters can be classified as an electrophilic attack on the multiply bonded imidazole nitrogen. 

Since /V-acylation is a reversible process, it has allowed the regiospecific alkylation of, for example, imidazoles to give the sterically less favored derivative. This principle is illustrated in Scheme 7 (80AHC(27)24l). 

Substituted imidazoles can be acylated at the 2-position by acid chlorides in the presence of triethylamine. This reaction proceeds by proton loss on the (V-acylated intermediate (241). An analogous reaction with phenyl isocyanate gives (242), probably via a similar mechanism. Benzimidazoles react similarly, but pyrazoles do not (80AHC(27)24l) cf. Section 4.02.1.4.6). 

Deacylations are known. C-Acyl groups in 1,3,4-thiadiazoles are cleaved by sodium ethoxide in ethanol (68AHC(9)165). Imidazole-2-carbaldehyde behaves similarly, yielding imidazole and ethyl formate this reaction involves an ylide intermediate. 3-Acylisoxazoles (405) are attacked by nucleophiles in a reaction which involves ring opening (79AHC(25)147). 

C-Acylation imidazoles in, 1, 463 ortiio-Acylation 2-alkylpyridines, 1, 436 Acylimines... 

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... 

Imidazole, 1 -hydroxy-2,4,5-triphenyl-3-oxides reactions, S, 455 Imidazole, iodo-nitrodehalogenation, 5, 396-397 Imidazole, 1-iodo-reactions, S, 454 stability, S, 110 Imidazole, 2-iodo-synthesis, S, 401 Imidazole, N-iodo-, S, 393 reactions, 5, 454 Imidazole, 4-iodo-5-methyl-iodination, 5, 400 Imidazole, 2-isopropyl-4-nitro-N-nitration, 5, 351 Imidazole, 2-lithio-reactions, S, 106, 448 Imidazole, 2-mercapto-l-methyl-as antithyroid drug, 1, 171 mass spectra, 5, 358 Imidazole, 1-methoxymethyl-acylation, S, 402 Imidazole, 5-methoxy-l-methyl-reactions... 

Imidazole, 1 -methyl-5-nitro-2-styryl-ozonolysis, 5, 437 Imidazole, l-methyl-2-phenyl- C NMR, 5, 354 Imidazole, l-methyl-4-phenyl- C NMR, 5, 355 Imidazole, 2-methyl-4-phenyl-acylation, 5, 402... 

These Br nsted-type plots often seem to be scatter diagrams until the points are collated into groups related by specific structural features. Thus, p-nitrophenyl acetate gives four separate, but parallel, lines for reactions with pyridines, anilines, imidazoles, and oxygen nucleophiles.Figure 7-4 shows such a plot for the reaction of trans-cmmm c anhydride with primary and secondary aliphatic amines to give substituted cinnamamides.All of the primary amines without substituents on the a carbon (R-CHi-NHi) fall on a line of slope 0.62 cyclopentylamine also lies on this line. If this line is characteristic of normal behavior, most of the deviations become qualitatively explicable. The line drawn through the secondary amines (slope 1.98) connects amines with the structure R-CHi-NH-CHi-R. The different steric requirements in the acylation reaction and in the model process... 

Ac-Imidazole, PtCl2(C2H4), 23°, 0.5-144 h, 51-87% yield. Platinum(II) acts as a template to catalyze the acetylation of the pyridinyl alcohol, C5H4N(CH2) CH20H. Normally, acylimidazoles are not very reactive acylating agents with alcohols. 

Cefpimizole (51) appears to be less active in vitro than cefotaxime and cefoperazone and to have a somewhat narrower activity spectrum although some strains of Pseudomonas are susceptible. It is not orally active, but its performance in vivo appears superior to what would be expected from its in vitro data. Its synthesis begins by acylation of cephaloglycin (48) with the bis acid chloride of imidazole-4,5-dicarboxylic acid (49) to give amide 50. The acetyl moiety at C-3 of this intermediate is displaced with 4-pyridineethanesulfonic acid and sodium iodide to give cef-pimazole (51) [16]. 

Acylation of the common starting 3,4-diaminonitrobenzene with furoyl chloride proceeds on the more basic amino group meta to the nitro group to give 140. This is then cyclized to imidazole 141 by means of acetic anhydride. Reduction of the nitro group (142), followed by condensation with ethyl acetoacetate affords furodazole (143) [26]. 

Although acyl imidazoles can be replaced by phenyl esters in some cases," acyl imidazoles are more effecdve for the acyladon of nitroalkanes A combinadon of diethyl phosphorcyani-dates and triethylamime allows the direct C-acyladon of nitromethane by aromadc carboxylic... 

Acylation of 2-aroylimidazoles 492 gave 1-acyl-4,5-disubstituted imidazoles 493, whose cyclocondensation with hydrazine hydrate gave (88JIC784) imidazotriazines 494. 

Bei der Herstellung von Aldehyden iiber die 1-Acyl-imidazole wird die Carbonsaure mit l-[Imidazolyl-(l)-carbonyI]-imidazol umgesetzt und das erhaltene Imidazol-Derivat ohne Isolierung zum Aldehyd reduziert5 ... 

In general, reduction of amides to alcohols is difficult. More commonly the amide is reduced to an amine. An exception uses LiH2NBH3 to give the alcohol. Reduction with sodium metal in propanol also gives the alcohol.Acyl imidazoles are also reduced to the corresponding alcohol with NaBH4 in aqueous HC1. °... 

The P-alanyl dipeptides carnosine and anserine (A -methylcarnosine) (Figure 31-2) activate myosin ATPase, chelate copper, and enhance copper uptake. P-Alanyl-imidazole buffers the pH of anaerobically contracting skeletal muscle. Biosynthesis of carnosine is catalyzed by carnosine synthetase in a two-stage reaction that involves initial formation of an enzyme-bound acyl-adenylate of P-alanine and subsequent transfer of the P-alanyl moiety to L-histidine. 

Related redox transformations allow the conversion of ynals to a,P-nnsaturated esters [33], as well as the ring expansion of formyl P-lactams [34], oxacycloalkane-2-carboxaldehydes [35], and 2-acyl-1-formyIcyclopropanes [36], Farther developments allow the synthesis of amides from a range of a-fnnctionalised compounds, but require an additive (imidazole, HO At or HOBt) for efficient amidation [37],... 

In addition to acyl halides and acid anhydrides, there are a number of milder and more selective acylating agents that can be readily prepared from carboxylic acids. Imidazolides, the (V-acyl derivatives of imidazole, are examples.115 Imidazolides are isolable substances and can be prepared directly from the carboxylic acid by reaction with carbonyldiimidazole. 

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