Acylimidazoles preparation

Table 3-1. Monoesters prepared from carboxylic acids and alcohols or phenols using AyV -carbonyldiimid-azole (CDI), N-acylimidazole (RCOIm), or AyV -sulfinyldiimidazole (ImSOIm).

Y/ .v-(3-Lactains have also been obtained by the Staudinger reaction carried out between divinylimine and /V-acylimidazoles possessing an electron-withdrawing group (EWG) in a position [111]. This latter were prepared by treatment of a-EWG substituted carboxylic acids with 1,1-carbonyldiimidazole. 

Methyl esters may be prepared by reaction of the aromatic carboxylic acid with diazomethane (cf. Section 4.2.25, p. 433) or, more conveniently, by reaction with a boron trifluoride-methanol reagent. The latter procedure is illustrated by the preparation of methyl m-chlorobenzoate and dimethyl terephthalate (Expt 6.164). t-Butyl esters may be prepared by conversion of the acid into an N-acylimidazole by reaction with N,N -carbonyldiimidazole, followed by reaction with t-butyl alcohol in the presence of DBU62 (Expt 6.165). 

Peracids can also be prepared from reaction of hydrogen peroxide with acyl halides, anhydrides, amides, dialkyl phosphates, N-acylimidazoles, aromatic aldehydes, lipase catalysis and esters (Figure 2.38).100-107... 

The requisite W-methoxy-W-methylamides may be pre >ared from acid chlorides by employing a slight excess of the commercially available W,G-dimetiiylhydroxylamine hydrochloride in the presence of pyridine. They have also been pre >ared from acylimidazoles and from mixed anhydrides of carboxylic acids. Once prepared, these systems X)ssess stability equivalent to that of most tertiary amides and, in... 

The synthesis of aldehydes [C5] can also be accomplished by controlled reduction of acylaziridines 3.178 [BK5] or of acylimidazoles 3.179 [W3] by LAH in Et20 at -10°C, by LTBA or by Red-A1 in [H3, M3] R can be aliphatic or aromatic (Figure 3.66). The N-methoxy-N-methylcarboxamides 3.180 are also cleanly reduced to aldehydes by LAH in excess in THF at low temperature or by DIBAH in THF at 0°C. In many cases, the latter reagent does not lead to formation of alcohols as byproducts resulting from a subsequent reduction of the aldehyde [NWl]. This behavior can be understood by the stabilization through chelation of the lithium or aluminum intermediate (Figure 3.66). a,p-Unsaturated aldehydes may also be prepared by this method, using DIBAH in THF [BS8, NBl]. 

Acylation of imidazole produces A-acylimidazoles via loss of proton from the initially-formed A-3-acyl-imidazolium salt. A-Acyl-imidazoles are even more easily hydrolysed than A-acyl-pyrroles moist air is sufficient. The ready susceptibility to nucleophilic attack at carbonyl carbon has been capitalised upon commercially available l,l -carbonyldiimidazole (CDI), prepared from imidazole and phosgene, can be used as a safe, phosgene synthon, and also in the activation of acids for formation of amides and esters via the A-acyl-imidazole. ... 

The use of a,P-unsaturated 2-acylimidazoles [151] as the dienophile increased the practicality of the approach, since the imidazole group can be removed readily from the product. The substrate scope is quite broad substituents at the alkene moiety (e.g., alkyl, aryl and 2-furanyl) were very well tolerated, hi all cases good to excellent enantioselectivies and diastereoselectivities were obtained, i.e., 80-98% ee for the endo isomer and endo. exo > 94 6, in the case of the 4,4 -dimethyl-2,2 -bipyridine ligand [152]. Moreover, the D-A reaction was successfully performed on a preparative scale (1 mmol), making it attractive from a synthetic point of view. 

Activation of Carboxylic Acids Synthesis of Acyl Imidazoles. iV,AA-Carbonyldiimidazole (1) converts carboxylic acids into the corresponding acylimidazoles (2) (eq 1). The method can be applied to a wide range of aliphatic, aromatic, and heterocyclic carboxylic acids, including some examples (such as formic acid and vitamin A acid) where acid chloride formation is difficult. The reactivity of (2) is similar to that of acid chlorides, but the former have the advantage that they are generally crystalline and easily handled. Isolation of (2) is sirr5>le, but often unnecessary further reaction with nucleophiles is usually performed in the same reaction vessel. Conversion of (2) into acid chlorides (via reaction with HCl), hydrazides, hydroxamic acids, and peroxy esters have all been described. Preparation of the more irr5)ortant carboxylic acid derivatives is described below. 

Aldehydes and Ketones from Carboxylic Acids. Reduction of the derived acylimidazole (2) with Lithium Aluminum Hydride achieves conversion of an aliphatic or aromatic carboxylic acid to an aldehyde (eq 6). DiisobutyUduminum Hydride has also been used, allowing preparation of a-acylamino aldehydes fromiV-protected amino acids. Similarly, reaction of... 

Reaction of acylimidazoles with the appropriate carbon nucleophile has also been used for the preparation of a-nitro ketones and /3-keto sulfoxides. 

C-Acylation. C-Acylation can be realized by treatment of acylimidazoles, derived from carboxylic acids and 1, with the magnesium salts of malonic esters prepared by using Bu2Mg. Acyl imidazoles can also undergo Claisen-type condensation with the dianion of -keto esters (eq 38). ... 

Protection of an alcohol function by esterification sometimes offers advantages over acetal protecting groups such as the tetrahydropyranyl ethers. Generally, acetals are stable in base and labile in acid, while esters are more stable in acid than acetals and are readily hydrolyzed in base. Esters are notably useful in reactions such as oxidations, but are not satisfactory in organometallic reactions. Acetates and benzoates are the most common ester protecting groups they can be conveniently prepared by reaction of unhindered alcohols with acetic anhydride or benzoyl chloride, respectively, in the presence of pyridine or other tertiary amine. The use of reactive amides such as N-acylimidazoles (imidazolides) allows the reaction to be carried out in the absence of added bases ... 

A number of acylated imidazoles are commercially available as acylating agents. Others are readily prepared by acylating imidazole in tetrahydrofuran with the appropriate acid chloride, or by condensation of the acid with carbonyl diimidazole. The imidazole portion of acylimidazole acylating reagents is, of course, the other product that appears during the acylation reaction besides the desired derivative, but at least in GLC analyses it volatilizes with or at least close to, the solvent peak and does not cause any interference. 

A soln. of 1-heptanoylimidazole prepared from heptanoic acid and N,N -thiongl-diimidazole in tetrahydrofuran allowed to react with the Mg-enolate of monoethyl malonate (s. Synth. Meth. 14, 888) ethyl heptanoylacetate. Y 74%.— The use of mild acylating agents, such as 1-acylimidazoles or carboxylic alkoxy-formic anhydrides, prevents diacylation, which occurs with acid chlorides. F. e. and modifications s. G. Bram and M. Vilkas, Bl. 1964, 945. 

A soln. of phenylmagnesium bromide prepared from bromobenzene and Mg in tetrahydrofuran added dropwise during 2 hrs. to N-(3-chlorobenzoyl) imidazole in the same solvent, and stirred 3 hrs. at room temp. 3-chlorobenzophenone. Y 94%.— This and other reactions (s. 441) are based on the great ease of nucleophilic substitution at the carbonyl group of the N-acylimidazoles. F. e. s. H. A. Staab and E. Jost, A. 655, 90 (1962). 

Thioesters.—Mixed anhydrides prepared from 2,4,6-trichlorobenzyl chloride and a carboxylic acid react with various thiols in the presence of 4-dimethyl-aminopyridine to give thioesters in 78—86% isolated yield.Somewhat less impressive yields were obtained in a few of the cases studied when l-fluoro-2,4,6-trinitrobenzene was used to couple the acid and the thiol.Treatment of 1-acylimidazoles with thiols in the presence of a catalytic amount of Mg(OEt)2 furnishes thioesters in good yields. Diphenyl-2-oxo-3-oxazolinylphosphonate brings about effective reaction between acids and thiols. Thiolacetates are efficiently prepared using the reaction of an alcohol with triphenylphosphine and di-isopropyl azodicarboxylate in the presence of thiolacetic acid/ A synthesis of some amino-acid derivatives containing the thioester functional group is achieved by the reaction of a vinyloxyborane with a Schiffs base (Scheme 56). ... 

Aryltrifluoromethyl ketones are prepared by reaction of an aryl-lithium with a,a,a-trifluoro-N,N-dimethylacetamide. 2-Acyloxypyridines and N-acylimidazoles, " in conjunction with trifluoroacetic acid, acylate arenes in good yield without the need for a classical Friedel-Crafts catalyst or a preformed mixed anhydride. However, imidazole in trifluoroacetic anhydride is reported to form 2-aryl-Af,JV -diacyl-4-imidazolines with arenes reactive towards electrophilic attack. These adducts are readily hydrolysed by sodium hydroxide to the corresponding aldehyde [equation (14)]. This sequence may offer advantages over the Vilsmeier method of formylation, in that the aldehyde is introduced in a protected form. 

Mixed carbonic anhydrides, acyl guanidine, N-acylimidazoles, N-acyl-N -methylimidazolium chloride and acyl phosphates are other agents that have been used to esterify starch in water [65-76]. Starch esters containing carboxylic acid group have been prepared by reaction with cyclic dibasic anhydrides [65]. 

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