Diazomethane carboxylic acid chloride reactions

Because of the high polarity of the C=N double bonds, cyanuric chloride (120, R= Cl) is comparable with a carboxylic acid chloride. This explains its smooth reaction with diazomethane to yield dichloro-(diazomcthyl)-l,3,5-triazine (121, R = The analogous com-... 

Thiophene- and benzo[6]thiophene-carboxylic acids undergo all the normal reactions of an aromatic carboxylic acid (63AHC(1)1, 70AHC(11)177). They can be converted to acid chlorides, amides and esters the esters can be used to make hydrazides. Benzo[6]thiophene-2-carboxylic acid chloride has been converted to the methyl ketone with dimethylcadmium and to the diazoketone with diazomethane. Bromodecarboxylation of the silver salts (Hunsdiecker reaction) has been used to prepare the dibromo compounds (340) and (341). 

Then as a result of reaction of 3a-acetoxy-lip-ol-18-one-pregnane lip,18-lactone 17-carboxylic acid and HCI the 3a-acetoxy-lip-ol-18-one-pregnane lip,18-lactone 17-carboxylic acid chloride was obtained. The 3a-acetoxy-lip-ol-18-one-pregnane lip,18-lactone 17-carboxylic acid chloride was treated with diazomethane to give 3a-acetoxy-lip-ol-18-one-pregnane lip,18-lactone 17-diazoketone. 

With very few exceptions ketenes cannot be isolated pure at room temperature (cf. Section 15.4). Consequently, they are prepared in situ and in the presence of the heteroatom nucleophile. The Wolff rearrangement of a-diazoketones is often used for this purpose (Section 14.3.2). a-Diazoketones can be obtained, for example, by the reaction between a carboxylic acid chloride and diazomethane (Figure 8.13 see also Figure 14.27) or hy treating the sodium enolate of a-formylketones with tosyl azide (Figure 14.29). 

Monohalo ketones may be prepared by starting from pure diazo ketones an ethereal or benzene solution or suspension of a carboxylic acid chloride (1 mole) is added during 1-2 h to a stirred solution of diazomethane (3 moles) at 0-5°, reaction is allowed to proceed at 20-25°, the solvent is removed in a vacuum, and the product is recrystallized 1169 -chloro ketones may be formed as by-products during preparation of the diazo ketone, particularly if an insufficient excess of diazomethane is used hydrogen halide is often added directly to the ethereal solution of acid chloride and diazomethane 1170,1171 if then, for example, HBr is used, the resulting a>bromo ketone will contain... 

Diazoketones such as 307 can be formed from acid chlorides by reaction with diazomethane. Subsequent treatment with aqueous Ag20 leads to the Wolff rearrangement and formation of a carboxylic acid of one carbon more than the starting acid chloride. This sequence is known as the Arndt-Eistert synthesis.252 a synthetic example using this is taken from Weinreb s studies toward the synthesis of cylindrospermopsin,253 iu which 315 was treated with (1) oxalyl chloride, (2) CH2N2 and (3) Ag20, MeOH to give a mixture of products 22% of 316 and 39% of 317. 

The Wolff rearrangement of a-diazocarbonyl compounds (8.58, R = H, alkyl, aryl, OR) has great synthetic importance because in most cases the ketenes formed react smoothly with water, alcohols, and amines (Scheme 8-34). An early application that still has considerable importance is the homologization of carboxylic acids (Arndt-Eistert reaction Arndt and Eistert, 1935). As shown in Scheme 8-34, the reaction starts from the chloride of the acid RCOOH, which leads to an a-diazo ketone with diazomethane (R = H), followed by the Wolff rearrangement and the hydrolysis of the ketene intermediate to give the homologous carboxylic acid (8.59, R =H). In alcohols and amines esters (8.60) and amides (8.61, R = H), respectively. 

The seventh item in Table 9.7, the reaction of phenylethanoyl chloride (the acid chloride of phenylacetic acid, C6H5CH2CO2H) with diazomethane (CH2N2), followed by hydrolytic (using H30" ) workup, creates a new carboxylic acid. When this reaction is combined with conversion of the carboxylic acid to the acid chloride (e.g., with thionyl chloride, SOCI2, as in item 3 of Table 9.6, vide supra) the two steps allow for increasing by one the number of carbons (as methylene units [-CH2-]) between... 

The safe and stable diazomethane substitutes arylsulphonyldiazomethane and trimethylsilyldiazomethane have both been shown to be acylated by carboxylic acid chlorides. Subsequent Wolff rearrangement then provides new and safe alternatives for the Arndt-Eistert reaction (Scheme 59). 

Benzothiepins synthesized by a double Knoevenagel condensation (see Section 2.1.1.2.) contain free carboxylic acid groups if the reaction product is isolated under acidic conditions. Rcesterification can be performed by two methods via formation of the acid chloride and subsequent alcoholysis, or by reaction with diazomethane, e.g. the conversion of 3-benzo-thiepin-2,4-diearboxylic acid (5, R = C02H) with thionyl chloride and methanol gives the dimethyl ester 5 (R = C02Me) in 47% yield, while the diazomethane pathway provides 60% of the dimethyl ester.65 Use of excess diazomethane leads to cycloadducts (see Section 2.2.4.). 

The equivalence of sulfur and oxygen in this ring system carries over to NSAIDs as well. Preparation of the sulfur analogue of isoxepac (6-4) starts with the alkylation of thiophenol (27-1) with benzyl chloride (26-1). Cyclization of the intermediate thioether (27-2) then affords the homothioxanthone (27-3). The carboxyl side chain is then extended by means of the Amdt-Eistert homologation reaction. The acid is thus hrst converted to its acid chloride by means of thionyl chloride. Reaction with excess diazomethane leads to the diazoketone (27-4). Treatment of that intermediate with silver benzoate and triethylamine leads the ketone to rearrange to an acetic acid. There is thus obtained tiopinac (27-5) [28]. 

One important application of this reaction is the chain extension of acyl chlorides to their homologous esters, known as the Amdt-Eistert reaction. Notice that the starting material for the Wolff rearrangement is easily made from RCO2H by reaction of the acyl chloride with diazomethane the product is RCH2CO2H—the carboxylic acid with one more carbon atom in the chain. A CH2 group, marked in black, comes from diazomethane and is inserted into the C-C bond between R and the carbonyl group. 

Reaction of 2-phenyloxazole-4-carbonyl chloride with diazomethane affords the crystalline diazomethyl ketone, which fails to undergo the Wolff rearrangement.389 In general the esters are smoothly hydrolyzed by aqueous alkali, but attempts to hydrolyze 5-aminooxazole-4-car-boxylates result in disruption of the ring system.389 The behavior of oxazole-4-carboxylic acids has been described in greater detail in The Chemistry of Penicillin .2... 

Surface oxides on graphite undergo the reactions typical of carboxylic acids, phenols and alcohols. Methylation with diazomethane or dimethylsulfate, silanization of—OH groups by reaction with halosilanes, formation of acyl chlorides by reaction with thionyl chloride, further reactions of these acyl chlorides, neutralization of acidic surface groups with different bases, ion exchange and more special reactions are used to characterize surface oxides on carbon and to modify their properties for technical applications . 

It has been stressed that the presence in a benzene derivative of two bulky substituents, such as chlorines ortho with respect to the reaction site may cause severe steric hindrance. As expected, the perchloroaryl carboxylic acids are not esterified by Meyer s acid-catalysed procedure either, although their methyl esters are readily prepared with diazomethane (Riera, 1961). In general, the synthesis of alkyl esters is successfully performed by acylation of alcohols with the overcrowded acid chlorides, the latter being obtained smoothly from the corresponding acids with thionyl chloride. 

This reaction was first reported by Arndt and Eistert in 1935. It is the extension of carboxylic acid by one CH2 unit via the reaction of acyl chloride with diazomethane and is generally known as the Arndt-Eistert synthesis. In addition, this reaction is also occasionally referred to as the Arndt-Eistert acid synthesis, Arndt-Eistert homologation," and Arndt-Eistert reaction. This reaction has been extensively reviewed. Other reagents instead of diazomethane have been similarly applied to extend the length of the carboxylic acids7... 

Esters can be prepared by acid-catalyzed esterification or by reaction of the acid chloride with the alcohol. In small-scale syntheses, it is often more convenient to prepare the ester by reaction of the carboxylic acid with the appropriate diazo compound. Diazomethane is routinely used for making methyl esters, but more highly substituted esters can be prepared if the corresponding diazo compound is available. Benzhydryl esters, for example, are readily prepared from carboxylic acids by reaction with diphenyldiazomethane ... 

Geometrical trans to cis isomerization of 3,3 -, 4,4 -, and 5,5 -disubstituted 2,2 -diphenoquinones has been studied by computational methods.The double bond isomerization of butene-catalysed l-ethyl-3-methyl-imidazolium chloride ionic liquid has been similarly examined and stepwise isomerization is suggested.The reaction of l,2-di(l-adamantyl)-2-thioxoethanone with diazomethane and 2-diazopropane gave 2-acylthiiranes via 2 - - 3-cycloaddition, elimination of nitrogen, and 1,3-dipolar electrocyclization of the intermediate acyl-substituted thiocarbonyl ylides. Rearrangement of pyrimidine-5-carboxylic acids esters to 5-acylpyrimidones does not occur in the examples studied and a [l,4]-phospho-Fries rearrangement has been reported. ... 

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