Acid using oxalyl chloride

Preparation of Phosphonic Acid Chlorides. Phosphonic acid dichlorides have been obtained in high yield (determined by NMR) at low temperature from the corresponding acids using oxalyl chloride and Pyridine (eq 1) ... 

Methods of acylating pyrrole similar to the present one have been reported using oxalyl chloride,5 trifluoroacetic anhydride,6 carbamic acid chloride,7 and trichloroacetyl chloride.8 In the last preparation, it was necessary to separate the product from highly colored by-products by alumina chromatography. Pyrrol-2-yl trichloromethyl ketone has also been prepared by the interaction of pyrrolylmagnesium halide and trichloroacetyl chloride.9... 

Alternatively, the lactone mixture 7 and 8 may be ring opened by hydrolysis, followed by the separation of the corresponding carboxylic acids. The desired atropisomer may be converted into the product alkaloid, whereas the undesired isomer may be recycled by conversion back to the lactone mixture using oxalyl chloride for the acyl activation36. 

Acid chlorides can be prepared from carboxylic acids using thionyl chloride (SOCl2), phosphorus trichloride (PC13), or oxalyl chloride (C1COCOC1) ... 

Chloro-1 -ethyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid (11, R = H) gave its ethyl ester (11, R = Et) (ClCC Et, Et3N, CHCI3 then EtOH 96%) 418 an analogous esterification used oxalyl chloride in the first stage. 

A promising method for the synthesis of unsymmctrical diorgano tellurium compounds uses carboxylic acid derivatives and diaryl ditellurium as starting materials. The carboxylic acid chloride, prepared in quantitative yield from the acid and oxalyl chloride is added slowly to a mixture of a diary] ditellurium and the sodium salt of 2-mercaptopyridine N-oxide in toluene at 35°. Under normal laboratory light the aryl tellurium radicals... 

Oxalyl chloride should be distilled if it is colored or contains solid. Studies by the submitters have shown that an excess of oxalyl chloride is needed for maximum conversion of the alkylbenzene to acid chloride. The checkers used oxalyl chloride available from Eastman Organic Chemicals. 

Acyl or acid chlorides are used frequently in amide formation as activated forms of the corresponding carboxylic acid. A wide selection of acyl chlorides is available commercially. Otherwise, they can be prepared readily from the corresponding carboxylic acid in the presence of reagents such as thionyl chloride (9), oxalyl chloride 5 (10), phosphorus trichloride (11), and phosphorus pentachloride (12). Reactions that use oxalyl chloride or thionyl chloride are promoted by the addition of a catalytic amount of DMF (13) (see Fig. 3). 

One example is Swern oxidation, which uses oxalyl chloride and DMSO and is particularly suitable for the selective oxidation of alcohols to aldehydes or ketones. The disadvantages of this oxidation method are the need for low temperatures, the smell of the dimethyl sulfide formed and the possible oxidation of other heteroatoms. Dess-Martin periodinane (DMP, 5) or iodoxybenzoic acid (IBX, 6) are also common oxidizing agents. The main advantage of these two methods is the short reaction time at room temperature. However, typical problems are the low solubility of IBX and the formation of byproducts. In this context, Finney et al. have reported an interesting procedure avoiding these problems by a variation of the temperature IBX is sufficiently soluble in solvents such as ethyl acetate or dichloromethane at elevated temperatures, whereas it is insoluble in these solvents at room temperature. Because of this, the remaining IBX as well as the IBX-derived byproducts can be separated from the reaction mixture by simple filtration. These reisolated IBX byproducts can then be reoxidized and reused. 

Substitution a to a cyclopropane ring has also been facilitated by using oxalyl chloride. Spiro[2.3]hexane afforded some 4-chlorocarbonylspiro[2.3]hexane on irradiation in the presence of oxalyl chloride. Treatment of 3- () R, l/ , 75 )-)3,l,5,5-tetramethylbicyclo[5.1.0]oct-2-en-3-yl propanoic acid with oxalyl chloride followed by tin(II) chloride gave three tricyclic products in 96% total yield. A similar reaction took place on irradiation of bertyadionol with 350-nm light." ... 

A related synthesis produces indolones by a different Friedel-Crafts route. The Stolle synthesis reacts with a secondary aryl amine such as diphenylamine with an a-chloro acid chloride or an a-bromo acid bromide to give an a-bromoamide (such as 315) or an a-chloroamide. An early version of the reaction used oxalyl chloride, but a more typical example is the reaction of 2-bromopropanoyl bromide with 314 to give 315. Friedel-Crafts cyclization (with AICI3) led to the indolone 316.1 ... 

In their studies of the characterization of the picolinyl esters of epoxides of polyunsaturated fatty acids, Balazy and Nies (21) prepared the picolinyl esters via unstable imidazolide intermediates, which were generated by reaction of the epoxy acids with 1,1 -carbonyldiimidazole. For the epoxides, a method using acid chlorides as intermediates (22) and thionyl choride as reagent was not recommended because of the instability of the epoxides in acidic solution. However, using oxalyl chloride as reagent for formation of the acid chloride (Scheme 1) is a viable route and was used in the formation of derivatives of ene-yne acids (19). Reaction with HMP yielded the desired picolinyl ester (Scheme 2). The method of Balazy and Nies (21) as well as the oxalyl chloride—based acid chloride method of Christie (19) are given. 

Greenhouse and colleagues have reported the regiospecific introduction of chlorine atoms into the 2-position of pyrrol-3-yl and indol-3-yl sulfoxides using oxalyl chloride [213]. For example, the pyrrol-3-yl sulfoxide (276), on treatment with oxalyl chloride followed by m-chloroperbenzoic acid oxidation (1.1 eq), gives the 2-chloro-substituted product (277) in 83% yield (Scheme 5.91). 

Oligothiophenes end-capped with polybenzyl ether dendrons were prepared by Frechet s group (Scheme 1.70) [508]. Benzyl ester-substituted quinquethiophene 5.65 was deprotected in basic medium to the carboxylic acid and converted to the corresponding acid chloride using oxalyl chloride. This was then connected to a G5-hydroxyl-terminated Frdchet dendron by ester linkages. Stille-type coupling of the terminally brominated quinquethiophene and 2,5-bis(trimethylstannyl)thiophene afforded the highly... 

The acid 17 was converted to its acid chloride using oxalyl chloride, and further reaction with A-methylhomopiperonylamine provided the amide 19. Bischler-Napieralski cyclization led to the key dehydrophthalideisoquinoline 20, and catalytic hydrogenation supplied the desired adlumidine and bicucul-line. ... 

There is one acid dichloride that is extremely useful oxalyl chloride (157). When 157 reacts with a carboxylic acid such as pentanoic acid (45) in the presence of an amine base (such as triethylamine), the acid is converted to an acid chloride (in this case, pentanoyl chloride, 158). Oxalyl chloride is a very efficient and very mild method for converting acids to acid chlorides. This method should be added to the reactions in Section 20.3 for the preparation of acid chlorides. It is used primarily with acids that are sensitive to acids or bases or when the acid chloride product is too reactive in the presence of acids or bases. 

Carboxylic acids react with thionyl chloride (SOQ2) to produce the corresponding add chlorides, as shown in the above reaction.Thionyl chloride is an attractive reagent due to its low cost, and the fact that both byproducts produced in the reaction are gases. Thus, the reaction is driven to completion by the evolution of HCl and SO2, and a nearly pure acid chloride is obtained. The major drawback to the reaction is that it produces a strong acid (HCl) and thus cannot be used with compounds that are acid sensitive. Oxalyl chloride is often used as an alternative reagent. 

The readily available 6-(methylsulfinyl)hexanoic acid 1873 is employed as a substitute for DM SO in Swern oxidation reactions using oxalyl chloride, whereby primary or secondary alcohols are smoothly converted to the corresponding aldehydes or ketones in high yield. 

Esterification.—iVAWW -Tetramethylchloroformamidinium chloride, which is readily prepared from iVAWW -tetramethylurea and oxalyl chloride, is an efficient reagent for the esterification of carboxylic acids with alcohols yields of between 66 and 97% are obtained, and the method has also been applied to macrolide synthesis. A modified one-pot procedure for the esterification of carboxylic acids, using phenyl dichlorophosphate-dimethylformamide complex, has appeared. A simple method of activation of carboxylic acids, using methanesulphonyl chloride and triethylamine followed by addition of the alcohol and 4-dimethylaminopyridine, leads to esters in 57— 96% yield for thirteen examples. 0-Methylcaprolactim reacts with carboxylic acids to give methyl esters in 73—91 % yield for seven examples and 2-iodoethyl esters are prepared from acyl chlorides, ethylene oxide, and sodium iodide. Transesterification, catalysed by titanium(iv) alkoxides, provides an effective method for synthesis of esters. Diethyl trichloromethylphosphonate reacts with carboxylic acids to give ethyl esters via transesterification, in 52 to 98 % yield. ... 

Our preparation of the PEG ester derivatives Involved generation of the fatty acid chlorides using oxalyl chloride followed by in situ condensation with PEG, eq. 5. The reaction proceeded smoothly and was of particular convenience for preparing small quantities of radioisotope-labelled monoester for use in phase partitioning studies. An obvious synthetic approach to monoesters... 

Treatment of [ C]malonic acid with oxalyl chloride in the presence of catalytic amounts of DMF affords [ C]malonyl chloride in nearly quantitative yield. The structure of the reagent was confirmed by acylation of 2-methoxypropene, which provided a 3 1 mixture of phloroglucinol monomethyl ether (428) and 4-hydroxy-6-methyl-2//-[2,4- " C]pyran-2-one (427). Etherification of the latter with dimethyl sulfate followed by ring opening upon treatment with sodium methoxide and recychzation afforded 429, which was combined with the original portion of 428 and etherified to give 1,3,5-trimethoxy-[1,3,5- C]benzene, which was used as a key intermediate in the synthesis of several carbon-14 labeled cholesterol acyltransferase inhibitors . ... 

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