Carboxylic acid anhydrides oxalyl chloride

Acyl chlorides are converted in good yield into symmetrical carboxylic acid anhydrides upon treatment with dilute aqueous sodium hydroxide at -I0°C in the presence of a tetra- -butylammonium salt [76, 77]. Yields are considerably lower when Aliquat is used. In a similar manner, chloroformates and ethyl oxalyl chloride are converted into carbonic hemi-ester anhydrides. 

The most important method for the preparation of aryl ketones is known as Friedel-Crafts acylation. The reaction is of wide scope. Reagents other than acyl halides can be used," including carboxylic acids," anhydrides, and ketenes. Oxalyl chloride has been used to give diaryl 1,2-diketones." Carboxylic esters usually give alkylation as the predominant product (see 11-11)." A-Carbamoyl p-lactams reacted with naphthalene in the presence of trifluoromethanesulfonic acid to give the keto-amide." ... 

Preparation of Carboxylic Acid Chlorides (and Anhydrides). Oxalyl chloride has found general application for the preparation of carboxylic acid chlorides since the reagent was introduced by Adams and Ulich. Acid chlorides produced by this means have subsequently featured in the synthesis of acyl azides, bromoalkenes, carboxamides, cinnolines, diazo ketones, (thio)esters, lactones, ketenes for cycloaddition reactions, intramolecular Friedel-Crafts acylation reactions, and the synthesis of pyridyl thioethers. ... 

Amides can be synthesized by reaction of amines with acid chlorides, anhydrides, or esters. Acid chlorides can be prepared from carboxylic acids using thionyl chloride, SOCIj, oxalyl chloride (COCOj, or PCI5. 

Treatment of carboxylic acids with half an equivalent of oxalyl chloride can generate anhydrides."... 

Synthesis of isomeric chiral protected (63 )-6-amino-hexahydro-2,7-dioxopyrazolo[l,2- ]pyrazole-l-carboxylic acid 280 is shown in Scheme 36. Crude vinyl phosphonate 275, obtained by treatment of diethyl allyloxycarbonylmethyl-phosphonate with acetic anhydride and tetramethyl diaminomethane as a formaldehyde equivalent, was used in the Michael addition to chiral 4-(f-butoxycarbonylamino)pyrazolidin-3-one 272. The Michael addition is run in dichloro-methane followed by addition of f-butyl oxalyl chloride and 2 equiv of Huning s base in the same pot to provide 276 in 58% yield. The allyl ester is deprotected using palladium catalysis to give the corresponding acid 277, which is... 

Structurally similar photochromic maleic anhydride derivatives 177 with a similar reaction mechanism were prepared by Irie (05CL64) by a one-pot synthesis from 2-methoxybenzothiophene, oxalyl chloride, and pentene-3-carboxylic acid (3-pentenoic acid) in dichloromethane in the presence of triethylamine at 5°C for 2 h according to Scheme 54. 

Two years later, the same group reported a formal synthesis of ellipticine (228) using 6-benzyl-6H-pyrido[4,3-f>]carbazole-5,ll-quinone (6-benzylellipticine quinone) (1241) as intermediate (716). The optimized conditions, reaction of 1.2 equivalents of 3-bromo-4-lithiopyridine (1238) with M-benzylindole-2,3-dicarboxylic anhydride (852) at —96°C, led regioselectively to the 2-acylindole-3-carboxylic acid 1233 in 42% yield. Compound 1233 was converted to the corresponding amide 1239 by treatment with oxalyl chloride, followed by diethylamine. The ketone 1239 was reduced to the corresponding alcohol 1240 by reaction with sodium borohydride. Reaction of the alcohol 1240 with f-butyllithium led to the desired 6-benzylellipticine quinone (1241), along with a debrominated alcohol 1242, in 40% and 19% yield, respectively. 6-Benzylellipticine quinone (1241) was transformed to 6-benzylellipticine (1243) in 38% yield by treatment with methyllithium, then hydroiodic acid, followed... 

The most important reactions of carboxylic acids are the conversions to various carboxylic acid derivatives, e.g. acid chlorides, acid anhydrides and esters. Esters are prepared by the reaction of carboxylic acids and alcohols. The reaction is acid catalysed and is known as Fischer esterification (see Section 5.5.5). Acid chlorides are obtained from carboxylic acids by the treatment of thionyl chloride (SOCI2) or oxalyl chloride [(COCl)2], and acid anhydrides are produced from two carboxylic acids. A summary of the conversion of carboxylic acid is presented here. All these conversions involve nucleophilic acyl substitutions (see Section 5.5.5). 

In the second step 20 is activated with oxalyl chloride to form a carboxylic acid chloride and treated in situ with a solution of (R)-4-benzyloxazolidine-2-thione 19 to produce 7 in 88 % yield. Alternatively the Crimmins group transformed 20 into a mixed pivalic anhydride 21 by means of pivaloyl chloride and triethylamine and converted it with the lithium salt of (7 )-4-benzyloxazolidin-2-one in 89 % yield to the corresponding oxazolidinone. In contrast to the sulfur analog, which is synthesized at temperatures between 0 °C and room temperature, the formation of an acyloxazolidinone had to take place at -78 °C. 

An analogous methodology can be seen in the proposal to use chloroformamidinium salts as dehydrating agents. A A A /V -Tetramethylchloroformamidinium chloride, used as the condensation agent, is easily available by the reaction of A A A A -tetramethylurea and oxalyl dichloiide. The reaction of carboxylic acids (equation 33) can be achieved at -30 C in the presence of tiiethylamine. Thus, for instance, 2-furoic acid, cinnamic acid and crotonic acid yield e anhydrides in 84%, 83% and 83%, respectively. 

Oxalyl chloride (reaction c) is more reactive than phthaloyl chloride and its use enables the chlorides to be obtained from sensitive carboxylic acids1116 or their Na salts in benzene1117 at ambient temperature or below. Some of the nitro derivatives of benzoic acid afford only the mixed anhydrides when 2 moles of the acid are heated with 1 mole of oxalyl chloride.1118 To obtain the free acid chloride, and not its hydrochloride, from basic carboxylic acids an alkali salt of this acid may be treated with oxalyl chloride. 

Y-carboxylic acid (74) by approaches involving either acyl chlorides (oxalyl chloride route) or mixed carbonic anhydrides (isobutyl chloroformate route) (Scheme 120). An alternative route to (73) involves selective attack at the Y-carbonyl of anhydride (71) with diazomethane however the DON precursor (72) could not be prepared using this method. 

---