Oxalyl chloride, reaction with acids

In his synthesis of the [4.4.4] propellane 19, Paquette made the diester 16 easily but wanted the mono methyl ketone 18. Rather than add MeLi directly, he first hydrolysed one ester to the free acid 17 and then made the acid chloride with oxalyl chloride. Reaction with Me2CuLi gave the ketone in excellent yield.5... 

Oxalic ester synthesis 16, 812 Oxalyl chloride, reaction with amines 16, 502 Oxamic acid derivatives... 

Diacyl dications have been examined in both experimental and theoretical studies. Attempts to directly observe the oxalyl dication (174) were not successful as ionization of oxalyl chloride (170) with SbFs leads to the chlorocarbonyl cation (172, Scheme 4).65 The initially formed chloroxa-lyl cation 171 immediately decarbonylates under the reaction conditions. Interestingly, complexation of the chloroxalyl cation 171 with excess Lewis acid is expected to generate superelectrophile 173. Theoretical calculations (MP2/6-31G level) indicate that the oxalyl dication (174) is at a minimum on the potential energy surface.66 Calculated bond lengths for... 

For the formation of carboxylic acid chlorides from carboxylic acids different procedures are known. Often thionyl chloride or oxalyl chloride, both with catalytic amounts of DMF, are used. The reaction with thionyl chloride requires elevated temperatures and often provides various byproducts. Oxalyl chloride is useable at room temperature or... 

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. 

A.iv. Reaction with Acid Chlorides. As briefly mentioned in Section 8.4.C.ii, the reaction of a dialkyl cuprate and an acid chloride is a preferred method to synthesize ketones.399,400 -phe reaction with acyl halides usually requires low temperatures to isolate the ketone product.388,387 -p is method is usually preferable to and more general than one that uses dialkylcadmium reagents (sec. 8.4.C.ii). Masamune et al. used this reaction to convert acid 422 to ketone 423 in a synthesis of erythronolide. In this case, oxalyl chloride was used to prepare the requisite acid chloride because of the sensitive nature of the molecule. 

The main applications of oxalyl chloride, as described in Chapter 4, are the formation of aryl isocyanates and chloroformates (by reactions with amines and hydroxylic substrates, respectively), and the formation of acyl chlorides from carboxylic acids under very mild conditions. Oxalyl chloride reacts with amides to give acyl isocyanates, and it is used with dimethyl sulfoxide as a mild reagent for the oxidation of alcohols (Swern-type oxidation). It is also used with N,N-dimethylformamide as a mild reagent for chlorination and formylation. Oxalyl chloride is widely used in commercial formulations of speciality polymers, antioxidants, photographic chemicals, X-ray contrasting agents, and chemiluminescent materials. Other physical properties are presented in Chapter 3. 

We reported that smooth oxidative addition of organic halides such as aryl, benzyl, and allyl halides to metallic nickel proceeded to afford organonickel halides under mild conditions, which yielded homocoupled products [11, 41] or ketones by the reaction with acid chlorides [42] or alkyl oxalyl chlorides [43]. We describe here a new method for the preparation of 3-aryl-2-hydroxy-l-propanones (4) in good yield by the Grignard-type addition of benzyl halides to 1,2-diketones mediated by metallic nickel under neutral conditions [44]. 

The traditional method for transforming carboxylic acids into reactive acylating agents capable of converting alcohols to esters or amines to amides is by formation of the acid chloride. Molecules devoid of acid-sensitive functional groups can be converted to acid chlorides with thionyl chloride or phosphorus pentachloride. When milder conditions are necessary, the reaction of the acid or its sodium salt with oxalyl chloride provides the acid chloride. When a salt is used, the reaction solution remains essentially neutral. 

Specialty Isocyanates. Acyl isocyanates, extensively used in synthetic appHcations, caimot be direcdy synthesized from amides and phosgene. Reactions of acid haUdes with cyanates have been suggested. However, the dominant commercial process utilizes the reaction of carboxamides with oxalyl chloride [79-37-8]. CycHc intermediates have been observed in these reactions which generally give a high yield of the desired products (86). 

Oxahc acid reacts with various metals to form metal salts, which are quite important as the derivatives of oxahc acid. It also reacts easily with alcohols to give esters. Crystalline dimethyl oxalate is, for example, produced by the reaction of oxahc acid dihydrate and methanol under reflux for a few hours. When oxahc acid is treated with phosphoms pentachloride, oxalyl chloride, ClCOCOCl, is formed (6). 

Oxalyl Chloride. This diacid chloride [79-37-8], ClCOCOCl, mol wt 126.9, is produced by the reaction of anhydrous oxaUc acid and phosphoms pentachloride. The compound vigorously reacts with water, alcohols, and amines, and is employed for the synthesis of agrochemicals, pharmaceuticals, and fine chemicals. 

Sorbic acid anhydride [13390-06-2] can be prepared by heating the polyester of 3-hydroxy-4-hexenoic acid with sorboyl chloride [2614-88-2] or by reaction of sorbic acid with oxalyl chloride (15,16). Preparation of the esters of sorbic acid must be controlled to prevent oxidation and polymerization. The lower sorbic acid esters have a pleasant odor. 

Because of the structural requirements of the bielectrophile, fully aromatized heterocycles are usually not readily available by this procedure. The dithiocarbamate (159) reacted with oxalyl chloride to give the substituted thiazolidine-4,5-dione (160) (see Chapter 4.19), and the same reagent reacted with iV-alkylbenzamidine (161) at 100-140 °C to give the 1 -alkyl-2-phenylimidazole-4,5-dione (162) (see Chapter 4.08). Iminochlorides of oxalic acid also react with iV,iV-disubstituted thioureas in this case the 2-dialkylaminothiazolidine-2,4-dione bis-imides are obtained. Thiobenzamide generally forms linear adducts, but 2-thiazolines will form under suitable conditions (70TL3781). Phenyliminooxalic acid dichloride, prepared from oxalic acid, phosphorus pentachloride and aniline in benzene, likewise yielded thiazolidine derivatives on reaction with thioureas (71KGS471). 

A more practical solution to this problem was reported by Larson, in which the amide substrate 20 was treated with oxalyl chloride to afford a 2-chlorooxazolidine-4,5-dione 23. Reaction of this substrate with FeCL affords a reactive A-acyl iminium ion intermediate 24, which undergoes an intramolecular electrophilic aromatic substitution reaction to provide 25. Deprotection of 25 with acidic methanol affords the desired dihydroisoquinoline products 22. This strategy avoids the problematic nitrilium ion intermediate, and provides generally good yields of 3-aryl dihydroisoquinolines. 

To a stirred suspension of p-(p-methoxvbenzyloxy)-phenylmalonic acid (125 mg) in methylene chloride (3 ml) are added triethylamine (55 All) and oxalyl chloride (26 AH) at -15°C, and the suspension is stirred for 40 minutes at 0°C. The mixture Is added to a solution of diphenylmethyl 7 -amino-7a-methoxy-3-(1 -methyltetrazol-5-yl)thiomethyl-1 -oxadethia-3-cephem-4methylene chloride (3 ml) and pyridine (63 AH), and the mixture is stirred for 30 minutes at 0°C. The reaction mixture is diluted with ethyl acetate, washed with aqueous 2 N-hydrochloric acid and water, dried over sodium sulfate, and concentrated to give crude product (212 mg), which Is chromatographed on silica gel (20 g) and... 

Many procedures for the formation of carboxylic acid amides are known in the literature. The most widely practiced method employs carboxylic acid chlorides as the electrophiles which react with the amine in the presence of an acid scavenger. Despite its wide scope, this protocol suffers from several drawbacks. Most notable are the limited stability of many acid chlorides and the need for hazardous reagents for their preparation (thionyl chloride, oxalyl chloride, phosgene etc.) which release corrosive and volatile by-products. Moreover, almost any other functional group in either reaction partner needs to be protected to ensure chemoselective amide formation.2 The procedure outlined above presents a convenient and catalytic alternative to this standard protocol. 

The Vilsmeier-Haack type adduct, formed by the reaction of oxalyl chloride with DMF can be also be employed for the activation of carboxylic acids, as shown in Fig. 8 [200]. 

Reaction of (S)-(+)-2-aminobutyrate hydrochloride with ethyl oxalyl chloride followed by replacing of the ethyl ester with amino alcohol, oxidation with Dess-Martin periodinate and cyclization using TFA/TFAA in acetic acid gave the cyclic product, which was further converted to the bromide. Sub-... 

A convenient modification of the Gassman oxindole synthesis was reported using ethyl (methylsulfinyl)acetate (101) activated by oxalyl chloride to generate the same chlorosulfonium salt 102 normally generated from ethyl (methylthio)acetate 100 and elemental chlorine <96TL4631>. Thus, treatment of the sulfoxide 101 with oxalyl chloride, followed by the addition of the desired aniline, triethylamine, and finally acid cyclization of 103 affords the oxindoles 104. This procedure is particularly convenient for reactions carried out on smaller scales and for anilines that ate susceptible to electrophiUc halogenation. 

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