Oxalyl chloride: reaction with carboxylic

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. 

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. 

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]. 

Treatment of N-benzoyl-L-alanine with oxalyl chloride, followed by methanolic triethylamine, yields methyl 4-methyl-2-phenyloxazole-5-carboxylate 32 <95CC2335>. a-Keto imidoyl chlorides, obtained from acyl chlorides and ethyl isocyanoacetate, cyclise to 5-ethoxyoxazoles by the action of triethylamine (e.g.. Scheme 8) <96SC1149>. The azetidinone 33 is converted into the oxazole 34 when heated with sodium azide and titanium chloride in acetonitrile <95JHC1409>. Another unusual reaction is the cyclisation of compound 35 to the oxazole 36 on sequential treatment with trifluoroacetic anhydride and methanol <95JFC(75)221>. 

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 acyl chloride. Molecules devoid of acid-sensitive functional groups can be converted to acyl 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 acyl chloride. When a salt is used, the reaction solution remains essentially neutral. 

The carboxylic functionalities inserted onto the tubes can be used as platforms to obtain further transformations (Fig. 3.5). A commonly utilized route is the reaction of carboxylic groups with thionyl chloride or oxalyl chloride to prepare the corresponding acyl chlorides, which are useful intermediates for amidation or esterification reactions. Amides can also be prepared directly from the acids by means of standard solution chemistry conditions, using carbodiimide derivatives in the presence of the selected amine. 

There are several chemical reactions that can be used as an alternative to achieve covalent functionalization of CNTs. Two of them are amidation and/or esterification reactions. Both reactions take advantage of the carboxylic groups sitting on the side-walls and tips of CNTs. In particular, they are converted to acyl chloride groups (-C0-C1) via a reaction with thionyl (SO) or oxalyl chloride before adding an alcohol or an amine. This procedure is very versatile and allows the functionalization of CNTs with different entities such as biomolecules [154-156], polymers [157], and organic compounds [158,159] among others. 

Eaton and co-workers also reported the synthesis of 1,3,5-trinitrocubane and 1,3,5,7-tetranitrocubane (39) ° The required tri- and tetra-substituted cubane precursors were initially prepared via stepwise substitution of the cubane core using amide functionality to permit ort/jo-lithiation of adjacent positions. The synthesis of precursors like cubane-1,3,5,7-tetracarboxylic acid was long and inefficient by this method and required the synthesis of toxic organomercury intermediates. Bashir-Hashemi reported an ingenious route to cubane-1,3,5,7-tetracarboxylic acid chloride (35) involving photochemical chlorocarbonylation of cubane carboxylic acid chloride (34) with a mercury lamp and excess oxalyl chloride. Under optimum conditions this reaction is reported to give a 70 8 22 isomeric mixture of 35 36 37... 

The formation of an acyl halide involves the reaction of a carboxylic acid with a halogen source. The common halogen sources tire compounds like PX3, PXj, ClOCCOCl (oxalyl chloride), or SO.V2> where. Y is a halogen. The most commonly used acyl halides are the chlorides, and the simplistic reaction is RCOOH —> RCOCl. Figure 12-15 illustrates the mechanism using thionyl... 

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... 

Even an oligopeptide has been attached to (Table 4.3, compound 130) [111]. This was achieved by a coupling reaction of the carboxylic group in the side chain of the cyclopropane ring as well. First, the tert-butylcarboxylate 129 was synthesized by the reaction of the corresponding diazomethylbenzoate with Cgg. After hydrolysis with trifluoromethanesulfonic acid, the acyl chloride was generated by treatment with oxalyl chloride. Finally, in a one-step procedure the fullerene peptide 130 was obtained by the reaction with the N-deprotected pentapeptide H-(L-Ala-Aib)2-L-Ala-OMe. 

The 7-lactam 120, which is very reactive, is obtained from the reaction of methyl 2-(2-methoxycarbonylmethyl-ene)-5-methyl-3,6-dihydro-2//-l,3-thiazine-4-carboxylate 119 with oxalyl chloride and in the presence of triethyl-amine (Scheme 5). Subsequent treatment with methanol affords 3,6-dihydro-2//-l,3-thiazine 121 as a mixture of isomers. Similar treatment of the 4-allyl carboxylate analogue with oxalyl chloride/triethylamine yielded the corresponding 7-lactam <1999J(P1)2449>. 

Acid chlorides are prepared from the corresponding carboxylic acids, most commonly from the reaction with thionyl chloride or oxalyl chloride (see Section 5.5.5). 

Preparation of acid chlorides The best way to make acid chlorides is the reaction of a carboxylic acid with either thionyl chloride (SOCI2) or oxalyl chloride (COCl)2 in the presence of a base (pyridine). The mechanism of formation of acid chloride is similar to the reaction of alcohol with SOCI2. 

RCOOH — RCHO. The iminium salt (1) formed on reaction of a carboxylic acid with the Vilsmeier reagent (formed from DMF and oxalyl chloride) is reduced by lithium tri-/-butoxyaluminum hydride (1 equiv.) to an aldehyde. The chemo-selectivity is noteworthy ester, nitrile, keto, and halide groups are not affected.3... 

Formyl derivative 362 was prepared when 9-hydroxymethylpyrido-pyrimidin-4-one 361 in dichloromethane was added to a cooled mixture of oxalyl chloride and dimethyl sulfoxide at - 50°C/ - 60°C in the presence of triethylamine. 9-Formyl derivative 362 was oxidized with silver nitrate in aqueous ethanol, and after 15 minutes of stirring the reaction mixture was treated with aqueous potassium nitrate for 2 hours at ambient temperature to give pyrido[ 1,2-a]pyrimidine-9-carboxylic acid 363 (91EUP453042). 

To a stirred solution of the (+)-6-ethyl-5-methyl-3,6-dihydro-2H-pyran-2-carboxylic acid (3.0 g, 17.65 mmol) in CH2CI2 (60 ml), and DMF (0.12 ml) at 0°C was added oxalyl chloride (1.82 ml, 21.18 mmol) over a 30 min-period. The reaction mixture was stirred at 0°C for 1 h, then at room temperature for 2 h. The solvent was evaporated in vacuum, and the residue was used directly in the next reaction without further purification. In a 50 ml, two-necked, round-bottomed flask equipped with a Teflon-covered magnetic stirring bar, a drierite filled trap, and a thermometer was placed the crude acid chloride in HMPA (16 ml). Freshly prepared trans-propenyltrimethyltin (4.34 g, 21.18 mmol) was then added followed by the addition of... 

To a stirred suspension of p-(p-methoxybenzyloxy)-phenylmalonic acid (125 mg) in methylene chloride (3 ml) are added triethylamine (55 I) and oxalyl chloride (26 I) at -15°C, and the suspension is stirred for 40 minutes at 0°C. The mixture is added to a solution of diphenylmethyl 7p-amino-7a-methoxy-3-(l-methyltetrazol-5-yl)thiomethyl-l-oxadethia-3-cephem-4-carboxylate (100 mg) in methylene chloride (3 ml) and pyridine (63 I), and the mixture is stirred for 30 minutes at 0°C. The reaction mixture is diluted with ethyl acetate, washed with aqueous 2N-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 eluted with a mixture of ethyl acetate and acetic acid (99 1) to give diphenylmethyl-7p-[a-p-(p-methoxybenzyloxy)phenyl-a-carboxyacetamido]-7a-methoxy-3-(l-methyltetrazol-5yl)thiomethyl-l-oxadethia-3-cephem-4-carboxylate as foam (71 mg). Yield 45%. 

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