Chlorides, acid preparation

From the acid chloride. By the interaction of the acid chloride (prepared from the acid and thionyl chloride) and the calculated quantity of the alcohol at 0°, for example ... 

Chlorophenylacetic acid [1878-65-5] M 170.6, m 74°, pK 4.11. Crystd from EtOH/water, or as needles from C6H6 or H2O (charcoal). The acid chloride (prepared by boiling with SOCI2) has b 127-129°/15mm. [Dippy and Williams J Chem Soc 161 1934 Misra and Shukla J Indian Chem Soc 28 480 1951.]... 

N-Silylated peptide esters are acylated by the acid chloride of N-Cbo-glycine to N-acylated peptide bonds [11]. Likewise, acid chlorides, prepared by treatment of carboxylic acids with oxalyl chloride, react with HMDS 2 at 24°C in CH2CI2 to give Me3SiCl 14 and primary amides in 50-92% yield [12]. Free amino acids such as L-phenylalanine or /5-alanine are silylated by Me2SiCl2 48 in pyridine to 0,N-protected and activated cyclic intermediates, which are not isolated but reacted in situ with three equivalents of benzylamine to give, after 16 h and subsequent chro-... 

However, because CDI reacts with HC1 to give phosgene (COCl2), reaction of the carboxylic acid with CDI must be complete before treatment with hydrochloric acid is undertaken. The yield of an acid chloride prepared by this one-pot reaction is comparable to those reported in Table 13-2. In general, acid chlorides are formed at room temperature within a few minutes. 

Acyl chlorides. Acyl chlorides are formed rapidly by reaction of carboxylic acids with SOCl2 and pyridine in CH2C12 at 25°. The dicyclohexylammonium salts of carboxylic acids react particularly rapidly (ca. 1 minute). The acid chlorides prepared in situ in this way react with amines in the presence of DMAP or DBU to form amides in >85% yield. This SOCl2-Py method is also useful for peptide synthesis with slight racemization. 

To 1 gramm-equivalent (g-eq) of dimethylaminoethanethiol in 150 ml of ether, a suspension of g-eq of 50% sodium hydride in 50-ml of anhydrous ether was added. After boiling for 1 hour, the reaction mixture was cooled to 0°C, whereupon g-eq of 9,9-dimethylacridan-10-carboxylic acid chloride (prepared from 9,9-dimethylacridan and phosghene - cf. Swiss Specification No. 

A list of ketones which have been prepared by the Friedel-Crafts stannic chloride method may be found in Table VI. Yields marked by an asterisk were obtained from acid chlorides prepared by the phosphorus pentachloride procedure all others were obtained from acid chlorides prepared from thionyl chloride. 

Copper-mediated addition of a functionalized alkylzinc iodide to an acid chloride preparation of 4-oxocyclohexyl 5-phenyl-5-oxopentanoate2... 

This reaction was exploited by Pass, Amit and Patchornik to directly couple two peptide fragments (Scheme 13.30) [117]. However, one of the main issues to date has been the preparation of such activable amino acids. Two approaches (which, unfortunately, are limited in their scope) are nitration of the parent indoline derivative after acylation with the amino acid, or use of the amino acid chloride prepared in situ. 

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... 

The acid chlorides prepared in this manner (for individual compounds, see reaction scheme) were not purified but converted to heterocyclic compounds through treatment with aluminum chloride3,4. 

Conditions for the efficient use of Fmoc-protected amino acid chlorides in stepwise peptide synthesis have been delineated. The acid chlorides are reasonably stable solids that are readily aminolyzed if a base is added to neutralize the hydrogen chloride liberated in the reaction. They form the corresponding oxazol-5(4//)-ones and undergo stereomutation if left in the presence of tertiary amines, however, amide formation without stereomutation can be obtained under appropriate conditions. The acid chlorides are advantageously applied to acylate weak nucleophiles and sterically hindered amino components, but their application may be limited by the lack of stability of tert-butyl-type side-chain protecting groups toward conditions of acid chloride preparation. 

Also, we discovered that tetrachloroethylene carbonate can be used as a highly effective chlorinating agent for acid chlorides preparation as depicted in scheme 179 (Ref. 231). 

The acylation of 4-aminoantipyrine 30 took place with acid chlorides 45d,f and the respective acid chlorides prepared in situ from the carboxylic acids 45a c,e. Thus, 2-cyanoarylacrylic acids 45a c.e, triethylamine and 4-aminopyrazol-3-one 30 at 0 °C were treated with phosphorus oxychloride while acid chlorides 45d,f were treated with triethylamine and pyrazol-3-one 30 at 0 °C to afford the corresponding A -(3-oxopyrazol-4-yl)acrylamides 46a-f in moderate yields (91JIC612) (Scheme 11). 

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