Thionyl Chloride carboxylic acid chlorides from acids

Zinc chloride thionyl chloride Carboxylic acid chlorides from carboxylic acids and carboxylic acid anhydrides s. 1, 424 ZnCIJSOCI,... 

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... 

Working in a hood, add the thionyl chloride/carboxylic acid mixture dropwise from a Pasteur pipette into a beaker containing 5 mL of ice-cold concentrated ammonium hydroxide. The reaction is very exothermic. Stir the mixture vigorously after the addition for about 5 minutes. When the reaction is complete, collect the product by vacuiun filtration and recrystallize it from water or from water-ethanol, using the mixed-solvents method (see Technique 11, Section 11.10). 

This modification of the continuous reactor (cf. benzoylacetanilide, p. 2) with countercurrent distillation is preferred for reactions in which a large amount of solvent or excess of one reactant is essential, but increase of total volume is undesirable. It is especially useful if the substances involved are heat-sensitive with this apparatus the reactants are heated for only a few minutes at most. It is particularly applicable to the preparation of acid chlorides from carboxylic acids and thionyl chloride (cf. Notes 3 and 4). An indefinite amount of product can be prepared by replenishing the reactants as they are consumed. 

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. 

Dihydrooxazoles are readily prepared from (V-acyl derivatives of /3-hydroxylamines by heating or by the action of thionyl chloride, sulfuric acid or phosphorus pentoxide (equation 167) (79JCS(P1)539>. The direct condensation of carboxylic acids with 13-hydroxylamines succeeds best with substituted compounds, such as norephedrine (equation 168). There are many variations of this general method, such as the use of imino ether hydrochlorides (equation 169) (78ACR375) and of cyanides (equation 170) (74LA996). 

The most general method involves the cyclization of diacyUiydrazides with a variety of reagents such as thionyl chloride, phosphorus oxychloride and sulphuric acid, usually under harsh reaction conditions. Further, most of these protocols are multi-step in nature and involve long reaction times. Only a few reliable and operationally facile examples have been reported for the one step synthesis of oxadiazoles, especially from readily available carboxylic acids and acid hydra-zides [16, 17]. 

Chloro-5-dichloromethylthieno[3,2-Z ]thiophene-2-carboxylic acid chloride (47) was synthesized by the reaction of thionyl chloride in Py with 5-formylthiophen-2-ylacrylic acid 48 (75BSF2575). 3-Chloro-5-dichlorometylthieno[2,3-Z ]thiophene-2-carboxylic acid chloride (50) was prepared analogously starting from isomer 49. 

Dehydration with thionyl chloride-dimethylformamide Nitriles from carboxylic acid amides... 

The reagent commonly used to prepare an acid chloride from a carboxylic acid is thionyl chloride, SOCI2. The reaction probably proceeds via the intermediate mixed anhydride 18 (Eq. 20.7), which is very reactive. Consequently, it undergoes rapid attack by chloride ion via a nucleophilic acyl substitution in which sulfur dioxide and chloride ion are lost and the acid chloride is produced. 

Aluminum chloride thionyl chloride Cyclic ketones from carboxylic acids O... 

The chemical transformations of the carboxyl group include formation of halo[ C]acetyl halides, amides, imides, alcohols, aldehydes and amines. Methods for the preparation of halo[ " C]acetyl halides from [ " C]acetic acid have already been mentioned. In addition, chloro[ " C]acetyl chloride has become available through treatment of chloro[ C]acetic acid with thionyl chloride or phthaloyl chloride, whereas for bromo[ " C]acetyl chloride, thionyl chloride or phosphorus pentachloride is recommended. Numerous applications of halol Clacetyl halides have been published, out of which the following C-, N- and 0-acylations may illustrate their versatility. 

Acyl chlorides are readily available They are prepared from carboxylic acids by reaction with thionyl chloride... 

The 3-o-ch orophenvl-5-methvlisoxa2ole4-carboxylic acid, from which the acid chloride was prepared, was obtained by hydrolysis of the ester product of the reaction between o-chloro-benzohydroxamic chlorideand ethyl acetoacetate in methanolic sodium methoxide. Reaction with thionyl chloride gave the starting material. 

To a suspension of 12.0 grams of 3-methylflavone-8-carboxylic acid in 200 ml of anhydrous benzene Is added 10.0 grams of thionyl chloride. The mixture is refluxed for 2 hours during which the suspended solid goes into solution. The solvent is completely removed by distillation, the residue extracted with benzene and the extract evaporated to dryness. The product, 3-methylflavone-8-carboxylic acid chloride, is recrystallized from ligroin to give crystals melting at 155° to 156°C. 

Methyl pyrazine-2-carboxylic acid is refluxed with thionyl chloride in anhydrous benzene for approximately 12 hours. Benzene and thionyl chloride excess is removed by distillation. Then some anhydrous dioxane is added and this acid chloride solution is allowed to drop into p-(/3-aminoethyl)-benzenesulfonamide suspension in dioxane and anhydrous pyridine. The resulting mixture is then refluxed for 3 hours. Dioxane is removed by distillation and then the residue is washed with water and acetic acid. The raw acylated sulfonamide is then filtered and crystallized from 95% ethanol, thus obtaining a product of MP 200 to 203 C. 

Acid chlorides are prepared from carboxylic acids by reaction with thionyl chloride (SOCl2), as we saw in the previous section. Similar reaction of a carboxylic acid with phosphorus tribromide (PB ) yields the acid bromide. 

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. 

PLLA-fr-PCL) multiblock copolymers were prepared from the coupling reaction between the bischloroformates of carboxylated PLLA with diol-terminated PCL in the presence of pyridine [140]. LLA was polymerized with SnOCt2 and 1,6-hexanediol followed by the reaction with succinic anhydride to provide the dicarboxylated PLLA. The carboxyl end groups were subsequently transformed to acid chloride groups by the reaction with thionyl chloride (Scheme 65). As expected, the molecular weight distributions were broad for all samples (1.84 < Mw/Mn < 3.17). 

Thiiranes (episulfides) have been suggested as intermediates in the reaction of thionyl chloride with various substrates including ketones and carboxylic acids.54 However, apart from one claim, later corrected, no such compounds have been isolated.55,56... 

A recent report indicates that thiophenes (not benzothiophenes) may be formed from alkyl phenyl ketones by treatment with a slight excess of thionyl chloride in the cold.58 Propiophenone, for example, yields 3,4-dibenzoyl-thiophene (47). Adipic acid and related carboxylic acids yield thiophene derivatives upon treatment with thionyl chloride in the presence of pyridine.59... 

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