Acid chlorides preparation from carboxylic acids

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

Esters are usually prepared from carboxylic acids by the methods already discussed. Thus, carboxylic acids are converted directly into esters by SK2 reaction of a carboxyfate ion with a primary alkyl halide or by Fischer esterification of a carboxylic acid with an alcohol in the presence of a mineral acid catalyst. In addition, acid chlorides are converted into esters by treatment with an alcohol in the presence of base (Section 21.4). 

Amides prepared from carboxylic acids and primary amines using azolides obtained from acid chloride/imidazolea) or ketene/imidazole systems.b)... 

In addition to acyl chlorides and acyl bromides, there are a number of milder and more selective acylating agents which can readily prepared from carboxylic acids, hnidazolides, the /V-acyl derivatives of imidazole, are examples.108 Imidazolides are isolable substances and can be prepared directly from the carboxylic acid by reaction with... 

Preparation of acid anhydrides Acid anhydrides are prepared from carboxylic acids by the loss of water. For example, acetic anhydride is prepared industrially by heating acetic acid to 800 °C. Other anhydrides are difficult to prepare directly from the corresponding carboxylic acids. Usually they are prepared from acid chloride and sodium carboxylate salt (see below). 

Ketenimines are usually prepared from carboxylic acid derivatives such as amides and imino chlorides via elimination and from nitriles via alkylation with alkyl halides under strong basic conditions (21,64). 

Carboxamides from CJiJCOOH. Carboxamides can be prepared from carboxylic acids directly rather than via the acid chlorides if the reaction with an amine and N(C2H5)3 is carried out in the presence of a Lewis acid. In reactions with a primary amine, BF, etherate is completely ineffective. In contrast, TiCL, is about equal to BF3 etherate in reactions with a secondary amine and has the further advantage that the rate of amidation is faster with TiCL, than with BF3 etherate. 

Acyl halides may be prepared from carboxylic acids by treatment with phosphorus pentachloride or, better, thionyl chloride (Scheme 3.63) the latter gives gaseous by-products. Oxalyl chloride may be used in the same way and again it gives volatile by-products. 

Silyl esters are generally prepared from carboxylic acids and the corresponding silyl chlorides or silyl triflates in the presence of base, e.g. pyridine, TEA, imidazole, in CH2CI2, CHCI3, DMF, or A-Methyl-C)-(trimethylsilyl)acetamide or A,0-bis(tri-... 

Amides have also been prepared from carboxylic acids as follows a mixture of 2-carboxypyrazine and triethylamine in methylene chloride treated with ethyl chloroformate and then morpholine gave 2-(A-morpholinocarbonyl)pyrazine (1351) 2-carboxy-5(and 6)-methylpyrazine in dioxane with tributylamine and ethyl chloroformate and then treated with ammonia gave 2-carbamoyl-5(and 6)-methylpyrazine (673), and 2-carbamoyl-5(and 6)-ethylpyrazine were prepared... 

Alternative methodologies for the indirect reduction of carboxylic derivatives employ as intermediates 2-substituted 1,3-benzoxathiolium tetrafluoborates (prepared from carboxylic acids, acyl chlorides, anhydrides, or esters) and dihydro-1,3-... 

Acyl chlorides (RCOCI), esters (RCO2R ). and nitriles (RCN) are all easily prepared from carboxylic acids (Chapter 17), and they all are more easily reduced. 

The reaction of an amine with an acyl chloride is one of the most widely used laboratory methods for the synthesis of amides, because acyl chlorides are themselves easily prepared from carboxylic acids. 

Esters are prepared from carboxylic acids by the reaction between an acid chloride and an alcohol or between a carboxylic acid and an alcohol under acidic conditions. Both sulfonic acids and sulfonyl chlorides react with alcohols to form sulfonate esters. When butanesulfonyl chloride (177) reacts with propanol, usually in the presence of a base such as triethylamine, propyl butanesulfonate (180) is formed. A wide range of sulfonyl esters can be formed this way from an alcohol and a sulfonic acid. 

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. 

Phthalocyanine sulfonic acids, which can be used as direct cotton dyes (1), are obtained by heating the metal phthalocyanines in oleum. One to four sulfo groups can be introduced in the 4-position by varying concentration, temperature, and reaction time (103). Sulfonyl chlorides, which are important intermediates, can be prepared from chlorosulfonic acid and phthalocyanines (104). The positions of the sulfonyl chloride groups are the same as those of the sulfonic acids (103). Other derivatives, eg, chlormethylphthalocyanines (105—107), / /f-butyl (108—111), amino (112), ethers (109,110,113—116), thioethers (117,118), carboxyl acids (119—122), esters (123), cyanides (112,124—127), and nitrocompounds (126), can be synthesized. 

This tertiary ester was developed to reduce aspartimide and piperidide formation during the Fmoc-based peptide synthesis by increasing the steric bulk around the carboxyl carbon. A twofold improvement was achieved over the the standard Fbutyl ester. The Mpe ester is prepared from the acid chloride and the alcohol and can be cleaved under conditions similar to those used for the r-butyl ester. ... 

Amino acids activated at the amino group by a benzotriazolide moiety react with amino acids under elimination of benzotriazole and C02 to give peptides. Reaction is achieved by warming up equimolar amounts of the components in anhydrous acetonitrile or aqueous acetone.[45] The benzotriazolylcarbonylamino acids are prepared from benzo-triazolyl-1-carboxylic acid chloride and amino acids.[46]... 

Nakagome and co-workers effected the successful cyclization of N-ethyl-N-arylaminomethylenemalonates (749) in poly phosphoric acid, prepared from orthophosphoric acid and phosphorus pentoxide in polyphosphate ester (PPE), prepared from phosphorus pentoxide and anhydrous diethyl ether in chloroform in phosphoryl chloride on the action of boron trifluoride etherate on the action of acetic anhydride and concentrated sulfuric acid or on the action of phosphorus pentoxide in benzene [71GEP2033971, 71JHC357 76JAP(K) 18440]. Depending on the work-up process, l-ethyl-4-oxoquinoline-3-carboxylates (750, R1 = Et), l-ethyl-4-oxoquinoline-3-carboxylic acids (750, R2 = H) and 3-ethoxycarbonyl-4-chloroquinolinium iodides (751) were obtained. Only the cyclization of... 

The preparation of furyl phosphorodichioridate is based upon a method to prepare 2-chlorofuran (16% yield, Hormi, Nasman unpublished). Later the preparation was extended to a general method to prepare furyl esters from carboxylic acid chlorides lacking a-hydrogens and alkyl furyl carbonates from primary (other than methyl) and secondary alkyl chloroformates. Phosphoryl chloride was the only acid chloride except carbon analogues found to give a furyl ester by the amine-catalyzed reaction. 

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