Amides from acyl halides

Although the formation of symmetric piperazine-2,5-diones is a well documented transformation (93AHC187), the unsymmetric -ones have been prepared from AAs or their amides with acyl halides, such as pyruvoyl chloride (81RTC73) and a-bromopropionyl bromide (91H923). 

Amides can be obtained from acyl halides, carboxylic anhydrides, or esters with amines or ammonia. The mechanisms of these reactions are very similar to the corresponding reactions of alcohols ... 

A highly favorable reaction of two solutes (say at 0.1 m concentration) is usually much faster than a low-driving-force side reaction of one of the solutes with solvent water (55 m). The Schotten-Baumann method for making amides from acyl or sulfonyl halides in water is a well-known example. 

The extent of resonance can be observed directly in the structures of carboxylic acid derivatives. In the progression from acyl halides to esters and amides, the C-L bond becomes progressively shorter, owing to increased double-bond character (Table 20-1). The NMR spectra of amides reveal that rotation about this bond has become restricted. For example, W,N-dimethylformamide at room temperature exhibits two singlets for the two methyl groups, because rotation about the C-N bond is very slow on the NMR time scale. The evidence points to considerable tt overlap between the lone pair on nitrogen and the carbonyl carbon, as a result of the increased importance of the dipolar resonance form in amides. The measured barrier to this rotation is about 21 kcal moF (88 kJ moF ). 

Some amide preparations from acyl halides require a primary or secondary amine that is too expensive to use also as the base to neutralize the hydrogen halide. Suggest a solution to this problem. 

Carboxylic acid hydiazides are prepared from aqueous hydrazine and tfie carboxylic acid, ester, amide, anhydride, or halide. The reaction usually goes poody with the free acid. Esters are generally satisfactory. Acyl halides are particularly reactive, even at room temperature, and form the diacyl derivatives (22), which easily undergo thermal dehydration to 1,3,4-oxadiazoles (23). Diesters give dihydtazides (24) and polyesters such as polyacrylates yield a polyhydrazide (25). The chemistry of carboxyhc hydrazides has been reviewed (83,84). 

The A-(l-acyloxyalkyl)amides or carbamates arc easily prepared from the corresponding hydroxy compounds by conventional acylation methods, such as heating with the required carboxylic acid in the presence of a strong acid or treatment with acyl halides or acid anhydrides1. 

Aldehydes have been prepared from carboxylic acids or acyl halides by first converting them to certain types of amides that are easily reducible. The following are some examples ... 

As with carboxylic acids obtained by palladium hydroxycarbonylation, their derivatives esters, amides, anhydrides and acyl halides are synthesized from alkenes, CO and HX (X = OR, NR2 etc.). The Pd-catalyzed methoxycarbonylation is one of the most studied reactions among this type of catalyzed carbonylations and has been reviewed and included in reports of homogeneous catalysis.625, 26 The methoxycarbonylation has been applied to many different substrates to obtain intermediates in organic syntheses as well as specific products. For instance, the reaction has been applied for methoxycarbonylation of alkynes666 Highly efficient homogeneous Pd cationic catalysts have been reported and the methoxycarbonylation of alkynes has been used to develop economically attractive and environmentally benign process for the production of methyl... 

A / -disubstituted acid amides are often prepared by reaction of acyl halides with secondary amines. This method is attractive when the acyl halide is readily available. This is not the case with pentynoyl chloride, which has to be synthesised by a two-step procedure from butyne (see exp. 8). In analogy with the carboxyalkylarion with alkyl chloroformates (exp. 2), an... 

Carboxylic acids and their derivatives like esters, amides, anhydrides, and acyl halides are formally synthesized from olefins, carbon monoxide, and compounds represented by Nu-H such as H2O, ROH, RNH2, RCOOH (Equations (4) and (5)). Alkynes also react under similar conditions to afford the corresponding unsaturated carboxylic acid derivatives. These reactions have been named hydrocarboxylation, hydroalkoxycarbonylation, and hydroaminocarbonylation. 

The acyl halide C,H2,COCI from (e) is reacted with the amine C,H2,NH2 from (fo), to form an amide that is then reduced. O... 

Resin-bound triazenes with a free NH group can be acylated by treatment with acyl halides, or carbamoylated by treatment with isocyanates [342]. The resulting triazene derivatives are stable towards strong bases, but undergo acidolysis when treated with TFA or TMSC1, yielding amides and ureas, respectively (Entries 1 and 2, Table 3.16). Polystyrene-bound triazenes devoid of a free NH group or carbamates can be cleaved from the support by treatment with acyl halides to yield amides (Entries 3 and 4, Table 3.16). 

The esterification of support-bound carboxylic acids has not been investigated as thoroughly as the esterification of support-bound alcohols. Resin-bound activated acid derivatives that are well suited to the preparation of esters include O-acylisoureas (formed from acids and carbodiimides), acyl halides [23,226-228], and mixed anhydrides (Table 13.15). A-Acylurea formation does not compete with esterifications as efficiently as it does with the formation of amides from support-bound acids. Esters can also be prepared from carboxylic acids on insoluble supports by acid-catalyzed esterification [152,229]. Alternatively, support-bound carboxylic acids can be esteri-fied by O-alkylation, either with primary or secondary aliphatic alcohols under Mitsu-nobu conditions or with reactive alkyl halides or sulfonates (Table 13.15). 

Write equations for the preparation of a given amide from an acyl halide, acid anhydride, or ammonium salt. 

There are several types of chiral derivatizing reagents commonly used depending on the functional group involved. For amines, the formation of an amide from reaction with an acyl halide [147,148], chloroformate reaction to form a carbamate [149], and reaction with isocyanate to form the corresponding urea are common reactions [150]. Carboxyl groups can be effectively esterified with chiral alcohols [151-153]. Isocynates have been used as reagents for enantiomer separation of amino acids, iV-methylamino acids, and 3-hydroxy acids [154]. In addition to the above-mentioned reactions, many others have been used in the formation of derivatives for use on a variety of packed and capillary columns. For a more comprehensive list, refer to References 155-159. 

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