Carboxylic acid amid Dimethylformamide

The carboxylic acid amides most conunonly studied as ligands are formamide, acetamide, and the W-substituted derivatives, particularly A,A-dimethylformamide (DMF). These compounds are often used as solvents and have high dielectric constants, particularly when they contain an N-H bond, and such uses helped to stimulate interest in the amides as ligands. There are two possible donor atoms, N or O, but all complexes of the simple amide ligands, characterized by X-ray structure determination at least, have M-O bonds. The amides are usually terminal ligands but can bridge between metal atoms in some instances. 

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

Diphenyl phosphoryl azide in dimethylformamide followed by triethylamine added at or below 0° to a soln. of N-carbobenzoxy-L-leucyl-L-leucine and L-valyl-L-phenylalanine methyl ester hydrochloride in the same solvent, stirred several hrs. at the above temp, and overnight at room temp. -> product. Y 87%. - Practically no racemization occurred. F. e., also direct prepn. of urethans from carboxylic acids (cf. Synth. Meth. 17, 393) by a simplified Curtius degradation, s. T. Shioiri, K. Ninomiya, and S. Yamada, Am. Soc. 94, 6203 (1972) Tetrah. Let. 1973, 2343 synthesis of N-subst. carboxylic acid amides and peptides with diethyl phosphoryl cyanide s. Tetrah. Let. 1973, 1595 coupling reagents in peptide synthesis, review, s. Y. S. Klausner and M. Bodansky, Synthesis 1972, 453 review of peptide synthesis s. J. Meienhofer, Chem. Technol. 3, 242 (1973). 

Mechanistic studies are reported of the esterification of carboxylic acids with dimethylformamide dimethyl acetal and other amide acetals. The reaction between phenylacetic acid (36), acetic anhydride, and o-hydroxybenzophenone (38) catalysed by EtsN yielded 3,4-diphenylcoumarin (40) in 78% yield.The mechanism presumably involves the initial formation of the mixed anhydride of acetic acid and phenylacetic acid (37), which then acylates the o-hydroxybenzophenone (38) to yield o-phenacyloxybenzophenone (39), cyclization of which, via the carbanion, produces the coumarin (40). Kinetic studies have been reported of the hydrothermal oxidation and hydrolysis of lactic acid at 300-400 °C and a nominal pressure of 27.6 MPa. ... 

Dimethylformamide-sulfur trioxidellithium hydroxide HCON(CH )2 SOjLiOH Subst. carboxylic acid amides from carboxylic acids... 

Different functional groups can be introduced at the 5-position of thieno[2,3- / -l,2,3-thiadiazole-6-carbo-xylates 43a and 43b by lithiation and subsequent reaction with the desired electrophile <1999JPR341>. For example, reaction of carboxylic acid 43a with lithium diisopropylamide (LDA) followed by CI3CCCI3 produced the 5-chloro product 44a while amide 43b treated with -BuLi then dimethylformamide (DMF) gave aldehyde 44b (Equations 4 and 5). 

The reactions can be catalyzed effectively by various additives. It has been shown that dimethylform-amide constitutes an effective catalyst in many cases, the reaction being thought to proceed via an intermediate imidoyl chloride (equation 2). ° The catalytic effect may be so pronounced that otherwise unreactive carboxylic acids can be transformed to their acid chlorides. An example is trichloroacetic acid which reacts only in the presence of N.N-dimethylformamide with thionyl chloride. Interestingly, this reaction can also be accomplished in the presence of an alkali metal chloride. Other catalysts being used include pyridine" and triphenylphosphine. The latter converts iso- and tere-phthalic acid quantitatively to the corresponding acid dichlorides. 

Thionyl chloride forms a fairly stable primary adduct (15) with DMF, which has been isolated. On heating it decomposes to SO2 and NA -dimethylformamide chloride (equation 4). Treatment of the adduct (15) with carboxylic acids affords iminium salts (16 equation S) in which the carboxylic acid function is strongly activated, e.g. for amide formation. With imines -lactams are formed, sodium azide is converted to acyl azides. ... 

Ketones may be prepared by the reaction of the lithio intermediate with a nitrile (Reaction 11) (6). Nitriles possessing no alpha hydrogens work best in this reaction. Formyl derivatives of aromatics may be synthesized by treating the lithiated species with dimethylformamide (Reaction 12) (19). Carboxylic acids are readily available by carbonation of such lithio intermediates (14,16). Treatment of these lithio intermediates with aryl or alkyl isocyanates yields amides (Reaction 13) (10). 

Acylating agents that have been employed are carbon dioxide, alkyl chloroformates, alkyl formates, add chlorides, esters, benzonitrile and dimethylformamide the expected acylation products from reaction with the above reagents were formed in each case. However, the N,N-dimethyl-amide derivatives of higher carboxylic acids did not yield acylated product as in the case of dimethylformamide . When R = H (equation 63), it was necessary to employ two equivalents of the lithiodithiane due to product enolate formation. 

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. 

A soln. of p-chlorobenzenediazonium hexafluorophosphate in dimethylform-amide added slowly with stirring at — 5° to a mixture of n-butylamine, powdered Na-carbonate, and dimethylformamide, warmed to 0°, and stirred a few min. until a negative test is obtained with 2-naphthol, ether added, filtered, the filtrate washed and dried, this soln. of the resulting crude l-(n-butyl)-3-(4-chlorophenyl)triazene (Y ca. 100% when isolated) treated with ethereal 3,5-dinitrobenzoic acid, and kept 1-2 hrs. at 25° until Ng-evolution ceases n-butyl 3,5-dinitrobenzoate. Y 63-73%.— Triazenes may be used as alkylating agents for carboxylic acids, phenols, mercaptans, and certain alcohols. F. e. s. E. H. White and H. Scherrer, Tetrah. Let. 1961, 758. 

A tertiary amide has no hydrogens on the nitrogen. Substituents on the nitrogen are listed alphabetically together with the other substituents from the carboxylic acid portion of the chain. As usual, the smaller members of the class have retained their common names, which are based on the common names for the smaller carboxylic acids. For example, you will often encounter AA -dimethylformamide (abbreviated DMF) because it is a usefiil polar, high-boiling solvent. 

O, -unsaturated carboxylic acids, esters, and amides are reduced easily to saturated derivatives by treating them with Sml2 in the presence of a proton source (Girard et al., 1980). The use of dimethylformamide (DMF) or A/, A/ -dimethyl acetamide (DMA) as a cosolvent with THF enhances the rates of reaction and improves yields considerably as shown in eqs. (8), (9) (Inanaga, 1990). 

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 ). 

The dielectric constants of amides are higher than those of carboxylic acids and esters of similar structure. The dielectric constants of formamide and dimethylformamide are 111 and 37, respectively. Dimethylformamide (DMF) is an excellent polar aprotic solvent. It dissolves inorganic salts such as halides used in Sj 2 reactions. 

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