Aliphatic carboxylic acid, condensation

An even simpler route to the fused-ring 1,3-dithiolium salts is by condensation of 203 with aromatic and even aliphatic carboxylic acids.131,13 > 137 The reaction, which is generally carried out in phosphorus oxychloride, proceeds rapidly and always in good yield. The parent member of this series of benzo-l,3-dithiolium salts is obtained in 80-90% yield when the acid used is formic acid (Table... 

Tetrakis(dimethylamino)titanium is a useful reagent for preparing amidines from secondary amides. From A X-thionyldiimidazole and secondary amides of boA aromatic and aliphatic carboxylic acids amidines (313 Scheme 50) are formed under mild conditions in moderate to good yields. N-Tosyl-amidines (314) can be obtained by reacting secondary thioamides (aliphatic and aromatic) with tosyl azide. Thiobenzamides have been condensed with anilines to afford amidines (315). Thioamides can be converted to amidines, e.g. (316), by treatment with ammonia in the presence of mercury acetate. ... 

Perkin reaction Condensation of aromatic aldehydes with the anhydrides of aliphatic carboxylic acids to afford a,P-unsaturated carboxylic acids. 338... 

A complication can occur when an aliphatic carboxylic acid amide is converted to the corresponding imidoyl halide, because isomerization to the corresponding enamine (IX) occurs. The generated enamine undergoes rapid reaction with the imidoyl halide to form the condensation product X. 

In the reaction of aliphatic carboxylic acid amides having hydrogens adjacent to the C=N bond, self-condensation of the generated imidoyl... 

If an ortho-substituted benzene ring is attached to the nitrogen, the self-condensation is minimized due to steric hindrance and the yield of imidoyl chlorides increases in this order CH3 < Cl < Br ( ). Likewise, lowering of the basicity of the nitrogen prevents condensation. For example, N-sulfonimidoyl chlorides of aliphatic carboxylic acids are obtained in excellent yield ( ). The carboxylic acid amides of a,j8-unsaturated acids also do not undergo tautomerization, because the formation of allenes is not favored under mild conditions... 

This reaction was first reported by Geuther in 1863 and subsequently studied by Claisen. It is a self-condensation of ester in the presence of alkali alkoxide in alcohol to form /3-keto esters (e.g. ethyl acetoacetate from ethyl acetate) and is generally known as acetoacetic ester condensation. This reaction was extensively explored by McElvain in 1930s. In general, it is carried out under basic conditions (e.g., NaOEt) to generate /3-keto-esters from aliphatic carboxylic acid esters. 

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

Condensation of aromatic or aliphatic esters with resin-supported acetyl carboxylic acids 28 followed by cyclisation with hydroxylamine, activation of the linker, and cleavage using amines, provided highly substituted isoxazoles 30 and 31. This general method gave products in excellent yields and purities in which the regioisomers ratio can be easily controlled . 

In spite of this variation in molecular weights and solubilities humic acid and fulvic acid have a very similar chemical composition. These acids consist of aromatic moieties such as phenols, benzenepolycarboxylic acids, hydroxybenzenepolycarbo-xylic acids, 1,2-dihydroxybenzene carboxylic acids, together with more complex condensed structures and polycylic compounds. It is conjectured that these various units are joined together by aliphatic chains (45, 54) the distribution of functional groups is presented in Table 5. 

Aromatic and aliphatic aldehydes can be oxidized after careful and individual optimization of the reaction conditions to carboxylic acids (Eq. (7), Table 12). With aromatic aldehydes yields are excellent, with aliphatic aldehydes good to satisfactory. The electrolyte has to be less alkaline than normal to suppress the aldol condensation. 2-Phenylpropanol is best oxidized at low temperatures to render the cleavage to benzoic acid more difficult, at 70 °C benzoic acid becomes main product (47 %). Double bonds in y,8- or even a,P-position are not touched in the oxidation. 

The reaction of cysteine with aliphatic aldehydes, 196 e.g. acetaldehyde, or with aromatic aldehydes, 196 197 e.g. benzaldehyde, leads to the corresponding 5-monosubstituted thiazoli-dine-4-carboxylic acid derivatives, whereas condensation of cysteine with ketones, such as... 

An alternative to the azlactone procedure for the preparation of short-chain dehydropeptides 19 is offered by the direct condensation of an a-oxo acid 17 on heating with one equivalent of a carboxylic acid amide or by the treatment of an a-oxo acid 17 with a nitrile in the presence of dry HC1 gas (Scheme 6). If the former reaction proceeds with the condensation of two molecules of amide per molecule of a-oxo acid, then the corresponding a,a-bis(acylamino) aliphatic acid 18 is formed, which on warming with acetic acid results in partial deamidation with formation of the corresponding dehydropeptide 19. 

DICARBOXYLIC ACIDS. The diacids are characterized by two carboxylic acid groups attached to a linear or branched hydrocarbon chain. Aliphatic, linear dicurbuxylic acids of the general formula HOOCiCH ) COOH and branched dicarboxylic acids are tile subject of this article. The bifunciionaJily of the diacids makes them versatile materials. ideally suited for a variety of condensation polymerization reactions. Several diacids are commercially important chemicals that are produced in mullimillion-kg quantities und hud application in a myriad of uses. 

The best preventive measure against racemization in critical synthetic steps (e.g. fragment condensation, see p. 239) is to use glycine (which is achiral) or proline (no azlactone) as the activated carboxylic acid component. The next best choice is an aliphatic monoamino monocarboxylic acid, especially with large alkyl substituents (valine, leucine). Aromatic amino acids (phenylalanine, tyrosine, tryptophan) and those having electronegative substituents in the /7-position (serine, threonine, cysteine) are, on the other hand, most prone to racemization. Reaction conditions that inhibit azlactone formation and racemization are non-polar solvents, a minimum amount of base, and low temperature. If all precautions are taken, one still has to reckon with an average inversion of 1 % per condensation reaction. This means, for example, that a synthetic hectapeptide contains only 0.99100 x 100% = 37% of the fully correct diastereomer (see p. 233 f.). 

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