Carboxylic acids, conversion dehydration

Non-oxidative conversion of a tetrahydro-)8-carboline into a 3,4-dihydro derivative has also been described. Dehydration of 1-hydroxymethyl-1,2,3,4-tetrahydro-j8-carboline (146) yielded 1-methyl-3,4-dihydro-j8-carboline (135). Harmaline and l-methyl-3,4-dihydro-j8-carboline-3-carboxylic acid were obtained in an analogous manner. ... 

Another way to esterify a carboxylic acid is to treat it with an alcohol in the presence of a dehydrating agent. One of these is DCC, which is converted in the process to dicyclohexylurea (DHU). The mechanism has much in common with the nucleophilic catalysis mechanism the acid is converted to a compound with a better leaving group. However, the conversion is not by a tetrahedral mechanism (as it is in nucleophilic catalysis), since the C—O bond remains intact during this step ... 

Various combinations of reactant(s) and process conditions are potentially available to synthesize polyesters [Fakirov, 2002 Goodman, 1988], Polyesters can be produced by direct esterification of a diacid with a diol (Eq. 2-120) or self-condensation of a hydroxy carboxylic acid (Eq. 2-119). Since polyesterification, like many step polymerizations, is an equilibrium reaction, water must be continuously removed to achieve high conversions and high molecular weights. Control of the reaction temperature is important to minimize side reactions such as dehydration of the diol to form diethylene glycol... 

Nitriles are most commonly prepared via the conversion of carboxylic acids to primary amides, followed by dehydration with boiling acetic anhydride, or other commonly employed dehydration reagents, e.g. SOCI2 or POCI3. This is a useful synthesis for amide, because it is not limited by steric hindrance. Alkyl nitriles can be prepared by the action of metal cyanides on alkyl halides (see Section 5.5.2). 

Carboxylic acid anhydrides generally react with sulfur tetrafluoride in the same manner as carboxylic acids to give acid fluorides, then trifluoromethyl derivatives. Various cyclic anhydrides, which are particularly stable under acidic conditions, react without cleavage to give, in a stepwise fashion, difluoro lactones and a,a,a, a -tetrafluoro ethers. Conversely, the corresponding diacids are readily dehydrated by sulfur tetrafluoride to give anhydrides in the first step of the reaction. Therefore, in this section reactions of carboxylic acids and carboxylic acid anhydrides are discussed together. 

MIESCHER DEGRADATION. Adaptation of the Barbier-Wieland carboxylic acid degradation to pcrmil simultaneous elimination of three carbon atoms, as in degradation of the bile acid side chain to the methyl ketone stage. Conversion of the methyl ester of the bile acid to the tertiary alcohol, followed by dehydration, bromination. dehydrohalogenatinn, and oxidation of the diene yields die required degraded ketone. 

Possibly the most important condensation reaction is that between a carboxylic acid and an amine to give an amide. A great many methods are known by which this formal dehydration process may be carried out, almost all of which involve the two step sequence (i) activation of CO2H COX, where X is a leaving group and (ii) aminolysis of RCOX. Japanese workers have recently advocated the use of 2,2-dichloro-5-(2-phenylethyl)-4-trimethylsilyl-3-furanone (1, "DPTF") for carboxyl activation, and its use for peptide formation is illustrated by the representative conversion 2 —> 3. The byproduct formed from DPTF in these reactions is 5-(2-phenylethyl)-4-trimethylsilylfuran-2,3-dione. 

The one-pot conversion of an aromatic carboxylic acid into the corresponding nitrile may be effected by reaction with ammonia in the presence of ethyl polyphosphate64 the initial stage is the formation of the amide and this is followed by dehydration to the nitrile. The reaction has been used successfully with a range of aromatic carboxylic acids. 

Conversion of the methyl ester of 1-adamantane carboxylic acid to 1-ada-mantyl dimethylcarbinol (66) by reaction with CH3Mgl followed by dehydration and subsequent hydrogenation provides a convenient route to 1-iso-propyladamantane (66a) 164> 20°). Simmons-Smith cyclopropanation of 1-isopropenyladamantane (67) followed by hydrogenolysis of the cyclopropane ring gives 1-r-butyladamantane (68) 204>. An alternative synthesis... 

Carboxylic acids can also be activated by converting them to their anhydrides. For this purpose they are dehydrated with concentrated sulfuric acid, phosphorus pentoxide, or 0.5 equivalents of SOCl2 (1 equivalent of SOCl2 reacts with carboxylic acids to form acid chlorides rather than anhydrides). However, carboxylic anhydrides cannot transfer more than 50% of the original carboxylic acid to a nucleophile. The other 50% is released—depending on the pH value—either as the carboxylic acid or as a carboxylate ion and is therefore lost. Consequently, in laboratory chemistry, the conversion of carboxylic acids into anhydrides is not as relevant as carboxylic acid activation. Nonetheless, acetic anhydride is an important acetylat-ing agent because it is commercially available and inexpensive. 

Although nitriles lack an acyl group, they are considered acid derivatives because they hydrolyze to carboxylic acids. Nitriles are frequently made from carboxylic acids (with the same number of carbons) by conversion to primary amides followed by dehydration. They are also made from primary alkyl halides and tosylates (adding one carbon) by nucleophilic substitution with cyanide ion. Aryl cyanides can be made by the Sandmeyer reaction of an aryldiazonium salt with cuprous cyanide. a-Hydroxynitriles (cyanohydrins) are made by the reaction of ketones and aldehydes with HCN. 

Dehydrative decarboxylation.1 The conversion of (3-hydroxy carboxylic acids to alkenes by reaction with a DMF dialkyl acetal involves an anr/-elimination, and thus is complementary to the known syn-elimination of these hydroxy acids via a (3-lactone (5, 22 9, 504). These reactions were used to obtain both the (E)- and the (Z)-l-alkoxy-l,3-... 

Primary alcohols are oxidized to aldehydes or acids, and secondary alcohols are oxidized to ketones. Tertiary alcohols resist oxidation, unless they are dehydrated in acidic media to alkenes, which are subsequently oxidized. The conversion of alcohols into carbonyl compounds can be achieved by catalytic dehydrogenation or by chemical oxidation. Catalytic dehydrogenation is especially of advantage with primary alcohols, because it prevents overoxidation to carboxylic acids. Examples are tabulated in equations 223-227 and 265-268. 

There are efficient ways in which to use starting materials that have the carboxylic acid component already installed on both heteroatoms conversion to bis(silyloxy) derivatives, or simply heating with p-toluenesulfonic acid. An excellent route to mono-acylated precursors utilises mixed anhydrides. A very mild method for the dehydrative ring closure of ortfto-hydroxyarylamino-amides utilises typical Mitsunobu conditions - triphenylphosphine and diethyl azodicarboxylate. ... 

Theanine was first chemically synthesized with a 9% yield from pyrrolidonecarbox-ylic acid (PCA) treated with 33% (v/v) aqueous solution of ethylamine at 37°C for 20 days (figure 16.5). L-Glutamic acid could be dehydrated, leading to 2-pyrrolidone-5-carboxylic acid. Abderhalden and Kautzsch " and Beecham reported a yield of 70-90% for conversion of glutamic acid to PCA. 

The biosynthesis of menaquinones in E. coli (Fig. 5) starts with the conversion of isochorismic acid and a-ketoglutaric acid in the presence of thiamine pyrophosphate [105-107] to 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylic acid (SHCHC) catalyzed by SHCHC synthase, and a-ketoglutarate decarboxylase, both encoded by the menD gene [104,108,109]. SHCHC is converted to o-succinylbenzoic acid by dehydration, catalyzed by a protein encoded by menC (Table 1) [110]. Palaniappan et al., [111] showed for the first time the biosynthesis of menaquinones via o-succinyl benzoic acid in B. subtilis including the activity of the enzymes. 

Oxazolines are formed directly from the reaction of carboxylic acids with 2-ami-no-2-methyl-l-propanol in refluxing toluene but a two-step procedure involving reaction of 2-amino-2-methyl-l-propanol with an acid chloride followed by treatment of the resultant amide with excess thionyl chloride as a dehydrating agent is generally preferred (Scheme 2.128].2 o 26i Alternatives include reaction of dimethylaziridine with a carboxylic acid in the presence of dicyclohexylcarbo-diimide to form the N-acylaziridine followed by acid-catalysed rearrange-ment or reaction of an orthoester, or an imidate ester, with an amino alcohol as illustrated by the conversion of 129.1 to 1293 [Scheme 2.129). ... 

After conversion to acetyl-AGP and malonyl-AGP, two carbons of the malonyl-AGP are introduced via the condensing enzyme, 6-ketoacyl-ACP synthetase. Loss of the malonyl carboxyl drives the reaction and in the first step of the sequence acetoacetyl-AGP is formed. The B-ketoacyl-ACP is then reduced to B-hydroxyacyl-AGP by NADPH and the enzyme B-ketoacyl-AGP reductase. The hydroxy acid is dehydrated to form a trans-2.3-enov1-ACP which can be reduced by NADH or NAOPH to the saturated AGP derivative (butyrate in the first series of steps). Gondensation with malony 1-ACP is then repeated and the cycle continues to produce acyl-ACP derivatives with two additional carbon atoms until palmitoy1-ACP results. A second B-ketoacyl-ACP synthetase accomplishes addition of two more malonyl carbon atoms to allow the formation of stearoyl-ACP. The B-ketoacyl-ACP synthetase has been shown to be a separate enzyme since it is more easily inhibited by arsenite and is less sensitive to the antibiotic, cerulenin, than the B-ketoacyl-ACP synthetase forming C to C g keto acids. 

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