Carboxylic acids dehydration

In the first case [7], the induced reaction is indicated shaped as before the conjugation. However, chemical induction changes the secondary reaction type as exemplified by equation (3.13). As the final equation (3.13) is compared with a different, secondary reaction, a conclusion is made [7] that the conjugation process changes the target reaction type (in this case, carboxylic acid dehydration). 

Under strongly acidic anhydrous conditions, carboxylic acids dehydrate to give the acylium ions, which you met as intermediates in the Friedel-Crafts reaction (Chapter 22),... 

A few carboxamides have been prepared. They may be hydrolyzed to carboxylic acids, dehydrated to nitriles, and homoamides also undergo the Hoffman reaction with alkaline sodium hypobromite to produce aminoalkylpurines. Table 31 lists reaction products of some typical purinecarboxamides. 

As the name indicates, carboxylic anhydrides are formally derived from the corresponding acids by loss of water. Although carboxylic acid dehydration is not a general method for anhydride synthesis, cyclic examples may be prepared by heating dicarboxylic acids. A condition for the success of this transformation is that the ring closure lead to a five- or six-membered ring product. 

In his cephalosporin synthesis methyl levulinate was condensed with cysteine in acidic medium to give a bicyclic thiazolidine. One may rationalize the regioselective formation of this bicycle with the assumption that in the acidic reaction mixture the tMoI group is the only nucleophile present, which can add to the ketone. Intramolecular amide formation from the methyl ester and acid-catalyzed dehydration would then lead to the thiazolidine and y-lactam rings. The stereochemistry at the carboxylic acid a-... 

Thiazole carboxylic acid hydrazides were prepared in a similar way (444, 445). Thus by refluxing thioacetamide or thiobenzamide with y-bromoaceto acetic ester arylhydrazones (83) for several hours in alcohol the 4-carboxythiazole derivatives (84) listed in Table II-ll were obtained (Scheme 36) (656). This reaction is presumed to proceed via dehydration of the intermediate, thiazoline-S-oxide. 

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). 

Condensa.tlon, A variety of condensation reactions involving the hydroxyl or the carboxyl or both groups occur with lactic acid. The important reactions where products can be obtained ia high yields are esterificatioa (both iatramolecular and with another alcohol or acid), dehydration, and aminolysis. 

Carboxylic acid derivatives on pyridopyrimidine rings appear to undergo normal reactions with electrophilic reagents, e.g. the 6-amide (70) is dehydrated to the 6-nitrile with phosphorus oxychloride. 

A -0-2-Isocephem-4-carboxylic acid, 1-P-phenoxyacetamido-3-methyl-1 -oxo-synthesis, 1, 430 Isochroman, 1,3-diphenyl-synthesis, 3, 787, 788 Isochroman, 3,4-diphenyI-conformation, 3, 631 Isochroman, 2-methyl-synthesis, 3, 788 Isochroman, 3-phenyl-synthesis, 3, 788 Isochroman, (-)-)-(i )-3-phenyI-stereoselective synthesis, 3, 789 Isochroman-4-carboxylic acid, l-oxo-3-phenyl-synthesis, 3, 860 Isochroman-I,3-diones, 4-acyI-synthesis, 3, 831 Isochromanols dehydration, 3, 767 isochroman synthesis from, 3, 789 Isochroman-1-one, 3-aryl-synthesis, 3, 858, 860... 

Merck and Maeder have patented the manufacture of arecaidine by loss of water from l-methyl-4-hydroxypiperidine-3-carboxylic acid. A method of producing the latter has been describd by Mannich and Veit and has been developed by Ugriumov for the production of arecaidine and arecoline. With the same objective, Dankova, Sidorova and Preobrachenski use what is substantially McElvain s process,but start by converting ethylene oxide, via the chlorohydrin and the cyanohydrin, into -chloropropionic acid. The ethyl ester of this with methylamine in benzene at 140° furnishes methylbis(2-carbethoxyethyl) amine (I) which on refluxing with sodium or sodium Moamyloxide in xylene yields l-methyl-3-carbethoxy-4-piperidone (II). The latter is reduced by sodium amalgam in dilute hydrochloric acid at 0° to l-methyl-3-carbethoxy-4-hydroxypiperidine (III) which on dehydration, and hydrolysis, yields arecaidine (IV R = H), convertible by methylation into arecoline (IV R = CH3). 

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. ... 

Isothiazole-3-carboxylic acid and its 4-bromo derivative have been obtained by oxidation of the corresponding aldehydes with silver oxide. They form acid chlorides, esters, and amides. The amides may be dehydrated to give the corresponding nitriles. ... 

Rearrangements and other side-reactions are rare. The ester pyrolysis is therefore of some synthetic value, and is used instead of the dehydration of the corresponding alcohol. The experimental procedure is simple, and yields are generally high. Numerous alkenes have been prepared by this route for the first time. For the preparation of higher alkenes (> Cio), the pyrolysis of the corresponding alcohol in the presence of acetic anhydride may be the preferable method." The pyrolysis of lactones 9 leads to unsaturated carboxylic acids 10 ... 

The preparation of a-iodocarboxylic acids is of particular interest, since iodide is a better leaving group as is chloride or bromide. A similar a-iodination with a phosphorus trihalide as catalyst is not known. However the iodination can be achieved in the presence of chlorosulfonic acid mechanistically the intermediate formation of a ketene 10 by dehydration of the carboxylic acid is assumed ... 

The reaction mechanism involves deprotonation of the carboxylic anhydride 2 to give anion 4, which then adds to aldehyde 1. If the anhydride used bears two a-hydrogens, a dehydration takes place already during workup a /3-hydroxy carboxylic acid will then not be isolated as product ... 

If the starting anhydride bears only one a-hydrogen, the dehydration step cannot take place, and a /3-hydroxy carboxylic acid is obtained as the reaction product. 

Nitriles are similar in some respects to carboxylic acids and are prepared either by SN2 reaction of an alkyl halide with cyanide ion or by dehydration of an amide. Nitriles undergo nucleophilic addition to the polar C=N bond in the same way that carbonyl compounds do. The most important reactions of nitriles are their hydrolysis to carboxylic acids, reduction to primary amines, and reaction with organometallic reagents to yield ketones. 

In practice, one proceeds as follows. The value of bh >s determined for the reaction with a series of acids of similar structure, that is, for carboxylic acids or ammonium ions, etc. Limiting the data to a single catalyst type improves the fit. since the inclusion of data for a second ype of acid catalyst might define a close but not identical line. This means that Ga may be somewhat different for each catalyst type. A plot of log(kBH/p) versus log(A BH(7//i) is then constructed. This procedure most often results in a straight line, within the usual —10-15 percent precision found for LFERs. One straightforward example is provided by the acid-catalyzed dehydration of acetaldehyde hydrate,... 

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 ... 

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