Carboxylic acids, by carbonylation

The phase-transfer method has also been used for the synthesis of aryl, benzyl, vinyl and heterocyclic carboxylic acids by carbonylation of the corresponding halides (equation 105).476... 

The synthesis of carboxylic acids by carbonylation of unsaturated hydrocarbons or alcohols was developed mainly by Reppe and his co-workers in the laboratories of BASF at Ludwigshafen. Many industrially important processes such as the synthesis of acrylic acid, propionic acid, and acetic acid were elaborated there in the period from the late 1930s to the mid-1950s [1, 2]. Reppe s introduction of metal carbonyls as catalysts for carbonylation reactions was of paramount importance and many processes, which are still industrially relevant today, were developed rapidly (eq. (1), [3]). 

Various molecules can serve as a starting material for the synthesis of carboxylic acids by carbonylation. Because of the differing chemical nature of the starting materials, special catalysts or catalytic systems have been developed. However, despite the fact that tremendous efforts have been made to develop large-scale processes, few have been brought to commercial maturity. 

Silver oxide/sulfuric acid Tert. carboxylic acids by carbonylation... 

The aryl halides can be converted into the corresponding carboxylic acid by carbonylation in presence of water. The use of PTC is a well established technique for carbonylation of organic halides.Carbonylation of organic halides using various types of phase transfer techniques has been extensively reviewed. ... 

All these facts—the observation of second order kinetics nucleophilic attack at the carbonyl group and the involvement of a tetrahedral intermediate—are accommodated by the reaction mechanism shown m Figure 20 5 Like the acid catalyzed mechanism it has two distinct stages namely formation of the tetrahedral intermediate and its subsequent dissociation All the steps are reversible except the last one The equilibrium constant for proton abstraction from the carboxylic acid by hydroxide is so large that step 4 is for all intents and purposes irreversible and this makes the overall reaction irreversible... 

Piimaiy and secondary alkyl peroxyesters thermally decompose by a nonradical process, giving almost quantitative yields of carboxylic acids and carbonyl compounds (213,241) ... 

Pyridazine aldehydes and ketones with the carbonyl group at the ring or in a side chain react in the usual manner. They form hydrazones, semicarbazides, oximes, etc. Side-chain aldehydes can be easily oxidized to pyridazinecarboxylic acids with silver nitrate and side-chain ketones are oxidized to carboxylic acids by treatment with potassium permanganate or hydrogen peroxide. 

Basic hydrolysis occurs by nucleophilic addition of OH- to the amide carbonyl group, followed by elimination of amide ion (-NH2) and subsequent deprotonation of the initially formed carboxylic acid by amide ion. The steps are reversible, with the equilibrium shifted toward product by the final deprotonation of the carboxylic acid. Basic hydrolysis is substantially more difficult than the analogous acid-catalyzed reaction because amide ion is a very poor leaving group, making the elimination step difficult. 

Amides may be hydrolysed to carboxylic acids by either acids or bases, though hydrolysis is considerably slower than with esters. Although amines are bases and become protonated on nitrogen via the lone pair electrons, we know that amides are not basic (see Section 4.5.4). This is because the lone pair on the nitrogen in amides is able to overlap into the carbonyl... 

Fig. 10 Synthesis of imidazolines or benzimidazoles by condensation of an additional amine with the carboxylic acid-derived carbonyl...

Cachaqa and aguardente de cana are the most consumed distilled spirits in Brazil exclusively made from cane-sugar juice. Sugar and caramel maybe added for colour adjustment. The total content of congeners is between 200 and 650 mg 0.1 L p.e. Like other spirits, the flavour of cacha a is mainly characterised by the presence of fermentation by-products such as higher alcohols, esters, carboxylic acids, and carbonyl compounds [41-43]. 

Primary and secondary alkyl peroxyesters thermally decompose by a nonradical process, giving almost quantitative yields of carboxylic acids and carbonyl compounds. Art-Alkyl peroxyesters are much less sensitive to radical-induced decompositions than diacyl peroxides. Induced decomposition is only significant in peroxyesters containing nonhindered a-hydrogens or a, /(-unsaturation. 

For this reason reactive groups are usually introduced before quinuclidine ring closure and various transformations are effected afterward. The carboxyl and carbonyl derivatives, e.g., quinuclidine-2-carboxylic acid, quinuclidin-3-one, and so on, are useful compounds containing such functional groups. Nearly all substituted quinuclidines were obtained from their carboxylic acids and carbonyl derivatives by common synthetic methods. 

On the pages which follow, general methods are illustrated for the synthesis of a wide variety of classes of organic compounds including acyl isocyanates (from amides and oxalyl chloride p. 16), epoxides (from reductive coupling of aromatic aldehydes by hexamethylphosphorous triamide p. 31), a-fluoro acids (from 1-alkenes p. 37), 0-lactams (from olefins and chlorosulfonyl isocyanate p. 51), 1 y3,5-triketones (from dianions of 1,3-diketones and esters p. 57), sulfinate esters (from disulfides, alcohols, and lead tetraacetate p. 62), carboxylic acids (from carbonylation of alcohols or olefins via carbonium-ion intermediates p. 72), sulfoxides (from sulfides and sodium periodate p. 78), carbazoles... 

The cyclic ketenes were generated from /V-acy 1-1,3-thiazolidine-2-carboxylic acids by means of Mukaiyama s reagent. The same reaction generated enantio-merically pure 1,3-thiazolidine-derived spiro-p-lactams, using optically active /V-A rt-butoxycarbonyl-1,3-thiazolidine-2-carboxylic acid derivatives as precursors of the asymmetrical chiral cyclic ketenes (7< r/-butoxy carbonyl Boc) [101]. 

Another way to potential antiinflammatory activity is to mimic a carboxylic acid by a tetrazole moiety (compare thepKa 4 8 for tetrazole itself). A good example is IntrazolR which is closely related to Indomethacin (an indolyl-3-acetic acid derivative). Therefore we have also reduced the carbonyl group in 39 yielding compounds of type 44 [84JHC1881], Unfortunately no compound of this series showed antiinflammatory activity. 

Thienooxazinediones (363) are obtained by reacting 2-aminothiophene-3-carboxylic acids with carbonyl chloride. These may then be alkylated and reacted with aldehydes to yield 3-substituted thiophenes (364) (Scheme 26) <86JCR(M)1063, 86JCR(M)2828, 86JCR(S)155, 86JCR(S)328>. 

Carboxylic acids are easily converted to a variety of acid derivatives. Each derivative contains the carbonyl group bonded to an oxygen or other electron-withdrawing element. Among these functional groups are acid chlorides, esters, and amides. All of these groups can be converted back to carboxylic acids by acidic or basic hydrolysis. 

The carbonylation of alcohols can proceed with formation of carboxylic acid by catalytic insertion of CO into the carbon-oxygen bond. An alternative reaction gives rise to oxalate or formate esters, when the CO is inserted into the oxygen-hydrogen bond. The members of the nickel triad carbonylate alcohols to give each of these products, and they will be discussed separately. 

The production of carboxylic acids via carbonylation catalysis is the second most important industrial homogeneous group of processes. Reppe developed most of the basic carbonylation chemistry in the 1930s and 1940s. The first commercial carbonylation process was the stoichiometric Ni(CO)4-based hydroxycarbonylation of acetylene to give acrylic acid (see Section 3.5 for details). This discovery has since evolved into a trae Ni-catalyzed process, used mainly by BASF. The introduction of rhodium catalysts in the 1970s revolutionized carboxylic acid production, particularly for acetic acid, much in the same way that Rh/PPhs catalysts changed the importance of hydroformylation catalysis. 

Addition reactions. a,0-Unsaturated carbonyl compounds 1 and 3 undergo exclusive 1,4-addition reactions with organolithium (and organomagnesium) compounds owing to steric hindrance of the carbonyl group. The adducts 2 and 4 are converted into carboxylic acids by cleavage with potassium t-butoxide and H2O in the case of 2 see potassium r-hutoxidc, this volume) and by treatment with ethanolic... 

This ring closure takes place readily whenever the carbonyl and amino groups occur in the relative positions shown above. Reduction of o-nitro-phenylacetonitrile by stannous chloride produces indole rather than the corresponding amino aldehyde. The synthesis is most useful for the preparation of indole-2-carboxylic acid by reduction of o-nitrophenyl-pyruvic acid with ferrous sulfate and ammonia or with sodium hydrosulfite. The ethyl ester is obtained by a similar reduction with zinc and acetic acid or by catalytic hydrogenation of ethyl o-nitrophenyl-pyruvate over platinum oxide catalyst. ... 

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