Carboxylic acids, from primary

Oxidation.1 Hydrated copper permanganate oxidizes alcohols in CH2C12 rapidly and in high yields. Ketones are obtained from secondary alcohols, and carboxylic acids from primary and benzylic alcohols. Primary or secondary allylic alcohols are also oxidized efficiently. Anhydrous reagent is much less active. 

Preparation of carboxylic acids from primary alcohols in the presence of dehydrogenating catalysts at 120-150° is described by Russian authors.481... 

Based on studies of the RuCls-catalyzed disproportionation of iodine(III) species to iodobenzene and iodylbenzene [53, 94-96], a mild and efficient tandem catalytic system for the oxidation of alcohols and hydrocarbons via a Ru(in)-catalyzed reoxidation of ArlO to ArI02 using Oxone as a stoichiometric oxidant has been developed [53, 96, 97]. In particular, various alcohols are smoothly oxidized in the presence of catalytic Phi and RuCls in aqueous acetonitrile at room temperature to afford the respective ketones from secondary alcohols, or carboxylic acids from primary alcohols, in excellent isolated yields (Scheme 4.59) [97]. 

Hunsen, M. Carboxylic acids from primary alcohols and aldehydes by a pyridinium chlorochromate-catalyzed oxidation. Synthesis 2005, 2487-2490. 

Hydrolysis of nitriles provides a valuable way to synthesize carboxylic acids from primary or secondary haloalkanes. To do so, add one carbon in the form of a cyano group (Table 8.1) to the carbon chain and convert this to a carboxyl group. 

Carboxylic acids can be prepared from nitriles by reaction with hot aqueous acid or base by a mechanism that we ll see in Section 20.9. Since nitriles themselves are usually made by Sts 2 reaction of a primary or secondary7 alkyl halide with CN , the two-step sequence of cyanide displacement followed by nitiile hydrolysis is a good way to make a carboxylic acid from an alkyl halide (RBr —> RC=N RC02H). 

Amides prepared from carboxylic acids and primary amines using CDI. Examples ... 

Amides prepared from carboxylic acids and primary amines using A /V -sulfinyldii-midazole (ImSOIm) or phenoxyphosphoryldiimidazole (Im2P(0)(OC6H5). ... 

Because of the highly negative reduction potentials ( —3.0 V vs. SCE) [32], the electroreduction of esters of aliphatic carboxylic acids to primary alcohols by direct electron transfer from the cathode is very difficult and the electrochemical Birch-type reduction of aliphatic esters in MeNH2 or liquid NH3 has not been reported until recently (Scheme 15) [33, 34]. This reaction is not a reduction by direct electron transfer from the cathode to the C=0 bonds of the ester but the reduction by a solvated electron. 

From carboxylic acids and primary alcohols H RC02H + R OH = RCOjR + HjO Generally limited to primary alcohols acidic catalysts include H2S04, HCI, BF3 for details and mechanism see Sections 15-4D and 18-3A. 

M. Kunz, A. Schwarz, and J. Kowalczyk, Process and apparatus for continous manufacture of di- and higher-oxidized carboxylic acids from carbohydrates or their derivatives or primary alcohols, Patent DE 19542287 (1997) Chem. Abstr., 127 (1997) 52504. 

Depending on the substituents in (61) and on the concentration of the catalyst, however, other products may also subsequently be formed. In some cases, SbCl5-complexed primary intermediates of type (65) could even be isolated and characterized by NMR spectroscopy as well as by well-defined chemical reactions (81JA1789). Treatment of tetraphenyl-1,2,4-trioxolane (67) with antimony pentachloride or liquid sulfur dioxide, a mild Lewis acid, gave benzophenone and phenyl benzoate in a molar ratio of 1 1 (80JA288). The formation of the ester corresponds to that of the carboxylic acid from (61) via path A or path B. 

FIGURE 7 Schematic of different coupling methods used (a) reaction between meleimide and thiol functions (b) formation of disulfide bond (c) reaction between carboxylic acid and primary amine group (d) reaction between hydrazide and aldehyde functions (e) cross-linking between two primary amine functions. (Reproduced from ref. 150 with permission of Elsevier.)... 

The initial product 508 of AFC reactions of aromatic aldehydes, primary amines, and indoles is highly reactive and further addition of indoles gives undesired adduct 509 (Scheme 104) <2006OL4939>. In addition, aromatic aldehydes are themselves known to react with indoles directly to afford the undesired bisindolyl product 509. After screening catalysts (AcOH, TFA, Sc(DS)3, dodecylbenzenesulfonic acid, carboxylic acids from -C7Hi5 to -Ci3H27), it was revealed that decanoic acid ( -C9Hi9C02H) efficiently promoted the reaction without formation of product 509. 

Cobalt(II) salts are effective catalysts for the oxidation of 1,2-glycols with molecular oxygen in aprotic polar solvents such as pyridine, 4-cyanopyridine, benzonitrile, DMF, anisole, chlorobenzene and sulfolane. Water, primary alcohols, fatty acids and nitrobenzene are not suitable as solvents. Aldehydic products are further oxidized under the reaction conditions. Thus, the oxidative fission of rram-cyclo-hexane-l,2-diol gives a mixture of aldehydes and acids. However, the method is of value in the preparation of carboxylic acids from vicinal diols on an industrial scale for example, decane-1,2-diol is cleaved by oxygen, catalyzed by cobalt(II) laurate, to produce nonanoic acid in 70% yield. ... 

Another route to carboxylic acids from aldehyde products (once again, generally produced via hydroformylation catalysis) was discovered by Wakamatsu and coworkers. They reported the carbonylation of aldehydes and primary organic amides to produce A-acylamino acids (equation 16). The reaction is efficiently catalyzed by HCo(CO)4 at 100 °C and 140 bar of 3 2 H2/CO (hydrogen is needed to help stabilize HCo(CO)4). Yields of over 90% of the appropriate... 

This represents probably one of the earliest interests in the chemistry of Ti compounds." Ketones, like cyclohexanone, are easily dimethylated by MeTiCb, Me2 IlCl2 and Me2Zn/riCU- " Depending upon the molecular ratio of Mc2Zn and TiCU, various products (43), (154) and (155) are obtained from cyclohexanone (equation 57), as is reported in Table 1S. The reaction proceeds dirough cationic intermediates various functionalities (e.g. carboxylic acid esters, primary and secondary alkyl halides) are well tolerated. Some problems arise when a,3-unsaturated ketones are utilized, because of the formation of two distinct dimethylated products (equation 58). ... 

Several Curtius reactions have been employed to produce a primary amino group. Triazole-4-carboxylic acid [from acetylene-1-carboxylic acid and hydrazoic acid in chloroform (46% yield)] was esterified (70%), then converted to the hydrazide (71%) and on to the urethane (52%) and 4-aminotriazole (20%) (57YZ452). The final stage went better for 4-amino-5-methyltriazole, which achieved a 53% throughput from the urethane (76JHC589). 4-Amino-1 -methyltriazole was obtained in 64% yield from 4-ethoxycarbonyl-l-methyltriazole in this way (59ACS888). 

Related anchored l,l,3,3-tetraphenyl-2-oxa-l,3-diphospholanium bis-triflate (39) has been prepared by reaction of brominated poly(styrene-co-divinylbenzene) resin 38 with the phosphorous anion generated from l,2-bis(diphenylphosphino)ethane and sodium naphthalenide followed by further oxidation and reaction with triflic anhydride (Scheme 7.13) [55]. This supported reagent has also been employed, to a lesser extent than 37, for the formation of esters and amides by reaction of carboxylic acids with primary alcohols and amines, respectively. 

When primary amines (43 R6 = H) are used as the amine component, hydantoinimides (42e) and thiohy-dantoinimides (42f) result from hydrogen cyanate and thiocyanate as the acid component HX.53,54 The most important acid components are the carboxylic acids. With primary amines (43 R6 = H) they yield a-acylaminocarboxamides (42g),39,55-57 whereas with secondary amines (42 R1, R2 = organyl), the di-acylimines (42h) are the products, provided that acylatable nucleophiles are absent.55,58,59 The diacyl-imides (42h) are acylating reagents that transfer an R CO group, and so are their precursors, the a-adducts (41 X = R CCh).55... 

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