Alkylative/arylative carboxylation

When an alkyl aryl ketone is heated with yellow ammonium polysulphide solution at an elevated temperature, an aryl substituted aliphatic acid amide is foimed the product actually isolated is the amide of the ci-aryl carboxylic acid together with a smaller amount of the corresponding ammonium salt of the oarboxylio acid. Thus acetophenone affords phenylacetamide (50 per cent.) and ammonium phenylacetate (13 per cent.) ... 

In addition to providing fully alkyl/aryl-substituted polyphosphasenes, the versatility of the process in Figure 2 has allowed the preparation of various functionalized polymers and copolymers. Thus the monomer (10) can be derivatized via deprotonation—substitution, when a P-methyl (or P—CH2—) group is present, to provide new phosphoranimines some of which, in turn, serve as precursors to new polymers (64). In the same vein, polymers containing a P—CH group, for example, poly(methylphenylphosphazene), can also be derivatized by deprotonation—substitution reactions without chain scission. This has produced a number of functionalized polymers (64,71—73), including water-soluble carboxylate salts (11), as well as graft copolymers with styrene (74) and with dimethylsiloxane (12) (75). 

The reaction of lithio derivatives with appropriate electrophiles has been utilized in the preparation of alkyl, aryl, acyl and carboxylic acid derivatives. Representative examples of these conversions are given in Scheme 79. Noteworthy is the two-step method of alkylation involving reaction with trialkylborane followed by treatment with iodine (78JOC4684). 

Carbamates can be used as protective groups for amino acids to minimize racem-ization in peptide synthesis. Racemization occurs during the base-catalyzed coupling reaction of an A-protected, carboxyl-activated amino acid and takes place in the intermediate oxazolone that forms readily from an A-acyl-protected amino acid (R = alkyl, aryl) ... 

Aughel and coworkers [63] studied the phase behavior of hydrocarbon-water mixtures in the presence of alkyl(aryl)polyoxyethylene carboxylates for enhanced oil recovery and found good salt tolerance with an alkyl ether carboxy-late (C13-C15) with 7 mol EO and a good microemulsion forming effect with the 3 EO type. 

Either or both of the R groups may be aryl. In general, dialkyl ketones and cyclic ketones react more rapidly than alkyl aryl ketones, and these more rapidly than diaryl ketones. The latter require sulfuric acid and do not react in concentrated HCl, which is strong enough for dialkyl ketones. Dialkyl and cyclic ketones react sufficiently faster than diaryl or aryl alkyl ketones or carboxylic acids or alcohols that these functions may be present in the same molecule without interference. Cyclic ketones give lactams. 

Very interesting transformations were reported in terminal alkynes RC=CH (R = alkyl, aryl, alkoxy, carboxylate, etc.). They react readily with nitric acid, in aqueous nitromethane (1 1) and in the presence of catalytic amounts of tetra-butylammonium tetrachloroaurate to give 3,5-disubstituted isoxazoles 15 in 35% to 50% isolable yield (92). The reaction might proceed via a nitrile oxide intermediate by attack of an electrophile (AuCh or H+) and of a nucleophile (N02 ) on the triple bond to form a vinyl nitrite, which is converted to a nitrile oxide by the action of gold(III) or of nitric acid (Scheme 1.8). 

The second method is advantageous over the Gould-Jacobs method with respect to (a) the cyclization step which proceeds smoothly under mild conditions (b) one-pot synthesis of the 1-substituted derivatives and bypassing the alkylation/arylation of the Ni-position of l,4-dihydro-4-oxoquinoline-3-carboxylate, which usually gives rise to mixed N1/O4-substituted products and (c) product versatility due to the ability to utilize a wide range of alkyl-and arylamines in the step before cyclization. 

Scheme 24 Cathodic alkylation of carboxylic acids to esters R alkyl, aryl, R alkyl, yields 24-96%.

Scheme 26 Cathodic reduction of aliphatic carboxylic acids in the presence of triphenylphosphineto aldehydes R alkyl, aryl, yields 36 -100%.

The heteroatom-substituted carbene complexes most frequently used in organic synthesis are carbonyl complexes of the type (CO)5M=C(X)R (M Cr, Mo, W X OR, NR2 R H, alkyl, aryl, vinyl, alkynyl, etc.). To some extent such complexes behave as carboxylic esters or amides, the (CO)5M=C group having electronic properties similar to those of a carbonyl group (Figure 2.16). 

Rhodium(II) forms a dimeric complex with a lantern structure composed of four bridging hgands and two axial binding sites. Traditionally rhodium catalysts faU into three main categories the carboxylates, the perfluorinated carboxylates, and the carboxamides. Of these, the two main bridging frameworks are the carboxylate 10 and carboxamide 11 structures. Despite the similarity in the bridging moiety, the reactivity of the perfluorinated carboxylates is demonstrably different from that of the alkyl or even aryl carboxylates. Sohd-phase crystal structures usually have the axial positions of the catalyst occupied by an electron donor, such as an alcohol, ether, amine, or sulfoxide. By far the most widely used rhodium] 11) catalyst is rhodium(II) acetate [Rh2(OAc)4], but almost every variety of rhodium] 11) catalyst is commercially available. 

Oxidation of an alkylated benzene (making an aryl carboxylic acid) is a method of converting an ortho-para activator into a meta director. The reduction of a nitro group to make an aryl amine is a way of changing a meta director into an ortho-para activator. 

The glyoxime dehydration route is compatible with various substituents including not only alkyl, aryl, and heteroaryl but also acyl, carboxyl, and amino groups for example, 3-amino-4-phenylfurazan is formed on heating a-(hydroxyimino)phenylacetamidoxime with sodium acetate in ethanol, and the same compound also results from treatment of benzoyl cyanide with hydroxylamine and sodium acetate in ethanol <87IJC(B)690>. 

Tetrakis-/i-(carboxylato)-dimolybdenum(II) complexes have been obtained by only one general route, namely by the direct interaction of carboxylic acids with molybdenum hexacarbonyl.8 This reaction requires elevated reaction temperatures and prolonged reaction times. These same compounds are obtained in comparable or better yields by the brief reaction of tetrachloro- or tetrabromotetrakis(tributylphosphine)dimolybdenum(II) with alkyl- or aryl-carboxylic acids in refluxing benzene. The bis-/i-(arylcarboxylato) complexes... 

In each table, substituted azoles are ordered in the following way alkyl, substituted alkyl, aryl, formyl, acetyl, carboxylic acid, alkoxycarbonyl, cyano, amino, azido, diazonium salt, nitroso, nitro, hydroxy, alkoxy, fluoro, chloro, bromo, and iodo. 

A fairly general route to 1,2-dihydroazocines (64) is provided by the [2+2] cycloaddition of DMAD to 1,2-dihydropyridines (62) (74JCS(Pi)2496,77JOC2903). The reaction gives good yields of the dihydroazocine-6,7-dicarboxylates with N- alkyl, -aryl or functionally substituted removable protective groups. Other substituents can be present at C-3 or -4 in the pyridine, but carboxyl substituents at N-l or C-5 of the pyridine reduce the enamine character, and Diels-Alder addition of the acetylene occurs at the diene system. The [4.2.0] bicyclic intermediates (63) can be detected at -10 to 0°C by NMR warming to 20 °C causes complete conversion to (64). 

Some of the amphipathic species that have been used in the investigation of reverse micelles are capable of dissociation under suitable conditions. Metal carboxylates, alkyl aryl sulfonates, sulfosuccinates, and alkyl ammonium salts are examples of compounds with a high degree of ionic character. Coulomb s law describes the force between two charges qK and q2 separated by a distance r in a medium of relative dielectric constant er... 

Carboxylic acids can be converted to symmetrical ketones by pyrolysis in the presence of thorium oxide. In a mixed reaction, formic acid and another acid heated over thorium oxide give aldehydes. Mixed alkyl aryl ketones have been prepared by heating mixtures of ferrous salts.1717 When the R group is large, the methyl ester rather than the acid can be decarb-methoxylated over thorium oxide to give the symmetrical ketone. 

Alkylation of carboxylic esters 0-97 Alkylation of aryl esters 0-98 Alkylation and alcoholysis of oxazines... 

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