Hydro carboxylation

Nefedov et al. (221) have reported that ethylene can be selectively hydro-carboxylated to form propyl propionate over NaX which had been exchanged with group VIII metal ions. The activity and selectivity decreased along the series Rh Pd > Ni > Co. In autoclave experiments they found that Rh, NaX (1% Rh) at 250°C and 60 atm CO pressure gave 100% conversion of ethylene in the presence of n-propanol and -propyl iodide with a selectivity of 98.7% to propyl propionate, i.e.,... 

Many other addition reactions of olefins, dienes, and acetylenes are known, which are catalyzed by metal carbonyls including Ni(CO)4, Fe(CO)5, and Co2(CO)8 and by carbonyl derivatives such as hydrocarbonyls or phosphine-substituted carbonyls. Among these are the hydro-carboxylation, hydroesterification, and hydrocyanation of olefins the synthesis of hydroquiniones from acetylenes, carbon monoxide, and water ... 

Phosphates and phosphinates are also recommended as ligands. (R)- or (S)-Binaphthol phosphates 3.54 are used in palladium-catalyzed asymmetric hydro-carboxylation of olefins [923] or in rhodium-catalyzed cycloadditions of diazo compounds to olefins, albeit with modest selectivities in the latter case [924], Seebach and coworkers [925] tested phosphinates and phosphites prepared from diol 2.50 (R = R = Me, Ar = Ph) as ligands for rhodium and palladium in various enantioselective metal-catalyzed reactions [925], Rhodium-catalyzed hydrosilyla-tions of arylmethyl- or ethylketones by Ph2SiH2 were the only interesting reactions with these ligands. 

Goossen and coworkers found optimal conditions for the Markovnikov hydro-carboxylation by combining (p-cymene)RuCl2 (0.8 mol% [Ru]) with trifuryl phos-phane (0.8 mol%) and Na2C03 (1.6 mol%) in toluene at 50°C for 16 h. Those conditions often gave enol esters in excess of 90% yield [167]. Astonishingly, combination of the same metal precursor (2 mol% [Ru]) with tris-(4-chlorophenyl)-phosphane (3 mol%) and 4-dimethylaminopyridine (4 mol%) as additive produced... 

An example of an industrial Heck reaction of an aryl bromide is the announced synthesis of Naproxen by Albermarle. Toward that end, 2-bromo-6-methoxynaphthalene is reacted with ethylene in the presence of a homogeneous palladium catalyst. Apparently, as a ligand a sterically hindered basic phosphine is used. Known Pd-catalyzed hydro-carboxylation of 2-methoxy-6-vinylnaphthalene and subsequent resolution give access to Naproxen (Scheme 3). In addition, it was shown that Ketoprofen can be produced by a similar reaction sequence. 

Conjugated unsaturated carboxylic acid esters can be obtained by hydro-carboxylation of acetylenes in the presence of alcohols. 

Oils with high o. content are obtained from - olive, Euphorbia lathyris and high-oleic - sunflower. Simple ->hydrolysis yields o. concentrations up to 90%. This new quality o. will bring new aspects to old products and processes (- glyceryl monooleate, ->metathesis, - ozonolysis, - epoxidation, - hydroformylation and - hydro-carboxylation). 

The methyl ketone shown in the example can enohze in only one direction and typifies the kind of reactant that can be converted to a carboxylic acid in synthetically accept able yield by the haloform reaction When C 3 of a methyl ketone bears enolizable hydro O... 

The melting points and boiling points of carboxylic acids are higher than those of hydro carbons and oxygen containing organic compounds of comparable size and shape and indicate strong mtermolecular attractive forces... 

Carboxylic acids are the most acidic class of compounds that contain only carbon hydro gen and oxygen With s of about 5 they are much stronger acids than water and alcohols The case should not be overstated however Carboxylic acids are weak acids a 0 1 M solution of acetic acid m water for example is only 1 3% ionized... 

It IS possible to use only one molar equivalent of amine m these reactions if some other base such as sodium hydroxide is present m the reaction mixture to react with the hydro gen chloride or carboxylic acid that is formed This is a useful procedure m those cases m which the amine is a valuable one or is available only m small quantities... 

Fats and oils (Section 26 2) Tnesters of glycerol Fats are solids at room temperature oils are liquids Fatty acid (Section 26 2) Carboxylic acids obtained by hydro lysis of fats and oils Fatty acids typically have unbranched chains and contain an even number of carbon atoms in the range of 12-20 carbons They may include one or more double bonds... 

This derivative is prepared from an A-protected amino acid and the anthryl-methyl alcohol in the presence of DCC/hydroxybenzotriazole. It can also be prepared from 2-(bromomethyl)-9,10-anthraquinone (Cs2C03). It is stable to moderately acidic conditions (e.g., CF3COOH, 20°, 1 h HBr/HOAc, t,/, = 65 h HCI/CH2CI2, 20°, 1 h) Cleavage is effected by reduction of the quinone to the hydroquinone i in the latter, electron release from the -OH group of the hydro-quinone results in facile cleavage of the methylene-carboxylate bond. 

Phenacyl-6-aminopenicillate HCI D-Phenylglycyl Chloride HCI 4-Hydro xy-1,5-naphthyridine-3-carboxylic acid-N-succinimide ester... 

Chemical Name 2-[ [3-(Trifluoromethyl)phenyl] amino]-3-pyridine carboxylic acid 1,3-di-hydro-3-0X0-1 -isobenzofuranyl ester... 

It was anticipated that fragments 147 and 214 could be united through an amide bond linking the nitrogen atom of the latter with C-8 of the former. Indeed, the active ester formed by treatment of carboxylic acid 147 with 1,3-diisopropylcarbodiimide and 1-hydro-xybenzotriazole reacts efficiently with amine 214 to afford dihydroxy amide 215 in 95 % yield. This convergent union creates a molecule that possesses all but two carbon atoms of the natural product. 

Methyl-l-phenyl-2(17/)-quinoxalinone (226) and methyl methacrylate (227) gave the photoadduct, methyl l,2a-dimethyl-3-oxo-4-phenyl-2,2a,3,4-tetra-hydro-l//-azeto[l,2-fl]quinoxaline-l-carboxylate (228) as a separable mixture of two stereoisomers (CH2CI2, MeOH, hv, N2, <15 h 40% each) analogs likewise. " ... 

S-(4a.7a, 1 Oa )]-octa-hydro-4-[[(phenylmethoxy)-carbonyl]amino]-5-oxo-7H-pyrido[2,1 -b][l, 3]-thiazepine-7-carboxylic ocid methyl ester (IV)... 

Reduction of 3-benzyl-8-chloro-4-oxo-4//-pyrido[l,2- ]pyrimidine-2-carboxylate <2004W004/064741> and 2-methyl-4-oxo-4//-pyrido[l,2-tf]pyrimidine-3-carboxylate <2003T4123> with DIBAL-H afforded 2- and 3-formyl derivatives, respectively. Reduction of /V-(4-fluorobenzyl)-3-hydroxy-8-[methoxy(methyl)amino]-4-oxo-6,7,8,9-tetra-hydro-4//-pyrido[l,2- ]pyrimidine-2-carboxamide with Zn-dust in aqueous AcOH afforded the 8-methylamino derivative, which was acylated with AcOH in the presence of Hiinig s base, HOBt, and l-(3-dimethylaminopro-pyl)-3-ethylcarbodiimide-HCl <2004W004/058756>. 3-(Perhydropyrido[l,2- ]pyrimidin-2-yl)propylamine was obtained by catalytic hydrogenation of 2-(perhydropyrido[l,2- ]pyrimidin-2-yl)propionitrile over a Pt02 catalyst <2003FRP1275647>. 

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