Carbonylation reaction pyridines

The term Knoevenagel reaction however is used also for analogous reactions of aldehydes and ketones with various types of CH-acidic methylene compounds. The reaction belongs to a class of carbonyl reactions, that are related to the aldol reaction. The mechanism is formulated by analogy to the latter. The initial step is the deprotonation of the CH-acidic methylene compound 2. Organic bases like amines can be used for this purpose a catalytic amount of amine usually suffices. A common procedure, that uses pyridine as base as well as solvent, together with a catalytic amount of piperidine, is called the Doebner modification of the Knoevenagel reaction. 

Dining preparation of an unspecified oxime, the carbonyl compound, pyridine, hydroxylamine hydrochloride and sodium acetate were heated in a stainless steel autoclave. At 90°C a sudden reaction caused a pressure surge to 340 bar, when the bursting disk failed. The reaction had been run previously and uneventfully on one-tenth scale in a glass lined autoclave. 

The direct carbonylation of heterocycles with CO and olefins proceeds efficiently. The reaction of pyridine, CO, and 1-hexene in the presence of Ru3(CO)12 at 150 °C gives a-acylated pyridines (Equation (84)).111,llla A number of olefins including ethene and 1-eicosene can be used in this carbonylation reaction. 

A selenium-assisted carbonylation reaction has been developed which gives 1,3-dihydro-2/f-imidazo[4,5-b]pyridin-2-ones (314) in an excellent yield (Scheme 30) <87BCJ1793>. Heating 2,3-diaminopyridine (312) with CO and an equimolar amount of selenium in the presence of N-methylpyrrolidine, proceeds through a selenolcarbonate intermediate (313) which then cyclizes to the desired product (314). 

A pyridine-2-carboxylato (N-0) complex of palladium(II) with a labile tosylato ligand has been shown to act as an efficient carbonylation catalyst for a series of alcohols and olefins. The catalyst precursor, [Pd(N-0)(0Ts)(PPh3)] (24), in conjunction with promoters (e.g. Lil, LiCl, TsOH), is active for the carbonylation of primary, secondary and tertiary alcohols as well as functionahzed terminal olefins with good selectivity and turnover frequency. This reaction has been further discussed in a report dealing with the kinetic modeling of this and other catalytic-carbonylation reactions. 

N[CeHa(N02)2].CO mw 570.42, N 14.73% ndls (from acet + alc), mp — dec readily sol in acet, chlf, ben2, acet ac, S phenol si sol in ale, eth, CSg CCI4 was prepd from reaction of 2, 4 -dinitro-diphenylamine-2-carbonyl chloride pyridine (Refs 2 3)... 

Reaction of N-(2-pyridinyl)piperazines with CO and ethylene in the presence of a catalytic amount of Rh4(CO)12 in toluene at 160°C results in a complicated carbonylation reaction, which involves dehydrogenation and carbonylation at a C-H bond (Eq. 29) [43]. In this reaction, the carbonylation proceeds at the C-H bond a to the nitrogen atom substituted by pyridine. It is found that the reaction involves two discrete reactions (a) dehydrogenation of the piperazine ring and (b) carbonylation at a C-H bond in the resulting olefin. An amide functionality can also serve as the directing group for carbonylation at the a C-H bond (Eq. 30) [44]. 

Representative examples of Pd-catalyzed heterocycle carbonylation reactions are shown below. Alkoxycarbonylation of 2,3-dichloro-5-(methoxymethyl)pyridine (79) took place regioselectively at C(2) to give ester 80 [79]. Aminocarbonylation of 2,5-dibromo-3-methylpyridine also proceeded preferentially at C(2) to give amide 81 despite the steric hindrance of the 3-methyl group [80]. 

In parallel with the directed hydroarylation of olefins, a series of papers described the formation of ketones from heteroarenes, carbon monoxide, and an alkene. Moore first reported the reaction of CO and ethylene with pyridine at the position a to nitrogen to form a ketone (Equation 18.28). Related reactions at the less-hindered C-H bond in the 4-position of an A/-benzyl imidazole were also reported (Equation 18.29). - Reaction of CO and ethylene to form a ketone at the ortho C-H bond of a 2-arylpyridine or an N-Bu aromatic aldimine has also been reported (Equations 18.30 and 18.31). Reaction at an sp C-H bond of an N-2-pyridylpiperazine results in both alkylative carbonylation and dehydrogenation of the piperazine to form an a,p-unsaturated ketone (Equation 18.32). The proposed mechanism of the alkylative carbonylation reaction is shown in Scheme 18.6. This process is believed to occur by oxidative addition of the C-H bond, insertion of CO into the metal-heteroaryl linkage, insertion of olefin into the metal-acyl bond, and reductive elimination to form the new C-H bond in the product. 

Cobalt, nickel, iron, ruthenium, and rhodium carbonyls as well as palladium complexes are catalysts for hydrocarboxylation reactions and therefore reactions of olefins and acetylenes with CO and water, and also other carbonylation reactions. Analogously to hydroformylation reactions, better catalytic properties are shown by metal hydrido carbonyls having strong acidic properties. As in hydroformylation reactions, phosphine-carbonyl complexes of these metals are particularly active. Solvents for such reactions are alcohols, ketones, esters, pyridine, and acidic aqueous solutions. Stoichiometric carbonylation reaction by means of [Ni(CO)4] proceeds at atmospheric pressure at 308-353 K. In the presence of catalytic amounts of nickel carbonyl, this reaction is carried out at 390-490 K and 3 MPa. In the case of carbonylation which utilizes catalytic amounts of cobalt carbonyl, higher temperatures (up to 530 K) and higher pressures (3-90 MPa) are applied. Alkoxylcarbonylation reactions generally proceed under more drastic conditions than corresponding hydrocarboxylation reactions. 

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