Pyridines carbonyl reactions

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. 

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. 

Some important reactions of chromium hexacarbonyl involve partial or total replacements of CO ligands by organic moieties. For example, with pyridine (py) and other organic bases, in the presence of UV hght or heat, it forms various pyridine-carbonyl complexes, such as (py)Cr(CO)5, (py)2Cr(CO)4, (py)3Cr(CO)3, etc. With aromatics (ar), it forms complexes of the type, (ar)Cr(CO)3. Reaction with potassium iodide in diglyme produces a potassium diglyme salt of chromium tetracarbonyl iodide anion. The probable structure of this salt is [K(diglyme)3][Cr(CO)4lj. 

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). 

Octahydroacridine units must be oxidatively functionalized at carbon atoms 4 and 5 in order to build up the fused-ring backbone of torand 1. The key pyridine-forming reactions (steps 6 and 11 in Scheme 6.1) both involve the condensation of a ketone with an a,p-unsaturated ketone. Unsymmetrically functionalized octahydroacridine derivatives are required so that each unit can be fused to a new pyridine ring first at one end and then at the other. The benzylidene groups serve as latent carbonyl groups that can be unmasked by ozonolysis. Step 2 introduces both a C-O bond at C4 and a benzylidene group at C5 in a convenient, one-pot reaction sequence. Scheme 6.3 shows the intermediates involved in this sequence converting 6 to 7. 

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. 

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]. 

The 3,4-dioxoperhydro derivative of (3) was obtained by cross carbonylation of 2-hydroxymethyl-pyridine <87CC125>. Reaction of Schiff bases, prepared from 2-aminopyridine and its 5,6-benzologue with aldehydes and dichlorocarbene, afforded 2-aryl-3-chloro-4-oxo-4/f derivatives of (12) and its 6,7-benzologue <9lKGS8io>. 

Being anionic carbonyl synthons, the nitroalkanes have been explored extensively for their conversion into the corresponding carbonyl compounds. For example, the embedment of a nitroalkane onto an activated basic silica gel or the blockage of the C-protonation of nitronate with a protonated concave pyridine. The reaction under the latter condition is called the soft Nef reaction. In addition, the introduction of a y-trimethylsilyl group is proved to smooth the Nef reaction. Moreover, when a primary nitroalkane is treated with nitrite/acetic acid, a carboxylic acid is resolved. Furthermore, the oxidative Nef reaction has successfully converted the nitro cyclohexadienes into the substituted phenols via a nucleophilic addition. 

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. 

Apart from halides, several neutral cocatalysts have been reported to increase the catalytic activity of Ruj(CO)i2 in carbonylation reactions of the kind here discussed [18, 19, 154, 170-172, 178-180]. In most cases, these cocatalysts are phosphines or heteroaromatic amines such as pyridine, Bipy or Phen, and are considered to act as ligands towards ruthenium. The question of the nuclearity of the active catalytic species has been examined only in the case of phosphines and it appears that the most active catalysts are mononuclear. In the case of nitrogen ligands, the question has not been examined in detail, but the same is probably also true. A more detailed discussion on this point is reported in Chapter 6. 

Transition-metal-promoted carbonylation reactions continue to provide interesting new routes to a-methylene lactones. The /runs -vinyl bromide (156) reacts with Ni(CO)4 to give the c -fused lactone (157) in 95% yield. By contrast, the reaction of the frans -acetylenic alcohol (158) with carbon monoxide and PdCl2 leads to the frans-fused lactone corresponding to (157). The ether (159) has been oxidized with CrOs-pyridine to the corresponding lactone, which was obtained as a mixture of isomers in modest yield. ... 

Carbonyl compounds are too weakly electrophilic to effect substitution of the pyridine ring. However, in the Emmert-Aisendorf reaction (an extension of which has already been discussed, p. 200), ketones and, to a smaller extent, aldehydes have been used to hydroxyalkylate pyridine. The reaction has been classified as a nucleophilic substitutionand for that reason is discussed here. 

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