Pyridines, from acetylene/nitrile

Yamazaki et al. (91, 119) and Bonnemann el at. (120) have recently reported catalytic syntheses of substituted pyridines from acetylenes and nitriles. Various cobalt complexes serve as active catalysts, in particular, CpCo(PPh3)2 (91) or Co(C8Hi2) (C8Hi3) (120). Similar reactions of acetylenes with CS2 or RNCS also give new heterocycles (91) ... 

Much recent work has been done on the synthesis of pyridines from alkynes and nitriles over cobalt catalysts. For example, 2-vtnylpyndine has heen obtained in good yield from acetylene and acrylonitrile using a cyclopentadienyl-cobalt catalyst. Pyridine has also been obtained from cyclopentadiene and ammonia over a sihca/alumina catalyst. 

A typical example of such an application is the one step synthesis of pyridines directly from acetylenes and nitriles (Bonnemann synthesis [4]). 

The organocobalt catalysed synthesis of substituted pyridines from alk-l-enes and nitriles (Equation 22) has been extended further by the discovery that the leaction is catalysed by cobaltocene, Co(i7 -05145)2, a more easily obtained complex than earlier catalysts.Acetylene reacts with substituted nitriles to give 2-sub-stituted pyridines in up to 60% yield, whereas mono-substituted acetylenes react to give mixtures of 2,4,6- and 2,3,6-trisubstituted pyridines in moderate yield. 

In the presence of Co(I)-catalysts alkynes and nitriles can be co-trimerized in organic solvents to yield substituted pyridines under rather harsh conditions. The reaction is biased by formation of large quantities of benzene derivatives and with acetylene gas as much as 30 % of all products may arise from homotrimerization. It has been found recently, that with cobalt(I) catalysts heterotrimerization of various nitriles and C2H2 could be achieved under ambient conditions using aqueous/organic biphasic systems and irradiating the reaction mixture with visible light (Scheme 7.12) [39,40]. 

N-Substituted amides derived from 2-chloro- or4-chloronicotinic acid react with CH-acidic nitriles in the presence of base to yield amino derivatives of [l,6]naphthytid-5(6//)-ones and [2,7]naphthyrid-l(2//)-ones <1997JHC397>. 3-(l-Alkylamino)pyridines react with electron-deficient alkynes (acetylene dicatboxylates) in the presence of acid to give l,2-dihydro[2,7]naphthyridine-3,4-dicarboxylates in up to 72% yield compounds unsubstituted at C-1 were readily oxidized with potassium permanganate to naphthyridine-l-ones <2005TL3953>. 

The formal addition of perfluorinated pyridine, pyrimidine, pyridazine or of pentafluorobenzo-nitrile to fluorinated acetylenes in the presence of cesium fluoride in sulfolane leads to fluorinated aryl-substituted alkenes. " In the first reaction step fluoride ion adds to the fluorinated acetylene to give a vinyl carbanion, which substitutes, in a second step, a fluoride ion from the perfluorinated aromatic compound. Some examples of this type of reaction are shown by the formation of... 

Pyridine was first isolated, like pyrrole, from bone pyrolysates the name is constrncted from the Greek for fire, pyr , and the suffix idine , which was at the time being used for all aromatic bases - phenetidine, toluidine, etc. Pyridine and its simple alkyl derivatives were for a long time produced by isolation from coal tar, in which they occur in quantity. In recent years this source has been displaced by synthetic processes pyridine itself, for example, can be produced on a commercial scale in 60-70% yields by the gas-phase high-temperatnre interaction of crotonaldehyde, formaldehyde, steam, air and ammonia over a silica-alumina catalyst. Processes for the manufacture of alkyl-pyridines involve reaction of acetylenes and nitriles over a cobalt catalyst. 

Cobalt metal catalyses the co-trimerization of one molecule of acetonitrile with two of 1 -pentyne or 1 -hexyne to yield mixtures of the pyridines 610 and 611 (R = Pr or Bu). The regioselctivity of the reaction of nitriles with terminal acetylenes has been investigated. It was found that, in general, mixtures of 2,4,6- and 2,3,6-trisubstituted pyridines are produced. The selectivity depends on the size of the substituents attached to the triple bond and the cyanide group. If either of these is large, only 2,4,6-substituted pyridines are obtained. Ethyl propiolate and aliphatic or aromatic nitriles (RCN) yield, in addition to the usual type of product, i.e. 612 and 613, the 2,3,5-isomer 614. Pyridines 617 result from the action of alkynes RC=CH (R = Ac, PrCO or C02Me) on the electron-rich... 

Pyrolysis of pyridine derivatives is a method for allylic and benzylic deamination the preparation of nitriles from aldehydes, and the preparation of isocyanates from acid chlorides or hydrazides Flash vacuum pyrolysis continues to yield interesting reactions and products. Recently, it has been reported that quite sensitive acetylene derivatives can be obtained by this method from 4-alkylideneisoxazol-5(4H)-ones by ring degradation. On the other hand, 2 carbamyl azide molecules cyclize under these conditions to form l,2,4-triazolidine-3,5-dione 1,2-ylids . 2H-Cyclohepta[b]furan-2-ones have been obtained by ring expansion of phenyl propiolates... 

A variety of pyridine derivatives has been prepared by cooligomerization of acetylene and nitriles (Wakatsuki and Yamazaki, 1973a, 1976). 1,2-Dithiopy-rones, W-methyl-2-thiopyridones, thiophenes, selenophenes, and pyrroles can be prepared from the cobaltacyclopentadiene and suitable unsaturated molecules containing a heteroatom or group (Wakatsuki and Yamazaki, 1973b Wakatsuki et al., 1974b). 

Polymers containing pyridine moieties in the mainchain (13) are likewise obtainable by the reaction of the polymers (3) with nitriles (scheme 9). In this case, polymers containing pyridine moieties (about 80%) are produced with an increase of the molecular weight of the polymers. The increase of the molecular weight is most probably due to the pyridine formation of the nitriles with the acetylene moieties at the polymer end catalyzed by the eliminated ( n -cyclopentadienyl)cobalt(I). In fact, it is also possible to prepare pyridine-containing polymers directly from diynes and nitriles in the presence of catalytic amount of 4 (scheme 10). Within the examined combinations, this catalytic polymerization by the pyridine-ring-formation process is... 

Another particularly significant breakthrough results from the direct synthesis of pyridine and of its derivatives by Co oligomerization of two molecules of acetylenes with a nitrile (Bonnemann synthesis [4]). The potentialities of the Bonnemann reaction are well illustrated by its application to the synthesis of heterocyclic systems, a particularly illustrative example being the synthesis of vitamine B6 [5g]. 

A direct synthesis of substituted pyridines in yields of about 50% is found in the treatment of acetylene and an alkyl nitrile in the presence of a cobalt catalyst. A general method for the synthesis of 3- and 3,4-substituted furans from ketones has been developed. A new route to various heterocycles with 2 or more heteroatoms has been presented, as well as a procedure involving 1,3- or 3,3-cyclization on difunctional nucleophiles, such as hydrazine, hydroxylamine, alkyl and aryl-diamines. 76 77... 

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