Pyridines 2-halogeno

Other interactions of /3-lactams with electrophiles include the oxidative decarboxylation of the azetidin-2-one-4-carboxylic acid (85) on treatment with LTA and pyridine (81M867), and the reaction of the azetidin-2-one-4-sulfinic acid (86) with positive halogen reagents. This affords a mixture of cis- and trans-4-halogeno-/3-lactams (87), the latter undergoing cyclization to give the bicyclic /3-lactam (88) (8UOC3568). 

The independence of the composition of the reaction products from the nature and position of the halogeno substituent clearly demonstrates that the amination of the isomeric 3- (27, X = Cl, Br, I) and 4-halogenopyridines (32, X = Cl, Br, I) proceeds exclusively via 3,4-pyridine (31). It is surprising that the 4-halogenopyridines did not... 

In an extensive investigation of the behavior of halogeno-pyridines and -quinolines towards potassium amide in liquid ammonia, tendencies to react according to the hetaryne type and other mechanisms were compared. The following results may be mentioned. 3-Fluoropyridine does not react via 3,4-pyridyne, but yields fluoro derivatives of 4,4 - and 2,4 -bipyridine. 3,6-Dibromopyridine is converted first into 6-bromo-3,4-pyridyne and not into 6-amino-3-bromopyridine. 2-Bromoquinoline yields 2-methylquinazoline together with 2-aminoquinohne. ... 

The catalytic effect of protons has been noted on many occasions (cf. Section II,D,2,c) and autocatalysis frequently occurs when the nucleophile is not a strong base. Acid catalysis of reactions with water, alcohols, mercaptans, amines, or halide ions has been observed for halogeno derivatives of pyridine, pyrimidine (92), s-triazine (93), quinoline, and phthalazine as well as for many other ring systems and leaving groups. An interesting displacement is that of a 4-oxo group in the reaction of quinolines with thiophenols, which is made possible by the acid catalysis. 

The 2-halogeno derivatives of thieno[3,2- ]pyridine are accessible through the lithium derivatives (84JHC785). 

Conversions of diazonium salts into halogenated derivatives have been reported for compounds of type 128 and 129 [73JCS(P1)2901 80JCS(P 1)2398], Although some 7-substituted pyrazolo[ 1,5-u]pyridines have been made from the lithiated precursors, no halogeno products have been reported (92JOC5538). 

Since the nitrogen in pyridine is electron attracting it seemed reasonable to predict that the trihalopyridynes would also show the increased electrophilic character necessary to form adducts with aromatic hydrocarbons under similar conditions to those employed with the tetra-halogeno-benzynes. The availability of pentachloropyridine suggested to us and others that the reaction with w-butyl-lithium should lead to the formation of tetrachloro-4-pyridyl-lithium 82 84>. This has been achieved and adducts obtained, although this system is complicated by the ease with which pentachloropyridine undergoes nucleophilic substitution by tetrachloro-4-pyridyl lithium. Adducts of the type (45) have been isolated in modest yield both in the trichloro- and tribromo- 58) series. 

Pyridylstannanes have also been prepared by the reaction of halogeno pyridines with hexamethyldistannane in the presence of a palladium catalyst (Equation (62)).200... 

D. la Intramolecular attack by the dialkylamino-group on a neighbouring ester group 254, D.lb Intramolecular nucleophilic attack by imidazole and pyridine 255, D.2 Intramolecular attack by the NHR group 256, D.3 The cyclization of halogeno-amines, etc. 256, D.4 Intramolecular nucleophilic attack on phosphorus 259... 

The a-, f3- and y-halogeno substituents in pyridines and their benzo analogues are each more susceptible to nucleophilic substitution than is the case for halobenzenes because of the overall electron deficiency of the heteroaromatic ring. Furthermore, halogen substituents a and y to nitrogen are usually more reactive than /3-halogens and this is particularly so in pyridinium type systems. 

A variant of this method produces xanthones from 2-halogeno-2 -methoxybenzo-phenones, cyclization being brought about by pyridine hydrochloride (72BSF2948). 

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