2 pyridine, reaction with bromine

When nicotinic acid is heated for 8 hours at 180° with thionyl chloride, a low yield of 5-chloronicotiriic acid is obtained.182 The orientation observed in this case suggests an electrophilic attack, perhaps on a complexed nicotinic acid chloride molecule (which would thus behave somewhat like a pyridine A-oxide). If the reaction is carried out at 150° and the reaction time lengthened to 50 hours, a 30% yield of 5,6-dichloronicotinic acid is obtained.182 Both mechanistic pathways may be involved here. Isonicotinic acid reacts with thionyl chloride at 180-220°, presumably by, way of an electrophilic attack since 3-chloro-and 3,5-dichloroisonicotinic acid are formed.182 Nicotinoyl chloride (from nicotinic acid and thionyl chloride—probably in the complexed form) gives an 87% yield of 5-bromonicotinic acid on reaction with bromine for 10 hours at 150-1700.185... 

Q Bromobenzene is readily synthesized from benzene by reaction with bromine in the presence of pyridine. Suggest a mechanism for this route. 

Perelman et aV of Eli Lilly and Co. found that the 19-nor-A -sleroid (1,19-nor-A < -androstene-17 3-ol-3-one) can be dehydrogenated smoothly to the 19-nor-A -3-ketosteroid (2) by reaction with bromine in pyridine or, more conveniently. 

An obvious consequence of this deiocaiization is the decreased basicity of the nitrogen atom and the increased acidity of the NH group. In fact, the pK of pyrrole acting as a base is about -4, and protonation occurs at carbon below pH -4. By contrast, the NH proton pK 16.5) can be removed by much weaker bases than those that can remove protons on normal secondary amines. The nucieophiiic nature of the ring means that pyrrole is attacked readily by electrophiles. Reaction with bromine requires no Lewis add and leads to substitution (confirming the aromaticity of pyrrole) at all four free positions. Contrast pyridine s reactivity with bromine (p. 731) it reacts just once, at nitrogen. 

If cold benzene is treated with bromine in the absence of sunlight, very little reaction occurs if, however, a halogen carrier, such as iron, iodine, pyridine, etc., is also present, a rapid reaction by substitution occurs, forming first... 

The reaction of a dibromochalcone with hydroxylamine hydrochloride in pyridine gave three products with the expected 2-isoxazoline product as the predominate compound. A ring bromination product and an isoxazole were also isolated (70UC796). The reaction of hydroxylamine with /S-thiosulfates of propiophenone at reflux produced 3-phenyl-2-isoxazo-line (455). At room temperature a bis-Michael product (456) was produced. The reaction with N -phenylhydroxylamine yielded a mono-Michael type product (457) (74CPB1990). 

Place 50 g. (57 ml.) of dry A.R. benzene and 0-5 ml. of dry pyridine (1) (dried over potassium hydroxide pellets) in a 500 ml. round-bottomed flask. Attach a reflux condenser to the flask and an inverted funnel (just dipping into some water in a beaker) to the top of the condenser (Fig. II, 13, 8, 6). Partially immerse the flask in a bath of cold water, supported upon a tripod and gauze. Carefully pour 125 g. (40 ml.) of bromine (for precautions to be taken with bromine, see Section 111,35, Wole 1) through a condenser and immediately insert the absorption device into the upper end of the condenser. A vigorous reaction soon occurs and hydrogen bromide is evolved which is absorbed by the water in the beaker when the reaction slackens, warm the bath to 25-30° for... 

Reaction of compound 37 with bromine in chloroform results in mono-bromination a to the sulfur. Treatment of this brominated derivative with NaBH3CN in AcOH gives a mixture of products resulting from reduction of the C=N double bond and of elimination of HBr. Reaction of 44 with sodium ethoxide results in the ethoxy-substituted derivative 45, whereas reaction with pyridine gives the dehydrobrominated derivative 46. Reaction of either 44 or 46 with sodium cyanide in dimethyl sulfoxide (DMSO) gives the cyano-derivative 47 <1983HCA971> (Scheme 13). 

Mixed trialkylstannyl and silyl derivatives have also been used in coupling reactions, with subsequent replacement of the silyl substituent by bromine, leading to species that are capable of undergoing further coupling reactions. This process was amply demonstrated by the recent synthesis of micrococcinic acid 203, which involved four palladium-catalyzed crosscoupling reactions on stannylated substrates, two palladium-catalyzed trimethylstannane replacements of bromine, two trimethylsilyl displacements by bromine, and a total of four bromine-lithium exchange reactions, on three different thiazole derivatives and one pyridine derivative (91-TL4263). 

Electrophilic addition to 9-vinylcarbazole occurs in the Markovnikov sense, thus hydrogen chloride,hydrogen bromide,chlorine, and bromine in carbon tetrachloride, and iodine chloride in pyridine are recorded as adding with initial electrophilic attack at the methylene. Mercuric acetate in methanol gave 9-(2-acetoxymercuri-l-methoxyethyl)carbazole. Although 9-vinylcarbazole gave an iodohydrin, comparable reaction with methanolic sodium hypochlorite led to 9-(2-chlorovinyl)carbazole. Catalytic reduction of the latter produced 9-(2-chloroethyl)carbazole. Tri-phenyltin hydride gave 96. ... 

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