2-Phenyl-6-methylpyridines, reaction with

There are numerous investigations of the reactivity of di- and polyhalo-pyridazines, particularly polyfluoropyridazines. Aminolysis of l-phenyl-4,5-dichloropyridazin-6-one has been studied in detail. In this and other reactions with nucleophiles, the halogen atom at position 4 is substituted preferentially, although a mixture of 4-amino and 5-amino derivatives is formed in the reaction between 4,5-dihalopyridazin-6-ones and ammonia or amines. It has been now firmly established that displacement reactions on 3,6-dichloropyridazine 1-oxide with sulfur nucleophiles take place at position 6 in contrast to nitrogen or oxygen nucleophiles, where the 3-chlorine atom is replaced preferentially. In connection with the previously observed self-condensation of 3-chloro-6-methylpyridazine to a tricyclic product, the reaction between 3,6-dichloropyridazine and pyridine N-oxides was investigated. 3,6-Dichloropyridazine with 2-methylpyridine N-oxide at 100°-110°C affords three compounds (171, 172, and 173). With 2,6-dimethylpyridine N-oxide, an ether (174) is also formed. The isolation of... 

The D-plycero-D-0u/o-heptono-l,5-lactone derivative (414) gave the heterocyclic heptopyranose derivative (415) on successive treatments with butyl- or phenyl-lithium and 2-bromopyridine. Heterocyclic derivatives related to (415) were also obtained when (414) reacted with 2-methylpyridine and benzothiazole, whereas it reacted with furan, thiophene, and 1-methylindole to give acyclic derivatives [e.g. (416)]. Chelation of the nitrogen atom of the heterocyclic ring with the intermediate alkoxide anion appears to deactivate C-1 towards further reaction with the former series of compounds. 

Thioesters, Selenoesters, and Thioamides.—Commercially available phenyl dichlorophosphate has been reported to be a superior reagent to MV-dimethyl-phosphoramidic dichloride (4, 244) for the preparation of thioesters directly from carboxylic acids and thiols. Carboxylic acid chlorides can be efficiently converted into thioesters by reaction with adducts formed between thiols and l-methylpyridine-3,5-dicarboxylates. Alternatively, copper(i) mercaptides, formed from thiols and CuaO, or thallous thiophenoxide can be used. The latter method can also be used to prepare selenoesters as well as a-phenylthio-and a-phenylseleno-acids and esters from a-halo-acids and a-halo-esters, respectively. 

Substitution. The kinetics of reactions of /ra/t -CPdClgCR SR ) ] complexes with a series of amines of various basicities and steric requirements have been studied in 1,2-dimethoxyethane at 298 K. In fact the first step is fast, and it is the second step whose kinetics have been examined here. Amine basicity is an important factor logarithms of second-order rate constants correlate linearly with amine pKa values in the absence of steric hindrance. Steric factors have a large effect when the incoming amine e.g. 2-methylpyridine) or the leaving sulphide (e.g. phenyl isopropyl sulphide) is bulky. The kinetic pattern for the reaction of [PdCl2(cod)] with 2,2 -bipyridyl in aqueous methanol has been interpreted by the reaction sequence shown in Scheme 3. The mechanism is dissociative with respect to the palladium centre. The rate law for the reaction of the [PdBr(dien)]+ cation with inosine has already been discussed in the introductory section to this chapter. 

With pyridine 1-oxide, sodium phenylmercaptide gives only pyridine, but with l-alkoxy-2- and -4-picolinium salts, reaction occurs at the methyl groups producing phenyl-2- and -4-pyridylmethylsulphide, respectively. However, l-alkoxy-4-picolinium salts react with alkylmercaptides both laterally and at the nucleus, giving by the latter mode both 2- and 3-alkylmercapto-4-methylpyridine. The 2-isomer presumably arises by direct nucleophilic substitution, and the 3-isomer may be formed ... 

Pyridine-carboxylic acids have been prepared by the reaction of the 3-pyridyl Grignard reagent 36a and of 2- and 3-pyridyl lithium with carbon dioxide. Nicotinic acid isotopically labelled in the carboxyl group has been obtained in this way . The reaction is especially useful for preparing pyridine-acetic acids and has been applied to 2-2t t and 4-picolyl lithium i. Under conditions where phenyl lithium adds to the azomethine linkage of 4-picoline, 2-phenylpyridine-4-acetic acid i is produced. 2,6-Lutidine gave 6-methylpyridine-2-acetic acid, but the reaction failed with 2-methyl-6-phenoxypyridine . ... 

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