Pyridine Chlorination

The N-oxides readily undergo nucleophilic addition followed by elimination, which forms the basis of several useful syntheses of 2-substituted pyridines. Chlorination of (13) with POCl to give 2-chloropyridine (17) is a good example (eq. 4) some chlorination may occur also at C-4 (11). 

A study by Abu-Raqabah and Symons (Abu-Raqabah, A. Symons, M. C. R., J. Am. Chem. Soc., 1990, 112, 8614) has characterized the pyridine-chlorine atom three-electron bonded species Py <— Cl by ESR and UV spectroscopy. In an earlier paper, Breslow and co-workers (Breslow, R. Brandi, M. Hunger, J. Adams, A. D., J. Am. Chem. Soc., 1987,109, 3799) considered ring acylated pyridine-chlorine radicals to be n radicals and anticipated special stability for the 4-carboalkoxypyridine-chlorine radical. 

Scheme 17 Para-X-pyridine---chlorine complexes (with X = H, NH2, Me, F, CN, and NO2).

Alky l-4-chloro-2,3-dihydro-6-0X0furo (3, 2-C) pyridine, chlorination of, 787... 

Related Reagents. Borane-Pyridine Chlorine-Pyridine Copper(II) Sulfate-Pyridine Di-r-butyl Chromate-Pyridine Dimethyl Sulfoxide-Sulfur Trioxide/Pyridine Sulfur Trioxide-Pyridine. 

Since the submission of this manuscript several publications of importance to its topic have appeared. The [N - Cl - N] and [N - F—N]" halogen bonds of [bis (pyridine)chlorine] and bis(pyridine)fluorine] that were previously only studied... 

Hydroxylamine Barium oxide and peroxide, carbonyls, chlorine, copper(II) sulfate, dichromates, lead dioxide, phosphorus trichloride and pentachloride, permanganates, pyridine, sodium, zinc... 

Iodine Acetaldehyde, acetylene, aluminum, ammonia (aqueous or anhydrous), antimony, bromine pentafluoride, carbides, cesium oxide, chlorine, ethanol, fluorine, formamide, lithium, magnesium, phosphorus, pyridine, silver azide, sulfur trioxide... 

Various halogenating agents have been used to replace hydroxyl with chlorine or bromine. Phosphoms trihaUdes, especially in the presence of pyridine, are particularly suitable (17,18). Propargyl iodide is easily prepared from propargyl bromide by halogen exchange (19). 

Pyrans and related compounds react with ammonia to give pyridines. A commercially useful example is the reaction of dehydroacetic acid (derived from diketene) with ammonia to give 2,6-dimethyl-4-pyridinone [7516-31 -6] via 2,6-dimethyl-4-pyridinone-3-carboxyhc acid [52403-25-5]. Chlorination of the pyridone gives clopidol [2971-90-6] (56), a coccidiostat (72,73). 

Trityl Ethers. Treatment of sucrose with four molar equivalents of chlorotriphenylmethyl chloride (trityl chloride) in pyridine gives, after acetylation and chromatography, 6,1, 6 -tri-O-tritylsucrose [35674-14-7] and 6,6 -di-O-tritylsucrose [35674-15-8] in 50 and 30% yield, respectively (16). Conventional acetylation of 6,1, 6 -tri-O-tritylsucrose, followed by detritylation and concomitant C-4 to C-6 acetyl migration using aqueous acetic acid, yields a pentaacetate, which on chlorination using thionyl chloride in pyridine and deacetylation produces 4,l, 6 -trichloro-4,l, 6 -trideoxygalactosucrose [56038-13-2] (sucralose), alow calorie sweetener (17). 

An economic synthesis of (3) has been patented (74,91). The process iavolves (/) synthesis of sucrose 6-acetate by way of sucrose 4,6-cychc orthoacetate (2), and (2) selective chlorination usiag thionyl chloride—pyridine—1,1,2-trichloroethane, followed by removal of the acetate group. 

In sulfamation, also termed A/-sulfonation, compounds of the general stmcture R2NSO2H are formed as well as their corresponding salts, acid hahdes, and esters. The reagents are sulfamic acid (amido—sulfuric acid), SO —pyridine complex, SO —tertiary amine complexes, ahphatic amine—SO. adducts, and chlorine isocyanate—SO complexes (3). 

Asphalts characteristically contain very high molecular weight molecular polar species, called asphaltenes, which are soluble in carbon disulfide, pyridine, aromatic hydrocarbons, chlorinated hydrocarbons, and tetrahydrofiiran. 

Nucleophilic Substitution. The kinetics of the bimolecular nucleophilic substitution of the chlorine atoms in 1,2-dichloroethane with NaOH, NaOCgH, (CH2)3N, pyridine, and CH COONa in aqueous solutions at 100—120°C has been studied (24). The reaction of sodium cyanide with... 

Liquid-phase chlorination of butadiene in hydroxyhc or other polar solvents can be quite compHcated in kinetics and lead to extensive formation of by-products that involve the solvent. In nonpolar solvents the reaction can be either free radical or polar in nature (20). The free-radical process results in excessive losses to tetrachlorobutanes if near-stoichiometric ratios of reactants ate used or polymer if excess of butadiene is used. The "ionic" reaction, if a small amount of air is used to inhibit free radicals, can be quite slow in a highly purified system but is accelerated by small traces of practically any polar impurity. Pyridine, dipolar aptotic solvents, and oil-soluble ammonium chlorides have been used to improve the reaction (21). As a commercial process, the use of a solvent requites that the products must be separated from solvent as well as from each other and the excess butadiene which is used, but high yields of the desired products can be obtained without formation of polymer at higher butadiene to chlorine ratio. 

The initiatoi is usually an azo compound and the sulfonation catalyst is usually a teitiaiy amine, ie, pyridine. Sulfuiyl chloride and chlorine may be used... 

Phosphorus pentasulfide in pyridine can be used also for simultaneous substitution of oxygen and chlorine in polysubstituted pyridazinones. For example, 4,5-dichloro- and... 

Pyridine, 4-methoxy-3-styryl-photoelectron spectroscopy, 2, 137 Pyridine, 2-methyI-alkylation, 2, 176 amination, 2, 233, 236 carboxylation, 2, 53 chlorination, 2, 201, 331 Claisen condensation, 2, 51 methiodide... 

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