Phosphorus Chloride deoxygenations

Phosphorus halides can deoxygenate pyridine 1-oxides (p. 387). Consequently, when a 4-hydroxypyridine 1-oxide is treated with phosphoryl chloride, deoxygenation and substitution can give the 4-chloropyridine . The experimental conditions are important with phosphoryl chloride at 60°, 3-chloro-4-hydroxypyridine 1-oxide gives 3,4-dichloropyridine 1-oxide, but at 90-100° 3,4-dichloropyridine results. ... 

The JV-oxide of (l,4-benzodiazepin-2-ylidene)malonate (503, R = H, n = 1) was deoxygenated by catalytic hydrogenation over Raney Nickel in a mixture of methanol and THF at atmospheric pressure for 5 hr (83USP4401597) and by treatment with phosphorus trichloride in methylene chloride at ambient temperature overnight (75JOC153 83USP-4401597). 

An unsuccessful attempt to repeat this reaction was made by Bird however, he was able to show that dibenzothiophene 5-oxide did, in fact, react with either thionyl chloride or phosphorus oxychloride to yield 2-chlorodibenzothiophene in good yield. Since all methods of nitration of dibenzothiophene yield a mixture of 2-nitrodibenzothio-phene and dibenzothiophene 5-oxide, which have identical melting points, it was concluded that the earlier workers had in fact been working with the sulfoxide and not the nitro compound. The reaction was rationalized as being a deoxygenative halogenation of a heterocyclic 5-oxide akin to the Meisenheimer reaction of A-oxides, which already had precedents in the sulfoxide field. Unfortunately the 2-chlorodibenzothiophene prepared by this route is contaminated with 2,8-dichlorodibenzothiophene which cannot be removed by crystallization. The best method of preparation of this compound is therefore via a Sandmeyer reaction on 2-aminodibenzothiophene. ... 

Complete deoxygenation of quinones to hydrocarbons is accomplished in yields of 80-85% by heating with a mixture of zinc, zinc chloride and sodium chloride at 210-280° [932]. Refluxing with stannous chloride in acetic and hydrochloric acid followed by refluxing with zinc dust and 2 N sodium hydroxide reduced 4 -bromobenzo[5. 6 1.2]anthraquinone to 4 -bromo-benzo[5. 6 1.2]anthracene in 95% yield [181], and heating with iodine, phosphorus and 47% hydriodic acid at 140° converted 2-chloroanthraquinone to 2-chloroanthracene in 75% yield [222]. Also aluminum in dilute sulfuric add can be used for reductions of the same kind [151]. 

Pyridine and quinoline /V-oxides react with phosphorus oxychloride or sulfuryl chloride to form mixtures of the corresponding a- and y-chloropyridines. The reaction sequence involves first formation of a nucleophilic complex (e.g. 270), then attack of chloride ions on this, followed by rearomatization (see also Section 3.2.3.12.5) involving the loss of the /V-oxide oxygen. Treatment of pyridazine 1-oxides with phosphorus oxychloride also results in an a-chlorination with respect to the /V-oxide groups with simultaneous deoxygenation. If the a-position is blocked substitution occurs at the y-position. Thionyl chloride chlorinates the nucleus of certain pyridine carboxylic acids, e.g. picolinic acid — (271), probably by a similar mechanism. 

Removal of an AT-oxide function utilizes the usual reagents such as zinc and acetic or hydrochloric acids, sodium borohydride, hydriodic acid, phosphoryl chloride, sodium dithionite, phosphorus trichloride or hydrogenation over Raney nickel. When l-hydroxy-2-methyl-5-phenylimidazole (262) reacts with butyllithium and hexachlofodisilane this also induces dehydroxylation (Scheme 152) (80AHC(27)24l). At times, as with other heterocyclic AT-oxides, deoxygenation with phosphorus halides can introduce a halogen atom at C-2 of imidazole (75JCS(P1)275). 

Treatment with phosphorus trichloride removes the /V-oxide function of 8-methylpyrido[2,3-phosphoryl chloride produced is not sufficient to convert the 5-oxo group into a chloro substituent. If, alternatively, phosphoryl chloride is added after the deoxygenation step, 5-chloro-8-methylpyrido[2,3-rf]pyridazine (2) results in 66% yield.56... 

In general, deoxygenation of heterocyclic JV-oxides is effected by the use of phosphorus trihalides or by catalytic reduction with Raney nickel.312 Because of their higher selectivity the phosphorus reagents are preferable. In the pyrido[2,3-a ]pyrimidine series, 3-oxides are deoxy-genated in moderate yield by phosphorus trichloride, by Raney nickel,309 or by titanium(III) chloride. 4... 

P3o-idine-I-oxides are comparatively resistant to reduction because of resonance stabilization by the aromatic system. Typical reagents that have been used for the formation of pyridones and pyridinols are Raney Nickel in methanol, palladium-on-charcoal, phosphorous trichloride, or phosphorus oxychloride in ethyl acetate. The N-oxides of pyridoxine, pyridoxal, and pyridoxamine have been deoxygenated catalytically. 4-Alkoxy-3-halopyri-dine-1-oxides are A-deoxygenated by phosphorous trichloride in chloroform. 2-Amino-3-pyridinol can be prepared ffom2-nitro-3-pyridinol-l-oxide (X1I450) in acetic acid by treatment with iron and mercuric chloride and then with zinc. 2-Halo-3-pyridinols can be prepared from XII-450 by treatment with phosphorous trihalides in chlorofiMm ... 

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