5.5- dichloro pyridine 1-oxide

Scheme X.12. The hydroxylation of 5a-cholestan-3-one by 2,6-dichloro-pyridine N-oxide catalyzed with ruthenium porphyrin.

ClaHi8Cl2N202Zn, Dichlorobis(2,6-lutidine N-oxide)zinc(II), 33B, 458 C1 aH2 2ClijCu2N20i S2, Di-jU (pyridine oxide)-bis(dichloro(dimethyl sulfoxide)copper(II)), 41B, 1120... 

The reactivity of the amino radical has not yet been investigated. Alkaline hypochlorite oxidation, known in the pyridine series to yield azo derivatives (155,156). and photolysis of N,N-dichloro derivatives, which may be obtained by action of sodium hypochlorite on amino derivatives in acidic medium (157). should provide interesting insight on this reactivitv. 

Dipyridiue-chromium(VI) oxide2 was introduced as an oxidant for the conversion of acid-sensitive alcohols to carbonyl compounds by Poos, Arth, Beyler, and Sarett.3 The complex, dispersed in pyridine, smoothly converts secondary alcohols to ketones, but oxidations of primary alcohols to aldehydes are capricious.4 In 1968, Collins, Hess, and Frank found that anhydrous dipyridine-chromium(VI) oxide is moderately soluble in chlorinated hydrocarbons and chose dichloro-methane as the solvent.5 By this modification, primary and secondary alcohols were oxidized to aldehydes and ketones in yields of 87-98%. Subsequently Dauben, Lorber, and Fullerton showed that dichloro-methane solutions of the complex are also useful for accomplishing allylic oxidations.6... 

The synthesis of pyrazolo[3,4-. ]pyridines can be achieved by reaction of 2,6-dichloro-3-lithiopyridine with 5-bromo-2-methoxybenzaldehyde 138 to provide the alcohol, which after Jones oxidation gave ketone 139. Treatment of the ketone with hydrazine furnished the desired pyrazolo[3,4-3]pyridine 140 (Scheme 8) <2006BML262>. 

Fur die direkte Herstellung von Bis-[isocyanat]-arenen, die iiber die als Nebenprodukte entstehenden Isocyanato-nitro-arene verlaufen, hat sich die Carbonylierung in Gegenwart von Palladium(II)-Molybdan(VI)-Eisen(III)-Aluminium-oxid/Pyridin3 bzw. Bis-[pyridin]-dichloro-palladium/Eisen(III)-Vanadin(V)-oxid bei 170-260°/250-300 atm bewahrt4 ... 

Acute pyridine treatment (single intraperitoneal dose of 200 mg/kg bw) increased the metabolism of 2-butanol twofold in Sprague-Dawley rat liver microsomes and threefold in rabbit (New Zealand White) liver microsomes (Page Carlson, 1993). In liver microsomes from pyridine-treated (one intraperitoneal injection of 100 mg/kg bw, daily for four days) male Sprague-Dawley rats, increased oxidative biotransformation of the chlorofluorocarbon l,2-dichloro-l,l,2-trifluoroethane was found the day after the last injection (Dekant et al, 1995). 

A number of reduction products of 2,8-dichloro-6,12-diphenyldibenzo[f>,/][l,5]diazocine (283) have been obtained (66JOC3356). LAH in ether gives mainly the frans-diphenyl-tetrahydro compound (282), whereas reduction in pyridine stops at the dihydro stage (284) (78%). Catalytic hydrogenation or zinc-acid reduction gives the tetracyclic indolo[3,2-6]indole system (286) which is readily oxidized back to the diazocine. Transannular cycliz-ation to (286) occurs on treatment of the dihydrodiazocine with NaH. Troeger s base derivatives, e.g. (287), were formed from the tetrahydro derivatives with formaldehyde. 

Ammino-derivatives of palladic salts are unknown, but pyridine derivatives containing tetravalent palladium have been described. The substances are easily obtained by the oxidation of dichloro-di-pyridino-palladium. 

Treatment 2,3-dichloro-5-(trichloromethyl)pyridine in anhydrous hydrogen fluoride with mercury(II) oxide (red) at room temperature for 22 hours provides 2,3-dichloro-5-(tri-fluoromethyl)pyridine in 98% yield.59... 

The only alkyl group reported as reductively removed is the di-phenylmethyl substituent from N3 in compound 165.153 Deoxygenation of N-oxides can be done thermally (heating in toluene with oxygen transfer to solvent) for compounds of type 166,44 or more commonly by use of phosphorus derivatives, as described for compounds 32, 33,45 166,44 and 167.61 Halogens can be reductively removed from [l,2,3]triazolo-[4,5-6]pyridines 160,146 168,220 and 169,142 and from pentachloro derivative 164, giving dichloro compound 170.208 Removal of thiol groups by reduction... 

Methylquinoxaline-2,3-dione (173) is oxidized with Co(OAc)2 Mn(OAc)2 in HBr/H20 to the 6-carboxylic acid (174),183 which on treatment with thionyl chloride is converted into 2,3-dichloro-quinoxaline-6-carbonyl chloride (175).184 The 6-sulfonyl chloride is obtained from quinoxaline-2,3-dione and chlorosulfonic acid and treatment of the resulting 6-chlorosulfonyl derivative with phosphoryl chloride and pyridine.185 Such derivatives are useful synthetic dye intermediates. 

Electrophilic chlorination of pyridine 1-oxides is more difficult than for the analogous pyridines. An example is chlorination of 2-acetamidopyridine 1-oxide with hydrogen chloride and hydrogen peroxide, which gives a mixture of 5-chloro and 3,5-dichloro derivatives. 

When 2,2 -bi(pyridine 1-oxide) (11) was heated with phosphoryl chloride, a mixture of the expected products was obtained. The 4,4 -dichloro derivative (12) gave mainly 13 along with a small quantity of 14, formed as a result of attack by the N-oxide function on the adjacent ring (Scheme 8). In contrast, the 4,4 -dinitro compound was subject to extensive nucleophilic chlorodenitration (83T291) (Scheme 9). 

Omeprazole is obtained [15] by the reaction of acetyl ethyl propionate 1 with ammonia to give ethyl -3-amino-2,3-dimethyl acrylate 2. Compound 2 was converted to to 2,4-dihydroxy-3,5,6-trimethyl pyridine 3 by treatment with methyl diethylmalonate. Treatment of compound 3 with phosphorous oxychloride produced 2,4-dichloro-3,5/6-trimethyl pyridine 4. 4-Chloro-3/5,6-trimethyl pyridine 5 was obtained by treatment of compound 4 with hydrogen. On treatment of compound 5 with hydrogen peroxide and acetic acid, 4-chloro-3,5,6-trimethyl-pyridine-N-oxide 6 was produced. Treatment of compound 6 with acetic anhydride gave 4-chloro-2-hydroxymethyl-3,5-dimethyl pyridine 7 which was converted to 2-hydroxymethyl-3,5-dimethyl-4-methoxypyridine 8 by treatment with sodium methoxide. Compound 8 was treated with thionyl chloride to produce 2-chloromethyl-3,5-dimethyl-4-methoxypyridinc 9. Compound 9 interacts with 5-methoxy-2-mercaptobenzimidazole to give 5-methoxy 2-[((4-methoxy-3,5-dimethyl-2-pyridinyl)methyl)thio]-lH-bcnzimidazole 10 which is oxidized to omeprazole 11. 

Certain pyridines react with Grignard reagents in the 1,4-manner when substituted by electron-withdrawing groups such as a carboxamide <2000J(P1)4245, 2005JOC2000>. The intermediate dihydropyridine can conveniently be oxidized to the pyridine structure. An example of this is seen in the reaction of 6-chloronicotinic acid derivative 125 with an excess of o-tolylmagnesium chloride, followed by oxidation with 2,3-dichloro-5,6-dicyano-l,4-benzoquinone... 

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