Pyridine 4,5-dihydroxy-2-methyl

Ethers of benzenepentol have been obtained by Dakin oxidation of the appropriately substituted acetophenone. Thus, the oxidation of 2-hydroxy-3,4,6-ttimethoxyacetophenone and 2-hydroxy-3,4,5-ttimethoxyacetophenone with hydrogen peroxide ia the presence of alkali gives l,2-dihydroxy-3,4,6-ttimethoxybenzene and l,2-dihydroxy-3,4,5-ttimethoxybenzene, respectively further methylation of these ethers yields the pentamethyl ether of benzenepentol (mp 58—59 degC) (253). The one-step aromatization of myoinositol to produce esters of pentahydroxybenzene is achieved by treatment with carboxylic acid anhydrides ia DMSO and ia the presence of pyridine (254) (see Vitamins). 6-Alkyl- or... 

A third synthesis which has resulted in the preparation of rieinine and a number of its derivatives is due to Schroeter, Seidler, Sulzbacher and Kanitz,i2 who foimd that cyanoacetyl chloride polymerises spontaneously to 6-chloro-2 4-dihydroxy-3-cyano-pyridine. The di-sodium derivative of this with methyl sulphate produces A -methyl-6-chloro-4-hydroxy-3-cyano-2-pyridone (6-chlororicininic acid), the mono-sodium derivative of which, with methyl bromide or sulphate, is converted into 6-chlororicinine and the latter is reduced by zinc and sulphuric acid to rieinine. A fourth synthesis, starting from 3-nitro-4-pyridone, is due to Reitmann. ... 

Preparation of 9, 11 -Epoxy-17a-21 -Dihydroxy-16 -Methyl-4-Pregnene-3 0-Dione 21-Acetate To a stirred solution of 100 mg of the 9a-bromo-11(3,17a,2Ttrihydroxy-16 3-methyl-4-pregnene-3,20-dione 21-acetate in 3 ml of tetrahydrofuran and 1 ml of methanol under nitrogen was added 1.02 ml of 0.215 N methanolic sodium methoxide. After 10 minutes at 25°C, 0.2 ml of acetic acid was added and the methanol removed in vacuo. The residue was acetylated with 1.00 ml of pyridine and 0.5 ml of acetic anhydride at 60°C for 70 minutes. The mixture was taken to dryness in vacuo, water added, and the product extracted into chloroform. The residue was crystallized from ether-acetone to give pure 9(3,11 (3-epoxy-17a,21-dihydroxy-16(3-methyl-4-pregnene-3,20-dione 21-acetate. 

Note FAP familial adenomatous polyposis ACF aberrant crypt foci FAD focal areas of dysplasia B[a]P benzo[a]pyrene DMBA 7,I2-dimethylbenz[a]nthracene TPA 12-O-tetradecanoyl-phorbol-13-acetate NNK 4-(methyl-nitrosamino)-I-(3-pyridyl)-l-butanone NQO 4-mtroquinoline 1-oxidase DMAB 3,2 -dimethyl-4-aminobiphenol PhIP 2-amino-l-methylimidazo[4,5-b]pyridine DHPN 2,2 -dihydroxy-di-n-propylnitrosamine EHEN jV-ethyl-jV-hydroxyethylnitrosamine. 

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. 

An, Angeloyl BAn, 3-bromoangeloyl DMB, 2,3-dihydroxy-2-methylbutyryl eDMB, (+)-e,o,JliTO-2,3-dihydroxy-2-methylbutyryl HMB, 2-hydroxy-2-methylbutyryl iB, isobutyryl K, ketone MB (-)-2-methylbutyryl Py, pyridine tDMB, (+ )-riireo-2,3-dihydroxy-2-methylbutyryl TDMB, 2-hydroxy-2-methyl-3-p-toluenesulfonylbutyryl Ts, p-toluenesulfonyl. b Attached carbon epimerized. c Cf, Chloroform. 

Benzoselenadiazoles were synthesized at room temperature in the solid state with ortho-aromatic diamines and selenium dioxide. Diamines and selenium dioxide were ground, respectively, and then were mixed in a ratio of 1 1 in a mortar at room temperature the process was monitored with X-ray diffraction (XRD) or IR. The results showed that the reactions were completed after 30 min of grinding and the desired products were obtained. The yields of the synthesized compounds are as follows 2,1,3-benzoselenadiazole 196 77% l,2,5-selenadiazolo-[3,4-A]pyridine 284 44% l,2,5-selenadiazolo[3,4-c]pyridine 285 23% 5-methyl-2,l,3-benzo-[3,4-c]selenadiazole 286 74% 1,2,5-selenadi-azole[3,4- /]pyrimidine-7-(6/7)-one 287 50% 5,7-dihydroxy-l,2,5-selenadiazolo-[3,4- 7]pyrimidine 288 19% and 2,l,3-naphtho-[2,3-c]-selenadiazole (289) 77% <2004MI1>. 

A solution of 1.0 g of 17-acetoxy-llfS,21-dihydroxy-6a-methyl-4-pregnene-3,20-dione in 20 ml of pyridine is combined with 3 ml of butyric anhydride and stirred at room temperature for 2 hours. The reaction solution is then allowed to flow into 150 ml of cooled 8% sulfuric acid and agitated for another... 

Oxazolo[5.4-b]pyridin 4,6-Dihydroxy-3-methyl- Elba, 712 (Pyridin-RingschluB)... 

Piperldin 3-Ethoxycarbonyl-l-methyl-4-oxo- VIII, 577 Pyridin 3.4-Dihydroxy-5-oxo-... 

Dichloropyrazines have also been prepared from the corresponding hydroxy compounds as follows 2,3-dihydroxypyrazine with phosphoryl chloride containing pyridine (481, 757) [see Schneller and May (828) re the use of phenylphosphonic dichloride at 150-170°] 2,3-dihydroxypyrazine and its methyl, dimethyl, phenyl, diphenyl, and 5-methy 1-6-phenyl derivatives with phosphoryl chloride (483, 829) [N.B. error in work of Minovici and Bente (830)] 2-chloro-5-hydroxypyrazine with phosphoryl chloride (831) 2-chloro-6-hydroxypyrazine with phosphoryl chloride at reflux for 6hours (832) and 2,5-dihydroxy-3-phenylpyrazine and3,5-dihydroxy-2-phenylpyrazine with phosphoryl chloride at 180-200° (829). 

For the synthesis of (69), the enol ether (71) from the indanone (70) was carboxylated with COa-n-butyl-Iithium in THF at —70 C to yield (72). The methyl ester (73) was converted into (75) via the maleic anhydride adduct (74), essentially as described in earlier work. Lithium aluminium hydride reduction followed by oxidation with dicyclohexylcarbodi-imide afforded the aldehyde (76). This was condensed with excess (77) to yield a mixture of the diastereomers (78). Oxidation with chromium trioxide-pyridine in methylene dichloride gave (79), which could be converted into the diketone (80) by treatment with excess benzenesulphonylazide. The diketo-lactam (81) was prepared from (80) as described for the synthesis of the analogous intermediate used in the synthesis of napelline. Reduction of (81) with lithium tri-t butoxyaluminohydride gave the desired dihydroxy-lactam (82). Methylation of (82) with methyl iodide-sodium hydride gave (83). Reduction of this lactam to the amine (84) with lithium aluminium hydride, followed by oxidation with potassium permanganate in acetic acid, gave (69). 

Treatment of 3-phcnylpyridazino[4,5-c]pyridazine-5,8-diol with phosphoryl chloride in pyridine yields 5,8-dichloro-3-phenylpyridazino[4,5-c]pyridazine (64%),10 whereas attempts to synthesize the 3-unsubstituted or 3-methyl compound by analogous methods are unsuccessful.8 Substitution of the chlorine atoms in 5,8-dichloro-3-phenylpyridazino[4,5-r]pyridazine by amines yields the corresponding morpholino or piperidino compounds (yield 74 and 42%, respectively).10 The preparation of 3-methylpyridazino[4,5-c]pyridazine-5,8-dithiol is achieved by the reaction of the corresponding dihydroxy compound with phosphorus pentasulfide in boiling pyridin yield 59% mp > 210°C (dec.).8... 

The title compounds are stable tautomers of the corresponding 2-hydroxypyrazine 1-oxides, and in fact l-acetoxy-2(lH)-pyrazinones, not 2-acetoxypyrazine A -oxides, are obtained on treatment with acetyl chloride in the presence of pyridine at room temperature <87JHC187>. Nevertheless, these compounds resemble the N-oxides in most of their reactions. Representative examples are deoxidative acetoxylation and chlorination. Treatment of l-hydroxy-3,5-diphenyl-2(l//)-pyr-azinone (100) with a refluxing mixture of acetic anhydride and acetic acid affords 2,6-diacetoxy-3,5-diphenylpyrazine (101), which is deacetylated with potassium hydrogen carbonate to give 2,6-dihydroxy-3,5-diphenylpyrazine (102) (or tautomer) (Scheme 23) <7UCS(C)2977>, Acetoxylation of a methyl substituent occurs exclusively and then that of the pyrazine ring is suppressed completely. 

Dimethyl-8-ethoxycarbonyl-5-hydroxy-2-oxo-2H-378 Eine Mischung aus 2g (0,01 mol) 4,6-Dihydroxy-3-ethoxycarbonyl-2-methyl-pyridin und 1,3 g (0,01 mol) 3-Amino-2-butensaure-ethylester wird 30 Min. auf 220° erhitzt. Den freiwerdenden Alkohol und Ammoniak laBt man durch ein kurzes Steigrohr entweichen. Nach 15 Min. erstarrt der Ansatz. Das Rohprodukt kristallisiert beim Anreiben mit Petrolether und Ether. Aus Xylol erhalt man farblose Nadeln Ausbeute 2,5 g (95%) Schmp. 265-270". 

Linstead and coworkers" investigated alkali-catalyzed y3-elimination of the diacetate and dimethanesulfonate of dimethyl (+ )-3,4-dihydroxy-hexanedioate [(-I-)-/3,j8 -dihydroxyadipate] resulting in a trans,trans-muconic acid derivative. An unusually facile, double (irons )-jS-elimina-tion was found" in the reaction of dimethyl galactarate (15) with methanesulfonyl chloride in pyridine dimethyl irons,frans-2,5-di(methyl-sulfonyloxy)mucoate (17) was obtained by esterification to give 16... 

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