Pyridines 3-cyano- from

A modification of the Reissert-Hen2e reaction employing ben2oyl chloride and (CH2)3SiCN gives good yields of 2-cyano pyridine (14) from pyridine... 

Ultraviolet irradiation of pyridines can prodnce highly strained species that can lead to isomerised pyridines or can be trapped. The three picolines and the three cyano-substituted pyridines constitute photochemical triads irradiation of any isomer, in the vaponr phase at 254 nm, results in the formation of all three isomers. From pyridines and from 2-pyridones 2-azabicyclo[2.2.0]-hexadienes and -hexenones can be obtained in the case of pyridines these are nsnally nnstable and revert thermally to the aromatic heterocycle. Pyridone-derived bicycles are relatively stable, 4-alkoxy- and -acyloxy-pyridones are converted in particnlarly good yields. Irradiation of iV-methyl-2-pyridone in aqueous solution prodnces a mixture of regio- and stereoisomeric 4n pins 4n photo-dimers. ... 

Olah s original preparative nitrations were carried out with mixtures of the aromatic compound and nitronium salt alone or in ether, and later with sulpholan as the solvent. High yields of nitro-compounds were obtained from a wide range of aromatic compounds, and the anhydrous conditions have obvious advantages when functional groups such as cyano, alkoxycarbonyl, or halogenocarbonyl are present. The presence of basic fimctions raises difficulties with pyridine no C-nitration occurs, i-nitropyridinium being formed. ... 

Pyridine, 4-(chloromethyl)-l,4-dihydro-4ff-azepines from, 7, 524 ring expansion, 7, 543-544 Pyridine, 2-chloro-6-trichloromethyl-as bactericide, 2, 514 Pyridine, 2-cyano-ions... 

Pyridin-3-one, 3-cyano-6-hydroxy-4-methyl-azo dyes from, 1, 331 Pyridin-4-one, 2-amino-synthesis... 

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. ... 

A solution of 1.1 g of the cyanohydrin in 6 ml of pyridine is treated with 0.6 ml of phosphorus oxychloride and allowed to stand at room temperature overnight. The reaction mixture is quenched with ice and water and the resulting crystalline precipitate is collected, washed with water and dried to yield 1.05 g. Recrystallization from aqueous pyridine affords 0.88 g (83%) of 20-cyano-21-hydroxy-3,3-ethylenedioxypregna-5,17(20)-dien-l l-one acetate mp 197-200°. 

A solution of the crude cyanohydrin (94a ca. 1 g) in pyridine (15 ml) and acetic anhydride (15 ml) is allowed to stand at room temperature for 52 hr. The solvents are evaporated under reduced pressure below 60°. The residue is dissolved in ether, and the ether solution is washed successively with 5 % hydrochloric acid, water and saturated salt solution. The solvent is evaporated under reduced pressure to give a crystalline residue. Recrystallization of the crude product from cyclohexane-acetone gives 3-methoxy-17a-cyano-estra-l,3,5(10)-trien-17i5-ol acetate (94b 0.9 g), mp 130-132°, as large prisms. 

The methyl groups adjacent to the pyridine nitrogens can also be modified without changing calcium channel blocking activity. The most significant change involves replacement of methyl by a nitrile group. Hantsch type condensation of the nitrobenzaldehyde 43 with methyl acetoacetate and the vinyl amine 44 from isopropyl 3-cyano-3-ketopropionate leads directly to nilvadipine (45) [13]. 

A solution of 1.0 g of A -3,11-diketo-20-cyano-21-acetoxy-pregnene in 10 cc of benzene is treated with 1.0 g of osmium tetroxide and 0.43 g of pyridine. After standing at room temperature for 18 hours, the resulting solution is treated successively with 50 cc of alcohol, and with 50 cc of water containing 2.5 g of sodium sulfite. The mixture is stirred for 30 hours, filtered, and the filtrate acidified with 0.5 cc of acetic acid and concentrated to small volume in vacuo. The aqueous suspension is then extracted four times with chloroform, the chloroform extracts are combined, washed with water and concentrated to dryness in vacuo. Recrystallization of the residue from acetone gives 3,11,20-triketo-17(a)-21-dihydroxy-pregnane MP 227° to 229°C. This compound is then treated with acetic anhydride and pyridine for 15 minutes at room temperature to produce 3,11,20-triketo-17(a)-hydroxy-21-acetoxy-pregnane or cortisone acetate. 

A mixture of 100 g of ethyl 2-cyano-2-(5H-[ 1 ] benzopyrano [2,3-b] -py rid in-7-y I [propionate, 500 ml of glacial acetic acid and 200 g of concentrated hydrochloric acid is refluxed for 48 hours. The reaction mixture is concentrated, and the residue is dissolved in hot water. The solution is adjusted to pH 2 to 3 by addition of 10% sodium hydroxide. The resulting crystalline precipitate Is washed thoroughly with water, and recrystallized from aqueous dioxane to give 74 g of 2-(5H-[1] benzopyrano [2,3-b] -pyridin-7-y I [propionic acid as white crystals melting at 183°Cto 183.5°C. 

B) 20 -cyano-4Q ,5Q -epoxandrostan-17(3-ol-3-one was prepared by treating 17(3-acetoxy-40 , 50 -epoxyandrostano [2,3-d] isoxazole with sodium methoxide, and was obtained in the form of tan crystals, melting point 257.8°C to 270.0°C (decomposition) (corrected) when recrystallized from a pyridine-dioxane mixture. 

The cycloadducts formed from the Diels-Alder reaction of 3-amino-5-chloro-2(17/)-pyrazinones with methyl acrylate in toluene are subject to two alternative modes of ring transformation yielding either methyl 6-cyano-l,2-dihydro-2-oxo-4-pyridinecarboxylates or the corresponding 3-amino-6-cyano-l,2,5,6-tetrahydro-2-oxo-4-pyridinecarboxylates. From the latter compounds, 3-amino-2-pyridones can be generated through subsequent loss of HCN <96 JOC(61)304>. Synthesis of 3-spirocyclopropane-4-pyridone and furo[2,3-c]pyridine derivatives can be achieved by the thermal rearrangement of nitrone and nitrile oxide cycloadducts of bicyclopropylidene <96JCX (61)1665>. 

The mechanism of formation of pyridines from a,P-unsatuiated nitriles and active cyano compounds has been investigated. These processes proceed through a Michael adduct which undergoes a regioselective cyclization to the corresponding pyridine <96H(43)33>. 

Hoomaert has studied Diels-Alder reactions of pyridine oquinodimethane analogs generated from functionalized o-bis(chloromethyl)pyridines <96T(52)11889>. The photochemical cycloaddition of 2-alkoxy-3-cyano-4,6-dimethylpyridine with methacrylonitrile gives a bicyclic azetine, 6-alkoxy-3,5-dicyano-2,5,8-trimethyl-7-azabicyclo[4.2.0]octa-2,7-diene, in moderate yield <96CC1349>. Regiospecific hydroxylation of 3-(methylaminomethyl)pyridine to 5-(methylaminomethyl)-2-(17/)-pyridone by Arthrobacter ureafaciens has been reported <96MI173>. 

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