Pyridine 1-oxide, 2,3,4,5-tetrahydro

A -Benzoyloxypyridinium chloride (72), prepared from pyridine oxide and benzoyl chloride, reacts with silver phenylacetylide selectively at position 2 to afford 2-(phenylethynyl)pyridine (73). The bromine atom of the tetrahydro-l,4-oxazin-2-one 74 is replaced by an alkynyl group on treatment with stannanes 75 (R = hexyl or Ph) the products 76 are transformed into ( S)-amino acids 77 by catalytic hydrogenation. ... 

Reduction. Quinoline may be reduced rather selectively, depending on the reaction conditions. Raney nickel at 70—100°C and 6—7 MPa (60—70 atm) results in a 70% yield of 1,2,3,4-tetrahydroquinoline (32). Temperatures of 210—270°C produce only a slightly lower yield of decahydroquinoline [2051-28-7]. Catalytic reduction with platinum oxide in strongly acidic solution at ambient temperature and moderate pressure also gives a 70% yield of 5,6,7,8-tetrahydroquinoline [10500-57-9] (33). Further reduction of this material with sodium—ethanol produces 90% of /ra/ j -decahydroquinoline [767-92-0] (34). Reductions of the quinoline heterocycHc ring accompanied by alkylation have been reported (35). Yields vary widely sodium borohydride—acetic acid gives 17% of l,2,3,4-tetrahydro-l-(trifluoromethyl)quinoline [57928-03-7] and 79% of 1,2,3,4-tetrahydro-l-isopropylquinoline [21863-25-2]. This latter compound is obtained in the presence of acetone the use of cyanoborohydride reduces the pyridine ring without alkylation. 

Imtdazo[4,5-c]pyridtne, 4,5,6,7-tetrahydro-synthesis, 5, 623, 640, 641 Imidazo[4,5-c]pyridine-6-carboxylic acid, 4,5,6,7-tetrahydro-synthesis, 5, 623, 641 Imidazopyridines as anthelmintic, 1, 202 synthesis, 5, 462 Imidazo[l,2-n]pyridines deuterium exchange, 5, 611 diazo coupling, 5, 614 Dimroth rearrangement, 5, 613 halogenation, 5, 611 hydrogenation, 5, 614 Mannich reaction, 5, 612 nitration, 5, 612 1-oxides... 

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>. 

Reactions of methoxycarbonylformonitrile, furonitrile and substituted benzoni-trile oxides (4-Me, 4-OMe, 3-OMe, 4-C1, 3-C1, 2,4-di-Cl, 4-F as substituents) with dimethyl 7-(diphenylmethylene)bicyclo[2.2. l]hept-2-ene-5,6-dicarboxylate led exclusively to exo cycloadducts 82 (R = C02Me, 2-furyl, substituted phenyl), which, on irradiation with a low-pressure mercury lamp, afforded 3-azabicyclo [4.3.0]nonadiene-7,8-dicarboxylates 83 as the only products. The 1,3-dipolar cycloaddition, followed by a photorearrangement, provides a new method for obtaining tetrahydro-27/ -pyridine derivatives from cyclopentadiene (245). 

As in the case of 2,2 -bipyridine, the most important synthetic routes to 4,4 -bipyridine use pyridine as starting material. One method of synthesizing 4,4 -bipyridine from pyridine was discovered by Dimroth in 1921. If pyridine in acetic anhydride is treated with zinc dust, l,l -diacetyl-l,r,4,4 -tetrahydro-4,4 -bipyridine is formed. This compound is readily oxidized and hydrolyzed by moist air to 4,4 -bipyridine. Various oxidizing agents assist in the conversion to 4,4 -bipyridine. By-products from the reaction include 1,1 -diacetyl-l,T-dihydro-4,4 -bipyridine. This method of synthesizing 4,4 -bi-pyridine has frequently been used. ° The reduction of pyridine in acetic anhydride by catalytic hydrogenation instead of by zinc dust is less satisfactory because of the formation of other reduction products. Several variations and improvements in the Dimroth reaction have subsequently... 

The most important synthesis of 4,4 -bipyridine involves the reaction of sodium on pyridine. This reaction was discovered as long ago as 1870, although the product was not deduced to be 4,4 -bipyridine until later. " 4,4 -Bipyridine is the predominant isomer formed, although varying amounts of other isomeric bipyridines, especially 2,2 -bipyridine and 2,4 -bipyridine, may be formed, depending on the reaction conditions. The reaction involves formation of the sodium derivative of pyridine, which is formulated as the radical 67. It then couples predominantly in the 4 positions to afford 68, which with water hydrolyzes to l,T,4,4 -tetrahydro-4,4 -bipyridine. Facile oxidation then gives 4,4 -bipyridine. ° If the reaction is carried out at the temperature of boiling pyridine (IIS C) instead of at lower temperatures, the proportion of bipyridines other than 4,4 -bipyridine increases, and some terpyridines may be formed as vvell. Oxidants... 

A number of other routes are available for the syntheses of diquaternary salts of 4,4 -bipyridines. One method that has been extensively studied involves reaction of a 1-alkylpyridinium salt with sodium amalgam (or sodium in liquid ammonia) to form the 1,1 -dialkyl-1,1, 4,4 -tetrahydro-bipyridine, which is readily oxidized to the corresponding l,l -dialkyl diquaternary salt. This reaction is analogous to the synthesis of 4,4 -bipyridine by the action of sodium on pyridine, followed by oxidation of the intermediate tetrahydrobipyridine. " The reduction may be achieved electrolytically or by reaction with zinc or magnesium. Various oxidizing agents have been used to assist the conversion to the di-quaternary Another synthesis of diquaternary salts of... 

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. 

The reduced pyridones 96 were obtained in good yield from the aldehydes 95a directly106 or via the phenylhydrazones 95b.107 Platinum oxide-catalyzed hydrogenation of the pyridine ring in 16 gave tetrahydro products (97 R2 = Me,H R4 = H,Me).61... 

Sodium-liquid ammonia reduction of the parent bicycle gave a smooth conversion to the 4,5,6,7-tetrahydro derivative 255 (R = H).165 Reduction of the pyridine ring to give 255 was also observed during hydrogenation of 2-hydroxypyrazolo[l,5-a] pyridine (240 R = OH) over platinum oxide.192... 

Oxidation of 6-formyl-5,7,8,9-tetrahydro-ll//-pyrido[2,l-b]quinazolin-11-one with potassium permanganate in pyridine at ambient temperature for 3 h gave 11 -oxo-5,7,8,9-tetrahydro-l 17/-pyrido[2,l-b]quinazoline-6-carboxylic acid in 24% yield (84JHC1301). 

The presence or absence of the dioxolane protecting group in dienes dictates whether they participate in normal or inverse-electron-demand Diels-Alder reactions.257 The intramolecular inverse-electron-demand Diels-Alder cycloaddition of 1,2,4-triazines tethered with imidazoles produce tetrahydro-l,5-naphthyridines following the loss of N2 and CH3CN.258 The inverse-electron-demand Diels-Alder reaction of 4,6-dinitrobenzofuroxan (137) with ethyl vinyl ether yields two diastereoisomeric dihydrooxazine /V-oxide adducts (138) and (139) together with a bis(dihydrooxazine A -oxide) product (140) in die presence of excess ethyl vinyl ether (Scheme 52).259 The inverse-electron-demand Diels-Alder reaction of 2,4,6-tris(ethoxycarbonyl)-l,3,5-triazine with 5-aminopyrazoles provides a one-step synthesis of pyrazolo[3,4-djpyrimidines.260 The intermolecular inverse-electron-demand Diels-Alder reactions of trialkyl l,2,4-triazine-4,5,6-tricarboxylates with protected 2-aminoimidazole produced li/-imidazo[4,5-c]pyridines and die rearranged 3//-pyrido[3,2-[Pg.460]

Sometimes the reaction is followed by oxidation and leads to 1,2-dihydro-pyridines instead of their 1,2,3,4-tetrahydro analogues. As often as not, such a situation is observed in the case of cyclic unsaturated ketones in the presence of triethylamine or piperidine [137,138,139, 140, 141, 142, 144, 147,148,149,150, 151] (Scheme 3.41). The possibility of such reactions occurring instead of a,(3-... 

Brewster ME, Kaminski JJ, Bodor N. Reactivity of biologically important reduced pyridines. 2. The oxidation of l-methyl-4-phenyl-l,2,3,6-tetrahydro-pyridine. J Am Chem Soc 1988 110 6337-6341. 

The acid 350 was demethylated with pyridine hydrochloride, then realkylated with benzyl bromide in aqueous potassium hydroxide to give 351. The latter was converted to the diazoketone 352 by the sequential treatment of 351 with oxalyl chloride and etheral diazomethane. Reaction of 352 with concentrated hydrobromic acid gave the bromoketone 353. The latter was reduced with sodium borohydride at pH 8 -9 to yield a mixture of diastere-omeric bromohydrins 354. Protection of the free hydroxyl as a tetrahydro-pyranyl ether and hydrogenolysis of the benzyl residue afforded 355. The phenol 355 was heated under reflux with potassium m/V-butoxide in tert-butyl alcohol for 5 hr to give a 3 1 epimeric mixture of dienone ethers 356 and 357 in about 50% yield. Treatment of this mixture with dilute acid gave the epimeric alcohols 358 and 359. This mixture was oxidized with Jones reagent to afford the diketone 349. 

Oxidation of 2,4,4-trimethyl - A1 -py rroline V-oxide with selenium dioxide, followed by treatment with hydrogen chloride, causes ringopening and reclosure to 2,3,4,5-tetrahydro-3,3-dimethyl-5-oxo-pyridine N-oxide (111). Clemmensen reduction of 111 forms 2,4,4-trimethyl-d 1-pyrroline (112) by ring-contraction.334... 

I, 2-Dihydroisoquinolines are reported to be formed when (a) the 1,2,3,4-tetrahydro derivatives are oxidized with oxygen in pyridine solution60 or with palladium chloride,51 (b) when 29 is treated with dry sodium hydroxide,52 or (c) when the benzylaminopropyne [(30) R = H or Me] is heated with polyphosphoric acid.53 When isoquinoline is reduced with sodium in liquid ammonia, one of the products was... 

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