Pyridine ring, 1,2,3,4-tetrahydro

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. 

Another quite common reaction involving nucleophilic attack at a carbon atom of the ring is the hydrolysis of hexahydro-oxazolo[3,4- ]pyridines and tetrahydro-oxazolo[3,4-tf]pyridin-l-ones. This reaction has been known for years and is best performed under acidic conditions, respectively, producing 2-hydroxymethyl-piperidines or pipe-colic acid derivatives in good yields representative examples are collected in Table 9. Ammoniolysis of tetrahydro-oxazolo[3,4-tf]pyridin-l -ones with amino acid derivatives has also been reported and produces substituted pipecolic acid amides in good yields <2003H(61)259>. 

It is quite difficult to reduce benzene or pyridine, because these are aromatic stmctures. However, partial reduction of the pyridine ring is possible by using complex metal hydrides on pyridinium salts. Hydride transfer from lithium aluminium hydride gives the 1,2-dihydro derivative, as predictable from the above comments. Sodium borohydride under aqueous conditions achieves a double reduction, giving the 1,2,5,6-tetrahydro derivative, because protonation through the unsaturated system is possible. The final reduction step requires catalytic hydrogenation (see Section 9.4.3). The reduction of pyridinium salts is of considerable biological importance (see Box 11.2). 

The pyridine ring is easily reduced in the form of its quaternary salts to give hexahydro derivatives by catalytic hydrogenation [446], and to tetrahydro and hexahydro derivatives by reduction with alane aluminum hydride) [447], sodium aluminum hydride [448], sodium bis 2-methoxyethoxy)aluminum hydride [448], sodium borohydride [447], potassium borohydride [449], sodium in ethanol [444, 450], and formic acid [318]. Reductions with hydrides give predominantly 1,2,5,6-tetrahydro derivatives while electroreduction and reduction with formic acid give more hexahydro derivatives [451,452]. 

The acetic anhydride-induced cyclodehydration of the symmetrical diamide 411, derived from the tetrahydro-benzothiophene / -amino ester 410 and diethyl malonate, afforded the thieno[2,3-r7 [h3]oxazine derivative 413 rather than the expected bis-oxazine 412 (Scheme 78). The reaction probably takes place through sequential cyclizations, in which the pyridine ring of 413 is produced by condensation of the exocyclic double bond of the enamine tautomeric form of the 1,3-oxazine moiety and the mixed anhydride formed by the carboxylic group and acetic anhydride <2003PS245>. 

Catalytic reduction of the derivatives of triazolopyridines invariably attacks the pyridine ring, leaving the triazole. There is no report of reduction of compound 1, but 3-nitrotriazolopyridine (154) gives as major product the tetrahydrotriazolopyridinamine 155.229 Reduction with palladium-charcoal takes a different course (see Section IV,F). The mesoionic derivatives of [l,2,4]triazolo[l,5-a]pyridine 156-15854 and 159230 are reduced to py-tetrahydro derivatives, as is compound 3,231 although it had previously been reported that 3-substituted derivatives of compound 3 were not reduced.65 Chloro[l, 2,3]triazolo[4,5-6]pyridine (160) is reductively dehalogenated with reduction of the pyridine ring by platinum or palladium catalysts.146 By addition of base the reduction can be stopped at compound 4 (see Section... 

The reduction of 1,10-phenanthroline (4) occurs preferentially in the pyridine rings. Chemical reduction affords a low yield of 1,2,3,4-tetrahydro- 1,10-phenanthroline,243 but hydrogenation with Raney nickel as catalyst gives good yields of the 1,2,3,4-tetrahydro (45) and/or the 1,2,3,4,7,8,9,10-octahydro (46) derivative depending on reaction conditions.244 Hydrogenation of certain substituted 1,10-... 

There has been considerable interest in the reduction of 4,7-phenanthrolines. Hydrogenation of 4,7-phenanthroline (10) under pressure with Raney nickel results in reduction of either the benzene ring or one of the pyridine rings. Both products, 5,6-dihydro- (48) and l,2,3,4-tetrahydro-4,7-phenanthrolines (47), are formed in approximately equal amounts (40% yield).101 This result contrasts with an... 

The pyridine ring in l,3-dimethylimidazo[l,2-a]pyridinium salts (196) is reduced in two two-electron steps in aqueous media to a dihydro- and then to a tetrahydro compound 197 [Eq. (116)],... 

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... 

Somewhat less useful is the aluminum hydride reduction of quaternary pyridinium salts. Reduction of the salts may be more conveniently performed by the use of sodium borohydride (see Section II, B, 6). Moreover, the aluminum hydride reductions of some dialkyl-pyridinium salts are accompanied by reductive cleavage of the pyridine ring,77 For example, methiodides of 2,5-dimethylpyridine,77 2-methyl-5-ethylpyridine,77 and 2-ethyl-5-methylpyridine61 afford mixtures of the corresponding tetrahydro and hexahydro bases along with a secondary amine, viz., 5-methylaminomethyl-2,4-hexadiene, 5-methylaminomethyl-2,4-heptadiene, and 7-methylamino-6-methyl-2,4-heptadiene, respectively. 

In Lukes reductions of quaternary salts of pyridine homologs, the ratio of the tetrahydro to the hexahydro product is strongly dependent of the position and bulkiness of the substituent on the pyridine ring. Only the tetrahydro base is obtained from 4-methylpyridine metho-bromide.83 On the other hand, both the tetrahydro and hexahydro bases (in the ratio 1 1) result from the reduction of 3-methylpyridine methobromide.82 The LukeS reductions of 2-methylpyridine metho-bromide and 2,6-dimethylpyridine methobromide (80) are accompanied by formation of by-products (81-83) due to reductive cleavage... 

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