Quinoline sodium borohydride reduction

Reduction is commonly employed to convert imino and oxo bisbenzyliso-quinoline alkaloids to identifiable derivatives, or to other alkaloids. Thus thalsimine (58) gave, with either Zn/H2S04 or NaBH4, a mixture of norheman-dezine (234) and its epimer (391) (81). Sodium borohydride reduction of thalictrinine (Section II,C,114) gave specifically dihydrothalictrinine (Section II,C,31), from attack at the less hindered side of the carbonyl (81). 

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. 

A solution of N-(2-aminobenzvl)-1-phenyl-2-metKylaminoethanol-1 was prepared by the reaction of a-bromo-acetophenone and (2-nitrobenzyl)methylamine, followed by hydrogenation of the nitro group by means of nickei on diatomaceous earth at room temperature and reduction of the CO group by means of sodium borohydride. The intermediate thus produced was dissolved in 100 ml of methylene chloride and introduced dropwise into 125 ml of sulfuric acid at 10° to 15°C. After a short standing, the reaction mixture was poured onto ice and rendered alkaline by means of a sodium hydroxide solution. Dy extraction with ether, there was obtained 1,2,3,4-tetrahydro-2-methyl-4-phenyl-8-amino-iso-quinoline. The base is reacted with maleic acid to give the maleate melting point of the maleate 199° to 201°C (from ethanol). 

Palladium catalysts are more often modified for special selectivities than platinum catalysts. Palladium prepared by reduction of palladium chloride with sodium borohydride Procedure 4, p. 205) is suitable for the reduction of unsaturated aldehydes to saturated aldehydes [i7]. Palladimn on barium sulfate deactivated with sulfur compounds, most frequently the so-called quinoline-5 obtained by boiling quinoline with sulfur [34], is suitable for the Rosenmund reduction [i5] (p. 144). Palladium on calcium carbonate deactivated by lead acetate Lindlar s catalyst) is used for partial hydrogenation of acetylenes to cw-alkenes [36] (p. 44). 

Reduction of quinoline with lithium aluminum hydride gives 1,2-dihydroquinoline. Neutral pyridines bearing electron-withdrawing substituents are also reduced by sodium borohydride (Scheme 32). 

Numerous reducing agents were tried at this point unsuccessfully. For example, lithium aluminum hydride destroyed the substrate, whereas DIBAH or lithium borohydnde in THF and sodium borohydride in ethanol led to reduction of the quinoline system. On the other hand, both potassium borohydride (either with or without 18-crown-6) and zinc borohydride (with or without ethanol) produced no reaction at all. Lithium triethylborohydride resulted in de-methoxylation, and sodium borohydride in refluxing THF gave a 45% yield of diol 16 together with overreduced product. 

As would be expected, the weaker reducing agent, sodium boro-hydride, has received little attention for the reduction of quinolines. The reaction of 2-chloro-3,7-dicarbomethoxy-5,6-benzoquinoline (80) has been reported by Walker to yield 3,7-dicarbomethoxy-5,6-benzo-1,4-dihydroquinoline (81) on reaction with sodium borohydride.96 The success of this reaction may depend upon the electron-withdrawing properties of the carbomethoxy groups. 

In contrast to the quinoline and isoquinoline series, thienopyridines are apparently resistant to reduction by tin-hydrochloric acid, since the parent systems can be obtained by reductive dehalogenation or chloro-derivatives. Quaternary salts are reduced to the JV-alkyl-4,5,6,7-tetra-hydrothienopyridine by sodium borohydride,45,48,89-91 and the azo-methine bond in dihydro derivatives (e.g. 69) is reduced by lithium aluminum hydride.47... 

Selective reduction of either the pyridine or the benzene rings in quinolines and isoquinoline can be achieved the heterocyclic ring is reduced to the tetrahydro level by sodium cyanoborohydride in acid solution,by sodium borohydride in the presence of nickel(II) chloride, by zinc borohydride," or, traditionally, by room temperature and room pressure catalytic hydrogenation in methanol. However, in strong acid solution it is the benzene ring which is selectively saturated " longer reaction times can then lead to decahydro-derivatives. 

In another variant of the Niementowski reaction, it was found that this transformation can be carried out under relatively mild, base-catalyzed conditions. Since a variety of substituted anthranilamides (29) can be prepared by a regiospecific ortho metalation-amination sequence, this method appears to be a very versatile modification of the Niementowski quinoline synthesis. Lithiation of 28 with 5-butyllithium was followed by treatment with tosyl azide. Reduction of the azide with sodium borohydride under phase transfer conditions furnished 29. After conversion of 29 into the corresponding imine 30, treatment of 30 with LDA afforded 31 in good yield. 

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