Reduction by sodium and alcohols

Ladenburg s preparation of piperidine from pyridine14 will be described as an example Pyridine (20 g) in anhydrous ethanol (150 g) is placed in a round-bottomed flask under a reflux condenser and warmed on the water-bath. Then sodium pieces (75 g) are added not too slowly. As soon as the reaction slackens or sodium ethoxide separates, more ethanol is added and the reaction is brought to conclusion as fast as possible. When all the sodium has been consumed, the mixture is allowed to cool, treated with an equal volume of water, and distilled in steam. The distillate is neutralized with hydrochloric acid and evaporated to dryness. Piperidine hydrochloride is obtained as residue in almost quantitative yield and can be recrystallized from ethanol. 

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Its low specific gravity indicates that it is an open-chain compound, and from its easy reduction by sodium and alcohol, into dihydroaplotaxene, and by hydrogen and platinum black into normal heptadecane OjjHj,., it is evident that aplotaxene is a tetraolefinic normal chain hydrocarbon. 

This assumption of Pauly s was confirmed by Knoop and Windaus, who found that histidine is resistant to reduction by sodium and alcohol whereas the pyrimidine rii is very unstable towards this reagent. On reducing Frankel s oxydesaminohistidine, which is obtained from histidine by the action of nitrous acid, they obtained /8-imidazole-propionic acid. This compound was identical with the synthetical product prepared from glyoxylpropionic acid, ammonia and formaldehyde — ... 

CH—CH=CH—CH—OH to give desoxycodeine-A [lxxix], which is known to give [lxxiv] and [lxxv] on sodium and alcohol reduction [281, 425]. (5 6-addition is improbable as it would involve an activating influence of the double bond not found in codeine, and 3 6-addition would yield desoxycodeine-E [lxxx] in which the double bond occupies a position that precludes reduction by sodium and alcohol [423].)... 

SchifT s bases A -Arylimides, Ar-N = CR2, prepared by reaction of aromatic amines with aliphatic or aromatic aldehydes and ketones. They are crystalline, weakly basic compounds which give hydrochlorides in non-aqueous solvents. With dilute aqueous acids the parent amine and carbonyl compounds are regenerated. Reduction with sodium and alcohol gives... 

Hydrocotarnine, C12HJ5O3N. HjO. This basic hydrolytic product of narcotine occurs in opium. It crystallises from light petroleum in colourless plates, m.p. 55-5-56-5°, and yields well-crystallised salts of which the hydrobromide, B. HBr, m.p. 236-7°, is sparingly soluble in water. On oxidation, hydrocotarnine is converted into cotarnine, and on reduction by sodium in alcohol it yields hydrohydrastinine (p. 164) by loss of a mcthoxyl group. 

If the a-phellandrene nitrite be heated with an alcoholic solution of potash, it is converted into nitrophellandrene, Ck,Hi5(N02). This bodyis converted by reduction with sodium and alcohol into tetrahydrocarvone, or by less energetic reduction with zinc and acetic acid, into carvotan-acetone. The relationship between these bodies is shown by the following formulas —... 

By the reduction of cedrone by means of sodium and alcohol, there is formed dihydro-isocedrol, CijH gO, boiling at 148° to 151° C. under a pressure of 9-5 mm. When cedrene is heated at 180° to 210° C. with hydriodic acid and red phosphorus, and the product formed is reduced by sodium and alcohol, a body Cj Hjg is obtained, which Semmler describes by the name dihydro-cedrene It boils at 116° to 122° C. under 12 mm. pressure its specific gravity is 0-9052 at 15° C. 

With phosphorus pentachloride it yields myrtenyl chloride, CioHi Cl, which by reduction with sodium and alcohol yields pinene. 

Dimethylpyrrolidine has been prepared by the hydrogenation of 5-amino-2,2-dimethylpyrroline-N-oxide or 5-imino-2,2-dimethylpyrrolidine in the presence of Raney nickel8 or by reduction with sodium and alcohol.8 This method is from unpublished work of the submitter. 

Generally, carboxylic acids are difficult to reduce either by catalytic hydrogenation or by sodium and alcohol. Nonetheless, reduction to primary alcohols proceeds smoothly with lithium aluminum hydride, LiAlH4 ... 

Rosenmund reduction of pyrazole acid chlorides to aldehydes never causes reduction of the ring.834,635,744,745 Attempts to prepare the aldehydes by the sodium amalgam reduction of the anilides, however, gave only traces of the required products,635 but the fate of the pyrazole ring is not recorded. It is the authors experience that pyrazoles unsubstituted on nitrogen are usually unaffected by sodium and alcohol, although the reduction to pyrazoline by sodium and alcohol at 130° and 20 atmospheres pressure has been patented.746 Reduction of Ar-phonyIpyrazoles is somewhat easier sodium and alcohol reduce them to A-phenylpyrazolines,77,78, 207,235, 447,567,... 

Decamethylenediamine has been obtained by reduction of sebaconitrile either catalytically 5 or by sodium and alcohol.7 It has also been obtained by hydrolysis of the condensation product from decamethylene iodide and phthalimide.8... 

Phenylethylamine has been made by a number of reactions, many of which are unsuitable for preparative purposes. Only the most important methods, from a preparative point of view, are given here. The present method is adapted from that of Adkins,1 which in turn was based upon those of Mignonac,2 von Braun and coworkers,3 and Mailhe.4 Benzyl cyanide has been converted to the amine by catalytic reduction with palladium on charcoal,5 with palladium on barium sulfate,6 and with Adams catalyst 7 by chemical reduction with sodium and alcohol,8 and with zinc dust and mineral acids.9 Hydrocinnamic acid has been converted to the azide and thence by the Curtius rearrangement to /3-phenyl-ethylamine 10 also the Hofmann degradation of hydrocinnamide has been used successfully.11 /3-Nitrostyrene,12 phenylthioaceta-mide,13 and the benzoyl derivative of mandelonitrile 14 all yield /3-phenylethylamine upon reduction. The amine has also been prepared by cleavage of N- (/3-phenylethyl) -phthalimide 15 with hydrazine by the Delepine synthesis from /3-phenylethyl iodide and hexamethylenetetramine 16 by the hydrolysis of the corre-... 

Naphthalene is reduced to 1,4-dihydronaphthalene by sodium and alcohol. Isomerization of this product to 3,4-dihydronaphthalene occurs with sodamide in liquid ammonia. Tetrahydronaphthalene (tetralin) is formed from naphthalene by sodium in amyl alcohol or by reduction with nickel-aluminum alloy and aqueous alkali. Catalytic hydrogenation of naphthalene can be stopped at the tetralin stage over copper chromite, Raney nickel, or alkali metal catalysts. cis-Decahydronaphthalene is produced by high-pressure hydrogenation of tetralin over Adams catalyst, whereas a mixture of cis- and trans-decalins is obtained from naphthalene under the same conditions. ... 

The reduction of esters by sodium and alcohol (Bouveault-Blanc) is widely used. An alcoholic solution of the ester is added to a large excess of sodium under benzene or toluene. The use of absolute alcohol is essential otherwise an appreciable quantity of acid is produced by saponification. Straight-chain primary alcohols containing up to thirty-five carbon atoms have been made by the reduction of the corresponding esters with sodium sand and n-butyl alcohol. An improved technique based on the mechanism of the reaction is described. By this procedure a xylene solution of the ester and the reducing alcohol is added to molten... 

The keto group of acetoacetic ester is protected as the ethylene ketal -during the reduction of the ester by sodium and alcohol. Hydrolysis of the ketal by acid then gives l-hydroxy-3-butanone in 44% over-all yield. ... 

Many amino alcohols have been made from esters of amino acids by catalytic reductions over Raney nickel and copper chromite catalysts. The yields are generally better than those obtained by reduction with sodium and alcohol." The action of ammonia or amines on /8-keto... 

Many of the methods listed for the preparation of hydroxy acids (Table 47) have been used to prepare lactones directly. Reduction of levulinic acid, CHjCOCHjCHjCOjH, by sodium and alcohol or by catalytic hydrogenation over Raney nickel leads to "y-valerolactone. S-Captolactone is prepared in a similar manner from y-acetobutytic acid. Other S-lactones have been formed by catalytic hydrogenation of the corresponding aldehydo... 

Reduction may also be brought about by sodium and alcohol, although extensive cleavage, of the cyanide group may occur, viz., RCN— RH + NaCN. Lithium aluminum hydride has been successfully employed for the reduction of aliphatic and aromatic nitriles as well as several cyanides in the thiophene series. ... 

Hydrogenation of -codeine in dilute acetic acid [65] or electrolytic reduction [55] affords dihydro- -codeine-B [xxv] obtained together with dihydro-i/r-codeine-C [xxvm] by reduction with sodium and alcohol [66]. These two compounds suffer Hofmann degradation in the usual way giving, respectively, dihydro-e-codeimethine-B [xxvi] [55, 60] and dihydro-e-codoimothine-C [xxix] [00], the latter also being... 

R = OMe] and on reduction with sodium and alcohol yields dihydro- r-codeine-C methyl ether [xxxix, R = OMe] [53]. Such ethers are readily formed by heating a-chlorocodide with alcohols [52, 54] or with the sodium salts of phenols in alcohol [49, 51]. a-Chloromorphide gives y-isomorphine-8-ethers under similar conditions [55]. 

The non-phenolic dihydrodesoxycodeine-D [xin] is produced, together with tetrahydrodesoxycodeine [xiv], by the hydrogenation of desoxycodeine-C hydrochloride in glacial acetic acid over platinum oxide [6], but only tetrahydrodesoxycodeine is formed by hydrogenation of the base. Electrolytic reduction proceeds with opening of the cyclic ether and production of dihydrodesoxycodeine-B [xv], obtained together with dihydrodesoxycodeine-C [xvi] by reduction with sodium and alcohol [3, 10],... 

Desoxy codeine-A is doubtless also an intermediate in the reduction of a-chlorocodide by sodium and alcohol, being reduced as fast as it is formed to dihydrodesoxycodeines B [xv] and C [xvi]. The latter two compounds must be produced from desoxycodeine-C [ix] by competing... 

Hydrogenation in neutral or weakly acid solution with a palladium catalyst affords tetrahydro-i/r-codeinone [xxix] [7, 28] which is further reduced by sodium and alcohol to tetrahydro-i/r-codeine [xxx], the latter being obtained directly from i/r-codeinone by sodium and alcohol reduction. In no case do derivatives of allo-[Pg.171]

This undoubtedly corresponds to one of the epimeric pair codeine isocodeine and is allotted the structure [v] for the following reasons. It cannot be reduced catalytically as sufficient ethyl mercaptan to poison the catalyst is immediately evolved, but it can be reduced by sodium and alcohol to dihydrothebainol-A [vi] identical [3] with the product of the parallel (sodium amalgam) reduction of dihydrothebai-none [vn] [4-5] and dihydrocodeinone [vin] [6]. This is only evidence for the location of the —SEt group at C-6 in so far as the relationship between a- and /3-etbylthiocodide is known, as the conditions of reduction are precisely those known to cause the a —> /3 isomerization. 

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