Sodium aluminium amide

Finally, mention can be made of the more exceptional titrants for inert media, such as sodium triphenylmethane, lithium aluminium hydride and lithium aluminium amide. 

Reduction of the amide (123 R1 = R2 = OMe) with sodium aluminium hydride gave a mixture of the bases (125 R1 = R2 = OMe), (127), and (130),165 and the last of these lost carbon monoxide when heated with tris(tri-phenylphosphine)rhodium chloride in benzene to give the dimethyl ketal of 14/3-methylcodeinone, which could be hydrolysed to 14j8-methylcodeinone, the 7,8-dihydro-derivative of which proved to be identical with material previously prepared by a different route (see Volume 9, p. 116). The corresponding morphinone and dihydromorphinone have been prepared.164... 

This method is very useful for the construction of 1-substituted 3,4-dihydroisoquinolines, which if necessary can be oxidized to isoquinolines. A P-phenylethylamine (l-amino-2-phenylethane) is the starting material, and this is usually preformed by reacting an aromatic aldehyde with nitromethane in the presence of sodium methoxide, and allowing the adduct to eliminate methanol and give a P-nitrostyrene (l-nitro-2-phenylethene) (Scheme 3.17). This product is then reduced to the p-phenylethylamine, commonly by the action of lithium aluminium hydride. Once prepared, the p-phenylethylamine is reacted with an acyl chloride and a base to give the corresponding amide (R = H) and then this is cyclized to a 3,4-dihydro-isoquinoline by treatment with either phosphorus pentoxide or phosphorus oxychloride (Scheme 3.18). Finally, aromatization is accomplished by heating the 3,4-dihydroisoquinoline over palladium on charcoal. 

During studies on the total synthesis of Aspidosperma type alkaloids, unexpected difficulty was encountered in attempts to reduce the amide carbonyl group of the intermediate 1. Thus, many attempts to reduce 1 with lithium aluminium hydride resulted in reduction of both the amide carbonyl group and the C=C double bond. In an effort to circumvent this problem 1 was reacted with hot phosphorus oxychloride and the intermediate thus obtained treated with sodium borohydride in anhydrous methanol. The product which was isolated, however, was the pentacyclic compound 2, which was obtained in 50% yield. 

One of the starting materials, the bromoindolinemesylate 183 was obtained from the commercially available 5-hydroxyindole by mesylation followed by successive treatment of the resulting indole derivative with sodium cyanoborohydride and bromine. Coupling of 183 with the known boronic acid 184 in the presence of zero valent palladium complex led directly to the lactam 185, the intermediate carbinolamine 186 formed initially in the reaction suffering facile aerial oxidation during work-up. On reduction with sodium (2-methoxyethoxy)aluminium-hydride, the amide 185 yielded the aminophenol 187 which on chromatography underwent oxidative aromatisation to 182 in 54% yield. 

Thioamides (86) are readily reduced to amines (93) (Scheme 50). The reduction generally occurs more easily than with amides and can be achieved with a variety of reducing agents, e.g. metal-acid, sodium amalgam, lithium aluminium hydride or Raney nickel. 

Phosgene reacts, sometimes violently, with a large number of common inorganic (Chapter 9) and organic (Chapter 10) substances. Hazardous reactions with lithium, sodium, potassium, aluminium, lithium amide, hexa-2,4-diyn-l, 6-diol, propan-2-ol, and hexafluoropropene have been mentioned specifically [1787]. Mixtures of potassium and phosgene are reported to explode when subjected to shock [1913a]. In addition, phosgene... 

Two novel complex hydrides are likely to find applications in steroid chemistry lithium perhydro-9b-boraphen yl hydride affords unusually high proportions of axial alcohols in model compounds sodium bis(methoxyethoxy)aluminium dihydride, Na (MeOCH2CH20)JAlH2, a very safe and convenient substitute for lithium aluminium hydride, readily reduces not only ketones but also acids, nitro-compounds, oximes, amides, lactones, etc. An improved procedure for Clemmensen reduction of steroid ketones involves saturating an ethereal solution with hydrogen chloride while stirring with zinc. 5a-Cholestane was obtained from the 3-one in 89% yield. ... 

A common intermediate in the synthesis of benzo[c]phenanthridines is the 2-aryl-l-tetralone, which provides rings A, B, and D of the alkaloid nucleus. In 1973, two independent research groups reported the synthesis of nitidine via the 3,4-dihydro-2-(3,4-dimethoxyphenyl)-6,7-methylenedioxy-(2/7)-naphthalone 29 (Scheme 2). The synthesis of this intermediate was arrived at by two different routes. Kametani ei al. (73JHC31) reduced 3-(3,4-methylenedioxyphenyl)proprionate 21 to the corresponding alcohol 22 with lithium aluminium hydride, which was then converted to the chloride 23 with thionyl chloride. After production of the nitrile 24 by reaction with sodium cyanide and subsequent hydrolysis to the carboxylic acid 25, Friedel-Crafts cyclization of the acid chloride 26 afforded the tetralone intermediate 27. Reaction with l-bromo-3,4-dimethoxybenzene 28 in the presence of sodium amide yielded the tetralone intermediate 29 in an overall yield of 4%. 

Lithium aluminium hydride is a more powerful reducing agent than sodium borohydride and reduces most of the commonly encountered organic functional groups (see Table 7.3). It reacts readily with water and other compounds that contain active hydrogen atoms and must be used under anhydrous conditions in a non-hydroxylic solvent diethyl ether and THF are commonly employed. Lithium aluminium hydride has found widespread use for the reduction of carbonyl compounds. Aldehydes, ketones, esters, carboxylic acids and lactones can all be reduced smoothly to the corresponding alcohols under mild conditions. Carboxylic amides are converted into amines or aldehydes, depending on the conditions and on the... 

Selective reduction of aldehydes in the presence of ketones can be effected with tetra-n-butylammonium triacetoxyborohydride and other reagents. Although lithium aluminium hydride is used most commonly for the reduction of carboxylic esters, sodium borohydride can provide some useful selectivity and its reactivity is enhanced in the presence of metal salts. For example, reduction of carboxylic esters in the presence of carboxylic amides is possible using sodium borohydride and calcium chloride. 

For the removal of the proton at the a-carbon atom, besides alkaline hydroxides or alcoholates in lower alcohols (methanol or ethanol), sodium or potassium amide in liquid ammonia, diethyl ether, toluene or benzene, sodium hydride in a toluene-THF mixture, or aluminium tri-r-butoxide in benzene have been used as bases. Aldol condensations have been performed over a temperature range between -33°C and around 100°C. The reaction times can vary from some minutes to several days. The yields of the aldol condensation reactions are enhanced by applying a large excess of the ketone. This can even lead to complete replacement of any other solvent by the keto compound. 

Louis Bouveault (Nevers, ii February 1864-Paris, 6 September 1909), assistant professor in the Paris Faculty of Sciences, worked out methods for the conversion of nitriles or amides to acids, the synthesis of aromatic aldehydes and acids by the use of aluminium chloride, the synthesis of aldehydes from nitro-olefins, and the reduction of aldehydes, ketones, and esters to alcohols by boiling with alcohol and sodium. ... 

Alternatively these compounds may be obtained from dialkylamino phosphine halides by reaction with alkyl magnesium halides ((7.168) and (7.169)), aluminium alkyls ((7.170) and (7.171)) or organolithium derivatives ((7.172) and (7.173)). Phenylphosphinous chloride can be condensed with a sodium amide derivative (7.174) or a trimethylsilyl derivative (7.175) to give a phosphinous amide. 

The unsymmetrical acetylene (43) yields cw-(CF3)iN-CH CH-CFs with hydrogen-Raney nickel at 20 C, undergoes slow hydration in the presence of aqueous sulphuric acid and mercuric sulphate at 53 °C to give the propion-amide (CFa)jN CO-CH2 CF3, combines with methanol in the presence of sodium methoxide to yield a 96 4 mixture of (CF3)aN-C(OMe) CH CF3 and (CFj)jN CH C(OMe)-CF3, and when subjected to photochemical hydrobromination gives the 1 1 adduct (CFs)jN-CH CBr-CF3 almost quantitatively. Slow electrophilic hydrobromination of the acetylene can be achieved in the presence of aluminium bromide at 20 °C, the main product being the same as that obtained in the photochemical reaction (H trans to Br in each case) this unexpected direction of addition is suggested to result... 

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