Lithium propylamine

The lithium- -propylamine reducing system has been found capable of reducing julolidine (113) to /d -tetrahydrojulolidine (114, 66% yield) and 1-methyl-1,2,3,4-tctrahydroquinoline to a mixture of enamines (87% yield), l-methyl-J -octahydroquinoline (115) and 1-methyl-al -octahydro-quinoline (116) 102). This route to enamines of bicyclic and tricyclic systems avoids hydroxylation, which occurs during mercuric acetate oxidation of certain bicyclic and tricyclic tertiary amines 62,85 see Section III.A). 

The lithium-propylamine reducing system has been found capable of reducing julolidine to a mixture of enamines377. Selective reduction of lactams with... 

Methyl-1,2,3,4-tetrahydro-chinolin wird durch Lithium/Propylamin in 50%-iger Ausbeute zu einem Gemisch aus 1-Methyl-1,2,3,4,4a,5,6,7- und 1-Methyl-... 

Methyl-l,2,3,4-tetrahydro-isochinolin liefert mit Lithium/Propylamin 2-Methyl-... 

Carbazol reagiert mit Lithium/Propylamin in 90%-iger Ausbeute zu 1,2,3,4-Tetrahy-dro-carbazol2 (F 119—120°). 

Methyl-carbazol bildet mit Lithium/Propylamin jedoch 9-Methyl-J, 2,3,4,4a,9a-hexahydro-carbazol2 (71% d.Th., Kp 125-135°), wahrend mit Natrium/Ammo-niak/Ammoniumchlorid 9-Mcthyl-l,4-dihydro-carbazol21 (F 93-95°) und mit Na-trium/Ammoniak/Athanol 9-Methyl-l,4,5,8-tetrahydro-carbazol3 (F 142-144°) entste-hen ... 

A recent modification of this technique utilizes A,A-d2-propylamine as the solvent for the lithium reduction, thereby eliminating the inconveniences associated with the preparation and handling of liquid deuterioammonia. Under these conditions the reaction can be carried out at room temperature and less overreduction of the carbonyl group is observed. For example, the reduction of A" -3-keto steroids (159) under these conditions, followed by back exchange in protic media, leads to the corresponding 5a-di-3-ketones (160) which exhibit good isotopic purity. ... 

A general procedure for the reduction with lithium in A,A-d2-propylamine is described by Fetizon and Gore, )... 

Treatment of oc-cyclopropyl ketones with lithium in a mixture of N,N-d2 propylamine and hexamethylphosphortriamide is a recently reported method for deuterium labeling via reductive ring opening. This reaction provides y-labeled ketones in good yield (70-100%) and isotopic purity (85-93%). 

Reduction of a,/3-unsaturated to saturated ketones was further achieved by electrolysis in a neutral medium using copper or lead cathodes (yields 55-75%) [766], with lithium in propylamine (yields 40-65%) [876], with potassium-graphite clathrate CgK (yields 57-85%) [807], and with zinc in acetic acid (yield 87%) [688]. Reduction with amalgamated zinc in hydrochloric acid (Clemmensen reduction) usually reduces both functions [877]. 

One gram of silver /3-alumina (see above) is placed into a fused quartz test tube about 2 cm in diameter and about 14 cm long. Five grams of lithium chloride is added. It is important that the lithium chloride used have a very low content of other alkali metal impurities, except Cs, since the ion exchange equilibria greatly favor the presence of the other alkali metals in the /3-alumina crystals over lithium. Essentially all of the impurity ends up in the crystals. The fused-quartz test tube is heated to 650° in a furnace. For crystals 1-cm in diameter the time to reach 99% equilibrium is approximately 16 hours. The molten salt is decanted and the crystals are allowed to cool to room temperature. Methyl alcohol containing about 10% propylamine or ethylenediamine is used to wash the product and thereby remove the silver chloride and residual lithium salts. The sample is dried at 400° and stored in a dessicator. The lithium /3-alumina crystals contain less than 0.05% Ag. If the lithium chloride used contains a trace of sodium or potassium, it can be prepurified by treatment with silver /3-alumina at 650°. Each gram of silver /3-alumina will remove about 30 mg of sodium from the melt. The molten lithium chloride, after decantation from the pretreatment silver /3-alumina, can be used to prepare the product, lithium 0-alumina. 

The preparation of this compound from silver (3-alumina is similar to the preparation of lithium /3-alumina. The melt consists of 10 g of potassium chloride. The exchange temperature is 800°. For crystals with diameters of 1 cm it takes about 16 hours to reach 99% of equilibrium. The potassium salts used should contain less than 0.1 wt % sodium. After decantation of the melt the crystals are washed with water containing 2% propylamine or ethylenediamine to remove residual potassium salts and silver chloride. The sample is dried at 200°. The potassium 0-alumina contains less than 0.05% silver. 

To a dry flask containing 415 ml of n-propylamine and 10.15 gm (1.45 gm-atoms) of chopped lithium wire segments is added, with stirring, 21.3 gm (0.125 mole) of l-methyl-l,2,3,4-tetrahydroquinoline, and the mixture is stirred for 16J hr under a nitrogen atmosphere. The un reacted lithium is removed, the excess n-propylamine is distilled from the flask, the semisolid residue is cooled in an ice bath, overlaid with ether, and then neutralized slowly with solid ammonium chloride. The mixture is cautiously diluted with water, the ether layer separated, the water layer extracted with ether, the ether layers combined, dried, concentrated, and the residue is distilled to alford 19.8 gm... 

Some strategies used for the preparation of support-bound thiols are listed in Table 8.1. Oxidative thiolation of lithiated polystyrene has been used to prepare polymeric thiophenol (Entry 1, Table 8.1). Polystyrene functionalized with 2-mercaptoethyl groups has been prepared by radical addition of thioacetic acid to cross-linked vinyl-polystyrene followed by hydrolysis of the intermediate thiol ester (Entry 2, Table 8.1). A more controllable introduction of thiol groups, suitable also for the selective transformation of support-bound substrates, is based on nucleophilic substitution with thiourea or potassium thioacetate. The resulting isothiouronium salts and thiol acetates can be saponified, preferably under reductive conditions, to yield thiols (Table 8.1). Thiol acetates have been saponified on insoluble supports with mercaptoethanol [1], propylamine [2], lithium aluminum hydride [3], sodium or lithium borohydride, alcoholates, or hydrochloric acid (Table 8.1). 

Ruff et al. in a series of publications described the synthesis of amine complexes of aluminum hydride [32, 33]. Their study investigated the reaction of these materials with typical Lewis bases in order to define the conditions for the stability of aluminum hydride derivatives in which the aluminum atom exhibits a coordination number of five. They first described methods for making tertiary alkyl amine complexes of aluminum hydride utilizing lithium aluminum hydride and an amine hydrochloride. A finely ground lithium aluminum hydride was placed together with trimethylammonium chloride (ratio 1 2). They prepared other trialkylamine alanes and the N-dialkylaminoalanes, in a similar fashion. These adducts of alane were found to sublime readily at temperatures up to 40 °C except for the tri-n-propylamine alane, which sublimed very slowly and could also be recrystallized from hexane at — 80 °C. 

Amides are more conveniently reduced with lithium aluminum hydride in ether solution to yield amines with the same carbon content, e.g, tri-ethylamine from N,N-diethylacetamide (50%) and ethyl-n-propylamine from N-ethylpropionamide (53%). ° The same conversion has been accomplished by an electrolytic reduction. ... 

Unsymmetrical secondary amines are readily prepared in good yields by the catalytic reduction of Schiff bases at moderate temperatures in high-or low-pressure equipment. Many examples have been cited. The intermediate imines are prepared from primary amines and aldehydes—very seldom from ketones—and may be used without isolation (cf. method 431). For the preparation of aliphatic amines, e.g., ethyl-w-propylamine and n-butylisoamylamine, a prereduced platinum oxide catalyst is preferred with alcohol as the solvent. Schiff bases from the condensation of aromatic aldehydes with either aromatic or aliphatic amines are more readily prepared and are reduced over a nickel catalyst. In this manner, a large number of N-alkylbenzylamines having halo, hydroxyl, or methoxyl groups on the nucleus have been made. Reductions by means of sodium and alcohol and lithium aluminum hydride have also been described,... 

Intramolecular animations of the benzyne intermediates are also possible, although the yields are lower than those of the intermolecular aminations. For example, iV-methyl tctra-hydroquinoline was formed from Af-methyl-3-(m-chlorophenyl)propylamine in 49% yield upon reaction with the combination of phenyl lithium and lithium diethylamide. The yield from the ortho-chloro analog was much lower, likely because the formation of the benzyne intermediates is hindered by steric effects in o-chloro compounds24. 

P. E. Koenig, J. M. Morris, E. 3. Blanchard, and P. S. Mason, 3. Org.,76,4111 (1961) Lithium-n-Propylamine. Leonard et al. have used this reducing combination to prepare enamines which are stable to hydrolysis because the functional group is contained in abi- or tricyclic system. Examples ... 

Use Air conditioning, catalyst in acetal formation, solubilizes lithium in propylamine, nucleonics. 

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