Lithium aluminum hydride derivatives

Al—Ti Catalyst for cis-l,4-PoIyisoprene. Of the many catalysts that polymerize isoprene, four have attained commercial importance. One is a coordination catalyst based on an aluminum alkyl and a vanadium salt which produces /n j -l,4-polyisoprene. A second is a lithium alkyl which produces 90% i7j -l,4-polyisoprene. Very high (99%) i7j -l,4-polyisoprene is produced with coordination catalysts consisting of a combination of titanium tetrachloride, TiCl, plus a trialkyl aluminum, R Al, or a combination of TiCl with an alane (aluminum hydride derivative) (86—88). 

Cationic rings are readily reduced by complex hydrides under relatively mild conditions. Thus isoxazolium salts with sodium borohydride give the 2,5-dihydro derivatives (217) in ethanol, but yield the 2,3-dihydro compound (218) in MeCN/H20 (74CPB70). Pyrazolyl anions are reduced by borohydride to pyrazolines and pyrazolidines. Thiazolyl ions are reduced to 1,2-dihydrothiazoles by lithium aluminum hydride and to tetrahydrothiazoles by sodium borohydride. The tetrahydro compound is probably formed via (219), which results from proton addition to the dihydro derivative (220) containing an enamine function. 1,3-Dithiolylium salts easily add hydride ion from sodium borohydride (Scheme 20) (80AHC(27)151). 

In most other reactions the azolecarboxylic acids and their derivatives behave as expected (cf. Scheme 52) (37CB2309), although some acid chlorides can be obtained only as hydrochlorides. Thus imidazolecarboxylic acids show the normal reactions they can be converted into hydrazides, acid halides, amides and esters, and reduced by lithium aluminum hydride to alcohols (70AHC(12)103). Again, thiazole- and isothiazole-carboxylic acid derivatives show the normal range of reactions. 

Isopyrazole quaternary salts (363) are key intermediates leading to the highly substituted A -pyrazolines. Lithium aluminum hydride gives the pentasubstituted derivatives (364 R = H) and Grignard reagents provide access to the fully substituted A -pyrazolines (364 R H) (68BSF3866, 70BSF1121). 

The photochemical cyclization of anthranilonitriles (190 Section 4.04.2.1.2) yields indazoles (72CC126). Reduction of o-benzonitrile with lithium aluminum hydride yields indazole (75ACS(B)1089). 2-Aminoindazole (576) has been prepared in 94% yield from (574) via the o-phthaloyl derivative (575 = o-phthaloyl) (72JOC2351). Similarly, treatment... 

Methylindole has also been prepared by lithium aluminum hydride reduction of 1-methylindoxyl. Compounds giving rise to NH absorption in the infrared (indole, skatole) can be completely removed by refluxing the crude 1-methylindole over sodium for 2 days and then distilling the unreacted 1-methylindole from the sodio derivatives and tarry decomposition products. 

Both the 4- (38) and 6-(31) nitrimines are reduced with sodium boro-hydride to the corresponding y5-nitramine derivatives, e.g., (41)], which are methylated with methyl iodide and potassium carbonate. The A -methyl derivative is reduced in modest yield to the 5a-fluoride (43) with lithium aluminum hydride. 

To overcome this, the A -acetyl group is reduced with lithium aluminum hydride. The resulting basic enamine then reacts extremely rapidly and selectively with peracid. The derived epoxide is hydrolyzed very easily with alkali during the workup. 

Replacement of an unactivated lone chlonne with hydrogen is also accom-phshed in good yield with lithium aluminum hydride. Chlorofluoronorcaranes are selectively dechlormated to give hydro derivatives, largely with retention of configuration The related monodeutcronorcaranes are prepared with lithium aluminum deutende [27] (equations 20a and 20b). 

Methyl-4-hydroxyquinazoline reacts with organic halides, in the presence of sodium methoxide, to give 3-substituted 2-methyl-4(3i/)-quinazolinones. The 0-acetyl derivative of 4-hydroxyquinazoline has been prepared under anhydrous conditions and gives the hydroxy compound with water or with lithium aluminum hydride. The N-3 acetyl derivative, however, is more stable and gives 3-methyl-4(31/)-quinazolinone with lithium aluminum hydride. ... 

R" = CH20H). The use of sodium borohydride in place of lithium aluminum hydride did not lead to ring closure but to 3-[j8-(A-l,2,3,4-tetrahydroisoquinolyl)ethyl]indole derivatives (53). Reductive cyclization by means of lithium aluminum hydride of the j8-(3-indolyl)ethyl-l-isoquinoline (52) to the pentacyclic tetrahydro-j8-carboline 49 (R = R = R" = H) has been reported. Strong acid alone sufficed to convert 52 into 54, the 0x0 derivative of 49. ... 

Tetrahydro derivatives are formed when either quinoxaline or 6-chloroquinoxaline is reduced with lithium aluminum hydride in ethereal solution. Similar reduction of 2,3-dimethylquinoxaline gives the meso-(cts)-1,2,3,4-tetrahydro derivative. This is shown to be a stereospecific reduction since lithium aluminum hydride does not isomerize the dl-(trans)-compound. Low temperature, platinum catalyzed, hydrogenation of 2,3-dimethylquinoxaline in benzene also gives meso (cis) -l,2,3,4-tetrahydro-2,3-dimethylquinoxaline. ... 

The Meerwein-Ponndorf-Verley procedure has largely been replaced by reduction procedures that use lithium aluminum hydride, sodium borohydride or derivatives thereof. The Meerwein-Ponndorf-Verley reduction however has the advantage to be a mild and selective method, that does not affect carbon-carbon double or triple bonds present in the substrate molecule. 

Synthesis of the CNS depressant/tranquil izer tioperidone (59) begins by alkylation of piperazine derivative with 4-chlorobutyronitrile to give Lithium aluminum hydride... 

A substituted benzoic acid serves as precursor for the nontricyclic antidepressant bipena-mol (175). Selective. saponification of ester 171 afford.s the half-acid 172. Reaction of the acid chloride derived from this intermediate (173) with ammonia gives the amide 174. Reduction of the last by means of lithium aluminum hydride gives bipenamol (175) [44]. 

A second example exploits the fact that the mixed hydride reagent is capable of hydrogenolysis of certain carbon-oxygen bonds. Thus, treatment of cyclohexanone ketal (Chapter 7, Section IX) with lithium aluminum hydride-aluminum chloride results in the rupture of a C-O bond to give the oxyethanol derivative. 

The dicyclobutanecarbonyl derivative (136.7 g) was dissolved in 200 ml of tetrahydrofuran and added dropwise to a suspension of 34.2 g of lithium aluminum hydride in 1 liters of tetrahydrofuran. The temperature of the mixture rose to reflux during the addition. Reflux was maintained for 2 hours after the addition was completed. After cooling, 110 ml of ethyl acetate was added dropwise, followed by 30 ml of water, followed by a solution of 53 g of ammonium chloride in 125 ml of water. The resulting mixture was filtered and the inorganic precipitate was washed with methanol. Evaporation of the combined filtrates gave 66 g of N-cyclobutYlmethyl-14-hYdroxydihydronormorphinone, melting point 229 to 231 . ... 

Woodward s strychnine synthesis commences with a Fischer indole synthesis using phenylhydrazine (24) and acetoveratrone (25) as starting materials (see Scheme 2). In the presence of polyphosphor-ic acid, intermediates 24 and 25 combine to afford 2-veratrylindole (23) through the reaction processes illustrated in Scheme 2. With its a position suitably masked, 2-veratrylindole (23) reacts smoothly at the ft position with the Schiff base derived from the action of dimethylamine on formaldehyde to give intermediate 22 in 92% yield. TV-Methylation of the dimethylamino substituent in 22 with methyl iodide, followed by exposure of the resultant quaternary ammonium iodide to sodium cyanide in DMF, provides nitrile 26 in an overall yield of 97%. Condensation of 2-veratryl-tryptamine (20), the product of a lithium aluminum hydride reduction of nitrile 26, with ethyl glyoxylate (21) furnishes Schiff base 19 in a yield of 92%. 

---