Lithium bromide hydride

Some instances of incomplete debromination of 5,6-dibromo compounds may be due to the presence of 5j5,6a-isomer of wrong stereochemistry for anti-coplanar elimination. The higher temperature afforded by replacing acetone with refluxing cyclohexanone has proved advantageous in some cases. There is evidence that both the zinc and lithium aluminum hydride reductions of vicinal dihalides also proceed faster with diaxial isomers (ref. 266, cf. ref. 215, p. 136, ref. 265). The chromous reduction of vicinal dihalides appears to involve free radical intermediates produced by one electron transfer, and is not stereospecific but favors tra 5-elimination in the case of vic-di-bromides. Chromous ion complexed with ethylene diamine is more reactive than the uncomplexed ion in reduction of -substituted halides and epoxides to olefins. ... 

The azido mesylate may also be reduced with lithium aluminum hydride in the same manner as previously described for iodo azide reductions. The sodium borohydride/cobalt(II)tris(a,a -dipyridyl)bromide reagent may be used, but it does not seem to offer any advantages over the more facile lithium aluminum hydride or hydrazine/Raney nickel procedures. 

Mescaline, a hallucinogenic amine obtained from the peyote cactus, has been synthesized in two steps from 3,4,5-trimethoxybenzyl bromide. The first step is nucleophilic substitution by sodium cyanide. The second step is a lithium aluminum hydride reduction. What is the structure of mescaline ... 

Alternatively, 25.0 g of either 3j3,5a-dihydroxy-17a-methyl-17j3-carbomethoxyandrostan-6-one (Ilia) or 25.0 g of its 3)3-acetate (Hlb), are dissolved in dry tetrahydrofuran (1,250 ml, freshly distilled over lithium aluminum hydride) and dry benzene (2,000 ml) is added. Methyl magnesium bromide in ether solution (3 M, 750 ml) is added to the stirred solution and the resulting mixture is stirred at room temperature for 16 hours. An additional quantity of methyl magnesium bromide solution in ether (2M, 375 ml) is added, and 1,250 ml of the solvent mixture are distilled off. The resulting mixture is refluxed for 5 hours and worked up as described above, yielding compound (V) as a colorless oil. 

Treatment of 19b with phenylmagnesium bromide gives diphenylacetylene (66) and the salt of benzenesulfmic acid Lithium aluminium hydride reacts with 19b similarly. These ring-opening reactions are similar to the reactions of organometallic reagents with the analogous thiirane dioxides (equation 17 above). 

Lithium aluminium hydride has been used to cleave a furfuryl group from a range of furfurylphosphonium salts, which are easily accessible by the reactions of trimethylsilylphosphines with furfuryl bromide. Thus, e.g., the reaction of diphenyltrimethyl-silylphosphine yields the salt (52) which, on treatment with... 

Preparation of the quaternary anticholinergic agent benzilonium bromide (47) is begun by conjugate addition of ethylamine to methylacrylate, giving aminoester 42. Alkylation of 42 with methyl bromo-acetate leads to diester 43, which is transformed into pyrrolidone 44 by Dieckmann cyclization, followed by decarboxylation. Reduction of 44 by lithium aluminum hydride leads to the corresponding amino-alcohol (45). Transesterification of alcohol 45 with methyl benzilate leads to 46. Benzilonium bromide (47) is obtained by alkylation of ester 46 with ethyl bromide. 2... 

In this series, too, replacement of the N-methyl by a group such as cyclopropylmethyl leads to a compound with reduced abuse potential by virtue of mixed agonist-antagonist action. To accomplish this, reduction of 24 followed by reaction with tertiary butylmagnesium chloride gives the tertiary carbinol 27. The N-methyl group is then removed by the classic von Braun procedure. Thus, reaction with cyanogen bromide leads to the N-cyano derivative (28) hydrolysis affords the secondary amine 29. (One of the more efficient demethylation procedures, such as reaction with ethyl chloroformate would presumably be used today.) Acylation with cyclopropylcarbonyl chloride then leads to the amide 30. Reduction with lithium aluminum hydride (31) followed by demethylation of the phenolic ether affords buprenorphine (32).9... 

Several total syntheses of antirhine (11) and 18,19-dihydroantirhine (14) have been developed during the last decade. Wenkert et al. (136) employed a facile route to ( )-18,19-dihydroantirhine, using lactone 196 as a key building block. Base-catalyzed condensation of methyl 4-methylnicotinate (193) with methyl oxalate, followed by hydrolysis, oxidative decarboxylation with alkaline hydrogen peroxide, and final esterification, resulted in methyl 4-(methoxycar-bonylmethyl)nicotinate (194). Condensation of 194 with acetaldehyde and subsequent reduction afforded nicotinic ester derivative 195, which was reduced with lithium aluminum hydride, and the diol product obtained was oxidized with manganese dioxide to yield the desired lactone 196. Alkylation of 196 with tryptophyl bromide (197) resulted in a pyridinium salt whose catalytic reduction... 

Direct hydrogenation of key intermediate 248 over the Adams catalyst and subsequent lithium aluminum hydride reduction yielded the two stereoisomeric alcohols 256 and 257, which were separately transformed to ( )-corynantheal (258) and ( )-3-epicorynantheal (259), respectively, by Moffatt oxidation, followed by Wittig reaction with methyltriphenylphosphonium bromide and, finally, by demasking the aldehyde function (151, 152). 

Corynantheidol (255) has been prepared by Hanaoka et al. (155), who started from piperideine derivative 268 and tryptophyl bromide (197). The key cyclization step, resulting in indolo[2,3-a]quinolizine 270 as the major product besides 271, was carried out by mercuric acetate oxidation in the presence of the disodium salt of ethylenediaminetetraacetic acid (EDTA), followed by sodium borohydride reduction. Finally, lithium aluminum hydride reduction of 270 provided ( )-corynantheidol in good yield (155). 

N-Methylethylamine has been prepared by heating ethyl-amine with methyl iodide in alcohol at 100° 3 by the hydrolysis of N-methyl-N-ethylarenesulfonamides,4-5 -nitroso-N-methyl-N-ethylaniline,6 or methylethylbenzhydrylidene ammonium iodide 7 by catalytic hydrogenation of ethyl isocyanate or ethyl isocyanide 8 and by the reduction of ethyl isocyanate by lithium aluminum hydride,9 of N-methylacetisoaldoxime by sodium amalgam and acetic acid,10 or of a nitromethane/ethylmagnesium bromide adduct by zinc and hydrochloric acid.11... 

Reduce 3,5-dimethoxybenzoic acid with lithium aluminum hydride to 3,5-dimethoxybenzyl alcohol (I), to 10.5 g (I) in 100 ml methylene chloride at 0° C add 15 g PBr3 warm to room temperature and stir for one hour. Add a little ice water and then more methylene chloride. Separate and then dry, evaporate in vacuum the methylene chloride. Add petroleum ether to precipitate about 11.5 g of the benzyl bromide (II). To 9.25 g (II), 15 g Cul, 800 ml ether at 0° C, add butyl (or other alkyl)-Li (16% in hexane), and stir for four hours at 0° C. Add saturated NH4C1 and extract with ether. Dry and evaporate in vacuum the ether (can distill 100/0.001) to get about 4.5 g olivetol dimethyl ether (HI) or analog. Distill water from a mixture of 90 ml pyridine, 100 ml concentrated HC1 until temperature is 210° C. Cool to 140 0 C and add 4.4 g (III) reflux two hours under N2. Cool and pour into water. Extract with ether and wash with NaHC03. Make pH 7 and dry, evaporate in vacuum to get 3.8 g olivetol which can be chromatographed on 200 g silica gel (elute with CHC13) or distill (130/0.001) to purify. 

B (Alternative) 20 g of the unrefluxed precipitate (ethyl-ester of (1)) from last part of step A in 100 ml ether. Add dropwise to a solution of 4 g lithium aluminum hydride in 900 ml ether at 0°. Reflux three hours and isolate the resulting tryptophol as described earlier. Dissolve 3 g of the tryptophol in 140 ml ether and stir at 0°. Add dropwise 1.8 g PBr3 in 30 ml ether and let stand sixteen hours at room temperature. Decant the ether and wash the precipitate with ether. Wash ether w ith water, NaHC03 and water, and dry, evaporate in vacuum the ether to get the bromide (recrystallize-ethanol). 2 g of the bromide and 1.5 g piperidine (or equimolar amount DEA. etc.) in 65 ml methanol and heat in sealed tube fifteen... 

The recent discovery that acetylated glycopyranosyl bromides may be reduced in high yields with lithium aluminum hydride to the corresponding 1,5-anhydroglycitols661 represents an improvement over the reductive desulfurization process and will doubtless make this class of compound even more readily available in the future. 

The ethylmagnesium bromide is prepared in dry tetrahydrofuran and stored no longer than 1 week in a 250-ml. tube fitted with a 3-way vacuum stopcock and a dropping buret. The solution is decanted into the buret, and the correct volume is transferred to the reaction flask with positive nitrogen pressure. The tetrahydrofuran is purified by distillation from lithium aluminium hydride. See Org. Syn., 46, 105 (1966), for warning regarding the purification of tetrahydrofuran. 

Alkyl bromides and especially alkyl iodides are reduced faster than chlorides. Catalytic hydrogenation was accomplished in good yields using Raney nickel in the presence of potassium hydroxide [63] Procedure 5, p. 205). More frequently, bromides and iodides are reduced by hydrides [505] and complex hydrides in good to excellent yields [501, 504]. Most powerful are lithium triethylborohydride and lithium aluminum hydride [506]. Sodium borohydride reacts much more slowly. Since the complex hydrides are believed to react by an S 2 mechanism [505, 511], it is not surprising that secondary bromides and iodides react more slowly than the primary ones [506]. The reagent prepared from trimethoxylithium aluminum deuteride and cuprous iodide... 

The difference in the reactivity of benzylic versus aromatic halogens makes it possible to reduce the former ones preferentially. Lithium aluminum hydride replaced only the benzylic bromine by hydrogen in 2-bromomethyl-3-chloro-naphthalene (yield 75%) [540]. Sodium borohydride in diglyme reduces, as a rule, benzylic halides but not aromatic halides (except for some iodo derivatives) [505, 541]. Lithium aluminum hydride hydrogenolyzes benzyl halides and aryl bromides and iodides. Aryl chlorides and especially fluorides are quite resistant [540,542], However, in polyfluorinated aromatics, because of the very low electron density of the ring, even fluorine was replaced by hydrogen using lithium aluminum hydride [543]. 

Lithium aluminum hydride reduced )J-azidoethylbenzene to j8-aminoethyl-benzene in 89% yield [600], The azido group was also reduced with aluminum amalgam (yields 71-86%) [149], with titanium trichloride (yields 54-83%) [601], with vanadous chloride (yields 70-95%) [217] Procedure 40, p. 215), with hydrogen sulfide (yield 90%) [247], with sodium hydrosulfite (yield 90%) [259], with hydrogen bromide in acetic acid (yields 84-97%) [232], and with 1,3-propanedithiol (yields 84-100%) [602]. Unsaturated azides were reduced to unsaturated amines with aluminum amalgam [149] and with 1,3-propane-dithiol [602]. 

Triphenylstannane reduced the double bond in dehydro-)J-ionone in 84% yield [872], Complex copper hydrides prepared in situ from lithium aluminum hydride and cuprous iodide in tetrahydrofuran at 0° [873], or from lithium trimethoxyaluminum hydride or sodium bis(methoxy-ethoxy)aluminum hydride and cuprous bromide [874] in tetrahydrofuran at 0° reduced the a,p double bonds selectively in yields from 40 to 100%. Similar selectivity was found with a complex sodium bis(iron tetracarbonyl)hydride NaHFe2(CO)g [875]. 

Since sodium borohydride usually does not reduce the nitrile function it may be used for selective reductions of conjugated double bonds in oc,/l-un-saturated nitriles in fair to good yields [7069,1070]. In addition some special reagents were found effective for reducing carbon-carbon double bonds preferentially copper hydride prepared from cuprous bromide and sodium bis(2-methoxyethoxy)aluminum hydride [7766], magnesium in methanol [7767], zinc and zinc chloride in ethanol or isopropyl alcohol [7765], and triethylam-monium formate in dimethyl formamide [317]. Lithium aluminum hydride reduced 1-cyanocyclohexene at —15° to cyclohexanecarboxaldehyde and under normal conditions to aminomethylcyclohexane, both in 60% yields [777]. 

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