Preparation butyllithiums

Allene 1,1-Dibromocyclopropane is dissolved in ether under nitrogen, and the solution is cooled to —10°. An excess of an ethereal solution of freshly prepared butyllithium is dropped in with stirring, after which the solution is kept for a further 10 min at —10° and then treated cautiously with water. The ethereal layer is separated, washed several times with water, and dried over magnesium sulfate. The solvent is distilled off and the allene is isolated from the residue by preparative gas chromatography. 

In some experiments the presence of hexane is undesirable in view of the volatility of the products. In these cases one can use butyllithium in pentane (prepared from butyllithium in hexane, by replacing the hexane with pentane see Exp. 10) or ethyllithium in diethyl ether, prepared from ethyl bromide and 11thiurn (see Exp. 1). 

The alkylations proceeded much more slowly, when ethyl- or butyllithium in diethyl ether, prepared from the alkyl bromides, had been used for the metallation of allene, in spite of the presence of THF and HMPT as co-solvents. 

In a similar way HjC=C=C(0CH3)(SnBuj), n 1.4955 (undistilled) was prepared in almost quantitative yield from 0.12 mol of butyllithium in 75 ml of hexane and 75 ml of diethyl ether, 0.14 mol of methoxyallene and 0.10 mol of tributyl-tin chloride. The product contained 8-10% of an impurity, possibly Bu3Sn-CH2CEC-0CH3. 

Another o-aminobenzyl anion equivalent is generated by treatment of A-trimethylsilyl-o-toluidinc with 2.2 eq. of n-butyllithium. Acylation of this intermediate with esters gives indoles[2]. This route, for example, was used to prepare 6.2D, a precursor of the alkaloid cinchonamine. 

Lithium diisopropylamide is commercially available Alternatively it may be prepared by the reaction of butyllithium with [(CH3)2CH]2NH (see Problem 14 4a for a related reaction)... 

Methylthiophene is metallated in the 5-position whereas 3-methoxy-, 3-methylthio-, 3-carboxy- and 3-bromo-thiophenes are metallated in the 2-position (80TL5051). Lithiation of tricarbonyl(i7 -N-protected indole)chromium complexes occurs initially at C-2. If this position is trimethylsilylated, subsequent lithiation is at C-7 with minor amounts at C-4 (81CC1260). Tricarbonyl(Tj -l-triisopropylsilylindole)chromium(0) is selectively lithiated at C-4 by n-butyllithium-TMEDA. This offers an attractive intermediate for the preparation of 4-substituted indoles by reaction with electrophiles and deprotection by irradiation (82CC467). 

Lithioisothiazoles are readily prepared by the action of butyllithium, and the isothiazole ring is desulfurized by Raney nickel (see Section 4.02.1.8). Few cycloaddition reactions are known. 

Most applications of this derivative have been for the preparation and modification of amino acids, although some applications in the area of carbohydrates have been reported. The derivative is stable to n-butyllithium and lithium diisopropylamide. 

Terephthalic acid has been obtained from a great many /)-disubstituted derivatives of benzene or cyclohexane by oxidation with permanganate, chromic acid, or nitric acid. The following routes appear to have preparative value from />-toluic acid, />-methylacetophenone,2 or dihydro-/)-tolualdehyde by oxidation with permanganate from f>-cymene by oxidation with sodium dichromate and sulfuric acid from />-dibromobenzene or from /i-chloro- or -bromobenzoic acid by heating at 250° with potassium and cuprous cyanides and from />-dibromo-benzene, butyllithium, and carbon dioxide. ... 

Diphenylbutadiene has been obtained from phenylacetic acid and cinnamaldehyde with lead oxide, by the dehydrogenation of l,4-diphenyl-2-butene with butyllithium, and by the coupling reaction of benzenediazonium chloride and cinnamyl-ideneacetic acid." The present method gives better yields than those previously reported, is adaptable to the preparation of a variety of substituted bistyryls, and is relatively easy to carry out. 

Kyba and eoworkers prepared the similar, but not identical compound, 26, using quite a different approach. In this synthesis, pentaphenylcyclopentaphosphine (22) is converted into benzotriphosphole (23) by reduction with potassium metal in THF, followed by treatment with o "t/20-dichlorobenzene. Lithium aluminum hydride reduction of 23 affords l,2-i>/s(phenylphosphino)benzene, 24. The secondary phosphine may be deprotonated with n-butyllithium and alkylated with 3-chlorobromopropane. The twoarmed bis-phosphine (25) which results may be treated with the dianion of 24 at high dilution to yield macrocycle 26. The overall yield of 26 is about 4%. The synthetic approach is illustrated in Eq. (6.16), below. 

Thiophenedithiol (170) has been prepared by halogen-metal interconversion between the lithium salt of 4-bromo-3-thiophenethiol and n-butyllithium at —70°C, followed by reaction with sulfur/ IR, NMR, and UV spectra showed that this compound exists in the dithiol form (170). The compound obtained as a by-product in the... 

Halogeno compounds have been prepared by direct halogena-tion or by Sandmeyer reaction on 4-aminoisothiazoles. As expected from general considerations, a halogen atom in the 4-position is less reactive than one in the 5-position, but nitriles are obtained in good yield with cuprous cyanide at elevated temperatures. With butyllithium, lithiation occurs exclusively in the 5-position, and no evidence of halogen displacement has been obtained. ... 

Tlie interest in the preparation and use of dithiolium salts in connection with the synthesis of TTF derivatives led to the development of a new uses of heteroaromatic cations in organic synthesis. Based on that, a new carbonyl olefination for the synthesis of numerous heterofulvalenes was developed (77S861). For example, 2-dimethoxyphosphinyl-l,3-benzodithiole was deprotonated with butyllithium in THF at -78°C and the resulting phosphonate carbanion reacted with 9-alkyl-acridones to give the dithia-azafulvalenes of type 45 (78BCJ2674) (Scheme 15). 

Ethynyl derivatives of 2-aryl-4,5,6,7-tetrahydroindazole were prepared from the p-chlorophenyl hydrazone of cyclohexanone. The hydrazone was treated with two equivalents of -butyllithium at —78°C to generate the dianion, which was then quenched with the appropriate substituted ethyl ester (94MT29). 

One such compound, bropirimine (112), is described as an agent which has both antineo-plastic and antiviral activity. The first step in the preparation involves formation of the dianion 108 from the half ester of malonic acid by treatment with butyllithium. Acylation of the anion with benzoyl chloride proceeds at the more nucleophilic carbon anion to give 109. This tricarbonyl compound decarboxylates on acidification to give the beta ketoester 110. Condensation with guanidine leads to the pyrimidone 111. Bromination with N-bromosuccinimide gives bropirimine (112) [24]. 

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