2-Butyllithium

This was nicely demonstrated by a high-field H nmr study of the aggregation and complexation of n-butyllithium in THF by McGarrity and Ogle148 a). For the above-mentioned equilibrium they determined the following values  

The entropy change observed for the dissociation of the tetramer to the dimer is indeed reasonably explained in form of restriction of four extra solvent molecules in the solvated dimer, relative to the tetramer. 

McGarrity and Ogle also determined the rate constants kj [s ] for the conversion of the tetramer to the dimer at various temperatures and the activation parameters of this reaction  

Undoubtedly, this /wteraggregate rearrangement reaction is very fast even at low temperatures. 

Earlier, Brown 1J 4 determined the activation energy for the dissociation of tetra-meric to dimeric methyllithium to be EA = 47 + 4 kJ/mol. The two values are in good agreement. 

Ortho-specific metal-promoted Fries rearrangement can be achieved, starting from orffeo-bromophenyl esters and sec-butyllithium. The reaction is performed at -95°C with 4 1 1 tetrahydrofuran diethyl ether hexane ratio followed by stirring for 30 min, followed by an additional 30 min at 78°C. The orfto-hydroxyaryl ketones are the sole isomers obtained, and the regioisomeric para-hydroxyaryl ketones are not obtained (Table 5.11). 

Comparative experiments show that the acyl migration step is an intramolecular process. Interestingly, it is shown that pivaloates 10, having the ester functionality separated from the aromatic nucleus by a carbon chain, can participate in this acyl migration reaction (Table 5.12). 

Baldwin s rules predict that exo-trig cyclization such as 11 — 12 (in equilibrium with the open form 13) is favored when n = 0-3. Accordingly, fhis rearrangemenf occurs readily for these substrates. Interestingly, the pivaloate 10 n = 1) furnishes only compound 14 (n = 1) in 86% yield conversely, the same process with n = 2 provides an approximately equal mixture of isomers 14 and 15 in 77% yield, whereas when n = 3, only the hydroxyketone 15 is isolated in 58% yield. 

Anionic ortho-Fries rearrangement is performed by freafment of variously subsfifufed aryl carbamates with sec-butyllithium at -78°C in tetramethylethylenediamine-tetrahydrofuran solution for 8-12 h. i The reaction involves the selective ortho-metalation of fhe aryl groups. The meta-cooperafive mefalafion effect is responsible for fhe producfion of some extremely hindered aromatic compounds (Table 5.13). 

The double 1,4-carbamoyl rearrangement to a hydroquinone diamide is performed in 25% yield. The Fries rearrangement is also observed in good yields in the naphthyl- phenanthryl-, pyridyl-, and quinolinyl 

Physical Data colorless liquid stable at rt eliminates LiH on heating 0.765 mp —76°C bp 80-90 °C/0.0001 mmHg dipole moment 0.97 D. C NMR, H NMR, Li NMR and MS studies have been reported.  

Solubility sol hydrocarbon and ethereal solvents, but should be used at low teir ierature in the latter solvent type half-lives in diethyl ether and THF have been reported reacts violently with H2O and other protic solvents. 

Form Supplied in commercially available as approximately 1.6 M, 2.5 M, and 10.0 M solution in hexanes and in cyclohexane, approximately 2.0 M solution in pentane, and approximately 1.7 M, and 2.7 M solution in n-heptane. Hexameric in hydrocarbons tetrameric in diethyl ether dimer-tetramer equilibrium mixture in THF when used in combination with tertiary polyamines such as TMFDA and DABCO, reactivity is usually increased.  

Analysis of Reagent Purity since the concentration of commercial solutions may vary appreciably it is necessary to standardize solutions of the reagent prior to use. A recommended method for routine analyses involves titration of the reagent with s-butyl alcohol using 1,10-phenanthroline or 2,2 -biquinoline as indicator. Several other methods have been described.  

Preparative Methods may be prepared in high yield fromw-butyl chloride or -butyl bromide and Lithium metal in ether or hydrocarbon solvents. 

CaC03 H2O + CI2 — CaCl2 + C02 -l- HOCL (CH3)3COH + HOC1 (CH3)3COCl + H20 

Chlorine is passed into a stirred suspension of 50 g. of calcium carbonate and 74 g. (1.0 mole) of fert-butyl alcohol in 1 1. of water. The mixture is held at 0-1° during this operation, and the rate of stirring is so adjusted that the calcium carbonate is just held in suspension. The product hydrolyzes at a rapid rate if faster stirring is maintained. The chlorine is introduced until all the calcium carbonate disappears. The upper liquid layer is separated, washed once with water, and distilled. The product boils at 77-79°, and the yield is 65 g., or 60%. The crude product before distillation (87 g., or 80% yield) is sufficiently pure for many purposes. 

The product should be stored out of contact with light and handled with adequate protection against possible explosive decomposition. 

Gilman, Beel, Brannen, Bullock, Dunn, and Miller, J. Am. Chem. Soc., 71, 1499 (1949). 

The alkyllithiums from the bromides listed below may be prepared in similar manner in the yields indicated n-propyl bromide, 78% n-amyl bromide, 81% and n-hexyl bromide, 77%. 

Somi-Reddy, M. Narender, M. Rama Rao, K., Tetrahedron Lett. 2005, 46, 1299. 

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Alkyllithium bases are generally less suitable for deprotofiation of compounds with strongly electron-withdrawing groups such as C=0, COOR and CsN. In these cases lithium dialkylamides, especially those with bulky groups (isopropyl, cyclohexyl), are the reagents of choice. They are very easily obtained from butyllithium and the dialkylamine in the desired solvent. 

A solution of 0.40 mol of butyllithium in about 270 ml of hexane was cooled to -50°C and 250 ml of dry THF or diethyl ether were added, while maintaining the temperature below -20°C. The allenic ether (0.42 mol, freshly distilled) was subsequently added in 16 min at -30°C. After an additional 10 min at this temperature the solution was ready for further conversions. 

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). 

Nate 7. An excess of butyllithium is used, as some butyllithium is destroyed by the competing reaction with the THF. 

Nate 2. During this period the excess of butyllithium has completely reacted with the THF. 

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. 

Note 1. If the lithiation of the allenic ether is performed with butyllithium in hexane and THF as a co-solvent, subsequent alkylation (in the presence of a small amount of HMPT) is much faster. The separation of the volatile product from the hexane and THF is difficult, however. 

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. 

Similar results are probably obtained when the metallation of the allenic ether is carried out with butyllithium in hexane-THF or diethyl ether. 

The dilithiation can also be carried out with butyllithium in a 1 1 mixture of hexane and THF at -20°C (reaction time about 45 min). Subsequent alkylation is much faster than in diethyl ether. 

Although the original procedure also gives excellent yields, our procedure seems more economic because the use of the expensive butyllithium is avoided. 

Butyllithium in a mixture of hexane and diethyl ether or THE can presumably also be used for the dilithiation of propargyl alcohol. 

In the flask was placed a solution of 0.44 mol of butyllithium in about 300 ml of hexane. To this solution were added, with coaling below -20°C, 800, 600 and 400 ml of dry diethyl ether (note 1) in the case of R = CH3, C2H5 and tert.-CuHj or Me3Si, respectively. Subsequently 0.46 mol of the alkyne [in the case of R = CH3, C2H5 a cooled (-30°C) solution in 50 ml of diethyl ether] was added in about 10 min, while keeping the temperature below -20 c. The suspension (in the... 

To a solution of 0.40 mol of butyllithium in about 280 ml of hexane were added 280 ml of dry THF with cooling below -10°C. Subsequently 0.40 mol of 1,1-diethoxy--2-propyne (see Chapter V, Exp. 28) was introduced in 15 min at -30 to -10°C. To the solution obtained was then added in 15 min with cooling at about -15°C 0.40 mol of chloromethyl ethyl ether (note 2). After the addition stirring was continued for 1 h without cooling. The mixture was then shaken with concentrated ammonium chloride solution and the ethereal layer was separated off. The aqueous layer was extracted twice with diethyl ether. After drying the ethereal solutions over magnesium sulfate the diethyl ether was evaporated in a water-pump vacuum. 

To a solution of 0.20 mol of butyllithium in about 140 ml of hexane were added 250 ml of dry diethyl ether below -10°C. Subsequently a solution of 0.25 mol of propyne in 25 ml of ether, cooled below -25°C, was added in 10 min, keeping the temperature of the reaction mixture below -20 C. Powdered sulfur (0.20 at) was... 

A mixture of 0.10 mol of freshly distilled 3-methyl-3-chloro-l-butyne (see Chapter VIII-3, Exp. 5) and 170 ml of dry diethyl ether was cooled to -100°C and 0.10 mol of butyllithium in about 70 ml of hexane was added at this temperature in 10 min. Five minutes later 0.10 mol of dimethyl disulfide was introduced within 1 min with cooling betv/een -100 and -90°C. The cooling bath vjas subsequently removed and the temperature was allowed to rise. Above -25°C the clear light--brown solution became turbid and later a white precipitate was formed. When the temperature had reached lO C, the reaction mixture was hydrolyzed by addition of 200 ml of water. The organic layer and one ethereal extract were dried over potassium carbonate and subsequently concentrated in a water-pump vacuum (bath... 

A solution of 0.21 mol of butyllithium in about 140 ml of hexane (note 1) was cooled below -40°C and 90 ml of dry THF ivere run in. Subsequently a cold (< -20 C) solution of 0.25 nol of propyne in 20 ml of dry THF was added with cooling below -20°C and a white precipitate was formed. A solution of 0.10 mol of anhydrous (note 2) lithium bromide in 30 ml of THF was added, followed by 0.20 mol of freshly distilled cyclopentanone or cyclohexanone, all at -30°C. The precipitate had disappeared almost completely after 20 min. The cooling bath was then removed and when the temperature had reached 0°C, the mixture was hydrolyzed by addition of 100 ml of a solution of 20 g of NHi,Cl in water. After shaking and separation of the layers four extractions with diethyl ether were carried out. The extracts were dried over magnesium sulfate and the solvents removed by evaporation in a water--pump vacuum. Careful distillation of the remaining liquids afforded the following... 

TO a solution of 0.10 mol of phenyl acetyl one (commercially available, see also Ref. 1) in 100 ml of dry THF was added a solution of 0.21 mol of butyllithium in about 145 ml of hexane. During this addition the temperature was kept below -20°C. The obtained solution was cooled to -65°C and a solution of 0.12 mol of KO-tert.--CijHg (commercially available, see Chapter IV, Exp. 4, note 2) in 100 ml of THF was added, while keeping the temperature below -55°C. After an additional 15 min the cooling bath was removed, the temperature was allowed to rise to -10°C and was kept at that level for 1 h (note 1). The reddish suspension was subsequently cooled to -50°C and 0.32 mol of trimethylchlorosi1ane was added in 10 min. The cooling bath was then removed and the temperature was allowed to rise to 10°C. 

A solution of 0.22 mol of butyllithium in 150 ml of hexane was cooled below -40°C and 140 ml of dry THF were added. Subsequently 0.20 mol of 1-dimethyl amino--4-methoxy-2-butyne (see Chapter V, Exp. 14) were added in 10 min with cooling between -35 and -45°C. After an additional 15 min 100 ml of an aqueous solution of 25 g of ammonium chloride were added with vigorous stirring. After separation of the layers four extractions with diethyl ether were carried out. The solutions were dried over potassium carbonate and then concentrated in a water-pump vacuum. Distillation of the residue gave a mixture of 8-10% of starting compound and 90-92% of the allenic ether, b.p. 50°C/12 mmHg, n 1.4648, in 82% yield (note 1). 

Note 2. Commercial butyllithium in hexane as solvent or butyllithium in diethyl... 

Note 7. Butyllithium in hexane can be used in principle, but the yield is lower because during the evaporation of the hexane some of the cumulenic ether is entrained. 

To a solution of 0.40 mol of butyllithium in about 280 ml of hexane were added 300 ml of dry THF at -20 to -40 0. Subsequently 0.40 mol of freshly distilled tert.-butyl propargyl ether was added, keeping the temperature below -30°C. Freshly distilled acetaldehyde (0.40 mol) was then added at the same temperature during about 15 min. The cooling bath was removed and, after an additional 15 min, 200 ml of an aqueous solution of 30 g of ammonium chloride were introduced. After separation of the layers the aqueous layer was extracted twice with diethyl ether and the combined solutions were dried over magnesium sulfate and concentrated in... 

The 120 g of residue were dissolved in 350 ml of dry diethyl ether and a solution of 0.35 mol of butyllithium in about 280 ml of hexane was added dropwise during 30 min, while maintaining the temperature at about -60°C. After the addition the temperature was allowed to rise to -25°C and stirring at that temperature was continued for an additional 30 min. The mixture was then poured with swirling into 1 1 of ice-water and the upper layer and two extracts of the aqueous layer were combined and dried over magnesium sulfate. The solvents were removed... 

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