Sodium hydride sulfoxide

The formation of the above anions ("enolate type) depend on equilibria between the carbon compounds, the base, and the solvent. To ensure a substantial concentration of the anionic synthons in solution the pA" of both the conjugated acid of the base and of the solvent must be higher than the pAT -value of the carbon compound. Alkali hydroxides in water (p/T, 16), alkoxides in the corresponding alcohols (pAT, 20), sodium amide in liquid ammonia (pATj 35), dimsyl sodium in dimethyl sulfoxide (pAT, = 35), sodium hydride, lithium amides, or lithium alkyls in ether or hydrocarbon solvents (pAT, > 40) are common combinations used in synthesis. Sometimes the bases (e.g. methoxides, amides, lithium alkyls) react as nucleophiles, in other words they do not abstract a proton, but their anion undergoes addition and substitution reactions with the carbon compound. If such is the case, sterically hindered bases are employed. A few examples are given below (H.O. House, 1972 I. Kuwajima, 1976). 

A AlI lation. 1-Substitution is favored when the indole ring is deprotonated and the reaction medium promotes the nucleophilicity of the resulting indole anion. Conditions which typically result in A/-alkylation are generation of the sodium salt by sodium amide in Hquid ammonia, use of sodium hydride or a similar strong base in /V, /V- dim ethyl form am i de or dimethyl sulfoxide, or the use of phase-transfer conditions. 

Base-catalyzed proton abstraction from trimethylsulfoxonium halides (1) with formation of dimethylsufoxonium methylide (2) was described by Corey in 1962. Solutions of (2) in dimethyl sulfoxide are conveniently prepared from the chloride or iodide (1) by stirring with one equivalent of sodium hydride at room temperature. 

To a solution consisting of 1 g (4.6 mmoles) of trimethylsulfoxonium iodide in 20 ml dry dimethyl sulfoxide is added 110 mg (4.6 mmoles) of sodium hydride powder or an equivalent amount of 50 % sodium hydride in mineral... 

On treatment with a strong base such as sodium hydride or sodium amide, dimethyl sulfoxide yields a proton to form the methylsulfinyl carbanion (dimsyl ion), a strongly basic reagent. Reaction of dimsyl ion with triphenylalkylphosphonium halides provides a convenient route to ylides (see Chapter 11, Section III), and with triphenylmethane the reagent affords a high concentration of triphenylmethyl carbanion. Of immediate interest, however, is the nucleophilic reaction of dimsyl ion with aldehydes, ketones, and particularly esters (//). The reaction of dimsyl ion with nonenolizable ketones and... 

Powdered sodium amide reacts with dimethyl sulfoxide to generate the sodium salt under the same conditions, with the evolution of ammonia, and is comparable to sodium hydride in its reactivity. 

A 1.5 to 2 M solution of methylsulfinyl carbanion in dimethyl sulfoxide is prepared under nitrogen as above from sodium hydride and dry dimethyl sulfoxide. An equal volume of dry tetrahydrofuran is added and the solution is cooled in an ice bath during the addition, with stirring, of the ester (0.5 equivalent for each 1 equivalent of carbanion neat if liquid, or dissolved in dry tetrahydrofuran if solid) over a period of several minutes. The ice bath is removed and stirring is continued for 30 minutes. The reaction mixture is then poured into three times its volume of water, acidified with aqueous hydrochloric acid to a pH of 3-4 (pH paper), and thoroughly extracted with chloroform. The combined extracts are washed three times with water, dried over anhydrous sodium sulfate, and evaporated to yield the jS-ketosulfoxide as a white or pale yellow crystalline solid. The crude product is triturated with cold ether or isopropyl ether and filtered to give the product in a good state of purity. 

Methylsulfinyl carbanion (dimsyl ion) is prepared from 0.10 mole of sodium hydride in 50 ml of dimethyl sulfoxide under a nitrogen atmosphere as described in Chapter 10, Section III. The solution is diluted by the addition of 50 ml of dry THF and a small amount (1-10 mg) of triphenylmethane is added to act as an indicator. (The red color produced by triphenylmethyl carbanion is discharged when the dimsylsodium is consumed.) Acetylene (purified as described in Chapter 14, Section I) is introduced into the system with stirring through a gas inlet tube until the formation of sodium acetylide is complete, as indicated by disappearance of the red color. The gas inlet tube is replaced by a dropping funnel and a solution of 0.10 mole of the substrate in 20 ml of dry THF is added with stirring at room temperature over a period of about 1 hour. In the case of ethynylation of carbonyl compounds (given below), the solution is then cautiously treated with 6 g (0.11 mole) of ammonium chloride. The reaction mixture is then diluted with 500 ml of water, and the aqueous solution is extracted three times with 150-ml portions of ether. The ether solution is dried (sodium sulfate), the ether is removed (rotary evaporator), and the residue is fractionally distilled under reduced pressure to yield the ethynyl alcohol. 

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

Treatment of isoquinoline tV-oxide (55) with sodium hydride in dimethyl sulfoxide results in ring expansion, albeit in poor yield, to the 3//-3-benzazepine 56, along with a trace of naphthalene (0.8%), and much tar.26... 

Liimsyl anion3 was prepared from 10.2 g. (0.24 mole) (Note 10 of 56.8% sodium hydride, which was washed with pentane and vacuurr dried, and 200 ml. of anhydrous dimethyl sulfoxide. The mixture was heated at 65-70° for about 50 minutes, until hydrogen evolution ceased. Caution This mixture should not be heated above 80°, because of the possibility of explosive decomposition. 

Corey and Chaykovsky had discovered that dimethyl sulfoxide is converted to methyl-sulfmyl carbanion upon treatment with sodium hydride " and that this conjugate base of DMSO reacts with various electrophiles This finding has opened up various reactions with a-sulfinyl carbanions derived from sulfoxides, since the sulfinyl function can be removed either by thermolysis or by subjecting the compound to reductive desulfurization. Thus a-sulfinyl carbanions have become versatile synthetically useful reagents. 

Chlorotrifluoromethy lbenzene See 4-Chlorotrifluoromethylbenzene Sodium dimethylsulfinate See Dimetbyl sulfoxide Sodium hydride... 

See Carbonyl diisothiocyanate, and Dinitrogen tetraoxide, and Hexachlorocyclot-riphosphazine, and Sodium hydride, all below See Perchloric acid Sulfoxides... 

Two violent pressure-explosions occurred during preparations of dimethylsulfinyl anion on 3-4 g mol scale by reaction of sodium hydride with excess solvent. In each case, the explosion occurred soon after separation of a solid. The first reaction involved addition of 4.5 g mol of hydride to 18.4 g mol of sulfoxide, heated to 70°C [1], and the second 3.27 and 19.5 g mol respectively, heated to 50°C [2], A smaller scale reaction at the original lower hydride concentration [3], did not... 

Meschino, J. A. et al., J. Org. Chem., 1971, 36, 3637, footnote 9 Interaction with dimethylsulfinate anion (from the sulfoxide and sodium hydride) at —5°C is very exothermic, and addition of the chloro compound must be slow to avoid violent eruption. 

Isopropylidene N-substituted aminomethylenemalonates (442, R1 = R2 = Me) were methylated with methyl iodide in dimethyl sulfoxide in the presence of sodium hydride at room temperature overnight to give the N-methyl derivatives (1615) in 56-90% yields [88JCS(P )863,88JCS(P2)759]. 

Though the PECH decomposes to indefinite fragments with n-butyl lithium or sodium hydride in THF at room temperature, it reacts with sodium methoxide with liberation of Cl in which the -elimination of hydrogen chloride predominates instead of nucleophilic substitution. For instance, PECH in DMSO was reacted with double the molar quantity of sodium methoxide at room temperature for 24 h to give the unsaturated polyether (DS 92.3%,v(C=C) 1630,5 (=CH2) 795 cm" ) after purification by dissolution(DMF)-precipitation (H20) technique. A similar unsaturated polyther was obtained by the pyrolysis of the sulfilimine 13 (110-130°C) but not of sulfoxide 12 (100-150°C). When the polymer 26, was heated to 90°C, the absorption of C=C and =CH2 decreased and a new absorption at 1720 cm appeared and increased. This is explained as a result of [3.3] sigmatropic rearrangement of to afford including C=CH2 and C=0 structure as shown in equation 7. 

Dimethylmethyleneoxosulfanenickel(O) diethylene complex, 2856 f Dimethyl sulfoxide, Sodium hydride, 0921... 

In a 100 mL round-bottomed flask equipped with a magnetic stir bar were placed (5)-3-(methylamino)-l-phenylpropan-l-ol 21 (4.10g, 25mmol) and dry dimethyl sulfoxide (20mL). Sodium hydride (60%) (1.19g, 30mmol) was added in three... 

The tricyclic compound 3-methoxytricyclo[5.4.0.02-8]undecan-9-one (21) was conveniently prepared in 91 % yield by treating 2-bromo-3-methoxybicyclo[5.4.0]undecan-9-one with sodium hydride in dimethyl sulfoxide.20... 

Confirmation of these results was provided by a different laboratory67 in studies with allyl a-L-fucopyranoside. Partial benzylation of this compound, under conditions similar to those described previously,66 also gave the 2,4- and 3,4-dibenzyl ethers in the ratio of 3 2. In both publications, the structures assigned were primarily confirmed by methylation of unreacted hydroxyl groups with methyl iodide-sodium hydride in dimethyl sulfoxide,68 followed by catalytic debenzylation, and isolation and characterization of the known methyl ethers. 

R. The use of butyllithium in tetrahydrofuran or ether-hexane affords the triene 1n only 50-60% yield. When the ylide was generated with sodium hydride or potassium tert-butoxide in dimethyl sulfoxide by the submitter, the Wittig reaction gave triene containing 10-20% of the Z isomer. Part C illustrates the selective hydroboration of a diene with disiamylborane.1 The reaction is best carried out by adding preformed disiamylborane to the triene. Lower yields of homogeraniol were obtained by the submitter when the triene was added to the borane reagent. 

Decarboxylation of (bromodifluoromethyl)malonates (9) reminiscent of Krapcho s deal-koxycarbonylation process, is observed on treatment with potassium fluoride in dimethyl sulfoxide at 170 °C to give 2-(trifluoromethyl)-substituted esters 10.43 The precursors are prepared by reacting diethyl malonates 8 with dibromodifluoromethane in the presence of sodium hydride. The exchange of bromine for fluorine in 9 followed by decarboxylation is an excellent method of introducing a trifluoromethyl group a- to an ester group. 

Sodium hydride in dimethyl sulfoxide medium acts also as an initiator for alkylation, predominantly N-alkylation, on the polyamide skeleton (/27). 

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