Dimethyl sulfate hydride

Alkylation at the ind-N of l,2,3,4-tetrahydro-j8-carbolines has been carried out with alkyl halide after treatment with sodamide in the usual manner. Cyanoethylation of a p /r-V-substituted tetrahydro-jS-carboline in the presence of Triton B yields the corresponding 9-cyanoethyl derivative. Similarly, treatment of p / -V-methyl-l,2,3,4,4a,9b-hexahydro-y-carboline with sodamide, followed by benzyl chloride, leads to the ind-A -benzyl-substituted derivatives. l-Oxo-l,2,3,4-tetrahydro-j8-carboline yields the ind-A -methyl derivative directly with dimethyl sulfate.Prolonged treatment with sodium hydride, followed by methyl iodide, yields the 2,9-dimethyl derivative. Heating with sodium hydride in acetone followed by the addition of dimethyl sulfate gives rise to the ind-V-methyl derivative. ... 

The indol-3-yl-substituted indolo[2,3-()]carbazole 143 has been isolated as a product from the complex mixture generated by the decomposition of urorosein (144) (99CHE561). Interestingly, when subjected to alkylation conditions involving sodium hydride and dimethyl sulfate in THF, 143 was transformed into the N. -dimethyl derivative 145 in 36% yield (00MI2). 

Sodium hydride Dimethyl sulfate Trifluoroacetic acid... 

Benzhydryl 3Sodium hydride, 24 mg (4B mg of a 50% suspension of NaH in mineral oil, which has been washed with hexane to remove the oil), is added. When hydrogen evolution has ceased, 126 mg dimethyl sulfate is added. The solution is stirred for one hour at room temperature,diluted with 100 ml benzene and washed six times with water the last wash is made to pH B, if necessary, by adding sodium bicarbonate. The solution is dried over MgS04, filtered and evaporated, leaving benzhydryl 3eluting with 25 1 chloroform-ethyl acetate. 

A novel route to synthesize l,3 -triazine-2,4(l//,3//)-diones through the desulfurization of thiocarboamides, such as 1,3-disubstituted 2-thioureas, trisubstituted thioureas and N-substituted thioamides by silver cyanate has been reported <00H(53)929>. Treatment of urazole 23 with one equivalent of sodium hydride under anhydrous conditions, followed by addition of dimethyl sulfate, leads to l,3,5-triazine-2,4-dione 24 in 80% yield . 

The value of methylation studies in structural determination of carbohydrates is well known. Methylation of sucrose has generally been achieved by the use of dimethyl sulfate-sodium hydroxide,34,35 methyl iodide-silver oxide-acetone,20 sodium hydride-methyl io-dide-N,N-dimethylformamide,35 or diazomethane-boron trifluoride etherate.36,37 The last method (already applied to monosaccharides38,39) has been found particularly useful for sucrose, because it proceeds without concomitant migration of acyl groups. The reaction of 2,3,6,T,3, 4, 6 -hepta-0-acetylsucrose (21) and 2,3,4,6,1, 3, 4 -hepta-O-acetylsucrose (22) with diazomethane in dichloromethane in the presence of a catalytic proportion of boron trifluoride etherate for 0.5 h at —5° gave the corresponding 4-methyl (23) and 6 -methyl (24)... 

Octa-O-methylsucrose has been prepared by treating sucrose with either dimethyl sulfate-sodium hydroxide, or sodium hydride and methyl iodide in A/,A/-dimethylformamide.35... 

Tetrahydrotetrazolo[l,5- ]pyridine 52 was reacted with dimethyl sulfate to give a mixture of quaternary salts 1-methyl 53 and 2-methyl compounds 54 from which the 1-alkyl compound was separated as a crystalline hexafluorophosphate salt 53 (A = PF6) in good yield. This salt when treated with potassium hydride in the presence of 18-crown-6 and KCN underwent deprotonation to give the saturated six-membered ring 55. 

The amino group of 5-benzimidazolyl- and 5-benzotriazolylaminomethy-lenemalonates (1471, X = CH and N) was alkylated with methyl iodide in DMF in the presence of potassium carbonate in 43-91% yields (89CCC713). 5-Benzimidazolylaminomethylenemalonate (1471, X = CH) was also alkylated on the amino group with ethyl iodide and benzyl chloride, or with methyl iodide in dimethoxyethane, or dimethyl sulfate in THF in the presence of sodium hydride. 

The reactions of 3-pyrazolylaminomethylenemalonate (1478, R = R1 = R2 = H) with dimethyl sulfate, ethyl iodide, or benzyl bromide in boiling THF in the presence of sodium hydride yielded -substituted AK3-pyrazolyl)aminomethylenemalonates (1478, R = R1 = H, R2 = Me, Et, PhCH2). 3-Pyrazolylaminomethylenemalonate (1478, R = COOfBu, R1 = R2 = H) was dimethylated with methyl iodide in DMF in the presence of sodium methylate at room temperature overnight to give /V-methyl-N-U -dimethyl-S-pyrazolyDaminomethylenemalonate (1478, R = COOfBu, R1 = R2 = Me) in 88% yield (85JHC729). 

Why does 3-ethylindole when treated with sodium hydride and then dimethyl sulfate give a mixture of 3-ethyl-2-methylindole and 2-ethyl-3-methylindole ... 

To a stirred flask containing a suspension of 4.8 gm (0.2 mole) of sodium hydride in 50 ml of THF under a nitrogen atmosphere is added dropwise 13.3 gm (0.2 mole) of cyclopentadiene. In a separate flask are mixed 19.8 gm (0.2 mole) of A-methyl-2-pyrrolidone and 25.2 gm (0.2 mole) of dimethyl sulfate. (NOTE Separately A-methyl-2-pyrrolidone and dimethyl sulfate should be anhydrous and should be purified by distillation before reacting with each other to form the complex.) The latter mixture is heated for 20 min on a steam bath, cooled, and then added dropwise to the cyclopentadienylsodium solution at —5°C. After the addition, the reaction mixture is stirred for 2 hr, filtered, the filtrate concentrated, and the residue is obtained as a brown oil. On cooling, the brown oil solidifies and is recrystallized from cyclohexane to afford pale-yellow needles weighing 14.0 gm (50%), m.p. 100°-101°C. 

Methyl Ethers. Methylation of sucrose is generally conducted under basic conditions. Etherification occurs initially at the most acidic hydroxyl groups, HO-2, HO-T, and HO-3f, followed by the least hindered groups, HO-6 and HO-6. Several reagents have found use in the methylation of sucrose, including dimethyl sulfate—sodium hydroxide (18,19), methyl iodide—silver oxide—acetone, methyl iodide—sodium hydride in N, N- dimethyl form amide (DMF), and diazomethane—boron trifluoride etherate (20). The last reagent is particularly useful for compounds where mild conditions are necessary to prevent acyl migration (20). 

Benzhydryl 3-carbamyloxymethyl-7a-hydroxy-7p-(2-thienylacetamino)-decephalosporanate Sodium hydride Dimethyl sulfate Trifluoroacetic acid... 

Methyl ethers are usually prepared by some variant of the Williamson ether synthesis in which an alcohol reacts with either iodomethane, dimethyl sulfate, or methyl triflate (HAZARD) in the presence of a suitable base. A word of caution dimethyl sulfate and methyl triflate, tike all powerful alkylating agents, are potentially carcinogenic and therefore should only be handled in a well-ventilated fume hood. For the 0-methylation of phenols (pKa 10) a comparatively weak base such as potassium carbonate in conjunction with dimethyl sulfate is sufficient,193 whereas simple aliphatic alcohols require stronger bases such as sodium hydride [Scheme 4.111]22 or lithium hexamethyldisilazide [Scheme 4.112].203 The latter transformation is notable for the fact that 0-methyiation was accomplished without competing elimination. 

N-Methylacetanilide is obtained in 96% yield by the action of methyl iodide or dimethyl sulfate on the sodium salt of acetanilide. The last compound is prepared from acetanilide and sodium wire in hot benzene. The reaction has been extended to other aliphatic and aromatic N-sub-stituted amides. Sodium hydride serves to convert the amide to its salt, and a variety of simple halides have been successfully employed as alkylating agents, ... 

Preparation of l,3-dimethylimidazo[4,5-c]pyrimidinium iodide (133) was accomplished by the lithium aluminum hydride reduction of l,3-dimethylimidazo[4,5-c]pyridin-2(3//)-one (132), prepared by the methylation of imidazo[4,5-c]pyridin-2(3//)-one with dimethyl sulfate (74KGS854), rather than by methylation of (128) or (130) (79MI41001). 

The aziridine derivative 117, a photochemical valence tautomerization product of berberinephenolbetaine, was also converted into the benzindan-oazepines by regioselective C-14—N bond cleavage (Scheme 24)." The treatment of 117 with p-toluenesulfonic acid in benzene under reflux gave rise to the benzindenoazepine 118 whose N-methylation with dimethyl sulfate in HMPA in the presence of sodium hydride afforded the n-methyl derivative 119." Since 119 has already been converted" to ( )-c -alpini-genine (120) and ( )-ds-alpinine (121), this synthesis constitutes a formal synthesis of these alkaloids. 

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