Bases Sodium hydride-Dimethylformamide

Benzodiazepine 7a undergoes a thermal rearrangement with ring contraction to give the quin-azoline 8a in 32- 37% yield.Benzodiazepine 7b is transformed to quinazoline 8b by either base (sodium hydride in dimethylformamide or potassium hydroxide in ethanol) or acid (hydrogen chloride in ethanol)." ... 

A somewhat related microwave-promoted 5 -0-allylation of thymidine has been described by the Zerrouki group (Scheme 6.108) [215], While the classical method for the preparation of 5 -0-allylthymidine required various protection steps (four synthetic steps in total), the authors attempted the direct allylation of thymidine under basic conditions. Employing sodium hydride as a base at room temperature in N,N-dimethylformamide resulted in the formation of per-allylated compounds along with the desired monoallylated product (75% yield). The best result was achieved when both the deprotonation with sodium hydride (1.15 equivalents) and the subsequent allylation (1.2 equivalents of allyl bromide) were conducted under... 

Acylation of sugars is generally carried out with acyl chlorides or anhydrides, in pyridine solution, at room temperature. Allylation and benzylation is njost efficiently achieved with he corresponding halides in anhydrous N, Af-dimethylformamide, in the presence of a base, ito generate the alcoholate. Sodium hydride is the most convenient one, but its use may... 

TV-Alkylation. 1-Substitution is favored when the indole ring is deprotonated and the reaction medium promotes the nudeophilicity of the resulting indole anion. Conditions which typically result in N-alkylation are generation of the sodium salt by sodium amide in liquid ammonia, use of sodium hydride or a similar strong base in IV,IV-dimethylformamide or dimethyl sulfoxide, or the use of phase-transfer conditions. 

A new method for a-phenol annulation involving base-induced cycloaromatization of readily available 4-bis (methylthio)-3-buten-2-one 114 was applied to 3,4-dihydro-l-benzothiepin-5(2//)-one 113 (Scheme 14) <2002JOC5398>. Equimolar quantities of the benzothiepinone 113 and 114 in the presence of sodium hydride were stirred in dimethylformamide (DMF) at 25 °C. Treatment of the reaction mixture with/>-toluenesulfonic acid in refluxing benzene furnished the phenol-annulated dihydrothiepine 116 in 62% yield. The reaction sequence involved formation of conjugate addition-elimination adduct 115, followed by intramolecular aldol condensation and cycloaromatization, affording 116. 

The cyclisation of (22) to the /J-lactam system, which is a thermodynamically unfavourable reaction, is promoted by using sodium hydride as the base in a dichloromethane-dimethylformamide solvent system at high dilution. 

To a stirred and refluxing solution of 40 parts of benzene and 35 parts of dimethylformamide (both solvents previously dried azeotropically) are added successively 1.6 parts of sodium hydride and 7.7 parts of a-(2,4-dichlorophenyl)imidazole-l-ethanol, (cooling on ice is necessary). After the addition is complete, stirring and refluxing is continued for 30 minutes. Then there are added 7.8 parts of 2.6-dichlorobenzyl chloride and the whole is stirred at reflux for another 3 hours. The reaction mixture is poured onto water and the product l-[2,4-dichloro-b-(2,6-dichlorobenzyloxy)phenethyl] imidazole, is extracted with benzene. The extract is washed twice with water, dried, filtered and evaporated in vacuo. The base residue is dissolved in a mixture of acetone and diisopropyl ether and to this solution is added an excess of concentrated nitric acid solution. The precipitated nitrate salt is filtered off and recrystallized from a mixture of methanol and diisopropyl ether, yielding l-[2,4-dichloro-b-(2,6-dichlorobenzyloxy)phenethyl]imidazole nitrate melting point 179°C. 

However, when the carbapen-2-am-3-carboxylate 80 was treated with 1.0 mol equiv. of DBU in dimethyl sulfoxide or in dimethylformamide in the presence of a slight excess of methyl iodide at room temperature for 15 min, the rearranged product 81 was obtained in 14% yield (85JOCI996). If sodium hydride was used as base in the latter reaction, the / -lactam ring underwent decomposition. 

Electrophilic cyclopropanes 392, which are useful intermediates in organic syntheses, can be prepared by the cyclopropanation of olefins with diethyl dibromomalonate and its derivatives (81MI4). The reaction is carried out in the presence of 1 mol equiv. of copper(II) bromide and 2-4 mol equiv. of DBU. Alternatively, the reaction can be effected with diethyl bromomalonate (83BCJ2687) in the presence of a catalytic amount of copper(II) bromide and a slight excess of DBU in benzene at ambient temperature. When some other base (e.g., triethylamine, DABCO, pyridine, or sodium hydride) was applied instead of DBU, the yield was lower or no reaction occurred. The use of other copper salts led to a decrease in the yield. When cyclopropanation was carried out in dimethyl sulfoxide, dimethylformamide, or acetonitrile, the yield of product 392 was again lower. 

Initial studies of solvent effects, on the reactions of triarylarsonium benzoylylides with p-nitrobenzaldehyde in N, A-dimethylformamide, dimethyl sulphoxide or methanol, indicated little solvent effect in these cases" ", but later studies of the more finely balanced reactions of semi-stabilized ylides have provided examples of strong influences due to the effect of different base and solvent when the ylide is generated in the presence of a carbonyl compound ". Thus, when benzyltriphenylarsonium bromide or p-chloroben-zyltriphenylarsonium bromide were treated with sodium hydride in benzene in the presence of a variety of p-substituted benzaldehydes the products were alkenes, but if sodium ethoxide in ethanol was used the isolated products were epoxides ". Likewise, when triphenylarsonium benzylylide was generated by phenyllithium in the presence of either benzaldehyde or acetaldehyde, the preponderant product was the epoxide whereas use of sodium amide as base provided mostly the alkene . Similar results were obtained when an allyltriphenylarsonium salt was deprotonated using different hexamethyldisilaz-... 

In the base-induced cyclization of a number of y-chloro-y-nitro carboxylic esters and derivatives, it was found that use of excess base led to elimination of nitrous acid resulting in methylenecyclopropanes. Thus, reaction of ethyl 4-chloro-4-nitropentanoate (1) with one equivalent of sodium hydride in dimethylformamide gave, in addition to a 53% yield of ethyl 2-methyl-2-nitrocyclopropanecarboxylate(2), 12% of ethyl 2-methylenecyclopropanecarboxylate (3). The latter could be prepared in 70% yield from the former, or in 55% yield from the starting ester by the use of two equivalents of sodium hydride. 

For these reactions, a large variety of base-solvent systems have been used, including sodium hydride in 1,2-dimethoxyethane or dimethylformamide, aqueous sodium hydroxide, butyl-lithium or phenyllithium in hexanes, potassium hydride in tetrahydrofuran, and sodium ethox-ide in ethanol. 

Alkylation of 2-substituted quinazolin-4(3//)-ones by reaction with sodium hydride in dimethylformamide followed by alkylation provided O-and N-alkyl derivatives. The extent of alkylation at the different sites was reasonably explained in terms of steric properties of the 2-substituents. The silver salt of quinazolin-4(3H)-one and tetra-0-acetyl-) -D-glucopyrano-syl bromide gave a 40% yield of the 0-glycosyl derivative in contrast with the mercury salt, which gave mainly the iV-3-glycosyl derivative. As in the alkylation of mercapto compounds, quinazoline-4(3H)-thione gave the S-glycosyl derivative. If sodium hydroxide was used as base a 56% yield of the... 

The medicinal chemistry route used pyridine as the reaction solvent medium and, sodium hydride as the base. It was later recognized from solvent screening studies that the reaction pathway for the ring closure was solvent dependent. When dimethylformamide (DMF) was used as the solvent, an alternate cyclization pathway was observed (Scheme... 

In dimethylformamide with sodium hydride as a base 1-substituted pyrido[2,3-(/]pyrimidine-2,4(1/7,3/7)-diones are alkylated in the 3-position.78... 

Hector s base is a strong monoacidic base (pK 13.5, from spectral data). According to13C-NMR measurements in trifluoroaceticacid, it is protonated predominantly at its exocyclic 2-imino group.37 Its alkylation with sodium hydride-methyl iodide in dimethylformamide yields the 3,5-dimethyl derivative (16).31 With Meldrum s acid (17), it reacts with elimination of acetone to yield a carboxylic acid formulated as 18, which is decarboxylated pyroly-tically to the acetyl derivative of Hector s base.37... 

Acylation of 3,5-diamino-1,2,4-thiadiazole by ethyl chloroformate yields the 3,5-bis(ethoxycarbonylamino) derivative.67 Phosphorochloridic esters [(RO)2POCl] attack the 3-position preferentially, producing the phosphor-amidic esters (509).390 The action of diphenylphosphinothioic chloride (Ph2PSCl) (see Section IV,C) on Hector s base in pyridine yields a monoacyl derivative, substitution occurring probably at the exocyclic imino group.391 Methylation of 3,5-bisanilino-l,2,4-thiadiazole with sodium hydride-methyl iodide in dimethylformamide produces the mono and dimethyl derivatives, of structures 510 and 511, as shown by 15N and 13C NMR spectroscopy.31... 

Phosphonium ylides (alkyhdene phosphoranes) can be prepared by a number of methods, but in practice they are usually obtained by action of a base on (alkyl)triphenylphosphonium salts, which are themselves readily available from an alkyl halide and triphenylphosphine. The phosphonium salt can usually be isolated and crystallized, but the phosphonium ylide is generally prepared in solution and used without isolation. Formation of the phosphonium ylide is reversible, and the reaction conditions and the strength of the base required depend entirely on the nature of the ylide. A common procedure is to add a stoichiometric amount of a solution of n-butyllithium to a solution or suspension of the phosphonium salt in ether or THF, followed, after an appropriate interval, by the carbonyl compound. Other bases, such as sodium hydride or sodium or potassium alkoxides, in solution in the corresponding alcohol or in dimethylformamide, are used commonly. 

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