Hexamethylphosphoric triamide solvent

Isoquinoline can be reduced quantitatively over platinum in acidic media to a mixture of i j -decahydroisoquinoline [2744-08-3] and /n j -decahydroisoquinoline [2744-09-4] (32). Hydrogenation with platinum oxide in strong acid, but under mild conditions, selectively reduces the benzene ring and leads to a 90% yield of 5,6,7,8-tetrahydroisoquinoline [36556-06-6] (32,33). Sodium hydride, in dipolar aprotic solvents like hexamethylphosphoric triamide, reduces isoquinoline in quantitative yield to the sodium adduct [81045-34-3] (25) (152). The adduct reacts with acid chlorides or anhydrides to give N-acyl derivatives which are converted to 4-substituted 1,2-dihydroisoquinolines. Sodium borohydride and carboxylic acids combine to provide a one-step reduction—alkylation (35). Sodium cyanoborohydride reduces isoquinoline under similar conditions without N-alkylation to give... 

Dianion formation from 2-methyl-2-propen-l-ol seems to be highly dependent on reaction conditions. Silylation of the dianion generated using a previously reported method was unsuccessful in our hands. The procedure described here for the metalation of the allylic alcohol is a modification of the one reported for formation of the dianion of 3-methyl-3-buten-l-ol The critical variant appears to be the polarity of the reaction medium. In solvents such as ether and hexane, substantial amounts (15-50%) of the vinyl-silane 3 are observed. Very poor yields of the desired product were obtained in dirnethoxyethane and hexamethylphosphoric triamide, presumably because of the decomposition of these solvents under these conditions. Empirically, the optimal solvent seems to be a mixture of ether and tetrahydrofuran in a ratio (v/v) varying from 1.4 to 2.2 in this case 3 becomes a very minor component. 

The Heck reaction is considered to be the best method for carbon-carbon bond formation by substitution of an olefinic proton. In general, yields are good to very good. Sterically demanding substituents, however, may reduce the reactivity of the alkene. Polar solvents, such as methanol, acetonitrile, N,N-dimethylformamide or hexamethylphosphoric triamide, are often used. Reaction temperatures range from 50 to 160 °C. There are various other important palladium-catalyzed reactions known where organopalladium complexes are employed however, these reactions must not be confused with the Heck reaction. 

Hexamethylphosphoric triamide (HMPT) is a high-boiling solvent particularly satisfactory for dissolving metals or organometallic compounds. It has been found to be an ideal solvent in which to conduct the reduction of a,jS-unsaturated ketones by alkali metals. 

Ar-Alkylations of 5//-dibenz[6,/]azcpines, e.g. 5 > 8 can be readily achieved via their nitranions, which are generated from the NH compounds by standard methodology, e.g. with sodium hydride, or sodamide, in refluxing toluene or xylene.30-J1-bt, 7° 124,1 s2 Occasionally, dioxane,187 or a mixture of tetrahydrofuran and hexamethylphosphoric triamide is used as solvent.137... 

The nucleophilic addition of Grignard reagents to a-epoxy ketones 44 proceeds with remarkably high diastereoselectivity70. The chelation-controlled reaction products are obtained in ratios >99 1 when tetrahydrofuran or tetrahydrofuran/hexamethylphosphoric triamide is used as reaction solvent. The increased diastereoselectivity in the presence of hexamethylphos-phoric triamide is unusual as it is known from addition reactions to a-alkoxy aldehydes that co-solvents with chelating ability compete with the substrate for the nucleophile counterion, thus reducing the proportion of the chelation-controlled reaction product (vide infra). 

This procedure, which involves the addition of an anion derived from a nitrile to an unactivated acetylenic bond under rather mild conditions, is a convenient general method for the synthesis of a-vinyl-nitriles (see Table I). The reaction proceeds smoothly in either dimethyl sulfoxide or hexamethylphosphoric triamide (see p. 103 for warning) as solvent with a tetraalkylam monium salt as catalyst. The products thus prepared are obtained in yields higher2 than those obtained under conventional conditions, which generally require higher temperatures and elevated pressures.3-4... 

The simple hexaalkylditins, RsSnSnRs, do not disproportionate on heating, but, in oxolane (tetrahydrofuran) or acetonitrile in the presence of a base such as a Grignard reagent, or in the more strongly basic solvent hexamethylphosphoric triamide (HMPT), disproportionation readily occurs at room temperature, and, in HMPT, addition occurs to such alkynes as phenylacetylene and diphenylbutadiyne. The disproportionation is considered to proceed by nucleophilic attack upon tin (259, 260), e.g.,... 

The chemistry of elemental sulfur and sulfur-rich molecules including polysulfides in liquid ammonia [82] and in primary as well as secondary amines [83] is complex because of the possible formation of sulfur-nitrogen compounds. Therefore, polysulfide solutions in these solvents will not be discussed here. Inert solvents which have often been used are dimethylfor-mamide (DMF) [84-86], tetrahydrofuran (THF) [87], dimethylsulfoxide (DMSO) [87], and hexamethylphosphoric triamide (HMPA) [86, 88]. 

The final ring coupling reaction is usually an O-alkylation of the sodium enolate with a methyl sulfonate-, bromo-, or chloro-butenolide in acetonitrile or an ether solvent (8.22-24). Use of the methyl sulfonate derivative is least preferred because of its poor stability (9,24). The isolated hydroxymethylene lactone can be allowed to react with the bromobutenolide using potassium carbonate in hexamethylphosphoric triamide (caution a potential carcinogen). 

Displacement of the 1 -chlorosulfate group in compound 55 has been achieved by the use of a dipolar, aprotic solvent. When compound 55 was heated in hexamethylphosphoric triamide at 95°, it gave, after chromatography on silica gel, 2,3,4,3, 4 -penta-0-benzoyl-6,l, 6 -trichloro-6,l, 6 -trideoxysucrose (56) in 63% yield.78 The yield of 56 was raised to 88% when compound 55 was treated with sodium chloride in hexamethylphosphoric triamide for 24 h at 95°. It is of interest that a similar displacement of the sulfonyloxy group at C-l has so far been unsuccessful. 

Caubere et al. [64, 65] also employed enolates as nucleophiles to intercept the intermediates produced from 32a and the mixture of sodium amide and a sodium enolate. Scheme 6.12 illustrates the results obtained by using the enolates of cyclohexanone and cyclopropyl methyl ketone. The former furnished only the ketone 43 in hexamethylphosphoric triamide as solvent, but almost exclusively the cyclobuta-... 

High-energy irradiation of the lower alcohols gives solvated electrons, solvated protons and radicals [64]. Solvated electrons are also obtained by irradiation of the aprotic amide solvents [65] frequently used in organic electrochemistry and by the irradiation of hexamethylphosphoric triamide [66], N-Methylpyrrolidone which has properties similar to dimethylformaraide, is a useful solvent for the generation of solvated electrons because the reaction between electrons and protons is relatively slower than with dimethylformamide [67],... 

DMSO and /V, A- dime th y I fo nn a in i d c (DMF) are particularly effective in enhancing the reactivity of enolate ions, as Table 1.2 shows. Both of these compounds belong to the polar aprotic class of solvents. Other members of this class that are used as solvents in reactions between carbanions and alkyl halides include N-mcthyI pyrro I i donc (NMP) and hexamethylphosphoric triamide (HMPA). Polar aprotic solvents, as their name implies, are materials which have high dielectric constants but which lack hydroxyl groups or other... 

A-Alkylation, -acylation and -sulfonation are also promoted by a polar solvent, such as HMPA (hexamethylphosphoric triamide).This acts to solvate the ions (promoting dissociation), but in a non-polar solvent like diethyl ether or tetrahydrofuran (THF), attack by most carbon electrophiles upon indolylmagnesium bromide proceeds at C-3 (Scheme 7.9). 

For A-(trimethylsilylmethyl)-5-methylisothioureas 262, cycloaddition with carbonyl compounds results in 2-aminooxazolines 263. ° Aliphatic and aromatic aldehydes and ketones can be employed successfully. However, reaction with ketones appears to be poor. Ylide generation with CsF is the method of choice although TBAF and KF have also been used but with lower yields. A polar solvent such as MeCN, DMF, or hexamethylphosphoric triamide (HMPA) is required for a succesful reaction (Scheme 8.73). 

After selective generation of the syn- or anH -enolate of an amide, it is usually reacted with a haloalkane, often the iodide. Allylic and benzylic bromides also react satisfactorily, and dimethyl and diethyl sulfate have also been used in some cases. A solution of the alkylating agent in an ethereal solvent, usually tetrahydrofuran, is added to the enolate, usually at low temperature. A polar, aprotic cosolvent, such as hexamethylphosphoric triamide, is frequently used as an additive in the alkylation step. The use of this suspected carcinogen is prohibited in some countries, which limits the usefulness of many of the reactions described below. However, similarly effective in many cases are some ureas, such as the commercially available 1,3-dimethyl-3,4,5,6-tetrahydro-2(l//)-pyrimidinone (DMPU)12. 

Solvents that have been less extensively used are N-methyl-2-pyrrolidinone and hexamethylphosphoric triamide.183 The author of this article183 also discussed the purification of chlorotrimethylsilane, and the anomalous results that may be obtained from the use of impure reagent have been commented on in the case of analyses of pentaerythritol.184 The various methods available for the bulk purification of methyl sulfoxide have been reviewed,185 and a symposium on this compound reviewed its use as a solvent in selected reactions.186... 

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