Hexamethylphosphoric triamide,

Alternate Names HMPA hexamethylphosphoramide hexam-etapol hempa HMPT. 

Physical Data mp 7.2 °C bp 230-232 °CV740 mmHg d 1.025 gcm mild amine odor. 

Drying distilled from CaH2 or BaO at reduced pressure and stored under N2 over molecular sieves. 

Handling, Storage, and Precautions has low to moderate acute toxicity in mammals. Inhalation exposure to HMPA htis been shown to induce nasal tumors in rats, and has been classified under Industrial Substances Suspect of Carcinogenic Potential for Man Adequate precautions must be taken to avoid all forms of exposure to HMPA. 

activating the aggregate through insertion into the aggregate site normally occupied by the anionic fragment,  

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HMPT = hexamethylphosphoric triamide (more correct than hexamethylphosphor-amide HMPA). 

The synthesis of phenoxaphosphine-containing PODs by the cyclodehydration of polyhydra2ides obtained from 2,8-dichloroformyl-lO-phenylphenoxaphosphine-lO-oxide and aUphatic and aromatic dihydra2ides has been described (60). All polymers are soluble in formic acid, y -cresol, and cone H2SO4, but insoluble or partially soluble in ben2ene, chloroform, and hexamethylphosphoric triamide. 

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... 

The first displacement reaction at C-2 position in carbohydrates was achieved during the study of sulfuryl chloride reaction with sucrose (92). Treatment of 3,4,6,3, 4, 6 -hexa-0-acetylsucrose 2,l -bis(chlorosulfate) with lithium chloride in hexamethylphosphoric triamide at 80°C for 20 h led to the corresponding 2,l -maimo derivative in 73% yield. 

Bromine or chlorine dissolved in hexamethylphosphoric triamide [680-31-9] (HMPT) with a base, eg, NaH2PO, present, oxidizes primary and secondary alcohols to carbonyl compounds in high yield (38). 

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. 

Catdion Hexamethylphoaphoric triamide vapors have been reported to cause cancer in rata [J. A. Zapp, Jr., Science, 190, 422 (1975)]. All operations uiith hexamethylphosphoric triamide should be perjormed in a good hood, and care should be taken to keep the liquid off the akin. 

The Roussel group has described recently a novel method for the synthesis of 2,2-dimethyl-A" -3-keto steroids. Thus addition of potassium t-butoxide to a solution of 19-nortestosterone (25) in tetrahydrofuran containing methyl iodide and hexamethylphosphorous triamide at —70° affords the 2,2-dimethyl compound (26) in good yield.Methylation of A" -3-ketone by the classical conditions, namely addition of methyl iodide to a solution of the steroid and potassium /-butoxide, leads to the 4,4-dimethyl product. 

Reactions of ionic or covalent azides with chalcogen halides or, in the case of sulfur, with the elemental chalcogen provide an alternative route to certain chalcogen-nitrogen compounds. Eor example, the reaction of sodium azide with cyclo-Sa in hexamethylphosphoric triamide is a more convenient synthesis of S7NH than the S2CI2 reaction (Section 6.2.1). Moreover, the azide route can be used for the preparation of 50% N-enriched S7NH. 

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. 

Hexamethylphosphorous triamide general reaction with aromatic and heteroaromatic aldehydes to give diaryl ethylene oxides, 46,... 

Ethyl l//-azepine-l-carboxylate and chlorotrimethylsilane, in hexamethylphosphoric triamide in the presence of magnesium, followed by quenching into water, yields the 1 2 trans-adduct 3.279 The reaction follows a similar path with dichlorodimethylsilane, whereas with dichloro-diphenylsilane a mixture of the 1 2 adduct 4 and the disiloxane 5 is obtained. 

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). 

On the other hand, the predominant formation of the diastereomeric aldols 3 b results from the titanium enolate 1 b of (S )-5,5-dimethyl-4-tert-butyldimethylsilyloxy-3-hexanone. For this purpose, the ketone is first deprotonated with A-(bromomagnesio)-2,2,6,6-tetramethylpiperidine and the magnesium enolate, presumably (E) configurated, formed is thereby treated with hexamethylphosphoric triamide and triisopropyloxytitanium chloride. After sonification, the aldehyde is added to give predominantly aldol adducts 3b the diastereomeric ratio of 3b/2b surpasses 95 5 and the chemical yields range from 85 to 88%53b. 

It is very interesting, however, that in alkane potassium diazoate alkylations with Meerwein s reagent (triethyloxonium tetrafluoroborate, Et30+BF4) in CH2C12 suspensions or with alkyl halides in hexamethylphosphoric triamide solutions, azoxy compounds (6.4) are formed, i.e., alkylation takes place at the (3-nitrogen (Moss et al., 1972). 

HMPT, see Hexamethylphosphoric triamide Host-guest complexation, general 289ff., 293ff., 321, see also Crown ether complexes... 

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... 

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