HMPT

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

To a solution of 0,35 mol of allenyll ithium in about 240 ml of hexane and 200 ml of THF, prepared according to Chapter II, Exp. 13, were added 35 g of dry HMPT at -85°C. r.-Hexyl bromide (0.30 mol) was then added dropwise in 15 min, whilst keeping the temperature of the reaction mixture close to -70 0 (liquid nitrogen bath). After the addition the mixture was held at -60°C for an additional 1 h. 

The alkylations proceeded much more slowly, when ethyl- or butyllithium in diethyl ether, prepared from the alkyl bromides, had been used for the metallation of allene, in spite of the presence of THF and HMPT as co-solvents. 

The reaction was strongly exothermic. After the addition the cooling bath was removed and after 20 min the almost clear solution was poured into 500 ml of water. After shaking and separation of the layers the organic solution was washed five times with 200-ml portions of water in order to remove the HMPT (note 2). 

Note 2. It is essential to remove the HMPT completely, as it cannot be separated... 

The salt gradually dissolved. After an additional 30 min (at -60°C) the solution was cooled to -75°C and 19 ml of dry, pure HMPT and 0.4 mol (large excess) of ethylene oxide (cooled below 0°C) were added successively in 1-2 min. The temperature of the mixture was held at -60°C for 2 h, and was then allowed to rise gradually in 2 h to 0°C. Ice-water (200 ml) was added (with stirring) and, after Separation of the layers, five extractions with diethyl ether were carried out. 

To a solution of 0.30 mol of ethyllithium (note 1) in about 270 ml of diethyl ether (see Chapter II, Exp. 1) v/as added 0.30 mol of methoxyallene at -20°C (see Chapter IV, Exp. 4) at a rate such that the temperature could be kept between -15 and -2Q°C. Fifteen minutes later a mixture of 0.27 mol of >z-butyl bromide and 100 ml of pure, dry HMPT ivas added in 5 min with efficient cooling, so that the temperature of the reaction mixture remained below 0°C. The cooling bath was then removed and the temperature was allowed to rise. After 4 h the brown reaction mixture was poured into 200 ml of ice-water. The aqueous layer was extracted twice with diethyl ether. The combined solutions were washed with concentrated ammonium chloride solution (which had been made slightly alkaline by addition of a few millilitres of aqueous ammonia, note 2) and dried over potassium carbonate. After addition of a small amount (2-5 ml) of... 

Note 1. If the lithiation of the allenic ether is performed with butyllithium in hexane and THF as a co-solvent, subsequent alkylation (in the presence of a small amount of HMPT) is much faster. The separation of the volatile product from the hexane and THF is difficult, however. 

A solution of 0.60 mol of ethyllithium (note 1) in about 400 ml of diethyl ether (see Chapter II, Exp. 1) was added in 30 min to a mixture of 0.25 mol of 1,4-diethoxy-2-butyne (see Chapter VIII-6, Exp. 8) and 100 ml of dry diethyl ether. The temperature of the reaction mixture was kept between -40 and -45°C. Fifteen minutes after the addition had been completed, 0.5 mol of methyl iodide was added at -40 C, then 100 ml of dry HMPT (for the purification see ref. 1) were added dropwise in 15 min while keeping the temperature at about -40°C. Thirty minutes after this addition the cooling bath was removed, the temperature was allowed to rise and stirring was continued for 3 h. The mixture was... 

In the flask were succesively placed 0.10 mol of the sulfinate (note 2), 25 ml of dry, pure HMPT (note 3), 4 g of powdered sodium iodide, 40 g of zinc dust and some boiling stones. After swirling for a few seconds the flask was connected with the other parts of the distillation apparatus, the system was evacuated immediately by means of the water pump (note 4) and the flask was then heated cautiously (free flame). A vigorous reaction started suddenly and the cumulene and part of the HMPT passed over. When the distillation had stopped completely... 

Vote 3. If more HMPT is used the yield of the cumulene will be lower the compound can remain longer in the hot reaction mixture, where it can polymerize. Mote 4. It is essential to follow the instructions given. The reaction sometimes starts very soon if in such a case the desired pressure (10-20 mmHg) has not yet been achieved, part of the cumulene may polymerize in the hot reaction mixture. 

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). 

For the NH azoles (Table 3), the two tautomeric forms are usually rapidly equilibrating on the NMR timescale (except for triazole in HMPT). The iV-methyl azoles (Table 4) are fixed chemical shifts are shifted downfield by adjacent nitrogen atoms, but more by a pyridine-like nitrogen than by a pyrrole-like iV-methyl group. 

Hi) The fact that the signal of the substituent in position 5 is more sensitive to solvent effects than that of the 3-substituent. This is true for protons and methyl groups, the best solvents for these studies being benzene, CDCI3, DMSO and HMPT. A beautiful illustration of this method is provided by the establishment of the structure of the six l,l -dimethyl-bipyrazolyl isomers (72JHC1373). 

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