Hexamethylphosphoric triamide

Structural formula
General
Surname	Hexamethylphosphoric triamide
other names	Hempa; Hexametapole; Tris (dimethylamino) phosphine oxide; Hexamethylphosphoramide; HMPT; HMPTA; HMPA; HPT; liquid cancer;
Molecular formula	C 6 H 18 N 3 OP
Brief description	colorless liquid
External identifiers / databases
EC number	211-653-8
ECHA InfoCard	100.010.595
PubChem	12679
Wikidata	Q416086
properties
Molar mass	179.20 g mol −1
Physical state	liquid
density	1.024 g cm −3 (25 ° C)
Melting point	7 ° C
boiling point	233 ° C
Vapor pressure	9 Pa (25 ° C)
solubility	Can be mixed with water as required
Refractive index	1.4579 (20 ° C)
safety instructions
GHS hazard labeling from Regulation (EC) No. 1272/2008 (CLP) , expanded if necessary danger
H and P phrases	H: 340-350
	P: 201-308 + 313
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . Refractive index: Na-D line , 20 ° C

Hexamethylphosphoric acid triamide ( HMPT for short ) is an organic compound that can be assigned to the substance group of phosphoric acid amides. It is used as a solvent in organic chemistry . The aprotic - polar solvent dissolves both inorganic and organic compounds, many plastics and gases.

Presentation and extraction

Hexamethylphosphoric triamide can be produced by reacting phosphorus oxychloride with dimethylamine .

{\ displaystyle \ mathrm {OPCl_ {3} +3 \, HN (CH_ {3}) _ {2} \ rightarrow OP (N (CH_ {3}) _ {2}) _ {3} +3 \, HCl }}

properties

Hexamethylphosphoric triamide is a colorless liquid that has a melting point of 7 ° C and a boiling point of 233 ° C under normal pressure . The compound is completely miscible with water. The heat capacity at 25 ° C is 321.3 J mol ⁻¹ K ⁻¹ or 1.793 J g ⁻¹ K ⁻¹ . At elevated temperatures, flammable vapor-air mixtures can be formed. The flash point is 105 ° C. The ignition temperature is 230 ° C. The substance therefore falls into temperature class T3.

use

In the DMF , DMSO and HMPT series , HMPT is the best aprotic-polar solvent. Hence it is used in organic synthesis. However, the disadvantage is that the substance is a particularly dangerous carcinogenic and mutagenic substance (in category 1B). Therefore the substance according to Annex II No. 6 of the German GefStoffV may only be manufactured or used in closed systems. Because of its carcinogenic properties, HMPT is sometimes also referred to as liquid cancer in laboratory jargon . Due to its toxic properties, attempts are being made to replace HMPT with other solvents - especially those mentioned above, or the urea derivatives dimethylpropyleneurea (DMPU) and 1,3-dimethyl-2-imidazolidinone (DMI). Other substitutes are N- methyl-2-pyrrolidone (NMP), sulfolane and carbonic acid esters .

safety instructions

The compound has been shown to be clearly carcinogenic in animal experiments. It is absorbed through the skin. HMPT causes the internal bridging of DNA - duplexes . The enzymatic metabolism of HMPT by means of cytochrome P450 leads to N - demethylation and consequently to the oxidative formation of formaldehyde . The high carcinogenic potential of phosphoramide could result from the interaction of the release of formaldehyde within cells and additional mitogenesis stimulation.

Individual evidence

↑ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l Entry on hexamethylphosphoric triamide in the GESTIS substance database of the IFA , accessed on January 8, 2020(JavaScript required) .
↑ ^a ^b ^c Entry on hexamethylphosphoric acid triamide. In: Römpp Online . Georg Thieme Verlag, accessed on December 15, 2017.
↑ David R. Lide (Ed.): CRC Handbook of Chemistry and Physics . 90th edition. (Internet version: 2010), CRC Press / Taylor and Francis, Boca Raton, FL, Physical Constants of Organic Compounds, pp. 3-280.
↑ Entry on Hexamethylphosphoric triamide in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on February 1, 2016. Manufacturers or distributors can expand the harmonized classification and labeling .
↑ BB Pavankumar, EV Goud, R. Selvakumar, SKA Kumar, A. Sivaramakrishna, K. Vijayakrishna, CVS Rao, KN Sabharwal, PC Jha: Function of substitents in coordination behavior, thermolysis and ligand crossover reactions of phosphine oxides. In: RSC Advances. 5, 2015, pp. 4727-4736, doi: 10.1039 / c4ra13645d .
↑ AF Vorob'ev, PN Yakovlev: The specific heats of dimethylformamide-water and hexamethylphosphoramide-water mixtures. In: Zhur. Fiz. Khim. 56, 1982, pp. 1933-1936.
↑ Hazardous Substances Ordinance. Status: April 2017.
↑ M. Wiecko: Complex divalent lanthanides and alkaline earth metals and new bonds with metals of Group 13. Cuvillier Verlag, Göttingen 2008, ISBN 978-3-86727-689-4 .
↑ Florian Mummy: Polymer supported organocatalysts for regio- and stereoselective synthesis. 2012. urn: nbn: de: kobv: 188-fudissthesis000000039472-8
↑ Marco Röben: NMR spectroscopic investigations of the Cph1-, Agp1-bound and the free chromophore to elucidate the phytochrome photocycle. 2012. urn: nbn: de: kobv: 188-fudissthesis000000036732-2
↑ Triptikumar Mukhopadhyay, Dieter Seebach : substitution of HMPT by the cyclic urea DMPU as a cosolvent for highly reactive nucleophilic and bases. In: Helvetica Chimica Acta . 65, 1982, pp. 385-391.
^ EW Vogel, AT Natarajan: DNA damage and repair in somatic and germ cells in vivo. In: Mutation Research. (330), 1995, p. 183.

[GESTIS-1] ↑ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l Entry on hexamethylphosphoric triamide in the GESTIS substance database of the IFA , accessed on January 8, 2020(JavaScript required) .

[Roempp-2] Entry on hexamethylphosphoric acid triamide. In: Römpp Online . Georg Thieme Verlag, accessed on December 15, 2017.

[CRC90_3_280-3] David R. Lide (Ed.): CRC Handbook of Chemistry and Physics . 90th edition. (Internet version: 2010), CRC Press / Taylor and Francis, Boca Raton, FL, Physical Constants of Organic Compounds, pp. 3-280.

[CLP_100.010.595-4] Entry on Hexamethylphosphoric triamide in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on February 1, 2016. Manufacturers or distributors can expand the harmonized classification and labeling .

[5] BB Pavankumar, EV Goud, R. Selvakumar, SKA Kumar, A. Sivaramakrishna, K. Vijayakrishna, CVS Rao, KN Sabharwal, PC Jha: Function of substitents in coordination behavior, thermolysis and ligand crossover reactions of phosphine oxides. In: RSC Advances. 5, 2015, pp. 4727-4736, doi: 10.1039 / c4ra13645d .

[6] AF Vorob'ev, PN Yakovlev: The specific heats of dimethylformamide-water and hexamethylphosphoramide-water mixtures. In: Zhur. Fiz. Khim. 56, 1982, pp. 1933-1936.

[7] Hazardous Substances Ordinance. Status: April 2017.

[8] M. Wiecko: Complex divalent lanthanides and alkaline earth metals and new bonds with metals of Group 13. Cuvillier Verlag, Göttingen 2008, ISBN 978-3-86727-689-4 .

[9] Florian Mummy: Polymer supported organocatalysts for regio- and stereoselective synthesis. 2012. urn: nbn: de: kobv: 188-fudissthesis000000039472-8

[10] Marco Röben: NMR spectroscopic investigations of the Cph1-, Agp1-bound and the free chromophore to elucidate the phytochrome photocycle. 2012. urn: nbn: de: kobv: 188-fudissthesis000000036732-2

[11] Triptikumar Mukhopadhyay, Dieter Seebach : substitution of HMPT by the cyclic urea DMPU as a cosolvent for highly reactive nucleophilic and bases. In: Helvetica Chimica Acta . 65, 1982, pp. 385-391.

[12] EW Vogel, AT Natarajan: DNA damage and repair in somatic and germ cells in vivo. In: Mutation Research. (330), 1995, p. 183.