Dimethylcarbamoyl chloride

from Wikipedia, the free encyclopedia
Structural formula
Structural formula of dimethylcarbamoyl chloride
General
Surname Dimethylcarbamoyl chloride
other names
  • N, N-dimethylaminocarbonyl chloride
  • Dimethylaminocarbamychloride
  • Chloroformic acid dimethylamide
  • DMCC
Molecular formula C 3 H 6 ClNO
Brief description

clear colorless to slightly yellowish liquid

External identifiers / databases
CAS number 79-44-7
EC number 201-208-6
ECHA InfoCard 100.001.099
PubChem 6598
Wikidata Q2563907
properties
Molar mass 107.54 g mol −1
Physical state

liquid

density
  • 1.168 g cm −3 at 20 ° C
  • 1.17 g cm −3
Melting point

−33 ° C

boiling point
  • 167 ° C
  • 167-168 ° C at 1.033 hPa
  • 55-57 ° C at 11 mmHg
Vapor pressure
  • 3.6 hPa at 20 ° C
  • 0.26 kPa at 25 ° C
solubility

Decomposes in water. Soluble in inert solvents such as benzene , xylene , chloroform , acetone , ethyl acetate , 1,4-dioxane , pyridine and carbon disulfide

Refractive index

1.4540 (20 ° C, 589 nm)

safety instructions
GHS hazard labeling from  Regulation (EC) No. 1272/2008 (CLP) , expanded if necessary
06 - Toxic or very toxic 08 - Dangerous to health

danger

H and P phrases H: 302-315-319-331-335-350
P: 201-261-280-304 + 340 + 311-308 + 313-403 + 233
Toxicological data
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

Dimethylcarbamoyl chloride ( DMCC ) is a reagent for transferring the dimethylcarbonyl function to alcoholic or phenolic hydroxyl groups with the formation of dimethyl carbamates, which have pharmacological and pesticidal activities. Due to its high toxicity and its carcinogenic properties in animal experiments and probably also in humans, dimethylcarbamoyl chloride may only be used under strict safety precautions.

Occurrence and representation

As early as 1879, the preparation of dimethylcarbamoyl chloride (referred to here as "dimethylurea chloride") from phosgene and dimethylamine (DMA) was reported.

Synthesis of dimethylcarbamoyl chloride (DMCC) with dimethylamine

In the reaction of phosgene with gaseous dimethylamine in a flow reactor , dimethylcarbamoyl chloride is formed in high yield (90%) at 275 ° C. To suppress the formation of ureas, an excess of phosgene (COCl 2  : DMA = 3: 1) is used.

The reaction can also be carried out on a laboratory scale with diphosgene or triphosgene and aqueous dimethylamine solution in the two-phase system benzene + xylene / water in a stirred reactor with sodium hydroxide as acid scavenger, but with considerably low yields (56%) because of the hydrolysis sensitivity of the DMCC.

The reaction of phosgene with trimethylamine also produces dimethylcarbamoyl chloride and methyl chloride

Synthesis of dimethylcarbamoyl chloride (DMCC) with trimethylamine

A more recent process starts from dimethylamine chloride, which is converted practically quantitatively to DMCC over a palladium catalyst under pressure with carbon monoxide at room temperature.

Synthesis of dimethylcarbamoyl chloride (DMCC) from chloramine

The Vilsmeier-Haack reaction can also produce small amounts (0-20 ppm) of dicarbamoyl chloride from dimethylformamide (DMF), as does the use of DMF as a catalyst in the conversion of carboxylic acids with thionyl chloride to form the corresponding carboxylic acid chlorides .

Synthesis of dimethylcarbamoyl chloride (DMCC) with dimethylformamide (DMF)

The tendency to form DMCC depends on the chlorination reagent (thionyl chloride> oxalyl chloride > phosphorus oxychloride ) and is higher in the presence of a base. However, DMCC hydrolyzes so quickly - with a half-life of approx. 6 minutes at 0 ° C - to dimethylamine, hydrochloric acid and carbon dioxide that less than 3 ppm DMCC is found in the Vilsmeier product after aqueous work-up.

properties

Dimethylcarbamoyl chloride is a clear, colorless, corrosive and flammable liquid with a pungent odor and tear-irritating effect, which decomposes quickly in water. Because of its unpleasant handling as well as its toxic, mutagenic and carcinogenic properties, which have been shown in animal experiments, DMCC should be handled with extreme caution.

Dimethylcarbamoyl chloride behaves like an acid chloride , the chlorine atom of which can be exchanged for other nucleophiles . It reacts with alcohols, phenols and oximes to form the corresponding N, N-dimethyl carbamates , with thiols to form thiolourethanes , with amines and hydroxylamine to form substituted ureas and with imidazoles and triazoles to form carbamoylazoles.

Reactions of dimethylcarbamoyl chloride (DMCC) with nucleophiles

DMCC is less reactive and less selective towards substrates with multiple nucleophilic centers than conventional acid chlorides.

Unsaturated conjugated aldehydes such as crotonaldehyde react with dimethylcarbamoyl chloride to form dienyl carbamates,

Synthesis of dienyl carbamates with dimethyl carbamoyl chloride (DMCC)

which can be used as dienes in Diels-Alder reactions .

The corresponding dimethylamides are formed in the reaction of dimethylcarbamoyl chloride with alkali metal carboxylates. DMCC reacts with anhydrous sodium carbonate or with excess dimethylamine to form tetramethylurea .

The reaction of DMCC with DMF produces tetramethylformamidinium chloride, an essential intermediate in the preparation of tris (dimethylamino) methane , a reagent for the introduction of enamine functions in connection with activated methylene groups and for the preparation of amidines .

Synthesis of tris (dimethylamino) methane with diethylcarbamoyl chloride (DMCC)

Dimethylcarbamoyl chloride is a starting material for the insecticide class of dimethyl carbamates, which act as inhibitors of acetylcholinesterase , including dimetilane,

Synthesis of dimetilane with dimethylcarbamoyl chloride

and the related compounds isolan , pirimicarb and triazamate .

The quaternary ammonium compounds neostigmine , which is obtained from 3-dimethylaminophenol and dimethylcarbamoyl chloride and subsequent quaternization with methyl bromide or dimethyl sulfate, are used in pharmaceuticals as acetylcholinesterase inhibitors

Synthesis of neostigmine with dimethylcarbamoyl chloride

and pyridostigmine , which is accessible from 3-hydroxypyridine and DMCC and subsequent reaction with methyl bromide.

Synthesis of pyridostigmine with dimethylcarbamoyl chloride

Dimethylcarbamoyl chloride is also used in the synthesis of the benzodiazepine camazepam.

Synthesis of camazepam using dimethylcarbamoyl chloride

Individual evidence

  1. ↑ a b c data sheet diethylcarbamoyl chloride from Sigma-Aldrich , accessed on September 20, 2016 ( PDF ).
  2. ↑ a b c data sheet dimethylcarbamoyl chloride from AlfaAesar, accessed on September 20, 2016 ( PDF )(JavaScript required) .
  3. ↑ a b c d e f Entry on dimethylcarbamoyl chloride in the GESTIS substance database of the IFA , accessed on January 10, 2017(JavaScript required) .
  4. ^ A b William M. Haynes: CRC Handbook of Chemistry and Physics, 96th Edition . CRC Press, Boca Raton, FL, USA 2015, ISBN 978-1-4822-6097-7 , pp. 3-206 .
  5. ↑ a b Entry on Dimethylcarbamoyl Chloride at TCI Europe, accessed on September 20, 2016.
  6. ↑ a b C.B. Kreutzberger, RA Olofson: Dimethylcarbamoyl Chloride . In: e-EROS Encyclopedia of Reagents for Organic Synthesis . 2001, doi : 10.1002 / 047084289X.rd319 .
  7. ↑ a b c Patent DOS2448015 : Process for the preparation of 3-N, N-dimethylcarbamoyl-oxy-1-methyl-5-phenyl-7-chloro-1,3-dihydro-2H-1,4-benzodiazepin-2-one . Applied on December 22, 1975 , published September 16, 1976 , applicant: Siphar SA. ‌
  8. ↑ a b Patent US2572579 : Disubstituted carbamic acid esters of 3-hydroxy-1-alkyl-pyridinium salts. Applied on May 18, 1948 , published October 23, 1951 , applicant: Hoffmann-La Roche Inc., inventor: R. Urban. ‌
  9. ↑ a b W. Michler, C. Escherich: Ueber multiply substituted ureas . In: Ber. German Chem. Ges. Volume 12 , no. 1 , 1879, p. 1162–1164 , doi : 10.1002 / cber.187901201303 .
  10. ↑ Entry on dimethylcarbamoyl chloride in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on December 16, 2016. Manufacturers or distributors can expand the harmonized classification and labeling .
  11. ↑ RP Pohanish: Sittig's Handbook of Toxic and Hazardous Chemicals and Carcinogens, 6th Edition . Elsevier, Amsterdam 2011, ISBN 978-1-4377-7869-4 , pp. 1045-1047 .
  12. ^ RJ Slocombe, EA Hardy, JH Saunders, RL Jenkins: Phosgene derivatives. The preparation of isocyanates, carbamyl chlorides and cyanuric acid . In: J. Am. Chem. Soc. tape 72 , no. 5 , 1950, pp. 1888-1891 , doi : 10.1002 / ja01161a009 .
  13. ↑ G. Karimipour, S. Kowkabi, A. Naghiha: New aminoporphyrins bearing urea derivative substitents: synthesis, characterization, antibacterial and antifungal activity . In: Braz. Arch. Biol. Technol. tape 58 , no. 3 , 2015, doi : 10.1590 / S1516-891320500024 ( scielo.br ).
  14. ^ H. Babad, AG Zeiler: Chemistry of Phosgene . In: Chem. Rev. Band 73 , no. 1 , 1973, p. 75-91 , doi : 10.1021 / cr60281a005 .
  15. ↑ T. Saegusa, T. Tsuda, Y. Isegawa: Carbamoyl chloride formation from chloramine and carbon monoxide . In: J. Org. Chem. Band 36 , no. 6 , 1971, p. 858-860 , doi : 10.1021 / jo00805a033 .
  16. ↑ M. Stare, K. Laniewski, A. Westermark, M. Sjögren, W. Tian: Investigation on the formation and hydrolysis of N, N-dimethylcarbamoyl chloride (DMCC) in Vilsmeier reactions using / GC / MS as the analytical detection method . In: Org. Process Res. Dev. Band 13 , no. 5 , 2009, p. 857-862 , doi : 10.1021 / op900018f .
  17. ^ D. Levin: Potential toxicological concerns associated with carboxylic acid chlorination and other reactions . In: Org. Process Res. Dev. Band 1 , no. 2 , 1997, p. 182 , doi : 10.1021 / op970206t .
  18. ^ A. Queen: Kinetics of the hydrolysis of acyl chlorides in pure water . In: Canad. J. Chem. Volume 45 , no. 14 , 1967, p. 1619-1629 , doi : 10.1139 / v67-264 .
  19. ↑ P. Jäger, CN Rentzea, H. Kieczka: Carbamates and Carbamoyl Chloride, in Ullmann's Fine Chemicals . Wiley-VCH, Weinheim 2014, ISBN 978-3-527-33477-3 , pp. 57-58 .
  20. ↑ Dimethylcarbamoyl Chloride, CAS No. 79-44-7. In: Report on Carcinogens, Thirteenth Edition. National Toxicology Program, Department of Health and Human Services, accessed September 25, 2016 .
  21. ↑ CB Kreutzberger, RA Olofson: Dimethylcarbamoyl Chloride. John Wiley & Sons, Ltd., February 1, 2007, accessed September 27, 2016 .
  22. ↑ PF De Cusati, RA Olofson: A simple synthesis of 1- (1,3-butadienyl) carbonates and carbamates . In: Tetrahedron Lett. tape 31 , no. 10 , 1990, pp. 1405-1408 , doi : 10.1016 / S0040-4039 (00) 88817-6 .
  23. ^ JK Lawson, Jr., JAT Croom: Dimethylamides from alkali carboxylates and dimethylcarbamoyl chloride . In: J. Org. Chem. Band 28 , no. 1 , 1963, p. 232-235 , doi : 10.1021 / jo1036a513 .
  24. ↑ Patent US3597478 : Preparation of tetramethylurea. Applied on September 14, 1967 , published August 3, 1971 , applicant: Nipak Inc., inventor: ML Weakly. ‌
  25. ^ Z. Arnold: The preparation of tetramethylformamidinium salts and their vinylogues . In: Coll. Czech. Chem. Commun. tape 24 , 1959, pp. 760-765 , doi : 10.1135 / cccc19590760 .
  26. ↑ H. Meerwein, W. Florian, N. Schön, G. Stopp: About acid amide acetals, urea acetals and lactam acetals . In: Justus Liebigs Ann. Chem. Band 641 , no. 1 , 1961, pp. 1-39 , doi : 10.1002 / jlac.19616410102 .
  27. ↑ H. Bredereck, F. Effenberger, Th. Brendle: Synthesis and reactions of Trisdimethylaminomethan . In: Angew. Chem. Band 78 , no. 2 , 1966, p. 147-148 , doi : 10.1002 / anie.19660780212 .
  28. ^ Compendium of Pesticide Common Names. Alan Wood, accessed September 27, 2016 .
  29. ↑ Patent US3452043 : Production of 1-N, N-dimethylcarbamoyl-5-methyl-3-N, N-dimethyl-carbamoyl-oxy-pyrazole. Applied March 8, 1967 , published June 24, 1969 , applicant: JR Geigy AG, inventor: T. Grauer, H. Urwyler. ‌
  30. ↑ JA Aeschlimann, M. Reinert: Pharmacological action of some analogues of physostigmine . In: J. Pharmacol. Exp. Ther. tape 43 , no. 3 , 1931, p. 413-444 .
  31. ↑ Patent US1905990 : Disubstituted carbamic acid esters of phenols containing a basic constituent. Applied on April 8, 1931 , published on April 25, 1933 , applicant: Hoffmann-La Roche Inc., inventor: JA Aeschlimann. ‌