Dimethylcarbamoyl chloride (DMCC) is a reagent for transferring a dimethylcarbamoyl group to alcoholic or phenolic hydroxyl groups forming dimethyl carbamates, usually having pharmacological or pesticidal activities. Because of its high toxicity and its carcinogenic properties shown in animal experiments and presumably also in humans,[1] dimethylcarbamoyl chloride can only be used under stringent safety precautions.
The production of dimethylcarbamoyl chloride from phosgene and dimethylamine was reported as early as 1879 (reported as "Dimethylharnstoffchlorid" – dimethylurea chloride).[2]
DMCC can be produced in high yields (90%) at 275 °C by reacting phosgene with gaseous dimethylamine in a flow reactor.[3] To suppress the formation of ureas, excess phosgene is used (in a 3:1 ratio).
The reaction can also be carried out at the laboratory scale with diphosgene or triphosgene and an aqueous dimethylamine solution in the two-phase system of benzene–xylene and water in a stirred reactor with sodium hydroxide as an acid scavenger. However, considerably lower yields (56%) are achieved due to the hydrolysis sensitivity of DMCC.[4]
A more recent process is based on chlorodimethylamine, which is converted practically quantitatively to dimethylcarbamoyl chloride on a palladium catalyst under pressure with carbon monoxide at room temperature.[6]
Dimethylcarbamoyl chloride is a clear, colorless, corrosive and flammable liquid with a pungent odor and a tear-penetrating effect, which decomposes rapidly in water.[10] Because of its unpleasant, toxic, mutagenic and carcinogenic properties,[11][12] it has to be used under extreme precautions.
The reaction of DMCC with DMF forms tetramethylformamidinium chloride,[16] which is a major intermediate in the preparation of tris(dimethylamino)methane, a reagent for the introduction of enamine functions in conjunction with activated methylene groups[17] and the preparation of amidines.[18]
^Pohanish, R. P. (2011). Sittig's Handbook of Toxic and Hazardous Chemicals and Carcinogens (6th ed.). Amsterdam: Elsevier. pp. 1045–1047. ISBN978-1-4377-7869-4.
^Slocombe, R. J.; Hardy, E. A.; Saunders, J. H.; Jenkins, R. L. (1950). "Phosgene derivatives. The preparation of isocyanates, carbamyl chlorides and cyanuric acid". Journal of the American Chemical Society. 72 (5): 1888–1891. doi:10.1002/ja01161a009 (inactive 1 November 2024).{{cite journal}}: CS1 maint: DOI inactive as of November 2024 (link)
^Babad, H.; Zeiler, A. G. (1973). "Chemistry of phosgene". Chemical Reviews. 73 (1): 75–91. doi:10.1021/cr60281a005.
^Saegusa, T.; Tsuda, T.; Isegawa, Y. (1971). "Carbamoyl chloride formation from chloramine and carbon monoxide". The Journal of Organic Chemistry. 36 (6): 858–860. doi:10.1021/jo00805a033.
^Stare, M.; Laniewski, K.; Westermark, A.; Sjögren, M.; Tian, W. (2009). "Investigation on the formation and hydrolysis of N,N-dimethylcarbamoyl chloride (DMCC) in Vilsmeier reactions using GC/MS as the analytical detection method". Organic Process Research & Development. 13 (5): 857–862. doi:10.1021/op900018f.
^Levin, D. (1997). "Potential toxicological concerns associated with carboxylic acid chlorination and other reactions". Organic Process Research & Development. 1 (2): 182. doi:10.1021/op970206t.
^Jäger, P.; Rentzea, C. N.; Kieczka, H. (2014). "Carbamates and carbamoyl chloride". Ullmann's Fine Chemicals. Weinheim: Wiley-VCH. pp. 57–58. ISBN978-3-527-33477-3.
^De Cusati, P. F.; Olofson, R. A. (1990). "A simple synthesis of 1-(1,3-butadienyl)carbonates and carbamates". Tetrahedron Letters. 31 (10): 1405–1408. doi:10.1016/S0040-4039(00)88817-6.
^Lawson, J. K. Jr.; Croom, J. A. T. (1963). "Dimethylamides from alkali carboxylates and dimethylcarbamoyl chloride". The Journal of Organic Chemistry. 28 (1): 232–235. doi:10.1021/jo1036a513 (inactive 1 November 2024).{{cite journal}}: CS1 maint: DOI inactive as of November 2024 (link)
^US 3597478, Weakly, M. L., "Preparation of tetramethylurea", issued 1971年08月03日, assigned to Nipak Inc.
^Arnold, Z. (1959). "The preparation of tetramethylformamidinium salts and their vinylogues". Collection of Czechoslovak Chemical Communications. 24 (3): 760–765. doi:10.1135/cccc19590760.
^Meerwein, H.; Florian, W.; Schön, N.; Stopp, G. (1961). "Über Säureamidacetale, Harnstoffacetale und Lactamacetale" [On acid amide acetals, urea acetals and lactam acetals]. Justus Liebigs Annalen der Chemie (in German). 641 (1): 1–39. doi:10.1002/jlac.19616410102.
^US 3452043, Grauer, T. & Urwyler, H., "Production of 1-N,N-dimethylcarbamoyl-5-methyl-3-N,N-dimethylcarbamoyloxypyrazole", issued 1969年06月24日, assigned to J. R. Geigy AG
^Aeschlimann, J. A.; Reinert, M. (1931). "Pharmacological action of some analogues of physostigmine". Journal of Pharmacology and Experimental Therapeutics. 43 (3): 413–444.
^US 1905990, Aeschlimann, J. A., "Disubstituted carbamic acid esters of phenols containing a basic constituent", issued 1933年04月25日, assigned to Hoffmann-La Roche Inc.
^US 2572579, Urban, R., "Disubstituted carbamic acid esters of 3-hydroxy-1-alkyl-pyridinium salts", issued 1951年10月23日, assigned to Hoffmann-La Roche Inc.
^DE 2558015, "Verfahren zur Herstellung des 3-N,N-Dimethylcarbamoyl-oxy-1-methyl-5-phenyl-7-chlor-1,3-dihydro-2H-1,4-benzodiazepin-2-on (Process for the preparation of 3-N,N-dimethylcarbamoyloxy-1-methyl-5-phenyl-7-chloro-1,3-dihydro-2H-1,4-benzodiazepin-2-one)", issued 1976年09月16日, assigned to Siphar SA
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