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| | Dimethylcarbamoyl chloride Chemical Properties |
| Melting point | −33 °C(lit.) | | Boiling point | 167-168 °C775 mm Hg(lit.) | | density | 1.168 g/mL at 25 °C(lit.) | | refractive index | n20/D 1.453 | | Fp | 155 °F | | solubility | Chloroform (Soluble), DMSO (Sparingly) | | form | Liquid | | pka | -1.85±0.70(Predicted) | | Specific Gravity | 1.172 | | color | Colorless to Yellow | | Water Solubility | Decomposes | | Sensitive | Moisture Sensitive | | BRN | 878197 | | Exposure limits | ACGIH: TWA 0.005 ppm (Skin) | | Stability: | Moisture Sensitive | | CAS DataBase Reference | 79-44-7(CAS DataBase Reference) | | IARC | 2A (Vol. 12, Sup 7, 71) 1999 | | NIST Chemistry Reference | Carbamic chloride, dimethyl-(79-44-7) | | EPA Substance Registry System | Dimethylcarbamoyl chloride (79-44-7) |
| Hazard Codes | T | | Risk Statements | 45-22-23-36/37/38 | | Safety Statements | 53-45-99 | | RIDADR | UN 2262 8/PG 2 | | WGK Germany | 3 | | RTECS | FD4200000 | | F | 9 | | TSCA | Yes | | HazardClass | 8 | | PackingGroup | II | | HS Code | 29241990 | | Hazardous Substances Data | 79-44-7(Hazardous Substances Data) | | Toxicity | A designated animal carcinogen
(IARC) and hazardous waste (EPA); a suspected carcinogen
in humans. It is a liquid boiling at 165_x0003_C that is used
primarily in the manufacture of drugs and pesticides. Dimethyl
carbamoyl chloride is extremely toxic. |
| | Dimethylcarbamoyl chloride Usage And Synthesis |
| Overview | Dimethylcarbamoyl chloride is a useful intermediate in the production of pharmaceuticals, pesticides, and dyes. However, due to its high toxicity that may induce both acute effects and be of cancer risk, it is strictly limited for application[1].
| | Production | Dimethylcarbamoyl chloride has been produced since 1961(IARC 1999)[2]. In 2009, it was produced commercially by one manufac¬turer in Europe and two manufacturers in India[3] and was available from 17 suppliers worldwide, including 8 U.S. suppliers[4]. No data on U.S. imports or exports of dimethyl¬ carbamoyl chloride were found. Under the U.S. Environmental Pro¬tection Agency’s Toxic Substances Control Act Inventory Update Rule, production plus imports of dimethylcarbamoyl chloride totaled be¬ tween 10,000 and 500,000 lb in 1990; no other inventory update re¬ports were filed[5].
Dimethylcarbamoyl chloride can be manufactured by the following several methods[6-8]:
- The reaction between phosgene and dimethylamine(DMA), which is the earliest method[6];
- The reaction between phosgene with trimethylamine[7];
- The reaction between dimethylamine chloride with carbon monoxide under pressure, room temperature and using palladium as catalyst[8].
| | Physiochemical properties | Dimethylcarbamoyl chloride appears as a clear liquid at room temperature with a pungent odor and a tear-penetrating effect, which decomposes rapidly in water[1-2].
Dimethylcarbamoyl chloride is similar with an acid chloride whose chlorine atom can be exchanged for other nucleophiles. Therefore, it is capable of reacting with alcohols, phenols and oximes to the corresponding N, N-dimethylcarbamates, with thiols to thiolourethanes, with amines and hydroxylamine to substituted ureas, and with imidazoles and triazoles to carbamoylazoles[9].
| | Applications | Dimethylcarbamoyl chloride is used as an intermediate in the production of pharmaceuticals, pesticides, and dyes[10]. It is a reagent being capable of transferring a dimethylcarbamoyl group to alcoholic or phenolic hydroxyl groups forming dimethyl carbamates with pharmacological or pesticidal activities[11]. Dimethylcarbamoyl Chloride is also a reagent used in the induction of apoptosis in human lung adenocarcinoma by T-type calcium channel antagonist[12].
Dimethylcarbamoyl chloride is used as the starting material for the insecticide class of the dimethyl carbamates which act as inhibitors of acetylcholinesterase such as dimetilane and the related compounds isolane, pirimicarb and triazamate[13,14].
Dimethylcarbamoyl chloride can be used for the manufacturing of the quaternary ammonium compounds neostigmine, which finds pharmaceutical applications as acetylcholinesterase inhibitors[15].
Dimethylcarbamoyl chloride is also used in the synthesis of the benzodiazepine camazepam[16].
| | Warning and Risk | Dimethylcarbamoyl chloride can cause acute effect if not used properly. It is also a potential carcinogenic regent due to its high toxicity[17-20].
Acute effect
Workers exposing to dimethylcarbamoyl chloride can suffer from both eye irritation and liver disturbance. Acute inhalation exposure to dimethylcarbamoyl chloride has been found to result in damaged mucous membranes of the nose, throat, and lungs and cause difficulty in breathing in rats. Rats and rabbits experiments have also demonstrated that acute dermal exposure can cause skin irritation as well as conjunctivitis and keratitis in eyes. In addition, acute exposure of rats has also demonstrated dimethylcarbamoyl chloride to have high acute toxicity via inhalation and moderate acute toxicity via ingestion[17].
Cancer Risk
There are inadequate data on the carcinogenic effects of dimethylcarbamoyl chloride in humans[18, 21,22]. However, cancer risk of dimethylcarbamoyl chloride has been demonstrated in the rats and mice experiments. Inhalation exposure has been found to induce nasal tract carcinomas in rats and male hamsters. Skin tumors have also been observed among dermally exposed mice. Moreover, local sarcomas have been observed following subcutaneous injection in mice[21,22].
| | References |
- https://ntp.niehs.nih.gov/ntp/roc/content/profiles/dimethylcarbamoylchloride.pdf
- http://www.allfordrugs.com/tag/dimethylcarbamoyl-chloride/
- SRI. 2009. Directory of Chemical Producers. Menlo Park, CA: SRI Consulting. Database edition. Last accessed: 4/22/09.
- ChemSources. 2009. Chem Sources Chemical Search. Chemical Sources International. http://www. chemsources.com/chemonline.html and search on dimethylcarbamoyl chloride. Last accessed: 5/09.
- EPA. 2004. Non-confidential IUR Production Volume Information. U.S. Environmental Protection Agency. http://www.epa.gov/oppt/iur/tools/data/2002-vol.html and search on CAS number. Last accessed: 4/21/05.
- G. Karimipour; S. Kowkabi; A. Naghiha[2015], "New aminoporphyrins bearing urea derivative substituents: synthesis, characterization, antibacterial and antifungal activity"[in German], Braz. Arch. Biol. Technol. 58[3], doi:10.1590/S1516-891320500024
- H. Babad; A.G. Zeiler[1973], "Chemistry of Phosgene"[in German], Chem. Rev. 73[1]: pp. 75–91, doi:10.1021/cr60281a005
- T. Saegusa; T. Tsuda; Y. Isegawa[1971], "Carbamoyl chloride formation from chloramine and carbon monoxide"[in German], J. Org. Chem. 36[6]: pp. 858–860, doi:10.1021/jo00805a033
- C.B. Kreutzberger, R.A. Olofson[2007-02-01]. "Dimethylcarbamoyl Chloride"[in German]. John Wiley&Sons, Ltd. Retrieved 2016-09-27.
- https://www.epa.gov/sites/production/files/2016-09/documents/dimethylcarbamoyl-chloride.pdf
- R.P. Pohanish[2011][in German], Sittig’s Handbook of Toxic and Hazardous Chemicals and Carcinogens, 6th Edition, Amsterdam: Elsevier, pp. 1045–1047, ISBN 978-1437778694
- https://www.trc-canada.com/product-detail/?D471295
- T. Grauer, H. Urwyler, "Production of 1-N, N-dimethylcarbamoyl-5-methyl-3-N, N-dimethyl-carbamoyl-oxy-pyrazole"
- J.A. Aeschlimann; M. Reinert[1931], "Pharmacological action of some analogues of physostigmine"[in German], J. Pharmacol. Exp. Ther. 43[3]: pp. 413–444
- J.A. Aeschlimann, "Disubstituted carbamic acid esters of phenols containing a basic constituent"
- "Verfahren zur Herstellung des 3-N, N-Dimethylcarbamoyl-oxy-1-methyl-5-phenyl-7-chlor-1,3-dihydro-2H-1,4-benzodiazepin-2-on"
- https://www.epa.gov/sites/production/files/2016-09/documents/dimethylcarbamoyl-chloride.pdf
- International Agency for Research on Cancer[IARC]. IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man: Some Carbamates, Thiocarbamates and Carbazides. Volume 12. World Health Organization, Lyon. 1976.
- U.S. Department of Health and Human Services. Hazardous Substances Data Bank[HSDB, online database]. National Toxicology Information Program, National Library of Medicine, Bethesda, MD. 1993.
- U.S. Department of Health and Human Services. Registry of Toxic Effects of Chemical Substances[RTECS, online database]. National Toxicology Information Program, National Library of Medicine, Bethesda, MD. 1993.
- International Agency for Research on Cancer[IARC]. IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans: Overall Evaluations of Carcinogenicity: An Updating of IARC Monographs Volumes 1 to 42. Supplement 7. World Health Organization, Lyon. 1987.
- U.S. Department of Health and Human Services[DHHS]. The 8th Report on Carcinogens. 1998 Summary. Public Health Service, National Toxicology Program. Research Triangle Park, NC. 1998.
| | Chemical Properties | Clear colorless liquid | | Uses | Dimethylcarbamyl chloride is used to make dyes and pharmaceuticals. | | Uses | As a chemical intermediate in the
manufacture of carbamate drugs and pesticides | | Uses | Dimethylcarbamoyl chloride has been used primarily as a chemical intermediate in the production of dyes, pharmaceuticals, pesticides, and rocket fuel (IARC 1999, HSDB 2009). | | Definition | ChEBI: Dimethylcarbamoyl chloride is a halide. It is functionally related to a carbamic acid. | | General Description | A colorless to yellow liquid with a pungent odor. Burns to skin, eyes and mucous membranes. A lachrymator. Used to make dyes and pharmaceuticals. | | Air & Water Reactions | Reacts with water or moisture in the air to form hydrochloric acid and dimethylcarbamic acid. | | Reactivity Profile | Dimethylcarbamoyl chloride is water reactive. Incompatible with strong oxidizing agents, alcohols, bases (including amines). May react vigorously or explosively if mixed with diisopropyl ether or other ethers in the presence of trace amounts of metal salts [J. Haz. Mat., 1981, 4, 291]. Gives toxic fumes of NOx and HCl when burned [USCG, 1999]. | | Health Hazard | Material is extremely destructive to the mucous membranes, upper respiratory tract, eyes, and skin. Symptoms of exposure include burning sensation, coughing, wheezing, laryngitis, shortness of breath, headache, nausea, and vomiting. | | Fire Hazard | Special Hazards of Combustion Products: Toxic fumes of NO x and HCl | | Safety Profile | Confirmed carcinogen
with experimental carcinogenic,
neoplastigenic, and tumorigenic data. Poison
by intraperitoneal route. Moderately toxic by
inhalation and ingestion. Human mutation
data reported. Can cause skin and paplllary
tumors by skin contact, and squamous cell
carcinoma by inhalation. Will react with
water or steam to produce toxic and
corrosive fumes. A powerful lachrymator.
When heated to decomposition it emits very
toxic fumes of Cland NOx. See also
CHLORIDES. | | Carcinogenicity | Dimethylcarbamoyl chloride is reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in experimental animals. | | Purification Methods | It must be distilled under high vacuum to avoid decomposition. [Beilstein 4 IV 224.] |
| | Dimethylcarbamoyl chloride Preparation Products And Raw materials |
| Raw materials | Chlorine-->Dimethylamine-->CARBON MONOXIDE-->METALLURGICAL COKE-->Chloramine-T | | Preparation Products | Isoproturon-->2-CYANOPYRIDINE-4-CARBOXALDEHYDE-->4-METHYL-PYRIDINE-2-CARBOXYLIC ACID-->ETHYL 2-CYANOPYRIDINE-4-CARBOXYLATE-->4-(HYDROXYMETHYL)PICOLINITRILE-->4-AMINOMETHYL-PYRIDINE-2-CARBOXYLIC ACID-->3-AMINOMETHYL-PYRIDINE-2-CARBOXYLIC ACID-->4-[(TERT-BUTOXYCARBONYLAMINO)METHYL]-2-CYANOPYRIDINE-->1,4,5,8-Naphthalenetetracarboxylic acid-->4-(BOC-AMINOMETHYL)PYRIDINE-2-CARBOXYLIC ACID-->3-(TERT-BUTOXYCARBONYLAMINO-METHYL)-PYRIDINE-2-CARBOXYLIC ACID-->4-(TRIMETHYL-UREIDO)-BENZENESULFONYL CHLORIDE-->2,2'-DINAPHTHYL KETONE-->N,N,N',N'-Tetramethylazodicarboxamide-->ethyl dimethylcarbamate-->AZIDITHION-->N,N-DIMETHYL-2-PIPERAZIN-1-YL-ACETAMIDE-->3-AMINOPHENYL N,N-DIMETHYLCARBAMATE, 97-->3-dimethylaminophenyl dimethylcarbamate-->2-CYANO-4-METHYLPYRIDINE-->3-Pyridyl dimethylcarbamate-->PIPERAZINE-1-CARBOXYLIC ACID DIMETHYLAMIDE-->4-CHLORO-PYRIDINE-2-CARBONITRILE-->Neostigmine bromide |
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