79-44-7 Usage
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
Different sources of media describe the Uses of 79-44-7 differently. You can refer to the following data:
1. Dimethylcarbamoyl chloride has been used primarily as a chemical intermediate in the production of dyes, pharmaceuticals, pesticides, and rocket fuel (IARC 1999, HSDB 2009).
2. As a chemical intermediate in the
manufacture of carbamate drugs and pesticides
3. Dimethylcarbamyl chloride is used to make dyes and pharmaceuticals.
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.]
Check Digit Verification of cas no
The CAS Registry Mumber 79-44-7 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 7 and 9 respectively; the second part has 2 digits, 4 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 79-44:
(4*7)+(3*9)+(2*4)+(1*4)=67
67 % 10 = 7
So 79-44-7 is a valid CAS Registry Number.
InChI:InChI=1/C3H6ClNO/c1-5(2)3(4)6/h1-2H3
79-44-7Relevant articles and documents
Discovery of 4-((2 S,4 S)-4-Ethoxy-1-((5-methoxy-7-methyl-1 H-indol-4-yl)methyl)piperidin-2-yl)benzoic Acid (LNP023), a Factor B Inhibitor Specifically Designed to Be Applicable to Treating a Diverse Array of Complement Mediated Diseases
Mainolfi, Nello,Ehara, Takeru,Karki, Rajeshri G.,Anderson, Karen,Mac Sweeney, Aengus,Liao, Sha-Mei,Argikar, Upendra A.,Jendza, Keith,Zhang, Chun,Powers, James,Klosowski, Daniel W.,Crowley, Maura,Kawanami, Toshio,Ding, Jian,April, Myriam,Forster, Cornelia,Serrano-Wu, Michael,Capparelli, Michael,Ramqaj, Rrezarta,Solovay, Catherine,Cumin, Frederic,Smith, Thomas M.,Ferrara, Luciana,Lee, Wendy,Long, Debby,Prentiss, Melissa,De Erkenez, Andrea,Yang, Louis,Liu, Fang,Sellner, Holger,Sirockin, Finton,Valeur, Eric,Erbel, Paulus,Ostermeier, Daniela,Ramage, Paul,Gerhartz, Bernd,Schubart, Anna,Flohr, Stefanie,Gradoux, Nathalie,Feifel, Roland,Vogg, Barbara,Wiesmann, Christian,Maibaum, Jürgen,Eder, J?rg,Sedrani, Richard,Harrison, Richard A.,Mogi, Muneto,Jaffee, Bruce D.,Adams, Christopher M.
, p. 5697 - 5722 (2020)
The alternative pathway (AP) of the complement system is a key contributor to the pathogenesis of several human diseases including age-related macular degeneration, paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), and various glomerular diseases. The serine protease factor B (FB) is a key node in the AP and is integral to the formation of C3 and C5 convertase. Despite the prominent role of FB in the AP, selective orally bioavailable inhibitors, beyond our own efforts, have not been reported previously. Herein we describe in more detail our efforts to identify FB inhibitors by high-throughput screening (HTS) and leveraging insights from several X-ray cocrystal structures during optimization efforts. This work culminated in the discovery of LNP023 (41), which is currently being evaluated clinically in several diverse AP mediated indications.
Dual inhibitors of Interleukin-6 and acetylcholinesterase for treatment of Alzheimer's disease: Design, docking, synthesis and biological evaluation
Bansal, Yogita,Kaur, Sukhvir
, (2021/11/13)
Multitarget compounds intercept two or more functionally complementary pathways simultaneously, and are therefore considered to have potential in effectively treating complex multifactorial diseases like Alzheimer's disease (AD). In the present study, novel molecules are designed by coupling a chromone and a N,N-disubstituted carbamoyl amine as pharmacophore for interleukin-6 (IL-6) and acetylcholinesterase (AChE) inhibition, respectively. Four series (Y1–Y4) of 40 compounds are designed by using alkyl linkers of different lengths (1–4 carbon atoms) for the coupling of the two selected pharmacophore. Docking of all designed compounds in AChE leads to the identification of twelve best fit compounds (Docking score >8.3). The data suggests that a 1- or 2-carbon atom linker is the most conducive to orient the pharmacophore for optimum binding with AChE active site. The predicted ADME properties of the 12 selected compounds suggest that these can cross the blood brain barrier (BBB) with good oral bioavailability. These compounds are synthesised and evaluated for anti-AChE activity. Five compounds, showing >45% inhibition of AChE, are further evaluated for IL-6 inhibitory activity. Compound Y1f is found to be the most potent inhibitor of both AChE and IL-6 (IC50 0.7 and 0.8 ?μM, respectively). It suggests that a chromone moiety connected to a piperidine ring through a 1-carbon atom linker may provide a useful template to medical chemists for the development of new chemical entities effective against AD.
Synthesis and Biological Evaluation of Celastrol Derivatives with Improved Cytotoxic Selectivity and Antitumor Activities
Feng, Jia-Hao,He, Qi-Wei,Hou, Ji-Qin,Hu, Xiao-Long,Long, Huan,Wang, Bao-Lin,Wang, Hao,Wang, Quan,Wang, Rong,Ye, Wen-Cai,Zhang, Li-Xin,Zhang, Xiao-Qi
, p. 1954 - 1966 (2021/07/20)
Cdc37 associates kinase clients to Hsp90 and promotes the development of cancers. Celastrol, a natural friedelane triterpenoid, can disrupt the Hsp90-Cdc37 interaction to provide antitumor effects. In this study, 31 new celastrol derivatives, 2a - 2d , 3a - 3g , and 4a - 4t , were designed and synthesized, and their Hsp90-Cdc37 disruption activities and antiproliferative activities against cancer cells were evaluated. Among these compounds, 4f , with the highest tumor cell selectivity (15.4-fold), potent Hsp90-Cdc37 disruption activity (IC50= 1.9 μM), and antiproliferative activity against MDA-MB-231 cells (IC50= 0.2 μM), was selected as the lead compound. Further studies demonstrated 4f has strong antitumor activities both in vitro and in vivo through disrupting the Hsp90-Cdc37 interaction and inhibiting angiogenesis. In addition, 4f exhibited less toxicity than celastrol and showed a good pharmacokinetics profile in vivo. These findings suggest that 4f may be a promising candidate for development of new cancer therapies.
