Dimethylacetamide

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|Watchedfields = changed

|verifiedrevid = 414427167

|ImageFile = Dimethylacetamide.svg

|ImageFile_Ref = {{chemboximage|correct|??}}

|ImageSize = 100

|ImageName = Skeletal formula of dimethylacetamide

|ImageFile1 = Dimethylacetamide-3D-balls-B.png

|ImageFile1_Ref = {{chemboximage|correct|??}}

|ImageSize1 = 160

|ImageName1 = Ball and stick model of dimethylacetamide

|PIN = N,N-Dimethylacetamide

|Section1={{Chembox Identifiers

|Abbreviations = DMA, DMAC, DMAc{{ cite journal |author1=Munro, D. D. |author2=Stoughton, R. B. | title = Dimethylacetamide (DMAC) and Dimethylformamide (DMFA). Effect on Percutaneous Absorption | journal = Archives of Dermatology | year = 1965 | volume = 92 | issue = 5 | pages = 585–586 | doi = 10.1001/archderm.1965.01600170101020 | pmid = 5844405}}

|CASNo = 127-19-5

|CASNo_Ref = {{cascite|correct|CAS}}

|PubChem = 31374

|ChemSpiderID = 29107

|ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

|UNII = JCV5VDB3HY

|UNII_Ref = {{fdacite|correct|FDA}}

|EINECS = 204-826-4

|MeSHName = dimethylacetamide

|ChEBI_Ref = {{ebicite|changed|EBI}}

|ChEBI = 84254

|ChEMBL = 11873

|ChEMBL_Ref = {{ebicite|correct|EBI}}

|RTECS = AB7700000

|Beilstein = 1737614

|SMILES = CN(C)C(C)=O

|StdInChI = 1S/C4H9NO/c1-4(6)5(2)3/h1-3H3

|StdInChI_Ref = {{stdinchicite|correct|chemspider}}

|StdInChIKey = FXHOOIRPVKKKFG-UHFFFAOYSA-N

|StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

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|Section2={{Chembox Properties

|C=4 | H=9 | N=1 | O=1

|Appearance = Colorless liquid

|Odor = Ammoniacal

|Density = 0.937 g/mL

|MeltingPtC = −20

|BoilingPtK = 438.2

|Solubility = Miscible

|LogP = −0.253

|VaporPressure = 300 Pa

|LambdaMax = 270 nm

|RefractIndex = 1.4375

|Viscosity = 0.945 mPa·s Iloukhani, H., K. Khanlarzadeh. "Densities, viscosities, and refractive indices for binary and ternary mixtures of N, N-dimethylacetamide (1)+ 2-methylbutan-2-ol (2)+ ethyl acetate (3) at 298.15 K for m liquid region and at ambient pressure". Journal of Chemical & Engineering Data, 51.4 (2006): 1226–1231. {{doi|10.1021/je050538q}}.

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|Section3={{Chembox Thermochemistry

|DeltaHf = −300.1 kJ/mol

|DeltaHc = −2.5835–−2.5805 MJ/mol

|HeatCapacity = 178.2 J/(K·mol)

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|Section4={{Chembox Hazards

|GHSPictograms = {{gHS exclamation mark}} {{gHS health hazard}}

|GHSSignalWord = DANGER

|HPhrases = {{h-phrases|312|319|332|360}}

|PPhrases = {{p-phrases|280|308+313}}

|NFPA-H = 2

|NFPA-F = 2

|NFPA-R = 0

|FlashPtC = 63

|AutoignitionPtC = 490

|ExploLimits = 1.8–11.5%

|LD50 = 2.24 g/kg (dermal, rabbit)
4.3 g/kg (oral, rat)
4.8 g/kg (oral, rat)
4.62 g/kg (oral, mouse)

|PEL = TWA 10 ppm (35 mg/m³) [skin]{{PGCH|0218}}

|IDLH = 300 ppm

|REL = TWA 10 ppm (35 mg/m³) [skin]

|LC50 = 2475 ppm (rat, 1 h){{IDLH|127195|Dimethyl acetamide}}

}}

|Section5={{Chembox Related

|OtherCompounds = {{Unbulleted list|dimethylformamide|acetamide|methylpyrrolidone}}

}}

Dimethylacetamide (DMAc or DMA) is the organic compound with the formula CH₃C(O)N(CH₃)₂. This colorless, water-miscible, high-boiling liquid is commonly used as a polar solvent in organic synthesis. DMA is miscible with most other solvents, although it is poorly soluble in aliphatic hydrocarbons.

Synthesis and production

DMA is prepared commercially by the reaction of dimethylamine with acetic anhydride or acetic acid. Dehydration of the salt of dimethylamine and acetic acid also furnishes this compound:{{ Ullmann | author = Cheung, H. | author2 = Tanke, R. S. | author3 = Torrence, G. P. | title = Acetic Acid | doi = 10.1002/14356007.a01_045.pub2}}

: CH₃CO₂H·HN(CH₃)₂ → H₂O + CH₃CON(CH₃)₂

Dimethylacetamide can also be produced by the reaction of dimethylamine with methyl acetate.{{cite web |last1=Grafmans |first1=Horst |last2=Maas |first2=Steffen |last3=Weck |first3=Alexander |last4=Rütter |first4=Heinz |last5=Schulz |first5=Michael |last6=Ross |first6=Karl-Heinz |title=Method for the production of n,n-dimethylacetamide (DMAC) |url=https://patents.google.com/patent/EP1828102B1/en |website=Google Patents |publisher=BASF SE |accessdate=18 July 2019}}

: File:Industrial synthesis of dimethylacetamide.svg

The separation and purification of the product is carried out by multistage distillation in rectification columns. DMA is obtained with essentially quantitive (99%) yield referred to methyl acetate.

Reactions and applications

The chemical reactions of dimethylacetamide are typical of N,N-disubstituted amides. Hydrolysis of the acyl-N bond occurs in the presence of acids:

: CH₃CON(CH₃)₂ + H₂O + HCl → CH₃COOH + (CH₃)₂NH₂⁺Cl⁻

However, it is resistant to bases. For this reason DMA is a useful solvent for reactions involving strong bases such as sodium hydroxide.{{OrgSynth | author = Zen, S. | author2 = Kaji, E. | title = Dimethyl nitrosuccinate | volume = 57 | pages = 60 | collvol = 6 | collvolpages = 503 | year = 1977 | prep = CV6P0503}}

Dimethylacetamide is commonly used as a solvent for fibers (e.g., polyacrylonitrile, spandex) or in the adhesive industry. It is also employed in the production of pharmaceuticals and plasticizers as a reaction medium.

A solution of lithium chloride in DMAc (LiCl/DMAc) can dissolve cellulose. Unlike many other cellulose solvents, LiCl/DMAc gives a molecular dispersion, i.e. a "true solution". For this reason, it is used in gel permeation chromatography to determine the molar mass distribution of cellulose samples.

Dimethylacetamide is also used as an excipient in drugs, e.g. in Vumon (teniposide), Busulfex (busulfan) or Amsidine (amsacrine).

Toxicity

Dimethylacetamide, like most simple alkyl amides, is of low acute toxicity. Chronic exposure can cause hepatotoxicity.U.S. Department of Health and Human Services & U.S. Department of Labor (1978) [https://www.cdc.gov/niosh/docs/81-123/pdfs/0218.pdf Occupational Health Guideline for Dimethyl Acetamide]. Now: Occupational Health Guideline for Chemical Hazards. [https://www.cdc.gov/niosh/docs/81-123/ DHHS (NIOSH) Publication Number 81-123]. January 1981. The National Institute for Occupational Safety and Health (NIOSH).{{ cite journal |author1=Baum, S. L. |author2=Suruda, A. J. | title = Toxic Hepatitis from Dimethylacetamide | journal = International Journal of Occupational and Environmental Health | year = 1997 | volume = 3 | issue = 1 | pages = 1–4 | doi = 10.1179/oeh.1997.3.1.1 | pmid = 9891094 }}{{ cite journal |author1=Lee, C.-Y. |author2=Jung, S.-J. |author3=Kim, S.-A. | author4=Park, K.-S. | author5=Ha, B.-G. | title = Incidence of dimethylacetamide induced hepatic injury among new employees in a cohort of elastane fibre workers | journal = Occupational and Environmental Medicine | year = 2006 | volume = 63 | issue = 10 | pages = 688–693 | doi = 10.1136/oem.2005.023580 | pmid = 16728503 | pmc = 2078052 }}{{ cite journal |author1=Gong, W. |author2=Liu, X. |author3=Zhu, B. | title = Dimethylacetamide-induced occupational toxic hepatitis with a short term recurrence: a rare case report | journal = Journal of Thoracic Disease | year = 2016 | volume = 8 | issue = 6 | pages = E408–E411 | doi = 10.21037/jtd.2016.04.44 | pmid = 27293868 | pmc = 4885965 |doi-access=free }} At high doses (400 mg/kg body mass daily), dimethylacetamide causes effects on the central nervous system (e.g. depression, hallucinations and delusion).{{ cite journal |author1= Weiss, A. J. |author2= Jackson, L. G. |author3= Carabasi, R. A. | author4= Mancall, E. L. | author5= White, J. C. | title = A Phase I Study of Dimethylacetamide | journal = Cancer Chemotherapy Reports | year = 1962 | volume = 16 | issue = February 1962 | pages = 477–485 | pmid = 14005853}}{{ cite journal |author1= Weiss, A. J. |author2= Mancall, E. L. |author3= Koltes, J. A. | author4= White, J. C. | author5= Jackson, L. G. | title = Dimethylacetamide: A Hitherto Unrecognized Hallucinogenic Agent | journal = Science | year = 1962 | volume = 136 | issue = 3511 | pages = 151–152| doi = 10.1126/science.136.3511.151| pmid = 14005854|bibcode= 1962Sci...136..151W |s2cid= 20098340 }}

Dimethylacetamide may be incompatible with polycarbonate or ABS. Devices (e.g. syringes) that contain polycarbonate or ABS can dissolve when coming into contact with dimethylacetamide.[https://web.archive.org/web/20150313171000/http://www.fda.gov/Drugs/DrugSafety/ucm437469.htm FDA warns health care professionals not to use Treanda Injection (solution) with closed system transfer devices, adapters, and syringes containing polycarbonate or acrylonitrile-butadiene-styrene]. 10 March 2015.

Regulation

In 2011, dimethylacetamide was identified in the EU as a Substance of very high concern (SVHC) because of its reproductive toxicity.[http://echa.europa.eu/documents/10162/13638/agreement_dmac_20111124_en.pdf Agreement of the Member State Committee on the Identification of N,N-Dimethylacetamide (DMAC) as a Substance of Very High Concern – Adopted on 24 November 2011]. In 2014, the European Commission has started an investigation to restrict the use of dimethylacetamide in the EU according to REACH.[http://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32014R0895&from=EN Commission Regulation (EU) No 895/2014], Official Journal of the European Union, 19.08.2014.

In 2015, the CNESST (Committee on Standards, Equity, Health and Safety at Work in Quebec) has adopted a tightened classification of dimethylacetamide:Commission des normes, de l'équité, de la santé et de la sécurité du travail (CNESST), Quebec, Canada: [http://www.csst.qc.ca/en/prevention/reptox/Pages/information-sheet-whmis.aspx?langue=a&no_produit=3251 WHMIS 2015 classification of N,N-Dimethylacetamide].

Description	Category	GHS hazard statement
class="wikitable"
Reproductive toxicity	2	Suspected of damaging fertility or the unborn child (H361)
Specific target organ toxicity – repeated exposure	2	May cause damage to organs through prolonged or repeated exposure (H373)
Serious eye damage/eye irritation	2	Causes serious eye irritation (H319)
Acute toxicity – inhalation	3	Toxic if inhaled (H331)
Specific target organ toxicity – single exposure – narcotic effects	3	May cause drowsiness or dizziness (H336)
Flammable liquid	4	Combustible liquid (H227)

References

External links

[http://www.inclusive-science-engineering.com/dimethylacetamide-production-acetic-acid-dimethylamine/ Process flowsheet of Dimethylacetamide Production from Acetic Acid and Dimethylamine]
[https://www.cdc.gov/niosh/npg/npgd0218.html CDC – NIOSH Pocket Guide to Chemical Hazards]

Category:Amide solvents

Category:Acetamides