Dimethylacetamide: Difference between revisions

|Verifiedfields = changed

|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<ref>{{ 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}}</ref>

|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}}

}}

|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 <ref>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}}.</ref>

}}

|Section3={{Chembox Thermochemistry

|DeltaHf = −300.1 kJ/mol

|DeltaHc = −2.5835–−2.5805 MJ/mol

|HeatCapacity = 178.2 J/(K·mol)

}}

|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&nbsp;g/kg <small>(dermal, rabbit)</small><br />4.3&nbsp;g/kg <small>(oral, rat)</small><br />4.8&nbsp;g/kg (oral, rat)<br />4.62&nbsp;g/kg (oral, mouse)<ref name=IDLH/>

|PEL = TWA 10 ppm (35&nbsp;mg/m³) [skin]<ref name=PGCH>{{PGCH|0218}}</ref>

|IDLH = 300 ppm<ref name=PGCH/>

|REL = TWA 10 ppm (35&nbsp;mg/m³) [skin]<ref name=PGCH/>

|LC50 = 2475 ppm (rat, 1&nbsp;[[hour|h]])<ref name=IDLH>{{IDLH|127195|Dimethyl acetamide}}</ref>

}}

|Section5={{Chembox Related

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

}}

'''Dimethylacetamide''' ('''DMAc''' or '''DMA''') is the [[organic compound]] with the [[chemical formula|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]] [[hydrocarbon]]s.

==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:<ref name=Ullmann>{{ Ullmann | author = Cheung, H. | author2 = Tanke, R. S. | author3 = Torrence, G. P. | title = Acetic Acid | doi = 10.1002/14356007.a01_045.pub2}}</ref>

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

Dimethylacetamide can also be produced by the reaction of [[dimethylamine]] with [[methyl acetate]].<ref name="production">{{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}}</ref>

: [[File:Industrial synthesis of dimethylacetamide.svg|550px|frameless|One route to dimethylacetamide]]

The separation and purification of the product is carried out by multistage [[distillation]] in rectification columns. DMA is obtained with essentially quantitive (99%) [[Yield (chemistry)|yield]] referred to methyl acetate.<ref name=production/>

==Reactions and applications==

The chemical reactions of dimethylacetamide are typical of ''N'',''N''-disubstituted [[amide]]s. [[Hydrolysis]] of the acyl-N bond occurs in the presence of [[acid]]s:

: 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]].<ref>{{OrgSynth | author = Zen, S. | author2 = Kaji, E. | title = Dimethyl nitrosuccinate | volume = 57 | pages = 60 | collvol = 6 | collvolpages = 503 | year = 1977 | prep = CV6P0503}}</ref>

Dimethylacetamide is commonly used as a solvent for fibers (e.g., [[polyacrylonitrile]], [[spandex]]) or in the [[adhesive]] industry.<ref name=Ullmann/> It is also employed in the production of [[pharmaceuticals]] and [[plasticizer]]s 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]].<ref name="cdc.gov">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).</ref><ref>{{ 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 }}</ref><ref>{{ 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 }}</ref><ref>{{ 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 }}</ref> At high doses (400&nbsp;mg/kg body mass daily), dimethylacetamide causes effects on the [[central nervous system]] (e.g. [[Major depressive disorder|depression]], [[hallucination]]s and [[delusion]]).<ref name="cdc.gov"/><ref>{{ 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}}</ref><ref>{{ 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 }}</ref>

Dimethylacetamide may be incompatible with [[polycarbonate]] or [[Acrylonitrile butadiene styrene|ABS]]. Devices (e.g. syringes) that contain polycarbonate or ABS can dissolve when coming into contact with dimethylacetamide.<ref>[https://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.</ref>

==Regulation==

In 2011, dimethylacetamide was identified in the EU as a [[Substance of very high concern]] (SVHC) because of its [[reproductive toxicity]].<ref>[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].</ref> In 2014, the European Commission has started an investigation to restrict the use of dimethylacetamide in the EU according to [[Registration, Evaluation, Authorisation and Restriction of Chemicals|REACH]].<ref>[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.</ref>

In 2015, the CNESST (Committee on Standards, Equity, Health and Safety at Work in [[Quebec]]) has adopted a tightened classification of dimethylacetamide:<ref>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].</ref>

{| class="wikitable"

|-

! Description !! Category !! [[GHS hazard statements|GHS hazard statement]]

|-

| 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)

|}

{{Reflist}}

==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]