Dimethylacetamide

Dimethylacetamide
Skeletal formula of dimethylacetamide
Ball and stick model of dimethylacetamide
Names
Preferred IUPAC name
N,N-Dimethylacetamide
Identifiers
3D model (JSmol)
Abbreviations DMA, DMAC, DMAc[1]
1737614
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.004.389 Edit this at Wikidata
EC Number
  • 204-826-4
MeSH dimethylacetamide
RTECS number
  • AB7700000
UNII
  • InChI=1S/C4H9NO/c1-4(6)5(2)3/h1-3H3 checkY
    Key: FXHOOIRPVKKKFG-UHFFFAOYSA-N checkY
  • CN(C)C(C)=O
Properties
C4H9NO
Molar mass 87.122 g·mol−1
Appearance Colorless liquid
Odor Ammoniacal
Density 0.937 g/mL
Melting point −20 °C (−4 °F; 253 K)
Boiling point 165.1 °C; 329.1 °F; 438.2 K
Miscible
log P −0.253
Vapor pressure 300 Pa
UV-vis (λmax) 270 nm
1.4375
Viscosity 0.945 mPa·s [2]
Thermochemistry
178.2 J/(K·mol)
−300.1 kJ/mol
−2.5835–−2.5805 MJ/mol
Hazards
GHS labelling:
GHS07: Exclamation mark GHS08: Health hazard
Danger
H312, H319, H332, H360
P280, P308+P313
NFPA 704 (fire diamond)
NFPA 704 four-colored diamondHealth 2: Intense or continued but not chronic exposure could cause temporary incapacitation or possible residual injury. E.g. chloroformFlammability 2: Must be moderately heated or exposed to relatively high ambient temperature before ignition can occur. Flash point between 38 and 93 °C (100 and 200 °F). E.g. diesel fuelInstability 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
2
2
0
Flash point 63 °C (145 °F; 336 K)
490 °C (914 °F; 763 K)
Explosive limits 1.8–11.5%
Lethal dose or concentration (LD, LC):
2.24 g/kg (dermal, rabbit)
4.3 g/kg (oral, rat)
4.8 g/kg (oral, rat)
4.62 g/kg (oral, mouse)[4]
2475 ppm (rat, 1 h)[4]
NIOSH (US health exposure limits):
PEL (Permissible)
 TWA 10 ppm (35 mg/m3) [skin][3]
REL (Recommended)
 TWA 10 ppm (35 mg/m3) [skin][3]
IDLH (Immediate danger)
 300 ppm[3]
Related compounds
Related compounds
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

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:[5]

CH3CO2H·HN(CH3)2 → H2O + CH3CON(CH3)2

Dimethylacetamide can also be produced by the reaction of dimethylamine with methyl acetate.[6]

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 referred to methyl acetate.[6]

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.[7]

Dimethylacetamide is commonly used as a solvent for fibers (e.g., polyacrylonitrile, spandex) or in the adhesive industry.[5] 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.[8][9][10][11] At high doses (400 mg/kg body mass daily), dimethylacetamide causes effects on the central nervous system (e.g. depression, hallucinations and delusion).[8][12][13]

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.[14]

Regulation

In 2011, dimethylacetamide was identified in the EU as a Substance of very high concern (SVHC) because of its reproductive toxicity.[15] In 2014, the European Commission has started an investigation to restrict the use of dimethylacetamide in the EU according to REACH.[16]

In 2015, the CNESST (Committee on Standards, Equity, Health and Safety at Work in Quebec) has adopted a tightened classification of dimethylacetamide:[17]

Description Category 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)

See Also

References

  1. ^ Munro, D. D.; Stoughton, R. B. (1965). "Dimethylacetamide (DMAC) and Dimethylformamide (DMFA). Effect on Percutaneous Absorption". Archives of Dermatology. 92 (5): 585–586. doi:10.1001/archderm.1965.01600170101020. PMID 5844405.
  2. ^ 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.
  3. ^ a b c NIOSH Pocket Guide to Chemical Hazards. "#0218". National Institute for Occupational Safety and Health (NIOSH).
  4. ^ a b "Dimethyl acetamide". Immediately Dangerous to Life or Health Concentrations (IDLH). National Institute for Occupational Safety and Health (NIOSH).
  5. ^ a b Cheung, H.; Tanke, R. S.; Torrence, G. P. "Acetic Acid". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a01_045.pub2. ISBN 978-3527306732.
  6. ^ a b Grafmans, Horst; Maas, Steffen; Weck, Alexander; Rütter, Heinz; Schulz, Michael; Ross, Karl-Heinz. "Method for the production of n,n-dimethylacetamide (DMAC)". Google Patents. BASF SE. Retrieved 18 July 2019.
  7. ^ Zen, S.; Kaji, E. (1977). "Dimethyl nitrosuccinate". Organic Syntheses. 57: 60; Collected Volumes, vol. 6, p. 503.
  8. ^ a b U.S. Department of Health and Human Services & U.S. Department of Labor (1978) Occupational Health Guideline for Dimethyl Acetamide. Now: Occupational Health Guideline for Chemical Hazards. DHHS (NIOSH) Publication Number 81-123. January 1981. The National Institute for Occupational Safety and Health (NIOSH).
  9. ^ Baum, S. L.; Suruda, A. J. (1997). "Toxic Hepatitis from Dimethylacetamide". International Journal of Occupational and Environmental Health. 3 (1): 1–4. doi:10.1179/oeh.1997.3.1.1. PMID 9891094.
  10. ^ Lee, C.-Y.; Jung, S.-J.; Kim, S.-A.; Park, K.-S.; Ha, B.-G. (2006). "Incidence of dimethylacetamide induced hepatic injury among new employees in a cohort of elastane fibre workers". Occupational and Environmental Medicine. 63 (10): 688–693. doi:10.1136/oem.2005.023580. PMC 2078052. PMID 16728503.
  11. ^ Gong, W.; Liu, X.; Zhu, B. (2016). "Dimethylacetamide-induced occupational toxic hepatitis with a short term recurrence: a rare case report". Journal of Thoracic Disease. 8 (6): E408–E411. doi:10.21037/jtd.2016.04.44. PMC 4885965. PMID 27293868.
  12. ^ Weiss, A. J.; Jackson, L. G.; Carabasi, R. A.; Mancall, E. L.; White, J. C. (1962). "A Phase I Study of Dimethylacetamide". Cancer Chemotherapy Reports. 16 (February 1962): 477–485. PMID 14005853.
  13. ^ Weiss, A. J.; Mancall, E. L.; Koltes, J. A.; White, J. C.; Jackson, L. G. (1962). "Dimethylacetamide: A Hitherto Unrecognized Hallucinogenic Agent". Science. 136 (3511): 151–152. Bibcode:1962Sci...136..151W. doi:10.1126/science.136.3511.151. PMID 14005854. S2CID 20098340.
  14. ^ 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.
  15. ^ 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.
  16. ^ Commission Regulation (EU) No 895/2014, Official Journal of the European Union, 19.08.2014.
  17. ^ Commission des normes, de l'équité, de la santé et de la sécurité du travail (CNESST), Quebec, Canada: WHMIS 2015 classification of N,N-Dimethylacetamide.