Dimethylformamide is an
organic compound with the
chemical formulaHCON(CH3)2. Its structure is HC(=O)−N(
−CH3)2. Commonly abbreviated as DMF (although this initialism is sometimes used for
dimethylfuran, or
dimethyl fumarate), this colourless liquid is
miscible with
water and the majority of organic liquids. DMF is a common
solvent for
chemical reactions. Dimethylformamide is odorless, but
technical-grade or degraded samples often have a fishy smell due to impurity of
dimethylamine. Dimethylamine degradation impurities can be removed by
sparging samples with an inert gas such as
argon or by
sonicating the samples under reduced pressure. As its name indicates, it is structurally related to
formamide, having two
methyl groups in the place of the two hydrogens. DMF is a
polar (
hydrophilic)
aprotic solvent with a high
boiling point. It facilitates reactions that follow polar mechanisms, such as
SN2 reactions.
Structure and properties
As for most
amides, the spectroscopic evidence indicates partial double bond character for the C−N and C−O bonds. Thus, the
infrared spectrum shows a C=O stretching frequency at only 1675 cm−1, whereas a ketone would absorb near 1700 cm−1.[6]
The ambient temperature
1H NMR spectrum shows two methyl signals, indicative of hindered rotation about the (O)C−N bond.[6] At temperatures near 100 °C, the 500 MHz NMR spectrum of this compound shows only one signal for the methyl groups.
DMF is miscible with water.[8] The vapour pressure at 20 °C is 3.5 hPa.[9] A
Henry's law constant of 7.47 × 10−5 hPa·m3/mol can be deduced from an experimentally determined equilibrium constant at 25 °C.[10] The
partition coefficient log POW is measured to −0.85.[11] Since the density of DMF (0.95 g·cm−3 at 20 °C[8]) is similar to that of water, significant flotation or stratification in surface waters in case of accidental losses is not expected.
Reactions
DMF is hydrolyzed by strong acids and bases, especially at elevated temperatures. With
sodium hydroxide, DMF converts to formate and dimethylamine. DMF undergoes
decarbonylation near its boiling point to give dimethylamine. Distillation is therefore conducted under reduced pressure at lower temperatures.[12]
In one of its main uses in
organic synthesis, DMF is a reagent in the
Vilsmeier–Haack reaction, which is used to formylate aromatic compounds.[13][14] The process involves initial conversion of DMF to a chloroiminium ion, [(CH3)2N=CH(Cl)]+, known as a
Vilsmeier reagent,[15] which attacks arenes.
Dimethylformamide forms 1:1
adducts with a variety of Lewis acids such as the soft acid
I2, and the hard acid
phenol. It is classified as a
hard Lewis base and its
ECW model base parameters are EB = 2.19 and CB = 1.31.[17] Its relative donor strength toward a series of acids, versus other Lewis bases, can be illustrated by
C-B plots.[18][19]
Production
DMF was first prepared in 1893 by the French chemist Albert Verley (8 January 1867 – 27 November 1959), by distilling a mixture of dimethylamine hydrochloride and potassium formate.[20]
The primary use of DMF is as a solvent with low evaporation rate. DMF is used in the production of
acrylic fibers and
plastics. It is also used as a solvent in
peptide coupling for pharmaceuticals, in the development and production of
pesticides, and in the manufacture of
adhesives, synthetic
leathers, fibers, films, and surface coatings.[8]
It is used in the manufacturing of solvent dyes as an important raw material. It is consumed during reaction.
Pure
acetylene gas cannot be compressed and stored without the danger of explosion. Industrial acetylene is safely compressed in the presence of dimethylformamide, which forms a safe, concentrated solution. The casing is also filled with
agamassan, which renders it safe to transport and use.
As a cheap and common reagent, DMF has many uses in a research laboratory.
DMF-d7 in the presence of a catalytic amount of
potassium tert-butoxide under microwave heating is a reagent for deuteration of polyaromatic hydrocarbons.
Safety
Dimethylformamide vapor exposure has shown reduced alcohol tolerance and skin irritation in some cases.[30]
On 20 June 2018, the
Danish Environmental Protective Agency published an article about DMF's use in
squishies. The density of the compound in the toy resulted in all squishies being removed from the Danish market. All squishies were recommended to be thrown out as household waste.
[31]
Toxicity
The acute
LD50 (oral, rats and mice) is 2.2–7.55 g/kg.[8] Hazards of DMF have been examined.[32]
^Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book). Cambridge:
The Royal Society of Chemistry. 2014. pp. 841, 844.
doi:
10.1039/9781849733069-FP001.
ISBN978-0-85404-182-4. The traditional name 'formamide' is retained for HCO-NH2 and is the preferred IUPAC name. Substitution is permitted on the –NH2 group.
^H. S. Gutowsky; C. H. Holm (1956). "Rate Processes and Nuclear Magnetic Resonance Spectra. II. Hindered Internal Rotation of Amides". J. Chem. Phys. 25 (6): 1228–1234.
Bibcode:
1956JChPh..25.1228G.
doi:
10.1063/1.1743184.
^IPCS (International Programme on Chemical Safety) (1991). Environmental Health Criteria 114 "Dimethylformamide" United Nations Environment Programme, International Labour Organisation, World Health Organization; 1–124.
^
abVilsmeier, Anton; Haack, Albrecht (1927). "Über die Einwirkung von Halogenphosphor auf Alkyl-formanilide. Eine neue Methode zur Darstellung sekundärer und tertiärer p-Alkylamino-benzaldehyde" [On the reaction of phosphorus halides with alkyl formanilides. A new method for the preparation of secondary and tertiary p-alkylamino-benzaldehyde]. Ber. Dtsch. Chem. Ges. A/B (in German). 60 (1): 119–122.
doi:
10.1002/cber.19270600118.
^Laurence, C. and Gal, J-F. Lewis Basicity and Affinity Scales, Data and Measurement, (Wiley 2010) pp 50-51 ISBN 978-0-470-74957-9
^Cramer, R. E.; Bopp, T. T. (1977). "Graphical display of the enthalpies of adduct formation for Lewis acids and bases". Journal of Chemical Education. 54: 612–613.
doi:
10.1021/ed054p612. The plots shown in this paper used older parameters. Improved E&C parameters are listed in
ECW model.
^Verley, A. (1893).
"Sur la préparation des amides en général" [On the preparation of amides in general]. Bulletin de la Société Chimique de Paris. 3rd series (in French). 9: 690–692. On p. 692, Verley states that DMF is prepared by a procedure analogous to that for the preparation of dimethylacetamide (see p. 691), which would be by distilling dimethylamine hydrochloride and
potassium formate.
^Weissermel, K.; Arpe, H.-J. (2003). Industrial Organic Chemistry: Important Raw Materials and Intermediates. Wiley-VCH. pp. 45–46.
ISBN3-527-30578-5.
^Redlich, C.; Beckett, W. S.; Sparer, J.; Barwick, K. W.; Riely, C. A.; Miller, H.; Sigal, S. L.; Shalat, S. L.; Cullen, M. R. (1988). "Liver disease associated with occupational exposure to the solvent dimethylformamide". Annals of Internal Medicine. 108 (5): 680–686.
doi:
10.7326/0003-4819-108-5-680.
PMID3358569.