Dimethylformamide

N,N-Dimethylformamide
IUPAC name N,N-Dimethylmethanamide
Other names DMF; Dimethylformamide; N,N-Dimethylformamide; DMFA
Identifiers
CAS number	68-12-2 Y
PubChem	6228
ChemSpider	5993 Y
UNII	8696NH0Y2X Y
DrugBank	DB01844
KEGG	C03134 Y
ChEBI	CHEBI:17741 Y
ChEMBL	CHEMBL268291 Y
RTECS number	LQ2100000
Jmol-3D images	Image 1
SMILES O=CN(C)C
InChI InChI=1S/C3H7NO/c1-4(2)3-5/h3H,1-2H3 Y Key: ZMXDDKWLCZADIW-UHFFFAOYSA-N Y InChI=1S/C3H7NO/c1-4(2)3-5/h3H,1-2H3 Key: ZMXDDKWLCZADIW-UHFFFAOYSA-N
Properties
Molecular formula	C3H7NO
Molar mass	73.09 g/mol
Appearance	Clear liquid
Density	0.944 g/cm3, liquid
Melting point	-61 °C, 212 K, -78 °F
Boiling point	153 °C, 426 K, 307 °F
Solubility in water	Miscible
Vapor pressure	0.3 kPa (@ 20°C)
Refractive index (nD)	1.4305 (20 °C), εr = 36.71 (25°C)
Viscosity	0.92 cP at 20 °C
Structure
Dipole moment	3.86 D (25 °C)
Hazards
MSDS	MSDS
R-phrases	R61 R20/21 R36
S-phrases	S53 S45
Main hazards	flammable
NFPA 704	2 1 0
Flash point	58 °C
Threshold Limit Value	10 ppm[1] (TWA)
Related compounds
Related amides	Acetamide, Formamide, hexamethylphosphoramide
Related compounds	Dimethyl sulfoxide, acetonitrile, N-Methylformamide
Y (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Dimethylformamide is an organic compound with the formula (CH₃)₂NC(O)H. Commonly abbreviated DMF (though this acronym is sometimes used for dimethylfuran), this colourless liquid is miscible with water and the majority of organic liquids. DMF is a common solvent for chemical reactions. Pure dimethylformamide is odorless whereas technical grade or degraded dimethylformamide often has a fishy smell due to impurity of dimethylamine. Its name is derived from the fact that it is a derivative of formamide, the amide of formic acid.

Dimethylformamide is a polar (hydrophilic) aprotic solvent with a high boiling point. It facilitates reactions that follow polar mechanisms, such as S_N2 reactions. Dimethylformamide can be synthesized from methyl formate and dimethylamine or by reaction of dimethylamine with carbon monoxide.^[2] Dimethylformamide is not stable in the presence of strong bases like sodium hydroxide or strong acids such as hydrochloric acid or sulfuric acid and is hydrolyzed back into formic acid and dimethylamine, especially at elevated temperatures.

Structure and properties

Due to the contribution of the two possible resonance structures of an amide, the bond order of the carbonyl C=O bond is reduced, while that of the carbon-nitrogen bond is increased. Thus the infrared spectrum of DMF shows a lower C=O stretching frequency at 1675 cm^−1[3] than an unsubstituted C=O bond. Also, because of the partial double bond character, the rotation about the C-N axis is slow at room temperature, making the two methyl groups inequivalent on the NMR time scale, giving rise to two singlets of 3 protons each at δ 2.97 and 2.88,^[3] instead of one singlet of 6 protons in the proton NMR spectrum.

N,N-Dimethylformamide (DMF) is miscible with water in all proportions.^[4] The vapour pressure at 20°C is 3.5hPa.^[5] 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.^[6] The partition coefficient logPOW is measured to –0.85.^[7] Since the density of DMF (0.95 g/cm³ at 20 °C^[4]) is very similar to that of water, significant flotation or stratification in surface waters in case of accidental losses is not expected.

The two resonance forms of DMF

Production

Dimethyl formamide is produced either via catalyzed reaction of dimethylamine and carbon monoxide in methanol or via the reaction of methyl formate with dimethylamine.^[2] It may also be prepared on a laboratory scale by reacting dimethylamine with formic acid.^{[citation needed]}

Applications

The primary use of dimethylformamide 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 as a reagent in the Bouveault aldehyde synthesis and in the Vilsmeier-Haack reaction, another useful method of forming aldehydes.
• It is also a common catalyst used in the synthesis of acyl halides, in particular the synthesis of acyl chlorides from carboxylic acids using oxalyl or thionyl chloride.^[9]
• DMF penetrates most plastics and makes them swell. This property makes it very suitable for solid phase peptide synthesis. It also frequently occurs as a component of paint strippers for this purpose.
• DMF is very effective at separating and suspending carbon nanotubes, and is recommended by the NIST for use in near infrared spectroscopy of such.^[10]
• DMF can be utilized as a standard in proton NMR allowing for a quantitative determination of an unknown chemical.
• DMF is used as a solvent to recover olefins such as 1,3-butadiene via extractive distillation.
• It is also 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 gas is, therefore, dissolved in dimethylformamide and stored in metal cylinders or bottles. The casing is also filled with agamassan, which renders it safe to transport and use.

Safety

Reactions including the use of sodium hydride in DMF as a solvent are somewhat hazardous; exothermic decompositions have been reported at temperatures as low as 26 °C. On a laboratory scale any thermal runaway is (usually) quickly noticed and brought under control with an ice bath and this remains a popular combination of reagents. On a pilot plant scale, on the other hand, several accidents have been reported.^[11]

Toxicity

DMF has been linked to cancer in humans, and it is thought to cause birth defects ^[12]. In some sectors of industry women are banned from working with DMF. For many reactions, it can be replaced with dimethyl sulfoxide. Most manufacturers of DMF list (Life) or (Chronic) as a health hazard in their MSDS since DMF is not readily disposed of by the body. According to IARC, DMF is a possible carcinogen, although EPA does not consider it a cancer risk.

References

1. ^ ScienceLab.com MSDS
2. ^ ^{a b} Klaus Weissermel, Hans-Jürgen Arpe. Industrial Organic Chemistry: Important Raw Materials and Intermediates. Wiley-VCH. pp. 45–46. ISBN 3527305785. 
3. ^ ^{a b} Spectral Database for Organic Compounds, Dimethylformamide, accessed 27 Jan 2007.
4. ^ ^{a b} Bipp, H. and Kieczka, H. (1989). Ullmann’s Encyclopedia of Industrial Chemistry. A12 (5 ed.). Weinheim: VCH Verlagsgesellschaft. pp. 1–12. 
5. ^ IPCS (International Programme on Chemical Safety) (1991). Environmental Health Criteria 114 “Dimethylformamide” United Nations Environment Programme, International Labour Organisation, World Health Organization; 1-124.
6. ^ Taft, R.W. et al. (1985). "The molecular properties governing solubilities of organic nonelectrolytes in water". Nature 313 (6001): 384–386. doi:10.1038/313384a0. 
7. ^ (BASF AG, department of analytical, unpublished data, J-No. 124659/08, 27.11.1987)
8. ^ Redlich, C; Beckett, W. S.; Sparer, J.; Barwick, K. W.; Riely, C. A.; Miller, H.; Sigal, S. L.; Shalat, S. L. et al. (1988). "Liver disease associated with occupational exposure to the solvent dimethylformamide". Ann. Intern. Med. 108 (5): 680–686. PMID 3358569. 
9. ^ Clayden, Jonathan (2001). Organic chemistry. Oxford: Oxford University Press. pp. 276–296. ISBN 0-19-850346-6. 
10. ^ Haddon, Robert; Itkis, Mikhail (March, 2008) (PDF). Measurement Issues in Single Wall Carbon Nanotubes. NIST. pp. 20. http://www.nist.gov/public_affairs/practiceguides/NIST%20SP960-19.pdf. Retrieved 2008-08-15. 
11. ^ UK Chemical Reaction Hazards Forum and references cited therein
12. ^ Hazardous substance fact sheet for Dimethylformamide

External links

• International Chemical Safety Card 0457
• NIOSH Pocket Guide to Chemical Hazards 0226
• Dimethylformamide usage on Organic Syntheses
• Concise International Chemical Assessment Document 31: N,N-Dimethylformamide
• Material Safety Data Sheet for DMF
• DMF Chronic Toxicity Summary (PDF)
• Dimethylformamide Technical Specs from BASF(pdf)
• DMF GHS MSDS from NuGenTec (PDF)