Dimethylformamide

Last updated
Dimethylformamide
Dimethylformamide-2D-skeletal.svg
Ball and stick model of dimethylformamide DMF-3D-balls.png
Ball and stick model of dimethylformamide
Spacefill model of dimethylformamide Dimethylformamide-3D-vdW.png
Spacefill model of dimethylformamide
Names
Preferred IUPAC name
N,N-Dimethylformamide [1]
Other names
Dimethylformamide
N,N-Dimethylmethanamide [2]
DMF
Identifiers
3D model (JSmol)
3DMet
605365
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.000.617 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 200-679-5
KEGG
MeSH Dimethylformamide
PubChem CID
RTECS number
  • LQ2100000
UNII
UN number 2265
  • InChI=1S/C3H7NO/c1-4(2)3-5/h3H,1-2H3 Yes check.svgY
    Key: ZMXDDKWLCZADIW-UHFFFAOYSA-N Yes check.svgY
  • CN(C)C=O
Properties
C3H7NO
Molar mass 73.095 g·mol−1
AppearanceColourless liquid
Odor Odorless, fishy if impure
Density 0.948 g/mL
Melting point −61 °C (−78 °F; 212 K)
Boiling point 153 °C (307 °F; 426 K)
Miscible
log P −0.829
Vapor pressure 516 Pa
Acidity (pKa)−0.3 (for the conjugate acid) (H2O) [3]
UV-vis (λmax)270 nm
Absorbance 1.00
1.4305 (at 20 °C)
Viscosity 0.92 mPa·s (at 20 °C)
Structure
3.86 D
Thermochemistry
146.05 J/(K·mol)
−239.4 ± 1.2 kJ/mol
−1.9416 ± 0.0012 MJ/mol
Hazards
GHS labelling:
GHS-pictogram-flamme.svg GHS-pictogram-exclam.svg GHS-pictogram-silhouette.svg
Danger
H226, H312, H319, H332, H360
P280, P305+P351+P338, P308+P313
NFPA 704 (fire diamond)
NFPA 704.svgHealth 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 58 °C (136 °F; 331 K)
445 °C (833 °F; 718 K)
Explosive limits 2.2–15.2%
30 mg/m3 (TWA)
Lethal dose or concentration (LD, LC):
  • 1.5 g/kg (rabbit, dermal)
  • 2.8 g/kg (rat, oral)
  • 3.7 g/kg (mouse, oral)
  • 3.5 g/kg (rat, oral)
3092 ppm (mouse, 2 h) [4]
5000 ppm (rat, 6 h) [4]
NIOSH (US health exposure limits):
PEL (Permissible)
TWA 10 ppm (30 mg/m3) [skin] [5]
REL (Recommended)
TWA 10 ppm (30 mg/m3) [skin] [5]
IDLH (Immediate danger)
500 ppm [5]
Related compounds
Related alkanamides
Related compounds
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Yes check.svgY  verify  (what is  Yes check.svgYX mark.svgN ?)

Dimethylformamide is an organic compound with the chemical formula H C O N(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.

Contents

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]

DMF is a classic example of a fluxional molecule. [7]

DmfDNMR.png

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.

Left: two resonance structures of DMF. Right: illustration highlighting delocalization. DMF resonances.png
Left: two resonance structures of DMF. Right: illustration highlighting delocalization.

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.

Organolithium compounds and Grignard reagents react with DMF to give aldehydes after hydrolysis in a reaction called Bouveault aldehyde synthesis. [16]

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]

DMF is prepared by combining methyl formate and dimethylamine or by reaction of dimethylamine with carbon monoxide. [21]

Although currently impractical, DMF can be prepared from supercritical carbon dioxide using ruthenium-based catalysts. [22]

Applications

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]

Acyl chloride via amide catalysis.png

As a cheap and common reagent, DMF has many uses in a research laboratory.

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]

Related Research Articles

<span class="mw-page-title-main">Amide</span> Organic compounds of the form RC(=O)NR′R″

In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula R−C(=O)−NR′R″, where R, R', and R″ represent any group, typically organyl groups or hydrogen atoms. The amide group is called a peptide bond when it is part of the main chain of a protein, and an isopeptide bond when it occurs in a side chain, as in asparagine and glutamine. It can be viewed as a derivative of a carboxylic acid with the hydroxyl group replaced by an amine group ; or, equivalently, an acyl (alkanoyl) group joined to an amine group.

In organic chemistry, an acyl chloride is an organic compound with the functional group −C(=O)Cl. Their formula is usually written R−COCl, where R is a side chain. They are reactive derivatives of carboxylic acids. A specific example of an acyl chloride is acetyl chloride, CH3COCl. Acyl chlorides are the most important subset of acyl halides.

<span class="mw-page-title-main">Formamide</span> Chemical compound

Formamide is an amide derived from formic acid. It is a colorless liquid which is miscible with water and has an ammonia-like odor. It is chemical feedstock for the manufacture of sulfa drugs and other pharmaceuticals, herbicides and pesticides, and in the manufacture of hydrocyanic acid. It has been used as a softener for paper and fiber. It is a solvent for many ionic compounds. It has also been used as a solvent for resins and plasticizers. Some astrobiologists suggest that it may be an alternative to water as the main solvent in other forms of life.

<span class="mw-page-title-main">Oxalyl chloride</span> Chemical compound

Oxalyl chloride is an organic chemical compound with the formula Cl−C(=O)−C(=O)−Cl. This colorless, sharp-smelling liquid, the diacyl chloride of oxalic acid, is a useful reagent in organic synthesis.

<span class="mw-page-title-main">Thionyl chloride</span> Inorganic compound (SOCl2)

Thionyl chloride is an inorganic compound with the chemical formula SOCl2. It is a moderately volatile, colourless liquid with an unpleasant acrid odour. Thionyl chloride is primarily used as a chlorinating reagent, with approximately 45,000 tonnes per year being produced during the early 1990s, but is occasionally also used as a solvent. It is toxic, reacts with water, and is also listed under the Chemical Weapons Convention as it may be used for the production of chemical weapons.

<span class="mw-page-title-main">Phosphorus pentachloride</span> Chemical compound

Phosphorus pentachloride is the chemical compound with the formula PCl5. It is one of the most important phosphorus chlorides/oxychlorides, others being PCl3 and POCl3. PCl5 finds use as a chlorinating reagent. It is a colourless, water-sensitive solid, although commercial samples can be yellowish and contaminated with hydrogen chloride.

<span class="mw-page-title-main">DABCO</span> Chemical compound

DABCO (1,4-diazabicyclo[2.2.2]octane), also known as triethylenediamine or TEDA, is a bicyclic organic compound with the formula N2(C2H4)3. This colorless solid is a highly nucleophilic tertiary amine base, which is used as a catalyst and reagent in polymerization and organic synthesis.

<span class="mw-page-title-main">Dimethylacetamide</span> Chemical compound

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.

The Vilsmeier–Haack reaction (also called the Vilsmeier reaction) is the chemical reaction of a substituted formamide (1) with phosphorus oxychloride and an electron-rich arene (3) to produce an aryl aldehyde or ketone (5):

<span class="mw-page-title-main">Dimethylamine</span> Chemical compound

Dimethylamine is an organic compound with the formula (CH3)2NH. This secondary amine is a colorless, flammable gas with an ammonia-like odor. Dimethylamine is commonly encountered commercially as a solution in water at concentrations up to around 40%. An estimated 270,000 tons were produced in 2005.

The Duff reaction or hexamine aromatic formylation is a formylation reaction used in organic chemistry for the synthesis of benzaldehydes with hexamine as the formyl carbon source. The method is generally inefficient. The reaction is named after James Cooper Duff.

<span class="mw-page-title-main">Iminium</span> Polyatomic ion of the form >C=N< and charge +1

In organic chemistry, an iminium cation is a polyatomic ion with the general structure [R1R2C=NR3R4]+. They are common in synthetic chemistry and biology.

<span class="mw-page-title-main">Phosphoryl chloride</span> Chemical compound

Phosphoryl chloride is a colourless liquid with the formula POCl3. It hydrolyses in moist air releasing phosphoric acid and fumes of hydrogen chloride. It is manufactured industrially on a large scale from phosphorus trichloride and oxygen or phosphorus pentoxide. It is mainly used to make phosphate esters.

<span class="mw-page-title-main">Formylation</span>

Formylation refers to any chemical processes in which a compound is functionalized with a formyl group (-CH=O). In organic chemistry, the term is most commonly used with regards to aromatic compounds. In biochemistry the reaction is catalysed by enzymes such as formyltransferases.

<span class="mw-page-title-main">Crotonaldehyde</span> Chemical compound

Crotonaldehyde is a chemical compound with the formula CH3CH=CHCHO. The compound is usually sold as a mixture of the E- and Z-isomers, which differ with respect to the relative position of the methyl and formyl groups. The E-isomer is more common (data given in Table is for the E-isomer). This lachrymatory liquid is moderately soluble in water and miscible in organic solvents. As an unsaturated aldehyde, crotonaldehyde is a versatile intermediate in organic synthesis. It occurs in a variety of foodstuffs, e.g. soybean oils.

<span class="mw-page-title-main">Carbonyl reduction</span> Organic reduction of any carbonyl group by a reducing agent

In organic chemistry, carbonyl reduction is the conversion of any carbonyl group, usually to an alcohol. It is a common transformation that is practiced in many ways. Ketones, aldehydes, carboxylic acids, esters, amides, and acid halides - some of the most pervasive functional groups, -comprise carbonyl compounds. Carboxylic acids, esters, and acid halides can be reduced to either aldehydes or a step further to primary alcohols, depending on the strength of the reducing agent. Aldehydes and ketones can be reduced respectively to primary and secondary alcohols. In deoxygenation, the alcohol group can be further reduced and removed altogether by replacement with H.

In organic chemistry, alkynylation is an addition reaction in which a terminal alkyne is added to a carbonyl group to form an α-alkynyl alcohol.

<span class="mw-page-title-main">Dimethylcarbamoyl chloride</span> Chemical compound

Dimethylcarbamoyl chloride (DMCC) is a reagent for transferring a dimethylcarbamoyl group to alcoholic or phenolic hydroxyl groups forming dimethyl carbamates, usually having pharmacological or pesticidal activities. Because of its high toxicity and its carcinogenic properties shown in animal experiments and presumably also in humans, dimethylcarbamoyl chloride can only be used under stringent safety precautions.

<span class="mw-page-title-main">3-Dimethylaminoacrolein</span> Chemical compound

3-Dimethylaminoacrolein is an organic compound with the formula Me2NC(H)=CHCHO. It is a pale yellow water-soluble liquid. The compound has a number of useful and unusual properties, e.g. it "causes a reversal of the hypnotic effect of morphine in mice" and has a "stimulating effect in humans".

<span class="mw-page-title-main">Vilsmeier reagent</span> Chemical compound

The Vilsmeier reagent is an organic compound with the formula [(CH3)2NCHCl]Cl. It is a salt consisting of the N,N-dimethyl­iminium cation ([(CH3)2N=CHCl]+) and chloride anion. Depending on the particular reaction, the anion can vary. In typical POCl3-based reactions, the anion is PO2Cl2−. The iminium cation [(CH3)2N=CHCl]+ is the reactive component of interest. This iminium species is a derivative of the imidoyl chloride CH3N=CHCl. Analogues of this particular reagent are generated when tertiary amides other than DMF are treated with POCl3.

References

  1. ↑ 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. ISBN   978-0-85404-182-4. The traditional name 'formamide' is retained for HCO-NH2 and is the preferred IUPAC name. Substitution is permitted on the –NH2 group.
  2. ↑ N,N-Dimethylmethanamide, NIST web thermo tables
  3. ↑ "Hazardous Substances Data Bank (HSDB) - N,N-DIMETHYLFORMAMIDE".
  4. 1 2 "Dimethylformamide". Immediately Dangerous to Life or Health Concentrations (IDLH). National Institute for Occupational Safety and Health (NIOSH).
  5. 1 2 3 NIOSH Pocket Guide to Chemical Hazards. "#0226". National Institute for Occupational Safety and Health (NIOSH).
  6. 1 2 "Dimethylformamide". Spectral Database for Organic Compounds. Japan: AIST. Retrieved 2012-06-28.[ permanent dead link ]
  7. ↑ 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.
  8. 1 2 3 4 Bipp, H.; Kieczka, H. "Formamides". Ullmann's Encyclopedia of Industrial Chemistry . Weinheim: Wiley-VCH. doi:10.1002/14356007.a12_001.pub2. ISBN   978-3527306732.
  9. ↑ IPCS (International Programme on Chemical Safety) (1991). Environmental Health Criteria 114 "Dimethylformamide" United Nations Environment Programme, International Labour Organisation, World Health Organization; 1–124.
  10. ↑ Taft, R. W.; Abraham, M. H.; Doherty, R. M.; Kamlet, M. J. (1985). "The molecular properties governing solubilities of organic nonelectrolytes in water". Nature . 313 (6001): 384–386. Bibcode:1985Natur.313..384T. doi:10.1038/313384a0. S2CID   36740734.
  11. ↑ (BASF AG, department of analytical, unpublished data, J-No. 124659/08, 27.11.1987)
  12. ↑ Comins, Daniel L.; Joseph, Sajan P. (2001). "N,N-Dimethylformamide". N,N-Dimethylformamide. Encyclopedia of Reagents for Organic Synthesis. John Wiley & Sons. doi:10.1002/047084289x.rd335. ISBN   9780470842898.
  13. 1 2 Vilsmeier, 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.
  14. 1 2 Meth-Cohn, Otto; Stanforth, Stephen P. (1993). "The Vilsmeier-Haack Reaction". In Trost, Barry M.; Heathcock, Clayton H. (eds.). Additions to CX π-Bonds, Part 2. Comprehensive Organic Synthesis: Selectivity, Strategy and Efficiency in Modern Organic Chemistry. Vol. 2. Elsevier. pp. 777–794. doi:10.1016/B978-0-08-052349-1.00049-4. ISBN   9780080405933.
  15. ↑ Jones, Gurnos; Stanforth, Stephen P. (2000). "The Vilsmeier Reaction of Non-Aromatic Compounds". Org. React. 56 (2): 355–686. doi:10.1002/0471264180.or056.02.
  16. ↑ Wang, Zerong (2009). Comprehensive organic name reactions and reagents. Hoboken, N.J.: John Wiley. pp. 490–492. ISBN   9780471704508.
  17. ↑ Vogel G. C.; Drago, R. S. (1996). "The ECW Model". Journal of Chemical Education. 73 (8): 701–707. Bibcode:1996JChEd..73..701V. doi:10.1021/ed073p701.
  18. ↑ 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
  19. ↑ 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.
  20. ↑ 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.
  21. ↑ Weissermel, K.; Arpe, H.-J. (2003). Industrial Organic Chemistry: Important Raw Materials and Intermediates. Wiley-VCH. pp. 45–46. ISBN   3-527-30578-5.
  22. ↑ Walter Leitner; Philip G. Jessop (1999). Chemical synthesis using supercritical fluids. Wiley-VCH. pp. 408–. ISBN   978-3-527-29605-7 . Retrieved 27 June 2011.
  23. ↑ Bouveault, Louis (1904). "Modes de formation et de préparation des aldéhydes saturées de la série grasse" [Methods of preparation of saturated aldehydes of the aliphatic series]. Bulletin de la Société Chimique de Paris. 3rd series (in French). 31: 1306–1322.
  24. ↑ Bouveault, Louis (1904). "Nouvelle méthode générale synthétique de préparation des aldéhydes" [Novel general synthetic method for preparing aldehydes]. Bulletin de la Société Chimique de Paris. 3rd series (in French). 31: 1322–1327.
  25. ↑ Li, Jie Jack (2014). "Bouveault aldehyde synthesis". Name Reactions: A Collection of Detailed Mechanisms and Synthetic Applications (5th ed.). Springer Science & Business Media. pp. 72–73. ISBN   978-3-319-03979-4.
  26. ↑ Oestreich, Martin, ed. (2009). The Mizoroki–Heck Reaction. John Wiley & Sons. ISBN   9780470716069.
  27. ↑ Clayden, J. (2001). Organic Chemistry . Oxford: Oxford University Press. pp.  276–296. ISBN   0-19-850346-6.
  28. ↑ Ansell, M. F. in "The Chemistry of Acyl Halides"; S. Patai, Ed.; John Wiley and Sons: London, 1972; pp 35–68.
  29. ↑ Haddon, R.; Itkis, M. (March 2008). "3. Near-Infrared (NIR) Spectroscopy" (pdf). In Freiman, S.; Hooker, S.; Migler; K.; Arepalli, S. (eds.). Publication 960-19 Measurement Issues in Single Wall Carbon Nanotubes. NIST. p. 20. Retrieved 2012-06-28.
  30. ↑ Lyle, W. H.; Spence, T. W.; McKinneley, W. M.; Duckers, K. (1979). "Dimethylformamide and alcohol intolerance". British Journal of Industrial Medicine. 36 (1): 63–66. doi:10.1136/oem.36.1.63. PMC   1008494 . PMID   444443.
  31. ↑ Magnus Løfstedt. "Skumlegetøj afgiver farlige kemikalier (in English- Squishies giving dangerous chemicals)". Archived from the original on 2021-09-03. Retrieved 2019-06-13.
  32. ↑ 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. PMID   3358569.
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