Dimethylformamide: Difference between revisions

|Watchedfields = changed

|verifiedrevid = 458446617

|ImageFile = Dimethylformamide-2D-skeletal.svg

|ImageFile_Ref = {{chemboximage|correct|??}}

|ImageSize = 100

|ImageName = Skeletal formula of dimethylformamide with one explicit hydrogen added

|ImageFileL1 = DMF-3D-balls.png

|ImageFileL1_Ref = {{chemboximage|correct|??}}

|ImageNameL1 = Ball and stick model of dimethylformamide

|ImageFileR1 = Dimethylformamide-3D-vdW.png

|ImageNameR1 = Spacefill model of dimethylformamide

|PIN = ''N'',''N''-Dimethylformamide<ref name=iupac2013>{{cite book | title = Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book) | publisher = [[Royal Society of Chemistry|The Royal Society of Chemistry]] | date = 2014 | location = Cambridge | pages = 841, 844 | doi = 10.1039/9781849733069-FP001 | isbn = 978-0-85404-182-4 | quote = The traditional name ‘formamide’ is retained for HCO-NH₂ and is the preferred IUPAC name. Substitution is permitted on the –NH₂ group.}}</ref>

|OtherNames = Dimethylformamide<br />''N'',''N''-Dimethylmethanamide<ref>[http://wtt-pro.nist.gov/wtt-pro/index.html?cmp=n.n-dimethylmethanamide ''N'',''N''-Dimethylmethanamide], NIST web thermo tables</ref><br />DMF

|Section1={{Chembox Identifiers

|CASNo = 68-12-2

|CASNo_Ref = {{cascite|correct|CAS}}

|PubChem = 6228

|ChemSpiderID = 5993

|ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

|UNII = 8696NH0Y2X

|UNII_Ref = {{fdacite|correct|FDA}}

|EINECS = 200-679-5

|UNNumber = 2265

|DrugBank = DB01844

|DrugBank_Ref = {{drugbankcite|correct|drugbank}}

|KEGG = C03134

|KEGG_Ref = {{keggcite|correct|kegg}}

|MeSHName = Dimethylformamide

|ChEBI = 17741

|ChEBI_Ref = {{ebicite|correct|EBI}}

|ChEMBL = 268291

|ChEMBL_Ref = {{ebicite|correct|EBI}}

|RTECS = LQ2100000

|Beilstein = 605365

|3DMet = B00545

|SMILES = CN(C)C=O

|StdInChI = 1S/C3H7NO/c1-4(2)3-5/h3H,1-2H3

|StdInChI_Ref = {{stdinchicite|correct|chemspider}}

|StdInChIKey = ZMXDDKWLCZADIW-UHFFFAOYSA-N

|StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

}}

|Section2={{Chembox Properties

|C=3|H=7|N=1|O=1

|Appearance = Colourless liquid

|Odor = Odorless, fishy if impure

|Density = 0.948 g/mL

|MeltingPtC = -61

|BoilingPtC = 153

|pKa = −0.3 (for the conjugate acid) (H₂O)<ref>{{cite web | title = Hazardous Substances Data Bank (HSDB) - N,N-DIMETHYLFORMAMIDE | url = https://pubchem.ncbi.nlm.nih.gov/source/hsdb/78}}</ref>

|Solubility = Miscible

|LogP = −0.829

|VaporPressure = 516 Pa

|LambdaMax = 270 nm

|Absorbance = 1.00

|RefractIndex = 1.4305 (at 20&nbsp;°C)

|Viscosity = 0.92 mPa·s (at 20&nbsp;°C)

}}

|Section3={{Chembox Structure

|Dipole = 3.86 D

}}

|Section4={{Chembox Thermochemistry

|DeltaHf = −239.4 ± 1.2 kJ/mol

|DeltaHc = −1.9416 ± 0.0012 MJ/mol

|HeatCapacity = 146.05 J/(K·mol)

}}

|Section5={{Chembox Hazards

|GHSPictograms = {{gHS flame}} {{gHS exclamation mark}} {{gHS health hazard}}

|GHSSignalWord = '''DANGER'''

|HPhrases = {{h-phrases|226|312|319|332|360}}

|PPhrases = {{p-phrases|280|305+351+338|308+313}}

|NFPA-H = 2

|NFPA-F = 2

|NFPA-R = 0

|FlashPtC = 58

|AutoignitionPtC = 445

|ExploLimits = 2.2–15.2%

|TLV-TWA = 30 mg/m³

|LD50 = {{unbulleted list|1.5 g/kg <small>(rabbit, dermal)</small>|2.8 g/kg <small>(rat, oral)</small>|3.7 g/kg <small>(mouse, oral)</small>|3.5 g/kg <small>(rat, oral)</small>}}

|PEL = TWA 10 ppm (30 mg/m³) [skin]<ref name=PGCH>{{PGCH|0226}}</ref>

|IDLH = 500 ppm<ref name=PGCH/>

|REL = TWA 10 ppm (30 mg/m³) [skin]<ref name=PGCH/>

|LC50 = 3092 ppm (mouse, 2 [[hour|h]])<ref name=IDLH>{{IDLH|68122|Dimethylformamide}}</ref>

|LCLo = 5000 ppm (rat, 6 h)<ref name=IDLH/>

}}

|Section6={{Chembox Related

|OtherFunction_label = alkanamides

|OtherFunction = {{unbulleted list|[[n-Methylformamide|''N''-Methylformamide]]|[[Diethylformamide]]|[[Deuterated DMF]]}}

|OtherCompounds = {{unbulleted list|[[n-Nitroso-N-methylurea|''N''-Nitroso-''N''-methylurea]]|[[ENU]]}}

'''Dimethylformamide''' is an [[organic compound]] with the [[chemical formula]] {{chem2|HCON(CH3)2|auto=1}}. Its structure is {{chem2|HC(\dO)\sN([[Methyl|\sCH3]])2}}. Commonly abbreviated as DMF (although this initialism is sometimes used for [[2,5-dimethylfuran|dimethylfuran]], or [[dimethyl fumarate]]), this colourless liquid is [[Miscibility|miscible]] with [[Water (molecule)|water]] and the majority of organic liquids. DMF is a common [[solvent]] for [[chemical reactions]]. Dimethylformamide is odorless, but [[chemical purity|technical-grade]] or degraded samples often have a fishy smell due to impurity of [[dimethylamine]]. Dimethylamine degradation impurities can be removed by [[Sparging (chemistry)|sparging]] samples with an inert gas such as [[argon]] or by [[sonication|sonicating]] the samples under reduced pressure. As its name indicates, it is structurally related to [[formamide]], having two [[methyl group]]s in the place of the two hydrogens. DMF is a [[polar molecule|polar]] ([[hydrophilic]]) [[aprotic solvent]] with a high [[boiling point]]. It facilitates reactions that follow polar mechanisms, such as [[SN2|S_N2]] reactions.

As for most [[amide]]s, the spectroscopic evidence indicates partial double bond character for the C−N and C−O bonds. Thus, the [[infrared spectroscopy|infrared spectrum]] shows a C=O stretching frequency at only 1675&nbsp;cm⁻¹, whereas a ketone would absorb near 1700&nbsp;cm⁻¹.<ref name=SDBS>{{cite web | publisher = AIST | location = Japan | work = Spectral Database for Organic Compounds | url = http://www.aist.go.jp/RIODB/SDBS/cgi-bin/cre_frame_disp.cgi?sdbsno=324 | title = Dimethylformamide | access-date = 2012-06-28}}{{Dead link|date=July 2019 |bot=InternetArchiveBot |fix-attempted=yes}}</ref>

DMF is a classic example of a [[fluxional molecule]].<ref>{{cite journal | author1 = H. S. Gutowsky | author2 = C. H. Holm | title = Rate Processes and Nuclear Magnetic Resonance Spectra. II. Hindered Internal Rotation of Amides | journal = J. Chem. Phys. | year = 1956 | volume = 25 | pages = 1228–1234 | doi=10.1063/1.1743184 | issue = 6|bibcode = 1956JChPh..25.1228G}}</ref>

[[Image:DmfDNMR.png|center|300px]]

The ambient temperature [[Nuclear magnetic resonance|¹H NMR spectrum]] shows two methyl signals, indicative of hindered rotation about the (O)C−N bond.<ref name=SDBS/> At temperatures near 100&nbsp;°C, the 500&nbsp;MHz NMR spectrum of this compound shows only one signal for the methyl groups.

DMF is miscible with water.<ref name=bipp>{{Ullmann | author = Bipp, H. | author2 = Kieczka, H. | title = Formamides | doi = 10.1002/14356007.a12_001.pub2}}</ref> The vapour pressure at 20&nbsp;°C is 3.5&nbsp;hPa.<ref>IPCS (International Programme on Chemical Safety) (1991). Environmental Health Criteria 114 "Dimethylformamide" United Nations Environment Programme, International Labour Organisation, World Health Organization; 1–124.</ref> A [[Henry's law]] constant of 7.47 × 10⁻⁵ hPa·m³/mol can be deduced from an experimentally determined equilibrium constant at 25&nbsp;°C.<ref>{{cite journal |author1=Taft, R. W. |author2=Abraham, M. H. |author3=Doherty, R. M. |author4=Kamlet, M. J. | title = The molecular properties governing solubilities of organic nonelectrolytes in water | journal = [[Nature (journal)|Nature]] | year = 1985 | volume = 313 | issue = 6001 | pages = 384–386 | doi = 10.1038/313384a0 |bibcode=1985Natur.313..384T |s2cid=36740734}}</ref> The [[partition coefficient]] log&nbsp;''P''_OW is measured to −0.85.<ref>(BASF AG, department of analytical, unpublished data, J-No. 124659/08, 27.11.1987)</ref> Since the density of DMF (0.95&nbsp;g·cm^&minus;3 at 20&nbsp;°C<ref name=bipp/>) is similar to that of water, significant flotation or stratification in surface waters in case of accidental losses is not expected.

[[File:DMF resonances.png|thumb|left|300px|Left: two resonance structures of DMF. Right: illustration highlighting delocalization.]]{{Clear left}}

==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.<ref>{{Cite encyclopedia|title = ''N'',''N''-Dimethylformamide|encyclopedia = Encyclopedia of Reagents for Organic Synthesis|last1 = Comins|first1 = Daniel L.|last2 = Joseph|first2 = Sajan P.|year = 2001|publisher = [[John Wiley & Sons]]|isbn = 9780470842898|doi = 10.1002/047084289x.rd335|chapter = N,N-Dimethylformamide}}</ref>

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.<ref name = VH1>{{cite journal|author-link1 = Anton Vilsmeier|last1 = Vilsmeier|first1 = Anton|last2 = Haack|first2 = Albrecht|title = Über die Einwirkung von Halogenphosphor auf Alkyl-formanilide. Eine neue Methode zur Darstellung sekundärer und tertiärer ''p''-Alkylamino-benzaldehyde|language = de|trans-title=On the reaction of phosphorus halides with alkyl formanilides. A new method for the preparation of secondary and tertiary ''p''-alkylamino-benzaldehyde|year = 1927|journal = [[Ber. Dtsch. Chem. Ges. A/B]]|volume = 60|issue = 1|pages = 119–122|doi = 10.1002/cber.19270600118}}</ref><ref name = VH2>{{cite book|last1 = Meth-Cohn|first1 = Otto|last2 = Stanforth|first2 = Stephen P.|chapter = The Vilsmeier-Haack Reaction|title = Additions to CX π-Bonds, Part 2|series = Comprehensive Organic Synthesis: Selectivity, Strategy and Efficiency in Modern Organic Chemistry|year = 1993|volume = 2|editor1-first = Barry M.|editor1-last = Trost|editor1-link = Barry M. Trost|editor2-first = Clayton H.|editor2-last = Heathcock|editor2-link = Clayton H. Heathcock|pages = 777–794|doi = 10.1016/B978-0-08-052349-1.00049-4|publisher = [[Elsevier]]|isbn = 9780080405933}}</ref> The process involves initial conversion of DMF to a chloroiminium ion, [(CH₃)₂N=CH(Cl)]⁺, known as a [[Vilsmeier reagent]],<ref>{{cite journal|title = The Vilsmeier Reaction of Non-Aromatic Compounds|first1 = Gurnos|last1 = Jones|first2 = Stephen P.|last2 = Stanforth|journal = [[Org. React.]]|year = 2000|volume = 56|issue = 2|pages = 355–686|doi = 10.1002/0471264180.or056.02}}</ref> which attacks arenes.

[[Organolithium compound]]s and [[Grignard reagent]]s react with DMF to give [[aldehyde]]s after hydrolysis in a reaction called [[Bouveault aldehyde synthesis]].<ref name="Wang-2009">{{cite book |last1=Wang |first1=Zerong |title=Comprehensive organic name reactions and reagents |date=2009 |publisher=John Wiley |location=Hoboken, N.J. |isbn=9780471704508 |pages=490–492}}</ref>

Dimethylformamide forms 1:1 [[adducts]] with a variety of Lewis acids such as the soft acid [[iodine|I₂]], and the hard acid [[phenol]]. It is classified as a [[HSAB theory|hard Lewis base]] and its [[ECW model]] base parameters are E_B = 2.19 and C_B = 1.31.<ref>{{cite journal|author1=Vogel G. C. |author2=Drago, R. S. |year=1996|journal=Journal of Chemical Education|volume=73|pages=701–707|title=The ECW Model|issue=8 |bibcode=1996JChEd..73..701V|doi=10.1021/ed073p701}}</ref> Its relative donor strength toward a series of acids, versus other Lewis bases, can be illustrated by [[ECW model|C-B plots]].<ref>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</ref><ref>{{cite journal|author1=Cramer, R. E. |author2=Bopp, T. T. |year=1977|title= Graphical display of the enthalpies of adduct formation for Lewis acids and bases |journal= Journal of Chemical Education |volume=54|pages=612–613|doi= 10.1021/ed054p612}} The plots shown in this paper used older parameters. Improved E&C parameters are listed in [[ECW model]]. </ref>

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.<ref>{{cite journal|last1=Verley|first1=A.|title=Sur la préparation des amides en général|journal=Bulletin de la Société Chimique de Paris|date=1893|volume=9|pages=690–692|url=https://babel.hathitrust.org/cgi/pt?id=uc1.a0008581456;view=1up;seq=700|series=3rd series|trans-title=On the preparation of amides in general|language=fr}} 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]].</ref>

DMF is prepared by combining [[methyl formate]] and [[dimethylamine]] or by reaction of dimethylamine with [[carbon monoxide]].<ref name="indchem">{{cite book |author1=Weissermel, K. |author2=Arpe, H.-J. | title = Industrial Organic Chemistry: Important Raw Materials and Intermediates | publisher = Wiley-VCH | isbn = 3-527-30578-5 | pages = 45–46 |year=2003}}</ref>

Although currently impractical, DMF can be prepared from [[supercritical carbon dioxide]] using [[ruthenium]]-based catalysts.<ref>{{cite book|author1=Walter Leitner|author2=Philip G. Jessop|title=Chemical synthesis using supercritical fluids|url=https://books.google.com/books?id=-9yqpBozUuYC&pg=PA408|access-date=27 June 2011|year=1999|publisher=Wiley-VCH|isbn=978-3-527-29605-7|pages=408–}}</ref>

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 [[leather]]s, fibers, films, and surface coatings.<ref name=bipp/>

*It is used as a reagent in the [[Bouveault aldehyde synthesis]]<ref>{{cite journal|last = Bouveault|first = Louis|author-link = Louis Bouveault|journal = Bulletin de la Société Chimique de Paris|year = 1904|series=3rd series|volume = 31|pages = 1306–1322|title = Modes de formation et de préparation des aldéhydes saturées de la série grasse|language = fr|trans-title = Methods of preparation of saturated aldehydes of the aliphatic series|url=https://babel.hathitrust.org/cgi/pt?id=uc1.a0004784781;view=1up;seq=1410}}</ref><ref>{{cite journal|last = Bouveault|first = Louis|author-link = Louis Bouveault|journal = Bulletin de la Société Chimique de Paris|year = 1904|series=3rd series|volume = 31|pages = 1322–1327|title = Nouvelle méthode générale synthétique de préparation des aldéhydes|trans-title = Novel general synthetic method for preparing aldehydes|language = fr|url=https://babel.hathitrust.org/cgi/pt?id=uc1.a0004784781;view=1up;seq=1426}}</ref><ref>{{cite book|last = Li|first = Jie Jack|title = Name Reactions: A Collection of Detailed Mechanisms and Synthetic Applications|edition = 5th|chapter = Bouveault aldehyde synthesis|pages = 72–73|chapter-url = https://books.google.com/books?id=HoXBBAAAQBAJ&pg=PA72|year = 2014|publisher = [[Springer Science & Business Media]]|isbn = 978-3-319-03979-4}}</ref> and in the [[Vilsmeier-Haack reaction]],<ref name = VH1 /><ref name = VH2 /> another useful method of forming [[aldehydes]].

*It is a common solvent in the [[Heck reaction]].<ref>{{cite book|title = The Mizoroki&ndash;Heck Reaction|editor-first = Martin|editor-last = Oestreich|publisher = [[John Wiley & Sons]]|year = 2009|isbn = 9780470716069}}</ref>

*It is a common catalyst used in the synthesis of [[acyl halides]], in particular the synthesis of [[acyl chlorides]] from [[carboxylic acids]] using [[oxalyl chloride|oxalyl]] or [[thionyl chloride]]. The catalytic mechanism entails reversible formation of an [[imidoyl chloride]] (also known as the 'Vilsmeier reagent'):<ref name = clayden>{{cite book | author = Clayden, J. | title = Organic Chemistry | publisher = Oxford University Press | location = Oxford | year = 2001 | pages = [https://archive.org/details/organicchemistry00clay_0/page/276 276–296] | isbn = 0-19-850346-6 | url-access = registration | url = https://archive.org/details/organicchemistry00clay_0/page/276}}</ref><ref>Ansell, M. F. in "The Chemistry of Acyl Halides"; S. Patai, Ed.; John Wiley and Sons: London, 1972; pp 35–68.</ref>

[[File:Acyl chloride via amide catalysis.png|650px|center]]

*DMF penetrates most [[plastics]] and makes them swell. Because of this property DMF is suitable for [[solid phase peptide synthesis]] and as a component of [[paint strippers]].

*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 is effective at separating and suspending [[carbon nanotubes]], and is recommended by the [[National Institute of Standards and Technology|NIST]] for use in [[near infrared spectroscopy]] of such.<ref name=miiswcn>{{cite book |author1=Haddon, R. |author2=Itkis, M. |editor1=Freiman, S. |editor2=Hooker, S. |editor3=Migler |editor4=K. |editor5=Arepalli, S. | title = Publication 960-19 Measurement Issues in Single Wall Carbon Nanotubes | chapter = 3. Near-Infrared (NIR) Spectroscopy | publisher = NIST |date=March 2008 | chapter-url = https://www.nist.gov/customcf/get_pdf.cfm?pub_id=852726 | chapter-format = pdf | page = 20 | access-date = 2012-06-28}}</ref>

*DMF can be utilized as a standard in proton NMR spectroscopy allowing for a quantitative determination of an unknown compound.

*In the synthesis of organometallic compounds, it is used as a source of [[carbon monoxide]] ligands.

*DMF is a common solvent used in [[electrospinning]].

*DMF is commonly used in the solvothermal synthesis of [[Metal-Organic Framework|metal–organic frameworks]].

*DMF-''d''₇ in the presence of a catalytic amount of [[Potassium tert-butoxide|potassium ''tert''-butoxide]] under microwave heating is a reagent for deuteration of polyaromatic hydrocarbons.

Dimethylformamide vapor exposure has shown reduced alcohol tolerance and skin irritation in some cases.<ref>{{cite journal | pmc=1008494 | year=1979 | last1=Lyle | first1=W. H. | last2=Spence | first2=T. W. | last3=McKinneley | first3=W. M. | last4=Duckers | first4=K. | title=Dimethylformamide and alcohol intolerance | journal=British Journal of Industrial Medicine | volume=36 | issue=1 | pages=63–66 | doi=10.1136/oem.36.1.63 | pmid=444443}}</ref>

On 20 June 2018, the [[Ministry of Environment (Denmark)|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.

<ref>{{cite web | title = Skumlegetøj afgiver farlige kemikalier (in English- Squishies giving dangerous chemicals) | url = https://mst.dk/service/nyheder/nyhedsarkiv/2018/jun/skumlegetoej-afgiver-farlige-kemikalier/ | author1 = Magnus Løfstedt | access-date = 2019-06-13 | archive-date = 2021-09-03 | archive-url = https://web.archive.org/web/20210903082250/https://mst.dk/service/nyheder/nyhedsarkiv/2018/jun/skumlegetoej-afgiver-farlige-kemikalier/ | url-status = dead}}</ref>

The acute [[LD50]] (oral, rats and mice) is 2.2–7.55 g/kg.<ref name=bipp/> Hazards of DMF have been examined.<ref name=dmf-uses>{{cite journal |author1=Redlich, C. |author2=Beckett, W. S. |author3=Sparer, J. |author4=Barwick, K. W. |author5=Riely, C. A. |author6=Miller, H. |author7=Sigal, S. L. |author8=Shalat, S. L. |author9=Cullen, M. R. | title = Liver disease associated with occupational exposure to the solvent dimethylformamide | journal = Annals of Internal Medicine | year = 1988 | volume = 108 | issue = 5 | pages = 680–686 | pmid = 3358569 | doi=10.7326/0003-4819-108-5-680}}</ref>

{{Reflist|35em}}

{{Authority control}}

[[Category:Formamides]]

[[Category:Amide solvents]]

[[Category:Hepatotoxins]]