N-Methylformamide

N-Methylformamide
IUPAC name N-Methylformamide
Other names NMF, methylformide
Identifiers
CAS number	123-39-7 Y
PubChem	31254
ChemSpider	28994 Y
KEGG	C11489 Y
ChEBI	CHEBI:7438 N
ChEMBL	CHEMBL9240 Y
RTECS number	LQ3000000
Jmol-3D images	Image 1
SMILES O=CNC
InChI InChI=1S/C2H5NO/c1-3-2-4/h2H,1H3,(H,3,4) Y Key: ATHHXGZTWNVVOU-UHFFFAOYSA-N Y InChI=1/C2H5NO/c1-3-2-4/h2H,1H3,(H,3,4) Key: ATHHXGZTWNVVOU-UHFFFAOYAO
Properties
Molecular formula	C2H5NO
Molar mass	59.067 g/mol
Appearance	Clear liquid
Density	1.003 g/cm3, liquid
Melting point	-3 °C, 270 K, 27 °F
Boiling point	198-200 °C (471-473 K)
Solubility in water	Miscible
Refractive index (nD)	1.432
Hazards
R-phrases	61-21
S-phrases	53-45
Flash point	111 °C
Related compounds
N (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

N-Methylformamide (NMF) is a colorless, nearly odorless, organic compound with molecular formula CH₃NHCHO, which is a liquid at room temperature. It is infinitely soluble in water. NMF is mainly used as a reagent in various organic syntheses with limited applications as a highly polar solvent.^[1]

NMF is closely related to other formamides, notably formamide and dimethylformamide (DMF). However, industrial use and production of NMF are far less than for either of these other formamides. DMF is favored over NMF as a solvent due to its greater stability.^[1] Annual production of NMF can be assumed to be significantly less than the production of either formamide (100,000 tons) or DMF (500,000 tons).^[1]

Structure and properties

Like DMF and formamide, each of the two rotamers of NMF are described by two principal resonance structures:

This description highlights the partial double bond that exists between the carbonyl carbon and nitrogen, which gives rise to a high rotational barrier. Thus, the molecule is not able to freely rotate around its main axis and the E-configuration is preferred due to steric repulsion of the larger substituents.^{[citation needed]}

Preparation

NMF is typically prepared by allowing methylamine to react with methyl formate:^[1]

CH₃NH₂ + HCOOCH₃ → CH₃NHCHO + CH₃OH

A less common alternative to this process is transamidation involving formamide:^[1]

HCONH₂ + CH₃NH₂ → CH₃NHCHO + NH₃

Uses

NMF is used in specialized amidation reactions where formamide would not be suitable. These reactions can generally be categorized by the following equation:

R-Lg + CH₃NHCHO → R-NCH₃CHO + H-Lg (where Lg is a leaving group)

These reactions typically proceed in high yields.^[1]

NMF is the precursor to methyl isocyanide, a ligand in coordination chemistry and an intermediate in the production of some pharmaceutical compounds.^[2]

References

1. ^ ^{a b c d e f} Hansjörg Bipp and Heinz Kieczka "Formamides" in Ullmann's Encyclopedia of Industrial Chemistry, Wiley-VCH, Weinheim, 2002. doi:10.1002/14356007.a12_001
2. ^ R. E. Schuster, James E. Scott, and Joseph Casanova, Jr. (1973), "Methyl_Isocyanide", Org. Synth., http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=CV5P0772 ; Coll. Vol. 5: 772