:Tetramethylurea

It is obtained by the reaction of dimethylamine with phosgene in the presence of sodium hydroxide solution.{{cite patent|country = US|number =3681457 |title=Method of making tetramethylurea |pubdate =1972-8-1 |fdate =1969-2-26 |inventor=H. Babad |assign=The Ott Chemical Co.}} A closely related method combines dimethylcarbamoyl chloride with excess dimethylamine.{{citation|surname1=J.K. Lawson Jr.|surname2=J.A.T. Croom|periodical=J. Org. Chem.|title=Dimethylamides from alkali carboxylates and dimethylcarbamoyl chloride |volume=28|issue=1|pages=232–235|date= 1963|language=German|doi=10.1021/jo01036a513}}{{cite patent |country = US|number =3597478 |title=Preparation of tetramethylurea |pubdate =1971-8-3 |fdate =1967-9-14 |inventor =M.L. Weakly |assign =Nipak, Inc.}} This reactions is highly exothermic. The removal of the resulting dimethylamine hydrochloride requires some effort.

File:Tetramethylharnstoff aus Phosgen.svg

The reaction of diphenylcarbonate with dimethylamine in an autoclave is also effective.

File:Tetramethylharnstoff aus Diphenylcarbonat.svg

Tetramethylurea is formed upon the oxygenation of tetrakis(dimethylamino)ethylene (TDAE).{{citation|surname1=H.E. Winberg|surname2=J.R. Downing|surname3=D.D. Coffman|periodical=J. Am. Chem. Soc.|title=The chemiluminescence of tetrakis(dimethylamino)ethylene |volume=87|issue=9|pages=2054–2055|date= 1965|language=German|doi=10.1021/ja01087a039}}

File:Oxidation von TDAE.svg

Tetramethylurea is also a common by-product formed in amide bond forming reactions and peptide synthesis with uronium and guanidinium-based reagents such as HATU, HBTU and TCFH.

Tetramethylurea is miscible with a variety of organic compounds, including acids such as acetic acid or bases such as pyridine and an excellent solvent for organic substances such as ε-caprolactam and benzoic acid. It dissolves even some inorganic salts such as silver nitrate and sodium iodide.{{citation|surname1=B.J. Barker|surname2=J.A. Caruso|title=The Chemistry of Nonaqueous Solvents, IV. Solution Phenomena and Aprotic Solvents|publisher=Academic Press|location=New York|pages=[https://archive.org/details/chemistryofnonaq0000lago/page/110 110–127]|isbn=978-0-12-433804-3|date=1976|language=German|url-access=registration|url=https://archive.org/details/chemistryofnonaq0000lago/page/110}}{{citation|surname1=B.J. Barker|surname2=J. Rosenfarb|surname3=J.A. Caruso|periodical=Angew. Chem.|title=Harnstoffe als Lösungsmittel in der chemischen Forschung |volume=91|issue=7|pages=560–564|date= 1979|language=German|doi=10.1002/ange.19790910707|bibcode=1979AngCh..91..560B }} Tetramethylurea is often used in place of hexamethylphosphoramide (HMPT), which is suspected of being carcinogenic.{{citation|surname1=A.J. Chalk|periodical=J. Organomet. Chem.|title=The use of sodium hydride as a reducing agent in nitrogen-containing solvents I. The reduction of chlorosilanes in Hexaalkylphosphoric triamides and tetraalkylureas |volume=21|issue=1|pages=95–101|date= 1970|language=German|doi=10.1016/S0022-328X(00)90598-9}}

Tetramethylurea is suitable as a reaction medium for the polymerization of aromatic diacid chlorides (such as isophthalic acid) and aromatic diamines (such as 1,3-diaminobenzene (m-phenylenediamine)) to aramids such as poly (m-phenylene isophthalamide) (Nomex®){{citation|surname1=G. Odian|title=Principles of Polymerization, 4th Edition |publisher=Wiley-Interscience|location=Hoboken, NJ|page=100|isbn=978-0-471-27400-1|date= 2004|language=German}}{{citation|surname1=H.G. Rodgers|surname2=R.A. Gaudiana|surname3=W.C. Hollinsed|surname4=P.S. Kalyanaraman|surname5=J.S. Manello|surname6=C. McGovern|surname7=R.A. Minns|surname8=R. Sahatjian|periodical=Macromolecules|title=Highly amorphous, birefringent, para-linked aromatic polyamides |volume=18|issue=6|pages=1058–1068|date= 1985|language=German|doi=10.1021/ma00148a003|bibcode=1985MaMol..18.1058R}}

The polymerization of 4-amino benzoic acid chloride hydrochloride in tetramethylurea provides isotropic viscous solutions of poly(p-benzamide) (PPB), which can be directly spun into fibers.{{citation|surname1=J. Preston|editor-surname1=A. Blumstein|title=Synthesis and Properties of Rodlike Condensation Polymers, in Liquid Crystalline Order in Polymers|publisher=Academic Press|location=New York|pages=[https://archive.org/details/liquidcrystallin0000unse/page/141 141–166]|isbn=978-0-12-108650-3|date=1978|language=German|url=https://archive.org/details/liquidcrystallin0000unse/page/141}}

File:Polymerisation von p-Aminobenzoylchlorid.svg

In a tetramethylurea-LiCl mixture stable isotropic solutions can be obtained up to a PPB polymer concentration of 14%.{{citation|surname1=S.L. Kwolek|surname2=P.W. Morgan|surname3=J.R. Schaefgen|surname4=L.W. Gulrich|periodical=Macromolecules|title=Synthesis, Anisotropic Solutions, and Fibers of Poly(1,4-benzamide) |volume=10|issue=6|pages=1390–1396|date= 1977|language=German|doi=10.1021/ma60060a041|bibcode=1977MaMol..10.1390K}}

Tetramethylurea also dissolves cellulose ester and swells other polymers such as polycarbonates, polyvinyl chloride or aliphatic polyamides, usually at elevated temperature.

Strong and hindered non-nucleophilic guanidine bases are accessible from tetramethylurea in a simple manner,{{OrgSynth|Kurzcode=CV9P0147 |author=D.H.R. Barton |author2=M. Chen |author3=J.C. Jászbérenyi |author4=D.K. Taylor |title=Preparation and Reactions of 2-tert-butyl-1,1,3,3-tetramethylguanidine: 2,2,6-trimethylcyclohexen-1-yl iodide |year=1997 |volume=74 |page=101 |ColVol=9 |ColVolSeiten=147 |doi=10.15227/orgsyn.074.0101}}{{citation|surname1=D.H.R. Barton|surname2=J.D. Elliott|surname3=S.D. Géro|periodical=J. Chem. Soc., Chem. Commun.|title=The synthesis and properties of a series of strong but hindered organic bases |issue=21|pages=1136–1137|date= 1981|language=German|doi=10.1039/C39810001136}} which are in contrast to the fused amidine bases DBN or DBU not alkylated.

File:2-tert.-Butyl-1,1,3,3-tetramethylguanidin.svg

A modification of the Koenigs-Knorr reaction for building glycosides from 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide (acetobromoglucose) originates from S. Hanessian who used the silver salt silver trifluoromethanesulfonate (TfOAg) and as a proton acceptor tetramethylurea.{{citation|surname1=S. Hanessian|surname2=J. Banoub|periodical=Carbohydr. Res.|title=Chemistry of the glycosidic linkage. An efficient synthesis of 1,2-trans-disaccharides |volume=53|pages=C13–C16|date= 1977|language=German|doi=10.1016/S0008-6215(00)85468-3}} This process variant is characterized by a simplified process control, high anomeric purity and high yields of the products. If the reaction is carried out with acetobromoglucose and silver triflate/tetramethylurea at room temperature, then tetramethylurea reacts not only as a base, but also with the glycosyl to form a good isolable uroniumtriflates in 56% yield.{{citation|surname1=K. Bock|surname2=J. Fernández-Bolanos Guzmán|surname3=S. Refn|periodical=Carbohydr. Res.|title=Synthesis and properties of 1,1,3,3-tetramethyl-2-(2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl)uronium triflate |volume=232|issue=2|pages=353–357|date= 1992|language=German|doi=10.1016/0008-6215(92)80067-B}}

File:Uroniumsalz mit Acetobromglucose.svg

The acute toxicity of tetramethylurea is moderate. However, it is embryotoxic and teratogenic towards several animal species.{{citation|surname1=The MAK Collection for Occupational Health and Safety|title=Tetramethylharnstoff [MAK Value Documentation in German language, 1979], Documentations and Methods |pages=1–6 |publisher=Wiley-VCH|location=Weinheim|date= 2012|language=German|doi=10.1002/3527600418.mb63222d0007|chapter=Tetramethylharnstoff [MAK Value Documentation in German language, 1979] |isbn=978-3-527-60041-0 |doi-access=free}} Tetramethylurea was demonstrated to not exhibit dermal corrosion but did exhibit dermal and eye irritation.{{Cite journal |last=Graham |first=Jessica C. |last2=Trejo-Martin |first2=Alejandra |last3=Chilton |first3=Martyn L. |last4=Kostal |first4=Jakub |last5=Bercu |first5=Joel |last6=Beutner |first6=Gregory L. |last7=Bruen |first7=Uma S. |last8=Dolan |first8=David G. |last9=Gomez |first9=Stephen |last10=Hillegass |first10=Jedd |last11=Nicolette |first11=John |last12=Schmitz |first12=Matthew |date=2022-06-20 |title=An Evaluation of the Occupational Health Hazards of Peptide Couplers |url=https://pubs.acs.org/doi/10.1021/acs.chemrestox.2c00031 |journal=Chemical Research in Toxicology |language=en |volume=35 |issue=6 |pages=1011–1022 |doi=10.1021/acs.chemrestox.2c00031 |issn=0893-228X |pmc=9214767 |pmid=35532537}} The sensitization potential of tetramethylurea was shown to be low compared (non-sensitizing at 1% in LLNA testing according to OECD 429{{Cite book |last=OECD |url=https://www.oecd-ilibrary.org/environment/test-no-429-skin-sensitisation_9789264071100-en |title=Test No. 429: Skin Sensitisation: Local Lymph Node Assay |date=2010 |publisher=Organisation for Economic Co-operation and Development |location=Paris |language=en}}).

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Category:Ureas

Category:Amide solvents