Chloroalkyl ether

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Chemical structure of chloromethyl methyl ether.

Chloroalkyl ethers are a class of organic compounds with the general structure R-O-(CH2)n-Cl, characterized as an ether connected to a chloromethyl group via an alkane chain.

Chloromethyl methyl ether (CMME) is an ether with the formula CH3OCH2Cl. It is used as an alkylating agent and industrial solvent to manufacture dodecylbenzyl chloride, water repellents, ion-exchange resins, polymers, and as a chloromethylation reagent. It is a known human carcinogen.[1] In organic synthesis the compound is used for the introduction of the methoxymethyl (MOM) protecting group.

Closely related compounds of industrial importance are bis(chloromethyl) ether (BCME) (closely related to chemical weapon sulfur mustard)[2] and benzyl chloromethyl ether (BOMCl).

Chloromethyl ether R Molar mass CAS number Boiling point °C
Benzyl chloromethyl ether Benzyl benzyl chloromethyl ether 156.61 3587-60-8 102 °C @ 14 mmHg (1.9 kPa)
Chloromethyl methyl ether Methyl methyl chloromethyl ether 80.51 107-30-2 55-57
Bis(chloromethyl) ether Bis(chloromethyl) ether.svg 114.96 542-88-1 106
tert-Butyl chloromethyl ether Butyl T-Butoxymethyl chloride.svg 124.5
Methoxyethyl chloromethyl ether Methoxyethoxymethyl chloride.svg 124.57 3970-21-6 50-52 °C @ 13 mmHg (1.7 kPa)
Dichloromethyl methyl ether Dichloromethyl methyl ether.svg 114.96 4885-02-3 82 - 85.5 °C
Representative chloroalkyl ethers[3]

Alcohol protection[edit]

2-Methoxyethoxymethyl (MEM) group is commonly used in organic synthesis as a protecting group for alcohols.

MTM-Ether.png

Most common protection methods[edit]

MEMprotectedalcohol.png

Most common deprotection methods[edit]

The 2-methoxyethoxymethyl protecting group can be cleaved with a range of Lewis acids, including but not limited to:

  • TiCl4 or ZnBr2 in dichloromethane at 0 °C to ambient temperature
  • If the solvent of choice is a protic solvent such as methanol, formic acid can be used to cleave MEM group at elevated temperatures

_____________________________

Methoxymethyl (MOM) is used as a protecting group for alcohols in organic synthesis.

MOM Ether.png

Most common protection methods[edit]

MOMProtectedAlcohol.png

[7]

  • For reactions carried out in more polar solvents such as tetrahydrofuran (THF) or N,N-dimethylformamide (DMF), protection of alcohol can be carried out using sodium hydride at 0 °C to ambient temperatures

Most common deprotection methods[edit]

MOM group can be cleaved with acid, commonly used conditions for deprotection of MOM alcohols include:[6]

MOMDepr.png

[8]

References[edit]

  1. ^ Bis(chloromethyl) Ether and Technical-Grade Chloromethyl Methyl Ether CAS Nos. 542-88-1 and 107-30-2, Report on carcinogens, Eleventh edition
  2. ^ Bis(Chloromethyl) ether Safety Data Sheet, Division of Occupational Health and Safety, US National Institutes of Health
  3. ^ http://www.sigmaaldrich.com
  4. ^ Corey, E. J.; Gras, Jean-Louis; Ulrich, Peter (1976-03-01). "A new general method for protection of the hydroxyl function". Tetrahedron Letters. 17 (11): 809–812. doi:10.1016/S0040-4039(00)92890-9. 
  5. ^ Lee, Hong Myung; Nieto-Oberhuber, Cristina; Shair, Matthew D. (2008-12-17). "Enantioselective Synthesis of (+)-Cortistatin A, a Potent and Selective Inhibitor of Endothelial Cell Proliferation". Journal of the American Chemical Society. 130 (50): 16864–16866. doi:10.1021/ja8071918. ISSN 0002-7863. PMID 19053422. 
  6. ^ a b Wuts, Peter G. M.; Greene, Theodora W. Greene's Protective Groups in Organic Synthesis, Fourth Edition - Wuts - Wiley Online Library. doi:10.1002/0470053488. 
  7. ^ Enders, Dieter; Geibel, Gunter; Osborne, Simon (2000-04-17). "Diastereo- and Enantioselective Total Synthesis of Stigmatellin A". Chemistry – A European Journal. 6 (8): 1302–1309. doi:10.1002/(SICI)1521-3765(20000417)6:83.0.CO;2-J. ISSN 1521-3765. 
  8. ^ Amano, Seiji; Takemura, Noriaki; Ohtsuka, Masami; Ogawa, Seiichiro; Chida, Noritaka (1999-03-26). "Total synthesis of paniculide A from d-glucose". Tetrahedron. 55 (13): 3855–3870. doi:10.1016/S0040-4020(99)00096-4.