Methylthiomethyl ether
Encyclopedia
In organic chemistry
a methylthiomethyl (MTM) ether
is a protective group for hydroxyl groups
. Hydroxyl groups are present in many chemical compounds and they must be protected during oxidation, acylation
, halogenation
, dehydration
and other reactions to which they are susceptible.
Many kinds of protective groups for hydroxyl groups have been developed and used in organic chemistry, but the number of protective groups for tertiary hydroxyl groups, which are susceptible to acid-catalyzed dehydration
, is still small because of their poor reactiveness. They can be easily protected with MTM ether
s and recovered in good yield.
To introduce an MTM ether
to a hydroxyl group, two methods are mainly used. One is a typical Williamson ether synthesis
using an MTM halide
as an MTM resource and sodium hydride
(NaH) as a base. The other is a special method, in which dimethyl sulfoxide
(DMSO) and acetic anhydride
(Ac2O) are used. In this case, the reaction proceeds with Pummerer rearrangement
:
MTM ether
s have another advantage. They are removed by neutral (but toxic) mercuric chloride, to which most other ethers are stable. As a result, the selective deprotection of polyfunctional molecules becomes possible using MTM ether
s as the protective groups for their hydroxyl groups.
Organic chemistry
Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, composition, reactions, and preparation of carbon-based compounds, hydrocarbons, and their derivatives...
a methylthiomethyl (MTM) ether
Ether
Ethers are a class of organic compounds that contain an ether group — an oxygen atom connected to two alkyl or aryl groups — of general formula R–O–R'. A typical example is the solvent and anesthetic diethyl ether, commonly referred to simply as "ether"...
is a protective group for hydroxyl groups
Hydroxide
Hydroxide is a diatomic anion with chemical formula OH−. It consists of an oxygen and a hydrogen atom held together by a covalent bond, and carrying a negative electric charge. It is an important but usually minor constituent of water. It functions as a base, as a ligand, a nucleophile, and a...
. Hydroxyl groups are present in many chemical compounds and they must be protected during oxidation, acylation
Acylation
In chemistry, acylation is the process of adding an acyl group to a compound. The compound providing the acyl group is called the acylating agent....
, halogenation
Halogenation
Halogenation is a chemical reaction that incorporates a halogen atom into a molecule in substitution of hydrogen atom. Halogenation takes place in the gas phase. There are four types of halogenation: fluorination, chlorination, bromination, and iodination...
, dehydration
Dehydration reaction
In chemistry and the biological sciences, a dehydration reaction is usually defined as a chemical reaction that involves the loss of water from the reacting molecule. Dehydration reactions are a subset of elimination reactions...
and other reactions to which they are susceptible.
Many kinds of protective groups for hydroxyl groups have been developed and used in organic chemistry, but the number of protective groups for tertiary hydroxyl groups, which are susceptible to acid-catalyzed dehydration
Dehydration
In physiology and medicine, dehydration is defined as the excessive loss of body fluid. It is literally the removal of water from an object; however, in physiological terms, it entails a deficiency of fluid within an organism...
, is still small because of their poor reactiveness. They can be easily protected with MTM ether
Ether
Ethers are a class of organic compounds that contain an ether group — an oxygen atom connected to two alkyl or aryl groups — of general formula R–O–R'. A typical example is the solvent and anesthetic diethyl ether, commonly referred to simply as "ether"...
s and recovered in good yield.
To introduce an MTM ether
Ether
Ethers are a class of organic compounds that contain an ether group — an oxygen atom connected to two alkyl or aryl groups — of general formula R–O–R'. A typical example is the solvent and anesthetic diethyl ether, commonly referred to simply as "ether"...
to a hydroxyl group, two methods are mainly used. One is a typical Williamson ether synthesis
Williamson ether synthesis
The Williamson ether synthesis is an organic reaction, forming an ether from an organohalide and an alcohol. This reaction was developed by Alexander Williamson in 1850. Typically it involves the reaction of an alkoxide ion with a primary alkyl halide via an SN2 reaction...
using an MTM halide
Halide
A halide is a binary compound, of which one part is a halogen atom and the other part is an element or radical that is less electronegative than the halogen, to make a fluoride, chloride, bromide, iodide, or astatide compound. Many salts are halides...
as an MTM resource and sodium hydride
Sodium hydride
Sodium hydride is the chemical compound with the empirical formula NaH. It is primarily used as a strong base in organic synthesis. NaH is representative of the saline hydrides, meaning it is a salt-like hydride, composed of Na+ and H− ions, in contrast to the more molecular hydrides such as...
(NaH) as a base. The other is a special method, in which dimethyl sulfoxide
Dimethyl sulfoxide
Dimethyl sulfoxide is an organosulfur compound with the formula 2SO. This colorless liquid is an important polar aprotic solvent that dissolves both polar and nonpolar compounds and is miscible in a wide range of organic solvents as well as water...
(DMSO) and acetic anhydride
Acetic anhydride
Acetic anhydride, or ethanoic anhydride, is the chemical compound with the formula 2O. Commonly abbreviated Ac2O, it is the simplest isolatable acid anhydride and is a widely used reagent in organic synthesis...
(Ac2O) are used. In this case, the reaction proceeds with Pummerer rearrangement
Pummerer rearrangement
The Pummerer rearrangement is an organic reaction whereby an alkyl sulfoxide rearranges to an α-acyloxy–thioether in the presence of acetic anhydride. In this reaction, sulfur is reduced while adjacent carbon is oxidized....
:
MTM ether
Ether
Ethers are a class of organic compounds that contain an ether group — an oxygen atom connected to two alkyl or aryl groups — of general formula R–O–R'. A typical example is the solvent and anesthetic diethyl ether, commonly referred to simply as "ether"...
s have another advantage. They are removed by neutral (but toxic) mercuric chloride, to which most other ethers are stable. As a result, the selective deprotection of polyfunctional molecules becomes possible using MTM ether
Ether
Ethers are a class of organic compounds that contain an ether group — an oxygen atom connected to two alkyl or aryl groups — of general formula R–O–R'. A typical example is the solvent and anesthetic diethyl ether, commonly referred to simply as "ether"...
s as the protective groups for their hydroxyl groups.