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Alcohol Protection (Benzyl (Bn) ether)
Benzyl, abbreviated as Bn, is commonly used in organic synthesis as a robust protecting group for alcohols and carboxylic acids.

Most common protection methods

 * Treatment of alcohol with a strong base such as powdered potassium hydroxide or sodium hydride and benzyl halide (BnX; X=Cl, Br)
 * Monobenzylation of diols can be achieved using Ag2O in dimethylformamide (DMF) at ambient to elevated temperatures
 * Primary alcohols can be selectively benzylated in presence of phenol functional groups using Cu(acac)2

Most common deprotection methods
Benzyl ethers can be removed under reductive conditions, oxidative conditions, and the use of Lewis Acids.

Reductive Conditions Oxidative Conditions Lewis Acid-Based
 * Removed using hydrogenolysis
 * Single electron process with Na/NH3 or Li/NH3
 * Benzyl protecting group can be removed using a wide range of oxidizing agents including:
 * CrO3/AcOH at ambient temperature
 * Ozone
 * N-Bromosuccinimide (NBS)
 * N-Iodosuccinimide (NIS)
 * Trimethylsilyl iodide (Me3SiI) in dichloromethane at ambient temperature (selectivity can be achieved under specific conditions)

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

Most common protection methods

 * Treatment of alcohol with bases such as sodium hydride or potassium hydride and 2-methoxyethoxymethyl chloride in tetrahydrofuran (THF) at 0 °C
 * MEM group can also be installed at ambient temperature with 2-methoxyethoxymethyl chloride and a mild base such as N,N-diisopropylethylamine (DIPEA) in dichloromethane

Most common deprotection methods
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

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



Most common protection methods

 * Treatment of alcohol with N,N-diisopropylethylamine (DIPEA) and methoxymethyl chloride (MOM chloride) in dichloromethane at 0 °C
 * 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
MOM group can be cleaved with acid, commonly used conditions for deprotection of MOM alcohols include:
 * Concentrated hydrochloric acid in methanol or water
 * Trifluoroacetic acid (TFA) in dichloromethane
 * Acetyl chloride in methanol at 0 °C

Alcohol Protection (p-Methoxybenzyl (PMB) ether)
p-Methoxybenzyl (PMB) is used as a protecting group for alcohols in organic synthesis.



Most common protection methods

 * Strong base such as powdered potassium hydroxide or sodium hydride and p-methoxybenzyl halide (BnX; X=Cl, Br)
 * 4-methoxybenzyl-2,2,2-trichloroacetimidate can be used to install the PMB group in presence of:
 * Scandium (III) triflate (Sc(OTf)3) in toluene at 0 °C
 * Trifluoromethanesulfonic acid (TfOH) in dichloromethane at 0 °C

Most common deprotection methods

 * 2,3-Dichloro-5,6-dicyano-p-benzoquinone (DDQ)
 * Conditions for deprotection of benzyl group are applicable for cleavage of PMB protecting group

Alcohol Protection (Methylthiomethyl (MTM) ether)
Methylthiomethyl (MTM) group is used as a protecting group for alcohols in organic synthesis. This type of alcohol protecting group is robust under mild acidic reaction conditions.



Most common protection methods

 * Treatment of alcohol with sodium hydride and methylthiomethyl halide
 * Dimethyl sulfoxide (DMSO) and acetic acid (AcOH) in acetic anhydride (Ac2O) at ambient temperature

Most common deprotection methods

 * Mercury (II) chloride (HgCl2); calcium carbonate (CaCO3) is used as an acid scavenger for acid sensitive substrates
 * Iodomethane (MeI) in presence of sodium bicarbonate (NaHCO3) at elevated temperatures (this type of reaction is generally carried out in acetone/H2O solution)
 * Magnesium iodide (MgI) and acetic anhydride (Ac2O) in ether at ambient temperature

Alcohol Protection (Pivaloyl (Pv) ester)
Pivaloyl (Pv) group is used as a protecting group in organic synthesis.



Most common protection methods

 * Treatment of alcohol with pivaloyl chloride (PvCl) in presence of pyridine
 * Pivaloic anhydride with Sc(OTf)3 or VO(OTf)2

Most common deprotection methods

 * Tetrabutylammonium hydroxide (Bu4NOH) at ambient temperatures
 * Treatment with aqueous methylamine (MeNH2)
 * Pivaloate esters can be cleaved with strong bases:
 * 0.5N sodium hydroxide (NaOH) in ethanol/water solution
 * Potassium carbonate (K2CO3) or sodium methoxide (NaOMe) in methanol


 * Methyl lithium (MeLi) in ether
 * Potassium tert-butoxide in water

Alcohol Protection (Tetrahydropyranyl (THP) ether)
In organic synthesis, 2-tetrahydropyranyl group (THP) is used as a protecting group for alcohols.



Most common protection methods

 * Treatment of alcohol with dihydropyran and p-toluenesulfonic acid in dichloromethane at ambient temperature
 * 2-hydroxytetrahydropyranyl, triphenylphosphine, diethyl azodicarboxylate (DEAD) in THF

Most common deprotection methods

 * Acetic acid (AcOH) in THF/water solution or p-toluenesulfonic acid in water
 * Pyridinium p-toluenesulfonate (PPTS) in ethanol

Alcohol Protection (Trimethylsilyl (TMS) ether)
In organic synthesis, TMS group is used as a protecting group for alcohols.



Most common protection methods

 * Trimethylsilyl chloride (TMSCl) or trimethylsilyl trifluoromethanesulfonate (TMSOTf) and base (ie. pyridine, triethylamine, or 2,6-lutidine) in dichloromethane
 * TMSCl and lithium sulfide (Li2S) in acetonitrile

Most common deprotection methods

 * TMS groups are susceptible to cleavage upon treatment with HF-based reagents
 * Tetrabutylammonium fluoride (Bu4NF) in THF
 * Fluorosilicic acid (H2SiF6)
 * Treatment with HCl in THF/water solution