The ''tert''-butyloxycarbonyl protecting group or ''tert''-butoxycarbonyl protecting group (BOC group) is a protecting group used in

organic synthesis Organic synthesis is a special branch of chemical synthesis and is concerned with the intentional construction of organic compounds. Organic molecules are often more complex than inorganic compounds, and their synthesis has developed into one o ...

. The BOC group can be added to the

amine In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituen ...

under aqueous conditions using di-''tert''-butyl dicarbonate in the presence of a base such as

sodium carbonate Sodium carbonate, , (also known as washing soda, soda ash and soda crystals) is the inorganic compound with the formula Na2CO3 and its various hydrates. All forms are white, odourless, water-soluble salts that yield moderately alkaline solutions ...

Protection of the amine can also be accomplished in

acetonitrile Acetonitrile, often abbreviated MeCN (methyl cyanide), is the chemical compound with the formula and structure . This colourless liquid is the simplest organic nitrile (hydrogen cyanide is a simpler nitrile, but the cyanide anion is not clas ...

solution using 4-dimethylaminopyridine (DMAP) as the base. Removal of the BOC in

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

s can be accomplished with strong acids such as

trifluoroacetic acid Trifluoroacetic acid (TFA) is an organofluorine compound with the chemical formula CF3CO2H. It is a structural analogue of acetic acid with all three of the acetyl group's hydrogen atoms replaced by fluorine atoms and is a colorless liquid with ...

dichloromethane Dichloromethane (DCM or methylene chloride, methylene bichloride) is an organochlorine compound with the formula . This colorless, volatile liquid with a chloroform-like, sweet odour is widely used as a solvent. Although it is not miscible with ...

, or with

HCl HCL may refer to: Science and medicine * Hairy cell leukemia, an uncommon and slowly progressing B cell leukemia * Harvard Cyclotron Laboratory, from 1961 to 2002, a proton accelerator used for research and development * Hollow-cathode lamp, a spe ...

methanol Methanol (also called methyl alcohol and wood spirit, amongst other names) is an organic chemical and the simplest aliphatic alcohol, with the formula C H3 O H (a methyl group linked to a hydroxyl group, often abbreviated as MeOH). It is a ...

. A complication may be the tendency of the ''t''-butyl cation intermediate to alkylate other nucleophiles; scavengers such as

anisole Anisole, or methoxybenzene, is an organic compound with the formula CH3OC6H5. It is a colorless liquid with a smell reminiscent of anise seed, and in fact many of its derivatives are found in natural and artificial fragrances. The compound is ...

thioanisole Thioanisole is an organic compound with the formula CH3SC6H5. It is a colorless liquid that is soluble in organic solvents. It is the simplest alkyl–aryl thioether. The name indicates that this compound is the sulfur analogue—the thioether rat ...

may be used. Selective cleavage of the ''N''-Boc group in the presence of other protecting groups is possible when using AlCl₃. Sequential treatment with trimethylsilyl iodide then methanol can also be used for Boc deprotection, especially where other deprotection methods are too harsh for the substrate. The mechanism involves silylation of the carbonyl oxygen and elimination of ''tert''-butyl iodide (),

methanolysis In organic chemistry, transesterification is the process of exchanging the organic group R″ of an ester with the organic group R' of an alcohol. These reactions are often catalyzed by the addition of an acid or base catalyst. The reaction can ...

of the silyl ester to the

carbamic acid Carbamic acid, which might also be called aminoformic acid or aminocarboxylic acid, is the chemical compound with the formula . It can be obtained by the reaction of ammonia and carbon dioxide at very low temperatures, which also yields an equ ...

() and finally

decarboxylation Decarboxylation is a chemical reaction that removes a carboxyl group and releases carbon dioxide (CO2). Usually, decarboxylation refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is t ...

to the amine ().

Amine protection

The ''tert''-butyloxycarbonyl (Boc) group is used as a protecting group for

s in

Common amine protection methods

*Simple rapid stirring of a mixture of the amine and di-''tert''-butyl dicarbonate (Boc₂O) suspended in water at ambient temperature, an example of an on-water reaction. *Heating a mixture of the amine to be protected and di-''tert''-butyl dicarbonate in

tetrahydrofuran Tetrahydrofuran (THF), or oxolane, is an organic compound with the formula (CH2)4O. The compound is classified as heterocyclic compound, specifically a cyclic ether. It is a colorless, water-miscible organic liquid with low viscosity. It is ma ...

(THF) at 40 °C *Add the amine to

sodium hydroxide Sodium hydroxide, also known as lye and caustic soda, is an inorganic compound with the formula NaOH. It is a white solid ionic compound consisting of sodium cations and hydroxide anions . Sodium hydroxide is a highly caustic base and alkali ...

and di-''tert''-butyl dicarbonate in water and THF at 0 °C then warm to ambient temperature. *Heating a mixture of the amine to be protected and di-''tert''-butyl dicarbonate in a biphasic mixture of chloroform and aqueous sodium bicarbonate at reflux for 90 minutes. *Add the amine to di-''tert''-butyl dicarbonate, 4-dimethylaminopyridine (DMAP), and

(MeCN) at ambient temperature : BOC-protected amines are prepared using the reagent di-''tert''-butyl-iminodicarboxylate. Upon deprotonation, this reagent affords a doubly BOC-protected source of NH, which can be ''N''-alkylated. The approach is complementary to the

Gabriel synthesis The Gabriel synthesis is a chemical reaction that transforms primary alkyl halides into primary amines. Traditionally, the reaction uses potassium phthalimide. The reaction is named after the German chemist Siegmund Gabriel. The Gabriel reaction ...

of amines.

Common amine deprotection methods

* Mix the protected carbamate to be deprotected with 3 M

hydrochloric acid Hydrochloric acid, also known as muriatic acid, is an aqueous solution of hydrogen chloride. It is a colorless solution with a distinctive pungent smell. It is classified as a strong acid Acid strength is the tendency of an acid, symbol ...

(HCl) in

ethyl acetate Ethyl acetate ( systematically ethyl ethanoate, commonly abbreviated EtOAc, ETAC or EA) is the organic compound with the formula , simplified to . This colorless liquid has a characteristic sweet smell (similar to pear drops) and is used in glues ...

for 30 min at ambient temperature * Heat the carbamate in a mixture of aqueous hydrochloric acid and

toluene Toluene (), also known as toluol (), is a substituted aromatic hydrocarbon. It is a colorless, water-insoluble liquid with the smell associated with paint thinners. It is a mono-substituted benzene derivative, consisting of a methyl group (CH3) at ...

at 65 °C * Dissolving desired protected compound in a 50/50 mix of

and

References

{{DEFAULTSORT:Butyloxycarbonyl protecting group, tert- Protecting groups Tert-butyl compounds