| Di-tert-butyl dicarbonate | |
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Di-t-butyl dicarbonate |
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Other names
di-tert-butyl pyrocarbonate |
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| Identifiers | |
| CAS number | 24424-99-5 |
| PubChem | 90495 |
| ChemSpider | 81704 |
| ChEBI | CHEBI:48500 |
| Jmol-3D images | Image 1 |
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| Properties | |
| Molecular formula | C10H18O5 |
| Molar mass | 218.25 g·mol−1 |
| Appearance | colourless solid |
| Density | 0.95 g·cm−3 |
| Melting point |
22–24 °C |
| Boiling point |
56–57 °C (0.5 mmHg) |
| Solubility in water | insol |
| Solubility in other solvents | most organic solvents |
| Structure | |
| Dipole moment | 0 D |
| Hazards | |
| Main hazards | toxic on inhalation T+ |
| Related compounds | |
| Related compounds | ethyl chloroformate phosgene |
| (verify) (what is: /?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) |
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| Infobox references | |
Di-tert-butyl dicarbonate is a reagent widely used in organic synthesis.[1] This carbonate ester reacts with amines to give N-tert-butoxycarbonyl or so-called t-BOC derivatives. These derivatives do not behave as amines, which allows certain subsequent transformations to occur that would have otherwise affected the amine functional group. The t-BOC can later be removed from the amine using acids. Thus, t-BOC serves as a protective group, for instance in solid phase peptide synthesis. It is unreactive to most bases and nucleophiles, allowing for an orthogonal Fmoc protection.
Contents |
Di-tert-butyl dicarbonate is inexpensive, so it is usually purchased. Classically, this compound is prepared from tert-butanol, carbon dioxide, phosgene, using DABCO as a base:[2]
This route is currently employed commercially by manufacturers in China and India. European and Japanese companies use the reaction of sodium tert-butylate with carbon dioxide, catalysed by p-toluenesulfonic acid or methanesulfonic acid. This process involves a distillation of the crude material yielding a very pure grade.
Boc anhydride is also available as a 70% solution in toluene or THF. Since boc anhydride is a low-melting solid, having the reagent in a solution simplifies storage and handling.
The Boc group can be added to the amine under aqueous conditions using di-tert-butyl dicarbonate in the presence of a base such as sodium bicarbonate. Protection of the amine can also be accomplished in acetonitrile solution using 4-dimethylaminopyridine (DMAP) as the base.
Removal of the t-BOC in amino acids can be accomplished with strong acids such as trifluoroacetic acid neat or in dichloromethane, or with HCl in methanol.[3][4][5] A complication may be the tendency of the t-butyl cation intermediate to alkylate other nucleophiles; scavengers such as anisole or thioanisole may be used.[6][7]
The synthesis of 6-acetyl-1,2,3,4-tetrahydropyridine, an important bread aroma compound from 2-piperidone was accomplished using t-boc anhydride.[8] (See Maillard reaction). The first step in this reaction sequence is the formation of the carbamate from the reaction of the secondary amine with boc anhydride in acetonitrile with DMAP as a base.