Di-tert-butyl dicarbonate
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| Names | |
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| IUPAC name
Di-t-butyl dicarbonate
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| Other names
di-tert-butyl pyrocarbonate
Boc anhydride Boc2O | |
| Identifiers | |
3D model (JSmol)
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| ChemSpider | |
| ECHA InfoCard | 100.042.021 |
PubChem CID
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CompTox Dashboard (EPA)
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| Properties | |
| C10H18O5 | |
| Molar mass | 218.25 g/mol |
| Appearance | colourless solid |
| Density | 0.95 g/cm3 |
| Melting point | 22–24 °C |
| Boiling point | 56–57 °C (0.5 mm Hg) |
| insol | |
| Solubility in other solvents | most organic solvents |
| Structure | |
| 0 D | |
| Hazards | |
| Occupational safety and health (OHS/OSH): | |
Main hazards
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toxic on inhalation T+ |
| Related compounds | |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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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.
Preparation
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 as a liquid simplifies storage and handling.
Protection and deprotection of amines
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]. It can also be removed using K2CO3/methanol at room temperature.[6]
Other uses
The synthesis of 6-acetyl-1,2,3,4-tetrahydropyridine, an important bread aroma compound from 2-piperidone was accomplished using t-boc anhydride.[7] (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.
External links
- Protection or deprotection conditions - Synthetic protocols from organic-reaction.com
References
- ^ Wakselman, M. “Di-t-butyl Dicarbonate” in Encyclopedia of Reagents for Organic Synthesis (Ed: L. Paquette) 2004, J. Wiley & Sons, New York. doi:10.1002/047084289.
- ^ Barry M. Pope, Yutaka Yamamoto, and D. Stanley Tarbell (1988). "Dicarbonic acid, bis(1,1-dimethylethyl) ester". Organic Syntheses
{{cite journal}}: CS1 maint: multiple names: authors list (link); Collected Volumes, vol. 6, p. 418. - ^ Robert M. Williams, Peter J. Sinclair, Duane E. DeMong, Daimo Chen, and Dongguan Zhai (2003). "4-Morpholinecarboxylic acid, 6-oxo-2,3-diphenyl-, 1,1-dimethylethyl ester, (2S,3R)-". Organic Syntheses. 80: 18
{{cite journal}}: CS1 maint: multiple names: authors list (link). - ^ E. A. Englund, H. N. Gopi, D. H. Appella (2004). "An Efficient Synthesis of a Probe for Protein Function: 2,3-Diaminopropionic Acid with Orthogonal Protecting Groups". Org. Lett. 6 (2): 213–215. doi:10.1021/ol0361599. PMID 14723531.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ D. M. Shendage, R. Fröhlich, G. Haufe (2004). "Highly Efficient Stereoconservative Amidation and Deamidation of α-Amino Acids". Org. Lett. 6 (21): 3675–3678. doi:10.1021/ol048771l. PMID 15469321.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Saul Jaime-Figueroa, Alejandro Zamilpa, Angel Guzma´n,and David J. Morgans,Jr. (2001). "N-3-Alkylation of uracil and derivatives via N-1-BOC protection". Synthetic Communication. 31 (24): 3739–3746. doi:10.1081/SCC-100108223.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Tyler J. Harrison and Gregory R. Dake (2005). "An Expeditious, High-Yielding Construction of the Food Aroma Compounds 6-Acetyl-1,2,3,4-tetrahydropyridine and 2-Acetyl-1-pyrroline". J. Org. Chem. 70 (26): 10872–10874. doi:10.1021/jo051940a. PMID 16356012.