Di-tert-butyl dicarbonate
IUPAC name	Di-t-butyl dicarbonate
Other names	di-tert-butyl pyrocarbonate Boc anhydride Boc2O
Identifiers
CAS number	24424-99-5 Y
SMILES	CC(C)(C)OC(=O)OC(=O)OC(C)(C)C
Properties
Molecular formula	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)
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	t-Butyl Chloroformate Phosgene
Y (what is this?)  (verify) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
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 1 Preparation 2 Protection and deprotection of amines 3 Other uses 4 References

[edit] Preparation

Di-tert-butyl dicarbonate is inexpensive, so it is usually purchased. Classically, this compound is prepared from tert-butyl alcohol, 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-tolylsulfonic acid or methylsulfonic 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.

[edit] 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]

[edit] 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.

[edit] References

1. ^ 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.
2. ^ Barry M. Pope, Yutaka Yamamoto, and D. Stanley Tarbell (1988), "Dicarbonic acid, bis(1,1-dimethylethyl) ester", Org. Synth., http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv6p0418 ; Coll. Vol. 6: 418 
3. ^ 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)-", Org. Synth. 80: 18, http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=v80p0018 
4. ^ 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: 213–215. doi:10.1021/ol0361599. 
5. ^ D. M. Shendage, R. Fröhlich, G. Haufe (2004). "Highly Efficient Stereoconservative Amidation and Deamidation of α-Amino Acids". Org. Lett. 6: 3675–3678. doi:10.1021/ol048771l. 
6. ^ 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. 
7. ^ 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.