Di-tert-butyl dicarbonate

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Di-tert-butyl dicarbonate
Names
Preferred IUPAC name
Di-tert-butyl dicarbonate
Other names
Di-t-butyl pyrocarbonate
Boc anhydride
Boc2O
Identifiers
3D model (
JSmol
)
ChEBI
ChemSpider
ECHA InfoCard
 100.042.021 Edit this at Wikidata
EC Number
  • 246-240-1
UNII
  • InChI=1S/C10H18O5/c1-9(2,3)14-7(11)13-8(12)15-10(4,5)6/h1-6H3 checkY
    Key: DYHSDKLCOJIUFX-UHFFFAOYSA-N checkY
  • InChI=1/C10H18O5/c1-9(2,3)14-7(11)13-8(12)15-10(4,5)6/h1-6H3
    Key: DYHSDKLCOJIUFX-UHFFFAOYAG
  • O=C(OC(=O)OC(C)(C)C)OC(C)(C)C
Properties
C10H18O5
Molar mass 218.249 g·mol−1
Appearance Colorless solid or oil
Density 0.95 g·cm−3
Melting point 22 to 24 °C (72 to 75 °F; 295 to 297 K)
Boiling point 56 to 57 °C (133 to 135 °F; 329 to 330 K) (0.5 mmHg)
Insoluble
Solubility in other solvents Soluble in most organic solvents
Hazards
Occupational safety and health (OHS/OSH):
Main hazards
 Very toxic on inhalation T+, LC50 = 100 mg/m3 (4 hr, rat)
Related compounds
Related compounds
 Ethyl chloroformate
Phosgene
Diethyl pyrocarbonate
Dimethyl dicarbonate
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkY☒N ?)

Di-tert-butyl dicarbonate is a

solid phase peptide synthesis. Boc-protected amines are unreactive to most bases and nucleophiles, allowing for the use of the fluorenylmethyloxycarbonyl
group (Fmoc) as an orthogonal protecting group.

Preparation

Di-tert-butyl dicarbonate is inexpensive, so it is usually purchased. Classically, this compound is prepared from

tert-butanol, carbon dioxide, and 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

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. As boc anhydride may melt at ambient temperatures, its storage and handling is sometimes simplified by using a solution.

Protection and deprotection of amines

Main article:
tert-butyloxycarbonyl protecting group

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

4-dimethylaminopyridine (DMAP) as the base.[3]

Removal of the Boc in

t-butyl cation intermediate to alkylate other nucleophiles; scavengers such as anisole or thioanisole may be used.[7][8]
Selective cleavage of the N-Boc group in the presence of other protecting groups is possible when using AlCl3.

Reaction with trimethylsilyl iodide in acetonitrile followed by methanol is a mild and versatile method of deprotecting Boc-protected amines.[9][10][11][12]

The use of

9-fluorenylmethoxycarbonyl, O- and S-benzyl and t-butylthio groups.[13]

Other uses

The synthesis of

2-piperidone was accomplished using t-boc anhydride.[14]
(See Maillard reaction). The first step in this reaction sequence is the formation of the carbamate from the reaction of the amide nitrogen with boc anhydride in acetonitrile using DMAP as a catalyst.

Schematic: synthesis of 6-acetyl-1,2,3,4-tetrahydropyridine

Di-tert-butyl dicarbonate also finds applications as a polymer blowing agent due to its decomposition into gaseous products upon heating.[15][16]

Hazards

Bottles of di-tert-butyl dicarbonate buildup of internal pressure in sealed containers caused by its slow decomposition to di-tert-butyl carbonate and ultimately tert-butanol and CO2 in the presence of moisture. For this reason, it is usually sold and stored in plastic bottles rather than glass ones.

The main hazard of the reagent is its inhalational toxicity. Its median lethal concentration of 100 mg/m3 over 4 hours in rats[17] is comparable to that of phosgene[18] (49 mg/m3 over 50 min in rats).

References

  1. doi:10.1002/047084289X
    .
  2. ISSN 0078-6209
    .
  3. PMID 11052078
    .
  4. ISSN 0078-6209
    .
  5. PMID 14723531
    .
  6. PMID 15469321
    .
  7. PMID 744685
    .
  8. ISBN 9783527321032
    .
  9. doi:10.1039/C39780000315
    .
  10. doi:10.1039/C39790000495
    .
  11. doi:10.1016/0040-4020(82)87002-6
    .
  12. PMID 25376704
    .
  13. ISSN 0040-4039
    .
  14. PMID 16356012
    .
  15. S2CID 215603770
    .
  16. ISBN 978-1-895198-99-7
    . Retrieved 4 May 2020.
  17. ^ "Material Safety Data Sheet" (PDF). CHEM-IMPEX INTERNATIONAL INC. Retrieved 2016-09-10.
  18. ^ "Phosgene". Wireless Information System for Emergency Responders. US National Library of Medicine. Retrieved 2016-09-10.

External links

  • Basel, Yochai; Hassner, Alfred (2001). "Imidazole and Trifluoroethanol as Efficient and Mild Reagents for Destruction of Excess Di-tert-butyl Dicarbonate [(BOC)2O]". Synthesis. 2001 (4): 0550.
    S2CID 97029361
    .
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