Facile tert-butoxycarbonylation of alcohols, phenols, and amines using BiCl3 as a mild and efficient catalyst

Article abstract of DOI:10.1080/00397910701749617

Facile tert-butoxycarbonylation of alcohols, phenols, and amines is described by treatment of alcohols, phenols, and amines with di-tert-butyl dicarbonate in the presence of a catalytic amount of bismuth(III) chloride, a mild and efficient catalyst, at room temperature in excellent yields. Copyright Taylor & Francis Group, LLC.

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Facile tert‐Butoxycarbonylation of Alcohols,
Phenols, and Amines using BiCl3 as a Mild and
Efficient Catalyst
N. Suryakiran a , P. Prabhakar a & Y. Venkateswarlu a
a Organic Chemistry Division I, Natural Products Laboratory, Indian Institute
of Chemical Technology, Hyderabad, India
Version of record first published: 18 Jan 2008
To cite this article: N. Suryakiran, P. Prabhakar & Y. Venkateswarlu (2008): Facile tert‐Butoxycarbonylation
of Alcohols, Phenols, and Amines using BiCl3 as a Mild and Efficient Catalyst, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 38:2, 177-185
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Synthetic Communicationsw, 38: 177–185, 2008
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701749617
Facile tert-Butoxycarbonylation of Alcohols,
Phenols, and Amines using BiCl3 as a Mild
and Efficient Catalyst
N. Suryakiran, P. Prabhakar, and Y. Venkateswarlu
Organic Chemistry Division I, Natural Products Laboratory, Indian
Institute of Chemical Technology, Hyderabad, India
Abstract: Facile tert-butoxycarbonylation of alcohols, phenols, and amines is described
by treatment of alcohols, phenols, and amines with di-tert-butyl dicarbonate in the
presence of a catalytic amount of bismuth(III) chloride, a mild and efficient catalyst, at
room temperature in excellent yields.
Keywords: alcohols, amine, BiCl3, phenols, tert-butoxycarbonylation
1
INTRODUCTION
Organic reactions using reusable and water-tolerant catalysts have received
much attention in recent years because they can be conveniently handled
and removed from the reaction mixture, making the experimental procedure
simple and ecofriendly.[1] On the other hand, organic reactions carried out
in the absence of solvent also attract the attention of chemists because of
ease of processing and environmental friendliness.
Among carbonic acid derivatives used as protecting groups, tert-butylcar-
bonates and tert-butylcarbamates are of great importance in organic
chemistry[2] because they are stable to a wide range of nucleophiles in
alkaline conditions and are very labile under moderately acidic conditions
Received July 26, 2007
Address correspondence to Y. Venkateswarlu, Organic Chemistry Division I,
Natural Products Laboratory, Indian Institute of Chemical Technology, Hyderabad
500 007, India. E-mail: luchem@iict.res.in
177

178
N. Suryakiran, P. Prabhakar, and Y. Venkateswarlu
to give the parent alcohols and amines. N-tert-Boc derivatives are extensively
used for protecting amino groups.[3–12] However, O-tert-Boc derivatives are
less widely used for protection of alcohols, and they are restricted to aryl
alcohols. Introduction of a tert-Boc group to alcohols is generally achieved by
using di-tert-butyl dicarbonate in the presence of dimethyl amino pyridine
(DMAP)[10] or tert-Boc transfer reactions using tert-Boc-imidazole[13] or tert-
butoxycarbonyl-1,2-dihydroisoquinoline.[14] All these methods involve basic
media or the presence of a Lewis base. However, Lewis acid–catalyzed tert-
Boc protection of alcohols and amines is less thoroughly investigated.[15–20]
Recently, N-tert-Boc 3-amino pyrazoles and compounds of this class have
proved to be efficient as ditipic proligands for metal salts.[21] However, the
reported method involves long reaction times (16 h) at refluxing temperature
in CH3CN. Bismuth(III) chloride is relatively nontoxic, inexpensive, and insen-
sitive to air, and no special care is required. It is used in various organic trans-
formations as a mild and efficient Lewis acid catalyst.[22,23] Also, to the best of
our knowledge, there is no report on the use of BiCl3 for the tert-butoxycarbo-
nylation of alcohols, phenols, or amines with di-tert-butyl dicarbonate.
Recently we reported BiCl3 as a mild and efficient Lewis acid catalyst for the
synthesis of 2,3-unsaturated glycopyranosides,[24] chemoselective deprotec-
tion of acetonides,[25] and regioselective ring opening of aziridines with
amines.[26] In continuation of our search for a chemoselective Lewis acid
catalyst in the multistep synthesis of natural products, we observed that
BiCl3 can be utilized efficiently for the tert-butoxycarbonylation of alcohols
and phenols with di-tert-butyl dicarbonate under solvent-free conditions.
2
RESULTS AND DISCUSSION
In this report (Scheme 1), we describe an efficient method for tert-butoxycarbo-
nylation of alcohols, phenols, and amines. This method does not need expensive
reagents or special care to exclude the moisture from the reaction medium.
BiCl3 is highly oxophilic, forms a labile bond with carbonyl oxygen of Boc
anhydride, and initiates the formation of a C-X bond with alcohols, phenols,
and amines (Scheme 2). During O-tert-butoxycarbonylation of phenols and
alcohols using BiCl3, the reaction conditions are very mild. Under the con-
ditions of the reaction, labile protecting groups such as acetonides and Boc-
protected amines are not affected, and Boc esters of alcohols formed neatly
(e.g., entries 4, 11, and 16 in Table 1). We first examined the reaction of
benzyl alcohol with di-tert-butyl dicarbonate in the presence of BiCl3
(5 mol%) at room temperature, giving the corresponding O-tert-butylcarbonate
Scheme 1.

tert-Butoxycarbonylation of Alcohols, Phenols, and Amines
179
Scheme 2. Plausible mechanism.
in 98% yield (Table 1, entry 1). To optimize reaction conditions, we compared
other Lewis acid catalysts, but the BiCl3 (5 mol%) was found to be most
effective under autosolvent conditions (Table 2). This success has encouraged
us to extend the generality of the reaction to various primary, secondary, and
aryl alcohols and phenols (Scheme 1, Table 1). Further, we extended the meth-
odology to N-Boc protection of 3-amino pyrazoles using 5 mol% bismuth(III)
chloride; they are also efficiently and smoothly converted into the correspond-
ing N-Boc derivatives in good to excellent yields (Scheme 1, Table 3). Further,
it is noticed that the tert-butoxycarbonylation of alcohols, phenols, and amines,
is not a reversible reaction under reaction conditions even after 6 h at room
temperature. From the forgoing results (Tables 1 and 3), it is evident that the
BiCl3 is an excellent catalyst for tert-butoxycarbonylation of alcohols,
phenols, and amines, especially 3-amino pyrazoles.
Further, we have studied the reusability of the catalyst without any modi-
fication of reaction conditions. After completion of the reaction, water was
added, and the product was extracted into ethyl acetate. The catalyst was
recovered from the aqueous layer by evaporation under reduced pressure
and reused without loss of its activity for six runs. From the foregoing
results (Tables 1 and 3), it is evident that BiCl3 is an efficient catalyst for
tert-butoxycarbonylation of alcohols, phenols, and amines.
3
CONCLUSION
In conclusion, we have described a facile tert-butoxycarbonylation of alcohols,
phenols, and amines using BiCl3 as an efficient catalyst under autosolvent con-
ditions. The present procedure has the advantage of short reaction times high
yields of the products, no organic solvent, and simple workup procedure,
which make it a useful and important addition to the existing methods.
4
EXPERIMENTAL
4.1 Typical Experimental Procedure
Di-tert-butyl dicarbonate (1.5 mmol) and finely powdered BiCl3 (5 mol%)
were added to a mixture of phenol/alcohol/amine (1 mmol), and the
reaction was stirred under solvent-free conditions at room temperature for

180
N. Suryakiran, P. Prabhakar, and Y. Venkateswarlu
Table 1. O-tert-Butoxycarbonylation of alcohols and phenols in the presence of
BiCl3
Entry
1
Substrate
Producta
Time (h) Yield (%)b
0.5
98
2
0.5
95
3
4
1.0
0.5
96
94
5
6
7
2.0
2.0
2.0
95
92
96
8
9
0.5
0.5
98
95
10
11
0.5
0.5
98
96
(continued)

tert-Butoxycarbonylation of Alcohols, Phenols, and Amines
Table 1. Continued
181
Entry
12
Substrate
Producta
Time (h) Yield (%)b
1.0
96
13
14
15
16
1.0
1.0
1.5
1.0
98
93
95
95
aThe structures of the products were established from their spectral data (1H NMR,
EIMS).
bIsolated yields obtained after column chromatography.
an appropriate time (Tables 1 and 3). After completion of the reaction as
monitored by thin-layer chromatography (TLC), water (10 mL) was added,
and the product was extracted into ethyl acetate (3 Â 20 mL). The
combined organic layer was washed with a brine solution and concentrated
Table 2. Comparison of the catalytic activity of bismuth(III) chloride with other cat-
alysts on the tert-butoxycarbonylation of benzyl alcohol under different conditions at
room temperature
Entry
Catalyst (mol%)
Solvent
Time (min)
Yield (%)
1
2
3
None
Zn(OAc)2 (10)
.
La(NO3)3 6H2O
No solvent
DCM
No solvent
180
360
30
30
98
60
(5)
I2 (10)
4
5
No solvent
No solvent
No solvent
No solvent
DCM
30
30
80
75
90
90
85
75
98
LiClO4 (5)
ZrCl4 (5)
ZrOCl2 (5)
BiCl3 (5)
BiCl3 (5)
BiCl3 (5)
6
180
60
7
8
360
360
30
9
10
CHCl3
No solvent

182
N. Suryakiran, P. Prabhakar, and Y. Venkateswarlu
Table 3. N-tert-Butoxycarbonylation of 3-amino pyrazoles in the presence of BiCl3
Time Yield
(%)b
Entry
1
Substrate
Producta
(h)
0.5
98
2
3
4
0.5
0.5
0.5
97
98
95
5
0.5
96
6
7
0.5
1.0
95
99
(continued)

tert-Butoxycarbonylation of Alcohols, Phenols, and Amines
Table 3. Continued
183
Time Yield
(%)b
Entry
8
Substrate
Producta
(h)
1.0
98
9
0.5
98
10
11
0.5
1.0
96
95
12
1.0
98
aThe structures of the products were established from their spectral data (1H NMR,
EIMS).
bIsolated yields obtained after column chromatography.

184
N. Suryakiran, P. Prabhakar, and Y. Venkateswarlu
under reduced pressure to give the crude product, which was purified over a
silica-gel column to afford the corresponding tert-Boc derivatives in
excellent yields. The catalyst was recovered from the aqueous layer by
removing water under reduced pressure and reused for six or more runs
without loss of its activity.
4.2 Data from Table 1
Entry 1. 1H NMR (300 MHz, CDCl3) d 1.30 (s, 9H, t-Bu), 4.40 (s, 2H, CH2),
7.39 (m, 5H, Ar-H); EIMS: m/z 208.
1
Entry 2. H NMR (300 MHz, CDCl3) d 1.30 (s, 9H, t-Bu), 2.20 (s, 3H,
ar-CH3), 4.41 (s, 2H, CH2), 7.39 (m, 5H, Ar-H); EIMS: m/z 222.
Entry 4. 1H NMR (300 MHz, CDCl3) d 1.30 (s, 9H, t-Bu), 1.35 (s, 3H, CH3),
1.40 (s, 3H, CH3), 3.56 (m, 1H, CH), 3.91 (d, 1H, CHa), 4.12 (d, 1H, CHb),
4.19 (d, 2H, CH2); EIMS: m/z 232.
Entry 5. 1H NMR (300 MHz, CDCl3) d 1.30 (s, 9H, t-Bu), 1.35–1.5 (m, 6H,
3CH2) 1.90 (m, 4H, 2CH2), 4.22 (m, 1H, CH); EIMS: m/z 200.
Entry 7. 1H NMR (300 MHz, CDCl3) d 1.30 (s, 9H, t-Bu), 2.90 (d, 2H, CH2),
7.44–7.60 (m, 3H, Ar-H), 7.70 (s, 1H, Ar-H); EIMS: m/z 234.
Entry 8. 1H NMR (300 MHz, CDCl3) d 1.31 (s, 9H, t-Bu), 2.90 (t, 1H, CHa),
3.00 (t, 1H, CHa), 3.50 (t, 1H, CHb), 4.25 (t, 1H, CHb), 7.40–7.44 (m, 4H, Ar-
H); EIMS: m/z 290.
Entry 11. 1H NMR (300 MHz, CDCl3) d 1.30 (s, 9H, t-Bu), 1.35 (s, 3H, CH3),
1.42 (s, 3H, CH3), 3.66 (s, 3H, OCH3), 4.13 (d, 2H, CH2), 4.50 (m, 1H, CH), 5.50
(d, 1H, CH), 7.40 (d, 2H, Ar-H), 7.64 (d, 2H, Ar-H); EIMS: m/z 338.
Entry 12. 1H NMR (300 MHz, CDCl3) d 1.30 (s, 9H, t-Bu), 7.32 (d, 1H, Ar-H),
7.43 (d, 1H, Ar-H), 7.66 (m, 2H, Ar-H), 8.01 (d, 1H, Ar-H), 8.10, (d, 1H, Ar-
H), 8.37 (m, 1H); EIMS: m/z 244.
4.3 Data from Table 3
Entry 1. 1H NMR (200 MHz, CDCl3): d 1.25 (s, 9H, t-Bu), 1.49 (s, 9H, t-Bu),
5.85 (s, 1H, Ar-H); EIMS: m/z 239.
Entry 2. 1H NMR (200 MHz, CDCl3): d 1.49 (s, 9H, t-Bu), 2.26 (s, 3H, CH3),
7.40 (s, 5H, Ar-H); EIMS: m/z 273.
Entry 10. 1H NMR (200 MHz, CDCl3): d 1.25 (t, 3H, CH3), 1.49 (s, 9H, t-Bu),
4.25 (q, 2H, CH2), 4.92 (s, 2H, CH2), 5.85 (s, 1H, Ar-H), 7.5 (m, 5H, Ar-H);
EIMS: m/z 345.

tert-Butoxycarbonylation of Alcohols, Phenols, and Amines
185
Entry 11. 1H NMR (200 MHz, CDCl3) d 1.49 (s, 9H, t-Bu), 6.02 (s, 1H, Ar-H),
7.15 (d, 2H, J ¼ 8.15, Ar-H), 7.35 (d, 2H, J ¼ 8.23, Ar-H), 7.60 (d, 2H,
J ¼ 8.15 , Ar-H), 8.10 (d, 2H, J ¼ 8.23, Ar-H); EIMS: m/z 413, 415.
ACKNOWLEDGMENTS
The authors are thankful to Council of Scientific and Industrial Research
(CSIR), Ministry of Earth Sciences (MoES), and Department of Biotechno-
logy (DBT) New Delhi for financial assistance and J. S. Yadav, director of
Indian Institute of Chemical Technology (IICT), for his constant encouragement.
REFERENCES
1. Tanaka, K.; Toda, F. Chem. Rev. 2000, 100, 1025.
2. Green, T. W.; Wuts, P. G. M. Protecting Groups in Organic Synthesis; John Wiley
& Sons: New York, 1999.
3. Burk, M. J.; Allen, J. G. J. Org. Chem. 1997, 62, 705.
4. Einhorn, J.; Enhorn, C.; Luche, J.-L.Synlett 1991, 37.
5. Guibe-Janpel, E.; Wakselamann, M. J. Chem. Soc., Chem. Commun. 1971, 267.
6. Guibe-Janpel, E.; Wakselamann, M. Synthesis 1977, 772.
7. Itoh, M.; Hagiwara, D.; Kamia, T. Tetrahedron Lett. 1975, 16, 4393.
8. Kim, S.; Lee. J. Chem. Lett. 1984, 237.
9. Barcelo, G.; Senet, J.-P.;Sennyey, G. Synthesis 1986, 627.
10. Basel, Y.; Hassner, A. J. Org. Chem. 2000, 65, 6368.
11. Pandey, R. K.; Dagade, S. P.; Upadhyaya, R. K.; Dongare, M. K.; Pradeep, K.
Arkivoc 2002, 7, 28.
12. Chakraborti, K. A.; Sunay, V. Org. Lett. 2006, 8, 3259.
13. Peri, F.; Binassi, E.; Manetto, A.; Marotta, E.; Mazzant, A.; Righi, P.; Scardovi, N.;
Rosini, G. J. Org. Chem. 2004, 69, 1353.
14. Ouchi, H.; Saito, Y.; Yamamoto, Y.; Takahahata, H. Org. Lett. 2002, 4, 585.
15. Sharma, G. V. M.; Reddy, J. J.; Lakshmi, P. S.; Krishna, P. R. Tetrahedron Lett.
2004, 45, 6963.
16. Chankeshwara, S. V.; Chakraborti, A. K. Tetrahedron Lett. 2006, 47, 1987.
17. Chakraborti, K. A.; Chankeshwara, S. V. Synthesis 2006, 2784.
18. Chakraborti, K. A.; Chankeshwara, S. V. Org. Biomol. Chem. 2006, 4, 2769.
19. Ravi, V.; Sreelatha, N.; Srinivas, R. A. J. Org. Chem. 2006, 71, 8283.
20. Bartoli, G.; Bosco, M.; Carlone, A.; Dalpozzo, R.; Locatelli, M.; Malechiorre, P.;
Palazzi, P.; Sambri, L. Synlett 2006, 2104.
21. Pask, C. M.; Camm, K. D.; Kilner, C. A.; Halcrow, M. S. Tetrahedron Lett. 2006,
47, 2531.
22. Hung, Y.-Z.; Zhou, Z.-L. In Comprehensive Organometalic Chemistry;
Abel, E. W., Stone, F.G.A. and Wilkinson, G. Eds.; Peragmon Press: New York,
1995, Vol. 11, 502.
23. Raghavendra Swamy, N.; Kumar, B. P.; Longquin, H. Tetrahedron Lett. 2006, 47, 389.
24. Raghavendra Swamy, N.; Venkateswarlu, Y. Synthesis 2002, 598.
25. Raghavendra Swamy, N.; Venkateswarlu, Y. Tetrahedron Lett. 2002, 43, 7549.
26. Raghavendra Swamy, N.; Venkateswarlu, Y. Synth. Commun. 2003, 33, 549.