General solvent-free highly selective N-tert-butyloxycarbonylation strategy using protic ionic liquid as

an efficient catalyst

Swapan Majumdara*

, Jhinuk Dea, Ankita Chakraborty

a and Dilip K. Maiti

b

aDepartment of Chemistry, Tripura University, Suryamaninagar, 799 022, INDIA,

E-mail: smajumdar@tripurauniv.in; Tel: +91-381-237-9070; Fax: +91-381-2374802; bDepartment of Chemistry, University of Calcutta, 92, A. P. C. Road, Kolkata 700 009, INDIA

General procedure for N-tert-butyloxycarbonylation of amines: A mixture of Boc2O (5.0 mmol), protic ionic liquid (5 mol%) and an

amine (5.0 mmol) was stirred at room temperature or 70oC for the time indicated in Table 2. After completion of reaction as revealed by

TLC, the mixture was diluted with water (5 ml) and extracted with ether or ethyl acetate (3 x 10 ml). The aqueous layer was recycled. The

combined organic layer was washed with water, dried over anhydrous sodium sulphate and concentrated under reduced pressure. The crude

products were essentially pure but for analytical data, the samples were passed through short pad silica-gel (60-120 mesh) to remove any

trace impurities.

3-(N-tert-butyloxy carbonyl)amino-1-propanol (5h:Table 3, entry 8): Yield: 99%; colourless syrup; IR (neat) 3368, 2978,

1689, 1526 cm-1

; 1H NMR ( CDCl3, 300 MHz) δ 4.97 (bs, 1H), 3.60 (bs, 2H), 3.41 (bs, 1H), 3.24-3.18 (m, 2H), 1.66 – 1.58 (m, 2H), 1.39

(s, 9H); 13

NMR (CDCl3, 75 MHz) δ 157.1, 79.5, 59.2, 37.0, 32.7, 28.3; EIMS m/z 176 (M++1), 175 (M

+), 145,120, 89, 76; HRMS Calcd

for C8H17NO3 175.2263 found 175.2260

Tert-butyl–[3-(N-tert-butyloxy carbonyl)amino propyl] carbonate (5i:Table 3, entry 9): Yield: 98%; colourless syrup; IR

(neat) 3369, 2980, 2932, 1742, 1696, 1394, 1369 cm-1

; 1H NMR (CDCl3, 300 MHz) δ 4.76 (bs, 1H ), 4.08 ( t, J = 6.3 Hz, 2H); 3.20-3.14

( m, 2H); 1.87-1.76 (m, 2H), 1.44 (s, 9H), 1.40 9 s, 9H); 13

C NMR (CDCl3, 75 MHz) δ 155.9, 153.6, 82.0, 79.2, 64.4, 37.2, 29.1, 28.8,

27.9; EIMS m/z 276 (M++1), 275 (M

+); 219, 204, 163, 102, 56; HRMS Calcd for C13H25NO5 275.3427 found 275.3422.

Electronic Supplementary Material (ESI) for RSC Advances.This journal is © The Royal Society of Chemistry 2014

N-tert-Butyloxycarbonyl L-Leucinol (6a: Table 4, entry 1): yield: 97%, colourless syrup; [α]D25

-28o (c 2, MeOH) {lit [α]D

20 -

27.5 ± 1o (c 2, MeOH), Fisher Scientific Ltd., Catalogue No. AC37620-0050}; IR (neat) 3367, 2928, 2873, 1690 cm

-1;

1H NMR (CDCl3,

300 MHz) δ 4.71 (bs, 1H), 3.66-3.58 (m, 2H), 3.49-3.43 (m, 1H), 2.98 (bs, 1H), 1.68-1.56 (m, 1H), 1.41 (s, 9H), 1.31-1.19 (m, 2H), 0.90

(d, J = 5.7 Hz, 6H); 13

C NMR (CDCl3, 75 MHz) δ 156.50, 79.50, 66.4, 51.1, 40.5, 28.3, 24.7, 23.0; EI MS m/z 218 (M++1), 186, 162,

144, 130, 86.

1H NMR spectra of 4a

NHBoc

4a

8 7 6 5 4 3 2 1 0Chemical Shift (ppm)

0

0.05

0.10

0.15

0.20

0.25

0.30

0.35

0.40

0.45

0.50

No

rma

lize

d In

ten

sity

9.000.580.641.551.55

7.9

3

7.9

1

7.8

8

7.8

4

7.5

7

7.5

6

7.5

4

7.5

2

7.5

0

7.3

7

7.3

0

1.6

6

1.6

5

1.6

0

1.3

5

1H NMR spectra of 4b

NHBoc

4b

8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0Chemical Shift (ppm)

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Norm

aliz

ed Inte

nsity

9.003.061.972.14

7.1

87.1

4

7.0

36.9

9

2.2

2

1.5

5

1.4

4

1H NMR spectra of 4d

NHBoc

4d

7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 -0.5Chemical Shift (ppm)

0

0.05

0.10

0.15

0.20

0.25

0.30

0.35

0.40

0.45

0.50

No

rma

lize

d In

ten

sity

8.980.440.220.670.954.21

7.3

17

.28

7.2

77

.25

7.2

27

.19

7.1

86

.96

6.9

3

6.4

1

1.6

71

.66

1.6

61

.56

1.4

5

1.1

4

0.9

40

.91

13 C NMR spectra of 4d

NHBoc

4d

160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10Chemical Shift (ppm)

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

No

rma

lize

d In

ten

sity

15

1.9

6

13

5.9

61

34

.21

13

0.7

41

28

.29

12

8.2

01

26

.71

12

6.0

21

25

.72

12

5.3

61

22

.15

82

.61

77

.44

77

.11

76

.80

27

.83

1H NMR spectra of 4h

1H NMR spectra of 4i

1H NMR spectra of 5f

NHBoc

OH

1H NMR spectra of 5g

7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0Chemical Shift (ppm)

0

0.05

0.10

0.15

0.20

0.25

Norm

aliz

ed I

nte

nsity

8.710.070.070.040.911.911.91

7.2

77.1

77.1

3

6.7

56.7

26.7

0

6.3

9

2.0

6

1.6

31.5

51.5

31.5

11.4

61.4

2

OH

NHBoc

1H NMR spectra of 5h

OHHN

O

O

13C NMR spectra of 5h

OHHN

O

O

1H NMR spectra of 5i

OHN

O O

O

O

13C NMR spectra of 5i

OHN

O O

O

O

1H NMR spectra of 6a

13C NMR spectra of 6a

1H NMR spectra of 6b

7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5Chemical Shift (ppm)

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

No

rma

lize

d In

ten

sity

9.000.313.221.132.031.03

7.2

7

4.3

74

.34

4.2

6

3.4

73

.45

3.3

8

2.2

72

.09

2.0

52

.00

1.9

71

.93

1.9

01

.73

1.7

31

.63

1.6

21

.48

1.4

31

.28

NCO2H

Boc

1H NMR spectra of 6g

8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0Chemical Shift (ppm)

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

No

rma

lize

d In

ten

sity

9.180.901.973.000.890.741.962.96

7.2

47

.22

7.2

27

.20

7.2

07

.09

7.0

77

.05

7.0

4

4.9

44

.90

4.5

54

.51

4.4

8

3.6

5

3.0

53

.02

2.9

9

1.5

81

.56

1.3

51

.32

0.0

1

PhCO2Me

NHBoc

NCO2CH2Ph

Boc

1H NMR spectra of 6i

1H NMR spectra of 6j

1H NMR spectra of 6k