β-Naphthyl chlorothionoformate: An efficient, powerful and a new reagent for dealkylation tertiary amines

Article abstract of DOI:10.1080/17415993.2012.688828

β-Naphthyl chlorothionoformate is introduced as a powerful dealkylating agent. This reagent reacts rapidly with tertiary amines at room temperature and produces their thiocarbamate derivatives, whose yields were from good to excellent. Rates of reactions and selectivity for alkyl group cleavage in amines were found to be superior or comparable to those previously reported with chloroformates.

Full text of DOI:10.1080/17415993.2012.688828

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β-Naphthyl chlorothionoformate: an
efficient, powerful and a new reagent
for dealkylation tertiary amines
Faezeh Ghotbi a , Mehdi M. Baradarani a & Davood Sheikh b
a Department of Chemistry, Faculty of Science, University of
Urmia, Urmia, 57135, Iran
b Faculty of Science, Hamedan Branch, Islamic Azad University,
Iran
Version of record first published: 29 Jun 2012
To cite this article: Faezeh Ghotbi, Mehdi M. Baradarani & Davood Sheikh (2012): β-Naphthyl
chlorothionoformate: an efficient, powerful and a new reagent for dealkylation tertiary amines,
Journal of Sulfur Chemistry, DOI:10.1080/17415993.2012.688828
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Journal of Sulfur Chemistry
iFirst, 2012, 1–6
β-Naphthyl chlorothionoformate: an efficient, powerful and a
new reagent for dealkylation tertiary amines
Faezeh Ghotbia, Mehdi M. Baradarania* and Davood Sheikhb
aDepartment of Chemistry, Faculty of Science, University of Urmia, Urmia 57135, Iran; bFaculty of Science,
Hamedan Branch, Islamic Azad University, Iran
(Received 15 February 2012; final version received 16 April 2012)
β-Naphthyl chlorothionoformate is introduced as a powerful dealkylating agent. This reagent reacts rapidly
with tertiary amines at room temperature and produces their thiocarbamate derivatives, whose yields were
from good to excellent. Rates of reactions and selectivity for alkyl group cleavage in amines were found
to be superior or comparable to those previously reported with chloroformates.
Keywords: β-Naphthyl chlorothionoformate; dealkylation; tertiary amines; β-naphthyl thiocarbamate
derivatives; synthesis
1. Introduction
N-Dealkylations, and more specifically debenzylations, are important in organic synthesis and
structure determination. The previously reported methods for dealkylation of tertiary amines
include the use of phenyl chlorothionoformate (1), thiophosgene and 1-chloroethyl chlorothiono-
formate (2), ethyl chloroformate (3), phenyl chloroformate (4), 1-chloroethyl chloroformate (5),
2,2,2-trichloroethyl chloroformate (6), vinyl chloroformate (7), propargyl chloroformate (8), elec-
tron deficient heteroaryl chlorides (9), 4-chlorophenyl chlorothionoformate, 2,4,6-tribromophenyl
chlorothionoformate (10) and aryl chlorothionoformates (11).
In this paper, we introduce the use of β-naphthyl chlorothionoformate 2 for dealkylation of
different tertiary amines. β-Naphthyl chlorothionoformate was even more reactive toward amines
than previously studied chlorothionoformates and its dealkylation reactions were found to take
place in higher yields and at room temperature.
*Corresponding author. Email: mmbaradarani@yahoo.com
ISSN 1741-5993 print/ISSN 1741-6000 online
© 2012 Taylor & Francis
http://dx.doi.org/10.1080/17415993.2012.688828
http://www.tandfonline.com

2
F. Ghotbi et al.
2. Result and discussion
The proposed route for dealkylation of tertiary amines with β-naphthyl chlorothionoformate
involves the nucleophilic attack of the tertiary amines 1 on β-naphthyl chlorothionoformate 2 and
subsequent decomposition of the salt 3 by chloride, forming the thiocarbamate 4 and an alkyl
chloride 5 (Scheme 1).
+
O
NR3 Cl–
O
NR2
O
Cl
CH2Cl2
rt
+
RCl
R3N
+
S
S
S
1
2
3
4
5
Scheme 1. Dealkylation of tertiary amines.
The dealkylation of tertiary amines with β-naphthyl chlorothionoformate was more rapid than
with the other reagents. By contrast, phenyl chlorothionoformate, 4-chlorothionoformate and
2,4,6-trichlorothionoformate converted N-methylpiperidine to the corresponding thicarbonates at
room temperature in dichloromethane within 1 h, 40 min and 2 h, respectively. While the use of
2 at the same condition occurred cleanly in only 1 min. When triethylamine, N-methylpiperidine
and N-methylmorpholine were treated with 2 in dichloromethane as a solvent, the de-ethylated
(Entry 2) and the demethylated products (Entries 3 and 4) were obtained within 1 min in excellent
amounts (Table 1).
When N, N-dimethylbenzylamine was treated with β-naphthyl chlorothionoformate in
dichloromethane, only debenzylation was observed, as expected, in the quantitative yield and
in only 1 min at room temperature (Entry 1). Exclusive debenzylation also occurred with N − t-
butyl-N-methylbenzylamine and with N-allyl-N-methylbenzylamine (Entries 7 and 8). On the
other hand, N-methylpyrrolidine and (-)-nicotine underwent primarily ring opening upon reaction
with β-naphthyl chlorothionoformate (Entries 5 and 6).
Reaction of N, N-diethylaniline with β-naphthyl chlorothionoformate rather surprisingly
dephenylation took place; this was proved by the isolation of a product that was shown
to be identical to the thionocarbamate obtained from triethylamine (Entry 9), while N, N-
dimethylcyclohexylamine resulted both in demethylation and in decyclohexylation (Entry 10).
3. Conclusion
In conclusion, we have found a facile and efficient method for the dealkylation of tertiary amines
by the reaction with β-naphthyl chlorothionoformate. The present procedure has many advantages
such as short reaction times, mild conditions, high yields and easy operation procedures.
4. Experimental
4.1. General
1H and 13C NMR spectra were measured on a Bruker 300 spectrometer (at 300 MHz for 1H spectra
and 75 MHz for 13C spectra) using TMS as an internal standard and CDCl3 as solvent. IR spectra
were recorded on Thermo Nicolet Nexus 670 spectrometer instrument (KBr). Mass spectra were
determined on an Agilent 6890-N-Network-GC system and melting points were recorded on an
Electrothermal digital 8100 series apparatus.

Journal of Sulfur Chemistry
3
Table 1. N-Dealkylation of tertiary amines with β-naphthyl chlorothionoformate.
Entry
Amines (1)
Time (min)
Products (4)
Yielda (%)
1
1
92
2
3
Et3N
1
1
95
90
4
5
1
1
90
90
6
1
80
7
8
9
1
84
72
80
180
30
10
1
48 + 80
Note: aIsolated yields.

4
F. Ghotbi et al.
Organic solutions were dried with anhydrous sodium sulfate and the solvent was removed by
evaporation under reduced pressure to give the products. Substances purchased commercially
were used without additional purification. The routine purifications of reagents and solvents were
carried out by standard laboratory procedures.
4.2. Typical procedure for the synthesis of β-naphthyl chlorothionoformate 2
A solution of thiophosgene (3.2 ml, 0.042 mol) in dry dichloromethane (45 ml) was placed in a
three-necked flask equipped with a water condenser, thermometer and a dropping funnel, in an ice-
water bath. Then, a mixture of β-naphthol (5.4 ml, 0.024 mol) and 20% aqueous NaOH (35 ml)
was added dropwise while stirring, and the resulting mixture was stirred at room temperature
for an additional 1 h. After completion of the reaction, as monitored by TLC using petroleum
ether/ethyl acetate (20/3), the organic layer was separated, washed with water (3 × 3 ml) and
dried. After removal of the solvent, the resulting red crystals were recrystallized from n-hexane to
yield pure product.Yellow crystals, mp 72 ◦C. FT-IR (KBr): 3058, 1626, 1508, 1356, 1232, 1011,
864, 757, 481, 230 cm−1. 1H NMR: δ = 7.28–7.33 (1H, m); 7.53–7.63 (3H, m); 7.86–7.96 (3H,
m). 13C NMR: δ = 118.5, 120.0, 126.6, 127.1, 128.0, 128.0, 130.1, 132.1, 133.6, 152.3, 185.9.
EI-MS: m/z (%) = 224 (M + 2)+, 222 (M+), 187, 143, 127 (100), 94, 78. Found: M+ 221.9906,
C11H7OSCl requires M+ 221.9906.
4.3. Typical procedure for dealkylation tertiary amines with β-naphthyl
chlorothionoformate
To the β-naphthyl chlorothionoformate 2 (0.1 g, 0.449 mmol) in dichloromethane (15 ml), tertiary
amine (0.898 mmol) was added and the solution stirred at 25 ◦C for an appropriate time (Table 1)
until the reaction was completed as monitored by petroleum ether/ethyl acetate (20/3). After
completion of the reaction, the mixture was cooled to room temperature and the solvent was
removed to obtain oily products that were crystallized from a mixture of n-hexane and ethanol
to give pure products. The thiocarbamate products were converted into the secondary amine
by treatment with dimethyl sulfate, followed by hydrolysis with water. All the products were
1
characterized by mass spectrometry (MS) and spectral data (IR, H NMR and 13C NMR). The
physical and spectral data for the thiocarbamates are given below:
4.3.1. β-Naphthyl N,N-dimethylthiocarbamate (4a)
Yellow crystals, mp 82 ◦C. FT-IR (KBr): 2928, 1629, 1532, 1508, 1393, 1293, 1244, 1146, 820,
747, 476 cm−1. H NMR: δ = 3.42 (3H, s, CH3), 3.51 (3H, s, CH3), 7.25–7.29 (1H, m, Ar),
1
7.47–7.52 (3H, m, Ar), 7.83–7.89 (3H, m, Ar). 13C NMR: δ = 38.8, 43.3, 119.5, 122.5, 125.7,
126.5, 127.7, 127.9, 129.0, 129.4, 133.4, 153.1, 187.1. EI-MS: m/z (%) = 231 (M+), 187, 143,
127, 104, 88 (100). Found: M+ 231.0717, C13H13NOS requires M+ 231.0718.
4.3.2. β-Naphthyl N,N-diethylthiocarbamate (4b)
Orange crystals, mp 50 ◦C. FT-IR (KBr): 3055, 2976, 2933, 1629, 1599, 1509, 1428, 1314,
1
1209, 1165, 967, 855, 751, 472 cm−1. H NMR: δ = 1.36 (3H, t, J = 6 Hz, CH3), 1.38 (3H,
t, J = 6.0 Hz, CH3), 3.75 (2H, q, J = 7.2 Hz, CH2), 3.95 (2H, q, J = 7.2 Hz, CH2), 7.26–7.29
(1H, m, Ar), 7.42–7.55 (3H, m, Ar), 7.72–7.89 (3H, m, Ar). 13C NMR: δ = 11.9, 13.6, 44.3,
48.4, 119.5, 122.5, 125.7, 126.5, 127.7, 127.9, 129.7, 131.5, 133.7, 151.5, 186.9. EI-MS: m/z

Journal of Sulfur Chemistry
5
(%) = 259 (M+), 187, 143, 132, 127 (100), 116. Found: M+ 259.1032, C15H17NOS requires M+
259.1031.
4.3.3. β-Naphthyl piperidine-1-thiocarboxylate (4c)
Orange crystals, mp 98 ◦C. FT-IR (KBr): 2935, 2920, 2857, 1628, 1508, 1439, 1352, 1235, 1166,
1009, 803, 751, 473 cm−1. 1H NMR: δ = 1.77 (6H, bs, 3CH2), 3.98 (2H, bs, CH2N), 4.15 (2H,
bs, CH2N), 7.24–7.28 (1H, m, Ar), 7.46–7.51 (3H, m, Ar), 7.80–7.88 (3H, m, Ar). 13C NMR:
δ = 24.2, 25.3, 26.1, 47.5, 51.8, 119.4, 122.5, 125.7, 126.4, 127.7, 127.9, 128.9, 131.5, 133.7,
151.6, 186.3. EI-MS: m/z (%) = 271 (M+), 187, 143, 130, 128, 127 (100). Found: M+ 271.1031,
C16H17NOS requires M+ 271.1030.
4.3.4. β-Naphthyl morpholine-4-thiocarboxylate (4d)
Brown crystals, mp 131 ◦C. FT-IR (KBr): 2923, 1628, 1508, 1488, 1437, 1288, 1231, 1114, 1042,
817, 746, 473 cm−1. 1H NMR: δ = 3.80–3.89 (4H, m, 2CH2N), 4.05 (2H, t, J = 4.5 Hz, CH2O),
4.20 (2H, t, J = 4.8 Hz, CH2O), 7.25 (1H, t, J = 6.0 Hz, Ar), 7.48–7.55 (3H, m, Ar), 7.81–7.89
(3H, m,Ar). 13C NMR: δ = 46.9, 50.2, 66.2, 66.4, 119.5, 122.3, 125.8, 126.6, 127.7, 127.9, 129.0,
131.6, 133.7, 151.3, 187.3. EI-MS: m/z (%) = 273 (M+), 187, 146 (100), 143, 130, 127. Found:
M+ 273.0825, C15H15NO2S requires M+ 273.0823.
4.3.5. β-Naphthyl N-(4-chlorobutyl)-N-methylthiocarbamate (4e)
1
Yellow oil. FT-IR (KBr): 2936, 1629, 1599, 1509, 1401, 1211, 856, 751, 473, 330 cm−1. H
NMR: δ = 1.89 (4H, d, J = 3.9 Hz, 2CH2), 3.34 (3H, s, CH3), 3.45 (3H, s, CH3), 3.62 (2H, q,
J = 6.3 Hz, CH2–Cl), 3.76–3.98 (2H, m, CH2–N), 7.27 (1H, t, J = 6.9 Hz, Ar), 7.46–7.56 (3H,
m, Ar), 7.82–7.90 (3H, m, Ar). 13C NMR: δ = 23.9, 25.3, 29.6, 29.7, 36.8, 41.6, 44.4, 44.7, 50.8,
54.5, 119.5, 122.6, 125.8, 126.5, 127.7, 128.0, 129.0, 131.6, 133.7, 151.6, 187.8. EI-MS: m/z
(%) = 309 (M+ + 2), 307 (M+), 187, 182, 180, 166, 164, 143 (100), 127. Found: M+ 307.0797,
C16H18ClNOS requires M+ 307.0797.
4.3.6. β-Naphthyl N-(4-chloro-4-(pyridin-3-yl)buty)l-N-methylthiocarbamate (4f)
Yellow oil. FT-IR (KBr): 2925, 1717, 1628, 1599, 1509, 1402, 1240, 1162, 810, 748, 473 cm−1
.
1H NMR: δ = 2.11–2.29 (4H, m, 2CH2), 3.33 (3H, s, CH3), 3.44 (3H, s, CH3), 3.79–4.11 (2H,
m, CH2-N), 4.93–5.10 (1H, m, CH-Cl), 7.42–7.50 (3H, m, Ar), 7.52–7.66 (4H, m, Ar), 7.72–7.97
(6H, m, Ar), 8.51–8.59 (2H, m, Ar). 13C NMR: δ = 24.0, 25.4, 29.7, 36.7, 36.9, 41.6, 50.7, 54.2,
59.9, 60.0, 119.5, 122.4, 124.0, 125.8, 126.6, 127.8, 129.1, 129.8, 131.5, 133.6, 134.9, 137.7,
147.8, 149.4, 151.4, 187.8. EI-MS: m/z (%) = 372 (M + 2)+, 370 (M+), 245, 243, 229, 227,
187, 143 (100), 127. Found: M+ 370.1030, C21H21ClNOS requires M+ 370.1032.
4.3.7. β-Naphthyl N-allyl-N-methylthiocarbamate (4g)
1
Yellow oil. FT-IR (KBr): 3056, 1600, 1509, 1398, 1211, 1164, 810, 751, 473 cm−1. H NMR:
δ = 3.33 (3H, s, CH3), 3.47 (3H, s, CH3), 3.38 (1H, d, J = 5.4 Hz, CH2), 4.60 (1H, d, J = 6 Hz,
CH2), 5.25–5.38 (2H, m, CH2), 5.92–5.97 (1H, m, CH), 7.26–7.32 (1H, m, Ar), 7.36–7.59 (3H,
m, Ar), 7.83–7.90 (3H, m, Ar). 13C NMR: δ = 36.2, 41.3, 53.9, 57.8, 117.8, 118.6, 119.5, 122.5,
125.8, 126.5, 127.8, 127.9, 129.0, 131.1, 131.5, 131.6, 133.7, 151.6, 187.9. EI-MS: m/z (%) = 257
(M+), 187, 143, 130, 127 (100), 114. Found: M+ 257.0876, C15H15NOS requires M+ 257.0874.

6
F. Ghotbi et al.
4.3.8. β-Naphthyl N-t-butyl-N-methylthiocarbamate (4h)
Brown oil. FT-IR (KBr): 3055, 2925, 1758, 1600, 1509, 1459, 1381, 1241, 1213, 1162, 824,
1
748, 696, 474 cm−1. H NMR: δ = 1.39 (9H, s, 3CH3), 3.59 (3H, s, CH3), 7.10–7.27 (3H, m,
Ar), 7.29–7.58 (3H, m, Ar), 7.76 (1H, q, J = 8.7 Hz, Ar). 13C NMR: δ = 24.9, 29.9, 30.3, 44.4,
54.0, 63.2, 118.4, 119.1, 121.0, 123.0, 126.6, 127.9, 129.1, 129.7, 131.3, 154.6, 187.1. EI-MS:
m/z (%) = 273 (M+), 187, 146, 143 (100), 130, 127. Found: M+ 273.1188, C16H19NOS requires
M+ 273.1187.
4.3.9. β-Naphthyl N-cyclohexyl-N-methylthiocarbamate (4i)
Yellow crystals, mp 107 ◦C. FT-IR (KBr): 2927, 2854, 1631, 1498, 1403, 1322, 1207, 1082, 969,
811, 751, 474 cm−1. H NMR: δ = 0.90 (3H, q, J = 4.2 Hz), 1.29–1.72 (4H, m), 1.93 (4H, t,
1
J = 10.8 Hz), 3.22 (s, 3H, CH3), 3.38 (3H, s, CH3), 7.27–7.30(1H, m, Ar), 7.45–7.52 (3H, m,
Ar), 7.81–7.90 (3H, m, Ar). 13C NMR: δ = 25.5, 25.7, 29.4, 29.7, 30.6, 31.0; 58.2, 61.4, 119.5,
122.6, 125.7, 126.4, 127.7, 127.9, 128.8, 131.5, 133.7, 151.6, 187.3. EI-MS: m/z (%) = 299
(M+), 187, 171, 155 (100), 143, 127. Found: M+ 299.1343, C18H21NOS requires M+ 299.1344.
Acknowledgements
The authors acknowledge the Urmia University Research Council for support of this work. We also thank Professor Joule
from the University of Manchester for his comments and Mr M. Qavidel for measuring the NMR spectra.
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