New Facile Synthesis of 2-Alkylthiopyrimidin-4(3 H)-ones by Tandem Aza-Wittig Reaction Starting from the Baylis-Hillman Adducts

Article abstract of DOI:10.1055/s-0036-1588947

Iminophosphoranes reacted with CS₂ at -5 °C to produce the isothiocyanates, which were treated with primary amine to give thioureas in 73-91% yields. The subsequent reaction of thioureas with alkyl bromides in the presence of solid K₂

Full text of DOI:10.1055/s-0036-1588947

SYNLETT
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
©
Georg Thieme Verlag Stuttgart · New York
2017, 28, A–D
A
letter
Synlett
J. Xiong et al.
Letter
New Facile Synthesis of 2-Alkylthiopyrimidin-4(3H)-ones by
Tandem Aza-Wittig Reaction Starting from the Baylis–Hillman
Adducts
Jun Xiong
1
O
1
. R NH2
COOMe
COOMe
Xiao Wei
R1
Ar
CS2
Ar
r.t., 12 h
Ar
N
Ming-Wu Ding*
CH2Cl2
2. K2CO3 (s)
MeCN
N
PPh3
N
C
S
–5 °C
SR2
N
Key Laboratory of Pesticide & Chemical Biology of
Ministry of Education, Central China Normal University,
Wuhan 430079, P. R. of China
4–6 h
1
5
0 °C, 5–6 h R = aryl, alkyl, H;
2
R2 = alkyl; Ar = aryl
17 examples
3
. R Br
6
8–88%
mwding@mail.ccnu.edu.cn
Received: 21.11.2016
Accepted after revision: 14.01.2017
Published online: 06.02.2017
O
O
N
NC
Cl
NH
DOI: 10.1055/s-0036-1588947; Art ID: st-2016-w0783-l
NH
N
S
Abstract Iminophosphoranes reacted with CS at –5 °C to produce the
SMe
2
Ph
isothiocyanates, which were treated with primary amine to give
thioureas in 73–91% yields. The subsequent reaction of thioureas with
alkyl bromides in the presence of solid K CO produced 2-alkylthiopy-
F
Me
Cl
1
2
2
3
rimidin-4(3H)-ones in 68–88% yield via tandem intramolecular cycliza-
tion–isomerization–S-alkylation.
O
MeO
MeO
I
NH
Key words pyrimidin-4(3H)-one, Baylis–Hillman reaction, aza-Wittig
reaction, isothiocyanate, isomerization
N
S
NO2
The 4(3H)-pyrimidinone scaffold represents a common
motif in many biologically relevant compounds. A wide va-
riety of derivatives of this ring system have shown good an-
3
Figure 1 Representative bioactive 2-alkylthio-pyrimidin-4(3H)-ones
(S-DABOs)
1
2
3
4
tiviral, anticancer, antimycobacterial, herbicidal, and di-
5
peptidyl peptidase IV (DPP-4) inhibitive activities. The hu-
Baylis–Hillman reaction has become an effective meth-
man immunodeficiency virus type 1 (HIV-1) reverse
transcriptase inhibitors have been one of the main ingredi-
ents of multidrug cocktails in AIDS patients therapy. Since
the dihydroalkyloxybenzyloxopyrimidines (DABOs)6 were
disclosed as HIV-1 reverse transcriptase inhibitors, the re-
lated 2-alkylthiopyrimidin-4(3H)-ones (S-DABOs) have also
been found to exhibit excellent anti-HIV-1 or anti-HBV
od for the preparation of organic molecules with functional
density through the construction of carbon–carbon bond in
a one-pot procedure.13 The Baylis–Hillman products have
been utilized recently in further preparation of various het-
14
15
erocycles, such as 4-quinolones, oxindoles, 1,3-thi-
azinane-2-thiones,16 and piperidines. The aza-Wittig re-
action has also provided a powerful method for the con-
struction of C=N double bond and has recently applied
17
(
hepatitis B virus) activity.7–12 For examples (Figure 1), S-
18
DABO compounds 1 and 2 showed high inhibitory activities
against wildtype and mutant HIV-1 in the low nanomolar
or subnanomolar range with an additional merit of low cy-
widely in the synthesis of many heterocyclic compounds.
The aza-Wittig reactions between iminophosphoranes and
CS2 produce isothiocyanate intermediates, which may be
utilized in preparing various heterocycles in further se-
quential reactions.19 By using such isothiocyanates as inter-
mediates, we have previously reported the efficient synthe-
sis of 2-thioxo-4-imidazolidinones, imidazolidine-2-thi-
7,8
totoxicity. The S-DABO compound 3 possessed anti-HBV
ability and could be used as potential agent against HBV in-
9
fection. Although there are some known approaches for
the preparation of these 2-alkylthio-substituted 4(3H)-py-
7–9
20
rimidinones, new synthetic methods are still desirable to
obtain diversely substituted S-DABOs for biological activity
studies.
ones, and thiazoles. The reaction process involves tandem
aza-Wittig–intermolecular nucleophilic addition–intramo-
lecular cyclizations. Continuing our interests in synthesis of
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–D

B
Synlett
J. Xiong et al.
Letter
heterocycles via aza-Wittig reactions,21 we reported herein
a facile synthesis of 2-alkylthiopyrimidin-4(3H)-ones by a
sequential aza-Wittig–intramolecular cyclization–isomeri-
zation–S-alkylation, starting from the Baylis–Hillman ad-
ducts.
OAc
COOMe
N3
Ar
PPh3
CH Cl
NaN3
COOMe
Ar
DMSO
r.t., 12 h
71–78%
2
2
r.t., 1–2 h
4
5
Azides 5, prepared from the reaction of Baylis–Hillman
COOMe
COOMe
22
adducts 4 with sodium azide in DMSO, reacted with
triphenylphosphine to generate iminophosphoranes 6 via
Staudinger reaction at room temperature. Initial attempts
Ar
CS2
Ar
–5 °C
N
PPh3
N
C
S
4–6 h
6
7
on reactions of iminophosphoranes 6 with CS at room or
2
refluxing temperature resulted in complex mixture proba-
bly due to side reactions. However, at low temperature (–5 °C),
the reactions were found to take place smoothly to produce
the isothiocyanate intermediates 7, which were further
treated with primary amine to give thioureas 8 in good
COOMe
Ar
1
R NH2
NHR1
N
C
S
r.t., 12 h
3–91%
H
7
1
9 examples
8
23
overall yields (73–91%, Scheme 1 and Table 1). As indicat-
ed in Table 1, various amines can be used in the above reac-
tion to prepare thioureas 8, including alkyl amines (Table 1,
entries 1–12), aromatic amines (Table 1, entries 13–18),
and ammonia (Table 1, entry 19). Even when the bulky t-
BuNH2 was utilized (Table 1, entry 6), 73% yield of the
thiourea 8f was also obtained.
Scheme 1 Preparation of thiourea intermediates 8
clization took place successfully to produce 10, which were
further treated with alkyl bromides to give 2-alkylthiopy-
rimidin-4(3H)-ones 11 (Table 1).24 The intermediate 9 can-
not be isolated but the intermediate 10 can be separated
before the addition of alkyl bromides. The formation of
compound 11 can be rationalized in terms of an initial cy-
clization of 8 to give 9. Further isomerization of the inter-
The cyclization of thioureas 8 to 2-thioxopyrimidin-
4(1H)-ones 9 or 10 did not occur in the presence of solid
K CO at room temperature (Scheme 2). But at 50 °C, the cy-
2
3
Table 1 Preparation of Compounds 8a–s and 11a–s
Entry
Ar
Ph
R1
n-Bu
Product
Yield (%)a
R2
n-Pr
Product
Yield (%)b
1
2
3
4
5
6
7
8
9
8a
8b
8c
8d
8e
8f
87
91
75
88
90
73
78
79
81
83
84
75
90
89
77
87
84
75
82
11a
11b
11c
11d
11e
11f
84
78
74
86
87
0
Ph
n-Pr
Et
n-Pr
Et
Ph
Ph
PhCH
2
Et
Ph
4-MeC
t-Bu
i-Pr
6
H
4
CH
2
i-Pr
Bn
Ph
Ph
8g
8h
8i
Et
11g
11h
11i
0
4-ClC
4-ClC
4-ClC
4-ClC
4-ClC
Ph
6
6
6
6
6
H
H
H
H
H
4
4
4
4
4
n-Bu
n-Pr
Et
Et
88
81
80
85
70
75
72
69
74
79
68
75
Et
10
11
12
13
14
15
16
17
18
19
8j
i-Pr
n-Bu
n-Pr
n-Pr
n-Pr
Et
11j
Bn
8k
8l
11k
11l
4-MeC
6
6
H
4
4
CH
2
Ph
8m
8n
8o
8p
8q
8r
11m
11n
11o
11p
11q
11r
11s
Ph
4-MeC
H
Ph
4-ClC
Ph
6
H
4
4-ClC
4-ClC
4-ClC
Ph
6
6
6
H
H
H
4
4
4
i-Pr
n-Bu
i-Pr
Et
4-MeC
6
H
4
4-ClC
H
6 4
H
8s
a
Yields based on azides 5.
Yields based on thioureas 8.
b
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–D

C
Synlett
J. Xiong et al.
Letter
mediate 9 through 1,3-H shift takes place to give 2-thioxo-
pyrimidin-4(1H)-one 10, which was S-alkylated to produce
The structure of 4(3H)-pyrimidinones 11 was con-
firmed by their spectral data. For example, the H NMR (600
1
2-alkylthiopyrimidin-4(3H)-one 11 under the basic condition.
MHz, CDCl ) spectrum of 11a shows a singlet at δ = 3.73
3
ppm due to the Bn group. The signals of NCH and SCH ap-
2
2
O
COOMe
pear at δ = 4.01 and 3.10 ppm as triplet absorptions. The
signals of other CH and CH appear at δ = 1.73–0.95 ppm as
K2CO3 (s)
Ar
R1
MeCN
2
3
Ar
N
N
C
S
NHR1
multiplets. The signals attributable to the pyrimidinone-6-
5
0 °C, 5–6 h
H
68–88%
N
S
H and other Ar-Hs are found at δ = 7.50 ppm as singlet and
H
17 examples
13
δ = 7.29–7.19 ppm as multiplets. The C NMR (150 MHz,
8
9
CDCl ) spectrum data in 11a showed the signal of the py-
rimidinone C-4 and C-2 carbon at δ = 162.1 and 160.0 ppm.
3
O
O
R1
N
R1
2
R Br
The signals attributable to NCH , SCH , and CH carbon are
2
2
2
Ar
Ar
N
found at δ = 44.7, 33.8, and 33.7 ppm, respectively. The IR
N
SR2
spectra of 11a revealed C=O absorption bands at 1669 cm .
–1
N
S
H
+
1
1
The HRMS spectrum of 11a shows [M + H] at m/z = 317.1683
1
0
(
calcd 317.1682).
Scheme 2 Preparation of 2-alkylthiopyrimidin-4(3H)-one 11
In conclusion, we have developed a facile synthesis of 2-
alkylthio-pyrimidin-4(3H)-ones (S-DABOs) by a new se-
quential aza-Wittig–intramolecular cyclization–S-alkyla-
tion/–isomerization reaction, starting from the Baylis–Hillman
adducts. Due to the easily accessible and versatile starting
material, this method has the advantage in the synthesis of
many biologically and pharmaceutically active S-DABOs de-
rivatives.
It is noteworthy that if solid K CO was added to the
2
3
1
mixture of thiourea 8 (R = alkyl) and alkyl bromide, the cy-
clization could take place even at room temperature to give
directly 2-alkylthiopyrimidin-4(3H)-one 11 (Scheme 3).25
In this case, the formation of compound 11 presumably in-
volves an initial S-alkylation of thiourea 8 to give the inter-
mediate 12, which undertakes further cyclization and
isomerization to produce 2-alkylthiopyrimidin-4(3H)-one
Acknowledgment
1
1 under the basic conditions. MS detection of the reaction
+
mixture of 8b showed the [M] at m/z = 334 of the interme-
diate 12b, which verified its existence during the reaction
process.
We gratefully acknowledge financial support of this work by the Na-
tional Natural Science Foundation of China (No. 21572075 and
21172085).
COOMe
2
COOMe
R Br
Ar
Supporting Information
Ar
K2CO3 (s)
C
SR2
NHR1
N
C
S
NHR1 MeCN
N
Supporting information for this article is available online at
H
http://dx.doi.org/10.1055/s-0036-1588947.
S
u
p
p
ortioIgnfmr oaitn
S
u
p
p
o
nrtogI
i
f
rm oaitn
r.t.
8
(R1 = alkyl)
12
References and Notes
O
N
O
R1
R1
(1) (a) Saladino, R.; Crestini, C.; Palamara, A. T.; Danti, M. C.;
Manetti, F.; Corelli, F.; Garaci, E.; Botta, M. J. Med. Chem. 2001,
44, 4554. (b) Singh, K.; Singh, K.; Balzarini, J. Eur. J. Med. Chem.
Ar
N
Ar
N
SR2
SR2
N
2013, 67, 428.
1
3
11
(2) Rashad, A. E.; Shamroukh, A. H.; Yousif, N. M.; Salama, M. A.; Ali,
H. S.; Ali, M. M.; Mahmoud, A. E.; El-Shahat, M. Arch. Pharm.
Chem. Life Sci. 2012, 345, 729.
Scheme 3 Preparation of 2-alkylthiopyrimidin-4(3H)-one 11 at room
temperature
(
3) Malothu, N.; Bhandaru, J. S.; Kulandaivelu, U.; Jojula, M.;
Adidala, R. R.; Umadevi, K. R.; Dusthackeer, A. V. N.; Kaki, V. R.;
Akkinepally, R. R. Bioorg. Med. Chem. Lett. 2016, 26, 836.
The reaction yields of compounds 11 are found to relate
1
1
(4) Taylor, E. C.; Zhou, P.; Tice, C. M.; Lidert, Z.; Roemmele, R. C. Tet-
rahedron Lett. 1997, 38, 4339.
with R group (Table 1). When R are alkyl or H groups, the
reactions proceeded smoothly to give the corresponding 2-
alkylthiopyrimidin-4(3H)-one 11a–e, 11h–l, and 11s in 70–
8% yields (Table 1, entries 1–5, 8–12, and 19). However, no
product was got as R are bulky i-Pr and t-Bu groups (11f
and 11g, Table 1, entries 6 and 7). In case that aromatic pri-
(
5) Zhang, Z.; Wallace, M. B.; Feng, J.; Stafford, J. A.; Skene, R. J.; Shi,
L.; Lee, B.; Aertgeerts, K.; Jennings, A.; Xu, R.; Kassel, D. B.;
Kaldor, S. W.; Navre, M.; Webb, D. R.; Gwaltney, S. L. II. J. Med.
Chem. 2011, 54, 510.
8
1
(6) Artico, M.; Massa, S.; Mai, A.; Marongiu, M. E.; Piras, G.;
1
Tramontano, E.; La Colla, P. Antivir. Chem. Chemother. 1993, 4,
mary amines (R = aryl, entries 13–18) were used, the prod-
ucts 11m–r were obtained in moderate yields (68–79%).
361.
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–D

D
Synlett
J. Xiong et al.
Letter
(7) Rotili, D.; Tarantino, D.; Nawrozkij, M. B.; Babushkin, A. S.;
mixture was stirred at r.t. for 1–2 h to form iminophosphorane
Botta, G.; Marrocco, B.; Cirilli, R.; Menta, S.; Badia, R.; Crespan,
E.; Ballante, F.; Ragno, R.; Esté, J. A.; Maga, G.; Mai, A. J. Med.
Chem. 2014, 57, 5212.
(TLC monitoring). The CS (1.52 g, 20 mmol) was then added at
2
–5 °C, and the mixture was continuing stirred at –5 °C for 4–6 h.
After the reaction was completed, the solvent and excess CS2
were removed in reduced pressure. Primary amine (2 mmol)
was added to the residue in CH Cl (10 mL), and the mixture
(
8) Ramajayam, R.; Mahera, N. B.; Neamati, N.; Yadav, M. R.;
Giridhar, R. Arch. Pharm. Chem. Life Sci. 2009, 342, 710.
9) Zhang, Y.; Sun, X.; Fan, N.; Zhao, J.; Tu, J.; Chen, X.; Liu, J.; Wang,
X. Med. Chem. Commun. 2015, 6, 1438.
10) Mai, A.; Artico, M.; Sbardella, G.; Massa, S.; Novellino, E.; Greco,
G.; Loi, A. G.; Tramontano, E.; Marongiu, M. E.; La Colla, P. J. Med.
Chem. 1999, 42, 619.
2
2
(
was stirred overnight at r.t. The solvent was removed, and the
residue was purified by column chromatography (PE–EtOAc,
4:1) to give thioureas 8.
(
Compound 8a: light yellow solid (yield 0.53 g, 87%), mp 72–74
1
°C. H NMR (600 MHz, CDCl ): δ = 7.85 (s, 1 H, =CH), 7.42–7.38
3
(
11) Mugnaini, C.; Alongi, M.; Togninelli, A.; Gevarija, H.; Brizzi, A.;
Manetti, F.; Bernardini, C.; Angeli, L.; Tafi, A.; Bellucci, L.; Corelli,
F.; Massa, S.; Maga, G.; Samuele, A.; Facchini, M.; Clotet-Codina,
I.; Armand-Ugón, M.; Esté, J. A.; Botta, M. J. Med. Chem. 2007, 50,
(m, 5 H, Ar–H), 6.59 (br, 2 H, 2NH), 4.49 (br, 2 H, NCH ), 3.82 (s, 3
2
H, OCH ), 3.38 (br, 2 H, NCH ), 1.49–1.29 (m, 4 H, 2CH ), 0.89 (t,
3
2
2
13
J = 7.2 Hz, 3 H, CH3). C NMR (150 MHz, CDCl ): δ = 181.1,
3
168.4, 143.5, 133.8, 129.5, 129.4, 128.8, 127.2, 52.5, 44.6, 41.2,
+
6580.
30.8, 19.9, 13.7. HRMS: m/z calcd for [C16H22N O S + H] :
2
2
(
12) Nawrozkij, M. B.; Rotili, D.; Tarantino, D.; Botta, G.; Eremiychuk,
A. S.; Musmuca, I.; Ragno, R.; Samuele, A.; Zanoli, S.; Armand-
Ugón, M.; Clotet-Codina, I.; Novakov, I. A.; Orlinson, B. S.; Maga,
G.; Esté, J. A.; Artico, M.; Mai, A. J. Med. Chem. 2008, 51, 4641.
13) (a) Basavaiah, D.; Reddy, B. S.; Badsara, S. S. Chem. Rev. 2010,
307.1475; found: 307.1479.
(24) General Procedure for the Preparation of 2-Alkylthiopyrimi-
din-4(3H)-ones 11
To the thioureas 8 (2 mmol) in MeCN (10 mL) was added solid
K CO (0.28 g, 2 mmol). The mixture was stirred at 50 °C for 5–6
(
2
3
1
2
10, 5447. (b) Declerck, V.; Martinez, J.; Lamaty, F. Chem. Rev.
009, 109, 1. (c) Singh, V.; Batra, S. Tetrahedron 2008, 64, 4511.
h to form 2-thioxopyrimidin-4(1H)-ones 10 (TLC monitoring).
The alkyl bromide (2 mmol) was then added with continuing
stir. After the reaction was completed, the solid was filtered.
The filtrate was removed, and the residue was purified by
column chromatography (PE–EtOAc, 20:1) to give 2-alkylthio-
pyrimidin-4(3H)-ones 11.
(
(
(
14) Reddy, R. S.; Lagishetti, C.; Kiran, I. N. C.; You, H.; He, Y. Org. Lett.
016, 18, 3818.
15) Yang, Y.; Ma, C.; Thumar, N. J.; Hu, W. J. Org. Chem. 2016, 81,
537.
2
8
16) Basavaiah, D.; Pal, S.; Veeraraghavaiah, G.; Bharadwaj, K. C. Tet-
rahedron 2015, 71, 4659.
Compound 11m: white solid (yield 0.502 g, 75%), mp 102–104
1
°C. H NMR (600 MHz, CDCl ): δ = 7.61 (s, 1 H, Ar–H), 7.51–7.21
3
(
(
17) Bharadwaj, K. C.; Tiwari, D. K. Tetrahedron 2016, 72, 312.
18) (a) Wei, H.; Li, Y.; Xiao, K.; Cheng, B.; Wang, H.; Hu, L.; Zhai, H.
Org. Lett. 2015, 17, 5974. (b) Hu, Y.; Li, X.; Wan, B. Tetrahedron
(m, 10 H, Ar–H), 3.77 (s, 2 H, CH ), 2.97 (t, J = 7.8 Hz, 2 H, SCH ),
2
2
13
1.66–1.60 (m, 2 H, CH ), 0.94 (t, J = 7.2 Hz, 3 H, CH ). C NMR
2
3
(150 MHz, CDCl ): δ = 162.4, 161.4, 149.7, 138.8, 135.9, 129.8,
3
2
015, 71, 6935. (c) Welsch, S. J.; Umkehrer, M.; Kalinski, C.; Ross,
129.7, 129.1, 128.5, 128.4, 126.3, 123.4, 34.2, 33.6, 21.9, 13.4.
+
G.; Burdack, C.; Kolb, J.; Wild, M.; Ehrlich, A.; Wessjohann, L. A.
Tetrahedron Lett. 2015, 56, 1025. (d) Ramachary, D. B.; Shruthi,
K. S. J. Org. Chem. 2016, 81, 2405. (e) Qu, F.; Hu, R.-F.; Gao, L.;
Wu, J.; Cheng, X.-H.; Wang, S.; He, P. Synthesis 2015, 47, 3701.
HRMS: m/z calcd for [C20H20N OS + H] : 337.1369; found:
2
337.1373.
(25) General Procedure for the Preparation of 2-Alkylthiopyrimi-
1
din-4(3H)-ones 11 (R = alkyl) at Room Temperature
(f) Nishimura, Y.; Cho, H. Synlett 2015, 26, 233.
To the thioureas 8 (2 mmol) and alkyl bromides (2 mmol) in
(
(
(
19) Palacios, F.; Alonso, C.; Aparicio, D.; Rubiales, G.; Santos, J. M.
MeCN (10 mL) was added solid K CO (0.28 g, 2 mmol). The
2
3
Tetrahedron 2007, 63, 523.
mixture was stirred at r.t. for 24–48 h. After the reaction was
completed, the solid was filtered. The filtrate was removed, and
the residue was purified by column chromatography (PE–
EtOAc, 20:1) to give 2-alkylthiopyrimidin-4(3H)-ones 11.
Compound 11a: colorless oil (yield 0.53 g, 84%). 1H NMR (600
20) (a) Ding, M. W.; Fu, B. Q.; Cheng, L. Synthesis 2004, 1067. (b) Xie,
H.; Liu, J. C.; Wu, L.; Ding, M. W. Tetrahedron 2012, 68, 7984.
21) (a) Yan, Y. M.; Rao, Y.; Ding, M. W. J. Org. Chem. 2016, 81, 1263.
(
(
b) Yuan, D.; Kong, H. H.; Ding, M. W. Tetrahedron 2015, 71, 419.
c) Wang, L.; Ren, Z. L.; Chen, M.; Ding, M. W. Synlett 2014, 25,
MHz, CDCl ): δ = 7.50 (s, 1 H, Ar–H), 7.29–7.19 (m, 5 H, Ar–H),
3
721. (d) Wang, Y.; Chen, M.; Ding, M. W. Tetrahedron 2013, 69,
9056. (e) Zhong, Y.; Wu, L.; Ding, M. W. Synthesis 2012, 44,
3085.
4.01 (t, J = 7.8 Hz, 2 H, NCH ), 3.73 (s, 2 H, CH ), 3.10 (t, J =7.2 Hz,
2
2
2 H, SCH ), 1.73–1.71 (m, 4 H, 2CH ), 1.43–1.39 (m, 2 H, CH ),
2
2
2
13
1.03–0.95 (m, 6 H, 2 CH3). C NMR (150 MHz, CDCl ): δ = 162.1,
3
(
22) (a) Yadav, J. S.; Gupta, M. K.; Pandey, S. K.; Reddy, B. V. S.; Sarma,
A. V. S. Tetrahedron Lett. 2005, 46, 2761. (b) Sá, M. M. J. Braz.
Chem. Soc. 2003, 14, 1005.
160.0, 149.2, 138.9, 129.0, 128.4, 126.2, 122.4, 44.7, 33.8, 33.7,
+
29.3, 22.1, 20.2, 13.7, 13.4. HRMS: m/z calcd for [C18H24N OS + H] :
2
317.1682; found: 317.1683.
(
23) General Procedure for the Preparation of Thioureas 8
To the azides 4 (2 mmol) in dry CH Cl (10 mL) was added drop-
2
2
wise Ph P (0.52 g, 2 mmol) in CH Cl (5 mL) under N . The
3
2
2
2
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–D