Synthesis of thioamides via one-pot A3-coupling of alkynyl bromides, amines, and sodium sulfide

Article abstract of DOI:10.1039/c3ob42275e

We herein describe a novel method for the synthesis of thioamides by a three component condensation of alkynyl bromides, amines, and Na ₂S·9H₂O. The developed method is applicable for a wide range of amines and alkynyl bromides bearing different functional groups furnishing the corresponding products in moderate to excellent yields. The Royal Society of Chemistry.

Full text of DOI:10.1039/c3ob42275e

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Synthesis of thioamides via one-pot A3-coupling
of alkynyl bromides, amines, and sodium sulfide†
Cite this: Org. Biomol. Chem., 2014,
12, 700
Yadong Sun,a,b Huanfeng Jiang,*a Wanqing Wu,a Wei Zenga and Jianxiao Lia
Received 14th November 2013,
Accepted 18th November 2013
We herein describe a novel method for the synthesis of thioamides by a three component condensation
of alkynyl bromides, amines, and Na2S·9H2O. The developed method is applicable for a wide range of
amines and alkynyl bromides bearing different functional groups furnishing the corresponding products in
moderate to excellent yields.
DOI: 10.1039/c3ob42275e
www.rsc.org/obc
eqn (1)). So far, the synthesis of thioamides in one pot has relied
heavily on the Willgerodt–Kindler reaction, starting from aryl
Introduction
Thioamides are prevalent structural motifs that are found in alkyl ketones, elemental sulfur, and secondary amines such as
many biologically active molecules1 and synthetic intermedi- morpholine.6 Recently, Nguyen and coworkers developed a
ates.2 They have attracted considerable attention in organic three-component reaction involving elemental sulfur and two
synthesis as versatile synthons due to their unique reactivity different aliphatic primary amines for the synthesis of thio-
and wide availability.3 For example, various important chemi- amides (Scheme 1, eqn (2)).7 However, this method has limited
cals including nitriles, amides, amidines, and sulfur-contain- applications because of the high reaction temperature and long
ing heterocycles (e.g., thiazoles, thiazolins, and thiazolinones) reaction time that are typically required. As a consequence, the
have been synthesized from thioamides.4 Compared with its development of new methods for the practical synthesis of thio-
analogue amides, the synthetic methods for the formation of amides under mild reaction conditions is still highly desirable.
thioamides are rather limited. Traditional methods for the
It has been demonstrated that haloalkynes are useful syn-
preparation of thioamides usually involve the condensation of thons in many organic transformations.8 Our group has
carboxyl derivatives and amines followed by thionation with reported several nucleophilic additions, homocoupling reac-
the aid of P4S10, Lawesson’s reagent, etc.,5 which often produce tions, and transition-metal-catalyzed bond formation reactions
toxic chemical wastes and need tedious procedures (Scheme 1, of haloalkynes.9 As part of our continuing program on the
functionalization of haloalkynes, herein we wish to report a
highly efficient method for the thioamide synthesis from
alkynyl bromides based on the three-component reaction
under convenient conditions.
On the basis of copper or iodine catalyzed reactions for the
formation of C–N and C–S bonds10,11 and the recent develop-
ment of new reactions or synthetic sequences starting from
ynamides,12 we envisioned that the condensation of alkynyl
bromides, amines and Na2S·9H2O would provide thioamides.
Results and discussion
Scheme 1 Synthetic approaches to thioamides.
The first reaction of phenylethynyl bromide (0.30 mmol),
diethylamine (0.45 mmol) and Na2S·9H2O (0.45 mmol) was
aSchool of Chemistry and Chemical Engineering, South China University of
Technology, Guangzhou 510640, China
carried out in water (2.5 mL) at 100 °C and no desired thio-
amide could be detected. To our delight, when the reaction
was performed in 1,4-dioxane, N,N-diethyl-2-phenylthioaceta-
mide (3a) was obtained. This result prompted us to screen suit-
able reaction conditions (Table 1). It was found that the
solvents played a critical role for the success of this process
bCollege of Chemistry and Chemical Engineering, Xinjiang University, Urumqi
830046, China. E-mail: jianghf@scut.edu.cn; Fax: +86 20-87112906;
Tel: +86 20-87112906
†Electronic supplementary information (ESI) available: Copies of 1H and 13C
NMR spectra for selected compounds. See DOI: 10.1039/c3ob42275e
700 | Org. Biomol. Chem., 2014, 12, 700–707
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of straight chain aliphatic secondary amines no matter
whether they are symmetrical or unsymmetrical. In all the
cases, the transformations proceeded smoothly and afforded
the desired products. Furthermore, some heterocyclic amines
such as pyrrolidine, morpholine, thiomorpholine and 1,2,3,4-
tetrahydroisoquinoline were also investigated. The results indi-
cated that they were good partners for this transformation.
Unfortunately, secondary arylamines were ineffective under
the standard reaction conditions.
Table 1 Optimization of reaction conditions for the formation of
thioamidea
Entry
Solvent
Temp. (°C)
Yieldb (%)
1
2
3
4
5
6
7
8
H2O
100
80
80
80
80
80
80
80
80
80
30
60
100
80
80
n.p.
72
n.p.
n.p.
39
36
54
40
Trace
91
n.p.
41
1,4-Dioxane
Toluene
CH3CN
Ethanol
DMSO
DME
NMP
HMPA
DMF
DMF
DMF
DMF
DMF
To expand the scope of this methodology, we also examined
a series of alkynyl bromides. As summarized in Table 3,
several different functional groups, including –CH3 (4b), –C2H5
(4c), ether (4d and 4e), fluoro (4f), chloro (4g and 4h), bromo
(4i), ketone (4j), and hydroxy (4k), were tolerated under the
optimized conditions and gave the corresponding thioamides
in moderate to excellent yields. For the para-electron-rich sub-
stituted aromatic 1-bromoalkynes, the coupling yields gradu-
ally decreased from methoxyl to ethyoxyl (Table 3, 4d–4e).
Clearly, the electronic effects played an important role in this
process. The presence of halo-substituents in the aromatic
groups did not interfere with the formation of the thioamide
bond, and these reactions afforded the corresponding pro-
ducts, which could be further functionalized by classical cross-
coupling reactions (Table 3, 4f–4i). Interestingly, the attempts
to use 4-(bromoethynyl)benzonitrile led to the formation of
4-(2-(diethylamino)-2-thioxoethyl)benzamide (Table 3, 4n), and
this compound containing both amide and thioamide moi-
eties was not easily prepared by traditional methods. Further-
more, other heterocyclic alkynyl bromides such as
2-(bromoethynyl)thiophene and 2-(bromoethynyl)pyridine
were also investigated and found to form the desired products
in good yields ranging from 84% to 87%. Moreover, we also
tested some aliphatic alkynyl bromides such as 1-bromo-
oct-1-yne, 1-bromo-3,3-dimethylbut-1-yne, (bromoethynyl)-
cyclohexane, (3-bromoprop-2-ynyloxy)benzene and (3-bromo-
prop-2-ynyloxy)benzene instead of aromatic alkynyl bromides.
9
10
11
12
13
14c
15d
87
83
91
DMF
a Unless otherwise noted, all reactions were carried out using
phenylethynyl bromide 1a (0.30 mmol), diethylamine 2a (0.45 mmol),
and Na2S·9H2O (0.45 mmol) in the indicated solvent (2.5 mL) at 80 °C
for 8 h. n.p. = no product. b Determined by GC using dodecane as the
internal standard. c Reaction time: 6 h. d Reaction time: 10 h.
(entries 3–10). Among all the solvents tested, DMF gave the
best result (entry 10), and was chosen as a standard solvent to
optimize the other reaction parameters. Results of the examin-
ation of the reaction temperature and the reaction time indicated
that 80 °C was the suitable reaction temperature and 8 h was the
optimal reaction time for the synthesis of 3a (entries 10–15).
After optimized reaction conditions, we next conducted a
survey of secondary amines with phenylethynyl bromide (1a)
to explore the scope of this transformation. As shown in
Table 2, the reactions appeared quite tolerant to the substrates
Table 2 The scope of secondary aminesa
Table 3 The scope of alkynyl bromidesa
a Reactions were carried out using phenylethynyl bromide (1.0 mmol), a Reactions were carried out using alkynyl bromide (1.0 mmol),
amine (1.5 mmol) and Na2S·9H2O (1.5 mmol) in DMF (2.5 mL) at diethylamine (1.5 mmol) and Na2S·9H2O (1.5 mmol) in DMF (2.5 mL)
80 °C for 8 h. Yields refer to the isolated yields.
at 80 °C for 8 h. Yields refer to the isolated yields.
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amines, affording the desired compounds in 45–85% yields.
For the straight-chain primary amines, the coupling yields
gradually increased from propylamine to hexylamine (5a, 5c,
5i). The butylamine was more reactive in this system than sec-
butylamine, iso-butylamine, and tert-butylamine, which indi-
cated that the steric bulk of the primary amines had some
impact on the reaction. Having screened a series of different
aliphatic amines, we also examined some aromatic amines
such as aniline. However, even at higher reaction temperature
(150 °C) and with prolonged reaction time (20 h), the aniline
was ineffective in the reaction.
To demonstrate the synthetic utility of this protocol, some
thioamides were employed for further transformations to
prepare a series of functionalized products (Scheme 3). The
[3 + 2] cyclization reactions of 3k and 2-bromo-1-phenyl-
ethanone delivered substituted thiophene 6 in good yields
(Scheme 3, eqn (1)). Thioamide 3a was successfully oxidized to
α-ketoamide 7 by Na2S2O8 (2 equiv.) in 81% yield (Scheme 3,
eqn (2)).
To further elucidate the reaction mechanism, several
control experiments were conducted (Scheme 4). We first used
acetophenone instead of alkynyl bromide to be the reaction
partner (eqn (1)) since a small amount of acetophenone
derived from phenylethynyl bromide was detected during the
course of the reaction. However, only a 2% GC yield of 3a
could be obtained under the optimized reaction conditions.
Moreover, when using N,N-diethyl-2-phenylacetamide and
Na2S·9H2O as the starting materials, the thionation reaction
did not occur (eqn (2)). On the basis of these results, we con-
clude that acetophenone and amide do not play a significant
role in the formation of thioamide. Control experiment 3
Scheme 2 Reaction of other alkynyl halides or tertiary amine.
However, no corresponding thioamide products could be
detected under the optimized reaction conditions. Accord-
ingly, we speculated that the Csp–Br bonds of aliphatic alkynyl
bromides were more stable than those of aromatic alkynyl bro-
mides and it is not easy to form new Csp–N bonds by the
nucleophilic substitution reaction.
We also extended this reaction to phenylethynyl chloride
and phenylethynyl iodide as substrates and found that the
reaction occurred to give 3a in 62% yield when phenylethynyl
chloride was employed (Scheme 2, eqn (1)). However, we were
surprised that 3b was formed in 32% yield instead of 3a when
phenylethynyl iodide was used, which presumably involved a
radical process (Scheme 2, eqn (2)). Furthermore, tertiary
amines such as triethylamine also reacted well to afford 3a in
good yield (Scheme 2, eqn (3)).
We then turned our attention to the coupling of primary
amines, which under the optimized conditions gave poor con-
version into products. Compared with secondary amines,
primary amines proved to be a weaker match as a nucleophile
for the phenylethynyl bromide. Taking into account this case,
we increased the reaction temperature to 110 °C and were
pleased to find that there was an obvious increase in the yield.
With the new conditions established, a series of primary
amines were employed to evaluate the scope of the reaction
(Table 4). The reaction worked efficiently with aliphatic
Scheme 3 Synthetic transformations of the thioamide products.
Table 4 The scope of primary bromidesa
a Reactions were carried out using phenylethynyl bromide (1.0 mmol),
amine (1.5 mmol), Na2S·9H2O (1.5 mmol), in DMF (2.5 mL) at 110 °C
for 8 h. Yields refer to the isolated yields. n.d. = not detected.
Scheme 4 Control experiments.
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obtained from commercial suppliers and used without further
purification.
General procedure for the synthesis of products
A mixture of alkynyl halide (1.0 mmol), amine (1.5 mmol), and
Na2S·9H2O (1.5 mmol) in DMF (2.5 mL) was placed in a sealed
tube (25 mL) equipped with a magnetic stirring bar. The
mixture was stirred at 80 °C (or 110 °C) for 8 h. After the reac-
tion was completed, the mixture was washed with brine and
extracted with ethyl acetate. The organic layer was dried with
anhydrous MgSO4, concentrated under vacuum and purified
by flash silica gel chromatography using petroleum ether–ethyl
acetate 15 : 1 to give the desired products.
Scheme 5 Tentative reaction mechanism.
suggested that deuterium product [D]n-3a was obtained exclu-
sively in 81% isolated yield, and the deuterium atom content
(67% examined by 1H NMR spectroscopy) was higher than
theoretic 50%, which unraveled that a H/D exchange occurred
as the consequence of the enolization of the target product
and one hydrogen atom of methylene in 3a came from the lib-
erated HBr, and the other hydrogen atom of methylene of 3a
came from water.
According to the above observations, a tentative mechanism
for the formation of thioamides was proposed. As shown in
Scheme 5, in the first step, the coupling of alkynyl bromide
with diethylamine provided ynamine A, which would be con-
verted to its isomer B. Then, a nucleophilic addition reaction
of B with sulfide occurred to afford intermediate C, which
would be converted to its isomer D. Finally, protonation of D
provided the target thioamide product.
N,N-Diethyl-2-phenylethanethioamide (3a).13 Yield: 91%. 1H
NMR (400 MHz, CDCl3) δ 7.32–7.21 (m, 5H), 4.29 (s, 2H), 4.00
(q, J = 7.1 Hz, 2H), 3.48 (q, J = 7.2 Hz, 2H), 1.28 (t, J = 7.1 Hz,
3H), 1.10 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3)
δ 198.9, 136.3, 128.7, 127.8, 126.8, 50.4, 47.6, 46.4, 13.1, 10.8.
MS (EI) m/z: 207, 174, 145, 135, 116, 91. IR νmax(KBr)/cm−1
:
2976, 2934, 1502, 1101, 748, 706.
N,N-Dimethyl-2-phenylethanethioamide (3b).14 Yield: 88%.
1H NMR (400 MHz, CDCl3) δ 7.34–7.26 (m, 5H), 4.32 (s, 2H),
3.50 (s, 3H), 3.20 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 200.6,
135.6, 128.8, 128.0, 126.9, 50.9, 44.8, 42.2. MS (EI) m/z: 179,
146, 131, 116, 91, 88. IR νmax(KBr)/cm−1: 3026, 2931, 1520,
1102, 760, 714.
2-Phenyl-N,N-dipropylethanethioamide (3c).15 Yield: 84%.
1H NMR (400 MHz, CDCl3) δ 7.23–7.15 (m, 5H), 4.21 (s, 2H),
3.81–3.77 (m, 2H), 3.30–3.26 (m, 2H), 1.74–1.64 (m, 2H),
1.50–1.40 (m, 2H), 0.84 (t, J = 7.4 Hz, 3H), 0.75 (t, J = 7.3 Hz,
3H). 13C NMR (100 MHz, CDCl3) δ 199.4, 136.3, 128.6, 127.7,
126.7, 54.8, 53.9, 50.6, 21.3, 18.8, 11.1, 11.0. MS (EI) m/z: 235,
202, 160, 144, 135, 91. IR νmax(KBr)/cm−1: 2964, 2874, 1499,
1107, 719.
Conclusions
In conclusion, an efficient thioamide synthesis based upon a
three-component coupling of alkynyl bromides, amines, and
Na2S·9H2O has been developed. Both alkynyl bromides and
amines were commercially available or easily prepared. The
diverse substrate scope, catalyst-free and mild conditions,
combined with an operationally simple procedure, render it a
powerful component to traditional approaches for the syn-
thesis of biologically important compounds containing thio-
amide frameworks. Further expansion of the scope of the
reaction is currently underway in our laboratory.
N,N-Dibutyl-2-phenylethanethioamide (3d).15 Yield: 92%.
1H NMR (400 MHz, CDCl3) δ 7.31–7.23 (m, 5H), 4.28 (s, 2H),
3.93–3.89 (m, 2H), 3.44–3.28 (m, 2H), 1.75–1.68 (m, 2H),
1.50–1.44 (m, 2H), 1.39–1.30 (m, 2H), 1.28–1.18 (m, 2H), 0.95
(t, J = 7.3 Hz, 3H), 0.87 (t, J = 7.3 Hz, 3H). 13C NMR (100 MHz,
CDCl3) δ 199.1, 136.3, 128.6, 127.7, 126.7, 53.1, 52.2, 50.6, 30.1,
27.5, 20.0, 19.9, 13.7, 13.5. MS (EI) m/z: 263, 230, 220, 174, 172,
135, 91. IR νmax(KBr)/cm−1: 2958, 2868, 1499, 1111, 719.
N,N-Diisobutyl-2-phenylethanethioamide (3e).16 Yield: 78%.
Experimental
Melting points were measured with a melting point instru- 1H NMR (400 MHz, CDCl3) δ 7.27– 7.13 (m, 5H), 4.26 (s, 2H),
ment and were uncorrected. 1H NMR and 13C NMR spectra 3.74 (d, J = 7.4 Hz, 2H), 3.22 (d, J = 7.6 Hz, 2H), 2.49– 2.39 (m,
were recorded on a Bruker Avance (400 and 100 MHz, respect- 1H), 2.05–1.95 (m, 1H), 0.83 (d, J = 6.6 Hz, 6H), 0.78 (d, J =
ively) instrument internally referenced to tetramethylsilane 6.7 Hz, 6H). 13C NMR (100 MHz, CDCl3) δ 201.1, 136.3, 128.6,
(TMS) or chloroform signals. IR spectra were obtained either 127.9, 126.8, 60.6, 60.2, 51.0, 28.0, 25.3, 20.1, 20.0. MS (EI) m/z:
as potassium bromide pellets or as liquid films between two 263, 231, 220, 175, 206, 135, 91. IR νmax(KBr)/cm−1: 2960, 2871,
potassium bromide pellets using a Bruker Vector 22 spectro- 1495, 1113, 761, 720.
meter. GC-MS was obtained using electron ionization (EI).
N,N-Dibenzyl-2-phenylethanethioamide (3f).17 Yield: 95%.
High-resolution mass spectra were obtained using an 1H NMR (400 MHz, CDCl3) δ 7.28–6.94 (m, 15H), 5.24 (d, J =
LCMS-IT-TOF mass spectrometer. TLC was performed using 5.9 Hz, 2H), 4.52 (d, J = 5.7 Hz, 2H), 4.29 (d, J = 5.9 Hz, 2H).
commercially prepared 100–400 mesh silica gel plates (GF254
)
13C NMR (100 MHz, CDCl3) δ 202.9, 135.8, 135.5, 134.7, 129.1,
and visualization was effected at 254 nm. All reagents were 128.8, 128.6, 128.0, 127.9, 127.9, 127.7, 127.1, 126.2, 55.4, 53.7,
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50.9. MS (EI) m/z: 331, 240, 206, 178, 135, 91. IR νmax(KBr)/ cm−1: 3022, 2924, 1489, 1152, 740, 712. HRMS (ESI) Calcd for
cm−1: 3028, 2924, 1490, 1152, 735, 697.
C12H15NNaS2 [M + Na]+ 260.0538, found m/z 260.0541.
N-Ethyl-2-phenyl-N-propylethanethioamide (3g). Yield: 89%,
1-(3,4-Dihydroisoquinolin-2(1H)-yl)-2-phenylethanethione
1 : 1 mixture of rotamers. Yellow liquid. 1H NMR (400 MHz, (3m). Yield: 69%, 2 : 1 mixture of rotamers. Yellow liquid. H
CDCl3) δ 7.32–7.21 (m, 10H), 4.29 (d, J = 3.1 Hz, 4H), 4.01 (q, NMR (400 MHz, CDCl3) (major rotamer) δ 7.34–6.80 (m, 8H),
J = 7.0 Hz, 2H), 3.89–3.85 (m, 2H), 3.48 (q, J = 7.1 Hz, 2H), 5.29 (s, 2H), 4.42 (s, 2H), 3.79 (t, J = 5.8 Hz, 2H), 2.61 (t, J =
3.38–3.34 (m, 2H), 1.83–1.73 (m, 2H), 1.57–1.48 (m, 2H), 1.27 5.8 Hz, 2H); 1H NMR (400 MHz, CDCl3) (minor rotamer)
(t, J = 7.0 Hz, 3H), 1.10 (t, J = 7.1 Hz, 3H), 0.93 (t, J = 7.4 Hz, δ 7.34–6.80 (m, 8H), 4.68 (s, 2H), 4.42 (s, 2H), 4.35 (t, J =
3H), 0.83 (t, J = 7.4 Hz, 3H). 13C NMR (100 MHz, CDCl3) 6.2 Hz, 2H), 2.97 (t, J = 6.2 Hz, 2H). 13C NMR (100 MHz,
δ 199.1, 199.0, 136.2, 136.2, 128.5, 128.5, 127.7, 127.7, 126.7, CDCl3) δ 199.4, 199.1, 135.6, 135.5, 134.9, 133.3, 132.3, 131.8,
126.7, 54.3, 53.3, 50.4, 50.4, 47.9, 46.9, 21.3, 18.9, 13.0, 11.1, 128.7, 128.7, 128.0, 127.8, 127.8, 127.7, 127.4, 126.8, 126.8,
10.9, 10.7. MS (EI) m/z: 221, 188, 146, 130, 118, 91. IR 126.8, 126.7, 126.5, 126.4, 125.7, 52.7, 51.6, 50.9, 49.1, 47.9,
νmax(KBr)/cm−1: 2967, 2932, 1500, 1104, 795, 712. HRMS (ESI) 29.0, 27.9. MS (EI) m/z: 267, 252, 234, 176, 132, 91. IR
1
Calcd for C13H19NS [M + H]+ 222.1311, found m/z 222.1324.
νmax(KBr)/cm−1: 3026, 2928, 1490, 1097, 740, 701. HRMS (ESI)
N-Benzyl-N-methyl-2-phenylethanethioamide
(3h). Yield: Calcd for C17H17NS [M + H]+ 268.1154, found m/z 268.1147.
90%, 1.1 : 1 mixture of rotamers. Yellow liquid. 1H NMR
N,N-Diethyl-2-p-tolylethanethioamide (4b). Yield: 85%.
(400 MHz, CDCl3) (major rotamer) δ 7.39–6.99 (m, 10H), 5.33 Yellow solid. MP = 62–64 °C. 1H NMR (400 MHz, CDCl3) δ 7.20
1
(s, 2H), 4.37 (s, 2H), 3.05 (s, 3H). H NMR (400 MHz, CDCl3) (d, J = 7.9 Hz, 2H), 7.11 (d, J = 7.9 Hz, 2H), 4.23 (s, 2H), 3.99 (q,
(minor rotamer) δ 7.39–6.99 (m, 10H), 4.72 (s, 2H), 4.35 (s, J = 7.1 Hz, 2H), 3.48 (q, J = 7.2 Hz, 2H), 2.32 (s, 3H), 1.27 (t, J =
2H), 3.41 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 201.7, 201.4, 7.1 Hz, 3H), 1.11 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz,
135.9, 135.4, 135.4, 134.7, 129.0, 128.7, 128.7, 128.6, 128.0, CDCl3) δ 199.2, 136.3, 133.2, 129.3, 127.6, 50.0, 47.5, 46.4, 20.9,
127.9, 127.9, 127.7, 127.7, 126.9, 126.9, 126.3, 58.5, 57.7, 51.0, 13.1, 10.8. MS (EI) m/z: 221, 188, 174, 159, 134, 116, 88. IR
50.6, 42.8, 39.1. MS (EI) m/z: 255, 223, 182, 146, 135, 91. IR νmax(KBr)/cm−1: 2975, 2930, 1506, 1097, 791. HRMS (ESI)
νmax(KBr)/cm−1: 3028, 2929, 1498, 1159, 728, 698. HRMS (ESI) Calcd for C13H19NS [M + H]+ 222.1311, found m/z 222.1314.
Calcd for C16H17NS [M + H]+ 256.1154, found m/z 256.1146.
N,N-Diethyl-2-(4-ethylphenyl)ethanethioamide (4c). Yield:
1
N-Benzyl-N-ethyl-2-phenylethanethioamide (3i). Yield: 91%, 87%. Yellow liquid. H NMR (400 MHz, CDCl3) δ 7.22 (d, J =
1
1.2 : 1 mixture of rotamers. Yellow liquid. H NMR (400 MHz, 7.9 Hz, 2H), 7.14 (d, J = 8.0 Hz, 2H), 4.25 (s, 2H), 4.00 (q, J =
CDCl3) (major rotamer) δ 7.40–7.04 (m, 10H), 4.65 (s, 2H), 4.27 7.1 Hz, 2H), 3.48 (q, J = 7.2 Hz, 2H), 2.62 (q, J = 7.6 Hz, 2H),
(s, 2H), 4.00 (q, J = 7.1 Hz, 2H), 1.24 (t, J = 7.1 Hz, 3H); 1H 1.28 (t, J = 7.1 Hz, 3H), 1.22 (t, J = 7.6 Hz, 3H), 1.11 (t, J =
NMR (400 MHz, CDCl3) (minor rotamer) δ 7.40–7.04 (m, 10H), 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 199.2, 142.8, 133.4,
5.34 (s, 2H), 4.39 (s, 2H), 3.47 (q, J = 7.2 Hz, 2H), 1.06 (t, J = 128.2, 127.7, 50.0, 47.6, 46.4, 28.4, 15.4, 13.2, 10.9. MS (EI) m/z:
7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 201.3, 200.6, 136.0, 235, 206, 202, 173, 135, 119, 116, 91. IR νmax(KBr)/cm−1: 2968,
135.9, 135.7, 134.9, 128.9, 128.7, 128.6, 128.5, 128.0, 127.8, 2931, 1505, 1097, 814. HRMS (ESI) Calcd for C14H21NS
127.7, 127.6, 127.5, 126.9, 126.8, 126.1, 54.8, 54.5, 50.8, 50.3, [M + H]+ 236.1467, found m/z 236.1476.
48.5, 45.7, 12.8, 10.5. MS (EI) m/z: 269, 236, 206, 178, 135, 91.
N,N-Diethyl-2-(4-methoxyphenyl)ethanethioamide (4d).20 Yield:
IR νmax(KBr)/cm−1: 3027, 2931, 1496, 1104, 728, 698. HRMS 67%. 1H NMR (400 MHz, CDCl3) δ 7.24 (d, J = 8.5 Hz, 2H), 6.85
(ESI) Calcd for C17H19NS [M + H]+ 270.1311, found m/z (d, J = 8.6 Hz, 2H), 4.21 (s, 2H), 3.99 (q, J = 7.1 Hz, 2H), 3.78 (s,
270.1324.
3H), 3.49 (q, J = 7.1 Hz, 2H), 1.27 (t, J = 7.1 Hz, 3H), 1.11 (t, J =
2-Phenyl-1-(pyrrolidin-1-yl)ethanethione (3j).18 Yield: 77%. 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 199.4, 158.4, 128.8,
1H NMR (400 MHz, CDCl3) δ 7.35–7.22 (m, 5H), 4.20 (s, 2H), 128.3, 114.1, 55.2, 49.6, 47.6, 46.3, 13.2, 10.8. MS (EI) m/z: 237,
3.86 (t, J = 6.3 Hz, 2H), 3.52 (t, J = 6.3 Hz, 2H), 1.91–1.99 (m, 204, 175, 164, 135, 121, 116, 91. IR νmax(KBr)/cm−1: 2933, 2835,
4H). 13C NMR (100 MHz, CDCl3) δ 196.8, 135.4, 128.5, 128.3, 1507, 1243, 1096, 1032, 815.
126.8, 54.0, 51.2, 50.8, 26.3, 24.2. MS (EI) m/z: 205, 172, 144,
114, 91. IR νmax(KBr)/cm−1: 2970, 2872, 1489, 1094, 759, 726.
2-(4-Ethoxyphenyl)-N,N-diethylethanethioamide (4e). Yield:
62%. Yellow liquid. H NMR (400 MHz, CDCl3) δ 7.23 (d, J =
1
1-Morpholino-2-phenylethanethione (3k).19 Yield: 63%. 1H 8.4 Hz, 2H), 6.84 (d, J = 8.5 Hz, 2H), 4.21 (s, 2H), 4.00 (p, J =
NMR (400 MHz, CDCl3) δ 7.23 (s, 4H), 7.17 (s, 1H), 4.27 (s, 6.9 Hz, 4H), 3.49 (q, J = 7.2 Hz, 2H), 1.40 (t, J = 7.0 Hz, 3H),
4H), 3.64 (s, 2H), 3.53 (s, 2H), 3.30 (s, 2H). 13C NMR (100 MHz, 1.27 (t, J = 7.0 Hz, 3H), 1.10 (t, J = 7.2 Hz, 3H). 13C NMR
CDCl3) δ 199.7, 135.6, 128.7, 127.6, 126.9, 66.1, 65.9, 50.6, 50.4, (100 MHz, CDCl3) δ 199.5, 157.9, 128.9, 128.1, 114.7, 63.4,
49.9. MS (EI) m/z: 221, 190, 162, 144, 135, 130, 91, 86, 77. IR 49.7, 47.6, 46.4, 14.8, 13.2, 10.9. MS (EI) m/z: 251, 218, 189,
νmax(KBr)/cm−1: 2967, 2855, 1488, 1111, 750, 707.
178, 160, 135, 116. IR νmax(KBr)/cm−1: 2977, 2931, 1507, 1238,
2-Phenyl-1-thiomorpholinoethanethione (3l). Yield: 66%. 1095, 1046, 814. HRMS (ESI) calcd for C14H21NOS [M + H]+
Yellow solid. MP = 98–100 °C. 1H NMR (400 MHz, CDCl3) δ 252.1417, found m/z 252.1420.
7.34–7.26 (s, 5H), 4.62–4.57 (m, 2H), 4.35 (s, 2H), 3.95–3.90 (m,
N,N-Diethyl-2-(4-fluorophenyl)ethanethioamide (4f). Yield:
2H), 2.76–2.71 (m, 2H), 2.26–2.21 (m, 2H). 13C NMR (100 MHz, 84%. Yellow liquid. 1H NMR (400 MHz, CDCl3) δ 7.32–7.28 (m,
CDCl3) δ 199.9, 135.6, 128.9, 127.8, 127.1, 53.0, 52.9, 51.0, 27.5, 2H), 7.00 (t, J = 8.6 Hz, 2H), 4.23 (s, 2H), 3.99 (q, J = 7.0 Hz,
26.9. MS (EI) m/z: 237, 204, 178, 144, 134, 91. IR νmax(KBr)/ 2H), 3.48 (q, J = 7.1 Hz, 2H), 1.27 (t, J = 7.0 Hz, 3H), 1.12
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(t, J = 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 198.6, 161.6 1.30–1.23 (m, 6H), 1.10 (t, J = 7.2 Hz, 3H), 1.05–0.98 (m, 2H),
(d, J = 243.7 Hz), 131.9 (d, J = 3.2 Hz), 129.3 (d, J = 7.8 Hz), 0.90 (t, J = 7.3 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 199.2,
115.4 (d, J = 21.2 Hz), 49.2, 47.5, 46.3, 13.1, 10.7. MS (EI) m/z: 146.4, 133.5, 127.6, 127.1, 50.0, 47.5, 46.4, 44.1, 39.0, 34.2,
225, 196, 192, 164, 153, 135, 116, 109. IR νmax(KBr)/cm−1: 2976, 33.1, 29.9, 13.1, 11.4, 10.9. MS (EI) m/z: 317, 284, 255, 244, 215,
2934, 1506, 1226, 1102, 823. HRMS (ESI) calcd for C12H16FNS 201, 173, 116, 72. IR νmax(KBr)/cm−1: 2922, 2850, 1505, 1099,
[M + H]+ 226.1060, found m/z 226.1062.
2-(4-Chlorophenyl)-N,N-diethylethanethioamide (4g).21 Yield: m/z 318.2264.
90%. 1H NMR (400 MHz, CDCl3) δ 7.27 (s, 4H), 4.22 (s, 2H),
N,N-Diethyl-2-(2,4-dimethylphenyl)ethanethioamide (4m). Yield:
807. HRMS (ESI) calcd for C20H31NS [M + H]+ 318.2250, found
1
3.99 (q, J = 7.0 Hz, 2H), 3.47 (q, J = 7.1 Hz, 2H), 1.27 (t, J = 89%. Yellow solid. MP = 72–74 °C. H NMR (400 MHz, CDCl3)
7.0 Hz, 3H), 1.13 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz, δ 7.04 (d, J = 7.7 Hz, 1H), 6.98–6.94 (m, 2H), 4.10 (s, 2H), 4.04
CDCl3) δ 198.3, 134.8, 132.6, 129.2, 128.7, 49.4, 47.6, 46.4, 13.2, (q, J = 7.0 Hz, 2H), 3.39 (q, J = 7.1 Hz, 2H), 2.28 (s, 3H), 2.21 (s,
10.8. MS (EI) m/z: 241, 243, 208, 181, 168, 134, 125. IR 3H), 1.32 (t, J = 7.1 Hz, 3H), 1.18 (t, J = 7.2 Hz, 3H). 13C NMR
νmax(KBr)/cm−1: 2976, 2933, 1498, 1093, 799.
(100 MHz, CDCl3) δ 199.6, 136.0, 135.2, 131.7, 130.8, 126.8,
2-(2-Chlorophenyl)-N,N-diethylethanethioamide (4h). Yield: 126.6, 47.4, 46.9, 46.3, 20.7, 19.3, 13.1, 10.7. MS (EI) m/z: 235,
87%. Yellow liquid. 1H NMR (400 MHz, CDCl3) δ 7.41–7.34 (m, 220, 202, 172, 133, 116, 91. IR νmax(KBr)/cm−1: 2973, 2931,
2H), 7.24–7.17 (m, 2H), 4.28 (s, 2H), 4.02 (q, J = 7.1 Hz, 2H), 1502, 1106, 928, 846, 719. HRMS (ESI) Calcd for C14H21NS
3.44 (q, J = 7.1 Hz, 2H), 1.29 (t, J = 7.1 Hz, 3H), 1.17 (t, J = 7.2 [M + H]+ 236.1467, found m/z 236.1477.
Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 198.0, 134.3, 133.2,
4-((Diethylthiocarbamoyl)methyl)benzamide
(4n). Yield:
129.1, 129.1, 128.0, 126.9, 47.5, 46.7, 46.4, 13.0, 10.7. MS (EI) 92%. Yellow solid. MP = 151–153 °C. 1H NMR (400 MHz,
m/z : 241, 206, 178, 158, 135, 125. IR νmax(KBr)/cm−1: 2976, CDCl3) δ 7.83 (d, J = 8.2 Hz, 2H), 7.73 (s, 1H), 7.40 (s, 1H), 7.34
2933, 1503, 1099, 754. HRMS (ESI) Calcd for C12H16ClNS (d, J = 8.2 Hz, 2H), 4.27 (s, 2H), 4.00 (q, J = 7.1 Hz, 2H), 3.47 (q,
[M + H]+ 242.0765, found m/z 242.0764.
J = 7.2 Hz, 2H), 1.28 (t, J = 7.1 Hz, 3H), 1.18 (t, J = 7.2 Hz, 3H).
2-(4-Bromophenyl)-N,N-diethylethanethioamide (4i). Yield: 13C NMR (100 MHz, CDCl3) δ 202.1, 197.9, 140.7, 137.7, 128.0,
1
88%. Yellow liquid. H NMR (400 MHz, CDCl3) δ 7.44 (d, J = 127.4, 49.7, 47.8, 46.6, 13.4, 10.9. MS (EI) m/z: 250, 232, 199,
8.4 Hz, 2H), 7.21 (d, J = 8.3 Hz, 2H), 4.21 (s, 2H), 3.99 (q, J = 160, 143, 116, 88. IR νmax(KBr)/cm−1: 3337, 3283, 3176, 3007,
7.1 Hz, 2H), 3.47 (q, J = 7.2 Hz, 2H), 1.27 (t, J = 7.1 Hz, 3H), 2975, 1629, 1519, 1424, 1232, 1090, 889. HRMS (ESI) Calcd for
1.14 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 198.3, C13H18N2NaOS [M + Na]+ 273.1032, found m/z 273.1027.
135.3, 131.8, 129.7, 120.7, 49.6, 47.7, 46.5, 13.3, 10.9. MS (EI)
m/z: 285, 287, 256, 252, 223, 168, 134, 116. IR νmax(KBr)/cm−1
N,N-Diethyl-2-(thiophen-2-yl)ethanethioamide (4o). Yield:
84%. Brown liquid. H NMR (400 MHz, CDCl3) δ 7.18 (dd, J =
1
:
2974, 2931, 1504, 1101, 793. HRMS (ESI) calcd for C12H16BrNS 4.0, 2.4 Hz, 1H), 6.94–6.92 (m, 2H), 4.40 (s, 2H), 3.98 (q, J =
[M + H]+ 286.0260, found m/z 286.0257.
7.1 Hz, 2H), 3.57 (q, J = 7.2 Hz, 2H), 1.26 (t, J = 7.1 Hz, 3H),
2-(4-Acetylphenyl)-N,N-diethylethanethioamide (4j). Yield: 1.18 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 197.7,
1
91%. Yellow liquid. H NMR (400 MHz, CDCl3) δ 7.92 (d, J = 138.2, 126.6, 125.2, 124.4, 47.7, 46.4, 45.0, 13.3, 10.7. MS (EI)
8.3 Hz, 2H), 7.43 (d, J = 8.4 Hz, 2H), 4.32 (s, 2H), 4.01 (q, J = m/z: 213, 180, 151, 140, 116, 88. IR νmax(KBr)/cm−1: 2975, 2932,
7.1 Hz, 2H), 3.48 (q, J = 7.2 Hz, 2H), 2.59 (s, 3H), 1.29 (t, J = 1507, 1467, 1289, 1229, 1097, 841, 700. HRMS (ESI) Calcd for
7.1 Hz, 3H), 1.15 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, C10H15NNaS2 [M + Na]+ 236.0538, found m/z 236.0534.
CDCl3) δ 197.9, 197.6, 141.9, 135.8, 128.7, 128.1, 50.0, 47.6,
N,N-Diethyl-2-(pyridin-2-yl)ethanethioamide
(4p). Yield:
46.5, 26.5, 13.3, 10.8. MS (EI) m/z: 249, 216, 160, 133, 116, 88. 87%. Brown liquid. 1H NMR (400 MHz, CDCl3) δ 8.51 (d, J =
IR νmax(KBr)/cm−1: 2795, 2933, 1681, 1605, 1505, 1426, 1357, 4.8 Hz, 1H), 7.68–7.63 (m, 1H), 7.59 (d, J = 7.8 Hz, 1H),
1267, 1098, 810. HRMS (ESI) calcd for C14H19NNaOS [M + Na]+ 7.19–7.16 (m, 1H), 4.44 (s, 2H), 4.00 (q, J = 7.1 Hz, 2H), 3.72 (q,
272.1080, found m/z 272.1075.
J = 7.2 Hz, 2H), 1.26 (t, J = 7.1 Hz, 3H), 1.16 (t, J = 7.2 Hz, 3H).
N,N-Diethyl-2-(3-hydroxyphenyl)ethanethioamide (4k). Yield: 13C NMR (100 MHz, CDCl3) δ 197.6, 156.7, 149.1, 136.6, 123.0,
68%. Yellow liquid. 1H NMR (400 MHz, CDCl3) δ 7.16 (t, J = 122.0, 52.9, 47.6, 46.7, 13.2, 10.8. MS (EI) m/z: 208, 175, 136,
7.9 Hz, 1H), 6.90 (s, 1H), 6.82 (d, J = 7.6 Hz, 1H), 6.72 (dd, J = 119, 93, 72. IR νmax(KBr)/cm−1: 2974, 2932, 1588, 1507, 1472,
8.1, 2.1 Hz, 1H), 4.23 (s, 2H), 3.99 (q, J = 7.1 Hz, 2H), 3.48 (q, 1429, 1290, 1212, 1103, 842, 751. HRMS (ESI) Calcd for
J = 7.2 Hz, 2H), 1.29 (t, J = 7.1 Hz, 3H), 1.12 (t, J = 7.2 Hz, 3H). C11H16N2NaS [M + Na]+ 231.0926, found m/z 231.0924.
13C NMR (100 MHz, CDCl3) δ 198.7, 156.2, 137.8, 129.9, 120.2,
2-Phenyl-N-propylethanethioamide (5a).22 Yield: 67%. 1H
114.6, 114.0, 50.2, 47.7, 46.6, 13.2, 10.9. MS (EI) m/z: 223, 190, NMR (400 MHz, CDCl3) δ 7.40–7.25 (m, 5H), 7.12 (s, 1H), 4.12
162, 133, 116, 88, 77. IR νmax(KBr)/cm−1: 3300, 2976, 2933, (s, 2H), 3.58 (q, J = 6.7 Hz, 2H), 1.61–1.52 (m, 2H), 0.85 (t, J =
1591, 1512, 1453, 1287, 1232, 1099, 782. HRMS (ESI) calcd for 7.4 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 201.7, 134.8, 129.4,
C12H17NNaOS [M + Na]+ 246.0923, found m/z 246.0919.
129.1, 127.7, 53.0, 47.7, 21.0, 11.1. MS (EI) m/z: 193, 179, 160,
N,N-Diethyl-2-(4-(4-ethylcyclohexyl)phenyl)ethanethioamide 135, 102, 91. IR νmax(KBr)/cm−1: 3241, 2963, 2932, 1532, 1455,
(4l). Yield: 80%. Yellow liquid. 1H NMR (400 MHz, CDCl3) δ 1409, 1093, 705.
7.22 (d, J = 8.0 Hz, 2H), 7.14 (d, J = 8.1 Hz, 2H), 4.24 (s, 2H),
N-Isopropyl-2-phenylethanethioamide (5b).23 Yield: 52%. 1H
3.99 (q, J = 7.1 Hz, 2H), 3.48 (q, J = 7.1 Hz, 2H), 2.43 (t, J = NMR (400 MHz, CDCl3) δ 7.40–7.30 (m 3H), 7.24 (d, J = 7.1 Hz,
12.2 Hz, 1H), 1.87 (d, J = 11.1 Hz, 4H), 1.47–1.38 (m, 2H), 2H), 6.80 (s, 1H), 4.69–4.60 (m, 1H), 4.09 (s, 2H), 1.15 (d, J =
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6.5 Hz, 6H). 13C NMR (100 MHz, CDCl3) δ 200.3, 134.9, 129.4, (100 MHz, CDCl3) δ 201.5, 134.8, 129.4, 129.1, 127.7, 53.0,
129.2, 127.8, 53.3, 47.5, 21.1. MS (EI) m/z: 193, 160, 134, 118, 46.1, 31.1, 27.5, 26.3, 22.3, 13.8. MS (EI) m/z: 235, 202, 178,
102, 91. IR νmax(KBr)/cm−1: 3238, 2971, 2929, 1527, 1455, 1411, 165, 135, 118, 91. IR νmax(KBr)/cm−1: 3238, 2928, 2859, 1532,
1093, 763, 707.
1456, 1409, 1101, 768, 705.
N-Butyl-2-phenylethanethioamide (5c).13 Yield: 76%. 1H
4-(3,4-Diphenylthiophen-2-yl)morpholine (6).26 Yield: 75%.
NMR (400 MHz, CDCl3) δ 7.39–7.30 (m, 3H), 7.25 (d, J = 6.7 Hz, 1H NMR (400 MHz, CDCl3) δ 7.27–7.16 (m, 8H), 7.10–7.06 (m,
2H), 7.10 (s, 1H), 4.12 (s, 2H), 3.61 (q, J = 6.7 Hz, 2H), 2H), 6.85 (s, 1H), 3.66–3.64 (m, 4H), 2.87–2.85 (m, 4H). 13C
1.55–1.48 (m, 2H), 1.31–1.21 (m, 2H), 0.87 (t, J = 7.4 Hz, 3H). NMR (100 MHz, CDCl3) δ 154.8, 142.0, 137.3, 135.6, 130.3,
13C NMR (100 MHz, CDCl3) δ 201.6, 134.8, 129.4, 129.1, 127.7, 129.0, 128.3, 128.0, 127.9, 126.6, 126.4, 114.0, 66.8, 53.2. MS
53.0, 45.8, 29.7, 19.9, 13.5. MS (EI) m/z: 207, 174, 135, 116, 91. (EI) m/z: 321, 262, 248, 202, 130, 77.
IR νmax(KBr)/cm−1: 3239, 2959, 2931, 1532, 1456, 1409, 1096,
N,N-Diethyl-2-oxo-2-phenylacetamide (7).27 Yield: 81%. 1H
NMR (400 MHz, CDCl3) δ 7.95–7.93 (m, 2H), 7.63 (t, J = 7.4 Hz,
769, 705.
N-sec-Butyl-2-phenylethanethioamide (5d).23 Yield: 61%. 1H), 7.51 (t, J = 7.7 Hz, 2H), 3.57 (q, J = 7.2 Hz, 2H), 3.25 (q, J =
1H NMR (400 MHz, CDCl3) δ 7.39–7.30 (m, 3H), 7.25 (d, J = 7.1 Hz, 2H), 1.29 (t, J = 7.2 Hz, 3H), 1.16 (t, J = 7.1 Hz, 3H). 13
C
7.0 Hz, 2H), 6.83 (s, 1H), 4.54–4.48 (m, 1H), 4.11 (q, J = NMR (100 MHz, CDCl3) δ 191.5, 166.7, 134.5, 133.2, 129.6,
16.4 Hz, 2H), 1.51–1.45 (m, 2H), 1.12 (d, J = 6.4 Hz, 3H), 128.9, 42.1, 38.7, 14.1, 12.8. MS (EI) m/z: 205, 177, 148, 133,
0.80 (t, J = 7.3 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 200.6, 100, 77.
134.9, 129.3, 129.1, 127.7, 53.3, 52.6, 28.2, 18.5, 9.9. MS (EI)
m/z: 207, 179, 152, 135, 116, 91. IR νmax(KBr)/cm−1: 3238, 2967,
2930, 1527, 1453, 1411, 1094, 761, 705.
Acknowledgements
N-Isobutyl-2-phenylethanethioamide (5e).24 Yield: 64%. 1H
NMR (400 MHz, CDCl3) δ 7.40–7.30 (m, 3H), 7.26 (d, J = 7.0 Hz, We are grateful to the National Natural Science Foundation of
2H), 7.16 (s, 1H), 4.14 (s, 2H), 3.44 (t, J = 6.2 Hz, 2H), 1.93–1.83 China (20932002, 21172076 and 21202046), the National Basic
(m, 1H), 0.82 (d, J = 6.7 Hz, 6H). 13C NMR (100 MHz, CDCl3) δ Research Program of China (973 Program) (2011CB808600),
201.7, 134.7, 129.4, 129.1, 127.8, 53.1, 53.0, 27.1, 19.9. MS (EI) the
Guangdong
Natural
Science
Foundation
m/z: 207, 192, 164, 135, 118, 91. IR νmax(KBr)/cm−1: 3245, 2959, (10351064101000000 and S2012040007088), and the China
2927, 1532, 1459, 1410, 1101, 769, 705.
Postdoctoral Science Foundation (2012T50673).
N-tert-Butyl-2-phenylethanethioamide (5f). Yield: 45%.
Yellow solid. MP = 71–73 °C. 1H NMR (400 MHz, CDCl3) δ 7.38
(t, J = 7.2 Hz, 2H), 7.32 (t, J = 7.3 Hz, 1H), 7.24 (d, J = 6.9 Hz,
2H), 6.80 (s, 1H), 4.06 (s, 2H), 1.45 (s, 9H). 13C NMR (100 MHz,
CDCl3) δ 200.6, 135.4, 129.4, 129.2, 127.7, 55.8, 55.7, 27.5. MS
(EI) m/z: 207, 151, 134, 117, 92, 65. IR νmax(KBr)/cm−1: 3343,
2968, 2925, 1525, 1415, 1363, 1211, 1113, 748, 699. HRMS
(ESI) Calcd for C12H17NNaS [M + Na]+ 230.0974, found m/z
230.0969.
Notes and references
1 (a) S. P. Ebert, B. Wetzel, R. L. Myette, G. Conseil,
S. P. C. Cole, G. A. Sawada, T. W. Loo, M. C. Bartlett,
D. M. Clarke and M. R. Detty, J. Med. Chem., 2012, 55,
4683; (b) P. Angehrn, E. Goetschi, H. Gmuender,
P. Hebeisen, M. Hennig, B. Kuhn, T. Luebbers, P. Reindl,
F. Ricklin and A. Schmitt-Hoffmann, J. Med. Chem., 2011,
54, 2207.
2 (a) Y. Suzuki, R. Yazaki, N. Kumagai and M. Shibasaki,
Angew. Chem., Int. Ed., 2009, 48, 5026; (b) M. Iwata,
R. Yazaki, I. H. Chen, D. Sureshkumar, N. Kumagai and
M. Shibasaki, J. Am. Chem. Soc., 2011, 133, 5554;
(c) H. Prokopcová and C. O. Kappe, J. Org. Chem., 2007, 72,
4440.
1
N-Isopentyl-2-phenylethanethioamide (5g).24 Yield: 56%. H
NMR (400 MHz, CDCl3) δ 7.40–7.31 (m, 3H), 7.24 (d, J = 6.9 Hz,
2H), 6.98 (s, 1H), 4.12 (s, 2H), 3.62 (q, J = 6.7 Hz, 2H),
1.56–1.46 (m, 1H), 1.40 (q, J = 7.2 Hz, 2H), 0.86 (d, J = 6.5 Hz,
6H). 13C NMR (100 MHz, CDCl3) δ 201.5, 134.8, 129.5, 129.2,
127.8, 53.1, 44.6, 36.5, 26.0, 22.3. MS (EI) m/z: 221, 178, 165,
135, 91. IR νmax(KBr)/cm−1: 3203, 3065, 2956, 1545, 1460, 1414,
1096, 764, 708.
N-Cyclohexyl-2-phenylethanethioamide (5h).25 Yield: 84%.
1H NMR (400 MHz, CDCl3) δ 7.37–7.28 (m, 3H), 7.24 (d, J =
7.2 Hz, 1H), 7.11 (s, 1H), 4.40–4.32 (m, 1H), 4.07 (s, 2H),
1.97–1.93 (m, 2H), 1.61–1.56 (m, 3H), 1.39–1.30 (m, 2H),
1.19–1.08 (m, 3H). 13C NMR (100 MHz, CDCl3) δ 199.9, 134.9,
129.1, 128.9, 127.5, 53.9, 53.0, 30.9, 25.1, 24.1. MS (EI) m/z:
233, 200, 176, 152, 135, 98, 91. IR νmax(KBr)/cm−1: 3235, 2931,
2854, 1527, 1489, 1411, 1113, 769, 719.
3 T. S. Jagodziński, Chem. Rev., 2003, 103, 197.
4 (a) M. Lim, W. Ren and R. S. Klein, J. Org. Chem., 1982, 47,
4595; (b) J. Hwang, M. G. Choi, S. Eor and S. Chang, Inorg.
Chem., 2012, 51, 1634; (c) R. C. Moreau, P. Loiseau,
E. G. Vairel and E. Sache, Eur. J. Med. Chem., 1977, 12, 365;
(d) T. Ozturk, E. Ertas and O. Mert, Chem. Rev., 2007, 107,
5210.
5 (a) T. Curphey, J. Org. Chem., 2002, 67, 6461;
(b) J. Bergman, B. Pettersson, V. Hasimbegovic and
P. H. Svensson, J. Org. Chem., 2011, 76, 1546; (c) Z. Kaleta,
B. T. Makowski, T. Soós and R. Dembinski, Org. Lett., 2006,
8, 1625; (d) S. Coats, J. S. Link and D. Hlasta, Org. Lett.,
N-Hexyl-2-phenylethanethioamide (5i).25 Yield: 85%. 1H NMR
(400 MHz, CDCl3) δ 7.39–7.30 (m, 3H), 7.25 (d, J = 6.8 Hz, 2H),
7.11 (s, 1H), 4.12 (s, 2H), 3.60 (q, J = 6.7 Hz, 2H), 1.56–1.49 (m,
2H), 1.28–1.22 (m, 6H), 0.85 (t, J = 6.8 Hz, 3H). 13C NMR
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2003, 5, 721; (e) C. T. Brain, A. Hallett and S. Y. Ko, J. Org. 12 (a) K. A. DeKorver, H. Li, A. G. Lohse, R. Hayashi, Z. Lu,
Chem., 1997, 62, 3808; (f) A. B. Charette and M. J. Grenon,
Org. Chem., 2003, 68, 5792; (g) F. Shibahara, R. Sugiura and
T. Murai, Org. Lett., 2009, 11, 3064; (h) M. Szostak and
J. Aubé, Chem. Commun., 2009, 7122.
Y. Zhang and R. P. Hsung, Chem. Rev., 2007, 110, 5064;
(b) G. Evano, A. Coste and K. Jouvin, Angew. Chem., Int. Ed.,
2010, 49, 2840.
13 E. C. Kornfeld, J. Org. Chem., 1951, 16, 131.
6 (a) K. Okamoto, T. Yamamoto and T. Kanbara, Synlett, 14 D. A. Androsov, M. L. Petrov and A. A. Shchipalkin,
2007, 2687; (b) O. I. Zbruyev, N. Stiasni and C. O. Kappe,
J. Comb. Chem., 2003, 5, 145.
7 T. B. Nguyen, L. Ermolenko and A. Al-Mourabit, Org. Lett.,
2012, 14, 4274.
Russ. J. Org. Chem., 2007, 43, 1870.
15 A. B. Kuliev, M. M. Dzhavadov and F. A. Kuliev, Neftekhi-
miya, 1981, 21, 299.
16 R. Mukherjee, Indian J. Chem., Sect. B, 1977, 15B, 502.
8 (a) A. Trofimov, N. Chernyak and V. Gevorgyan, J. Am. 17 W. Walter and O. H. Bauer, Liebigs Ann., 1976 (9), 1584.
Chem. Soc., 2008, 130, 13538; (b) Y. Weng, B. Cheng, C. He 18 R. J. Sundberg, C. P. Walters and J. D. Bloom, J. Org. Chem.,
and A. Lei, Angew. Chem., Int. Ed., 2012, 51, 9547.
9 (a) Y. Li, X. Liu, H. Jiang and Z. Feng, Angew. Chem., Int. 19 F. M. Moghaddam, H. Z. Boeini, M. Bagheri, P. Ruedi and
Ed., 2010, 49, 3338; (b) Y. Li, X. Liu, H. Jiang, B. Liu, A. Linden, J. Sulfur. Chem., 2005, 26, 245.
1981, 46, 3730.
Z. Chen and P. Zhou, Angew. Chem., Int. Ed., 2011, 50, 6341; 20 K. Kindler, Liebigs Ann., 1923, 431, 187.
(c) Z. Chen, H. Jiang, A. Wang and S. Yang, J. Org. Chem., 21 A. B. Kuliev, M. M. Kurbanov, F. Yu. Aliev and F. A. Kuliev,
2010, 75, 6700; (d) Z. Chen, H. Jiang, Y. Li and C. Qi, Chem.
Neftekhimiya, 1983, 23, 268.
Commun., 2010, 46, 8049; (e) Z. Chen, J. Li, H. Jiang, 22 P. Yates and L. L. Williams, Tetrahedron Lett., 1968, 9, 1205.
S. Zhu, Y. Li and C. Qi, Org. Lett., 2010, 12, 3262.
10 (a) T. Hamada, X. Ye and S. S. Stahl, J. Am. Chem. Soc.,
23 T. Lundstedt, R. Carlson and R. Shabana, Acta Chem.
Scand. Ser. B, 1987, B41, 157.
2008, 130, 833; (b) K. Jouvin, A. Coste, A. Bayle, F. Legrand, 24 M. Z. Terada, Physiol. Chem., 1927, 170, 289.
G. Karthikeyan, K. Tadiparthi and G. Evano, Organometal- 25 P. Reynaud, Patent FR, 1466416, 1967.
lics, 2012, 31, 7933.
26 O. Zeika and H. Hartmann, Tetrahedron, 2004, 60, 8213.
11 B. Gabriele, R. Mancuso, G. Salerno and R. C. Larock, 27 J. Liu, R. Zhang, S. Wang, W. Sun and C. Xia, Org. Lett.,
J. Org. Chem., 2012, 77, 7640.
2009, 11, 1321.
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