Regioselectivity, scope, and limitations of the addition of organolithium and allylmagnesium reagents to 1H-pyridine-2-thiones; access to 3,4-, 3,6-, and 5,6-dihydropyridine-2-thiones

Article abstract of DOI:10.1016/j.tet.2007.09.029

Organolithium and lithium allyldibutylmagnesate reagents add to readily available NH, NMe, NBn, and NPh substituted pyridine-2-thiones yielding 4- and/or 6-substituted 3,4- or 3,6-dihydropyridine-2-thiones, respectively. The regioselectivity of the additi

Full text of DOI:10.1016/j.tet.2007.09.029

Tetrahedron 63 (2007) 11862–11877
Regioselectivity, scope, and limitations of the addition of
organolithium and allylmagnesium reagents to 1H-pyridine-2-
thiones; access to 3,4-, 3,6-, and 5,6-dihydropyridine-2-thiones
*
ꢀ
Jacek G. Sosnicki
Szczecin University of Technology, Institute of Chemistry and Environmental Protection, Al. Piastoꢀw 42, PL-71065 Szczecin, Poland
Received 14 July 2007; revised 31 August 2007; accepted 13 September 2007
Available online 22 September 2007
Abstract—Organolithium and lithium allyldibutylmagnesate reagents add to readily available NH, NMe, NBn, and NPh substituted pyridine-
2-thiones yielding 4- and/or 6-substituted 3,4- or 3,6-dihydropyridine-2-thiones, respectively. The regioselectivity of the addition is dependent
on the solvent, temperature, substituent at the nitrogen, and the type or organometallic reactant used, and allows tailoring of both systems. A
simple conversion of 6-substituted b,g-unsaturated d-thiolactams into their a,b-unsaturated isomers makes the above processes a highly
versatile synthetic methodology to access 6-substituted 5,6-dihydropyridine-2-thiones—valuable Michael acceptors.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
Recently, regioselective 1,6-allylation of nonactivated
N-allyl 2-pyridones by using lithium allydibutylmagnesium
‘ate’ complex was described as the first step in the synthesis
in quinolizidines.11
The piperidine ring occurs in a number of pharmaceuticals
and natural products. Due to the wide range of biological ac-
tivities1 associated with the piperidine moiety, the synthesis
of multifunctionalized piperidines is still an attractive syn-
thetic enterprise.2 In the functionalization of the piperidine
ring, 1,4-nucleophilic addition is often used to introduce
a new functionality. This synthetic approach is readily
employed in a,b-unsaturated 2-,3 3-4 or 4-piperidinones.5
Amongst the reactions leading to unsaturated piperidinones
from the derivatives of pyridine, those using nucleophilic
addition of organometallics to N-acyl activated 4-alkoxypyr-
idines yielding unsaturated 4-piperidinones have been the
most commonly undertaken,6 while the straightforward nu-
cleophilic addition of organometallic reagents to pyridones
has enjoyed less interest. The addition of organolithium
reagents to NH 2-pyridone (2-hydroxypyridine) has been
described,7 while an example of the addition of tertiary
lithium compound to N-benzyl 2-pyridone is also known.8
In both cases, different regioselectivities, respectively, 1,6-
and 1,4-addition, were observed. Regioselective 1,4-
addition of Grignard reagents to N-galactosyl-2-pyridone
was performed after activation of the latter using triisopro-
pylsilyltrifluoromethanesulfonate (TIPSOTF).9 The intramole-
cular version of the 1,6-addition to 2-pyridone ring was also
applied in the synthesis of (+)-cytisine and (ꢀ)-anagyrine.10
In the last decade, a,b-unsaturated piperidine-2-thiones have
been recognized as Michael acceptors and several 1,4-
addition reactions of C-, N- and S-nucleophiles, affording
4-substituted d-thiolactams were reported.12 Moreover, the
interest in thiolactams still grows as their synthetic potential
lies in the highly convertible character of the C]S group,
which opens up possibilities of further functionalizations,13
also after the Michael addition step.12b,c
Exploring the concept of functionalization of the piperidine
ring via unsaturated d-thiolactams, we have recently pub-
lished two preliminary reports on the addition of organo-
metallics to 1H-pyridine-2-thiones as simple precursors.
One concerned the addition of n-BuLi to NH-substituted
pyridine-2-thione (commercially available as 2-mercapto-
pyridine).14 The addition product—3,6-dihydropyridine-2-
thione—was further submitted to stereoselective synthesis
of bicyclic 2-piperidinones, in which the DBU-catalyzed
Michael addition of 2-nitro-propane was the key step and
was performed without isolation of the intermediate 5,6-dihy-
dropyridine-2-thione. The second communication reported
the synthesis of unsaturated 4- and 6-allyl substituted d-thio-
lactams by addition of lithium allyldibutylmagnesate to
NH- and NMe substituted pyridine-2-thiones, respectively.15
Keywords: Pyridine-2-thiones; Dihydropyridine-2-thiones; Organolithium
reagents; Lithium allyldibutylmagnesates; Regioselectivity; Addition.
* Tel.: +48 91 4494798; fax: +48 91 4494639; e-mail: sosnicki@ps.pl
In continuation of our ongoing program aimed at the devel-
opment of a general approach to polysubstituted piperidines
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.09.029

J. G. Soꢀsnicki / Tetrahedron 63 (2007) 11862–11877
11863
from readily available starting materials, we now report a de-
tailed study on the application of NH (1), NMe (2), NBn (3),
and NPh (4) substituted derivatives of 1H-pyridine-2-thiones
in the reaction with a broad spectrum of organolithium
reagents (alkyl- allyl- and phenyl derivatives). The investi-
gation of the allylation reaction was extended by the
application of allyl-, 2-methylallyl-, and 3,3-dimethylallyl-
magnesium reagents comprising standard Grignard reagents
and lithium allyldibutylmagnesates.15 The application of the
allylmagnesates aimed at checking their further usefulness
in allylation reactions in comparison to standard allylmagne-
sium and allyllithium derivatives. Finally, as the double bond
in b,g-unsaturated thioamides was recognized to be easily
moved from b,g- to a,b-position12b,16and a,b-unsaturated
d-thiolactam (5,6-dihydropyridine-2-thiones) were proved
to be valuable substrates in the 1,4-nucleophilic additions re-
actions, we present a simple synthesis of 6-substituted a,b-
unsaturated precursors by simple isomerization of obtained
3,6-dihydropyridine-2-thiones, using DBU as base. So far,
5,6-dihydropyridine-2-thiones were obtained from acy-
clic ketothioamides,17a,b by thionation of appropriate 5,6-
dihydropyridine-2-ones12a or by dehydration of saturated
d-thiolactams.14,17c
Moreover, the color change was used to determine the
molarity of the organolithium solutions.
Lithium reagents applied in this study exhibited various
activities toward addition to NLi pyridine-2-thione (1Li).
Amongst them, t-BuLi in pentane was the most reactive
and due to its relatively short lifetime in ether at 0 ꢁC18 the
reaction was initiated at a low temperature before subse-
quently raising the temperature. In the remaining cases the
reactions were conducted at temperatures ranging from
0 to 20 ꢁC and were quenched after few hours. The pro-
longed reaction time and the use of more than 3-fold excess
of RLi reagent led to lower yields. With PhLi, the reaction
required 18 h of stirring at 20 ꢁC in Bu2O as a solvent (Table
1, entry 15). The use of Et2O resulted in lower yields (Table
1, entry 14). Surprisingly, MeLi was not reactive at all even
when the reagent was used in a 6-fold excess (Table 1, entry
1). The allylation reactions proceeded easily upon treatment
of 1Li with allyllithiums or lithium allyldibutylmagnesates,
providing 4-substituted isomers 6 in good yields (Table 1,
entry 16, 18–21). (Lithium allyldibutylmagnesates were pre-
pared simply by mixing 1 equiv of allylMgCl in THF and
2 equiv of n-BuLi in alkane.)15 Allylmagnesium chloride
was not reactive (Table 1, entry 17).
2. Results and discussion
As far as regioselectivity is concerned the investigated reac-
tions could be divided into three groups: the first group com-
prised the reactions with alkyllithium reagents (except
isobutyllithium), which gave regioselectively 6-substituted
addition products 5, especially when the reactions were con-
ducted in THF; the second group included the reactions with
t-BuLi, PhLi, and isobutyllithium, performed in Et2O or
Bu2O, which gave a mixture of 4- (6) and 6-substituted ad-
ducts (5). Allylation reactions belonging to the third group
gave 4-allyl substituted adducts regioselectively. The differ-
ent regioselectivity of allylation with respect to alkylation,
observed in the case of lithium allyl- and 2-methylallyldibu-
tylmagnesate reagents was proved to be the effect of Cope
rearrangement (Scheme 2).15 According to this process,
the more thermodynamically stable 4-allyl substituted prod-
uct forms from the primarily formed but less stable 6-allyl
isomer. The evidence of the above was achieved by monitor-
ing the reaction progress and by determination of the ratio of
isomers 5/6 at several time intervals. Quenching the reaction
after 0.5 h allowed the isolation of 5i in 13% yield (Table 1,
entry 18) and permitted a full spectroscopic analysis. The
same effect seemed to be true for applications of allyl-
lithiums. The formation of 6-substituted product was not
observed when using 3,3-dimethylallyldibutylmagnesate,
suggesting that the formation of 4-(1,1-dimethylallyl)-3,4-
dihydropyridine-2-thione as a sole product (6j) was caused
by steric effects (Table 1, entry 20).
2.1. Addition of organometallics to NH pyridine-2-thi-
one (1)
At the first stage of our study, we investigated the NH-
substituted 1H-pyridine-2-thione (1) in reaction with alkyl-,
allyl- and phenyllithium reagents (Scheme 1). The results
and conditions are presented in Table 1. RLi of 2–3 equiv,
with respect to NH pyridine-2-thione (1), was required in or-
der to obtain product 5 and/or 6 in optimum yields. The first
equivalent of RLi converted 1 into the lithiated salt 1Li and
the second one induced the addition yielding 6- (5) or 4-
addition products (6) (Scheme 1, Table 1). The lithium salt
1Li, formed in THF, is colorless and the appearance of yellow
color indicated that an excess of RLi was added and that
the complete conversion of 1 into salt 1Li took place. This
titration-like effect allowed the use of the available (or
the cheapest) organolithium reagent—mostly n-BuLi—as
the first lithium reagent and thus minimized the use of the
more expensive organolithium reagents. This operation
was applied in the addition of ethyllithium and allyllithium
derivatives (Table 1, entries 2 and 16–21, respectively).
R
1. RM
1. RM
+
2. aq. NH4Cl
S
2. aq. NH4Cl
S
N
Li
1Li
N
S
R
N
S
N
R1
2-4
R1
5
R1
6
As mentioned earlier, solvent was another factor affecting
the regioselectivity. In general, the reactions performed in
THF were the most regioselective, providing more amounts
of 6-adducts, while those performed in Et2O (Table 1, entry
5, 7, 9, and 10) and the one in toluene (Table 1, entry 6) were
less selective.
R1=Me (2); Bn (3); Ph (4)
DBU
RLi - RH
N
S
R
N
R1
8
S
H
1
In the case of sec-BuLi, the addition was not diastereoselec-
tive and provided products in 1:1 ratio of diastereoisomers
(Table 1, entry 11).
Scheme 1.

11864
J. G. Soꢀsnicki / Tetrahedron 63 (2007) 11862–11877
Table 1. Reaction conditions, ratios, and yields of 5/6 obtained in addition reactions of 1 with organolithium and organomagnesium reagents
Entry
1.
RM
RM (equiv)
3–6
Solvent
Temp
[ꢁC]
Time Ratio of 5/6 in the Ratio of 5/6 Conversion Total yields
isolated
[h]
crude mixturea
of 1a [%] of 5 and 6 [%]
Li
THF/cumene
20
24
—
—
0
0
1 BuLi
1.4
Li
Li
2.
3.
THF/Bu2O/hexane ꢂ5
2.5
99:1
94:6
99:1
>99
>99
73
61
a
2.5
3
Bu2O
0
1.5
95d:5
Li
Li
4.
5.
THF/hexane
Et2O/hexane
0–2
0–2
2
2
>99:1
98:2
92:8
95
93
73
63
b 2
2.3
90:10
0
20
0.5
2
Li
6.
7.
Toluene
81:19
80:20
82
42
0–2
20
0.25
2
b
Li
c 2.8
Et2O/hexane
75:25
97:3
78:22
98:2
69
95
37
55
Li
Li
8.
9.
3
d
3
THF/hexane
Et2O/hexane
0–2
0–2
2.5
3
91: 9
67:33
90:10
51:49
71
37
29
b
c
10.
11.
e 2.5
Et2O/pentane
THF/C6H12
20
1
1
100
Li
f
3
0–2
98:2
97:3
>99:1
70
86
57
50
Li
ꢂ60
0.3
1.25
12.
13.
14.
15.
16.
17.
2.2
2.2
2.1
2
THF/pentane
Et2O/pentane
Et2O/Bu2O
Bu2O
Li
ꢂ60 to 0
98:2
g
ꢂ78
1
1
Li
ꢂ78 to 20
63:37
65:35
60:40
100
100
83
19
Li
20
24
ca. 74:26
h
20
18
2
ca. 54:46
0:100
48:52
0:100
58
98
31
72
Li
1 BuLi
1.3 AllylLi
e
Li
THF/hexane
THF/hexane
0–2
1 BuLi
1.3 AllylMgCl
0
rt
0
5
24
0.2
0.5
0.5
1.0
3.5
MgCl
i
—
—
0
0
73:27
49:51
22:78
5:95
1 BuLi
1.3 Allyl-
MgBu2Li
0
41:59
ca. 35
31
MgBu2Li
18.
THF/hexane
rt
rt
rt
0:100
0:100
0:100
>99
80
60
e,f
Li
1 BuLi
1.3 3,3-dimethylallylLi
19.
20.
THF/hexane
THF/hexane
0–2
2.5
0:100
100
j
1 BuLi
1.3 3,3-dimethyl-
allylMgBu2Li
0
rt
0.2
0.5
>1:99
>1:99
f
MgBu2Li
0:100
>99
>99
65
0
0
0.2
1.0
2.0
3.0
90:10
70:30
6:94
1 BuLi
1.3 2-methyl-
allylMgBu2Li
21.
k
MgBu2Li
THF/hexane
rt
rt
0:100
0:100
74
Estimated using 1H NMR spectroscopy.
RLi obtained in the reaction of RI with 2 t-BuLi.22
1:1 mixture of diastereomers.
Partly converted to a,b-unsaturated isomer.
Allyllithium prepared from AllylBu3Sn (see Section 4).
1,1-Dimethylallyl substituent is in the product.
a
b
c
d
e
f
2.2. Addition of organometallics to N-substituted
pyridine-2-thione 2–4
regioselectivity toward the organometallics tested in com-
parison than NH- substituted pyridine-2-thione 1 (Table 2,
Scheme 1). Primary and secondary alkyllithium, and phenyl-
lithium reagents were not sufficiently reactive to produce ad-
ducts. Only n-BuLi gave a 4-adduct in moderate yield in the
In general, the N-substituted 1H-pyridine-2-thiones 2–4
were characterized by a different type of reactivity and

J. G. Soꢀsnicki / Tetrahedron 63 (2007) 11862–11877
11865
R
R
R
Bu
Mg
Bu
Li
R
S
N
Li
S
R
N
Li
S
N
Li
S
N
-LiCl
Li
1Li
H3O+
H3O+
MgCl + 2n-BLi
Cope [3,3] sigmatropic
rearrangment
5i,k
6i,k
R = H, Me
Scheme 2.
Table 2. Reaction conditions, ratios, and yields of 5/6 obtained in addition reaction of 2–4 with organolithium and organomagnesium reagents
Entry R1
RM
RM
(equiv)
Solvent
Temp [ꢁC] Time Ratio of 5/6 in
[min] the crude
Ratio of 5/6 Conversion Total yields
isolated
2–4a [%]
of 5 and 6 [%]
mixturea
Li
1.
2.
Bn
1.3
1.2
THF/Et2O
ꢂ60 to rt
1.5
60
—
—
—
w10
0
0
Li
THF/hexane
0
Complex mixture
80
Me
b
Li
Li
Li
3.
4.
5.
1.3
1.5
1.1
THF/hexane ꢂ60
THF/hexane
60
30
30
—
0c:100
30
99
95
Traces
15
Bn
Ph
l
0
20:80
m
THF/hexane
0
>1:99
0:100
37
b
6.
7.
8.
9.
Med
Bn
Ph
n
o
p
1.2
1.2
1.2
1.3
THF/hexane ꢂ60
THF/hexane ꢂ60
THF/hexane ꢂ60
0.25
2:98
0:100
11:89
—
w80
>99
>99
5
35
81
83
0
Li
0.25
0.25
0.5
1:99
12:88
—
Li
Li
Bn
Bu2O/THF
ꢂ60
Li
e
e
Li
Li
10.
11.
12.
13.
14.
1.2
THF/hexane
0
30
72:28
95:5
71:29
95:5
81
95
45
86
64
80
75
1.2
THF/hexane ꢂ70
THF
30
40
30
30
MgCl
Me
q
1.6
0
96:4
94:6
88
MgBu2Li
MgBu2Li
1.05
1.05
THF/hexane
0
85:15
>99:1
84:16
100:0
100
85
THF/hexane ꢂ72
THF/hexane
THF/hexane ꢂ70
e
Li
15.
16.
17.
18.
19.
1.2
0
15
15
40
30
30
56:44
96:4
56:44
97:3
>99
>99
85
75
87
70
79
88
Li
1.2
MgCI
Bn
r
1.6
THF
0
69:31
68:32
97:3
70:30
67:33
96:4
MgBu2Li
MgBu2Li
1.30
1.10
THF/hexane
0
100
100
THF/hexane ꢂ72
THF/hexane
THF/hexane ꢂ70
e
Li
20.
21.
22.
23.
24.
1.3
1.2
1.5
1.1
1.25
0
30
30
40
40
30
15:85
52:48
27:73f
20:80f
71:24
14:86
53:47
30:70
28:72
73:27
92
>99
98
69
91
68
85
96
e
Li
MgCI
Ph
s
THF
0
MgBu2Li
MgBu2Li
THF/hexane
0
99
THF/hexane ꢂ72
99
25.
26.
27.
1.5
THF
0
40
30
60
65:35
77:23
98:2
64:36
77:23
98:2
99
99
91
75
74
80
MgCI
Me
t
1.2
THF/hexane
0
MgBu2Li
MgBu2Li
1.15
THF/hexane ꢂ72
(continued)

11866
J. G. Soꢀsnicki / Tetrahedron 63 (2007) 11862–11877
Table 2. (continued)
Entry R1
RM
RM
(equiv)
Solvent
Temp [ꢁC] Time Ratio of 5/6 in
[min] the crude
Ratio of 5/6 Conversion Total yields
isolated
2–4a [%]
of 5 and 6 [%]
mixturea
28.
1.4
THF
0
0
30
20
45
60
39:61
58:42
84:16
95:5
38:62
57:43
84:16
96:4
86
91
67
76
90
87
MgCI
29.
Bn
30.
1.05
1.1
THF/hexane
MgBu2Li
MgBu2Li
MgBu2Li
u
THF/hexane ꢂ45
THF/hexane ꢂ72
100
95
31.
32.
1.05
1.5
THF
0
0
20
20
17:83
36:64
18:82
39:61
100
99
87
82
MgCI
33.
Ph
v
1.05
THF/hexane
MgBu2Li
34.
35.
1.1
1.3
THF/hexane ꢂ72
THF
30
60
66:34
3:97
68:32
3:97
91
87
76
79
MgBu2Li
MgCI
g
0
Me
Bn
w
x
g
g
MgBu2Li
36.
1.2
THF/hexane ꢂ72
THF
THF/hexane ꢂ72
THF
30
4:96
4:96
90
80
g
MgCI
37.
38.
1.3
1.3
0
60
15
>1:99
>1:99
0:100
0:100
90
99
72
78
MgBu2Li
g
MgCI
39.
1.3
1.2
0
30
15
>1:99
>1:99
0:100
0:100
>99
92
74
Ph
y
g
MgBu2Li
40.
THF/hexane ꢂ72
86
Estimated using 1H NMR spectroscopy.
Traces of the dimeric product was detected by GC–MS.
Product is present but could not be isolated in the pure state.
By-product 7e was isolated in 20% yield.
a
b
c
d
(dr ~ 9:1)
t-Bu
4'
3
6
N
N
S
S
7e
e
f
Allyllithium was prepared from AllylBu3Sn (see Section 4).
Could not be estimated with sufficient accuracy.
1,1-Dimethylallyl substituent is in the product.
g
reaction with NPh derivative 4 (Table 2, entry 5). tert-
Butyllithium and all applied allylation reagents afforded
products in satisfactory yield. However, amongst them, the
NMe derivative gave lower yields in some cases (allyl-
lithium 0 ꢁC, Table 2, entry 10; t-BuLi ꢂ60 ꢁC Table 2, entry
6) presumably due to the acidic character of the NCH2 pro-
tons, which led to undesired side-reactions in the presence of
strong bases (Table 2, entry 3, footnote b). In support of this,
small amounts of dimer with an introduced t-Bu group were
isolated from the products formed in the reaction between 2
and t-BuLi (Table 2, footnote, 7e). High acidity of CHsp3
group, adjacent to nitrogen was observed earlier when
N-methyl 2-pyridone was treated with n-BuLi19 and was
also applied in functionalization of (ꢂ)-cytisine at NCH.20
exhibited similar reactivity and reacted well also at low tem-
peratures, to give products 5 and 6 in good or very good
yields, in general. It should be noted that lithium allyldibu-
tylmagnesates exhibited lower basicity than allyllithum be-
cause it provided products 5q and 6q in good yield for
NMe derivative 2 at 0 ꢁC (Table 2, entry 13).
With respect to regioselectivity, the product distribution is
opposite to that observed for NH- substituted pyridine-2-thi-
one (1). The alkylation of N(alkyl, phenyl) substituted deri-
vatives led mainly to 4-substituted adduct 6, while their
allylation led mostly to a greater amount of 6-substituted
product 5. The quantity of the latter increased in the se-
quence of NPh, NBn, NMe substituted derivatives and
with decreasing temperature. Similarly to the reaction with
NH pyridine-2-thione (1) the reaction of 3,3-dimethylallyl-
magnesiumchloride and the corresponding magnesate with
2–4 gave mainly 4-(1,1-dimethylallyl) substituted isomers
Allylmagnesium chloride gave a positive result but only at
0 ꢁC. At a lower temperature (ca. ꢂ40 ꢁC) reaction did not
occur. Allyllithium and lithium allyldibutylmagnesates

J. G. Soꢀsnicki / Tetrahedron 63 (2007) 11862–11877
Table 3. Synthesis of 5,6-dihydropyridine-2-thiones 8
11867
availability, and reactivity similar to that of allyllithiums,
it can be used instead of allyllithium, whose application is
limited by less availability, higher cost, and toxicity of their
often used precursors—allyltin compounds.
Entry
R1
R
DBU
[equiv]
Time
[h]
Yield 8
[%]
1.
2.
3.
4.
5.
6.
7.
8.
a
b
c
d
e
f
g
h
i
j
k
l
m
n
H
H
H
H
H
H
H
H
Me
Bn
Ph
Me
Bn
Ph
Ethyl
n-Butyl
0.1
0.3
0.2
0.3
0.1
0.2
0.2
0.2
0.3
0.3
0.3
0.3
0.3
0.3
0.5
1
1
1
0.7
2
2.5
0.5
0.5
0.5
0.3
0.5
0.5
0.3
81
80
69
66
71
72
76
70
92
92
85
83
95
93
The regioselectivity of the addition, being dependent on the
solvent, temperature, and substituent at the nitrogen, can be
slightly tuned by changing these factors. As the regioselec-
tivity depends on the type of organolithium reagent, the
target synthesis of either 3,4- (6) or 3,6-dihydropyridine-
2-thione (5) systems is also possible by the choice of the
appropriate organolithium reactant.
n-Pentyl
n-Hexyl
Isobutyl
sec-Butyla
tert-Butyl
Phenyl
Allyl
Allyl
Allyl
9.
10.
11.
12.
13.
14.
2-Methylallyl
2-Methylallyl
2-Methylallyl
Since organometallic reagents and pyridine-2-thiones 1–4
used in this synthetic procedure are readily available and
the conversion of 6-substituted b,g-unsaturated d-thiolactams
5 into its a,b-unsaturated isomers 8 can be easily realized,
the process described stands as a highly versatile synthetic
methodology to access the 6-substituted d-thiolactams being
valuable Michael acceptors.
a
1:1 mixture of diastereomers.
6w–y. This regioselectivity, caused probably by the steric
effect, is independent of temperature and substituents at
nitrogen.
Finally, we converted the obtained 6-substituted b,g-unsatu-
rated d-thiolactams 5 into their a,b-unsaturated isomers 8,
using catalytic DBU in acetonitrile at rt (Table 3, Scheme 1).
In contrast to the reactions of the analogous lactams, in
which the equilibrium between the b,g and a,b-unsaturated
isomers does not permit exclusive isolation of the a,b-
unsaturated isomer,21 the isomerization of thiolactams 5 is
complete after a few hours and gives the products 8 in
good yield.
4. Experimental
4.1. General
Melting points were determined on a Boetius hot stage appa-
1
ratus. H and 13C NMR spectroscopic measurements were
performed on a Bruker DPX 400 spectrometer equipped
with an 5 mm 1H/BB—inverse probehead operating at
400.13 and 100.62 MHz. TMS was used as internal refer-
ence. Two-dimensional spectra were acquired using stan-
dard Bruker software. Mass spectra (70 eV) were recorded
on an HP 6890 (Hewlett–Packard) GC–MS spectrometer
equipped with a mass detector HP 5973. Silica gel (0.04–
0.063 mm) purchased from Merck was used for preparative
column chromatography. Elemental analyses were
performed on EuroEA 3000 series, EuroVector CHNS-O
Elemental Analyzer.
The structures of 8 and all regioisomeric products 5 and 6
separated easily by column chromatography were deter-
mined on the basis of 1D NMR (1H, 13C, and 13C-DEPT)
and 2D NMR (1H, 1H COSY, 13C, and 1H COSY) spectros-
copy. 1H NMR spectroscopy made it possible to differentiate
both regioisomers. The chemical shifts (d) of ]CH protons
were the main identification criteria. In the 1H NMR spectra
of 4-substituted regioisomers (6) signals for protons ]CH-5
and ]CH-6 appeared at separate chemical shifts ca.
5.4 ppm (as dd) and ca. 6.1 ppm (mainly as ddd), respec-
4.2. Compounds
1
tively, while in the H NMR spectra of 6-substituted deri-
vatives (5) protons ]CH-4 and ]CH-5 gave overlapped
multiplets in the region of ca. 5.7–6.1 ppm.
Pyridine-2-thione 1, n-BuLi (2.5 M in hexane), sec-BuLi
(1.4 M in cyclohexane), t-BuLi (1.7 M in pentane), PhLi
(2.0 M in Bu2O), n-hexyllithium (2.3 M in hexane),
allylMgCl (2.0 M in THF), and 2-methylallylMgCl (0.5 M
in THF) were purchased from Aldrich. EtLi (1.7 M in
Et2O), MeLi (1.6 M in Et2O), and n-BuLi (2.6 M in toluene)
were purchased from Acros Organics. Not commercially
available alkyllithiums were prepared from appropriate
iodoalkanes and t-BuLi.22 3,3-Dimethylallylmagnesiumbro-
mide was prepared as described earlier.23 Solvents (THF,
Et2O, and toluene) were purified over sodium in argon atmo-
sphere according to a standard procedure prior to use.
3. Conclusion
We have described an efficient access to 6-substituted
b,g- and 4-substituted g,d-unsaturated piperidine-2-thiones
obtained in the reaction between organolithium regents and
NH, NMe, NBn, and NPh substituted pyridine-2-thiones.
Although in some reactions the yields are not very high
the reactions can be performed on a multigram scale and 1
as well as the majority of the lithium and allylmagnesium
Grignard reagents used are commercially available. Allyl-
lithium and especially the lithium allyldibutylmagnesate
reagent were found to be the most useful.
4.3. Synthesis of NMe (2), NBn (3), and NPh (4) deri-
vatives of 1H-pyridine-2-thione (starting materials)
1H-Pyridine-2-thiones (2–4) were prepared from the corres-
ponding 1H-pyridine-2-ones according to a standard proce-
dure using Lawesson reagent in refluxing toluene (230 mL)
in the molar ratio of 14.9:27.0 mmol (Lawesson reagent/pyr-
idine-2-one). The oxygen–sulfur exchange was completed
In the field of allylation reactions the present study has illus-
trated the unprecedented worth of allyldibutylmagnesate as
allylation reagents. Due to their simple preparation,

11868
J. G. Soꢀsnicki / Tetrahedron 63 (2007) 11862–11877
after 0.5 h (established by TLC). Most of the solvent was
distilled off in vacuo and the remaining mixture was twice
chromatographed on silica gel: one run was performed using
n-hexane/ethyl acetate (7:3) and the second run using
CHCl3/MeOH (98:2) as eluent. The obtained solids were
crystallized from appropriate solvents.
combined organic layers were dried over MgSO4. Filtration,
concentration in vacuo, and purification by flash column
chromatography (silica gel, n-hexane/ethyl acetate) yielded
5 and 6. Note 1: in the case of 1, 0.059 mol of n-BuLi can
be used instead of the first equivalent of RLi when THF
was applied as solvent (Table 1). Note 2: allyllithiums
were prepared by stirring the appropriate allyltributyltin
compounds (1.0 equiv) with 1.0 equiv of n-BuLi at rt under
argon over 30 min and were prepared prior to use.
4.3.1. 1-Methyl-1H-pyridine-2-thione (2). Yellow solid
(3.14 g, 93%), mp 88–90 ꢁC from n-hexane/ethyl acetate.
IR (KBr pellet): n¼3064, 3044, 3008, 1620, 1538, 1486,
1424, 1410, 1188, 1144, 1124, 1114, 1056, 1024, 804,
4.5. Procedure of allylation of 1 by using lithium
allyldibutylmagnesates
1
756 cmꢂ1; H NMR (400.1 MHz, CDCl3): d¼3.99 (3H, s,
NCH3), 6.65 (1H, td, J 7.0, 1.5 Hz, CH-5), 7.21 (1H, ddd,
J 8.6, 7.0, 1.5 Hz, CH-4), 7.67–7.72 (2H, m, CH-3, CH-6);
13C NMR (100.6 MHz, CDCl3): d¼46.0 (NCH3), 113.4
(CH-5), 134.1 (CH-4), 136.1 (CH-2), 140.8 (CH-6), 180.4
To a cooled and stirred solution of 1 (3.33 g, 0.03 mol) in
dry THF (70 mL) at 0 ꢁC a portion of 0.03 mol of n-BuLi
solution in alkane was added via syringe over 5 min under
argon. Simultaneously, in another Schlenk flask,
0.039 mol of allylMgCl or their allylic derivative in
20 cm3 THF was kept under argon. n-BuLi (0.078 mol)
was added via syringe at 0 ꢁC over 5 min and the white
suspension formed was stirred for 5 min. Subsequently,
the suspension containing the lithium allyldibutylmagne-
sate was transferred to the solution of lithiated pyridine-
2-thione via syringe. The resulting brown-orange solution
was stirred for an appropriate temperature and time (Table
1). After quenching with aqueous saturated NH4Cl
(10 mL), the water layer was extracted with ethyl acetate
(2ꢄ100 mL) and the combined organic layers were dried
over MgSO4. Filtration, concentration in vacuo, and puri-
fication by flash column chromatography (silica gel,
n-hexane/ethyl acetate¼8:2) yielded 6i–k as a yellow
solid, which was recrystallized from n-hexane.
ꢃ
(C-2); GC–MS (EI, 70 eV): m/z¼125 (100, M+ ), 97 (8), 81
(39), 80 (36). Found: C, 57.45; H, 5.62; N, 11.14; S, 25.72.
C6H7NS requires: C, 57.56; H, 5.64; N, 11.19; S, 25.61%.
4.3.2. 1-Benzyl-1H-pyridine-2-thione (3). Yellow solid
(5.33 g, 98%), mp 93–95 ꢁC from n-hexane/ethyl acetate
[lit. 85–87 ꢁC benzene].24 IR (KBr pellet): n¼3030, 2968,
1620, 1530, 1494, 1466, 1415, 1358, 1334, 1250, 1182,
1156, 1114, 1084, 1028, 824, 752, 738, 724, 697 cmꢂ1
;
1H NMR (400.1 MHz, CDCl3): d¼5.81 (2H, s, NCH2),
6.60 (1H, td, J 6.7, 1.5 Hz, CH-5), 7.15 (1H, ddd, J 8.7,
6.7, 1.7 Hz, CH-4), 7.29–7.40 (5H, m, C6H5), 7.56 (1H,
dd, J 6.7, 1.7 Hz, CH-6), 7.75 (1H, d, J 8.7 Hz, CH-3);
13C NMR (100.6 MHz, CDCl3): d¼58.7 (NCH2), 113.6
(CH-5), 128.3, 129.0, 129.0, 135.1 (C6H5), 133.7 (CH-4),
136.4 (CH-2), 139.9 (CH-6), 181.0 (C-2); GC–MS (EI,
ꢃ
70 eV): m/z¼201 (73, M+ ), 168 (78), 124 (9), 91 (100), 79
(13), 65 (26). Found: C, 71.53; H, 5.58; N, 7.00; S, 16.00.
C12H11NS requires: C, 71.60; H, 5.51; N, 6.96; S, 15.93%.
4.6. Procedure of allylation of 2–4 by using lithium
allyldibutylmagnesates
4.3.3. 1-Phenyl-1H-pyridine-2-thione (4). Yellow solid
(4.70 g, 93%), mp 103–105 ꢁC from n-hexane/ethyl acetate
[lit. 102–104 ꢁC].25 IR (KBr pellet): n¼3088, 3064, 3016,
The procedure is the same as above but initial addition of
n-BuLi is omitted. It means that pure pyridine-2-thiones
2–4 are applied for allylation.
1616, 1526, 1448, 1404, 1264, 1148, 768, 748, 694 cmꢂ1
;
1H NMR (400.1 MHz, CDCl3): d¼6.70 (1H, td, J 6.8,
1.5 Hz, CH-5), 7.26 (1H, ddd, J 8.8, 6.8, 1.9 Hz, CH-4),
7.34 (2H, dd, J 7.8, 1.5 Hz, C6H5), 7.46–7.57 (3H, m,
C6H5), 7.60 (1H, dd, J 6.8, 1.9 Hz, CH-6), 7.76 (1H,
d, J 8.8 Hz, CH-3); 13C NMR (100.6 MHz, CDCl3):
d¼111.8 (CH-5), 125.6, 128.2, 128.7, 143.8 (C6H5), 133.4
(CH-4), 135.6 (CH-2), 139.8 (CH-6), 181.2 (C-2); GC–MS
4.7. Procedure of allylation of 2–4 by using standard
allyl Grignard reagents
The procedure is the same as above but instead of lithium
allyldibutylmagnesate a standard Grignard reagent is used.
4.7.1. 6-Ethyl-3,6-dihydro-1H-pyridine-2-thione (5a).
Paleyellow solid, mp 72–74 ꢁCfromn-hexane. IR (KBr pellet):
n¼3176 br, 3064 br, 2968, 2936, 2876, 1676, 1570, 1396, 1388,
ꢃ
(EI, 70 eV): m/z¼187 (46, M+ ), 186 (100), 115 (6), 93 (6),
77 (10), 51 (12). Found: C, 70.53; H, 4.59; N, 7.60; S,
17.00. C11H9NS requires: C, 70.55; H, 4.84; N, 7.48; S,
17.12%.
1340, 1296, 1142, 1092, 958, 864, 812, 728, 690 cmꢂ1; H
1
NMR (400.1 MHz, CDCl3): d¼0.95 (3H, t, J 7.5 Hz,
CH2CH3), 1.61–1.80 (2H, m, CH2CH3), 3.46 (2H, ddd, J 4.9,
3.2, 1.7 Hz, CH2-3), 4.00–4.08 (1H, m, CH-6), 5.72 (1H, dm,
J 10.3 Hz, ]CH-4), 5.79 (1H, dtd, J 10.3, 3.2, 1.7 Hz,
]CH-5), 9.07 (1H, br s, NH); 13C NMR (100.6 MHz,
CDCl3): d¼8.6 (CH2CH3), 28.9 (CH2CH3), 39.1 (CH2-3),
56.2 (CH-6), 122.0, 123.4 (]CH-4, ]CH-5), 198.8 (C-2);
4.4. Procedure of addition of organolithium compounds
to 1–4
To a cooled and stirred solution of 0.059 mol of 1H-pyri-
dine-2-thiones (1–4) in dry solvent (see Tables 1 and 2)
(100 mL) a portion of 0.059–0.177 mol of RLi solution
(see Tables 1 and 2) was added via syringe over 5 min under
argon (Notes 1 and 2). The mixture was stirred at the temper-
ature and in the period indicated in Tables 1 and 2. After
quenching with aqueous saturated NH4Cl (25 mL), the water
layer was extracted with ethyl acetate (2ꢄ150 mL) and the
ꢃ
GC–MS (EI, 70 eV): m/z¼141 (84, M+ ), 112 (100), 78 (60),
67 (18). Found: C, 59.67; H, 7.96; N, 9.90; S, 22.83.
C7H11NS requires: C, 59.53; H, 7.85; N, 9.92; S, 22.70%.
4.7.2. 4-Ethyl-3,4-dihydro-1H-pyridine-2-thione (6a).
Yellow oil. IR (film): n¼3204 br, 2964, 2924, 1500 br,

J. G. Soꢀsnicki / Tetrahedron 63 (2007) 11862–11877
11869
1
1320, 1144 cmꢂ1; H NMR (400.1 MHz, CDCl3): d¼0.94
6.9 Hz, CHH-3), 5.34 (1H, dd, J 7.6, 4.0 Hz, ]CH-5),
5.99 (1H, ddd, J 7.6, 4.3, 1.8 Hz, ]CH-6), 9.58 (1H, br s,
NH); 13C NMR (60.1 MHz, CDCl3): d¼14.0 (CH3), 24.1,
30.5, 31.7, 33.9 (4ꢄCH2), 31.5 (CH-4), 44.4 (CH2-3),
115.9 (]CH-5), 123.5 (]CH-6), 200.1 (C-2); GC–MS
(3H, t, J 7.3 Hz, CH2CH3), 1.37–1.50 (2H, m, CH2CH3),
2.28–2.39 (1H, m, CH-4), 2.75 (1H, dd, J 17.1, 9.8 Hz,
CHH-3), 3.05 (1H, dd, J 17.1, 6.8 Hz, CHH-3), 5.42 (1H,
dd, J 7.8, 3.9 Hz, ]CH-5), 6.07 (1H, ddd, J 7.8, 4.4,
1.9 Hz, ]CH-6), 9.23 (1H, br s, NH); 13C NMR
(100.6 MHz, CDCl3): d¼10.9 (CH2CH3), 27.0 (CH2CH3),
32.1 (CH-4), 44.1 (CH2-3), 115.5 (]CH-5), 123.6 (]CH-6),
ꢃ
(EI, 70 eV): m/z¼183 (50, M+ ), 150 (14), 112 (100), 78
(43); HRMS (EI) for C10H17NS: calculated 183.1082; found
141.1079.
ꢃ
200.4 (C-2); GC–MS (EI, 70 eV): m/z¼141 (70, M+ ), 112
(100), 78 (40), 67 (7); HRMS (EI) for C7H11NS: calculated
141.0612; found 141.0625.
4.7.7. 6-Hexyl-3,6-dihydro-1H-pyridine-2-thione (5d).
Yellow oil. IR (film): n¼3180, 3044, 2924, 2856, 1672,
1560, 1464, 1396, 1334, 1114 cmꢂ1
;
1H NMR
4.7.3. 6-Butyl-3,6-dihydro-1H-pyridine-2-thione (5b).
Pale yellow solid, mp 50–51 ꢁC from n-hexane. IR (KBr pel-
let): n¼3156, 3044, 2956, 2940, 2860, 1562, 1390, 1328,
(400.1 MHz, CDCl3): d¼0.88 (3H, t, J 6.9 Hz, CH3),
1.24–1.41 (m, 8H, 4ꢄCH2), 1.56–1.72 (2H, m, CH2),
3.42–3.47 (2H, m, CH2-3), 4.00–4.11 (1H, m, CH-6),
5.70–5.80 (2H, m, ]CH-4, ]CH-5), 9.19 (1H, br s, NH);
13C NMR (100.6 MHz, CDCl3): d¼14.0 (CH3), 22.5, 24.3,
29.0, 31.6, 36.0 (5ꢄCH2), 38.4 (CH2-3), 55.3 (CH-6),
121.5 (]CH-4), 123.9 (]CH-5), 198.6 (C-2); GC–MS
1148, 1116, 1096, 1076 cmꢂ1 1H NMR (400.1 MHz,
;
CDCl3): d¼0.85–0.95 (3H, m, CH3), 1.28–1.40 (4H, m,
2ꢄCH2), 1.59–1.72 (2H, m CH2), 3.43–3.47 (2H, m, CH2-3),
4.00–4.06 (1H, m, CH-6), 5.70–5.79 (2H, m, ]CH-4,
]CH-5), 9.08 (1H, br s, NH); 13C NMR (100.6 MHz,
CDCl3): d¼13.95 (CH3), 22.5 (CH2), 26.5 (CH2), 35.7
(CH2), 38.9 (CH2-3), 55.4 (CH-6), 121.6, 123.9 (]CH-4,
]CH-5), 198.8 (C-2); GC–MS (EI, 70 eV): m/z ¼169 (35,
ꢃ
(EI, 70 eV): m/z¼197 (61, M+ ), 196 (53), 164 (52), 126
(12), 112 (100), 78 (41), 67 (9), 41 (11). Found: C, 67.08;
H, 9.90; N, 7.20; S, 16.03. C9H15NS requires: C, 66.95;
H, 9.70; N, 7.10; S, 16.25%.
ꢃ
M+ ), 136 (4), 112 (100), 78 (32). Found: C, 63.72; H,
8.90; N, 8.22; S, 19.03. C9H15NS requires: C, 63.85; H,
8.93; N, 8.27; S, 18.94%.
4.7.8. 4-Hexyl-3,4-dihydro-1H-pyridine-2-thione (6d).
Pale yellow solid, mp 54–57 ꢁC from n-hexane. IR (KBr pel-
let): n¼3196, 3144, 3000, 2956, 2924, 2856, 1522, 1360,
4.7.4. 4-Butyl-3,4-dihydro-1H-pyridine-2-thione (6b).
Pale yellow solid, mp 50–53 ꢁC from n-hexane. IR (KBr pel-
let): n¼3192, 3140, 3000, 2952, 2920, 2856, 1522, 1364,
1144, 812, 736 cmꢂ1 1H NMR (400.1 MHz, CDCl3):
;
d¼0.88 (3H, t, J 7.0 Hz, CH3), 1.22–1.46 (10H, m,
5ꢄCH2), 2.33–2.44 (1H, m, CH-4), 2.74 (1H, dd, J 16.9,
9.4 Hz, CHH-3), 3.03 (1H, dd, J 16.9, 6.9 Hz, CHH-3),
5.41 (1H, dd, J 7.5, 4.0 Hz, ]CH-5), 6.06 (1H, ddd, J 7.5,
4.1, 1.6 Hz, ]CH-6), 9.41 (1H, br s, NH); 13C NMR
(100.6 MHz, CDCl3): d¼14.1 (CH3), 22.6, 26.3, 29.2,
31.7, 34.0 (5ꢄCH2), 30.5 (CH-4), 44.4 (CH2-3), 115.9
(]CH-5), 123.5 (]CH-6), 200.3 (C-2); GC–MS (EI,
70 eV): m/z¼197 (61), 196 (53), 164 (52), 126 (12), 112
(100), 78 (41), 67 (9), 41 (11). Found: C, 66.79; H, 9.90;
N, 7.12; S, 16.30. C9H15NS requires: C, 66.95; H, 9.70;
N, 7.10; S, 16.25%.
1336, 1300, 1144, 812, 740, 704 cmꢂ1
;
1H NMR
(400.1 MHz, CDCl3): d¼0.90 (3H, t, J ca. 7 Hz, CH3),
1.25–1.46 (6H, m, 3ꢄCH2), 2.33–2.45 (1H, m, CH-4),
2.74 (1H, dd, J 16.9, 9.3 Hz, CHH-3), 3.03 (1H, dd,
J 16.9, 6.9 Hz, CHH-3), 5.42 (1H, dd, J 7.6, 4.0 Hz,
]CH-5), 6.06 (1H, ddd, J 7.6, 4.2, 1.7 Hz, ]CH-6), 9.46
(1H, br s, NH); 13C NMR (100.6 MHz, CDCl3): d¼14.0
(CH3), 22.6, 28.5, 33.7 (3ꢄCH2), 30.5 (CH-4), 44.4
(CH2-3), 115.9 (]CH-5), 123.5 (]CH-6), 200.2 (C-2);
ꢃ
GC–MS (EI, 70 eV): m/z¼169 (32, M+ ), 136 (4), 126 (5),
112 (100), 78 (26). Found: C, 63.72; H, 8.90; N, 8.22; S,
19.03. C9H15NS requires: C, 63.71; H, 8.79; N, 8.33; S,
19.11%.
4.7.9. 6-Isobutyl-3,6-dihydro-1H-pyridin-2-thione (5e).
Pale yellow solid, mp 41–43 ꢁC from n-hexane. IR (KBr pel-
let): n¼3156, 2952, 2916, 2868, 1672, 1558, 1396, 1320,
4.7.5. 6-Pentyl-3,6-dihydro-1H-pyridine-2-thione (5c).
Yellow oil. IR (film): n¼3172, 3052, 2924, 2856, 1672,
1176, 1140, 846, 820, 720, 712 cmꢂ1 1H NMR
;
(400.1 MHz, CDCl3): d¼0.96 (6H, d, J 6.6 Hz, 2ꢄCH3),
1.42–1.59 (2H, m, 6-CH2), 1.79 (1H, heptet, J 6.6 Hz,
CH(CH3)2), 3.44–3.48 (2H, m, CH2-3), 4.00–4.10 (1H, m,
CH-6), 5.71–5.80 (2H, m, ]CH-4, ]CH-5), 8.84 (1H, br
s, NH); 13C NMR (100.6 MHz, CDCl3): d¼22.4, 22.8
(2ꢄCH3), 24.3 (CH(CH3)2), 38.9 (CH2-3), 45.4 (6-CH2),
53.7 (CH-6), 121.2, 124.2 (]CH-4, ]CH-5), 198.7 (C-2);
1556, 1462, 1396, 1334, 1136, 1114 cmꢂ1 1H NMR
;
(300.1 MHz, CDCl3): d¼0.76 (3H, t, J 6.4 Hz, CH3), 1.17
(6H, br s, 3ꢄCH2), 1.45–1.57 (2H, m, CH2), 3.29–3.36
(2H, br s, CH2-3), 5.61 (2H, br s, ]CH-4, ]CH-5), 9.00
(1H, br s, NH); 13C NMR (60.1 MHz, CDCl3): d¼14.0
(CH3), 22.5, 24.1, 31.5, 35.9 (4ꢄCH2), 38.9 (CH2-3), 55.4
(CH-6), 121.5, 123.9 (]CH-4, ]CH-5), 198.7 (C-2);
ꢃ
GC–MS (EI, 70 eV): m/z¼169 (52, M+ ), 112 (100), 78
ꢃ
GC–MS (EI, 70 eV): m/z¼183 (33, M+ ), 182 (21), 150
(26). Found: C, 63.80; H, 8.90; N, 8.20; S, 19.06.
C9H15NS requires: C, 63.85; H, 8.93; N, 8.27; S, 18.94%.
(19), 124 (6), 112 (100), 78 (29);. HRMS (EI) for
C10H17NS: calculated 183.1082; found 141.1089.
4.7.10. 4-Isobutyl-3,4-dihydro-1H-pyridine-2-thione
(6e). Pale yellow solid, mp 52–53 ꢁC from n-hexane. IR
(KBr pellet): n¼3200, 3148, 2956, 2896, 1516, 1368,
4.7.6. 4-Pentyl-3,4-dihydro-1H-pyridine-2-thione (6c).
Yellow oil. IR (Nujol): n¼3188, 3136, 2928, 2852, 1656,
1
1522, 1414, 1366, 1320, 1144, 808, 736, 704 cmꢂ1; H
1350, 1308, 1142, 918, 740, 706 cmꢂ1 1H NMR
;
NMR (300.1 MHz, CDCl3): d¼0.81 (3H, t, J 7.1 Hz, CH3),
1.12–1.39 (8H, m, 4ꢄCH2), 2.23–2.39 (1H, m, CH-4), 2.66
(1H, dd, J 16.9, 6.9 Hz, CHH-3), 2.96 (1H, dd, J 16.9,
(400.1 MHz, CDCl3): d¼0.89 (3H, d, J 6.5 Hz, CH3), 0.90
(3H, d, J 6.5 Hz, CH3), 1.21 (1H, dt, J 13.6, 7.4 Hz,
3-CHH), 1.31 (1H, dt, J 13.6, 7.2 Hz, 3-CHH), 1.69 (1H,

11870
J. G. Soꢀsnicki / Tetrahedron 63 (2007) 11862–11877
heptet, J 6.8 Hz, CH(CH3)2), 2.41–2.53 (1H, m, CH-4), 2.71
(1H, dd, J 16.8, 9.2 Hz, CHH-3), 3.02 (1H, dd, J 16.8,
6.7 Hz, CHH-3), 5.42 (1H, dd, J 7.5, 4.0 Hz, ]CH-5),
6.06 (1H, ddd, J 7.5, 4.2, 1.5 Hz, ]CH-6), 9.43 (1H, br s,
NH); 13C NMR (100.6 MHz, CDCl3): d¼22.5, 22.5
(2ꢄCH3), 24.7 (CH(CH3)2), 28.2 (CH-4), 43.0 (4-CH2),
44.6 (CH2-3), 116.0 (]CH-5), 123.5 (]CH-6), 200.1 (C-2);
acetate. IR (KBr pellet): n¼3144 br, 3056, 2968, 1672,
1564, 1328, 1124, 840, 740, 704, 684 cmꢂ1 1H NMR
;
(400.1 MHz, CDCl3): d¼3.44–3.63 (2H, m, CH2-3), 5.02–
5.07 (1H, m, CH-6), 5.78–5.87 (2H, m, ]CH-4, ]CH-5),
7.22–7.28 (2H, m, C6H5), 7.31–7.44 (3H, m C6H5), 8.99
(1H, br s, NH); 13C NMR (100.6 MHz, CDCl3): d¼38.6
(CH2-3), 59.6 (CH-6), 121.1 (]CH-4), 123.8 (]CH-5),
127.2, 128.7, 129.2, 139.2 (C6H5), 197.9 (C-2); GC–MS
(EI, 70 eV): m/z¼189 (100), 188 (33), 156 (23), 147 (16),
130 (39), 129 (60), 128 (34), 115 (37), 112 (33), 104 (11),
91 (11), 78 (16), 77 (21), 51 (13). Found: C, 69.89; H,
5.70; N, 7.45; S, 17.01. C11H11NS requires: C, 69.80; H,
5.86; N, 7.40; S, 16.94%.
ꢃ
GC–MS (EI, 70 eV): m/z¼169 (42, M+ ), 112 (100), 78
(30). Found: C, 63.69; H, 8.99; N, 8.19; S, 19.00.
C9H15NS requires: C, 63.85; H, 8.93; N, 8.27; S, 18.94%.
4.7.11. 6-sec-Butyl-3,6-dihydro-1H-pyridine-2-thione
(5f). Mixture of diastereomers¼1:1, yellow oil. IR (film):
n¼3184 br, 3052, 2960, 2932, 2876, 1672, 1564, 1460,
1
1398, 1328, 1116 cmꢂ1; H NMR (400.1 MHz, CDCl3):
4.7.15. 4-Phenyl-3,4-dihydro-1H-pyridine-2-thione (6h).
Orange semi-solid. IR (KBr pellet): n¼3200 br, 1646,
d¼0.88 (3H, d, J 6.8 Hz, CH3CH), 0.91 (3H, d, J 6.9 Hz,
CH3CH), 0.94 (3H, t, J 7.4 Hz, CH3CH2), 0.95 (3H, t,
J 7.4 Hz, CH3CH2), 1.15–1.29 (2H, m, 2ꢄCHHCH3),
1.40–1.53 (2H, m, 2ꢄCHHCH3), 1.64–1.81 (2H, m,
2ꢄCHCH3), 3.42–3.48 (4H, m, 2ꢄCH2-3), 3.99–4.07 (2H,
br s, 2ꢄCH-6), 5.67–5.86 (4H, m, 2ꢄ]CH-4, 2ꢄ]CH-5),
9.05 (1H, br s, NH), 9.22 (1H, br s, NH); 13C NMR
(100.6 MHz, CDCl3): d¼11.9, 11.9 (2ꢄCH3CH2), 14.0,
14.1 (2ꢄCH3CH), 24.9 25.1 (2ꢄCH2CH3), 39.2, 39.3
(2ꢄCH2-3), 40.4, 40.6 (2ꢄCHCH3), 59.7, 59.7 (2ꢄCH-6),
121.3, 122.4, 122.5, 122.9 (2ꢄ]CH-4, 2ꢄ]CH-5), 198.9,
199.4 (2ꢄC-2); GC–MS (EI, 70 eV): m/z¼169 (54), 112
(100), 78 (38). Found: C, 63.76; H, 8.99; N, 8.40; S, 19.03.
C9H15NS requires: C, 63.85; H, 8.93; N, 8.27; S, 18.94%.
1
1494, 1320, 1138, 760, 698 cmꢂ1; H NMR (400.1 MHz,
CDCl3): d¼3.06 (1H, dd, J 17.1, 9.8 Hz, CHH-3), 3.29
(1H, dd, J 17.1, 7.3 Hz, CHH-3), 3.65–3.72 (1H, m, CH-
4), 5.55 (1H, dd, J 7.6, 4.5 Hz,]CH-5), 6.22 (1H, ddd,
J 7.6, 4.4, 1.9 Hz, ]CH-6), 7.19–7.23 (2H, m, C6H5),
7.30–7.35 (2H, t, J 7.6 Hz, C6H5), 7.45 (1H, t, J 7.5 Hz,
C6H5), 9.63 (1H, br s, NH); 13C NMR (100.6 MHz,
CDCl3): d¼36.9 (CH-4), 46.4 (CH2-3), 114.2 (]CH-5),
124.4 (]CH-6), 127.1, 128.9, 129.6, 142.2 (C6H5), 199.1
ꢃ
(C-2); GC–MS (EI, 70 eV): m/z¼189 (100, M+ ), 188 (65),
156 (21), 130 (68), 115 (25), 103 (12), 91 (10), 78 (13),
77 (15), 51 (8). Found: C, 69.77; H, 5.79; N, 7.33; S, 16.99.
C11H11NS requires: C, 69.80; H, 5.86; N, 7.40; S, 16.94%.
4.7.12. 6-tert-Butyl-3,6-dihydro-1H-pyridine-2-thione
(5g). Pale yellow solid, mp 136–138 ꢁC from n-hexane/
ethyl acetate. IR (KBr pellet): n ¼3140, 3004, 2960, 1526,
4.7.16. 6-Allyl-3,6-dihydro-1H-pyridine-2-thione (5i).
Yellow oil. IR (film): n¼3168, 3048, 1558, 1392, 1332,
1
1128, 922 cmꢂ1; H NMR (400.1 MHz, CDCl3): d¼2.34
1360, 1140, 914, 812, 762, 732, 688 cmꢂ1
;
1H NMR
(1H, dt, J 14.0, 7.1 Hz, CHH-3), 2.42–2.50 (1H, m, CHH-3),
3.44–3.48 (2H, m, 6-CH2), 4.42–4.12 (1H, m, CH-6),
5.18–5.26 (2H, m, ]CH2), 5.70–5.82 (3H, m, ]CH-4,
]CH-5, ]CH), 8.84 (1H, br s, NH); 13C NMR
(100.6 MHz, CDCl3): d¼39.0 (6-CH2), 40.4 (CH2-3), 54.5
(CH-6), 120.3 (]CH2), 122.0, 123.3, 131.9 (]CH-4,
]CH-5, ]CH), 199.04 (C-2); GC–MS (EI, 70 eV):
m/z¼153 (M+, 49), 112 (100), 78 (46). Found: C, 62.79;
H, 7.09; N, 9.25; S, 21.14. C8H11NS requires: C, 62.70; H,
7.24; N, 9.14; S, 20.92%.
(400.1 MHz, CDCl3): d¼0.98 (9H, s, 3ꢄCH3), 3.38 (1H,
ddd, J 23.2, 4.7, 0.7 Hz, CHH-3), 3.53 (1H, ddd, J 23.3,
3.9, 2.8 Hz, CHH-3), 3.64–3.68 (1H, m, CH-6), 5.81–5.90
(2H, m, ]CH-4, ]CH-5), 8.47 (br s, NH); 13C NMR
(100.6 MHz, CDCl3): d¼25.6 (C(CH3)3), 37.4 (C(CH3)3),
39.3 (CH2-3), 64.7 (CH-6), 121.7, 123.2 (]CH-4, ]CH-5),
199.9 (C-2); GC–MS (EI, 70 eV): m/z¼169 (54, M+), 113
(35), 112 (100), 80 (22), 78 (32), 57 (12), 41 (11). Found:
C, 63.81; H, 8.79; N, 8.21; S, 18.88. C9H15NS requires: C,
63.85; H, 8.93; N, 8.27; S, 18.94%.
4.7.17. 4-Allyl-3,4-dihydro-1H-pyridine-2-thione (6i).
Pale yellow solid, mp 53–55 ꢁC from n-hexane. IR (KBr pel-
let): n¼3188 br, 3144 br, 2996, 1640, 1522, 1436, 1404,
1364, 1324, 1300, 1140, 1106, 1056, 992, 976, 936, 914,
4.7.13. 4-tert-Butyl-3,4-dihydro-1H-pyridine-2-thione
(6g). Pale yellow solid, mp 66–68 ꢁC from n-hexane/ethyl
acetate. IR (KBr pellet): n¼3180, 3060, 2964, 2872, 1668,
1
1554, 1394, 1334, 1112, 972, 922, 818, 784, 734 cmꢂ1; H
812, 742, 708 cmꢂ1 1H NMR (400.1 MHz, CDCl3):
;
NMR (400.1 MHz, CDCl3): d¼0.92 (9H, s, 3ꢄCH3), 2.17
(1H, dddd, J 9.0, 7.9, 4.1, 2.0 Hz, CH-4), 2.92 (1H, dd,
J 17.3, 9.0 Hz, CHH-3), 3.01 (1H, dd, J 17.3, 7.9 Hz, CHH-
3), 5.44 (1H, dd, J 7.8, 4.1 Hz, ]CH-5), 6.14 (1H, ddd, J
7.8, 4.3, 2.0 Hz, ]CH-6), 9.44 (1H, br s, NH); 13C NMR
(100.6 MHz, CDCl3): d¼26.8 (C(CH3)3), 33.4 (C(CH3)3),
40.5 (CH2-3), 41.1 (CH-4), 112.8 (]CH-5), 124.2 (]CH-
6), 201.0 (C-2); GC–MS (EI, 70 eV): m/z¼169 (50, M+),
113 (40), 112 (100), 80 (24), 78 (28), 57 (12), 41 (11). Found:
C, 63.78; H, 9.01; N, 8.26; S, 19.00. C9H15NS requires: C,
63.85; H, 8.93; N, 8.27; S, 18.94%.
d¼2.15 (2H, t, J 7.1 Hz, 4-CH2), 2.44–2.56 (1H, m, CH-4),
2.77 (1H, dd, J 17.0, 9.7 Hz, CHH-3), 3.02 (1H, dd,
J 17.0, 6.9 Hz, CHH-3), 5.06–5.13 (2H, m, ]CH2), 5.41
(1H, dd, J 7.5, 3.8 Hz, ]CH-5), 5.66–5.79 (1H, m,
]CH), 6.09 (1H, ddd, J 7.5, 4.3, 1.8 Hz, CH-6), 9.72 (1H,
br s, NH); 13C NMR (100.6 MHz, CDCl3): d¼30.2
(CH-4), 38.1 (4-CH2), 43.9 (CH2-3), 114.9 (]CH-5), 117.8
(]CH2), 123.8 (]CH-6), 134.6 (]CH), 199.9 (C-2);
GC–MS (EI, 70 eV): m/z¼153 (33, M+ꢃ), 112 (100), 78
(46). Found: C, 62.64; H, 7.40; N, 9.05; S, 21.35.
C8H11NS requires: C, 62.70; H, 7.24; N, 9.14; S, 20.92%.
4.7.14. 6-Phenyl-3,6-dihydro-1H-pyridine-2-thione (5h).
Pale yellow solid, mp 125–128 ꢁC from n-hexane/ethyl
4.7.18. 4-(1,1-Dimethylallyl)-3,4-dihydro-1H-pyridine-2-
thione (6j). Pale yellow solid, mp 58–60 ꢁC from n-hexane.

J. G. Soꢀsnicki / Tetrahedron 63 (2007) 11862–11877
11871
ꢃ
IR (KBr pellet): n¼3152 br, 3004, 2964, 1526, 1412, 1366,
1324, 1138, 912, 766 cmꢂ1 1H NMR (400.1 MHz,
(C-2); GC–MS (EI, 70 eV): m/z¼245 (24, M+ ), 244 (30),
188 (100), 156 (7), 130 (8), 104 (8), 77 (28), 51 (9). Found:
C, 73.35; H, 7.92; N, 5.82; S, 12.93. C15H19NS requires:
C, 73.42; H, 7.80; N, 5.71; S, 13.07%.
;
CDCl3): d¼1.01 (6H, s, 2ꢄCH3), 2.24–2.32 (1H, m
CH-4), 2.88 (1H, dd, J 17.4, 9.2 Hz, CHH-3), 2.98 (1H,
dd, J 17.4, 7.9 Hz, CHH-3), 4.98–5.08 (2H, m, ]CH2),
5.41 (1H, dd, J 7.8, 4.0 Hz, ]CH-5), 5.71 (1H, dd, J 17.4,
10.8 Hz, ]CH), 6.13 (1H, ddd, J 7.7, 4.3, 1.9 Hz, ]CH-
6), 9.44 (1H, br s, NH); 13C NMR (100.6 MHz, CDCl3):
d¼23.6, 23.7 (2ꢄCH3), 39.5 (CH-4), 40.0 (C(CH3)3), 40.4
(CH2-3), 112.1 (]CH-5), 112.9 (]CH2), 124.4 (]CH-6),
145.4 (]CH), 200.7 (C-2); GC–MS (EI, 70 eV): m/z¼181
(18, M+), 112 (100), 78 (30). Found: C, 66.19; H, 8.40; N,
7.75; S, 17.71. C10H15NS requires: C, 66.25; H, 8.34; N,
7.73; S, 17.69%.
4.7.22. 4-tert-Butyl-1-methyl-3,4-dihydro-1H-pyridine-2-
thione (6n). Yellow oil. IR (film): n¼2960, 1476, 1378,
1126, 1138, 1026 cmꢂ1; H NMR (400.1 MHz, CDCl3):
1
d¼0.91 (9H, s, C(CH3)3), 3.01 (1H, dd, J 16.8, 9.5 Hz,
CHH-3), 3.12 (1H, dd, J 16.8, 7.4 Hz, CHH-3), 3.48 (3H,
s, NCH3), 5.48 (1H, dd, J 12.0, 7.8 Hz, ]CH-5), 6.22
(1H, dd, J 7.8, 1.9 Hz, ]CH-6); 13C NMR (100.6 MHz,
CDCl3): d¼26.8 (C(CH3)3), 32.9 (C(CH3)3), 41.2 (CH-4),
41.7 (NCH3), 42.8 (CH2-3), 114.6 (]CH-5), 130.4
(]CH-6), 198.4 (C-2); GC–MS (EI, 70 eV): m/z¼183
(M+, 41), 126 (100), 111 (10), 94 (30). Found: C, 65.55;
H, 9.30; N, 7.51; S, 17.54%. C10H17NS requires: C, 65.52;
H, 9.35; N, 7.64; S, 17.49%.
4.7.19. 4-(2-Methyl-allyl)-3,4-dihydro-1H-pyridine-2-
thione (6k). Pale yellow solid, mp 51–53 ꢁC from n-hexane.
IR (KBr pellet): n¼3148 br, 3000, 1648, 1526, 1436, 1362,
1
1324, 1140, 932, 976, 896, 812, 742, 720 cmꢂ1; H NMR
(400.1 MHz, CDCl3): d¼1.71 (3H, s, CH3), 2.03–2.15
(2H, m, 4-CH2), 2.55–2.66 (1H, m, CH-4), 2.73 (1H, dd,
J 16.8, 9.7 Hz, CHH-3), 3.00 (1H, dd, J 16.8, 6.6 Hz,
CHH-3), 4.74 (1H, br s, ]CHH), 4.85 (1H, br s, ]CHH),
5.41 (1H, dd, J 7.6, 3.8 Hz, ]CH-5), 6.08 (1H, ddd, J 7.6,
4.3, 1.8 Hz, ]CH-6), 9.52 (1H, br s, NH); 13C NMR
(100.6 MHz, CDCl3): d¼22.1 (CH3), 28.4 (CH-4), 42.0
(4-CH2), 44.0 (CH2-3), 113.4 (]CH-5), 115.3 (]CH2),
123.7 (]CH-6), 141.7 (]CCH3), 199.9 (C-2); GC–MS
(EI, 70 eV): m/z¼167 (M+, 17); 112 (100), 78 (58). Found:
C, 64.49; H, 7.69; N, 8.44; S, 19.04. C9H13NS requires: C,
64.62; H, 7.83; N, 8.37; S, 19.17%.
4.7.23. 1-Benzyl-4-tert-butyl-3,4-dihydro-1H-pyridine-2-
thione (6o). Yellow oil. IR (film): n¼3064, 2960, 1460,
1
1452, 1384, 1156, 1108, 944 cmꢂ1; H NMR (400.1 MHz,
CDCl3): d¼0.89 (9H, s, C(CH3)3), 2.12–2.19 (1H, m,
CH-4), 3.07 (1H, dd, J 16.8, 9.6 Hz, CHH-3), 3.20 (1H,
dd, J 16.8, 7.3 Hz, CHH-3), 5.27 (1H, d, J 14.8 Hz,
NCHH), 5.39 (1H, d, J 14.8 Hz, NCHH), 5.47 (1H, dd,
J 8.0, 3.7 Hz, ]CH-5), 6.20 (1H, ddd, J 8.0, 2.1, 0.5 Hz,
]CH-6), 7.25–7.37 (5H, m, C6H5); 13C NMR (100.6 MHz,
CDCl3): d¼26.9 (C(CH3)3), 33.0 (C(CH3)3), 41.2 (CH-4),
43.3 (CH2-3), 55.4 (NCH2), 115.0 (]CH-5), 127.8, 127.9,
128.7, 135.5 (C6H5), 128.7 (]CH-6), 199.2 (C-2); GC–
MS (EI, 70 eV): m/z¼259 (M+, 36), 202 (48), 170 (16),
112 (7), 91 (100), 65 (8). Found: C, 74.16; H, 8.00; N,
5.31; S, 12.54. C15H17NS requires: C, 74.08; H, 8.16; N,
5.40; S, 12.36%.
4.7.20. 1-Benzyl-4-butyl-3,4-dihydro-1H-pyridine-2-thi-
one (6l). Yellow oil. IR (KBr pellet): n¼3060, 2924, 1496,
1
1450, 1424, 1384, 1156, 1106, 948, 726, 696 cmꢂ1. H
NMR (400.1 MHz, CDCl3): d¼0.88 (3H, t, J 7.1 Hz, CH3),
1.24–1.41 (6H, m, 3ꢄCH2), 2.32–2.43 (1H, m, CH-4), 2.92
(1H, dd, J 16.4, 9.5 Hz, CHH-3), 3.22 (1H, dd, J 16.4,
6.6 Hz, CHH-3), 5.32 (1H, d, J 14.9 Hz, NCHH), 5.37
(1H, d, J 14.9 Hz, NCHH), 5.45 (1H, dd, J 7.7, 4.2 Hz,
]CH-5), 6.13 (1H, dd, J 7.7, 5.7 Hz, ]CH-6), 7.25–7.36
(5H, m, C6H5); 13C NMR (100.6 MHz, CDCl3): d¼14.0
(CH3), 22.6, 28.5, 33.4 (3ꢄCH2), 30.6 (CH-4), 47.2
(CH2-3), 55.4 (NCH2), 118.0 (]CH-5), 127.6, 127.8,
128.7, 135.6 (C6H5), 128.0 (]CH-6), 198.6 (C-2); GC–
4.7.24. 4-tert-Butyl-1-phenyl-3,4-dihydro-1H-pyridine-2-
thione (6p). Yellow solid, mp 57–58 ꢁC from n-hexane. IR
(KBr pellet): n¼2960, 2816, 1646, 1596, 1492, 1418,
1
1360, 1154, 760, 736, 696 cmꢂ1; H NMR (400.1 MHz,
CDCl3): d¼0.99 (9H, s, C(CH3)3), 2.27 (1H, tdd, J 7.8,
4.5, 1.8 Hz, CH-4), 3.26 (2H, d, J 7.8 Hz, CH2-3), 5.56
(1H, ddt, J 7.8, 4.5, ca. 0.6 Hz, ]CH-5), 6.34 (1H, dd,
J 7.8, 1.8 Hz, ]CH-6), 7.24 (2H, dd, J 8.7, 1.6 Hz, C6H5),
7.37 (1H, tt, J 7.6, 1.2 Hz, C6H5), 7.43–7.48 (2H, m,
C6H5); 13C NMR (100.6 MHz, CDCl3): d¼27.0 (C(CH3)3),
33.4 (C(CH3)3), 41.4 (CH-4), 43.8 (CH2-3), 113.4 (]CH-5),
126.8, 128.3, 129.5, 144.5 (C6H5), 130.7 (]CH-6), 200.7
(C-2); GC–MS (EI, 70 eV): m/z¼245 (M+, 63), 189 (57),
188 (100), 186 (33), 156 (42), 130 (12), 77 (26). Found: C,
73.46; H, 7.88; N, 5.67; S, 12.99. C15H19NS requires: C,
73.42; H, 7.80; N, 5.71; S, 13.07%.
ꢃ
MS (EI, 70 eV): m/z¼259 (37, M+ ), 226 (11), 202 (45),
168 (22), 91 (100), 65 (9). Found: C, 73.98; H, 8.35; N,
5.29; S, 12.29. C16H21NS requires: C, 74.08; H, 8.16; N,
5.40; S, 12.36%.
4.7.21. 4-Butyl-1-phenyl-3,4-dihydro-1H-pyridine-2-thi-
one (6m). Yellow oil. IR (film): n¼2956, 2924, 2868,
1
2856, 1596, 1492, 1404, 1356, 1152, 764, 692 cmꢂ1; H
NMR (400.1 MHz, CDCl3): d¼0.92 (3H, t, J 7.2 Hz, CH3),
1.30–1.52 (6H, m, 3ꢄCH2), 2.45–2.55 (1H, m, CH-4),
3.03 (1H, dd, J 16.3, 9.3 Hz, CHH-3), 3.30 (1H, ddd,
J 16.3, 6.3, 0.8 Hz, CHH-3), 5.54 (1H, dd, J 7.6, 4.1 Hz,
]CH-5), 6.25 (1H, dd, J 7.6, 1.2 Hz, ]CH-6), 7.26 (2H,
dd, J 8.3, 1.3 Hz, C6H5), 7.37 (1H, tt, J 7.5, 1.3 Hz, C6H5),
7.45 (2H, tt, J 7.3, ca. 1.5 Hz, C6H5); 13C NMR
(100.6 MHz, CDCl3): d¼14.0 (CH3), 22.7, 28.6, 33.0
(3ꢄCH2), 30.8 (CH-4), 47.7 (CH2-3), 116.6 (]CH-5),
126.9, 129.5, 130.0, 144.5 (C6H5), 128.3 (]CH-6), 200.1
4.7.25. 6-Allyl-1-methyl-3,6-dihydro-1H-pyridine-2-thi-
one (5q). Pale yellow oil. IR (film): n¼3076, 3044, 2976,
2932, 1678, 1640, 1516, 1432, 1392, 1350, 1328, 1230,
1128, 1082, 996, 922 cmꢂ1
;
1H NMR (400.1 MHz,
CDCl3): d¼2.42–2.58 (2H, m, 6-CH2), 3.46 (1H, br d,
J ca. 22.7 Hz, CHH-3), 3.53 (3H, s, NCH3), 3.72 (1H, dt,
J 22.7, ca. 3.6 Hz, CHH-3), 4.16 (1H, septet, J 3.5 Hz,
CH-6), 5.13–5.21 (2H, m, ]CH2), 5.64–5.7 (1H, m,
]CH), 5.79–5.89 (2H, m, ]CH-4, ]CH-5); 13C NMR
(100.6 MHz, CDCl3): d¼38.1 (6-CH2), 41.7 (CH2-3), 41.8

11872
J. G. Soꢀsnicki / Tetrahedron 63 (2007) 11862–11877
(NCH3), 62.6 (CH-6), 120.0 (]CH2), 123.1, 124.0, 131.2
(]CH-4, ]CH-5, ]CH), 196.7 (C-2); GC–MS (EI,
70 eV): m/z¼167 (M+, 57), 134 (9), 126 (100), 111 (20).
Found: C, 64.87; H, 7.79; N, 8.33; S, 19.11. C9H13NS
requires: C, 64.62; H, 7.83; N, 8.37; S, 19.17%.
754, 696 cmꢂ1
;
1H NMR (400.1 MHz, CDCl3): d¼2.41
(2H, dd, J 13.8, 7.4 Hz, 6-CH2), 3.64 (1H, dm, J ca.
23 Hz, CHH-3), 3.86 (1H, ddd, J 23.2, 4.0, 2.7 Hz, CHH-3),
4.42 (1H, m, CH-6), 5.12–5.21 (2H, m, ]CH2), 5.70–
5.82 (1H, m, ]CH), 5.90–6.01 (2H, m, ]CH-4, ]CH-5),
7.24 (2H, d, J 7.5 Hz, C6H5), 7.40 (1H, tt, J 7.4, 1.1 Hz,
4.7.26. 4-Allyl-1-methyl-3,4-dihydro-1H-pyridine-2-thi-
one (6q). Pale yellow oil. IR (film): n¼3076, 2976, 2924,
C6H5), 7.50 (2H, t, J
7.5 Hz, C6H5); 13C NMR
(100.6 MHz, CDCl3): d¼34.9 (6-CH2), 42.6 (CH2-3), 63.9
(CH-6), 119.9 (]CH2), 123.1, 124.4 (]CH-4, ]CH-5),
127.5 br, 128.0, 129.6 br, 144.7 (C6H5), 131.5 (]CH),
199.6 (C-2); GC–MS (EI, 70 eV): m/z¼229 (M+, 65), 228
(25), 189 (31), 188 (100), 186 (44), 173 (10), 154 (14),
130 (13), 109 (16), 104 (15), 78 (21), 77 (43), 51 (13).
Found: C, 73.16; H, 6.67; N, 6.01; S, 13.85. C14H15NS
requires: C, 73.32; H, 6.59; N, 6.11; S, 13.98%.
1640, 1480, 1378, 1252, 1136, 1052, 996, 920, 728 cmꢂ1
;
1H NMR (400.1 MHz, CDCl3): d¼2.12 (2H, t, J 7.1 Hz,
4-CH2), 2.41–2.52 (1H, m, CH-4), 2.85 (1H, dd, J 16.5,
10.1 Hz, CHH-3), 3.13 (1H, dd, J 16.5, 6.5 Hz, CHH-3),
3.50 (3H, s, NCH3), 5.04–5.12 (2H, m, ]CH2), 5.45 (1H,
dd, J 7.6, 3.9 Hz, ]CH-5), 5.66–5.79 (1H, m, ]CH),
6.18 (1H, dd, J 7.6, 1.9 Hz, ]CH-6); 13C NMR
(100.6 MHz, CDCl3): d¼30.4 (CH-4), 37.9 (4-CH2), 41.8
(N-CH3), 46.2 (CH2-3), 116.5 (]CH-5), 117.6 (]CH2),
130.0 (]CH-6), 134.7 (]CH), 197.5 (C-2); GC–MS (EI,
70 eV): m/z¼167 (M+, 73), 126 (100), 111 (22), 94 (8), 85
(7), 70 (13). Found: C, 64.66; H, 7.85; N, 8.51; S, 19.22.
C9H13NS requires: C, 64.62; H, 7.83; N, 8.37; S, 19.17%.
4.7.30. 4-Allyl-1-phenyl-3,4-dihydro-1H-pyridine-2-thi-
one (6s). Pale yellow oil. IR (film): n¼3072, 2920, 1640,
1594, 1492, 1404, 1364, 1150, 920, 694 cmꢂ1; H NMR
1
(400.1 MHz, CDCl3): d¼2.23 (2H, t, J 7.2 Hz, 4-CH2),
2.56–2.67 (1H, m, CH-4), 3.06 (1H, dd, J 16.4, 9.6 Hz,
CHH-3), 3.30 (1H, dd, J 16.4, 6.4 Hz, CHH-3), 5.10–5.17
(2H, m, ]CH2), 5.52 (1H, dd, J 7.6, 4.0 Hz, ]CH-5),
5.74–5.86 (1H, m, ]CH), 6.28 (1H, dd, J 7.6, 1.8 Hz,
]CH-6), 7.25 (2H, d, J 7.2 Hz, C6H5), 7.37 (1H, tt, J 7.5,
1.2 Hz, C6H5), 7.46 (2H, tt, J 7.5, 1.7 Hz, C6H5); 13C
NMR (100.6 MHz, CDCl3): d¼30.6 (CH-4), 38.1 (4-CH2),
47.3 (CH2-3), 115.4 (]CH-5), 117.8 (]CH2), 126.8,
128.3, 129.5, 144.5 (C6H5), 130.4 (]CH-6), 134.7
(]CH), 199.7 (C-2). GC–MS (EI, 70 eV): m/z¼229 (M+,
55), 189 (35), 188 (100), 173 (10), 154 (17), 130 (19), 109
(13), 104 (13), 93 (8), 78 (22), 77 (43), 51 (14). Found: C,
73.40; H, 6.66; N, 5.99; S, 14.04. C14H15NS requires: C,
73.32; H, 6.59; N, 6.11; S, 13.98%.
4.7.27. 6-Allyl-1-benzyl-3,6-dihydro-1H-pyridine-2-thi-
one (5r). White solid, mp 78–80 ꢁC from n-hexane/ethyl
acetate. IR (KBr pellet): n¼1500, 1448, 1394, 1350, 1328,
1180, 1166, 926, 732 cmꢂ1
;
1H NMR (400.1 MHz,
CDCl3): d¼2.36–2.54 (2H, m, 6-CH2), 3.51 (1H, dm,
J 22.2 Hz, CHH-3), 3.88 (1H, ddd, J 22.2, 4.9, 1.9 Hz,
CHH-3), 4.02–4.09 (1H, m, CH-6), 4.40 (1H, d, J 15.0 Hz,
NCHH), 5.10–5.18 (2H, m, ]CH2), 5.64–5.77 (1H, m,
]CH), 5.79 (1H, ddd, J 9.7, 4.6, 3.1 Hz, ]CH-5), 5.86
(1H, ddd, J 9.7, 5.0, 1.9 Hz, ]CH-4), 6.55 (1H, d,
J 15.0 Hz, NCHH), 7.24–7.37 (5H, m C6H5); 13C NMR
(100.6 MHz, CDCl3): d¼37.8 (6-CH2), 42.6 (CH2-3), 54.3
(NCH2), 58.7 (CH-6), 119.8 (]CH2), 123.4 (]CH-4),
125.0 (]CH-5), 127.5, 127.7, 128.8, 135.1 (C6H5), 131.7
(]CH), 198.6 (C-2); GC–MS (EI, 70 eV): m/z¼243 (M+,
38), 242 (41), 210 (16), 202 (18), 168 (14), 152 (8), 149
(7), 148 (15), 132 (17), 112 (12), 91 (100), 65 (9). Found:
C, 74.16; H, 7.05; N, 5.56; S, 13.22. C15H17NS requires:
C, 74.03; H, 7.04; N, 5.76; S, 13.18%.
4.7.31. 1-Methyl-6-(2-methyl-allyl)-3,6-dihydro-1H-pyri-
dine-2-thione (5t). Pale yellow oil. IR (film): n¼3076, 2964,
2936, 1646, 1520, 1392, 1348, 1328, 1228, 1124, 1084,
1
898 cmꢂ1; H NMR (400.1 MHz, CDCl3): d¼1.79 (3H, s,
]CCH3), 2.28 (1H, dd, J 13.4, 8.5 Hz, 6-CHH), 2.49 (1H,
dd, J 13.4, 4.2 Hz, 6-CHH), 3.45 (1H, br d, J ca. 22.6 Hz,
CHH-3), 3.52 (3H, s, NCH3), 3.74 (1H, ddd, J 22.6, 4.6,
2.6 Hz, CHH-3), 4.13–4.22 (1H, m, CH-6), 4.76 (1H, s,
]CHH), 4.90 (1H, t, J 1.5 Hz, ]CHH), 5.77–5.87 (2H,
m, ]CH-4, ]CH-5); 13C NMR (100.6 MHz, CDCl3):
d¼23.0 (]CCH3), 41.7 (CH2-3), 42.3 (N-CH3), 42.3
(6-CH2), 62.1 (CH-6), 115.1 (]CH2), 122.7, 124.8 (]CH-4,
]CH-5), 140.0 (]CCH3), 196.6 (C-2); GC–MS (EI,
70 eV): m/z¼181 (M+, 23), 148 (14), 126 (100), 111 (9),
42 (19). Found: C, 66.19; H, 8.44; N, 7.82; S, 17.80.
C10H15NS requires: C, 66.25; H, 8.34; N, 7.73; S, 17.69%.
4.7.28. 4-Allyl-1-benzyl-3,4-dihydro-1H-pyridine-2-thi-
one (6r). Yellow oil. IR (film): n¼3064, 2924, 1640, 1496,
1448, 1382, 1352, 1252, 1206, 1156, 1102, 996, 950, 920,
726, 696 cmꢂ1
;
1H NMR (400.1 MHz, CDCl3): d¼2.12
(2H, t, J 7.1 Hz, 4-CH2), 2.43–2.54 (1H, m, CH-4), 2.94
(1H, dd, J 16.5, 9.9 Hz, CHH-3), 3.21 (1H, dd, J 16.5,
6.3 Hz, CHH-3), 5.03–5.10 (2H, m, ]CH2), 5.30–5.39
(2H, m, NCH2), 5.44 (1H, dd, J 7.7, 3.9 Hz, ]CH-5),
5.65–5.78 (1H, m, ]CH), 6.16 (1H, dd, J 7.7, 1.9 Hz,
]CH-6), 7.25–7.37 (5H, m, C6H5); 13C NMR
(100.6 MHz, CDCl3): d¼30.4 (CH-4), 37.8 (4-CH2), 46.7
(CH2-3), 55.4 (NCH2), 116.9 (]CH-5), 117.7 (]CH2),
127.6, 127.8, 128.7, 135.5 (C6H5), 128.4 (]CH-6), 134.7
(]CH), 198.3 (C-2); GC–MS (EI, 70 eV): m/z¼243 (M+,
28), 202 (48), 168 (5), 124 (4), 91 (100), 65 (6). Found: C,
74.16; H, 7.00; N, 5.70; S, 13.05. C15H17NS requires: C,
74.03; H, 7.04; N, 5.76; S, 13.18%.
4.7.32. 1-Methyl-4-(2-methyl-allyl)-3,4-dihydro-1H-pyri-
dine-2-thione (6t). Pale yellow oil. IR (film): n¼3076, 2964,
2924, 1648, 1476, 1378, 1136, 892, 728 cmꢂ1; H NMR
1
(400.1 MHz, CDCl3): d¼1.70 (3H, br s, ]CCH3), 2.05
(2H, d, J 7.6 Hz, 4-CH2), 2.80 (1H, dd, J 16.5, 10.4 Hz,
CHH-3), 3.12 (1H, dd, J 16.5, 6.3 Hz, CHH-3), 3.51 (3H,
s, N-CH3), 4.72 (1H, br s, ]CHH), 4.84 (1H, br s,
]CHH), 5.45 (1H, dd, J 7.6, 3.7 Hz, ]CH-5), 6.17 (1H,
dd, J 7.6, 1.9 Hz, ]CH-6); 13C NMR (100.6 MHz,
CDCl3): d¼22.2 (]CCH3), 28.6 (CH-4), 41.8 (N-CH3),
41.9 (4-CH2), 46.4 (CH2-3), 113.2 (]CH2), 116.8 (]CH-5),
4.7.29. 6-Allyl-1-phenyl-3,6-dihydro-1H-pyridine-2-thi-
one (5s). Pale yellow oil. IR (film): n¼3080, 2932, 1640,
1596, 1492, 1462, 1404, 1388, 1310, 1240, 1144, 926,

J. G. Soꢀsnicki / Tetrahedron 63 (2007) 11862–11877
11873
129.9 (]CH-6), 141.8 (]CCH3), 197.5 (C-2); GC–MS (EI,
70 eV): m/z¼181 (M+, 93), 148 (11), 127 (30), 126 (100),
111 (36), 94 (14), 78 (24), 42 (19). Found: C, 66.38; H,
8.39; N, 7.66; S, 17.70. C10H15NS requires: C, 66.25; H,
8.34; N, 7.73; S, 17.69%.
5.49; S, 13.23. C15H17NS requires: C, 74.03; H, 7.04; N,
5.76; S, 13.18%.
4.7.36. 4-(2-Methyl-allyl)-1-phenyl-3,4-dihydro-1H-pyri-
dine-2-thione (6v). Pale yellow oil. IR (film): n¼3072,
2968, 2928, 1648, 1596, 1492, 1348, 1152, 894, 748, 726,
1
4.7.33. 1-Benzyl-6-(2-methyl-allyl)-3,6-dihydro-1H-pyri-
dine-2-thione (5u). Pale yellow oil. IR (film): n¼3072,
3028, 2963, 1646, 1452, 1348, 1192, 1068, 898, 730,
700 cmꢂ1; 1H NMR (400.1 MHz, CDCl3): d¼1.74 (3H, br s,
]CCH3), 2.26 (1H, dd, J 13.3, 8.9 Hz, 6-CHH), 2.46 (1H,
dd, J 13.3, 4.5 Hz, 6-CHH), 3.52 (1H, dm, J ca. 21 Hz,
3-CHH), 3.92 (1H, dm, J ca. 21 Hz, 3-CHH), 4.07–4.14
(1H, m, CH-6), 4.37 (1H, d, J 15.0 Hz, NCHH), 4.75 (1H, s,
]CHH), 4.87 (1H, quintet, J 1.5 Hz, ]CHH), 5.82–5.88
(2H, m, ]CH-4, ]CH-5), 6.55 (1H, d, J 15.0 Hz, NCHH),
7.24–7.37 (5H, m, C6H5); 13C NMR (100.6 MHz, CDCl3):
d¼22.8 (]CCH3), 41.9 (6-CH2), 42.5 (CH-3), 54.7 (NCH2),
58.0 (6-CH), 115.0 (]CH2), 123.2 (]CH-4), 125.9 (]CH-5),
127.5, 127.8, 128.8, 135.1 (C6H5), 140.2 (]CCH3), 198.3
(C-2); GC–MS (EI, 70 eV): m/z¼257 (M+, 12), 256 (12),
224 (12), 202 (14), 148 (11), 112 (7), 91 (100), 65 (13).
Found: C, 74.65; H, 7.58; N, 5.21; S, 12.33. C16H19NS
requires: C, 74.66; H, 7.44; N, 5.44; S, 12.46%.
694 cmꢂ1; H NMR (400.1 MHz, CDCl3): d¼1.75 (3H, br
s, ]CCH3), 2.16 (2H, d, J 7.6 Hz, 4-CH2), 2.67–2.79 (1H,
m, CH-4), 3.00 (1H, dd, J 16.3, 10.0 Hz, CHH-3), 3.28
(1H, ddd, J 16.3, 6.2, 0.6 Hz, CHH-3), 4.78 (1H, br s,
]CHH), 4.87 (1H, br s, ]CHH), 5.52 (1H, dd, J 7.6,
3.8 Hz, ]CH-5), 6.27 (1H, dd, J 7.6, 1.8 Hz, ]CH-6),
7.26 (2H, dd, J 6.7, 1.4 Hz, C6H5), 7.37 (1H, tt, J 7.4,
1.2 Hz, C6H5), 7.46 (2H, t, J 7.4 Hz, C6H5); 13C NMR
(100.6 MHz, CDCl3): d¼22.3 (]CCH3), 28.8 (CH-4),
42.0 (N-CH2), 47.4 (CH2-3), 113.4 (]CH2), 115.9 (]CH-
5), 126.9, 128.3, 129.5, 144.4 (C6H5), 130.2 (]CH-6),
141.7 (]CCH3), 199.7 (C-2); GC–MS (EI, 70 eV):
m/z¼243 (M+, 65), 210 (13), 190 (18), 189 (42), 188 (100),
186 (46), 173 (13), 156 (13), 155 (14), 154 (19), 132 (14),
130 (20), 109 (14), 104 (14), 78 (24), 77 (44); HRMS (EI)
for C7H11NS: calculated 243.1082; found 243.1072.
4.7.37. 4-(1,1-Dimethyl-allyl)-1-methyl-3,4-dihydro-1H-
pyridine-2-thione (6w). Pale yellow oil. IR (film):
4.7.34. 1-Benzyl-4-(2-methyl-allyl)-3,4-dihydro-1H-pyri-
dine-2-thione (6u). Pale yellow oil. IR (film): n¼3068,
3028, 2932, 1648, 1496, 1458, 1424, 1384, 1352, 1158,
n¼3080, 2968, 1478, 1376, 1132, 1004, 916 cmꢂ1
;
1H
NMR (400.1 MHz, CDCl3): d¼1.00 (6H, s, 2ꢄCH3), 2.25
(1H, dddd, J 9.6, 7.3, 4.0, 2.1 Hz, CH-4), 2.97 (1H, dd,
J 16.8, 9.6 Hz, CHH-3), 3.10 (1H, dd, J 16.8, 7.3 Hz,
CHH-3), 3.47 (3H, s, NCH3), 4.99 (1H, dd, J 17.3, 1.2 Hz,
]CHH), 5.03 (1H, dd, J 10.7, 1.2 Hz, ]CHH), 5.44 (1H,
dd, J 7.8, 4.0 Hz, ]CH-5), 5.70 (1H, dd, J 17.3, 10.7 Hz,
]CH), 6.21 (1H, dd, J 7.8, 2.1 Hz, ]CH-6); 13C NMR
(100.6 MHz, CDCl3): d¼23.6, 23.8 (2ꢄCH3), 39.0
((CH3)2C), 40.2 (CH-4), 41.7 (NCH3), 42.6 (CH2-3), 112.7
(]CH2), 113.9 (]CH-5), 130.6 (]CH-6), 145.4 (]CH),
198.1 (C-2); GC–MS (EI, 70 eV): m/z¼195 (M+, 15), 126
(100). 111 (10), 78 (7), 42 (7); HRMS (EI) for C11H17NS:
calculated 195.1082; found 195.1087.
1104, 948, 894, 728, 696 cmꢂ1 1H NMR (400.1 MHz,
;
CDCl3): d¼1.70 (3H, s, ]CCH3), 2.06 (2H, d, J 7.6 Hz,
4-CH2), 2.54–2.65 (1H, m, CH-4), 2.90 (1H, dd, J 16.5,
10.0 Hz, CHH-3), 3.19 (1H, dd, J 16.5, 6.2 Hz, CHH-3),
4.70 (1H, quartet,
J 0.8 Hz, ]CHH), 4.83 (1H,
s, ]CHH), 5.32 (1H, d, J 14.8 Hz, NCHH), 5.39 (1H, d,
J 14.8 Hz, NCHH), 5.45 (1H, dd, J 7.6, 3.8 Hz, ]CH-5),
6.15 (1H, dd, J 7.6, 1.8 Hz), 7.27–7.37 (5H, m, C6H5); 13
C
NMR (100.6 MHz, CDCl3): d¼22.2 (]CCH3), 28.6 (CH-
4), 41.8 (4-CH2), 46.9 (CH2-3), 55.4 (NCH2), 113.3
(]CH2), 117.3 (]CH-5), 127.6, 127.8, 128.7, 135.6
(C6H5), 128.3 (]CH-6), 141.7 (]CCH3), 198.3 (C-2);
GC–MS (EI, 70 eV): m/z¼257 (M+, 52), 224 (9), 202 (75),
168 (11), 124 (11), 91 (100), 65 (18). Found: C, 74.71; H,
7.51; N, 5.45; S, 12.49. C16H19NS requires: C, 74.66; H,
7.44; N, 5.44; S, 12.46%.
4.7.38. 1-Benzyl-4-(1,1-dimethyl-allyl)-3,4-dihydro-1H-
pyridine-2-thione (6x). Pale yellow oil. IR (film):
n¼3084, 2964, 2928, 2876, 1650, 1496, 1452, 1412, 1388,
1
1164, 1100, 920, 752, 698 cmꢂ1; H NMR (400.1 MHz,
CDCl3): d¼0.99 (6H, s, 2ꢄCH3), 2.23–2.29 (1H, m,
CH-4), 3.04 (1H, dd, J 16.9, 9.8 Hz, CHH-3), 3.18 (1H,
dd, J 16.9, 7.2 Hz, CHH-3), 4.98 (1H, dd, J 17.4, 1.1 Hz,
]CHH), 5.01 (1H, dd, J 10.8, 1.1 Hz, ]CHH), 5.27 (1H,
d, J 14.7 Hz, NCHH), 5.36 (1H, d, J 14.7 Hz, NCHH),
5.43 (1H, dd, J 7.9, 3.9 Hz, ]CH-5), 5.69 (1H, dd, J 17.4,
10.8 Hz, ]CH), 6.20 (1H, dd, J 7.9, 2.1 Hz, ]CH-6),
7.26–7.36 (5H, m, C6H5); 13C NMR (100.6 MHz, CDCl3):
d¼23.7, 23.8 (2ꢄCH3), 39.2 ((CH3)2C), 40.2 (CH-4), 43.2
(CH2-3), 55.5 (NCH2), 112.9 (]CH2), 114.4 (]CH-5),
127.9, 127.9, 128.7, 135.48 (C6H5), 128.9 (]CH-6), 145.4
(]CH), 198.9 (C-2). GC–MS (EI, 70 eV): m/z¼271 (M+, 17),
202 (71). 168 (7), 124 (11), 91 (100), 65 (15), 41 (10);
HRMS (EI) for C17H21NS: calculated 271.1395; found
271.1416.
4.7.35. 6-(2-Methyl-allyl)-1-phenyl-3,6-dihydro-1H-pyri-
dine-2-thione (5v). Pale yellow oil. IR (film): n¼3052,
2968, 2936, 1646, 1596, 1492, 1462, 1406, 1342, 1316,
1242, 1142, 896, 746, 730, 696 cmꢂ1
;
1H NMR
(400.1 MHz, CDCl3): d¼1.61 (3H, s, ]CCH3), 2.24 (1H,
dd, J 13.2, 10.0 Hz, 6-CHH), 2.56 (1H, dd, J 13.2, 4.1 Hz,
6-CHH), 3.66 (1H, dm, J 22.3 Hz, CHH-3), 3.90 (1H,
ddd, J 22.3, 4.8, 2.7 Hz, CHH-3), 4.39–4.52 (1H, m, CH-
6), 4.73 (1H, s, ]CHH), 4.84 (1H, br s, ]CHH), 5.91
(1H, ddd, J 10.1, 4.2, 3.0 Hz, ]CH-4), 6.01 (1H, ddd, J
10.1, 4.2, 3.0 Hz, ]CH-5), 7.24 (2H, d, J 7.8 Hz, C6H5),
7.40 (1H, tt, J 7.5, 1.2 Hz, C6H5), 7.50 (2H, t, J 7.7 Hz,
C6H5); 13C NMR (100.6 MHz, CDCl3): d¼22.6
(]CCH3), 42.3 (6-CH2), 42.5 (CH2-3), 63.1 (CH-6),
114.4 (]CH2), 122.4 (]CH-4), 125.0 (]CH-5), 127.6
br, 128.1, 129.6, 140.1 (C6H5), 144.8 (]CCH3), 199.3 (C-
2); GC–MS (EI, 70 eV): m/z¼243 (M+, 20), 188 (100),
186 (30), 104 (13), 77 (33). Found: C, 73.91; H, 7.19; N,
4.7.39. 4-(1,1-Dimethyl-allyl)-1-phenyl-3,4-dihydro-1H-
pyridine-2-thione (6y). Pale yellow solid, mp 57–59 ꢁC
from n-hexane. IR (KBr pellet): n¼2968, 2924, 1648,

11874
J. G. Soꢀsnicki / Tetrahedron 63 (2007) 11862–11877
1640, 1596, 1494, 1412, 1364, 1310, 1156, 920, 764, 742,
(100), 84 (28), 78 (57), 67 (8), 58 (22), 45 (12), 39 (15).
Found: C, 59.51; H, 8.00; N, 10.04; S, 22.55. C7H11NS
requires: C, 59.53; H, 7.85; N, 9.92; S, 22.70%.
1
696 cmꢂ1; H NMR (400.1 MHz, CDCl3): d¼1.09 (3H, s,
CH3), 1.10 (3H, s, CH3), 2.37 (1H, tdd, J 7.9, 4.4, 1.9 Hz,
CH-4), 3.23 (2H, dd, J 7.9, 0.5 Hz, CH2-3), 5.05 (1H, dd,
J 17.3, 1.1 Hz, ]CHH), 5.08 (1H, dd, J 10.7, 1.1 Hz,
]CHH), 5.51 (1H, dd, J 7.8, 4.4 Hz, ]CH-5), 5.80 (1H,
dd, J 17.3, 10.7 Hz, ]CH), 6.33 (1H, dd, J 7.8, 1.9 Hz,
]CH-6), 7.22–7.26 (2H, m, C6H5), 7.34–7.39 (1H, m,
C6H5), 7.42–7.48 (2H, m, C6H5); 13C NMR (100.6 MHz,
CDCl3): d¼23.7, 24.0 (2ꢄCH3), 39.5 (C(CH3)2), 40.4
(CH-4), 43.6 (CH2-3), 112.7 (]CH-5), 113.0 (]CH2),
126.7, 128.3, 129.5, 144.5 (C6H5), 130.9 (]CH-6), 145.4
(]CH), 200.3 (C-2); GC–MS (EI, 70 eV): m/z ¼257 (29,
M+), 189 (39), 188 (100), 173 (9), 154 (13), 130 (13), 77
(26). Found: C, 74.82; H, 7.56; N, 5.45; S, 12.59.
C16H19NS requires: C, 74.66; H, 7.44; N, 5.44; S, 12.46%.
4.8.2. 6-Butyl-5,6-dihydro-1H-pyridine-2-thione (8b).
Yellow solid (289 mg, 80%), mp 55–57 ꢁC from n-hexane.
IR (KBr pellet): n¼3196 br, 3024, 2956, 2928, 2856, 1626,
1530, 1376, 1352, 1308, 1148, 1112, 1060 cmꢂ1; 1H NMR
(400.1 MHz, CDCl3): d¼0.90 (3H, t, J 8.3 Hz, CH3),
1.30–1.45 (4H, m 2ꢄCH2), 1.52–1.77 (2H, m, CH2), 2.14
(1H, ddt, J 11.5, 2.0 Hz, CHH-5), 2.40 (1H, dt, J 18.0,
5.4 Hz, CHH-5), 3.55 (1H, sextetd, J 6.4, 1.8 Hz, CH-6),
6.32–6.42 (2H, m, CH-3, CH-4), 8.32 (1H, br s, NH); 13C
NMR (100.6 MHz, CDCl3): d¼13.8 (CH3), 22.4 (CH2),
27.3 (CH2), 28.4 (CH2-5), 33.9 (CH2), 52.2 (CH-6), 130.2
(CH-4), 133.3 (CH-3), 192.0 (C-2); GC–MS (EI, 70 eV):
ꢃ
m/z¼169 (28, M+ ), 136 (2), 126 (4), 112 (100), 87 (7), 78
4.7.40. 6-(4-tert-Butyl-2-thioxo-3,4-dihydro-2H-pyridin-
1-ylmethyl)-1-methyl-3,6-dihydro-1H-pyridine-2-thione
(7e). Pale red oil. IR (film): n¼2960, 2872, 1648, 1512,
(21). Found: C, 63.99; H, 8.86; N, 8.11; S, 19.11.
C9H15NS requires: C, 63.85; H, 8.93; N, 8.27; S, 18.94%.
1
1458, 1384, 1348, 1156, 1116, 914, 732 cmꢂ1; H NMR
4.8.3. 6-Pentyl-5,6-dihydro-1H-pyridine-2-thione (8c).
Yellow oil (270 mg, 69%). IR (film): n¼3192 br, 2932,
(400.1 MHz, CDCl3): d¼0.92 (9H, s, C(CH3)3), 2.11–2.18
(1H, m, CH-40), 3.04 (1H, dd, J 16.7, 8.9 Hz, CHH-30),
3.12 (1H, dd, J 16.7, 7.6 Hz, CHH-30), 3.48 (1H, dm,
J 23.3 Hz, CHH-3), 3.56 (3H, s, NCH3), 3.78 (1H, dd,
J 13.1, 2.5 Hz, NCHH), 3.83 (1H, ddd, J 23.2, 4.8, 1.7 Hz,
CHH-3), 4.40 (1H, dd, J 13.1, 6.0 Hz, NCHH), 4.78–4.85
(1H, br m, CH-6), 5.51 (1H, dd, J 7.9, 4.3 Hz, ]CH-50),
5.90 (1H, ddd, J 9.9, 4.8, 3.2 Hz, ]CH-4 or ]CH-5), 5.96
(1H, ddd, J 9.9, 5.0, 1.8 Hz, ]CH-4 or ]CH-5), 6.12
(1H, dd, J 7.9, 1.9 Hz, ]CH-60); 13C NMR (100.6 MHz,
CDCl3): d¼25.9 (C(CH3)3), 32.2 (C(CH3)3), 39.9 (CH-40),
41.0 (CH2-3), 41.8 (NCH3), 42.2 (CH2-30), 55.9 (NCH2),
57.8 (CH-6), 113.7 (]CH-50), 122.2, 124.1 (]CH-4,
]CH-5), 129.2 (]CH-60), 195.7, 199.0 (C-2, C-20);
GC–MS (EI, 70 eV): m/z¼308 (M+, 1), 275 (4). 251 (19),
167 (11), 139 (31), 126 (100), 112 (7), 94 (7), 42 (8);
HRMS (EI) for C16H24N2S2: calculated 308.1381; found
308.1383.
2856, 1620, 1524 br, 1326, 1150 cmꢂ1
;
1H NMR
(400.1 MHz, CDCl3): d¼0.90 (3H, t, J 6.8 Hz, CH3),
1.24–1.41 (6H, m, 3ꢄCH2), 1.56–1.73 (2H, m, CH2), 2.14
(1H, dddd, J 18.1, 11.8, 2.6, 2.3 Hz, CHH-5), 2.39 (1H, dt,
J 18.1, 5.6 Hz, CHH-5), 3.50–3.59 (1H, m, CH-6), 6.34
(1H, ddd, J 9.5, 5.3, 2.8 Hz, ]CH-4), 6.41 (1H, dm,
J 9.5 Hz, ]CH-3), 7.88 (1H, br s, NH); 13C NMR
(100.6 MHz, CDCl3): d¼14.0 (CH3), 22.5 (CH2), 25.0
(CH2), 28.7 (CH2-5), 31.5 (CH2), 34.5 (CH2), 52.4 (CH-6),
130.4 (]CH-3), 133.3 (]CH-4), 192.5 (C-2); GC–MS
(EI, 70 eV): m/z¼183 (33, M+), 182 (31), 150 (6), 126 (7),
112 (100), 84 (9), 78 (25). Found: C, 65.49; H, 9.40; N,
7.75; S, 17.60. C10H17NS requires: C, 65.52; H, 9.35; N,
7.64; S, 17.49%.
4.8.4. 6-Hexyl-5,6-dihydro-1H-pyridine-2-thione (8d).
Yellow oil (278 mg, 66%). IR (film): n¼3188 br, 2924,
1
2856, 1622, 1522, 1328, 1152, 1110, 760 cmꢂ1; H NMR
4.8. Synthesis of 5,6-dihydropyridine-2-thiones 8
(400.1 MHz, CDCl3): d¼0.89 (3H, t, J ca. 7.0 Hz, CH3),
1.23–1.45 (8H, 4ꢄCH2), 1.51–1.73 (2H, m, CH2), 2.14
(1H, ddt, J 18.0, 11.8, 2.6 Hz, CHH-5), 2.39 (1H, dt,
J 18.0, 11.8, 2.6 Hz, CHH-5), 3.55 (1H, sextetd, J 6.7,
1.7 Hz, CH-6), 6.35 (1H, ddd, J 9.7, 5.2, 2.8 Hz, ]CH-4),
6.40 (1H, br d, J 9.7 Hz, ]CH-3), 7.92 (1H, br s, NH);
13C NMR (100.6 MHz, CDCl3): d¼14.0 (CH3), 22.5, 25.3,
28.7, 29.0, 31.6, 34.5 (6ꢄCH2), 52.4 (CH-6), 130.4, 133.3
(]CH-3, ]CH-4), 192.4 (C-2); GC–MS (EI, 70 eV): m/z¼
The mixture of 5 (2.14 mmol) and catalytic amount of DBU
(Table 3) in acetonitrile (5 mL) was stirred at rt for an appro-
priate time (Table 3). After addition of aqueous saturated
NH4Cl (5 mL), the water layer was extracted with ethyl ace-
tate (2ꢄ50 mL) and the combined organic layers were dried
over MgSO4. Filtration, concentration in vacuo, and purifi-
cation by column chromatography (silica gel, n-hexane/
ethyl acetate¼8:2 to 7:3) afforded 7 as yellow product.
ꢃ
197 (36, M+ ), 196 (42), 164 (8), 126 (9), 112 (100), 84 (8),
78 (24). Found: C, 66.99; H, 9.90; N, 7.15; S, 16.25.
C11H19NS requires: C, 66.95; H, 9.70; N, 7.10; S, 16.25%.
4.8.1. 6-Ethyl-5,6-dihydro-1H-pyridine-2-thione (8a).
Yellow oil (245 mg, 81%). IR (film): n¼3196, 2936, 2876,
1622, 1524, 1348, 1154, 1140 cmꢂ1
;
1H NMR
4.8.5. 6-Isobutyl-5,6-dihydro-1H-pyridine-2-thione (8e).
Yellow oil (257 mg, 71%). IR (KBr pellet): n¼3450 v br,
3188 br, 2952, 1624, 1526, 1464, 1428, 1416, 1382, 1312,
(400.1 MHz, CDCl3): d¼1.00 (3H, t, J 7.3 Hz, CH3), 1.64
(1H, septet, J 7.4 Hz, 6-CHH), 1.73 (1H, septet, J 7.4 Hz,
6-CHH), 2.14 (1H, ddt, J 18.1, 11.7, 2.4 Hz, CHH-5), 2.41
(1H, dt, J 18.1, 5.4 Hz, CHH-5), 3.50 (1H, sextet, J ca.
6 Hz, CH-6), 6.36 (1H, ddd, J 9.3, 5.4, 2.9 Hz, ]CH-4),
6.41 (1H, dm, J 9.3 Hz, ]CH-3), 7.98 (1H, s, NH); 13C
NMR (100.6 MHz, CDCl3): d¼9.77 (CH3), 27.4 (6-CH2),
28.2 (CH2-5), 53.7 (CH-6), 130.7 (]CH-3), 133.4 (]CH-4),
192.3 (C-2); GC–MS (EI, 70 eV): m/z¼141 (75, M+), 112
1
1160, 1138, 1112, 1048, 762 cmꢂ1; H NMR (400.1 MHz,
CDCl3): d¼0.94 (6H, d, J 6.5 Hz, 2ꢄCH3), 1.40 (1H, ddd,
J 14.0, 7.6, 6.6 Hz, 6-CHH), 1.59 (1H, dt, J 14.0, ca.
6.9 Hz, 6-CHH), 1.74 (1H, sepd, J 6.6, 0.8 Hz, CH(CH3)2),
2.11 (1H, ddt, J 18.0, 11.7, ca. 2.9 Hz, CHH-5), 2.39 (1H,
dt, J 18.0, 5.7 Hz, CHH-5), 3.58–3.68 (1H, m, CH-6), 6.35
(1H, ddd, J 9.5, 5.2, 2.9 Hz, ]CH-4), 6.41 (1H, br d, J ca.

J. G. Soꢀsnicki / Tetrahedron 63 (2007) 11862–11877
11875
9.7 Hz, ]CH-3), 7.80 (1H, br s, NH); 13C NMR
(100.6 MHz, CDCl3): d¼22.4 (CH3), 22.6 (CH3), 24.3
(CH(CH3)2), 29.1 (CH2-5), 43.5 (6-CH2), 50.4 (CH-6),
130.5 (]CH-3), 133.3 (]CH-4), 192.5 (C-2); GC–MS
6.12 (1H, m, ]CH-4), 6.50 (1H, dd, J 9.5, 3.0 Hz, ]CH-
3); 13C NMR (100.6 MHz, CDCl3): d¼26.7 (CH2-5), 35.1
(6-CH2), 42.6 (N-CH3), 59.7 (CH-6), 119.1 (]CH2),
127.7 (]CH-4), 132.0 (]CH-3), 133.5 (]CH), 188.9
(C-2); GC–MS (EI, 70 eV): m/z¼167 (M+, 48), 166 (28),
134 (23), 126 (100), 111 (30), 97 (10), 85 (13), 42 (39).
Found: C, 64.86; H, 7.82; N, 8.25; S, 18.99. C9H13NS
requires: C, 64.62; H, 7.83; N, 8.37; S, 19.17%.
ꢃ
(EI, 70 eV): m/z¼169 (51, M+ ), 112 (100), 78 (28). Found:
C, 63.99; H, 9.00; N, 8.35; S, 18.71. C9H15NS requires: C,
63.85; H, 8.93; N, 8.27; S, 18.94%.
4.8.6. 6-sec-Butyl-5,6-dihydro-1H-pyridine-2-thione (8f).
Mixture of diastereomers¼1:1. Yellow solid (261 mg, 72%).
IR (KBr pellet): n¼3176, 2960, 2872, 1622, 1530, 1460,
4.8.10. 6-Allyl-1-benzyl-5,6-dihydro-1H-pyridine-2-thi-
one (8j). Yellow oil (479 mg, 92%). IR (film): n¼3072,
2936, 1620, 1484, 1452, 1348, 1320, 1190, 1152, 756,
1
1416, 1378, 1352, 1152, 754 cmꢂ1; H NMR (400.1 MHz,
CDCl3): d¼0.91–1.01 (12H, m, 4ꢄCH3), 1.12–1.35 (2H,
m, 2ꢄCHH), 1.40–1.60 (2H, m, 2ꢄCHH), 1.60–1.78 (2H,
m, 2ꢄ6-CH), 2.18–2.32 (4H, m, 2ꢄCH2-5), 3.47–3.57
(2H, m, 2ꢄCH-6), 6.32–6.43 (4H, m, 2ꢄ]CH-3,
2ꢄ]CH-4), 7.87, 7.95 (two br s, 2ꢄNH); 13C NMR
(100.6 MHz, CDCl3): d¼11.5, 11.7, 14.6, 15.0 (4ꢄCH3),
24.4 (CH2-5), 25.1 (CH2), 25.6 (CH2, CH2-5), 37.9, 38.1
(2ꢄ6-CH), 56.3, 56.6 (2ꢄCH-6), 130.3 (2ꢄ]CH-3),
133.6, 133.6 (2ꢄ]CH-4), 192.8, 192.9 (2ꢄC-2); GC–MS
732, 698 cmꢂ1
;
1H NMR (400.1 MHz, CDCl3): d¼2.30
(1H, dd, J 18.4, 6.4 Hz, CHH-5), 2.30–2.50 (3H, m,
6-CH2, CHH-5), 3.56–3.65 (1H, m, CH-6), 4.28 (1H, d,
J 14.9 Hz, NCHH), 5.05–5.15 (2H, m, ]CH2), 5.59–5.71
(1H, m, ]CH), 6.05–6.10 (1H, m, ]CH-4), 6.33 (1H, d,
J 14.9 Hz, NCHH), 6.62 (1H, dd, J 9.5, 2.8 Hz, ]CH-3),
7.25–7.39 (5H, m, C6H5); 13C NMR (100.6 MHz,
CDCl3): d¼26.9 (CH2-5), 34.5 (6-CH2), 55.2 (NCH2), 55.3
(CH-6), 119.1 (]CH2), 127.7, 127.8, 128.8, 136.5 (C6H5),
127.8 (]CH-4), 132.3 (]CH-3), 133.6 (]CH), 189.7
(C-2); GC–MS (EI, 70 eV): m/z¼243 (M+, 11), 242 (18),
202 (7), 168 (11), 152 (8), 132 (30), 112 (19), 97 (14), 91
(100), 65 (14). Found: C, 74.11; H, 6.88; N, 5.88; S,
13.25. C15H17NS requires: C, 74.03; H, 7.04; N, 5.76;
S, 13.18%.
ꢃ
(EI, 70 eV): m/z¼169 (43, M+ ), 112 (100), 78 (31). Found:
C, 63.75; H, 8.99; N, 8.29; S, 18.98. C9H15NS requires: C,
63.85; H, 8.93; N, 8.27; S, 18.94%.
4.8.7. 6-tert-Butyl-5,6-dihydro-1H-pyridine-2-thione
(8g). Yellow solid (275 mg, 76%), mp 68–70 ꢁC from n-
hexane. IR (KBr pellet): n¼3244 br, 2960, 2868, 1624, 1506,
1
1376, 1318, 1134, 1094, 1116, 760, 710 cmꢂ1; H NMR
4.8.11. 6-Allyl-1-phenyl-5,6-dihydro-1H-pyridine-2-thi-
one (8k). Yellow oil (417 mg, 85%). IR (film): n¼3072,
2940, 1622, 1596, 1492, 1440, 1388, 1388, 1338, 1312,
(400.1 MHz, CDCl3): d¼1.00 (9H, s, C(CH3)3), 2.23 (1H,
ddt, J 18.2, 12.9, 2.0 Hz, CHH-5), 2.30–2.39 (1H, m, CHH-5),
3.29 (1H, ddd, J 12.9, 6.2, 1.5 Hz, CH-6), 6.37 (1H, ddd,
J 9.6, 5.5, 2.7 Hz, ]CH-4), 6.42 (1H, dm, J 9.6 Hz,
]CH-3), 7.53 (1H, br s, NH); 13C NMR (100.6 MHz,
CDCl3): d¼24.1 (CH2-5), 25.8 (C(CH3)3), 33.4 (C(CH3)3),
61.3 (CH-6), 130.0 (]CH-3), 133.7 (]CH-4), 193.3 (C-
1
1166, 922, 760, 698 cmꢂ1; H NMR (400.1 MHz, CDCl3):
d¼2.44–2.62 (3H, m, CHH-5, 6-CH2), 2.77 (1H, ddt,
J 18.3, 7.2, 2.6 Hz, CHH-5), 3.88–3.96 (1H, m, CH-6),
5.04–5.12 (2H, m, ]CH2), 5.50–5.63 (1H, m, ]CH),
6.22 (1H, dddd, J 9.6, 6.3, 2.6, 1.0 Hz, ]CH-4), 6.67 (1H,
ddd, J 9.6, 2.8, 0.7 Hz, ]CH-3), 7.30 (2H, dd, J 7.9,
1.3 Hz, C6H5), 7.38 (1H, tt, J 7.5, 1.2 Hz, C6H5), 7.48 (2H,
t, J 7.8 Hz, C6H5); 13C NMR (100.6 MHz, CDCl3):
d¼26.9 (CH2-5), 35.0 (6-CH2), 60.2 (CH-6), 119.1
(]CH2), 127.8, 128.1, 129.6, 145.2 (C6H5), 128.5 (]CH-4),
132.7 (]CH-3), 133.4 (]CH), 191.0 (C-2); GC–MS (EI,
70 eV): m/z¼229 (M+, 50), 228 (42), 188 (100), 186 (89),
173 (13), 109 (10), 104 (69), 85 (13), 77 (90), 51 (25).
Found: C, 73.30; H, 6.70; N, 6.22; S, 13.99. C14H15NS
requires: C, 73.32; H, 6.59; N, 6.11; S, 13.98%.
ꢃ
2); GC–MS (EI, 70 eV): m/z¼169 (43, M+ ), 112 (100), 78
(26), 41 (6). Found: C, 63.99; H, 8.95; N, 8.34; S, 19.11.
C9H15NS requires: C, 63.85; H, 8.93; N, 8.27; S, 18.94%.
4.8.8. 6-Phenyl-5,6-dihydro-1H-pyridine-2-thione (8h).
Yellow solid (283 mg, 70%), mp 127–130 ꢁC from n-
hexane/ethyl acetate. IR (KBr pellet): n¼3450 v br, 3168
br, 2984, 1620, 1512 br, 1452, 1416, 1376, 1332, 1304, 1134,
762, 700 cmꢂ1
;
1H NMR (400.1 MHz, CDCl3): d¼2.53–
2.61 (2H, m, CH2-5), 4.67 (1H, ddd, J 11.6, 6.6, 1.5 Hz,
CH-6), 6.38 (1H, ddd, J 9.5, 5.3, 3.2 Hz, ]CH-4), 6.51
(1H, dm, J ca. 9.6 Hz, ]CH-3), 7.33–7.44 (5H, m, C6H5),
7.76 (1H, br s, NH); 13C NMR (100.6 MHz, CDCl3):
d¼31.6 (CH2-5), 57.1 (CH-6), 126.8, 128.9, 129.2, 139.6
(C6H5), 130.4 (]CH-3), 132.6 (]CH-4), 193.2 (C-2);
4.8.12. 1-Methyl-6-(2-methyl-allyl)-5,6-dihydro-1H-pyri-
dine-2-thione (8l). Pale yellow oil (322 mg, 83%). IR (film):
n¼3072, 2932, 1624, 1500, 1398, 1346, 1324, 1240, 1124,
896, 746 cmꢂ1
;
1H NMR (400.1 MHz, CDCl3): d¼1.75
ꢃ
GC–MS (EI, 70 eV): m/z¼189 (100, M+ ), 154 (5), 128
(3H, s, ]CCH3), 2.27–2.41 (3H, m, 6-CH2, CHH-5), 2.61
(1H, ddt, J 18.3, 7.4, 2.6 Hz, CHH-5), 3.49 (3H, s,
N-CH3), 3.77 (1H, quartet, J 7.4 Hz, CH-6), 4.74 (1H, s,
]CHH), 4.89 (1H, s, ]CHH), 6.04–6.11 (1H, m, ]CH-
4), 6.51 (1H, dd, J 9.5, 3.0 Hz, ]CH-3); 13C NMR
(100.6 MHz, CDCl3): d¼22.2 (]CCH3), 26.4 (CH2-5),
38.3 (6-CH2), 42.3 (N-CH3), 58.2 (CH-6), 114.9 (]CH2),
127.7 (]CH-4), 132.0 (]CH-3), 140.9 (]CCH3), 188.8
(C-2); GC–MS (EI, 70 eV): m/z¼181 (M+, 24), 148 (12),
126 (100), 85 (8), 78 (24), 42 (38). Found: C, 66.30; H,
8.38; N, 7.77; S, 17.81. C10H15NS requires: C, 66.25; H,
8.34; N, 7.73; S, 17.69%.
(11), 112 (10), 106 (36), 84 (52), 77 (15), 58 (11). Found:
C, 69.89; H, 5.80; N, 7.45; S, 17.01. C11H11NS requires: C
69.80; H, 5.86; N, 7.40; S, 16.94%.
4.8.9. 6-Allyl-1-methyl-5,6-dihydro-1H-pyridine-2-thi-
one (8i). Yellow oil (329 mg, 92%). IR (film): n¼3072,
1
2924, 1624, 1502, 1346, 1320, 1240, 1112, 922 cmꢂ1; H
NMR (400.1 MHz, CDCl3): d¼2.30–2.47 (3H, m, 6-CH2,
CHH-5), 2.64 (1H, ddt, J 18.4, 7.5, 2.7 Hz, CHH-5), 3.49
(3H, s, N-CH3), 3.67 (1H, quartet, J 7.4 Hz, CH-6), 5.08–
5.17 (2H, m, ]CH2), 5.64–5.77 (1H, m, ]CH), 6.05–

11876
J. G. Soꢀsnicki / Tetrahedron 63 (2007) 11862–11877
Piperidines and its Derivatives; Elsevier: Amsterdam, 1991;
For selected reviews on piperidines see: (a) Buffat, M. G. P.
Tetrahedron 2004, 60, 1701–1729; (b) Laschat, S.; Dickner,
T. Synthesis 2000, 1781–1813; (c) Sardina, F. J.; Rapoport,
H. Chem. Rev. 1996, 96, 1825–1849 and references cited
therein.
4.8.13. 1-Benzyl-6-(2-methyl-allyl)-5,6-dihydro-1H-pyri-
dine-2-thione (8m). Yellow oil (523 mg, 95%). IR (film):
n¼3072, 3028, 2936, 1622, 1482, 1452, 1386, 1348, 1322,
1194, 1152, 1096, 950, 896, 758, 734, 700 cmꢂ1; 1H NMR
(400.1 MHz, CDCl3): d¼1.68 (3H, s, ]CCH3), 2.22–2.34
(2H, m, CHH-5, 6-CHH), 2.35–2.43 (1H, m, CHH-5), 2.43
(1H, dd, J 13.6, 10.2 Hz, 6-CHH), 3.66–3.74 (1H, m, CH-6),
4.26 (1H, d, J 14.8 Hz, NCHH), 4.71 (1H, s, ]CHH),
4.86 (1H, t, J 1.4 Hz, ]CHH), 6.08 (1H, dddd, J 9.5, 6.4,
2.3, 1.2 Hz, ]CH-4), 6.33 (1H, d, J 14.8 Hz, NCHH),
6.62 (1H, dd, J 9.5, 2.6 Hz, ]CH-3), 7.27–7.40 (5H, m,
C6H5); 13C NMR (100.6 MHz, CDCl3): d¼22.2 (]CCH3),
26.8 (CH2-5), 38.0 (6-CH2), 53.7 (CH-6), 55.1 (NCH2),
114.8 (]CH2), 127.8, 127.9, 128.8, 136.6 (C6H5), 132.2
(]CH-3), 140.9 (]CCH3), 189.6 (C-2); GC–MS (EI,
70 eV): m/z¼257 (M+, 34), 256 (31), 224 (12), 202 (21),
200 (12), 168 (16), 166 (13), 112 (28), 97 (15), 91 (100),
65 (15). Found: C, 74.49; H, 7.33; N, 5.23; S, 12.44.
C16H19NS requires: C, 74.66; H, 7.44; N, 5.44; S, 12.46%.
3. (a) Pineschi, M.; Moro, F. D.; Gini, F.; Minnaard, A. J.; Feringa,
B. L. Chem. Commun. 2004, 1244–1246; (b) Ecija, M.; Diez,
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Chiaroni, A.; Marazano, C. Synthesis 2000, 14, 2117–2126;
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(d) Imanishi, T.; Yagi, N.; Hanaoka, M. Chem. Pharm. Bull.
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Nakai, A.; Hanaoka, M. Chem. Pharm. Bull. 1983, 31, 1183–
1190; (f) Imanishi, T.; Shin, H.; Hanaoka, M.; Momose, T.;
Imanishi, I. Chem. Pharm. Bull. 1982, 30, 4037–4045; (g)
Imanishi, T.; Yagi, N.; Shin, H.; Hanaoka, M. Chem. Pharm.
Bull. 1982, 30, 4052–4059.
4.8.14. 6-(2-Methyl-allyl)-1-phenyl-5,6-dihydro-1H-pyri-
dine-2-thione (8n). Yellow oil (484 mg, 93%). IR (film):
n¼3072, 2936, 1646, 1622, 1596, 1492, 1440, 1388, 1338,
;
1316, 1166, 898, 760, 732, 696 cmꢂ1 1H NMR
5. (a) Donohoe, T. J.; Johnson, D. J.; Mace, L. H.; Bamford, M. J.;
Ichihara, O. Org. Lett. 2005, 7, 435–438; (b) Sebesta, R.;
Pizzuti, M. G.; Boersma, A. J.; Minnaard, A. J.; Feringa,
B. L. Chem. Commun. 2005, 1711–1713; (c) Klegraf, E.;
Follmann, M.; Schollmeyer, D.; Kunz, H. Eur. J. Org. Chem.
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Chem. 2003, 68, 8867–8878; (e) Comins, D. L.; Killpack,
M. O.; Despagnet, E.; Zeller, E. Heterocycles 2002, 58, 505–
520; (f) Heintzelman, G.; Fang, W.-K.; Keen, S. P.; Wallace,
G. A.; Weinreb, S. M. J. Am. Chem. Soc. 2001, 123, 8851–
8853; (g) Xie, C.; Runnegar, M. T. C.; Snider, B. B. J. Am.
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LaMunyon, D. H.; Chen, X. J. Org. Chem. 1997, 62, 8182–
8187; (i) Heintzelman, G. R.; Weinreb, S. M.; Parvez, M.
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Killpack, M. O. J. Am. Chem. Soc. 1992, 114, 10972–10974;
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794–795; (l) Comins, D. L.; Dehghani, A. J. Chem. Soc.,
Chem. Commun. 1993, 1838–1839; (m) Dodd, D. S.;
Oehlschlager, A. C. J. Org. Chem. 1992, 57, 2794–2803.
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(400.1 MHz, CDCl3): d¼1.54 (3H, br s, ]CCH3), 2.41
(1H, dd, J 13.5, 4.0 Hz, 6-CHH), 5.50 (1H, ddd, J 18.3, 6.4,
1.2 Hz, CHH-5), 2.58 (1H, dd, J 13.5, 11.0 Hz, 6-CHH),
2.75 (1H, ddt, J 18.3, 7.1, 2.4 Hz, CHH-5), 3.97–4.06 (1H,
m, CH-6), 4.71 (1H, br s, ]CHH), 4.84 (1H, br s, ]CHH),
6.21 (1H, dddd, J 9.6, 6.4, 2.5, 1.2 Hz, ]CH-4), 6.68 (1H,
ddd, J 9.6, 2.9, 0.6 Hz, ]CH-3), 7.31 (2H, dd, J 8.5,
1.4 Hz, C6H5), 7.38 (1H, tt, J 7.4, 1.2 Hz, C6H5), 7.48 (2H,
br t, J 7.4 Hz, C6H5); 13C NMR (100.6 MHz, CDCl3):
d¼21.8 (]CCH3), 26.7 (CH2-5), 38.4 (6-CH2), 58.9 (CH-6),
114.6 (]CH2), 127.7, 128.0, 129.6, 145.3 (C6H5), 128.5
(]CH-4), 132.7 (]CH-3), 141.0 (]CCH3), 190.8 (C-2);
GC–MS (EI, 70 eV): m/z¼243 (M+, 34), 242 (20), 188
(100), 186 (72), 173 (11), 104 (45), 77 (48), 51 (11). Found:
C, 73.99; H, 7.05; N, 5.70; S, 13.11. C15H17NS requires: C,
74.03; H, 7.04; N, 5.76; S, 13.18%.
Acknowledgements
The support by the National Committee for Scientific
Research (KBN, Grant No. 3 T09A 106 28) is gratefully
acknowledged.
9. (a) See Ref. 5c; (b) Klegraf, E.; Knauer, S.; Kunz, H. Angew.
Chem., Ind. Ed. 2006, 45, 2623–2626.
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