Diverse reactions of sulfonyl chlorides and cyclic imines

Article abstract of DOI:10.1080/10426507.2011.608097

Although alkanesulfonyl chlorides react with linear imines to give rise to β-sultam derivatives, in this study, they were reacted with various cyclic imines, including 1-pyrroline, oxazoline, 5,6-dihydro-4H-oxazines and thiazines, 4,5-dihydro-3H-benzo[c]azepine, and 3,4-dihydroisoquinoline, to produce diverse products instead of β-sultam derivatives. The results indicate that alkanesulfonyl chlorides react with cyclic imines to generate N-alkanesulfonyl cyclic iminium ions, which are attacked by nucleophiles, such as water and chloride anion, in the reaction systems, affording addition products. The iminium intermediates cannot undergo a ring closure to form β-sultam derivatives. Arenesulfonyl chlorides showed similar behavior when they reacted with cyclic imines. The scope and limitation of the reaction between sulfonyl chlorides and imines were investigated. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426507.2011.608097

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Phosphorus, Sulfur, and Silicon and the
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Diverse Reactions of Sulfonyl Chlorides
and Cyclic Imines
Jing Liu a , Shili Hou a & Jiaxi Xu a
a State Key Laboratory of Chemical Resource Engineering,
Department of Organic Chemistry, Faculty of Science, Beijing
University of Chemical Technology, Beijing, China
Version of record first published: 31 Oct 2011.
To cite this article: Jing Liu , Shili Hou & Jiaxi Xu (2011): Diverse Reactions of Sulfonyl Chlorides and
Cyclic Imines, Phosphorus, Sulfur, and Silicon and the Related Elements, 186:12, 2377-2391
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Phosphorus, Sulfur, and Silicon, 186:2377–2391, 2011
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2011.608097
DIVERSE REACTIONS OF SULFONYL CHLORIDES
AND CYCLIC IMINES
Jing Liu, Shili Hou, and Jiaxi Xu
State Key Laboratory of Chemical Resource Engineering, Department of Organic
Chemistry, Faculty of Science, Beijing University of Chemical Technology,
Beijing, China
GRAPHICAL ABSTRACT
N
N
Ph
O
Ph
CHO
O
S
H
N
Ph
SO2Cl
N
Ph
S
Ph
O
O
N
+
N
Ph
+
Ph
O
S
Ph
N
N
O
O
O
OH
S
O
S
N
N
O
(+)
(+)
Abstract Although alkanesulfonyl chlorides react with linear imines to give rise to β-sultam
derivatives, in this study, they were reacted with various cyclic imines, including 1-pyrroline,
oxazoline, 5,6-dihydro-4H-oxazines and thiazines, 4,5-dihydro-3H-benzo[c]azepine, and 3,4-
dihydroisoquinoline, to produce diverse products instead of β-sultam derivatives. The results
indicate that alkanesulfonyl chlorides react with cyclic imines to generate N-alkanesulfonyl
cyclic iminium ions, which are attacked by nucleophiles, such as water and chloride anion, in
the reaction systems, affording addition products. The iminium intermediates cannot undergo
a ring closure to form β-sultam derivatives. Arenesulfonyl chlorides showed similar behavior
when they reacted with cyclic imines. The scope and limitation of the reaction between sulfonyl
chlorides and imines were investigated.
Keywords Alkanesulfonyl chloride; arenesulfonyl chloride; imine; β-sultam; sulfonyl chloride
INTRODUCTION
β-Sultams (1,2-thiazetidine 1,1-dioxides) have been considered as important sul-
fur analogs of β-lactams, and are key skeletons in pharmaceutical chemistry and crucial
Received 30 May 2011; accepted 18 July 2011.
Address correspondence to Jiaxi Xu, State Key Laboratory of Chemical Resource Engineering, Department
of Organic Chemistry, Faculty of Science, Beijing University of Chemical Technology, Beijing 100029, China.
E-mail: jxxu@mail.buct.edu.cn
2377

2378
J. LIU ET AL.
intermediates in synthetic organic chemistry.1,2 Several synthetic methods for β-sultams
have been developed.3 They have been synthesized via the reaction of alkanesulfonyl
chlorides and imines3–6 and via the reaction of alkylaminosulfonyl chlorides and electron-
rich olefins7,8 through β-aminoalkanesulfonyl halides,3,8,9 which were prepared from the
Michael addition of amines to alkyl α,β-alkenesulfonates, hydrolysis, and subsequent halo-
genation,8 or from nucleophilic ring opening of thiiranes with amines or aziridines with
hydrogen sulfide and subsequent oxidation with chlorine or N-chlorosuccimide (NCS),7
via cyclization of β-hydroxyalkanesulfonamides through their methanesulfonates10 or via
cyclization of α-haloalkanesulfonamides in the presence of bases.11
Since most of efficient β-lactam antibiotics are polycyclic compounds containing a
fused β-lactam moiety, polycyclic compounds containing a fused β-sultam moiety are also
of pharmaceutical interest.2,9,12 β-sultam-fused polycycles have only been prepared either
by cyclocondensation of 2-aminoethanesulfonyl chloride hydrochloride derivatives in ethyl
acetate in the presence of potassium carbonate as base9 or by cyclization of amines with
vinylsulfonyl fluoride derivatives via tandem Michael addition and aminolysis in multiple
steps with limitation of the structural diversity of products.8 We investigated the reactivity
of various alkanesulfonyl chlorides and cyclic imines and present herein our results.
RESULTS AND DISCUSSION
Synthesis of Alkanesulfonyl Chlorides
Alkanesulfonyl chlorides can be prepared from the corresponding alkanethiols, alkyl
disulfides, and alkylthio acetates via chlorine13,14 or NCS15 oxidation (Scheme 1). Benzylth-
iol and butanethiol were oxidized with chlorine and NCS, respectively. The results indicate
that the chlorine oxidation gave rise to higher yields of products than the NCS oxidation
(Table 1, entries 1–4). However, alkanesulfinyl chlorides were observed (by NMR analysis
for the products) under chlorine oxidation when insufficient chlorine was bubbled in. It
is inconvenient to control the amount of chlorine gas in laboratory and excessive chlorine
gas also pollutes the environment. The NCS oxidation is a convenient and maneuverable
procedure despite that it produced lower yields of the products. Thus, ethyl disulfide and
N-acetylthiomethylphthalimide were oxidized with NCS to afford ethanesulfonyl and ph-
thalimidomethanesulfonyl chlorides, respectively, in satisfactory yields (Table 1, entries
5–6).
Cl2, CHCl3
R
SH
R
SO2Cl
SO2Cl
80% AcOH
R
SH
NCS
S
R
R
S
R
2M HCl-MeCN
O
R
S
R = Ph, Pr, Me, PhthN
Scheme 1 Synthesis of alkanesulfonyl chlorides.

DIVERSE REACTIONS OF SULFONYL CHLORIDES AND CYCLIC IMINES
2379
Table 1 Synthesis of alkanesulfonyl chlorides
Entry
Thiol/disulfide/thioester
Oxidant
Product
Yield (%)
1
2
3
4
5
6
BnSH
BuSH
BnSH
BuSH
EtSSEt
PhthNCH2SAc
Cl2
Cl2
NCS
NCS
NCS
NCS
BnSO2Cl13
BuSO2Cl14
BnSO2Cl
98.5
80
67.6
67.6
47.9
48.5
BuSO2Cl
EtSO2Cl15
PhthNCH2SO2Cl16
Reactions of Sulfonyl Chlorides and Imines
Although it has been reported that alkanesulfonyl chlorides react with linear imines
to yield β-sultam derivatives, only imines generated from alkylamines and arylmethy-
lamines were used in the reported examples.3–6 To investigate the generality of the re-
action, we conducted the reactions of alkanesulfonyl chlorides with two equivalents of
N-benzylidenebenzylamine according to the reported procedure.3–6 The reactions of ben-
zylsulfonyl and ethanesulfonyl chlorides produced the corresponding cis- and trans-2-
benzyl-3,4-diphenyl-β-sultams (cis-1a and trans-1a) or cis- and trans-2-benzyl-4-methyl-
3-phenyl-β-sultams (cis-1b and trans-1b), respectively, in lower yields, as reported.4 In
the reaction of ethanesulfonyl chloride, N-benzyl-ethanesulfonamide was also obtained,
with a yield of 39%. N-Benzyl-butanesulfonamide was obtained as sole product, with
a 3% yield, in the reaction of butanesulfonyl chloride and N-benzylidenebenzylamine.
However, no reaction occurred between phthalimidomethanesulfonyl chloride and N-
benzylidenebenzylamine (Scheme 2). We also conducted the reactions of all prepared
alkanesulfonyl chlorides with N-benzylideneaniline. No reaction occurred in each of the
cases (Scheme 2). We also attempted the reaction of benzylsulfonyl chloride with one
equivalent of N-benzylideneaniline and benzylamine, respectively, in the presence of tri-
ethylamine (as the Staudinger reaction of acyl chlorides and imines).17 Trans-stilbene was
Ph
Bn
O
Ph
Bn
O
H
N
N2
Bn
N
S
O
N
S
O
R
SO2Cl
+ Ph
N
+
R
+
S
Bn
RT
O
O
R
R
(+)
cis-1a 18% trans-1a 22%
1b 1b
(+)
R = Ph
R = Me
R = Pr
cis-
5% trans-
8%
29%
3%
R = PhthNCH2 No reaction
N2
RT
Ph
R
SO2Cl
+
No Rxn
Ph
N
R = Ph, Pr, Me, PhthN
THF, N2
Bn
Ph
Ph
SO2Cl
+
Ph
N
Ph
Et3N, RT
20%
Scheme 2 Reactions of alkanesulfonyl chlorides with linear imines.

2380
J. LIU ET AL.
obtained as sole product instead of the desired β-sultams (Scheme 2). Juzo et al. proposed
the formation mechanism of trans-stilbene.18 On the basis of the reported results3–6 and our
findings, we can conclude that alkanesulfonyl chlorides can only react with N-alkylimines to
yield β-sultams, with the excessive imines themselves acting as bases to dehydrochlorinate.
Since no example on the reaction of alkanesulfonyl chlorides and cyclic imines
has been reported till now, we first attempted to react benzylsulfonyl and ethanesulfonyl
chloride with dibenzo[b,f][1,4]oxazepine, a cyclic imine with an N-aryl group. Like linear
N-aryl imines, no reaction occurred. Both linear and cyclic N-arylimines cannot react
with alkanesulfonyl chloride, possibly because N-arylimines show weaker basicity than N-
alkylimines and cannot dehydrochlorinate from alkanesulfonyl acid derivatives (Scheme 3).
O
N2
R
SO2Cl
+
No Rxn
RT
N
R = Ph, Me
Scheme 3 Attempted reaction of alkanesulfonyl chlorides with dibenzo[b,f][1,4]oxazepine, a cyclic imine with
an N-aryl group.
In a further investigation, we only applied cyclic imines with N-alkyl
groups. A series of cyclic N-alkyl-imines, including 1-pyrroline, oxazoline, 4,5-
dihydro-3H-dihydrooxazines, thiazines, 4,5-dihydro-3H-benzo[c]azepine, and 3,4-
dihydroisoquinoline, was synthesized according to the reported procedure and reacted
with alkanesulfonyl chlorides. Diverse results were obtained.
2-Phenyl-1-pyrroline reacted with benzylsulfonyl chloride to give 1-benzylsulfonyl-
2-phenyl-2-pyrroline (2) via N-benzylsulfonylation and the double bond shift (Scheme 4).
The results indicate that the acidity of the hydrogen atom in the C3 atom of the pyrrolinium
is stronger than that in the Cα of the N-benzylsulfonyl group in the 1-benzylsulfonyl-2-
phenyl-1-pyrrolinium intermediate, generated from 2-phenyl-1-pyrroline and benzylsul-
fonyl chloride.
Ph
O
N
THF, N2
RT
O
Ph
SO2Cl +
Ph
S
N
Ph
2
30%
Scheme 4 Reaction of benzylsulfonyl chloride with 2-phenyl-1-pyrroline.
Interestingly, 2-phenyloxazoline and 2-phenyl-5,6-dihydro-4H-1,3-oxazine reacted
with benzylsulfonyl chloride to give rise to N-(2-hydroxyethyl)benzamide (3a) and N-(3-
hydroxypropyl)benzamide (3b), respectively. It is obviously different from the reaction with
alkanoyl chlorides, in which N-(2-hydroxyethyl)- and N-(3-hydroxypropyl)alkanamides
were obtained rather than the corresponding benzamides.19 In the current cases, benzamides
were generated rather than benzylsulfonamides, revealing that N-benzylsulfonylation did
not occur and the corresponding benzamides yielded via sulfonic acid-catalyzed hydrol-
ysis during workup. The sulfonic acid was formed from sulfonyl chloride reacting with

DIVERSE REACTIONS OF SULFONYL CHLORIDES AND CYCLIC IMINES
2381
water during workup (Scheme 5). However, no reaction was observed when ethyl 5,5-
dimethylthiazolidine-4-carboxylate and 5,6-dihydro-4H-1,3-thiazines reacted with benzyl-
sulfonyl chloride (Scheme 5).
N
O
THF, N2
RT
Ph
SO2Cl +
Ph
OH
n
n
O
N
Ph
H
3a, n = 1, 21%
3b
, n = 2, 11%
S
THF, N2
Ph
SO2Cl
SO2Cl
+
No Rxn
0 oC to RT
N
CO2Et
N
THF, N2
0 oC to RT
Ph
+
R
No Rxn
S
R = Me, Ph, 4-MeOC6H4
Scheme 5 Reaction of benzylsulfonyl chloride with oxazoline, thiazoline, 5,6-dihydro-4H-1,3-oxazine and
thiazines.
4,5-Dihydro-3H-benzo[c]azepine reacted with alkanesulfonyl chloride to give rise
to N-[3-(2-formylphenyl)propyl]alkanesulfonamides (4) via N-alkanesulfonylation and
the further hydrolysis during workup as the reaction of oxazoline with acyl chlorides19
(Scheme 6).
CHO
N
THF, N2
H
N
R
SO2Cl
+
RT
S
R
O
O
4a, R = Ph, 51%
4b
, R = Me, 63%
Scheme 6 Reaction of alkanesulfonyl chlorides and 4,5-dihydro-3H-benzo[c]azepine.
The reaction of 3,4-dihydroisoquinoline with alkanesulfonyl chlorides led to
complex products (Scheme 7). It gave rise to rel-(8S,9aS,12aS)- and rel-(8R,9aR,12aS)-
9-phenyl-5,6,9,9a,14,15-hexahydro-16aH-diisoquinolino[2,1-b:2ꢁ,1ꢁ-d][1,2,4]thiadiazine-
8,8-dioxides (SSS-5 and RRS-5), a formal [2 + 2 + 2] cycloadduct generated
from benzylsulfonyl chloride and two molecules of 3,4-dihydroisoquinoline and 2-
(benzylsulfonyl)-1,2,3,4-tetrahydroisoquinolin-1-ol (6), generated via benzylsulfonylation
and subsequent addition with water and deprotonation during workup, in very low yields
when it reacted with benzylsulfonyl chloride, while it produced 1-chloro-2-(ethylsulfonyl)-
1,2,3,4-tetrahydroisoquinoline (7) as sole product, generated via ethanesulfonylation
and subsequent addition with chloride anion in the reaction system, when it reacted
with ethanesulfonyl chloride. The results indicate that the N-alkanesulfonyliminium ions
generated in the reactions could not undergo a ring closure to produce β-sultams, but

2382
J. LIU ET AL.
THF, N2
0 oC to RT
+
N
Ph
N
+
+
SO2Cl
Ph
Ph
O
N
S
Ph
N
O
O
O
OH
S
S
N
O
N
6a
O
2%
5
(+)-SSS-
5
(+)-RRS-
2%
4%
THF, N2
0 oC to RT
N
H
S
Ph
SO2Cl +
N
O
N
S
O
O
O
O
Cl
6a
7a
2%
Scheme 7 Reaction of alkanesulfonyl chlorides with 3,4-dihydroisoquinoline.
underwent an addition with another molecule of 3,4-dihydroisoquinoline and subsequent
ring closure to generate formal [2 + 2 + 2] products, or underwent nucleophilic additions
with chloride anion in the reaction system or with water during workup, affording
1-chloro-2-alkylsulfonyl- 1,2,3,4-tetrahydroisoquinoline (6) or 2-alkylsulfonyl-1,2,3,4-
tetrahydroisoquinolin-1-ol (7), respectively (Scheme 8). For linear and other cyclic imines,
the water addition to the N-sulfonylated iminium ions resulted in the hydrolysis of the
iminium ions to afford N-alkylsulfonamide derivatives (Schemes 2 and 6).
The structures of products 5 were determined via 1H and 13C NMR, and mass spectra
and were confirmed by an X-ray structure analysis. On comparison with the corresponding
+
OH
OH2
O
O
O
O
S
S
-H+
Bn
N
Bn
N
6a
H2O
Cl
O
O
O
O
Cl-
S
S
PhCH2SO2Cl
-Cl-
Bn
N
Bn
N
N
7
N
+
Ph
O
Ph
O
Ph
O
Ph
O
N
N+
N+
N
N
S
O
S
S
S
O
N
N
N
N
-
NH+
O
O
(+)-SSS-5
(+)
(+)
(+)-RRS-5
Scheme 8 Mechanism of in the reaction of alkanesulfonyl chlorides with 3,4-dihydroisoquinoline.

DIVERSE REACTIONS OF SULFONYL CHLORIDES AND CYCLIC IMINES
2383
Figure 1 ORTEP structure of compound ( )-SSS-5.
desired β-sultam, five more aliphatic protons and four more aromatic protons were ob-
served in their 1H spectra and three more aliphatic carbons and four or five more aromatic
carbons were found in their 13C NMR spectra. Their high-resolution mass spectra indi-
cated that the products were composed of one molecule of PhCH SO2 and two molecules
of 3,4-dihydroisoquinoline. Referring to the formation mechanism of the products from
one molecule of ketene and two molecules of imines,20–22 the structures of products
5 were suggested as 9-phenyl-5,6,9,9a,14,15-hexahydro-16aH-diisoquinolino[2,1-b:2ꢁ,1ꢁ-
d][1,2,4]thiadiazine-8,8-dioxides with rel-(8S,9aS,12aS)- and rel-(8R,9aR,12aS)- configu-
rations because the vicinal CH CH group shows coupling constants of 10.4 and 9.6 Hz,
respectively, demonstrating that these two protons exhibit the trans-position in the 1,2,4-
thiadiazine ring. It was assumed that ( )-SSS-5 was generated in a lower yield (2%) than
( )-RRS-5 (4%) due to steric hindrance in the ring closure because the formation of the
1,3-anti-structure in ( )-RRS-5 is more favorable than that of the 1,3-syn-structure in ( )-
SSS-5 (Scheme 8). The structure of ( )-SSS-5 was further confirmed by X-ray structural
analysis (Figure 1).
1
The structure of product 6 was identified via H and 13C NMR, and mass spec-
tra. Its 13C NMR spectrum illustrated that was composed of benzylsulfonyl and 3,4-
1
dihydroisoquinoline. Its H NMR spectrum indicated that 3,4-dihydroisoquinoline was
benzylsulfonylated because a singlet peak at 4.35 (2H) and nine aromatic protons were
observed. Additionally, two doublet peaks at 2.94 (1H) and 6.02 (1H), respectively, with a
coupling constant J = 5.3 Hz were observed and the peak at 2.94 disappeared after addition
of a drop of D2O, revealing that it was due to OH and that the peak at 6.02 was connected
with an aromatic carbon, an oxygen, and a nitrogen atom. The mass spectrum also supports
the structure. After identification of the structure of product 6, it is very easy to determine
the structure of product 7 because a peak at 6.74 (s, 1 H) in its 1H NMR is connected with

2384
J. LIU ET AL.
Table 2 Selected bond lengths (Å)
Bond
Distance
Bond
Distance
S1 O2
S1 O1
S1 N1
S1 C19
N1 C1
N1 C1ꢁ
N1 C9
N2 C9
N2 C18
N2 C10
1.433(2)
1.439(2)
1.648(2)
1.797(2)
1.372(2)
1.395(2)
1.496(2)
1.450(2)
1.465(2)
1.472(2)
C1 C2
1.516(1)
1.534(1)
1.397(2)
1.517(2)
1.517(2)
1.506(3)
1.393(2)
1.519(2)
1.574(2)
1.511(2)
C1ꢁ C2ꢁ
C3 C8
C8 C9
C10 C11
C11 C12
C12 C17
C17 C18
C18 C19
C19 C20
an aromatic carbon, a nitrogen, and a chlorine atom. The mass spectrum also supports the
suggested structure.
It is well known that hemiacetals and N-hemiacetals are generally unstable in acidic
aqueous solution. Although product 6a possesses a structural feature of N-sulfonylated
N-hemiacetals, it is still stable due to the intramolecular hydrogen bond between the
hydroxyl group and the oxygen atom in the sulfonyl group. A similar phenomenon was
observed previously for the oxidation of 2-(2-methoxyphenyl)-4-phenyl-2,3-dihydro-1H-
1,5-benzodiazepine with m-chloroperbenzoic acid.23
A crystal (0.53 × 0.46 × 0.42 mm3) of compound ( )-SSS-5 (C25H24N2O2S, Mr =
416.52) was crystallized from a mixture of ethyl acetate and petroleum ether (60–90◦C). It
crystallizes in the monoclinic space group P21/n, with cell dimensions a = 0. 9852(2) nm,
b = 1.5942(4) nm, c = 1.3118(3) nm, α = 90◦, β = 95.199(3)◦, γ = 90◦, V = 2.0519(8)
nm3, Z = 4, Dc = 1.348 mg·m−3, F(000) = 880, and µ = 18.3 cm−1. The structure was
solved by direct methods and refined by full-matrix least squares. The final discrepancy
factor is 0.0369 for 5428 observed reflections. The selected bond lengths and bond angles
are compiled in Tables 2 and 3.
Table 3 Selected bond angles (◦)
Angle
(◦)
Angle
(◦)
O2 S1 O1
O2 S1 N1
O1 S1 N1
O2 S1 C19
O1 S1 C19
N1 S1 C19
C1 N1 C1ꢁ
C1 N1 C9
C1ꢁ N1 C9
C1 N1 S1
C1ꢁ N1 S1
C9 N1 S1
C9 N2 C18
C9 N2 C10
118.3(1)
108.1(1)
109.0(1)
110.1(1)
108.1(1)
102.1(1)
46.8(2)
120.1(2)
122.3(2)
125.3(2)
114.5(2)
112.1(1)
112.3(1)
116.1(1)
C18 N2 C10
N1 C1 C2
112.6(1)
114.3(5)
110.4(4)
113.9(6)
112.6(1)
110.7(1)
111.0(1)
110.3(1)
111.4(1)
111.4(1)
115.2(1)
111.0(1)
107.9(1)
109.9(6)
N1 C1ꢁ C2ꢁ
C3 C2ꢁ C1ꢁ
N2 C9 N1
N2 C9 C8
N1 C9 C8
N2 C18 C17
N2 C18 C19
C17 C18 C19
C20 C19 C18
C20 C19 S1
C18 C19 S1
C3 C2 C1

DIVERSE REACTIONS OF SULFONYL CHLORIDES AND CYCLIC IMINES
2385
From the above reactions, we found that the N-sulfonylated iminum ions can undergo
addition reactions with weak nucleophiles, such as water and chloride anions. To explore
the reactivity of N-alkanesulfonyl-3,4-dihydroisoquinolinium ions with weak nucleophiles,
we conducted the reactions of 4-nitrobenzenesulfonyl chloride and 3,4-dihydroisoquinoline
in the presence of weak nucleophilic ether solvents or additives. We used the arenesulfonyl
chloride instead of alkanesulfonyl chlorides to avoid the formation of cyclization products
for convenient purification of addition products. The reaction of 4-nitrobenzenesulfonyl
chloride and 3,4-dihydroisoquinoline in toluene with strained oxirane as an additive
gave rise to N-(4-nitrobenzenesulfonyl)-1,2,3,4-tetrahydroisoquinolin-1-ol (6b) and 1-(2-
chloroethoxy)-N-(4-nitrobenzenesulfonyl)- 1,2,3,4-tetrahydroisoquinoline (8a). The yield
of the product of water addition (6b) was indeed improved to 36% here. The yield of 6b is
higher than that of 8a, possibly because oxirane is more bulky than water in nucleophilic
attack. The reaction of 4-nitrobenzenesulfonyl chloride and 3,4-dihydroisoquinoline in 1,4-
dioxane generated N-(4-nitrobenzenesulfonyl)-1,2,3,4-tetrahydroisoquinolin-1-ol (6b) and
1-chloro-N-(4-nitrobenzenesulfonyl)-1,2,3,4-tetrahydroisoquinoline (7b), and 1-ethoxy-N-
(4-nitrobenzenesulfonyl)-1,2,3,4-tetrahydroisoquinoline (9) as well. The mechanism of
the formation of product 9 is not clear now (Scheme 9). 1-(2-Chloroethoxy)-N- (4-
nitrobenzenesulfonyl)-1,2,3,4-tetrahydroisoquinoline (8a) was generated via arenesulfony-
lation and oxirane nucleophilic addition to the iminium intermediate, followed by nu-
cleophilic ring opening of the oxirane ring in the generated intermediate with chloride
(Scheme 10).
toluene, N2
O
O2N
SO2Cl
+
+
N
NO2
NO2
N
O
S
N
+
S
O
O
O
O
Cl
OH
6b 36%
8a 6%
O
O
N2
O2N
SO2Cl
+
N
NO2
NO2
NO2
+
+
N
N
N
S
S
S
O
O
O
O
O
O
OH
Cl
7b 2%
EtO
6b 5%
9 6%
Scheme 9 Reaction of arenesulfonyl chlorides with 3,4-dihydroisoquinoline in the presence of weak nucleophilic
ethers.

2386
J. LIU ET AL.
Cl
O+
O
S
O
O
O
O
O
O
O
Cl-
S
S
ArSO2Cl
-Cl-
Ar
N
N
Ar
N
Ar
N
8a
O
O
O
O+
O
O
O
O
O
S
S
N
Ar
Ar
N
9
Scheme 10 Mechanism of the reaction of arenesulfonyl chlorides with 3,4-dihydroisoquinoline in the presence
of weak nucleophilic ethers.
CONCLUSION
In conclusion, the scope and limitation of the reaction of imines with sulfonyl chlo-
rides were evaluated. The results indicate that only acyclic N-alkylimines can react with
alkanesulfonyl chlorides to afford β-sultam derivatives. Reactions of several alkanesulfonyl
chlorides and various cyclic imines were investigated. The reactions studied cannot pro-
duce the corresponding β-sultam product, instead of the double bond shifted, ring-opened,
nucleophilic addition products in low yields. The results reveal that it is hard to prepare
fused polycyclic β-sultam derivatives from alkanesulfonyl chlorides and cyclic imines via
cycloaddition.
EXPERIMENTAL
General
Melting points were obtained on a Yanaco MP-500 melting point apparatus and
1
are uncorrected. The H NMR and 13C NMR spectra were recorded on Varian Mercury
200, Varian Mercury 300 Plus, or Bruker 400 or 600 spectrometer with TMS as an in-
ternal standard in CDCl3 solution and the chemical shifts (δ) are reported in parts per
million (ppm). The IR spectra (KBr pellets, v [cm−1]) were taken on a Nicolet 5700 FTIR
spectrometer. HRMS measurements were carried out on an Agilent LC/MSD TOF mass
spectrometer. TLC separations were performed on silica gel GF254 plates, and the plates
were visualized with UV light. Analytic data of all synthetic alkanesulfonyl chlorides are
identical to those reported.13–16 All cyclic imines (pyrroline,24 oxazoline,18 5,6-dihydro-4H-
oxazine25 and thiazines,26 3,4-dihydroisoquinoline,27 4,5-dihydro-3H-benzo[c]azepine,28
and dibenzo[b,f][1,4]oxazepine29) were synthesized according to reported methods. PE
and EA are abbreviations for petroleum ether (60–90◦C) and ethyl acetate, respectively.

DIVERSE REACTIONS OF SULFONYL CHLORIDES AND CYCLIC IMINES
2387
Reaction of Alkanesulfonyl Chlorides with Imines: General Procedure
To a solution of an imine (10 mmol) in anhydrous THF (10 mL) was added dropwise a
solution of an alkanesulfonyl chloride (5 mmol) in anhydrous THF (10 mL) in an ice-water
bath (for the reaction of ethanesulfonyl chloride with benzylidene benzylamine without
solvent). After addition, the resulting mixture was further stirred in the ice-water bath for
24 h and further at r.t. for 48 h. After the filtration of salts and removal of solvent, the
residue was purified via silica gel column chromatography (PE/EA 1:1 to 10:1, v/v) to
afford colorless crystals.
( )-cis-2-Benzyl-3,4-diphenyl-β-sultam (cis-1a). Colorless crystals, 0.33 g (18%).
mp 156–157◦C.4 mp 156–157◦C. Rf = 0.30 (PE/EA = 3:2, v/v). 1H NMR (200 MHz) δ:
4.30 (d, J = 14.2 Hz, 1H, CH2), 4.54 (d, J = 14.4 Hz, 1H, CH2), 4.87 (d, J = 8.2 Hz, 1H,
NCH), 5.73 (d, J = 8.2 Hz, 1H, SCH), 7.09 Å) 7.49 (m, 15 H, ArH).
( )-trans-2-Benzyl-3,4-diphenyl-β-sultam (trans-1a). Colorless crystals, 0.40 g
(22%); mp 98–100◦C.4 mp 98–100◦C. Rf = 0.60 (PE/EA = 3:2, v/v). 1H NMR (200 MHz)
δ: 4.23 (d, J = 14.4 Hz, 1H, CH2), 4.3 (d, J = 14.4 Hz, 1H, CH2), 4.36 (d, J = 6 Hz, 1H,
NCH), 5.22 (d, J = 6 Hz, 1H, SCH), 7.31–7.51 (m, 15 H, ArH).
( )-cis-2-Benzyl-4-methyl-3-phenyl-β-sultam (cis-1b). Colorless crystals, 21 mg
(5%); mp 60–62◦C. Rf = 0.50 (PE: EA = 5:1, v/v). IR: 1353 (S O), 1140 (S O). 1H NMR
(300 MHz) δ: 1.09 (d, J = 7.2 Hz, 3H, CH3), 4.17 (d, J = 14.4 Hz, 1H, CH2), 4.35 (d,
J = 14.4 Hz, 1H, CH2), 4.49 (d, J = 8.1 Hz, 1H, CH), 4.35 (dt, J = 7.2, 8.1 Hz, 1H, CH),
7.27–7.36 (m, 10H, ArH). HRMS (ESI) m/z for C16H18NO2S+ [M + H]+: Calc., 288.1053;
Found, 288.1063.
( )-trans-2-Benzyl-4-methyl-3-phenyl-β-sultam (trans-1b). Colorless crystals,
16 mg (8%); mp 108–110◦C. Rf = 0.70 (PE: EA = 5:1, v/v). IR: 1324 (S O), 1156
(S O). 1H NMR (300 MHz) δ: 1.56 (d, J = 6.9 Hz, 3H, CH3), 3.69 (d, J = 6.3 Hz, 1H,
CH), 4.06 (d, J = 14.1 Hz, 1H, CH2), 4.16 (dt, J = 6.9, 6.3 Hz, 1H, CH), 4.28 (d, J = 14.1
Hz, 1H, CH2), 7.31–7.51 (m, 10 ArH). HRMS (ESI) m/z for C16H18NO2S+ [M + H]+:
Calc., 288.1053; Found, 288.1063.
N-Benzyl-ethanesulfonamide. Colorless crystals, 0.58 g (29%); mp 60–62◦C.30
mp 56–58◦C. 1H NMR (200 MHz) δ: 1.33 (t, J = 7.5 Hz, 3H, CH3), 2.97 (q, J = 7.5 Hz,
2H, CH2), 4.31 (d, J = 4.0 Hz, 2H, NCH2), 4.52 (bs, 1H, NH), 7.33–7.37 (m, 5H, ArH).
N-Benzyl-butanesulfonamide. Colorless crystals, 0.34 g (3%); mp 72–74◦C.31 mp
72–74◦C. 1H NMR (200 MHz) δ: 0.87 (t, J = 7.5 Hz, 3H, CH3), 1.38 (m, 2H, CH2), 1.72
(m, 2H, CH2N), 2.91 (t, J = 7.5 Hz, 2H, CH2S), 4.31 (d, J = 4.0 Hz, 2H, NCH2), 4.57 (bs,
1H, NH), 7.30–7.40 (m, 5 H, ArH).
1-Benzylsulfonyl-2-phenyl-2-pyrroline (2). Colorless crystals, 0.12 g in 1-mmol
scale (29%), mp 162◦C, Rf = 0.4 (PE:EA = 1/1, v/v). IR: 1610 (C C), 1323 (S O), 1124
(S O). 1H NMR (600 MHz) δ: 2.41 (ddd, J = 18.7, 14.3, 9.1 Hz, 1H, CH2), 2.71 (dd, J =
14.3, 7.3 Hz, 1H, CH2), 4.12 (s, 2H, CH2), 4.09–4.15 (m, 1H in CH2), 4.29 (ddd, J = 16.7,
8.9, 1.3 Hz, 1H, CH2), 4.72 (d, J = 9.9 Hz, 1H, CH), 7.35–7.37 (m, 2H, ArH), 7.39–7.42
(m, 5H, ArH), 7.45 (t, J = 7.3 Hz, 1H, ArH), 7.80 (d, J = 7.3 Hz, 2H, ArH). 13C NMR
(75 MHz) δ: 27.9, 59.1, 60.4, 68.3, 126.9, 128.4, 128.5, 128.9, 129.1, 130.8, 131.0, 133.0,
165.4. HRMS (ESI) m/z C17H19NO2S+ for [M + H]+: Calcd., 300.1053; Found, 300.1053.
N-(2-Hydroxyethyl)benzamide (3a). Colorless crystals, 0.17 g (21%); mp
93–95◦C,32 mp 61–63◦C. Rf = 0.50 (PE: EA = 1:1, v/v). 1H NMR (600 MHz) δ: 3.81 (q,
J = 5.4 Hz, 2H, CH2), 3.88 (q, J = 5.4 Hz, 2H, CH2), 4.36 (bs, 1H, OH), 6.67 (bs, 1H,
NH), 7.44 (t, J = 7.2 Hz, 2H, ArH), 7.52 (t, J = 7.2 Hz, 1H, ArH), 7.79 (t, J = 7.2 Hz,
2H, ArH). 13C NMR (150 MHz) δ: 41.6, 44.1, 126.9, 128.6, 131.7, 134.1, 167.6.

2388
J. LIU ET AL.
N-(3-Hydroxypropyl)benzamide (3b). Colorless crystals, 0.10 g (11%); mp
56–58◦C.33 mp 56–58◦C. Rf = 0.50 (PE: EA = 1:1, v/v). 1H NMR (600 MHz) δ: 2.09 (q,
J = 6.5 Hz, 2H, CH2), 3.58 (t, J = 6.5 Hz, 2H, NCH2), 3.61 (t, J = 6.5 Hz, 2H, OCH2),
6.86 (bs, 1H, NH), 7.39 (t, J = 7.8 Hz, 2H, ArH), 7.48 (t, J = 7.8 Hz, 1H, ArH), 7.78 (d,
J = 7.8 Hz, 2H, ArH).
N-[3-(2-Formylphenyl)propyl]benzylsulfonamide (4a). Colorless oil, 80 mg in
0.5-mmol scale (51%). Rf = 0.50 (PE: EA = 1:1, v/v). IR (neat): 3290 (NH), 1693 (C O),
1
1322 (S O), 1151 (S O), 1083 (S N). H NMR (400 MHz) δ: 10.0 (s, 1H, CHO),
7.71–7.16 (m, 9 H, ArH), 4.19 (s, 2H, CH2S), 2.97–2.90 (m, 4H, 2CH2), 1.68 (q, J =
7.2 Hz, 2H, CH2). 13C NMR (100 MHz) δ: 193.2, 143.5, 134.3, 133.9, 133. 6, 131.2, 130.6,
129.4, 128.8, 128.7, 126.9, 58.8, 43.2, 32.0, 29.8. HRMS (ESI) m/z C17H20NO3S+ for [M
+ H]+: Calcd., 318.1158; Found, 318.1160.
N-[3-(2-Formylphenyl)propyl]ethanesulfonamide (4b). Colorless oil, 90 mg in
0.5-mmol scale (63%). Rf = 0.50 (PE:EA = 1/1, v/v). IR (neat): 3286 (NH), 1693 (C O),
1
1317 (S O), 1141 (S O), 1084 (S N). H NMR (400 MHz) δ: 10.2 (s, 1H, CHO),
7.81–7.30 (m, 4H, ArH), 3.19 (q, J = 7.2 Hz, 2H, CH2), 3.11 (t, J = 7.2 Hz, 2H, CH2),
3.06 (q, J = 7.6 Hz, 2H, CH2), 1.87 (m, 2H, CH2), 1.38 (t, J = 7.2 Hz, 3H, CH3). 13C NMR
(100 MHz) δ: 193.4, 143.6, 134.5, 134.0, 131.3, 126.9, 121.9, 46.8, 42.7, 32.1, 29.9, 8.3.
HRMS (ESI) m/z C12H18NO3S+ for [M + H]+: Calcd., 256.1002; Found, 256.1006.
rel-(8S,9aS,12aS)-9-Phenyl-5,6,9,9a,14,15-hexahydro-16aH-diisoquinolino-[2,
1-b:2ꢁ,1ꢁ-d][1,2,4]thiadiazine-8,8-dioxide [( )-SSS-5]. Colorless crystals, 80 mg (4%);
mp 145–147◦C. Rf = 0.70 (PE:EA = 1/2, v/v). IR: 3100 (CH), 1334 (S O), 1136 (S O),
1093 (S N). 1H NMR (400 MHz) δ: 7.33–5.92 (m, 13H, ArH), 5.48 (s, 1H in CH2), 4.77
(d, J = 9.6 Hz, 1H, CH), 4.73 (d, J = 9.6 Hz, 1H, CH), 4.34 (m, 1H, CH2), 4.23 (m, 1H,
CH2), 3.35 (m, 2H, CH2), 3.31 (m, 2H, CH2), 3.00 (m, 1H, CH2), 2.89 (m, 1H, CH2). 13
C
NMR (100 MHz) δ: 135.5, 135.2, 134.5, 133.6, 131.9, 129.2, 129.0, 128.7, 128.0, 127.7,
127.4, 126.6, 125.7, 124.8, 79.8, 71.3, 59.3, 47.3, 41.0, 30.0, 28.5. HRMS (ESI) Calcd.
C25H25N2O2S+ for [M + H]+, 417.1631; Found, 417.1640.
rel-(8R,9aR,12aS)-9-Phenyl-5,6,9,9a,14,15-hexahydro-16aH-diisoquinolino-[2,
1-b:2ꢁ,1ꢁ-d][1,2,4]thiadiazine-8,8-dioxide [( )-RRS-5]. Colorless crystals, 30 mg (2%);
mp 126–128◦C. Rf = 0.80 (PE:EA = 1/2, v/v). IR: 3062 (CH), 1381 (S O), 1146 (S O),
919 (S N). 1H NMR (400 MHz) δ: 7.32–6.17 (m, 13H, ArH), 6.07 (s, 1H, CHN), 5.12 (d,
J = 10.6 Hz, 1H, CH), 4.58 (d, J = 10.6 Hz, 1H, CH), 3.75 (m, 1H, CH2), 3.62 (m, 1H,
CH2), 3.22 (dt, J = 14.5, 10.8 Hz, 1H, CH2), 3.00 (m, 2H, CH2), 2.70 (m, 2H, CH2), 2.67
(m, 1H, CH2). 13C NMR (100 MHz) δ: 135.6, 134.5, 132.5, 132.0, 129.7, 129.0, 128.9,
128.6, 128.5, 127.9, 127.8, 127.3, 127.0, 124.5, 75.1, 64.8, 63.8, 37.7, 29.2, 29.2, 39.5.
HRMS (ESI) m/z C25H25N2O2S+ for [M + H]+:Calcd., 417.1631; Found, 417.1640.
2-(Benzylsulfonyl)-1,2,3,4-tetrahydroisoquinolin-1-ol (6a). Colorless crystals, 30
mg (2%); mp 204–205◦C. Rf = 0.50 (PE:EA = 1/2, v/v). IR: 3496 (OH), 3000 (CH), 1333
1
(S O), 1146 (S O), 914 (S N). H NMR (400 MHz) δ: 7.31–7.09 (m, 9H, ArH), 6.02
(d, J = 5.3 Hz, 1H, CH), 4.35 (s, 2H, CH2), 3.55 (ddd, J = 12.8, 5.6, 2.4 Hz, 1H, CH2),
3.30 (dt, J = 12.4, 0.4 Hz, 1H, CH2), 2.94 (d, J = 5.4 Hz, 1H, OH), 2.77 (ddd, J = 16.3,
11.7, 6.0, Hz, 1H, CH2), 2.66 (dt, J = 16.1, 3.2 Hz, 1H, CH2). 13C NMR (100 MHz) δ:
134.0, 133.7, 130.9, 130.7, 128.7, 128.6, 128.4, 126.7, 77.1, 59.7, 38.8, 29.0. HRMS (ESI)
m/z C32H34N2NaO6S2+ for [2M + Na]+: Calcd., 629.1750; Found, 629.1756.
1-Chloro-2-(ethylsulfonyl)-1,2,3,4-tetrahydroisoquinoline (7a). Colorless crys-
tals, 10 mg (2%); mp 170–172◦C. Rf = 0.50 (PE:EA = 1/1, v/v). IR: 1471 (S O), 1145
(S O), 1022 (S N). 1H NMR (400 MHz) δ: 7.69–7.15 (m, 4H, ArH), 6.74 (s, 1H, CH),

DIVERSE REACTIONS OF SULFONYL CHLORIDES AND CYCLIC IMINES
2389
3.89 (ddt, J = 13.2, 5.6, 1.2 Hz, 1H, CH2), 3.56 (dt, J = 12.8, 3.6 Hz, 1H, CH2), 3.07 (q,
J = 7.2 Hz, 2H, CH2), 3.16–2.98 (m, 1H, CH2), 2.77 (ddd, J = 16.4, 3.6, 1.6 Hz, 1H, CH2),
1.26 (t, J = 7.2 Hz, 3H, CH3). 13C NMR (100 MHz) δ: 135.6, 130.1, 129.6, 129.0, 128.3,
126.7, 85.9, 47.4, 38.8, 28.9, 7.7. HRMS (ESI) m/z C11H14NO2S+ for [M – Cl]+: Calcd.,
224.0740; Found, 224.0740.
Reaction of Benzylsulfonyl Chloride and N-Benzylidenebenzylamine
in the Presence of Triethylamine
To a solution of N-benzylidenebenzylamine (1.31 g, 6.7 mmol) and triethylamine
(0.97 g, 9.63 mmol) in anhydrous THF (10 mL) was added dropwise a solution of benzyl-
sulfonyl chloride (1.4 g, 7.4 mmol) in anhydrous THF (10 mL) in an ice-water bath. After
the addition, the resulting mixture was further stirred in the ice-water bath for 24 h and at
r.t. for 48 h. After the filtration of salts and removal of solvent, the residue was purified
via silica gel column chromatography (PE/EA 50:1, v/v) to afford colorless crystals 1.9 g
(20%), mp 132–134◦C.32 mp 125–127◦C. Rf = 0.8 (PE/EA = 30:1). 1H NMR (300 MHz)
δ: 7.12 (s, 2H, 2CH), 7.25–7.54 (m, 10 H, ArH). 13C NMR (75 MHz) δ: 126.5, 127.6,
128.6, 137.3.
Reaction of 4-Nitrobenzenesulfonyl Chloride and
3,4-Dihydroisoquinoline in Toluene with Oxirane as Additive
To a solution of 3,4-dihydroisoquinoline (1.31 g, 10 mmol) and oxirane (0.88 g,
1 mL, 20 mmol) in anhydrous toluene (10 mL) was added dropwise a solution of 4-
nitrobenzenesulfonyl chloride (1.11 g, 5 mmol) in anhydrous toluene (10 mL) in an ice-
water bath. After addition, the resulting mixture was further stirred in the ice-water bath for
24 h and at r.t. for 48 h. After the filtration of salts and removal of solvent, the residue was
purified via silica gel column chromatography (PE/EA 3:1, v/v) to afford colorless crystals.
2-(4-Nitrophenylsulfonyl)-1,2,3,4-tetrahydroisoquinolin-1-ol (6b). Light-brown
crystals, 40 mg (3%); mp 136–138◦C. Rf = 0.6 (PE:EA = 1/3, v/v). IR: 3491 (OH),
1
1356 (S O), 1176 (S O), 943 (S N). H NMR (400 MHz) δ: 8.32(d, J = 8.8 Hz, 2H,
ArH), 8.10 (d, J = 8.8 Hz, 2H, ArH), 7.27–7.12 (m, 4H, ArH), 6.36 (d, J = 5.6 Hz, 1H,
CH), 3.87 (dddd, J = 12.8, 5.6, 2.4, 0.8 Hz, 1H, CH2), 3.40 (dt, J = 12.0, 8.4 Hz, 1H in
CH2), 2.95 (ddd, J = 16.4, 12.0, 6.0 Hz, 1H, CH2), 2.90 (d, J = 5.6 Hz, 1H, OH), 2.82 (dt,
J = 19.6, 3.4 Hz, 1H, CH2). 13C NMR (100 MHz) δ: 150.1, 146.0, 133.8, 133.2, 129.1,
128.7, 128.3, 127.1, 124.2, 77.2, 38.4, 28.7. HRMS (ESI) m/z C15H15N2O5S+ for [M +
H]+: Calcd., 335.0696; Found, 335.0704.
1-(2-Chloroethoxy)-2-(4-nitrophenylsulfonyl)-1,2,3,4-tetrahydroisoquinoline
(8a). Colorless oil, 0.12 g (7%); Rf = 0.5 (PE:EA = 1/3, v/v). IR: 3104 (CH), 1383 (S O),
1167 (S O), 945 (S N). 1H NMR (400 MHz) δ: 8.23 (d, J = 8.8 Hz, 2H, ArH), 7.93 (d,
J = 8.8 Hz, 2H, ArH), 7.27–6.98 (m, 4H, ArH), 6.11 (s, 1H, CH), 4.01 (ddd, J = 11.2, 6.0,
0.8 Hz, 1H, CH2), 3.93 (ddd, J = 11.2, 6.0, 4.4 Hz, 1H, CH2), 3.82 (dddd, J = 14.0, 6.0,
3.2, 0.8 Hz, 1H, CH2), 3.71–3.62 (m, 3H, 1H, CH2, CH2), 2.69 (dt, J = 4.0, 16.4 Hz, 1H,
CH2), 2.49 (ddd, J = 16.4, 11.2, 6.0 Hz, 1H in CH2). 13C NMR (100 MHz) δ: 149.9, 146.3,
133.1, 132.1, 129.2, 128.7, 128.5, 128.1, 126.9, 124.2, 83.6, 67.8, 42.8, 39.0, 26.6. HRMS
(ESI) m/z C17H17ClN2O5NaS+ for [M + Na]+: Calcd., 419.0439; Found, 419.0433.

2390
J. LIU ET AL.
Reaction of 4-Nitrobenzenesulfonyl Chloride with
3,4-Dihydroisoquinoline in 1,4-Dioxane
To a solution of 3,4-dihydroisoquinoline (1.31 g, 10 mmol) in anhydrous 1,4-dioxane
(10 mL) was added dropwise a solution of 4-nitrobenzenesulfonyl chloride (1.11 g, 5 mmol)
in anhydrous 1,4-dioxane (10 mL) in an ice-water bath. After addition, the resulting mixture
was further stirred in the ice-water bath for 24 h and at r.t. for 48 h. After the filtration of
salts and removal of solvent, the residue was purified via silica gel column chromatography
(PE/EA 50:1, v/v) to afford colorless crystals.
1-Chloro-2-(4-nitrophenylsulfonyl)-1,2,3,4-tetrahydroisoquinoline (7b). Color-
less crystals, 80 mg (5%); mp 215◦C. Rf = 0.5 (PE:EA = 1/3, v/v). IR: 3100 (CH),
1347 (S O), 1168 (S O), 963 (S N). 1H NMR (400 MHz) δ: 8.26 (d, J = 9.2 Hz, 2H,
ArH), 8.10 (d, J = 9.2 Hz, 2H, ArH), 7.19–6.93 (m, 4H, ArH), 6.81 (s, 1H, CH), 4.08–4.02
(m, 1H, CH2), 3.67 (ddd, J = 13.6, 11.2, 5.6 Hz, 1H, CH2), 2.66–2.51 (m, 2H, CH2). 13
C
NMR (100 MHz) δ: 150.1, 146.4, 132.8, 132.1, 128.9, 128.6, 128.4, 128.2, 127.1, 124.5,
81.9, 39.5, 26.8. HRMS (ESI) m/z C15H13N2O4S+ for [M – Cl]+: Calcd., 317.0591; Found,
317.0594.
1-Ethoxy-2-(4-nitrophenylsulfonyl)-1,2,3,4-tetrahydroisoquinoline (9). Light-
yellow granular solid, 0.11 g (6%); mp 78–80◦C. Rf = 0.7 (PE:EA = 1/3, v/v). IR: 3099
1
(CH), 1351 (S O), 1168 (S O), 1110 (C O C), 918 (S N). H NMR (400 MHz) δ:
8.22(d, J = 8.8 Hz, 2H, ArH), 7.93 (d, J = 8.8 Hz, 2H, ArH), 7.23–6.97 (m, 4H, ArH),
6.04 (s, 1H, CH), 3.85–3.74 (m, 1H, CH2), 3.68–3.61 (m, 1H, CH2), 3.76–3.66 (q, J =
6.8 Hz, 2H, CH2), 2.68 (ddd, J = 16.8, 4.4, 3.2 Hz, 1H, CH2), 2.50 (ddd, J = 16.4, 11.6,
6.4 Hz, 1H, CH2), 1.12 (t, J = 6.8 Hz, 3H, CH3). 13C NMR (100 MHz) δ: 149.9, 146.6,
133.1, 132.8, 128.9, 128.7, 128.3, 128.1, 126.8, 124.1, 83.4, 63.6, 38.9, 26.8, 14.9. HRMS
(ESI) m/z C17H18N2O5NaS+ [M + Na]+: Calcd., 385.0829; Found, 385.0828.
CCDC-831814 contains the supplementary crystallographic data of 9. These data can
be obtained free of charge via www.ccdc.cam.ac.uk/retrieving.html or from the Cambridge
Crystallographic Data Centre, 12, Union Road, Cambridge, B2 1EZ, UK (fax +44-1223-
336033; E-mail: deposit@ccdc.cam.ac.uk).
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