Novel thiofomylation of primary and secondary amines using N-aryl-1,2,3,4,5,7-pentathiazocanes

Article abstract of DOI:10.1080/10426501003773407

Heating of N-aryl-1,2,3,4,5,7-pentathiazocanes 1 in the presence of primary and secondary amines afforded N-Alkyl or N,N-dialkylthioformamides 5, and similar heating of 1 in the absence of amines afforded an inseparable mixture of acyclic polysulfides 4 bearing a thioformanilide moiety on each terminal. Bisthioformanilides 4 were also converted into 5 by treating with these amines, and the thioformylation was assumed to proceed through a pathway involving the ring fission of 1 and the subsequent nucleophilic attack of these amines onto the thioformyl group of 4. Copyright Taylor & Francis Group.

Full text of DOI:10.1080/10426501003773407

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Phosphorus, Sulfur, and Silicon and the
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Novel Thiofomylation of Primary
and Secondary Amines Using N-
Aryl-1,2,3,4,5,7-Pentathiazocanes
Kazuaki Shimada a , Hiroki Shibuya a , Kenshiro Makino a , Tatsuya
Otsuka a , Yuki Onuma a , Shigenobu Aoyagi a & Yuji Takikawa a
a Department of Chemical Engineering, Faculty of Engineering ,
Iwate University , Morioka, Iwate, Japan
Published online: 27 May 2010.
To cite this article: Kazuaki Shimada , Hiroki Shibuya , Kenshiro Makino , Tatsuya Otsuka , Yuki
Onuma , Shigenobu Aoyagi & Yuji Takikawa (2010) Novel Thiofomylation of Primary and Secondary
Amines Using N-Aryl-1,2,3,4,5,7-Pentathiazocanes, Phosphorus, Sulfur, and Silicon and the Related
Elements, 185:5-6, 1077-1089, DOI: 10.1080/10426501003773407
To link to this article: http://dx.doi.org/10.1080/10426501003773407
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Phosphorus, Sulfur, and Silicon, 185:1077–1089, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426501003773407
NOVEL THIOFOMYLATION OF PRIMARY
AND SECONDARY AMINES USING
N-ARYL-1,2,3,4,5,7-PENTATHIAZOCANES
Kazuaki Shimada, Hiroki Shibuya, Kenshiro Makino, Tatsuya
Otsuka, Yuki Onuma, Shigenobu Aoyagi, and Yuji Takikawa
Department of Chemical Engineering, Faculty of Engineering, Iwate University,
Morioka, Iwate, Japan
Heating of N-aryl-1,2,3,4,5,7-pentathiazocanes 1 in the presence of primary and secondary
amines afforded N-Alkyl or N,N-dialkylthioformamides 5, and similar heating of 1 in the
absence of amines afforded an inseparable mixture of acyclic polysulfides 4 bearing a
thioformanilide moiety on each terminal. Bisthioformanilides 4 were also converted into 5
by treating with these amines, and the thioformylation was assumed to proceed through
a pathway involving the ring fission of 1 and the subsequent nucleophilic attack of these
amines onto the thioformyl group of 4.
Keywords Bisthioformanilide; 1,2,3,4,5,7-pentathiazocane; polysulfide chain thioformyla-
tion; thioformamide
INTRODUCTION
Cyclic polysulfides bearing tri-, tetra-, and pentasulfane moieties have been widely
recognized as useful sulfur sources, and synthetic and practical uses of various cyclic poly-
sulfides as syntheric intermediates, potent antibacterial drugs, natural flavors, and industrial
vulcanizing agents have also long been extensively studied. However, the difficulty of prepa-
ration and the general liability of these compounds often causes limitation in the synthetic
application in spite of the potentiality of sulfur-introducing and thiocarbonyl-introducing
reactions. Among such compounds, thioacetals having cyclic polysulfide moieties bound
with a polysulfane chain have been of great interest in light of the possibility that they could
generate reactive sulfur species along with hydrolytic formation of thiocarbonyl groups and
polysulfanes. In the course of our extensive studies on the syntheses and reactions of cyclic
aminochalcogenoacetals, we previously found an efficient preparation of novel cyclic poly-
sulfides, 1,2,3,4,5,7-pentathiazocanes 1, possessing a pentasulfide chain connected with an
Received 2 December 2008; accepted 25 December 2008.
Dedicated to Professor Naomichi Furukawa on the occasion of his 70th birthday.
This work was partially supported by a Grant-in-Aid for Scientific Research (No. 12650843) from the
Ministry of Education, Science, Sports, Culture, and Technology. We thank Mr. Yuzo Sato and Ms. Yoriko
Fujisawa at Iwate University for the elemental analysis measurements.
Address correspondence to Kazuaki Shimada, Department of Chemical Engineering, Faculty of Engineering,
Iwate University, Morioka, Iwate, Japan. E-mail: shimada@iwate-u.ac.jp
1077

1078
K. SHIMADA ET AL.
Scheme 1 Thioformylation of primary and secondary amines via thermal ring fission of N-aryl-1,2,3,4,5,7-
pentathiazocanes 1.
aminothioacetal moiety in the ring system, through oxidation of 1,5,3,7-dithiadiazocanes
2.1,2 Furthermore, we also found an unprecedented thermal ring fission of the ring system of
1 to afford acyclic polysulfide 4 bearing a thioformanilide moiety on each terminal.1 It was
naturally expected that the anilino moieties on the thioformyl group of 4 or their precursors
A would be easily replaced by the attack of amines possessing higher nucleophilicity than
anilines to give the corresponding N-alkyl or N,N-dialkylthioformamides 5 along with gen-
eration of free anilines, and such expectation prompted us to expand the synthetic utility
of cyclic polysulfides 1 for novel and environmentally benign thioformylation of amines
as shown in Scheme 1. In this article, we wish to describe a full account of the convenient
conversion of primary and secondary amines into the corresponding N-alkyl- and N,N-
dialkylthioformamides 5 using cyclic polysulfides 1 as masked thioformylating agents.
RESULTS AND DISCUSSION
Preparation of N-Aryl-1,2,3,4,5,7-pentathiazocanes 1 by Treating
1,5,3,7-Dithiadiazocanes 2 with Br2-Elemental Sulfur or Disulfur Dichloride
1,5,3,7-Dithiadiazocanes 2a–d were prepared from a primary arylamine, formalin,
and H2S gas according to the reported methods.1–6 A dichloromethane solution of 2 was
then treated with bromine-elemental sulfur or disulfur dichloride (S2Cl2) at −78◦C, and
in both cases, N-aryl-1,2,3,4,5,7-pentathiazocanes 1a–d were efficiently obtained through
oxidative ring contraction of 1,5,3,7-dichalcogenadiazocines as shown in Scheme 2.7,8
Conversion of 2 into 1 was assumed to proceed through a mechanism involving in situ
formation of 1,5,3,7-dithiadiazabicyclo[3.3.0]octane-type mesocyclic dications 3 [9–26]
followed by ring contraction and sulfur insertion.27–30
Scheme 2 Preparation of N-aryl-1,2,3,4,5,7-pentathiazocanes 1.

THIOFOMYLATION WITH N-ARYL-1,2,3,4,5,7-PENTATHIAZOCANES
1079
Reaction of N-Aryl-1,2,3,4,5,7-pentathiazocanes 1 with Primary
or Secondary Amines
When a benzene solution of N-phenyl-1,2,3,4,5,7-pentathiazocane (1a) was treated
with diethylamine (10 mol amt.) at room temperature for a long time, 1a was gradually
converted into N,N-diethylthioformamide (5, R1 = R2 = C2H5) as expected, and 5 was
obtained in 19% yield besides the recovery of 1a (58%) after 1 week of stirring of the reac-
tion mixture. The yield of 5 (R1 = R2 = C2H5) was dramatically improved by carrying out
the same reaction at refluxing temperature in benzene, and free aniline (7a) and elemental
sulfur were formed along with the desired thioformamide 5 after complete consumption
of 1a. Similar treatment of 1a–d with various primary or secondary amines also gave the
corresponding N-alkyl- or N,N-dialkylthioformamides 5 in moderate to high yields. Inter-
estingly, treatment of a benzene solution of 1 with a primary amine at higher temperature
afforded the corresponding symmetrical N,Nꢁ-dialkylthioureas 6 in moderate yields. All the
results of the reactions of 1 with a primary or secondary amine are shown in Table I.
Thermal Ring Fission of N-Aryl-1,2,3,4,5,7-pentathiazocanes 1 in the
Absence of Amines
N-Aryl-1,2,3,4,5,7-pentathiazocanes 1 were thermally stable under heating up to the
refluxing temperature in benzene (80◦C) in the absence of primary or secondary amines, and
addition of triethylamine (excess) to the reaction mixture was ineffective for acceleration
Table I Reaction of N-aryl-1,2,3,4,5,7-pentathiazocanes 1 with primary or secondary amines
R1R2NH
NR1R2
H
NR1R2
NR1R2
S
S
(10 mol amt.)
S
S
Ar
N
S
S
+
S
+
ArNH2
+
S8
Benzene
7
6
1
5
Substrate
Amine
Yield /%a,b
Temp
/◦C
Time
/h
Ar
1
R1
C2H5
C2H5
C4H9
R2
5
6
7
Recov.
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
1c
C2H5
C2H5
C4H9
R.T.
168
7
7
7
5
4
6
6
5
19
43
46
63
62
51
0
25
Trace
Trace
57 (62)e
51 (60)e
0
0
0
0
58
0
0
0
0
0
0
0
0
0
0
0
Reflux
Reflux
Reflux
Reflux
50
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
(71)c
d
d
d
d
d
d
d
d
(CH2)5-
(CH2)2O(CH2)2-
0
0
0
41
35
41
55
0
C4H9
C4H9
H
H
H
H
H
C2H5
C2H5
n-C8H17
C6H5CH2
c-C6H11
C2H5
4
6
6
p-ClC6H4
p-CH3C6H4
69
62
C2H5
0
aIsolated yields.
bNo products originated from thioformaldehyde was isolated at all.
cThe yield was estimated from the integration of the 1H NMR spectrum of the crude mixture.
dAniline (7a) was detected in the crude reaction mixture.
eNMR yield is presented in parenthesis.

1080
K. SHIMADA ET AL.
Table II Thermal ring fission of N-aryl-1,2,3,4,5,7-pentathiazocanes 1 in the absence of amines
S
S
CHS
S
CHS
S
∆
S
S
+
S8
Ar
N
S
Ar
N
N Ar
Sx
1
4
Substrate
Yield/%
S8
Solvent
Temp
/◦C
Time
/h
Ar
1
4
Recovery of 1
C6H5
C6H5
p-CH3OC6H4
1a
1a
1d
Benzene
Toluene
Toluene
Reflux
Reflux
Reflux
24
7
7
0
−
+
+
98
0
0
89 (4a)a
93 (4d)a
aEstimation of the yields was based on the average value of x to be 1.5 for 4a and 4d.
of ring fission of 1. However, heating of a toluene solution of 1 at refluxing temperature in
the presence or absence of triethylamine afforded an inseparable mixture of polysulfide 4
with a thioformanilide moiety on each terminal in all cases. The mass spectra of mixtures
of 4 revealed the set of parent ion peaks of the main components consistent with the
numbers of sulfur atoms (x = 1 and 2), and the 1H NMR spectra of the mixture of 4 also
showed several characteristic singlet signals at the δ = 9.20–9.40 region, assignable to the
thioformyl protons, and the δ = 5.20–5.50 region, assignable to the methylene protons, in
all cases. The 13C NMR spectra of 4 also exhibited several thioformyl carbon signals at
the δ = 189–190 region and several methylene carbon signals at the δ = 55–60 region,
respectively. The elemental analysis data of 4 suggested that the average values of x for 4
were approximately estimated to 1.5 in all cases. Especially, trisulfide 4a (Ar = C6H5, x =
1) was isolated in 8% yield as an inseparable syn/anti geometrical mixture (major:minor =
2:1) after repeated chromatographic separation. All the results of thermal conversion of 1
into 4 are shown in Table II.
Compounds 4 were thermally stable enough even at the refluxing temperature of
toluene. However, compounds 4 were sensitive to aerobic exposure, and the corresponding
mixtures of sulfines 11 having a trisulfide chain were formed almost quantitatively when a
dichloromethane solution of the mixture of 4 was stirred under an aerobic condition at room
temperature for several days. Actually, elemental analysis data of 11a (Ar = C6H5) was
much consistent with the trisulfide structure, and the mass spectrum of 11a revealed a parent
ion peak at m/z 412. The 1H NMR spectrum of 11a also showed several singlet signals at the
δ = 9.2–9.4 region, assignable to thioformyl and the syn/anti mixture of sulfinyl protons.
Furthermore, the mixture of 11a was gradually converted into an inseparable mixture of
bisformamides 12a (Ar = C6H5, x = 0, approximately 1:1 geometrical mixture, 64% from
11a) along with extrusion of elemental sulfur by stirring at room temperature for 1 month
in dichloromethane. Reduction of the resulting mixture of 12a using LiAlH4 (excess) in
THF followed by treating with CH3I (2.0 mol amt.) afforded methylthio derivative 13a
(Ar = C6H5) in 61% yield based on the starting 4a. These results supported the structures
of 4 bearing a thioformanilide moiety on each terminal. All the results of the conversion
sequence of 1a into formanilide 13a are shown in Scheme 3.

THIOFOMYLATION WITH N-ARYL-1,2,3,4,5,7-PENTATHIAZOCANES
1a (Ar = C6H5)
1081
Benzene
Reflux, 6 h
∆
O
S
S
CHS
S
CHS
S
Air
C6H5
N
N C6H5
S
H
N
S
S
N
H
3-4 days
Sx
C6H5
C6H5
4a (89%, x = 1 and 2)
11a (quant, geometrical mixture)
Air, 1 month
- S8
1) LiAlH4 (excess)
THF, R.T.
O
H
CHO
CHO
C6H5
N
N C6H5
N
SCH3
S
S
2) CH3I (2.0 mol amt.)
C6H5
13a (61%)
12a (64%, 1:1 geometrical mixture, x = 0)
Scheme 3 Structural confirmation of bisthioformanilide 4a.
Attempts for Detection or Trapping of Reactive Intermediates
When a benzene solution of 1a was treated with diethylamine at refluxing temperature
for 6 h in the presence of norbornene (10 mol amt.), 1,2,3-trithiolane 8 was obtained in
63% yield besides N,N-diethylthioformamide 5a (R1 = R2 = C2H5). Similar trapping
experiment of reactive sulfur species was carried out by using 2,3-dimethyl-1,3-butadiene,
by which a mixture containing 5a (43%), 1,2-dithiin 9 (25%), and 1,2,3,4-tetrathiocine 10
(25%) was also obtained. Heating of a toluene solution of 1a and norbornene (5.0 mol
amt.) under refluxing in the absence of amines afforded 8 (28%) along with 4a (48%), and
a mixture of 9(14%), 10 (20%), and 4a (32%) was formed in a similar case using 2,3-
dimethyl-1,3-butadiene as a trapping agent. All these results suggested in situ generation
of some reactive sulfur species, such as triatomic sulfur (S3), diatomic sulfur (S2), and so
on, through thermally or amine-induced ring fission of N-aryl-1,2,3,4,5-pentathiazocanes
1.31–41 However, the yield of 8 obtained through thermal reaction of 1a and norbornene in
the absence of an amine was relatively lower than the case of the similar trapping experiment
in the presence of diethylamine. Greer and Brzostowska already reported a novel generation
of triatomic sulfur (S3) through a similar ring fission of varacin by nucleophilic attack of the
internal primary amino group toward a sulfur atom of the 1,2,3,4,5-pentathiepin ring,35,36
and these results suggested that ring fission of 1 was initiated by added amines. All the
results of trapping of reactive sulfur species are shown in Table III.
When a C6D6 solution of 1a (Ar = C6H5) was heated in a sealed NMR tube below
1
80◦C and the reaction was monitored by using H NMR, no mean change was observed
in the spectrum except for slight broadening of the doublet signals assignable to the
methylene protons of 1a. On the other hand, the spectral pattern became complicated along
with decreasing the signals of 1a when the heating temperature was raised up to 100◦C.
Especially, several new signals assignable to N-phenyl-N-sulfanylmethylthioformamide
(14a, Ar = C6H5), δ = 3.28 (1H, t, J = 8.9 Hz) for N CH2 SH, δ = 4.71 (2H, d, J = 8.9
Hz) for N CH2 SH, and δ = 9.10 (1H, s) for N CHS), and 1,2,4-dithioazolidines 15a
(Ar = C6H5), δ = 4.21 (4H, s) for N CH2 S, were observed among the uncharacterizable

1082
K. SHIMADA ET AL.
Table III Trapping of reactive sulfur species generated through ring fission of 1a
∆
S
S
S
S
S
S
S
1a (Ar = C6H5)
+
S
+
4a
+
+
5a
S
Trapping Agent
Solvent, Reflux, 6 h
8
9
10
Yield/%
Trapping agenta
(mol amt.)
Diethylamine
(10 mol amt.)
Solvent
8b
9c
10c
4ab
5ab
A (10)
B (10)
A (5.0)
B (5.0)
C (5.0)
+
+
−
−
−
Benzene
Benzene
Toluene
Toluene
Toluene
63
—
28
—
—
25
—
14
—
43
—
20
0
0
48
32
47
43
—
—
—
Complex mixtutre
aTrapping agents: A: norbornene, B: 2,3,-dimethyl-1,3-butadiene, C: phenylacetylene.
bIsolated yield.
cYields were estimated by the integration of the 1H NMR signals of the mixture of 9 and 10.
signals for several hours. After a long time heating 1a, complex signals involving the signals
of a mixture of 4a became mainly observed along with the disappearance of those of 1a,
14a, and 15a in the spectrum. It was assumed that 1 underwent thermal ring fission to
generate an equilibration mixture of A, 14, 15, and elemental sulfur, and A may finally
afford a mixture of 4 having various polysulfide chains after dimerization as shown in
Scheme 4. In contrast, a similar 1H NMR monitoring of the reaction of 1a (Ar = C6H5)
CHS
S
CHS
- S8
S8
100 °C
CDCl3
S
S
C6H5
N
1a (Ar = C6H5)
C6H5 N
C6H5
N
SH
SH
Sx
15a
14a
A
CHS
S
CHS
S
C6H5
N
N C6H5
Sx
4a
Scheme 4 Plausible generation of N-sulfanylmethylthioformanilide 14a and 1,2,4-dithiazolidine 15a through
thermal ring fission of N-phenyl-1,2,3,4,5,7-pentathiazocane 1a.
and diethylamine in an NMR tube at room temperature only afforded complicated spectrum.
All attempts for isolation of plausible precursors of 4, i.e., 14a or 15a, in the crude reaction
mixture obtained by heating 1a in the absence of an amine were also unsuccessful. Thermal
reactions of 1a in the presence of CH3I (excess) for trapping of A or 14 only gave 4a, and
the trapping experiment using phenylacetylene was also unsuccessful.
Plausible Formation Pathway of Thioformamides 5 and Thioureas 6
Through the Reaction of N-Aryl-1,2,3,4,5,7-Pentathiazocanes 1 with Amines
Our experimental results indicated that N-aryl-1,2,3,4,5,7-pentathiazocanes 1 were
converted into thioformamides 5 even at room temperature in the case of the reactions

THIOFOMYLATION WITH N-ARYL-1,2,3,4,5,7-PENTATHIAZOCANES
1083
carried out in the presence of amines. Furthermore, N,N-diethylthioformamide (5) (R1
= R2 = C2H5) was obtained in 47% yield when a benzene solution of a mixture of
bisthioformanilide 4a (R = C6H5, x = 1–2) was subjected to heating in the presence
of diethylamine (10 mol amt.) as shown in Equation (1). These results suggested that
the nucleophilic attack of amines may occur at the S-2 and/or S-3 positions to result in
ring contraction of 1 to form an equilibrated mixture of 1,2,4-dithiazolidine intermediates
15, N-sulfanylmethylthioformanilides 14, polysulfane intermediates A, and reactive sulfur
species as triatomic sufur (S3) and diatomic sulfur (S2). Formation of thioformamides 5
was explained by nucleophilic addition-elimination of thioformanilide moieties of in situ
formed 4, A, or 14 along with elimination of anilines.
Furthermore, N-butylthioformamide (5, R1 = C4H9) was obtained in 51% yield
when the reaction of 1a and butylamine was carried out at lower temperture, and N,Nꢁ-
dibutylthiourea (6, 41%) became a main product by heating the reaction mixture in benzene.
Independent treatment of a benzene solution of N-octylthioformamide (5, R1 = n-C8H17,
R2 = H) with n-octylamine (10 mol amt.) in the presence of elemental sulfur (5 mol
amt.) under heating also afforded N,Nꢁ-dioctylthiourea (6, R1 = n-C8H17, R2 = H) in 43%
yield along with the recovery of 5 (33%) as shown in Equation (2). This result strongly
suggested the formation of thioureas 6 through a Willgerodt–Kindler type oxidation of 5
induced by some reactive sulfur species generated from an amine and elemental sulfur.42–46
The plausible formation pathway of thioformanides 5 and thioureas 6 through the reaction
of 1 was finally summarized as shown in Scheme 5.
R1R2NH
or ∆
S
S
S
R1R2NH
Sx
1
H
N
S
S
N
H
H
NR1R2
- ArNH2 (7)
Ar
Ar
5
4 (x = 1-2)
R1NH2
S2, S3
(R2 = H)
R1NH-Sx-H
S
R1HN
NHR1
6
Scheme 5 Plausible formation pathway of thioformamides 5 and thioureas 6 by treating N-aryl-1,2,3,4,5,7-
pentathiazocanes 1 with a primary or a secondary amine.

1084
K. SHIMADA ET AL.
CONCLUSION
We found a conversion of primary and secondary amines into thioformamides by
treating with N-aryl-1,2,3,4,5,7-pentathiazocanes 1. The unique thioformylation reaction
was assumed to proceed through a plausible pathway involving ring fission of 1 and the
subsequent nucleophilic attack of amines toward the thiocarbonyl carbons of resulting 4 or
the intermediary 14 or A. Further attempts for the synthetic use of 1 as sulfurating agents
are underway in our laboratory.
EXPERIMENTAL
Instruments
The melting points were determined with a Bu¨chi 535 micro-melting-point apparatus.
1H NMR spectra were recorded on a Bruker AC-400P (400 MHz) spectrometer, and the
chemical shifts of the 1H NMR spectra are given in δ relative to internal tetramethylsilane
(TMS). 13C NMR spectra were recorded on a Bruker AC-400P (100 MHz). Mass spectra
were recorded on a Hitachi M-2000 mass spectrometer with electron-impact ionization at
20 or 70 eV using a direct inlet system. IR spectra were recorded for thin-film (neat) or
KBr disks on a Jasco FT/IR-7300 spectrometer. Elemental analyses were performed using
a Yanagimoto CHN corder MT-5.
Materials
Column chromatography was performed using silica gel (Merck, Cat. No. 7734
or 9385) without pretreatment. Dichloromethane (CH2Cl2) and chloroform (CHCl3) were
dried over P4O10, and were freshly distilled before use. Benzene, hexane, triethylamine, and
N,N-dimethylformamide (DMF) were dried over calcium hydride (CaH2) and freshly dis-
tilled before use. Diethyl ether and tetrahydrofuran (THF) were dried over lithium tetrahy-
dridoaluminate (LiAlH4) and were freshly distilled before use. Ethanol and methanol were
dried over anhydrous magnesium sulfate (MgSO4) and were freshly distilled before use.
All of the substrates and reagents, including aniline, p-chloroaniline, p-methoxyaniline,
p-methylaniline, diethylamine, dibutylamine, piperidine, morpholine, benzylamine, n-
octylamine, cyclohexylamine, elemental sulfur, disulfur dichloride (S2Cl2), lithium tetrahy-
dridoaluminate (LiAlH4), iodomethane, sodium hydroxide, concentrated hydrochloric acid,
phenylacetylene, norbornene, 2,3-dimethyl-1,3-butadiene, deuteriochloroform (CDCl3),
and benzene-d6 (C6D6) were commercially available reagent grade and were used without
any pretreatment.
General Procedure for the Reaction of N-Aryl-1,2,3,4,5,7-
pentathiazocane 1 with a Primary or a Secondary Amine
A 20 mL benzene solution of N-aryl-1,2,3,4,5,7-pentathiazocane 1 (1.10 mmol) was
treated with a primary or a secondary amine (10.0 mol amt.) at an ambient temperature.
The reaction mixture was cooled to room temperature, quenched with an excess amount of
water, and extracted with benzene. The organic layer was then washed with water and dried
over anhydrous Na2SO4 powder. After removing the solvent in vacuo, the residual yellow oil
was subjected to 1H NMR measurement in order to estimate the yields of thioformamides 5,
thioureas 13, aniline derivatives 14, and recovery of 1 through the integration of the spectra

THIOFOMYLATION WITH N-ARYL-1,2,3,4,5,7-PENTATHIAZOCANES
1085
of the mixture. Then the crude mixture was subjected to chromatographic purification using
silica gel to obtain thioformamides 5 and thioureas 6 as yellow oils.
General Procedure for the Trapping of Reactive Intermediates
Generated In Situ Through Heating of N-Phenyl-1,2,3,4,5,7-
pentathioazocane (1a) in the Presence of Diethylamine and a Trapping
Agent (Norbornene or 2,3-Dimethyl-1,3-butadiene)
A 20 mL benzene solution of N-phenyl-1,2,3,4,5,7-pentathioazocane (1a, 279 mg,
1.00 mmol) was treated diethylamine (10 mmol) and a trapping agent [norbornene (940 mg,
10.0 mmol)] or 2,3-dimethyl-1,3-butadiene (824 mg, 10.0 mmol) at refluxing temperature
for 6 h. The reaction mixture was cooled to room temperature and extracted with benzene.
The organic layer was washed with water and dried over anhydrous Na2SO4 powder. After
removing the solvent in vacuo, the residual yellow oil was subjected to chromatographic
separation to isolate the corresponding trapping products as 1,2,3-trithiolane 8, 1,2-dithiin
9 and 1,2,3,4-tetrathiocine 10, as well as N,N-diethylthioformamide (5) (R1 = R2 = C2H5).
Actually when norbornene was used as a trapping agent, 8 (121 mg, 63%) was obtained in
addition to N,N-diethylthioformamide (5a, 108 mg, 47%), and an approximate 1:1 mixture
of 9 and 10 (89 mg, 25% and 25% yields, respectively, estimated by using the integration
of the 1H NMR signals of the mixture) was also obtained in addition to 5a (99 mg, 43%)
and a complex mixture when 2,3-dimethyl-1,3-butadiene was used as a trapping agent.
General Procedure for Thermal Ring Fission of N-Aryl-1,2,3,4,5,7-
Pentathiazocane 1
A 100 mL toluene solution of N-aryl-1,2,3,4,5,7-pentathiazocane (1, 1.00 mmol)
was heated at refluxing temperature for several hours under an Ar atmosphere, and the
solvent was removed in vacuo. The residual yellow solid was subjected to chromatographic
purification using silica gel to obtain an inseparable mixture of bisthioformanilides 4 (x =
1.5, approximately) as yellow oil. Actually, when 1a (Ar = C6H5, 273 mg, 1.00 mmol) was
subjected to heating, a mixture of 4a (179 mg, 89% yield) was obtained, and after repeated
chromatographic separation, pure 4a (x = 1, 54 mg, 27% yield) was obtained as yellow oil.
4a [Ar = C6H5, approximately 1:1 mixture of 4a (x = 1) and 4a (x = 2)].
Yellow oil; MS (m/z) 428 (M+(x = 2); 0.2%), 396 (M+(x = 1); 0.3%), 364 (M+(x = 2)-S2
or M+(x = 1)-S; 16%,), 182 (C6H5N(CHS)CH2S; 98%), 150 (C6H5N(CHS)CH2; bp); IR
1
(neat) 2925, 1682, 1593, 1492, 1445, 1347, 1234, 1190, 1059, 939, 759, 694 cm−1; H
NMR (CDCl3) δ = 9.24 (s), 9.26 (s), 9.27 (s), 9.28 (s), 9.30 (s), 9.38 (s); 13C NMR (CDCl3)
δ = 189.7 (s), 189.8 (s). Calcd for C16H16N2S5.5: C, 46.57; H, 3.91; N, 6.79%. Found: C,
46.11; H, 3.84; N, 6.66%.
4a [Ar = C6H5, approximately 2:1 mixture of 4a (x = 1) after chromato-
graphic purification]. Yellow oil; MS (m/z) 396 (M+; 0.1%), 364 (M+-S; 0.3%), 182
((M+-S)/2; 21%), 135 (C6H5NCS; bp); IR (neat) 2924, 1682, 1593, 1493, 1444, 1347,
1
1234, 1186, 1058, 939, 760, 695 cm−1; H NMR (CDCl3) major isomer δ = 5.42 (s),
7.30–7.50 (10H, m), 9.56 (1H, s), minor isomer δ = 5.58 (s), 7.30–7.50 (10H, m), 9.57
(1H, s); 13C NMR (CDCl3) major isomer δ = 59.3 (br.t), 123.3 (d), 128.3 (d), 129.9 (d),
144.2 (s), 189.85 (s), minor isomer δ = 58.9 (br.t), 123.5 (d), 128.1 (d), 130.0 (d), 144.0
(s), 189.92 (s). Calcd for C16H16N2S5: 48.45; H, 4.07; N, 7.06%. Found: C, 48.34; H, 4.02;
N, 6.87%.

1086
K. SHIMADA ET AL.
4d [R = p-CH3OC6H4, approximately 1:1 mixture of 4c (x = 1) and 4c (x =
2)]. Yellow oil; MS (m/z) 488 (M+(x = 2); 0.1%), 456 (M+(x = 1); 0.1%), 346 (4%), 212
(ArN(CHS)CH2S; 40%), 166 (ArN(CHS); bp); IR (neat) 2933, 1608, 1510, 1454, 1343,
1300, 1252, 1182, 1059, 1030, 940, 831, 734 cm−1; 1H NMR (CDCl3) major components
δ = 3.82 (6H, s), 4.98 (s), 5.14 (s), 5.36 (s), 5.51 (s), 5.52 (s), 5.60 (s), 5.62 (s), 6.80–7.00
(m), 7.05–7.30 (m), 9.30–9.40 (2H, m); 13C NMR (CDCl3) major components δ = 25.5
(q), 32.8 (q), 55.7 (dd), 59.5 (dd), 114.8 (d), 125.1 (d), 126.7 (d), 137.1 (s), 137.2 (s), 159.2
(s), 189.3 (s), 190.1 (s). Calcd for C18H20N2O2S5.5: C, 45.73; H, 4.26; N, 5.93%. Found:
C, 45.67; H, 4.26; N, 5.98%.
General Procedure for Aerobic Oxidation of Bisthioformanilide 4
A 20 mL dichloromethane solution of bisthioformanilide 4a (Ar = C6H5, 100 mg,
2.52 mmol) was kept standing at room temperature under an aerobic condition for a few
days. After removing the solvent in vacuo, the residual crude mixture was subjected to
chromatographic separation on silica gel to give an inseparable geometrical mixture of
sulfines 11a (Ar = C6H5, 104 mg) along with extrusion of a small amount of elemental
sulfur. A dichloromethane solution of the resulting mixture of 11a (72 mg, 1.75 mmol)
was then subjected to additional standing at room temperature under aerobic condition for
24 days. After removing the solvent in vacuo, the residual crude mixture was subjected
to chromatographic separation on silica gel to give an inseparable geometrical mixture of
bisformanilides 12a (Ar = C6H5, 37 mg, 64% yield).
11a (Ar = C6H5, x = 1). Pale yellow oil; MS (m/z) 412 (M+; 0.2%), 364 (M+-SO;
16%), 300 (M+-SO-S2; 7%), 214 (M+-C8H8NOS2; 18%), 182 (M+-C8H8NOS3; 98%), 150
(C6H5N(CHS)CH2; bp); IR (neat) 2925, 1682, 1593, 1492, 1445, 1347, 1234, 1190, 1059,
939, 759, 694 cm−1; 1H NMR (CDCl3) δ = 5.20 (s), 5.27 (s), 5.31 (s), 5.35 (s), 5.36 (s),
5.37 (s), 5.44 (s), 7.20–7.50 (m), 9.24 (s), 9.26 (s), 9.27 (s), 9.28 (s), 9.30 (s), 9.38 (s); 13C
NMR (CDCl3) δ = 58.7 (dd), 59.5 (dd), 123.1 (d), 124.3 (d), 128.0 (d), 129.0 (d), 129.8
(d), 130.0 (d), 143.8 (s), 144.0 (s), 189.7 (s), 189.8 (s). Calcd for C16H16N2OS5: C, 46.57;
H, 3.91; N, 6.79%. Found: C, 46.11; H, 3.84; N, 6.66%.
12a (Ar = C6H5, x = 1, approximately 1:1 syn/anti mixture). Pale yellow
oil; MS (m/z) 332 (M+; 20%), 268 (M+-S2; 5%), 198 (M+- C8H8NS2; 2%), 135 (bp); IR
(neat) 3067, 1682 (sh), 1599, 1494, 1441, 1347, 1239, 1180, 1033, 1010, 920, 760 cm−1
;
1H NMR (CDCl3) δ = 4.99 (s), 5.20 (s), 5.25 (s), 5.31 (s), 7.10–7.60 (10H, m), 8.42 (s),
8.45 (s); 13C NMR (CDCl3) δ = 53.0 (t), 119.3 (d), 124.8 (t), 129.7 (d), 136.9 (d), 162.2
(d). Calcd for C16H16N2O2S2: C, 57.81; H, 4.85; N, 8.43%. Found: C, 57.45; H, 4.69; N,
8.32%.
Conversion of a Mixture of Bisthioformanilides 12a (Ar = C6H5) into
Formanilide 13a
A 100 mL diethyl ether solution of a mixture of bisformanilides 12a (Ar = C6H5,
180 mg, 0.54 mmol) was treated with LiAlH4 (excess) at 0◦C for several minutes, and
reaction mixture was then treated with ethanol (10 mL, excess) and iodomethane (153 mg,
1.08 mmol). The reaction was quenched with an excess amount of water and extracted
with dichloromethane. The organic layer was washed with water and was dried over
anhydrous Na2SO4 powder. After removing the solvent in vacuo, the residual yellow solid

THIOFOMYLATION WITH N-ARYL-1,2,3,4,5,7-PENTATHIAZOCANES
1087
was subjected to chromatographic purification using silica gel to obtain formanilide 13a
(Ar = C6H5, 110 mg, 61%) as a pale yellow oil.
13a (Ar = C6H5). Yellow oil; MS (m/z) 182 (M+; 5%), 151 (3%), 124 (4%), 107
(bp); IR (neat) 3067, 1682, 1599, 1491, 1441, 1347, 1239, 1180, 1033, 1010, 920, 760
cm−1; 1H NMR (CDCl3) δ = 1.26 (3H, s), 5.00 (2H, s), 7.20–7.50 (5H, m), 8.46 (1H, s);
13C NMR (CDCl3) δ = 29.7 (q), 53.0 (t), 124.8 (d), 127.6 (d), 139.7 (s), 162.3 (d). Calcd
for C9H11NOS: C, 59.64; H, 6.12; N, 7.73%. Found: C, 60.12; H, 6.38; N, 7.75%.
Trapping of Reactive Sulfur Species Generated In Situ Through Heating
of N-Phenyl-1,2,3,4,5,7-pentathioazocane (1a) Using Norbornene,
2,3-Dimethyl-1.3-butadiene, or Phenylacetylene
A 20 mL toluene solution of N-phenyl-1,2,3,4,5,7-pentathioazocane (1a) (279 mg,
1.00 mmol) was treated with a trapping agent [norbornene (470 mg, 5.00 mmol), 2,3-
dimethyl-1,3-butadiene (412 mg, 5.00 mmol), or phenylacetylene (515 mg, 5.00 mmol)] at
refluxing temperature for 6 h. The reaction mixture was cooled to room temperature and
extracted with benzene. The organic layer was washed with water and dried over anhydrous
Na2SO4 powder. After removing the solvent in vacuo, the residual yellow oil was subjected
to chromatographic separation to isolate the trapping products as 8, 9, and 10. Actually
when norbornene was used as a trapping agent, 8 (53 mg, 28%) and 4a (101 mg, 48%) were
obtained, and when 2,3-dimethyl-1,3-butadiene was used, an approximately 1:1 mixture of
9 and 10 (64 mg, 14% and 20% yield, respectively, estimated by using the integration of
1
the H NMR signals of the mixture) was obtained, in addition to 4a (183 mg, 32%). On
the other hand, only a complex mixture was obtained when phenylacetylene was used as a
trapping agent.
1H NMR Monitoring of Thermal Reaction of N-Phenyl-1,2,3,4,5,7-
pentathiazocane (1a)
Thermal reaction of a C6D6 solution of N-phenyl-1,2,3,4,5,7-pentathiazocane (1a)
1
(28 mg, 0.100 mmol) in a sealed NMR tube was monitored by H NMR at an ambient
temperature for 2 h. As soon as the C6D6 solution of 1a was heated to 100◦C, the signals
assignable to N-phenyl-N-sulfanylmethylthioformamide (14a) [δ = 3.28 (1H, t, J = 8.9
Hz) for N CH2 SH, δ = 4.71 (2H, d, J = 8.9 Hz) for N CH2 SH, and δ = 9.10 (1H, s)
for N CHS)] and N-phenyl-1,2,4-dithiazolidine (15a) [δ = 4.21 (4H, s) for N CH2 S)]
were observed among a complex signal of uncharacterized species along with decreasing
the signals of 1a and increasing the signals of 4a.
Reaction of Bisthioformanilide 4a (Ar = C6H5) with Diethylamine
A 20 mL benzene solution of bisthioformanilide 4a (Ar = C6H5, 178 mg, 0.45 mmol)
was treated with diethylamine (329 mg, 4.50 mmol) at refluxing temperature for 6 h. The
reaction mixture was cooled to room temperature, quenched with an excess amount of
water, and extracted with benzene. The organic layer was then washed with water and
dried over anhydrous Na2SO4 powder. After removing the solvent in vacuo, the residual
yellow oil was subjected to chromatographic purification using silica gel to obtain N,N-
diethylthioformamides (5a) (R1 = R2 = C2H5, 99 mg, 47% yield) as a yellow oil.

1088
K. SHIMADA ET AL.
Reaction of N-Octylthioformamide (5) with Octylamine in the Presence
of Elemental Sulfur
A 20 mL benzene solution of N-octylthioformamide (5) (R1 = n-C8H17, R2 = H,
36 mg, 0.21 mmol) was treated with n-octylamine (258 mg, 2.10 mol amt.) and elemental
sulfur (34 mg, 1.05 mmol) at refluxing temperature for 6 h. The reaction mixture was cooled
to room temperature, quenched with an excess amount of water, and extracted with benzene.
The organic layer was washed with water and dried over anhydrous Na2SO4 powder. After
removing the solvent in vacuo, the residual yellow oil was subjected to chromatographic
purification using silica gel to obtain N,Nꢁ dioctylthiourea (6) (R1 = n-C8H17, R2 = H, 27
mg, 43% yield) as colorless solids in addition to the recovery of the starting thioformamide
5 (11 mg, 33%).
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