Thiadiazolium ylides: Substituted 2H-1,3,5-thiadiazines and 1,4,5-trisubstituted-imidazoles from 1,2,4- and 1,2,5-thiadiazolium-2-unsubstituted methanide (ylide) systems: Ring expansions and ring interconversions via sulfur-nitrogen heterotriene intermediates. Mechanistic ab initio calculations. Azolium 1,3-dipoles

Article abstract of DOI:10.1039/a901148j

Quaternisation of 3,5-diaryl-1,2,4-thiadiazoles with trimethylsilylmethyl triflate at 40°C occurred at N-2. Separate desilylation of the salts resulted in a ring expansion to substituted 2H-1,3,5-thiadiazines 5. Heating of these with ethanolic sodium ethoxide caused sulfur extrusion and ring contraction to 2,4-disubstituted imidazoles 6. 3,4-Diaryl-1,2,5-thiadiazoles were less reactive to alkylation and trimethylsilylmethylation required heating at 80°C. Treatment of the salts with CsF unexpectedly gave 1-trimethylsilylmethyl-4,5-diarylimidazoles 21.¹H, ¹³C, ¹⁵N NMR spectra are described and the mechanisms were studied by ab inito calculations with the GAUSSIAN94 series of programmes using the HF/6-31G* theoretical level.

Full text of DOI:10.1039/a901148j

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Thiadiazolium ylides: Substituted 2H-1,3,5-thiadiazines and 1,4,5-
trisubstituted-imidazoles from 1,2,4- and 1,2,5-thiadiazolium-2-
unsubstituted methanide (ylide) systems: ring expansions and ring
interconversions via sulfur-nitrogen heterotriene intermediates.
Mechanistic ab initio calculations. Azolium 1,3-dipoles
Richard N. Butler,*a Martin O. Cloonan,a John M. McMahona and Luke A. Burkeb
a Chemistry Department, National University of Ireland, Galway, Ireland
bChemistry Department, Rutgers University, Camden, New Jersey, 08102, USA
Received (in Cambridge) 10th February 1999, Accepted 23rd April 1999
Quaternisation of 3,5-diaryl-1,2,4-thiadiazoles with trimethylsilylmethyl triflate at 40 ЊC occurred at N-2. Separate
desilylation of the salts resulted in a ring expansion to substituted 2H-1,3,5-thiadiazines 5. Heating of these with
ethanolic sodium ethoxide caused sulfur extrusion and ring contraction to 2,4-disubstituted imidazoles 6. 3,4-Diaryl-
1,2,5-thiadiazoles were less reactive to alkylation and trimethylsilylmethylation required heating at 80 ЊC. Treatment
of the salts with CsF unexpectedly gave 1-trimethylsilylmethyl-4,5-diarylimidazoles 21. 1H, 13C, 15N NMR spectra are
described and the mechanisms were studied by ab inito calculations with the GAUSSIAN94 series of programmes
using the HF/6-31G* theoretical level.
Exocyclic azolium unsubstituted methanide 1,3-dipoles can
be generated from azolium N-trimethylsilylmethyl triflate salts
by treatment with CsF,1–3 following a literature procedure
developed4,5 with Schiff bases. We have recently generated1–3
the oxadiazole and triazole species 11 and 12 (see Scheme 2).
When it is valency-allowed these unstable intermediates rapidly
ring-open and recyclise via a 1,3,5-heterotriene.1–3 Ab initio cal-
culations showed a large free energy fall and low activation
energies for this rearrangement.2 The reaction with the species
11 (from 8) provided a route to the 1,2,5-oxadiazine ring which
despite earlier misconceptions is not well-known.6
1,3,4-thiadiazole system where ring-opening to hetero-1,3,5-
trienes is not valency permitted and the ylides behaved as new
1,3-dipoles giving cycloaddition rearrangement sequences.11 In
a forthcoming paper we will complete the thiadiazole series
with the 1,2,3-thiadiazole case. We are particularly interested in
the unsubstituted methanide series, rather than more amenable
cases bearing stabilising electron withdrawing groups, since
these unsubstituted methanides are the carbon analogues of the
azole N-oxides.
Renewed interest in the chemistry of organo-sulfur sys-
tems7–9 prompted us to explore the influence of sulfur and to
extend this work into the full thiadiazole series. Herein we
report the behaviour of the 1,2,4- and 1,2,5-thiadiazolium
unsubstituted methanides species 3 and 13 respectively. Valency
permitted ring-opening of these would result in the hetero-
trienes 4 and 16 containing C᎐S and N᎐S moieties. In the event
desilylation of the salts 2 and 10 gave new routes to 2H-1,3,5-
thiadiazines 5 and 1,4,5-trisubstituted imidazoles 21 respect-
ively. New routes to 2-unsubstituted imidazoles are still of
interest because of the pharmaceutical importance of the sys-
tem.10 Recently we have reported11 the N-methanides of the
Results and discussion
(a) 1,2,4-Thiadiazoles
Alkylation of the 1,2,4-thiadiazole series 1 with trimethylsilyl-
methyl trifluoromethanesulfonate at 40 ЊC in CH2Cl2 occurred
at N-2 giving the compounds 2 (Scheme 1, Table 1). The struc-
ture of these was established from microanalyses, IR, H, 13C
1
᎐
᎐
and 15N NMR spectra showing all of the expected signals, as
well as their subsequent reactions. The ring 13C shifts of the
quaternised compounds 2 showed small shielding shifts as
expected12 relative to the parent molecules 1 but the changes
were too small to be of structural diagnostic value other than
Table 1 Substrates and products
Compound
(Substrate)
Yield
(%)
Compound
(Product)
Yield
(%)
Entry
Mp (T/ЊC)
Mp (T/ЊC)
1
2
3
4
5
6
7
8
9
2a
2b
2c
2d
7a
7b
7c
7d
5a
5c
151a
79
73
76
5a
5b
93–94e
111–112e
149–150e
142–143e
120–121d
120–121d
118–119d
107–108d
168
81
76
71
66f
24
21
26
20
69
65
143–144a
b
—
—
5c
c
c
—
5d
83–85d
107–108d
98–100d
130–132d
93–94e
42
20
33
27
81
71
21a
21b
21c
21d
6a
10
149–150e
6c
185
a From CH2Cl2–Et2O. b Unstable in air, used immediately. c Not isolated, used in situ. d From hexane. e From CH2Cl2–hexane. f Yield over two steps
from 1d.
J. Chem. Soc., Perkin Trans. 1, 1999, 1709–1712
1709

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Table 2 Reaction energetics for Scheme 1 (relative to structure 3 for
the e series)
– 85.4
R
R
187.9
– 86.9
186.5
R
N
N
ii
N
i
S
S
∆E/kcal
∆S/cal
∆H/kcal
∆G/kcal
S
Structure
molϪ1
molϪ1 KϪ1
molϪ1
molϪ1
N +
N
N +
R
R
OTf –
R
173.7
172.2
– 124.8
– 195.7 CH2SiMe3
–
CH2
3
0.0000
6.9455
0.000
Ϫ1.000
7.245
3.765
6.577
1.334
Ϫ0.676
3.820
6.426
Ϫ1.133
Ϫ2.459
0.00
6.38
Ϫ46.31
Ϫ45.84
Ϫ45.92
Ϫ32.91
Ϫ60.63
Ϫ43.80
Ϫ44.31
26.92
0.00
6.67
Ϫ48.47
Ϫ46.97
Ϫ47.88
Ϫ33.31
Ϫ60.42
Ϫ44.94
Ϫ46.22
27.25
4.5
45.9
TS (3 to 4)
4
Ϫ47.6586
Ϫ46.5470
Ϫ47.3714
Ϫ33.6156
Ϫ63.1668
Ϫ44.4633
Ϫ45.7206
27.1393
3
TS (4 to 4cc)a
1
2
4cc
TS (4cc to 5)
R
2
6CH2
R
1
N3
5
S
1
S
N
TS (4 to 4ccЈ)
4ccЈ
4
3
4
2
5 N
N 5
TS (4ccЈ to 6S)
6S
a For cc notation see the Experimental section.
R
R
Ϫ39.5721
Ϫ37.08
Ϫ36.34
CH 62
4ct
4cc
R
173.5
– 84.3
N
S
R
S
bond is nearly perpendicular to the rest of the molecule.
Attempts to find a near planar structure for 4 all proved fruit-
less. There are two possible routes from 4 which involve rotation
around the single C4–N5 bond pictured in Scheme 1. One
involves the CH2 group rotating up to meet the S atom out of
the CNCN plane to form 5. On the way structure 4 passes
through a transition state (TS) to a cis, cis intermediate (4cc),
then through another TS which leads to 5 (the term cis, cis
refers to the rotational isomers of the single 2–3 and 4–5 bonds
respectively throughout, cf. the Experimental section). The
other route has the rotation in the opposite direction passing
through an equivalent cis, cis intermediate (4ccЈ) and corre-
sponding TS structures where the CH2 group bonds upwards to
the C atom of the CS group ultimately giving structure (6S)
which is a [3.1.0] bicyclic compound. The energetics for these
reactions are in Table 2 where the energies and entropies are
given relative to structure 3. There is a substantial barrier
between 4ccЈ and 6S which precludes this route compared to
that leading to structure 5.
R
4.8
48.0
H
S –
N
N
R
N
N
H
– 136.7
163.0
+
N
R
R
CH2
5
H
H
4cc′
iii
R
R
N
S
N
R = Ph
R = p-MeC6H4
R = p-MeOC6H4
R = p-BrC6H4
R = H
a
N
b
c
R
N
R
d
e
H
H
H
6
6S
Scheme 1 Reagents: (i) Me3SiCH2OTf; (ii) CsF; (iii) NaOEt, heat.
Some 1H, 13C, and 15N NMR shifts shown for series a in CDCl3.
agreeing with the overall structure. However quaternisation at
N-2 was confirmed by the 15N shifts which showed a shielding
shift of >70 ppm (Scheme 1) at the quaternised N-atom
adjacent to sulfur. Similar effects have been observed13 for
N-alkyl quaternisation of other sulfur azoles. The stability of
the salts 2 depended on the substituents R and compound 2c
had to be used immediately on isolation while compound 2d
decomposed on attempted purification and had to be reacted
in situ (Table 1).
(b) 1,2,5-Thiadiazoles
The 1,2,5-thiadiazoles 7 proved to be less reactive than the
1,2,4-isomers 1 when treated with trimethylsilylmethyl triflate.
Heating at temperatures of 80 ЊC for 12 h with 2.5 mol of the
reagent as solvent was necessary to achieve complete alkylation
to give the salts 10 as gummy residues. Treatment with CsF
in CH2Cl2 unexpectedly gave the imidazoles 21 (<30%) and
decomposition resins. The structures of the products 21 were
indicated by 1H and 13C NMR spectra which showed all of the
expected signals. These structures were proved by unequivocal
synthesis of the 4,5-diarylimidazoles18 followed by separate
alkylation with trimethylsilylmethyl trifluoromethanesulfonate
giving the same compounds 21. We interpret the formation of
the products 21 as shown in Scheme 2. It is likely that the
expected ylides 13 were formed from the salts 10 and they
should behave as did the oxygen and nitrogen analogues 11 and
12. For example with the triazole case 12, ring opening to 15
gave a mixture of 1-aminoimidazoles and the triazines 18.3 The
precursor to the 1-aminoimidazole product was the species 20
(NϪRЈ for SϪ) which aromatised to the 1-aminoimidazole by a
1,3-H shift. With the sulfur system the intermediate 20 should
lose sulfur leading to the final product 21 which can arise by
in situ alkylation of the imidazole with the excess unreacted
trimethylsilylmethyl triflate. The possible 1,2,5-thiadiazine 19
could not be found in these reactions although it could have
been formed and also given rise to the 4,5-diarylimidazoles by
ring-contraction with sulfur extrusion. The calculations (Table
3) suggest that the reactions 13 through 16 to 19 and to 21 are
different from those found for the 1,2,4-thiadiazole reaction.
Structure 16 was found to be nearly planar. This means that
When the salts 2 were desilylated with CsF4,5 the expected
1,3-dipoles 3 could not be trapped with alkyne or alkene
dipolarophiles. Instead the 2H-1,3,5-thiadiazines 5 were iso-
lated in good yields (Table 1). The structures of these products
were established from microanalyses as well as 1H, 13C and 15
N
NMR spectra which showed all of the expected signals (Scheme
1). A significant feature of these molecules is the unsubstituted
methylene group between S-1 and N-3. When heated with eth-
anolic sodium ethoxide the thiadiazines extruded sulfur and
ring-contracted to the 2,4- disubstituted imidazoles 6 but under
normal conditions they were stable in solution. By comparison
with our earlier results for triazoles and oxadiazoles1–3 we inter-
pret this ring expansion as progressing through the unstable
intermediates 3 and 4 the latter of which gives the products 5 by
a bond rotation to 4cc and a 1,6-heteroelectrocyclisation.14 In a
related type of reaction with N-alkylthiazolium salts containing
a stabilising electron withdrawing substituent in the N-alkyl
group a ring-expansion to 2H-1,3-thiazines was found to
proceed through a stable heterotriene intermediate.15,16 The
reactions 3e through 4e to 5e were studied (i.e. with H-atoms at
all sites) using ab initio molecular orbital methods including
frequency calculations to ensure verifying transition state struc-
tures. All calculations were performed with the GAUSSIAN94
series of programs17 using the HF/6-31G* theoretical level.
Structure 3 was found to open to structure 4 where the C᎐S
rotation of the N᎐CH group will lead to the six-membered ring
᎐
2
᎐
1710
J. Chem. Soc., Perkin Trans. 1, 1999, 1709–1712

View Article Online
Table 3 Reaction energetics for Scheme 2 (relative to structure 13 for
the 1,2,5-thiadiazoles 7 were obtained from the reaction of
the e series)
the corresponding diaryl acetylenes, prepared by oxidation of
p-substituted benzil bishydrazones,20 with S4N4.21 NMR
spectra were measured on a JEOL LAMBDA 400 MHz instru-
ment with tetramethysilane as reference for 13C and proton
shifts and nitromethane for 15N shifts. IR spectra were meas-
ured on a Perkin-Elmer 983G spectrophotometer and micro-
analyses were measured on a Perkin-Elmer model 240 CHN
analyser. The following examples show typical experimental
procedures:
∆E/kcal
∆S/cal
∆H/kcal
∆G/kcal
Structure
molϪ1
molϪ1 KϪ1
molϪ1
molϪ1
13
0.000
15.9071 Ϫ0.765
0.000
0.00
15.27
Ϫ1.65
0.50
Ϫ7.07
Ϫ5.88
Ϫ8.64
4.41
Ϫ39.83
0.51
1.02
4.54
Ϫ39.85
0.00
15.50
TS (13 to 16ct)a
16ct
Ϫ1.9909
0.9484
Ϫ7.4954
Ϫ5.5680
Ϫ9.1171
4.8605
5.508
2.987
5.799
2.710
4.869
0.276
Ϫ3.29
Ϫ0.39
Ϫ8.80
Ϫ6.69
Ϫ10.09
4.33
Ϫ39.59
Ϫ0.39
Ϫ0.72
4.40
TS (16ct to tt)
16tt
TS (16tt to tc)
16tc
TS (16c to 20)
20
TS (16ct to cc)
16cc
(ia) 3,5-Diphenyl-2-trimethylsilylmethyl-1,2,4-thiadiazol-2-ium
trifluoromethanesulfonate (2a) (Table 1, entry 1)
Ϫ42.0447 Ϫ0.792
0.8266
0.6639
5.0036
3.018
5.863
0.458
A solution of 3,5-diphenyl-1,2,4-thiadiazole (1.0 g, 4.5 mmol)
and trimethylsilylmethyl trifluoromethanesulfonate (1.8 cm3,
9.0 mmol) in dry CH2Cl2 (5 cm3) was stirred at 40 ЊC under a
reflux condenser for 24 h, evaporated under reduced pressure
and the white residue washed with diethyl ether to give the
compound 2a, mp 151 ЊC (from CH2Cl2–Et2O) (79%) (Found:
C, 47.6; H, 4.1; N, 5.9. C19H21F3N2O3S2Si requires C, 48.0; H,
4.4; N, 5.9%); δH (CD2Cl2) 0.1 (s, 9H, SiMe3), 4.5 (s, 2H, CH2-
N), 7.6–7.8 (m, 6H, Hmeta, para, Ph), 7.95–7.97 (m, 2H, Hortho, Ph),
8.10–8.12 (m, 2H, Hortho, Ph); δC (CD2Cl2) Ϫ2.1 (SiMe3), 45.9
(N-CH2), 186.5, 172.2 (C-5 and C-3), 128.2, 126.2 (C-1Ј of
3-C-Ph and 5-C-Ph), 130.4, 129.5 (C-3Ј of 3-C-Ph and 5-C-Ph),
130.9 and 130.8 (C-2Ј of 3-C-Ph and 5-C-Ph), 136.8, 134.5
(C-4Ј of 3-C-Ph and 5-C-Ph); δN (in CDCl3 from CH3NO2)
Ϫ195.7 (N-2), Ϫ86.9 (N-4).
TS (16cc to 19)
19
Ϫ41.3830 Ϫ0.702
Ϫ39.64
a For ct notation see the Experimental section.
N
R
R
N
– 60.6
R
R
N
Y
N
R
R
i
ii
Y
Y
N +
N
+
– 134.4
OTf –
– 40.2
– CH2
CH2SiMe3
11
12
13
Y = O
8
9
Y = O
Y = NR′
10 Y = S
Y = S
7
Y = NR′
Y = S
(ib) 4,6-Diphenyl-2H-1,3,5-thiadiazine (5a)
N2
R
3
N
N
R
R
A solution of 2a (0.47 g, 1.02 mmol) in dry dichloromethane
(10 cm3) was treated with CsF (300 mg, 2 mmol), stirred at
ambient temperature for 24 h, filtered to remove salts and then
evaporated under reduced pressure. The residue in dichloro-
methane (2 cm3) was placed on a silica gel-60 column (70–230
mesh ASTM). Elution with methylene chloride gave compound
5a (81%) mp 93–94 ЊC (from CH2Cl2–hexane 1:1 v/v) (Found:
C, 71.2; H, 5.0; N, 11.2. C15H12N2S requires C, 71.3; H, 4.8; N,
Y
Y 1
4
R
5 N
6
CH2
17
18
19
14 Y = O
15 Y = NR′
16 Y = S(ct)
Y = O
Y = NR′
Y = S
'
Y = S
11.1%); νmax (mull) 1602.9, 1571.9 cmϪ1 C᎐N; δ (CDCl ) 4.8 (s,
᎐
H
3
– S
+ N
– 129.4
2H, SCH2N), 7.4–7.6 (m, 6H, Hmeta, para, Ph), 8.2–8.3 (m, 4H,
Hortho, Ph); δC (CDCl3) 48.0 (SCH2N), 163.0 (C-4), 173.5 (C-6),
137.2, 136.4 (C-1Ј of 4-Ph and 6-Ph), 129.0, 128.9 (C-2Ј of 4-Ph
and 6-Ph), 128.4, 128.1 (C-3Ј of 4-Ph and 6-Ph), 133.5, 131.1
(C-4Ј of 4-Ph and 6-Ph); δN (in CDCl3 from CH3NO2) Ϫ84.3
and Ϫ136.7, N-5 and N-3.
N
R
R
– Sx
i
R
R
– 170.2
N
N
H
CH2SiMe3
R = Ph
a
b
c
d
e
R = p-MeC6H4
R = p-MeOC6H4
R = p-ClC6H4
R = H
21
20
3,5-Diphenyl-1,2,4-thiadiazole (19%) was also recovered
from the column.
Scheme 2 Reagents: (i) Me3SiCH2OTf; (ii) CsF. 15N shifts for 7a, 10a
and 21a shown.
(ii) 4,6-Bis(p-bromophenyl)-2H-1,3,5-thiadiazine (5d) (Table 1,
entry 4)
A solution of 3,5-bis(p-bromophenyl)-1,2,4-thiadiazole (0.5 g,
1.26 mmol) and trimethylsilylmethyl trifluoromethanesulfonate
(0.5 cm3, 2.5 mmol) in chlorobenzene (10 cm3) was heated at
80 ЊC for 24 h. The resultant mixture was cooled to ambient
temperature, treated with CsF (0.38 g, 2.5 mmol) stirred for 24
h and filtered to remove salts. After evaporation under reduced
pressure the solution was placed on a column of silica gel-60
(70–230 mesh ASTM). Elution with dichloromethane gave 5d,
mp 142–143 ЊC (from CH2Cl2–hexane) (0.34 g, 66%) (Found: C,
43.8; H, 2.3; N, 6.6. C15H10Br2N2S requires C, 43.9; H, 2.45; N,
6.8%); νmax (mull) 1601.5, 1587.9 cmϪ1 (C᎐N); δ (CDCl3) 4.8
(s, 2H, SCH2N), 7.55, 8.09 (4H, ds, AAЈBBЈ, JAB 8.7 Hz), 7.63,
8.02 (4H, ds, JAB 7.8 Hz), two p-BrC6H4; δC (CDCl3) 48.0
(SCH2N), 172.7, 161.9 (C-6, C-4), 135.9, 135.2 (C-1Ј of 4-Ar,
6-Ar), 132.2, 131.6 (C-2Ј of 4-Ar, 6-Ar), 130.2, 129.6 (C-3Ј 4-Ar,
6-Ar), 128.6, 125.9 (C-4Ј of 4-Ar, 6-Ar). 3,5-Bis(p-bromo-
phenyl)-1,2,4-thiadiazole (20%) was also eluted from the
column.
19 while rotation of both the N᎐CH and N᎐S groups leads to
᎐
᎐
2
20. Defining 16 as the cis, trans configuration (16ct), structure
16 goes to 19 by passing through a cis, cis intermediate, or 16
goes to 20 by passing through a trans, trans then a trans, cis
intermediate, (cf. the Experimental section). The energetics
(Table 3) are such that the two routes are competitive. In any
case, loss of sulfur from 19 or 20 can each be expected to give 21
under these conditions. Table 3 gives the energies and entropies
relative to structure 13. Also of interest from the calculations is
the result that ring-opening of the 1,2,5-thiadiazolium ylide 13
has a significantly higher activation barrier than that for the
1,2,4-isomer 3.
᎐
H
Experimental
Mps were measured on an Electrothermal apparatus. The 3,5-
diaryl-1,2,4-thiadiazoles 1 were prepared by treating thiobenz-
amide with butyl nitrite following a literature procedure19 and
J. Chem. Soc., Perkin Trans. 1, 1999, 1709–1712
1711

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(iii) 1-Trimethylsilylmethyl-4,5-diphenyl-1H-imidazole (21a)
(Table 1, entry, 5)
cis S᎐C group going through the structure 4cc to give 5. A
disrotatory direction goes through 4ccЈ to give ultimately 6S by
᎐
attack on the C᎐S group by the terminal CH . In these two
᎐
2
A solution of 3,4-diphenyl-1,2,5-thiadiazole (0.3 g, 1.26 mmol)
and trimethylsilylmethyl trifluoromethanesulfonate (0.63 cm3,
3.15 mmol) was stirred at 80 ЊC for 12 h and cooled to give a
residue containing the salt 10a, δH (CDCl3) 0.2 (s, 9H, SiMe3),
4.0 (s, 2H, CH2-N), 7.0–7.3 (m, 10H, Ph); δC (CDCl3) Ϫ1.3
(SiMe3), 39.0 (N-CH2), 160.8 (C-3), 159.7 (C-4), 118.1, 121.2
(C-1Ј of 3-C-Ph and 4-C-Ph), 127.9, 128.6 (C-2Ј of 3-C-Ph and
4-C-Ph), 130.6, 129.4 (C-3Ј of 3-C-Ph and 4-C-Ph), 133.4, 131.1
(C-4Ј of 3-C-Ph and 4-C-Ph); δN (in CDCl3 from CH3NO2)
Ϫ60.6 and Ϫ134.4, N-5 and N-2. This residue in dichloro-
methane (5 cm3) was treated with CsF and stirred for 12 h at
ambient temperature placed on a Merck silica gel column (70–
230 mesh ASTM) and when eluted with gradient mixtures of
dichloromethane–diethyl ether (1:0–1:1 v/v) gave the title
compound 21a, mp 120–121 ЊC (hexane) (24%) (Found: C,
74.2; H, 7.4; N, 9.0. C19H22N2Si requires C, 74.5; H, 7.2; N,
9.2%); δH (CDCl3) 0.0 (9H, s, SiMe3), 3.40 (2H, s, CH2), 7.56
(1H, s, H-2), 7.13–7.50 (10H, m, Ph); δC (CDCl3) Ϫ2.4 (SiMe3),
36.1 (CH2), 136.1 (C-2), 134.6 (C-5), 137.7 (C-4), 126.1, 126.4,
128.0, 128.5, 128.9, 130.9, 131.1 (aromatic CH), one signal not
observed due to overlap in the 126–131 ppm region; δN (CDCl3
from CH3NO2) Ϫ129.4 and Ϫ170.2, N-2 and N-1 respectively.
Remaining resinous decomposition products were washed
from the column with methanol as well as traces of 4,5-
diphenylimidazole.
cases the S᎐C group remains cis. In the reaction of 1,2,5-
᎐
thiadiazolo case, for the intermediate 16 the conrotatory
rotation of the N–CH2 group also leads to a six membered ring
19. However, rotation of the N᎐S group may also occur before a
᎐
disrotary rotation, forming a nearly planar tt structure. Sub-
sequent rotation of the N–CH2 group then ultimately gives rise
to the structure 20 via a trans, cis intermediate.
References
1 R. N. Butler, P. D. McDonald, P. McArdle and D. Cunningham,
J. Chem. Soc., Perkin Trans. 1, 1994, 1653.
2 R. N. Butler, K. M. Daly, J. M. McMahon and L. A. Burke,
J. Chem. Soc., Perkin Trans. 1, 1995, 1083.
3 R. N. Butler, P. D. McDonald, P. McArdle and D. Cunningham,
J. Chem. Soc., Perkin Trans. 1, 1996, 1617.
4 E. Vedejs, S. Larsen and F. G. West, J. Org. Chem., 1985, 50, 2170.
5 R. C. F. Jones, J. R. Nichols and M. T. Cox, Tetrahedron Lett., 1990,
31, 2333.
6 R. K. Smalley, Comprehensive Heterocyclic Chemistry II, series eds.
A. R. Katritzky, C. W. Rees and E. F. V. Scriven, Pergamon, Oxford,
1996, vol. 6 (vol. ed., A. J. Boulton), pp. 681–694.
7 C. W. Rees, J. Heterocycl. Chem., 1996, 33, 1419 and references
therein.
8 D. Clarke, K. Emayan and C. W. Rees, J. Chem. Soc., Perkin
Trans. 1, 1998, 77; K. Emayan, R. F. English, P. A. Koutentis and
C. W. Rees, J. Chem. Soc., Perkin Trans. 1, 1997, 3345.
9 R. Huisgen and J. Rapp, Heterocycles, 1997, 45, 507; R. Huisgen,
J. Rapp and H. Huber, Liebigs Ann./Recl., 1997, 1517; R. Huisgen,
G. Mlosten and K. Polborn, J. Org. Chem., 1996, 61, 6570.
10 For reviews see C. R. Ganellin, in Medicinal Chemistry, ed., S. M.
Roberts and B. J. Price, Academic Press, London, 1985, p. 93;
G. J. Durant, Chem. Soc. Rev., 1985, 14, 375.
11 R. N. Butler, M. O. Cloonan, P. McArdle and D. Cunningham,
J. Chem. Soc., Perkin Trans. 1, 1998, 1295.
12 R. N. Butler, E. C. McKenna, J. M. McMahon, K. M. Daly,
D. Cunningham and P. McArdle J. Chem. Soc., Perkin Trans. 1,
1997, 2919.
(iv) 2,4-Diphenyl-1H-imidazole (6a) (Table 1, entry 9)
A solution of 4,6-diphenyl-2H-1,3,5-thiadiazine 5a (0.19 g,
0.753 mmol) in ethanol (5 cm3) was treated with sodium ethox-
ide (0.09 g, 1.3 mmol), heated under reflux for 3 h, cooled and
evaporated under reduced pressure and the residue in dichloro-
methane (2 cm3) was placed on a silica gel-60 column (70–230
mesh ASTM). Elution with diethyl ether gave 6a, mp 168 (lit.,22
168 ЊC) (from CH2Cl2–hexane) (0.11 g, 69%) (Found: C, 81.5;
H, 5.2; N, 12.4. C15H12N2 requires C, 81.7; H, 5.5; N, 12.7%); δH
(CDCl3) 7.3–7.7 (11H, m, Ar), 8.5 (1H, br s, NH).
13 G. L’Abbé, P. Delberke, L. Bastin, W. Dehaen and S. Toppet,
J. Heterocycl. Chem., 1993, 30, 301.
14 For comments on the concept and term “heteroelectrocyclisation”
cf. W. M. F. Fabian, V. A. Bakulev and C. O. Kappe, J. Org. Chem.,
1998, 63, 5801.
Calculations
15 A. Rolfs, P. G. Jones and J. Liebscher, J. Chem. Soc., Perkin Trans. 1,
1996, 2339; A. Rolfs and J. Liebscher, Angew. Chem., Int. Ed. Engl.,
1993, 32, 712.
All calculations were carried out using the Gaussian94 series of
programs.17 The HF//6-31G* theoretical level was chosen for
all structures. The nature of the stationary points on the poten-
tial energy surfaces were all identified using analytical second
derivatives to compute vibrational frequencies. The normal
mode of the single negative frequency obtained for transition
state structures was inspected to insure that it connects the
reactant and product of interest.
In order to keep track of the possible isomers a cis–trans
notation was given for the rotations about the single C–N
bonds. Upon opening from the five-membered thiadiazolo ring,
single bonds are formed at the 2–3 and 4–5 positions of the
resulting open chains and the rotational isomers are given a
cis or trans designation in this respective order. Thus the first
isomer to be formed upon ring opening is designated ct. The
trans positions give a nearly planar component whereas the cis
positions give a dihedral angle of ca. 60Њ about the appropriate
single C–N bond.
16 A. Rolfs and J. Liebscher, J. Org. Chem., 1997, 62, 3480.
17 GAUSSIAN94 (Revision E.2), M. J. Frisch, G. W. Trucks, H. B.
Schegel, P. M. W. Gill, B. G. Johnson, M. A. Robb, J. R. Cheeseman,
T. A. Keith, G. A. Petersson, J. A. Montgomery, K. Ragavachari,
M. A. Al-Laham, V. G. Kakrzewski, J. V. Ortiz, J. B. Foresman,
J. Cioslowski, B. B. Stefanov, A. Nanayakkara, M. W. Wong,
J. L. Andres, E. S. Replogle, R. Gomperts, R. L. Martin, D. J. Fox,
J. S. Binkley, D. J. Defrees, J. Baker, J. P. Stewart, M. Head-Gordon,
C. Gonzalez and J. A. Pople, GAUSSIAN, Inc., Pittsburgh, PA,
1997.
18 A. O. Fitton and R. K. Smalley, in Practical Heterocyclic Chemistry,
Academic Press, London, 1968, p. 21.
19 M. W. Cronyn and T. W. Nakagawa, J. Am. Chem. Soc., 1952, 74,
3693.
20 A. C. Cope, D. S. Smith and R. J. Cotter, Org. Synth., 1963, Coll.
Vol. IV, 377.
21 M. Villena-Blanco and W. M. Jolly, Inorg. Synth., 1967, 9, 98;
M. Tashiro, J. Heterocycl. Chem., 1979, 16, 1009.
22 P. G. Haines and E. C. Wagner, J. Am. Chem. Soc., 1949, 71, 2793.
Thus for example, in the reaction 3 to 4 the resulting isomer
of 4 is ct (i.e. C2–N3 cis and C4–N5 trans). The trans N᎐CH
᎐
2
group can then rotate in a conrotatory direction relative to the
Paper 9/01148J
1712
J. Chem. Soc., Perkin Trans. 1, 1999, 1709–1712