Ring expansions of N-methyl-1,2,5-oxadiazolium and 1,2,3-triazolium perchlorate salts with bases to six-membered azines: Direct detection of an addition intermediate in an addition-elimination mechanism and a degradation of 1,2,5-oxadiazolium salts to aα-cyano nitrones

Article abstract of DOI:10.1039/a701233k

Reactions of 2-methyl-1,2,5-oxadiazolium perchlorate salts and 1-methyl-2-aryl-1,2,3-triazolium perchlorate salts with the bases KCN, NaOEt, KOBu^f, LiNPr^l₂ give ring expansions to substituted 1,2,5-oxadiazines and 1,2,4-triazines. With cyanide as base the reactions follow an addition-elimination pathway and in two cases the addition intermediate has been isolated or directly detected by low-temperature NMR spectroscopy. The oxadiazolium system with cyanide also gives a useful new route to α-cyano nitrones via a ring degradation which competes with ring expansion. The reactions with KOBu^t and LiNPrⁱ₂ do not involve an addition of the base to the azolium salt. Reactions have been monitored by ¹³C NMR spectroscopy by using ¹³CN^-. An X-ray crystal structure is reported for (E)-N-(α-cyanobenzylidene)methylamine N-oxide.

Full text of DOI:10.1039/a701233k

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Ring expansions of N-methyl-1,2,5-oxadiazolium and 1,2,3-
triazolium perchlorate salts with bases to six-membered azines: direct
detection of an addition intermediate in an addition–elimination
mechanism and a degradation of 1,2,5-oxadiazolium salts to á-cyano
nitrones
Richard N. Butler,* Elaine C. McKenna, John M. McMahon, Karen M. Daly,
Desmond Cunningham and Patrick McArdle
Chemistry Department, University College Galway, Ireland
Reactions of 2-methyl-1,2,5-oxadiazolium perchlorate salts and 1-methyl-2-aryl-1,2,3-triazolium
perchlorate salts with the bases KCN, N aOEt, KOBut, LiN Pri2 give ring expansions to substituted 1,2,5-
oxadiazines and 1,2,4-triazines. With cyanide as base the reactions follow an addition–elimination
pathway and in two cases the addition intermediate has been isolated or directly detected by low-
temperature N M R spectroscopy. The oxadiazolium system with cyanide also gives a useful new route
to á-cyano nitrones via a ring degradation which competes with ring expansion. The reactions with
KOBut and LiN Pri2 do not involve an addition of the base to the azolium salt. Reactions have been
monitored by 13C N M R spectroscopy by using 13CN Ϫ. An X-ray crystal structure is reported for
(E)-N-(á-cyanobenzylidene)methylamine N-oxide.
The reactions of azolium salts with bases have attracted wide
interest in the past and recently.1–14 For azolium systems con-
taining ring C᎐H bonds removal of a ring proton may give rise
to an internal azolium ylide1,2 or an isoelectronic stable azole
carbene system 3–5 depending on the nature of the azolium sub-
strate (Scheme 1, path 2). These options are not available with
fully substituted azolium salts. With such systems the base may
(i) add to the iminium site giving an intermediate which may
undergo an elimination or alternatively a fragmentation caus-
ing opening and destruction of the azole ring6,7 or (ii) attack an
activated exocyclic α-CH bond giving ultimately substitution at
this site.8 With azolium N-alkoxides nucleophilic addition at an
unsubstituted iminium carbon may be followed by elimination
of the N-alkoxy group as an alcohol (Scheme 1, path 1; Y =
RO). Alternatively proton loss from the iminium carbon may be
followed by electrophilic attack at this site via the azolium ylide
(Scheme 1, path 2).8,9 This type of reaction has been widely used
for electrophilic substitution with higher azoles, particularly the
tetrazoles.10–14 The range of possible alternative pathways has
been classified by Begtrup.9 One of the rarest pathways is
generation of an exocyclic double bond at an azole ring carbon
by α-proton loss (Scheme 1, path 3). In the present work 15 we
have observed a previously undetected pathway comparable to
path 3 in which an addition–elimination process abstracts the
α-CH of an N-methyl substituent thereby generating a double
bond exocyclic to a ring nitrogen (Scheme 1, path 4). This leads
ultimately to a ring expansion of the azole to an azine. A com-
bined loss of the N-methyl group and the adjacent bonded
nucleophile (Scheme 1, path 4a) may also occur leading to the
parent unquaternised azole.
Results and discussion
1,2,3-Triazolium salts, 1
Previously, in studies of azolium 1,3-dipoles, we have noted 16
that treatment of the N-methyltriazolium salts 1 with ethoxide
base in toluene resulted in ring expansion to the triazines 2
along with lesser yields of the imidazoles 3. No intermediates
could be detected in these reactions and it was thought that the
process involved a Hoffmann E2-type proton abstraction from
the CH3 group with concerted ring-opening of the azolium sys-
tem to give the conjugated triazatriene species 6A (Scheme 2).
This leads on to the products 2 and 3 by competing electro-
cyclisations.16 Similar ring expansions of the N-methyl-1,2,5-
oxadiazolium systems 8 to the oxadiazines 9 (Scheme 3) have
now been observed on treatment with bases15 testifying to the
generality of the process. The oxygen analogue of the inter-
mediate 6A is 12 (Scheme 3). An early example of a ring expan-
sion of this type was found by Kohler and co-workers17 with an
isoxazolium system but they did not recognise the ring-
expanded structure of the product and the structure was sub-
sequently established by King and Durst.18 Similar ring expan-
sions have now been induced by bases such as potassium tert-
butoxide and lithium diisopropylamide giving products 2 and 3
in yields similar to sodium ethoxide but the efficiency of the
reaction (conversion yields) may vary with the base, possibly
due to solubility variations (Table 1). With KCN as base the
same products 2 and 3 were again formed with 2 as the main
product but in this case low yields of the parent triazoles 4 were
Nu
Z
Z
X
Z
Nu
–HY
H
Y
N
N
Nu–
X
1
E
Z
R
Y
–
Z
Nu–
2
E+
N+
N+
N+
Y
X
X
X
Y
Nu–
3
4
Nu–
R
Z
–
Z
N+
N
Z
X
Y
X
Y
Nu
N
X
CH3
–NuH
4
4a –MeNu
R
Z
R
Z
R
Z
–
N
X
N+
N
X
X
Scheme 1 R = H for 1,2; R = alkyl for 3; R = aryl for 4
J. Chem. Soc., Perkin Trans. 1, 1997
2919

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Table 1 Reactions of N-methyltriazolium salts 1 with basesa
Products: yield % (conversion %)
Entry
Substrate
Base (T /ЊC)
2
3
4
1 (recovered)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
1a
1a
1a
1a
1b
1b
5bb
1b
1b
1c
1c
1c
5c
5c
1c
1c
1d
1d
1d
1d
1e
1e
NaOEt
KCN
75 (69)
33 (8)
58 (18)
84 (69)
52 (26)
38 (13)
32
62 (31)
65 (46)
50 (24)
38 (12)
38 (12)
32
16 (14)
31 (7)
17 (6)
16 (13)
21 (11)
35 (12)
20
30 (16)
32 (23)
42 (20)
38 (12)
36 (11)
31
—
35 (10)
—
—
—
22 (17)
7
—
—
—
18 (5)
18 (5)
30
—
—
—
—
20 (5)
—
—
(8)
(73)
(70)
(18)
(50)
(68)
—
(49)
(30)
(54)
(66)
(67)
—
KOBut
LiNPri2
NaOEt
KCN
—
KOBut
LiNPri2
NaOEt
KCN (45)
KCN (65)
(45)c
(65)c
49
46
—
KOBut
LiNPri2
NaOEt
KCN
45 (23)
48 (23)
80 (56)
52 (12)
67 (40)
79 (52)
92 (83)
30 (9)
36 (19)
40 (20)
19 (13)
19 (4)
24 (14)
20 (13)
(49)
(43)
(30)
(77)
(40)
(34)
(9)
KOBut
LiNPri2
NaOEt
KCN
d
—
—
19 (6)
23 (7)
(67)
a
Reactions employed 1.1 mol base in toluene at ambient temperatures except for LiNPri2 for which the solvent was dry tetrahydrofuran; reaction
12 h for NaOEt, 24 h for other bases. b Generated at Ϫ10 ЊC and warmed to ambient temperatures. c Stirred in toluene. d Trace quantities only
were encountered.
151–152
145–147
156–157
R
Ph
R
N
O
Ph
Ph
Ph
Ph
N
Ar
N
N
N
base
N
base
O
N
Ar
+
+
N
+
N
–
–
ClO4
ClO4
5.3–5.4
78.3–78.4
N
R
158–160
R
154–156
N
Ph
138–142
N
CH3
CH3 4.1–4.2
28–39
NHAr
8
9
1
2
3
CN–
Ar
Ph
N
13CN–
N
R
R
R
R
R
N
N
N
O
N
Ph
–HCN
A
O
••
O
–
+
N
N
N
R
6A
CH3
NC
144.2
12
10
11
Ph
Ph
Ph
N
N
–HCN
N
Ar
N
Ar
121–122
••
+
N
O–
B
R
N
–
Ph
+
+
N
RC
N
13CN
CH3
CN
CH3
2.71
36.9
4.3
55–56
76.7
114–115
114.5
13
14
5
6
O–
CN
(i)
+
N
a R = Ph
Ph
b R = p-BrC6H4
c R = p-ClC6H4
d R = p-MeC6H4
e R,R = (CH2)4
CN
15
CH3
N
N
N
Ar
Ph
N
Ph
CO2Me
N
Ar
+ MeCN
N
Scheme 3 Some 1H and 13 C NMR shifts ranges shown
Ph
CO2Me
4
7
terised. The intermediate 5b was generated and held in solution
at Ϫ10 to 5 ЊC in CD2Cl2 and its proton and carbon-13
NMR spectra measured. On warming solutions of the species
5b and 5c in toluene they changed into the products 2, 3 and 4.
a Ar = Ph
b Ar = p-BrC6H4
c Ar = p-NO2C6H4
d Ar = p-MeC6H4
e Ar = p-MeOC6H4
1
This process was followed by H and 13C NMR spectra for
solutions in CD2Cl2 both for normal substrates and for sub-
strates using carbon-13 labelled cyanide. In all of the reactions
of 1 with cyanide ion the parent triazoles 4 were formed by loss
of MeCN from 5. No intermediates could be detected by NMR
between 5 and the products 2 and 3 but the species 6 was a likely
possibility. The species 6 is a 1,2,3-triazolium-1-methanide
1,3-dipole which we have previously generated by a different
Scheme 2 NMR shift ranges for 1, (CD3)2SO and 5b in CD2Cl2 shown.
᎐
Reagent: (i) MeO2CC᎐CCO2Me.
᎐
also formed. The extent of conversion was lower with cyanide
ion than with theother basesbeingin therange25–40%(Table1).
In the reaction with cyanide ion the intermediates 5 were readily
detected. Compound 5c was a stable solid and was fully charac-
2920
J. Chem. Soc., Perkin Trans. 1, 1997

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Table 2 Reactions of N-methyloxadiazolium salts 8 with basesa
Products
9
14
13
Mp
(T /ЊC)
Yield
(%)
Yield
(%)
Mp
(T /ЊC)
Yield
(%)
Entry
Substrate
Base
f
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
8a
8a
8a
8a
8b
8b
8b
8b
8c
8c
8c
8c
8d
8d
8d
8d
8e
NaOEt
KCN
116–118b
”
10
23
91
80
11
16
86
83
9
18
97
80
12
19
77
73
—
72
68
—
—
78
68
—
—
74
53
—
—
81
50
—
—
—
—
95–96e
62
—
—
d
KOBut
LiNPri2
NaOEt
KCN
”
”
—
—
d
f
108–110b
—
—
”
”
”
131–133e
64
—
—
KOBut
LiNPri2
NaOEt
KCN
—
—
d
d
f
82–84b
—
—
”
”
”
116–117e
50
—
—
KOBut
LiNPri2
NaOEt
KCN
—
—
d
d
f
93–95c
—
—
”
”
”
—
95–97e
—
63
—
—
KOBut
LiNPri2
KCN
d
d
—
—
115–117 (15) 83
a
Reactions with 1.1–1.3 mol base in toluene at ambient temperatures except for LiNPri2 for which the solvent was dry tetrahydrofuran. b From
dichloromethane-hexane. c From hexane. d Not detected. e From dichloromethane–light petroleum (bp 40–60 ЊC). f Intractable oils were
encountered.
route.19 Its presence was confirmed when it was trapped from
the intermediate 5b with dimethyl acetylenedicarboxylate
(DMAD). Thus when a solution of 5b, generated at 0–5 ЊC in
CH2Cl2 was treated with DMAD and stirred at ambient tem-
peratures for 48 h the adduct 7b (28%) was isolated along with
products 2b (40%) and 4b (12%). The intermediate 6 could not
be trapped from any of the reactions with the other bases. Thus
cyanide ion reacts with the triazolium salts 1 by an addition–
elimination process which is different to the reaction with hard
bases although the products are similar.
1,2,5-Oxadiazolium salts 8
Treatment of the salts 8 with bases gave the products 9, 13
and 14. Interestingly in this case the reactions with ethoxide
paralleled those with cyanide. The ring-expanded product 9
alone was obtained in high yield from potassium tert-butoxide
and lithium diisopropylamide (Scheme 3, Table 2). Mixtures of
the products 9, 13 and 14 were obtained from the reaction with
KCN and comparable yields of 9 and 13 were also obtained
from the reaction with NaOEt. The expected intermediate 10
from cyanide addition to the oxadiazolium salts could not be
directly detected because it was too short-lived. However its
presence was clearly signalled by its fragmentation into the
products 13 and 14 (path B, Scheme 3) which were the major
products. The reaction provides a useful route to α-cyano
substituted nitrones 14 which are not readily available. The
alternative path A (Scheme 3) from the intermediate 10 was a
relatively minor pathway which gave rise to low yields of
the products 9. The oxadiazolium methanide dipole 11, the
analogue of 6, could not be trapped. Theoretical calculations as
well as extensive experimental attempts15 to generate this dipole
have indicated that it is much less stable than 6 and likely to
undergo almost spontaneous opening to 12, the precursor to 9.
In the reactions with ethoxide base, while the products 9 and 13
were obtained in yields similar to those from cyanide (Table 2)
the α-ethoxy derivatives of 14 (EtO for CN) were not isolated
and only intractable oils were obtained from chromatographic
separations. With the substrate 8e, where the nitrile fragment
from the intermediate 10 cannot leave the molecule, the product
from the cyanide reaction was the interesting nitrone 15.
Fig. 1 X-Ray crystal structure of nitrone 14a
the bases potassium tert-butoxide and lithium diisopropyl-
amide steric constraints appear to block this initial addition.
No benzonitriles are formed and the yields of the oxadiazines
9 are raised to the range 70–97% (Table 2). In these cases the
deprotonation of the N-methylazolium salts bypasses the inter-
mediate 10 and probably involves direct E2 attack by the base at
the N-methyl group in a Hoffmann-type process.
Structure and formation of products
The structures of the products 5, 9, 14 and 15 were established
from microanalysis, IR, proton and carbon-13 NMR spectra
which showed all of the expected signals. Carbon-13 NMR
assignments were supported by DEPT and off-resonance
decoupled spectra and by the use of C-13 labelled cyano groups
for the species 5. An X-ray crystal structure of 14a (Fig. 1)
confirmed the E-configuration with the CN group cis to the Me
substituent.† The nitrones did not isomerise under the reaction
† Atomic coordinates, thermal parameters and bond lengths and angles
have been deposited at the Cambridge Crystallographic Data Centre
(CCDC). See Instructions for Authors, J. Chem. Soc., Perkin Trans. 1,
1997, Issue 1. Any request to the CCDC for this material should quote
the full literature citation and the reference number 207/129.
These results suggest that the reactions with cyanide and
ethoxide involve additions of the nucleophile at the iminium
carbon followed by degradation of the intermediate 10. With
J. Chem. Soc., Perkin Trans. 1, 1997
2921

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conditions and early monitoring of the product mixture showed
that the E-nitrone only was present in the reaction solution
before the work-up. Stereoelectronic studies of the addition of
nucleophiles to iminium ions in six-membered rings,20 including
N-alkyloxazinium salts,21 have shown that the developing lone-
pair on nitrogen is trans to the incoming nucleophile. It is likely
that initially in the species 5 and 10 the CN is also trans to the
lone-pair on the adjacent N-atom and that the products 13 and
14 arise from a rapid 1,3-dipolar cycloreversion in 10. This
cycloreversion did not occur in the intermediates 5 where the
stronger conjugated N᎐NAr bond replaces the N᎐O bond of
10. Nitrogen inversions could of course occur in these species
but the CN and CH3 groups are required to be cis for elimin-
ation of HCN and MeCN from 5. The products 2, 3, 4, 7b and
13 are known compounds.16,19 In the present work these prod-
ucts were identified by comparison with authentic samples.
toluene (15 cm3) was treated with potassium cyanide (0.12 g, 1.8
mmol) and the mixture stirred at ambient temperature for 24 h,
filtered to remove salts, evaporated and the residue in dichloro-
methane (5 cm3) placed on a column (Merck silica gel 60, 230–
400 mesh ASTM). Elution with light petroleum (bp 40–60 ЊC)–
dichloromethane (60:40 v/v) delivered benzonitrile 13a
(68%); using the same eluents in a 20:80 v/v mixture gave (E)-
N-(α-cyanobenzylidene) methylamine N-oxide 14a, mp 95–96 ЊC
(from dichloromethane–light petroleum, bp 40–60 ЊC) (150 mg,
62%) (Found: C, 67.4; H, 5.0; N, 17.3. C9H8N2O requires C,
67.5; H, 5.0; N, 17.5%); νmax(Nujol)/cmϪ1 1570 (C᎐N), 2214
᎐
ϩ
Ϫ
᎐
(C᎐N), 1240 (N ᎐O ); δ (CDCl ) 4.3 (s, 3H, NMe), 7.4 (m,
᎐
H
3
3H, Ph, Hm, Hp), 8.2–8.3 (m, 2H, Ph, Ho); δC 55.8 (NMe),
114.6 (CN), 121.0 (methine C᎐N), 128.0, 127.4, 128.6, 131.4
᎐
(Ph, C-1Ј, C-2Ј, C-3Ј, C-4Ј resp.). Compound 9a (23%) was
finally recovered from the column using CH2Cl2–EtOAc (95:5
v/v) as eluent. A similar reaction with NaOEt as base gave
compound 13a (72%), 9a (10%) and intractable oils.
Experimental
(b) A solution of 8e (0.61 g, 2.55 mmol) in dry dichlorometh-
ane (25 cm3) was treated with potassium cyanide (0.2 g, 3.07
mmol), stirred at ambient temperature for 2 h, filtered to
remove salts, evaporated under reduced pressure and the resi-
due crystallised from methanol to give (E)-(1,5-dicyanopentyl-
idene)methylamine N-oxide 15, mp 115–117 ЊC (MeOH) (0.3 g,
83%) (Found: C, 58.1; H, 6.8; N, 25.3. C8H11N3O requires C,
Mps were measured on an Electrothermal apparatus. IR
spectra were measured with
a
Perkin-Elmer 983G
spectrophotometer. NMR spectra were measured on JEOL
JNM-GX-270 and JEOL LAMBDA 400 MHz instruments
with tetramethylsilane as internal reference and deuteriochloro-
form or hexadeuteriodimethyl sulfoxide as solvents; J values are
given in Hz. All carbon-13 NMR assignments were supported
by DEPT and off-resonance decoupled spectra and CN signals
were confirmed using labelled 13CN groups. Microanalyses were
measured on a Perkin-Elmer model 240 CHN analyser. The
substrates 8 were prepared by heating the 3,4-diarylfurazans22
at 80 ЊC in dimethyl sulfate (2–5 mmol in 5 cm3) for 48 h and
treating the cooled solution with aqueous sodium perchlorate
followed by diethyl ether to precipitate the salts which were
recrystallised from acetone–diethyl ether: 8a, mp 140–141 ЊC
(90%) (Found: C, 53.3; H, 3.9; N, 8.2. C15H13ClN2O5 requires
C, 53.5; H, 3.85; N, 8.3%); 8b, mp 188–190 ЊC (91%) (Found: C,
36.6; H, 2.35; N, 5.80. C15H11Br2ClN2O5 requires C, 36.4; H,
2.20; N, 5.65%); 8c, mp 174–175 ЊC (88%) (Found: C, 44.3; H,
2.6; N, 6.6. C15H11Cl3N2O5 requires C, 44.4; H, 2.7; N, 6.9%);
8d, mp 120–122 ЊC (81%) (Found: C, 56.2; H, 4.5; N, 7.4.
C17H17ClN2O5 requires C, 56.0; H, 4.65; N, 7.7%); 8e, mp 99–
101 ЊC (76%) (Found: C, 35.4; H, 4.45; N, 11.6. C7H11ClN2O5
requires C, 35.25; H, 4.6; N, 11.75%).
58.2; H, 6.65; N, 25.45%); νmax(Nujol)/cmϪ1 1634 (C᎐N), 2202,
᎐
2246 (two CN); δH (CDCl3) 1.75–1.77 (m, 4H), 2.42–2.45 (m,
2H), 2.59 (m, 2H) [(CH2)4CN], 4.07 (s, 3H, NMe); δC 16.4, 23.5,
23.6, 27.4 (4-cyanobutyl, C-4, C-3, C-2, C-1 resp.), 52.9
(NMe), 113.9 (α-CN), 118.9 (4-cyanobutyl, CN), 123.5
(methine C᎐N).
᎐
Reactions of the triazolium salts 1 with bases
The following are typical examples.
KCN; intermediates 5. (a) A suspension of 1-methyl-2-
(p-bromophenyl)-4,5-diphenyl-1,2,3-triazolium perchlorate 1b
(0.16 g, 0.3 mmol) in CD2Cl2 (1.5 cm3) was treated with KCN
(0.09 g, 1.4 mmol), stirred at 0 ЊC for 24 h, then filtered to
remove salts and unreacted 1b. The NMR spectra of the yellow
solution (Solution A) measured at Ϫ20 ЊC showed that it con-
tained pure 1-methyl-2-(p-bromophenyl)-4,5-diphenyl-5-cyano-
2,5-dihydro-1H-1,2,3-triazole 5b, δH 2.71 (s, 3H, NMe), 7.26–
7.33 (m), 7.47–7.51 (m) (8H, 5-Ph, 4-Ph, Hm,p, 5-Ph, Ho),
7.38 and 7.56 (ABq, 4H, JAB, 8.7, 2-NC6H4Br-p, AAЈBBЈ);
7.67–7.69 (m, 2H, 4-Ph, Ho); δC 36.9 (NMe), 76.7 (C-5), 114.5
(CN), 144.2 (C-4), 145.0, 113.9, 123.5, 119.5 (2-NC6H4Br-p,
C-1Ј, C-2Ј, C-3Ј, C-4Ј resp.), 135.3, 134.3 (5-Ph, 4-Ph, C-1Ј),
130.8, 130.5 (5-Ph, 4-Ph, C-4Ј), 127.4, 129.1, 129.7, 132.5
(remaining Ph, CH). Solution (A) was stirred at ambient tem-
perature for 24 h, placed on a silica gel-60 column (230–400
mesh ASTM) and eluted with dichloromethane to give 4b (7%),
2b (32%) and eluted with EtOAc to give 3b (20%). When a
solution (A) (prepared from 0.30 g, 0.6 mmol, 1b in CH2Cl2, 5
cm3) was first treated with DMAD (0.1 cm3) in CH2Cl2 (10 cm3)
at 0 ЊC prior to stirring at ambient temperature and worked up
as described eluting initially with gradient mixtures of light
petroleum (bp 40–60 ЊC)–dichloromethane (9:1 to 7:3 v/v) gave
the following products: 4b (15%), 7b (27%), mp 142–144 ЊC
(lit.,19 mp 142–144 ЊC), 2b (32%) and 3b (<4%) and some
intractable oils [a crude unstable sample of 5b, mp 37–40 ЊC
(Found: C, 63.8; H, 4.0; N, 12.2. C22H17BrN4 requires C, 63.3;
H, 4.1; N, 13.4%) was isolated by treating a toluene solution
with Et2O at Ϫ5 ЊC but the compound was best kept in solu-
tion] (Table 1, entries 6,7).
Reactions of oxadiazolium salts 8 with bases
The following are typical examples.
LiNPri2. A three-necked flask was charged with finely cut
lithium (23 mg, 3.26 mmol) followed by pure diisopropylamine
(0.36 g, 3.6 mmol) and freshly dried tetrahydrofuran (10 cm3)
and the mixture subjected to sonication and treated dropwise
with isoprene (0.12 g, 1.8 mmol). When the lithium had dis-
solved a solution of compound 8a, (1 g, 2.97 mmol) in tetra-
hydrofuran (10 cm3) was introduced and the mixture was stirred
at ambient temperature for 5 min, filtered to remove salts,
evaporated under reduced pressure and the residue in dichloro-
methane (5 cm3) placed on a column (Merck silica gel 60, 230–
400 mesh ASTM) and eluted with CH2Cl2–EtOAc (95:5 v/v) to
give 3,4-diphenyl-6H-1,2,5-oxadiazine 9a, mp 116–118 ЊC
(dichloromethane–hexane) (560 mg, 80%) (Found: C, 76.15; H,
5.2; N, 11.6. C15H12N2O requires C, 76.3; H, 5.1; N, 11.85%);
δH (CDCl3) 5.28 (s, 2H, CH2), 7.1–7.3 (10H, m, Ar); δC 78.3
(NCH2), 157.4 (C-3), 156.25 (C-4), 135.1, 128.3, 128.5, 130.4
(C-3-phenyl, C-1Ј, C-2Ј, C-3Ј, C-4Ј resp.), 132.1, 127.9, 128.3,
130.1 (C-4-phenyl, C-1Ј, C-2Ј, C-3Ј, C-4Ј resp.).
KOBut. A solution of 8a (1 g, 2.97 mmol) in toluene (30 cm3)
was treated with potassium tert-butoxide (0.4 g, 3.56 mmol)
and the mixture stirred at ambient temperature for 20 h, filtered
to remove salts, evaporated and the residue worked up on a
column as described to give 9a (91%).
(b) A mixture of 1c (0.3 g, 0.7 mmol) in toluene (3 cm3) was
treated with K13CN (0.2 g, 3.1 mmol), stirred at ambient
temperatures under a nitrogen atmosphere for 24 h, filtered to
remove salts and unreacted 1c (47%), cooled at 0 ЊC and treated
with light petroleum (bp 40–60 ЊC) causing separation of 1-
methyl-2-(p-nitrophenyl)-4,5-diphenyl-5-cyano-2,5-dihydro-1H-
KCN and NaOEt. (a) A solution of 8a (0.51 g, 1.5 mmol) in
2922
J. Chem. Soc., Perkin Trans. 1, 1997

View Article Online
Table 3 Crystal data for 14a
The reactions with potassium tert-butoxide were similar to
those with sodium ethoxide.16
Empirical formula
C9H8N2O
M
T/K
160.17
293(2)
X-Ray crystal structure determination of compound 14a
Crystal data are given in Table 3. The structure was solved by
direct methods, SHELX-86,23 and refined by full matrix least
squares using SHELX-93.24 SHELX operations were rendered
paperless using ORTEX which was also used to obtain the
drawings.25 Data were corrected for Lorentz and polarization
effects but not for absorption. Hydrogen atoms were included
in calculated positions with thermal parameters 30% larger
than the atom to which they were attached. The non-hydrogen
atoms were refined anisotropically. All calculations were per-
formed on a Silicon Graphics R4000 computer.
λ/Å
0.710 69
Monoclinic
P21/n
a = 6.5967(6) Å
b = 9.1775(12) Å; β = 101.084(9)Њ
c = 13.793(2) Å
819.5(2)
Crystal system
Space group
Unit cell dimensions
V/Å3
Z
Dc
4
1.298 Mg mϪ3
Absorption coefficient
F(000)
Crystal size
θ range for data collection
Index ranges
Reflections collected
Independent reflections
Reflections observed (>2σ)
Refinement method
Data/restraints/parameters
Goodness-of-fit F 2
Final R indices [I > 2σ(I)]
R indices (all data)
Largest diff. peak and hole
0.88 mmϪ1
336
0.24 × 0.15 × 0.09 mm
2.68 to 31.93Њ
Ϫ7 р h р 7; 0 рk р 10; 0 р l р 14
2203
Acknowledgements
E. C. McK., J. M. McM. and K. M. D. acknowledge grants
from the Irish Government Science Agency, FORBAIRT.
2077 [R(int) = 0.0494]
944
Full matrix least-squares on F 2
2077/0/110
0.901
References
R1 = 0.0581 wR2 = 0.1571
R1 = 0.1233 wR2 = 0.1855
0.173 and Ϫ0.163 e ÅϪ3
1 M. Begtrup and K. V. Poulsen, Acta Chem. Scand., 1971, 25, 2087;
M. Begtrup and P. A. Kristensen, Acta. Chem. Scand., 1969, 23, 2733.
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3 A. J. Arduengo III, R. L. Harlow and M. Kline, J. Am. Chem. Soc.,
1991, 113, 361.
R indices; R1 = [Σ |Fo| Ϫ |Fc| ]/Σ|Fo| (based on F), wR2 = {[Σw(|Fo2 Ϫ
¹
Fc |)2]/[Σw(Fo2)2]}² (based on F 2) w = 1/[(σFo)2 ϩ (0.2866*P)2] P =
2
2
Goodness-of-fit = [Σw(Fo2 Ϫ Fc )2/(Nobs Ϫ
2
2
(Max
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4 A. J. Arduengo III, H. V. R. Dias, R. L. Harlow and M. Kline,
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5 D. Enders, K. Breuer, G. Raabe, J. Runsink, J. H. Teles, J.-P. Melder,
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7 R. N. Butler, J. P. Duffy, E. P. NiBhradaigh, P. McArdle and
D. Cunningham, J. Chem. Res. (S), 1994, 216.
1,2,3-triazole 5c, mp 102–104 ЊC (from toluene–light petroleum,
bp 40–60 ЊC at ambient temperature) (0.12 g, 48% conversion)
(Found: C, 69.4; H, 4.6; N, 18.4. C22H17N5O2 requires C, 68.9;
H, 4.4; N, 18.3%); δH (CD2Cl2) 2.90 (s, 3H, NMe), 7.68 and 8.22
(ABq, JAB 8.3, AAЈBBЈ, p-NO2C6H4), 7.34–7.54 (m, 10H,
8 M. Begtrup and P. Vedso, J. Chem. Soc., Perkin Trans. 1, 1992, 2555.
9 M. Begtrup, Heterocycles, 1992, 33, 1129.
13
2 × Ph); δC 40.4 (NMe), 76.1 (d, JC᎐ CN, 79.4), (C-5), 114.6
(CN), 144.2 (C-4), 148.9, 116.4, 125.7, 142.9 (2-NC6H4NO2-p,
C-1Ј, C-2Ј, C-3Ј, C-4Ј resp.), 135.7, 127.4, 129.8, 131.1 and
135.7, 127.8, 129.2, 130.5 (4- and 5-Ph, C-1Ј, C-2Ј, C-3Ј, C-4Ј).
When a toluene solution of the salt 1c was heated with KCN or
when a toluene solution of 5c was heated separately similar
mixtures of the known 16 compounds 2c, 3c and 4c were
obtained (Table 1, entries 11–14).
(c) A mixture of 1-methyl-2-(p-tolyl)-4,5-diphenyl-1,2,3-
triazolium perchlorate 1d (0.3 g, 0.7 mmol) in toluene (15 cm3)
was treated with KCN (0.06 g, 0.9 mmol), stirred at ambient
temperatures for 24 h, filtered to remove salts and unreacted 1d
(77%), evaporated under reduced pressure and the residue in
CH2Cl2 (3 cm3) placed on a silica gel-60 column (230–400 mesh
ASTM) and eluted with CH2Cl2 to give 4d (0.01 g, 5%) followed
by 2d (0.028 g, 12%), mp 98–100 ЊC (lit.,16 mp 98–100 ЊC).
Elution with EtOAc gave 3d (0.01 g, 4%, mp 173–174 ЊC (lit.,16
mp 173–175 ЊC) (Table 1, entry 18).
10 R. Weiss and R. H. Lowack, Angew Chem., Int. Ed. Engl., 1991, 30,
1162.
11 S. Araki, Y. Wanibe, F. Uno, A. Morikawa, K. Yamamoto,
K. Chiba and Y. Butsugan, Chem. Ber., 1993, 126, 1149.
12 V. P. Karavai and P. N. Gaponik, Khim Geterotsikl. Soedin., 1991, 66
(Chem. Abstr., 1991, 115, 71 484).
13 R. H. Lowack and R. Weiss, J. Am. Chem. Soc., 1990, 112, 333.
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Soedin., 1988, 1699 (Chem. Abstr., 1989, 111, 194 674).
15 A part of the present work on oxadiazoles has been published
in a preliminary communication; R. N. Butler, K. M. Daly,
J. M. McMahon and L. A. Burke, J. Chem. Soc., Perkin Trans. 1,
1995, 1083.
16 R. N. Butler, J. P. Duffy, D. Cunningham and P. McArdle, J. Chem.
Soc., Perkin Trans. 1, 1992, 147.
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E. P. Kohler and N. K. Richtmeyer, J. Am. Chem. Soc., 1928, 50,
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J. Chem. Soc., Perkin Trans. 1, 1996, 1617.
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24 G. M. Sheldrick, SHELXL-93 a computer program for crystal
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25 P. McArdle, J. Appl. Crystallogr., 1995, 28, 65.
LiNiPr2. A three-necked flask was charged with finely cut
lithium (36 mg, 5.14 mmol) followed by pure diisopropylamine
(0.8 cm3, 5.71 mmol) and dry tetrahydrofuran (20 cm3) and the
mixture subjected to sonication and treated dropwise with iso-
prene at 10 ЊC giving a light yellow solution which was added to
a mixture of 1a (1.0 g, 2.43 mmol) in dry tetrahydrofuran (20
cm3) and stirred at ambient temperature for 24 h, filtered to
remove salts and unreacted 1a (18%) and the filtrate partitioned
between water (150 cm3) and chloroform (50 cm3). The aqueous
extract was further extracted with chloroform (2 × 50 cm3) and
the combined extract dried over anhydrous magnesium sulfate
and evaporated giving a residue which, in CH2Cl2 (4 cm3), was
placed on a silica gel column (270–400 mesh ASTM) and eluted
first with CH2Cl2 to give 2a (0.52 g, 69%) followed by EtOAc to
give compound 3a (0.1 g, 13%) (Table 1, entry 4).
Paper 7/01233K
Received 21st February 1997
Accepted 19th May 1997
J. Chem. Soc., Perkin Trans. 1, 1997
2923