Aromatic azapentalenes: 1H- and (mesoionic) 2H-pyrrolotetrazoles. Part 2. Reaction with electrophiles

Article abstract of DOI:10.1039/b007874n

Protonation, acetylation, benzoylation, carbamoylation, formylation, bromination, azo coupling, nitrosation and addition to DMAD were studied. Monosubstitution occurred as a rule (bromination excepted), the preferred site of attack being C(5) if both the 5 and 7 positions were free. A number of observations point to a slightly higher reactivity of the mesoionic isomers 2; this is consistent with AM1 calculations. 1,3-Dipolar cycloaddition behaviour of 2 towards DMAD, a conceivable process, could not be detected; only linear addition was observed. Nitroso derivatives of the series 3,4 and 8 were not isolated as such but as the ring-opened nitrile oxides 11 and 12; at elevated temperature analogous valence isomers arise also from the nitroso derivative 7e and the azo compounds 3e and 4e.

Full text of DOI:10.1039/b007874n

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Aromatic azapentalenes: 1H- and (mesoionic) 2H-pyrrolo-
tetrazoles. Part 2.1 Reaction with electrophiles
Dietrich Moderhack,* Dirk Decker and Bernhard Holtmann
1
Institut für Pharmazeutische Chemie der Technischen Universität, D-38106 Braunschweig,
Germany
Received (in Cambridge, UK) 28th September 2000, Accepted 9th February 2001
First published as an Advance Article on the web 19th March 2001
Protonation, acetylation, benzoylation, carbamoylation, formylation, bromination, azo coupling, nitrosation and
addition to DMAD were studied. Monosubstitution occurred as a rule (bromination excepted), the preferred site
of attack being C(5) if both the 5 and 7 positions were free. A number of observations point to a slightly higher
reactivity of the mesoionic isomers 2; this is consistent with AM1 calculations. 1,3-Dipolar cycloaddition behaviour
of 2 towards DMAD, a conceivable process, could not be detected; only linear addition was observed. Nitroso
derivatives of the series 3, 4 and 8 were not isolated as such but as the ring-opened nitrile oxides 11 and 12; at elevated
temperature analogous valence isomers arise also from the nitroso derivative 7e and the azo compounds 3e and 4e.
Table 1 AM1 atomic charges for 1a and 2a
Introduction
In the preceding Part1 we showed that pyrrolotetrazoles 1 and
1a
2a
2—new classes of aromatic azapentalenes—are accessible in a
straightforward manner. These compounds were characterised
by physical methods; for completion, we investigate the
behaviour towards electrophilic agents.2 Reactivity is antici-
pated from the properties of related systems such as IA–C
Total
π
Total
π
N(1)
N(2)
N(3)
N(4)
C(5)
C(6)
C(7)
C(7a)
Ϫ0.199
0.017
0.020
Ϫ0.135
Ϫ0.099
Ϫ0.159
Ϫ0.197
Ϫ0.024
1.669
1.126
1.175
1.543
1.124
1.065
1.166
1.110
Ϫ0.061
Ϫ0.067
Ϫ0.046
Ϫ0.048
Ϫ0.181
Ϫ0.119
Ϫ0.199
Ϫ0.079
1.269
1.444
1.362
1.417
1.220
1.022
1.165
1.105
bonds occur uniformly at C(5) [i.e. C(1) of the pyrrolo-
benzimidazole], whereas C(7) [C(3)] reacts only in the case of
5-[1-]substituted derivatives.5 Such selectivity is consistent with
semiempirical calculations which, in addition, show that C(6)
[C(2)] is electronically disfavoured.6 Hence, the presence of a
substituent at this position, which is encountered with practic-
ally all substrates I studied, does not detract from the above
orientation rule. Azapentalenes of type II with a free pyrrolic
half-ring are represented by a derivative having c = NR;
here H–D exchange experiments7 suggest that class 2 will be
primarily attacked at C(5), too. This view is supported by AM1
computations which we performed with the pyrrolotetrazoles
1a and 2a (Table 1).
Results
As expected, derivatives 1 and 2 are capable of forming stable
salts with strong acids, exemplified by the picrate of 1b1 and the
perchlorates of 1c and 2c. The site of protonation with both
classes is C(5) (Table 2: ‘α-cation’). This follows, for 1, from an
NOE experiment with 1cؒHClO4 (enhancement between the
one-proton singlet at δ 7.38 and the three-proton singlet at
δ 4.43), and for 2, from the similarity of the spectrum of
2cؒHClO4 with that of the aforementioned substance. The same
set of NMR signals was obtained from solutions of the bases 1c
and 2c in trifluoroacetic acid, confirming that on preparation of
the above perchlorates species that might have eluded isolation
were not formed. In contrast to 1c and 2c, the 5-methyl deriv-
including 4H-pyrrolo[1,2-a]benzimidazole (I; ab = CC of
benzo, c = NR).3,4 The ample material demonstrates that pro-
tonation, SE-reactions and additions to activated multiple
DOI: 10.1039/b007874n
J. Chem. Soc., Perkin Trans. 1, 2001, 729–735
This journal is © The Royal Society of Chemistry 2001
729

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Table 2 Protonation of the pyrrolotetrazoles 1c,e and 2c,ea
α-Cation
β-Cation
Percentage
Compound
5-H2/5-HMe
7-H
Me
7-H2
Me
α-Cation
β-Cation
1cؒHClO4
5.84b
5.86
5.87
5.89
6.13 (q, J 7.2)
6.16 (dq, J 7.2, 1.0)
7.38b
7.36
7.26
7.30
7.31
7.21 (d, J 1.0)
4.43
4.43
4.71
4.74
100
100
100
100
67
0
0
0
0
33
80
1c
2cؒHClO4
2c
1e
2e
1.98 (d, J 7.2), 4.46
1.95, 4.74
4.57 (br)
4.47 (q, J 1.9)
2.78 (t, J 1.7), 4.54
2.75 (t, J 1.9), 4.77
20
a NMR study in CF3CO2H [δH values; unspecified signals are singlets. Cf. δH of bases in CDCl3 (5-H/7-H/Me and 7-H/Me, respectively): 7.46/5.78/
3.97 (1c),2 7.42/6.17/4.25 (2c),1 5.60/2.64, 3.99 (1e),1 6.00/2.61, 4.32 (2e)1]. b Assignment by means of an NOE experiment.
atives 1e and 2e are protonated also at C(7), the 2H-isomer† 2e
to an even greater extent (‘β-cation’). While the results concern-
ing 1c,e and 2c match findings with congeners of I3,4c–f and II,7
the behaviour of 2e has no direct precedent.
As substrates for SE-reactions we chose the pyrrolotetrazoles
1b–h and 2b–h. These compounds were transformed as shown
in Schemes 1 and 2 to give, depending on starting material and
reagent, four categories of substitution products, i.e. 3/4, 5/6,
7/8 and 9/10. The derivatives of type 3/4 demonstrate the
preferential attack of the electrophile at position 5 as evi-
denced by NMR (δ7-H 5.5–6.5, δC(7) 78–87; data to be com-
pared with those of the substrates collected in Part 11).
Double substitution was observed only on bromination (5/6).
Although the substrates 1f–h and 2f–h bear a deactivating
substituent at C(7), they proved sufficiently reactive to afford
products of type 7/8. Compound 8f was envisaged as a
potential monobromo derivative of series 4, but efforts to
remove the ester group without affecting the bromo function
remained unrewarded.8 Finally, the derivatives of class 9/10
serve to illustrate the rule that C(7) is attacked only if pos-
ition 5 is occupied. Except for bromination, all of the reac-
tions performed with the acceptor-free 1H-pyrrolotetrazoles
1b–e have a precedent with azapentalenes I.3,4a,b,5a
The influence of both the starting bicycle (type 1 or 2) and
the substituent R4 on reactivity became apparent in certain
cases: thus, acetylation of 2c proceeded distinctly faster com-
pared to that of 1c, and 1f—in contrast to 2f—reacted only in
the presence of sodium acetate;9 also the conversion of 2h with
DMAD (see later) occurred more rapidly than that of 1h. These
observations are consistent with the calculations of Table 1
[higher electron density at C(5) for 2a]. Regarding the effect of
R4, the derivative 1b having the electron-releasing 6-methyl
group underwent acetylation considerably faster than did 1c;
Scheme 1 Reagents: i, Ac2O (for 3a,b and 4a,b), DMF–POCl3 for 3c
and 4c), DMAD (for 3d and 4d), PhN2Cl (for 3e and 4e), NaNO2–
AcOH (for 3f–h and 4f,g), Bz2O (for 3i), PhNCO (for 3j).
the same is true of benzoylation.10 Finally, comparing acetyl-
ation of the 6-methyl compounds 1f/2f to that of the 6-phenyl
congeners 1g/2g, the latter couple (including 2g!) failed to react
at all.
A remarkable finding, already reported,2 concerns nitro-
sation: substitution products of class 3/4 such as 3f–h and 4f,g
once formed are converted into the valence-isomeric nitrile
oxides 11a–c and 12a,b [Scheme 3, eqns. (1) and (2)]. Pyrrole
ring opening is impeded by an acceptor group at C(7) so as to
allow isolation of the derivatives 7d,e.2 With this in view, we
attempted to prepare the isomers 8d,e but found that the
materials isolated exist under the same conditions predomin-
antly as the nitrile oxides 12e,f [Scheme 3, eqn. (5); see also
Table 3]. Here obviously the ‘stabilising’ effect of the acceptor
substituent is offset by the less nucleophilic N(4) atom of a
(monocyclic) 2H-tetrazole ring.11 The differing stabilities of the
1H- and 2H-systems have recently been described for isomeric
† The term ‘2H-pyrrolotetrazole’ is used to accord with established
literature practice. See ref. 5 of Part 1.1
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Table 3 Equilibrium between the nitroso derivative 8e and the nitrile
oxide 12f a
Temperature/ЊC
K[12f]/[8e]
Percentage 8e
26
0
Ϫ10
Ϫ20
Ϫ30
17.5
11.8
10.4
9.9
5.4
7.8
8.8
9.2
9.4
9.6
a Determined in CD2Cl2 utilising δH 3.68, 4.42 (12f) and 3.83, 4.59 (8e).
Scheme 2 Reagents: i, Ac2O (for 7a and 8a), DMAD (for 7b and 8b),
PhN2Cl (for 7c and 8c), NaNO2–AcOH (for 7d,e and 8d,e), Br2 (for 8f);
ii, Ac2O (for 9a), PhN2Cl (for 9b).
Scheme 3 Reagents and conditions: i, DMAD, heat.
5-nitrosoimidazo[1,2-d]tetrazoles.12 Nitroso derivatives that are
stable at room temperature such as 7d,e ring-open on being
heated and can be trapped with DMAD to give, like 11a and
12a, the respective isoxazoles 13 or 14 (cf. ref. 2). The azo com-
pounds 3e and 4e, which are isolable in contrast to 3f–h and
4f,g, undergo pyrrole ring cleavage also at elevated temperature
to afford, in the presence of DMAD, the pyrazoles 13d2 and
14d [Scheme 3, eqns. (3) and (4)]. In agreement with the much
easier ring opening of 8d,e compared to 7d,e, the azo derivative
4e reacts more readily than does 3e. Nevertheless, the acceptor-
substituted congener 8c proved entirely unreactive (as paral-
leled by 7c2).
non-classical heteropentalenes,14 are 1,3-dipoles (Scheme 4).
While the azimine function of the tetrazolic half-ring need not
be considered,15 the potential azomethine imine might give rise
to a cyclazine such as 15 [reaction (a); cf. ref. 16]. This species,
because of three adjacent azane-type nitrogen atoms, is
expected to ring-open immediately giving the 6H-pyrrolo-
[1,2-b]pyrazole 16. However, we had no indications of the
occurrence of such a process and observed only linear addition
(as with 1c,h) [reaction (b)]. But in contrast with the stable
fumarates (E)-3d and (E)-7b, the 2H-analogues (E)-4d and
(E)-8b tend to isomerise into the maleates, the former
remarkably readily: thus, a solution of pure (E)-4d showed as
soon as 5 minutes after dissolving the material in chloroform
a 1 : 1 mixture of the (E)- and (Z)-forms, and 30 minutes
later there was a mere 5% of the starting isomer detectable.
We believe that the ease of this interconversion is a con-
sequence of the enhanced electron density at C(5) of the 2H-
pyrrolotetrazole series (Table 1), which facilitates polarisation
of the olefinic double bond; an acceptor group at C(7), pres-
ent with 8b, inhibits this so as to slow down isomerisation.
The predominance of the (Z)-adduct derived from 2 parallels
observations made earlier in the pyrrolo[2,1-b]thiazole series
(I; a = b = CH/CR, c = S).5a
Michael-type addition of the 1H-pyrrolotetrazoles 1c and
1h onto DMAD, proceeding in a 1 : 1 molar ratio, gave the
fumarates (E)-3d and (E)-7b, respectively. In both cases we
obtained only one stereoisomer. Assignment was made on the
3
basis of the JC(5),H(vinyl) coupling constants (9.4 and 10.1 Hz,
respectively), in conjunction with the shift value of the β carbon
1
atom of the vinyl group (δC 124.6 and 128.6; JC,H 166 Hz)
which, in the case of a (Z)-isomer, would adsorb at higher field
(δC < 120; see ref. 13 and Experimental section for the respective
derivatives of 4 and 8). Also from class 2 we obtained 1 : 1
adducts. The substrates, belonging to ‘type C’ of Ramsden’s
J. Chem. Soc., Perkin Trans. 1, 2001, 729–735
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with chloroform–diethyl ether (3a, 7a, 10), chloroform–light
petroleum (3b), dichloromethane–light petroleum (4a,b),
dichloromethane–diethyl ether (8a) or diethyl ether–light
petroleum (9a).
3a: Yield 0.24 g (67%), mp 121–122 ЊC (Found: C, 53.9; H,
5.7; N, 31.4%. C8H10N4O requires C, 53.9; H, 5.7; N, 31.4%);
νmax(KBr)/cmϪ1 3120 and 1630; δH(CDCl3) 2.55 (3 H, s), 2.64
(3 H, s), 4.08 (3 H, s) and 5.62 (1 H, s); δC(CDCl3) 15.7 (q), 29.4
(q), 34.7 (q), 80.9 (d), 117.2 (s), 135.4 (s), 140.7 (s) and 185.2 (s).
3b: Yield 0.37 g (77%), mp 119–121 ЊC (Found: C, 64.9;
H, 5.1; N, 23.4. C13H12N4O requires C, 65.0; H, 5.0; N, 23.3%);
νmax(KBr)/cmϪ1 3125 and 1625; δH(CDCl3) 2.28 (3 H, s), 4.11
(3 H, s), 5.77 (1 H, s), 7.38–7.43 (3 H, m) and 7.46–7.49 (2 H,
m); δC(CDCl3) 29.0 (q), 34.8 (q), 80.7 (d), 116.3 (s), 128.1
(2 × d), 128.2 (d), 129.6 (2 × d), 135.4 (s), 135.6 (s), 143.0 (s)
and 185.0 (s).
4a: Yield 0.39 g (81%), mp 139–141 ЊC (Found: C, 64.65; H,
5.1; N, 23.4. C13H12N4O requires C, 65.0; H, 5.0; N, 23.3%);
νmax(KBr)/cmϪ1 1631; δH(CDCl3) 2.63 (3 H, s), 2.64 (3 H, s),
5.99 (1 H, s), 7.49–7.57 (3 H, m) and 8.15–8.17 (2 H, m);
δC[(CD3)2SO] 15.9 (q), 29.1 (q), 86.9 (d), 119.9 (s), 120.4 (2 × d),
130.2 (2 × d), 130.7 (d), 136.9 (s), 141.4 (s), 147.8 (s) and 183.0
(s).
4b: Yield 0.30 g (62%), mp 96–97 ЊC (Found: C, 65.0; H, 5.1;
N, 23.3. C13H12N4O requires C, 65.0; H, 5.0; N, 23.3%);
νmax(KBr)/cmϪ1 1616; δH(CDCl3) 2.09 (3 H, s), 4.53 (3 H, s),
6.07 (1 H, s) and 7.42–7.49 (5 H, m); δC(CDCl3) 28.1 (q), 42.0
(q), 86.8 (d), 114.4 (s), 128.20 (2 × d), 128.24 (d), 129.7 (2 × d),
136.0 (s), 143.9 (s), 148.5 (s) and 184.2 (s).
7a: Yield 0.10 g (23%), mp 130–131 ЊC (lit.,17 130–131 ЊC);
νmax(KBr)/cmϪ1 and δH(CDCl3) consistent with ref. 17.
8a: Yield 0.28 g (50%), mp 259 ЊC (Found: C, 63.8; H, 5.0; N,
19.7. C15H14N4O2 requires C, 63.8; H, 5.0; N, 19.85%);
νmax(KBr)/cmϪ1 1657 and 1644; δH(CDCl3) 2.71 (3 H, s), 2.73
(3 H, s), 2.99 (3 H, s), 7.59–7.67 (3 H, m) and 8.25–8.28 (2 H,
m); δC(CDCl3) 13.9 (q), 30.1 (q), 30.5 (q), 100.9 (s), 116.8 (s),
120.4 (2 × d), 129.9 (2 × d), 131.1 (d), 136.9 (s), 145.0 (s), 149.9
(s), 185.9 (s) and 191.2 (s).
9a: Yield 0.36 g (71%), mp 67–69 ЊC (Found: C, 66.0; H, 5.55;
N, 22.3. C14H14N4O requires C, 66.1; H, 5.55; N, 22.0%);
νmax(KBr)/cmϪ1 1635; δH(CDCl3) 1.82 (3 H, s), 2.32 (3 H, s),
4.54 (3 H, s), 7.32–7.35 (2 H, m) and 7.39–7.48 (3 H, m);
δC(CDCl3) 8.9 (q), 28.9 (q), 37.5 (q), 97.1 (s), 111.3 (s), 127.9 (d),
128.4 (2 × d), 130.2 (s), 130.4 (2 × d), 134.7 (s), 135.4 (s) and
191.7 (s).
10: Yield 0.06 g [62%; from 0.08 g (0.38 mmol) 2e and 1.00 g
(ca. 10 mmol) acetic anhydride], mp 163–164 ЊC (Found: C,
66.2; H, 5.6; N, 22.0. C14H14N4O requires C, 66.1; H, 5.55; N,
22.0%); νmax(KBr)/cmϪ1 1640; δH(CDCl3) 2.33 (3 H, s), 2.34
(3 H, s), 4.45 (3 H, s) and 7.34–7.44 (5 H, m); δC(CDCl3) 9.3 (q),
29.1 (q), 41.8 (q), 96.7 (s), 109.6 (s), 127.4 (d), 127.8 (2 × d),
130.3 (2 × d), 134.3 (s), 134.5 (s), 148.0 (s) and 188.9 (s).
Scheme 4 Reagents and conditions: i, DMAD, rt.
Experimental
For instruments used and preparation of starting pyrrolo-
tetrazoles 1 and 2, see ref. 1. AM1 calculations were performed
on an IBM 100 MHz Pentium PC using version 4.5 of the
HyperChem program (Hypercube, Inc., 419 Philip Street,
Waterloo N2L 3X2, Canada). The geometries of 1a and 2a
were optimised (Polak-Ribiere optimiser, RMS gradient ≤10Ϫ1
kcal ÅϪ1 molϪ1, convergence limit ≤10Ϫ5 kcal molϪ1).
1-/2-Methyl-6-phenyl-1H-/2H-pyrrolotetrazolium perchlorates
1cؒHClO4, 2cؒHClO4. General procedure
To a solution of the pyrrolotetrazole 1c (0.60 g, 3 mmol) or 2c
(0.30 g, 1.5 mmol) in hot acetic acid (10 cm3; 80 ЊC) was added
dropwise 10 M HClO4. After cooling, the salt was filtered off
and recrystallised from methanol–water (9 : 1).
1cؒHClO4: Yield 0.78 g (87%), mp 206–209 ЊC (Found: C,
44.2; H, 3.6; N, 18.7. [C11H11N4]ClO4 requires C, 44.2; H, 3.7;
N, 18.8%); for δH, see Table 2.
2cؒHClO4: Yield 0.27 g (60%), mp 256 ЊC (Found: C, 44.1; H,
3.8; N, 18.6. [C11H11N4]ClO4 requires C, 44.2; H, 3.7; N, 18.8%);
for δH, see Table 2.
1-/2-Methyl-6-phenyl-1H-/2H-pyrrolotetrazole-5-carbaldehydes
3c, 4c. General procedure
Phosphoryl chloride (0.61 g, 4 mmol) was cautiously mixed
with dimethylformamide (DMF; 0.44 g, 6 mmol) at 0 ЊC. 30
min later a solution of the pyrrolotetrazole 1c or 2c (0.40 g,
2 mmol) in DMF (2.00 g) was added and the mixture was
stirred at 0 ЊC for another 15 min. Then aqueous sodium car-
bonate (10%; 20 cm3) and ethanol or methanol (5 cm3) were
added; after heating under reflux for 1 h, the solution was
extracted with dichloromethane to afford the product which
was recrystallised from chloroform–diethyl ether (3c) or
dichloromethane–light petroleum (4c).
Substituted 5-acetyl- and 7-acetyl-1H-/2H-pyrrolotetrazoles
3a,b, 4a,b, 7a, 8a, 9a, 10. General procedure
Acetic anhydride (5.0–8.0 g, ca. 50–80 mmol) was added to the
appropriate pyrrolotetrazole 1 or 2 (2 mmol) and the mixture
was kept as detailed below: 1b: 20 ЊC, 24 h; 1c: 20 ЊC, 7 d or
100–110 ЊC, 3.5 h; 1e: 20 ЊC, 3 d; 1f: 100–110 ЊC, 2 d [after
addition of anhydrous sodium acetate (0.33 g, 4 mmol)]; 2b:
120 ЊC, 2.5 h; 2c: 20 ЊC, 24 h; 2e: 20 ЊC, 24 h; 2f: 120 ЊC, 8 h. For
work-up, the cooled solution was diluted with water (10–20
cm3) to allow hydrolysis of the unconsumed reagent whereupon
the mixture was neutralised with sodium carbonate and
extracted with dichloromethane. Recrystallisation was effected
3c: Yield 0.31 g (68%), mp 128–129 ЊC (Found: C, 63.8; H,
4.4; N, 24.85. C12H10N4O requires C, 63.7; H, 4.5; N, 24.8%);
νmax(KBr)/cmϪ1 3130 and 1630; δH(CDCl3) 4.17 (3 H, s), 5.92
(1 H, s), 7.42–7.48 (3 H, m), 7.51–7.54 (2 H, m) and 9.66 (1 H,
732
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s); δC(CDCl3) 34.9 (q), 79.9 (d), 116.0 (s), 128.81 (2 × d), 128.84
(d), 129.6 (2 × d), 133.2 (s), 137.3 (s), 146.4 (s) and 175.6 (d).
4c: Yield 0.26 g (57%), mp 144–146 ЊC (Found: C, 63.7; H,
4.4; N, 24.7. C12H10N4O requires C, 63.7; H, 4.5; N, 24.8%);
νmax(KBr)/cmϪ1 1634; δH(CDCl3) 4.53 (3 H, s), 6.18 (1 H, s),
7.42–7.48 (3 H, m), 7.56–7.58 (2 H, m) and 9.60 (1 H, s);
δC(CDCl3) 42.1 (q), 85.6 (d), 113.8 (s), 128.7 (d), 128.8 (2 × d),
129.6 (2 × d), 133.5 (s), 146.2 (s), 150.0 (s) and 174.6 (d).
1730 and 1715; δH(CDCl3) 3.206 (3 H, s), 3.67 (3 H, s), 4.37
(3 H, s), 6.25 (1 H, br), 6.62 (1 H, s), 7.25–7.29 (1 H, m), 7.34–
7.38 (2 H, m) and 7.41–7.43 (2 H, m); δC(CDCl3) 41.6 (q), 51.7
(q), 52.4 (q), 82.5 (d), 104.2 (s), 121.0 (d), 127.3 (d), 128.5
(4 × d), 133.5 (s), 136.3 (s), 140.7 (s), 147.4 (s), 165.5 (s) and
167.5 (s).
(Z)-4d: Mp 138–139 ЊC (Found: C, 60.0; H, 4.7; N, 16.4.
C17H16N4O4 requires C, 60.0; H, 4.7; N, 16.5%); νmax(KBr)/cmϪ1
1740 and 1710; δH(CDCl3) 3.208 (3 H, s), 3.71 (3 H, s), 4.46
(3 H, s), 6.09 (1 H, s), 6.54 (1 H, s) and 7.36 (5 H, s); δC(CDCl3)
41.9 (q), 51.4 (q), 51.9 (q), 87.3 (d), 106.1 (s, 3JC,H 6.3), 107.4 (d),
127.5 (2 × d), 127.9 (d), 130.0 (2 × d), 134.6 (s), 138.0 (s), 142.1
(s), 148.0 (s), 166.2 (s) and 166.8 (s).
Substituted dimethyl (1H-pyrrolotetrazol-5-yl)fumarates (E)-3d,
(E)-7b. General procedure
A solution of the 1H-pyrrolotetrazole 1c or 1h (1 mmol) and
DMAD (0.57 g, 4 mmol) in methanol (20 cm3) was stirred at
room temperature for 1 h (1c) or heated under reflux for 3 h
(1h). After evaporation of the solvent and treatment of the
residue with diethyl ether the product was filtered off and
recrystallised from chloroform–diethyl ether [(E)-3d] or
methanol–diethyl ether [(E)-7b].
[(E)-3d]: Yield 0.13 g (38%), mp 131–133 ЊC (Found: C,
59.95; H, 4.7; N, 16.3. C17H16N4O4 requires C, 60.0; H, 4.7; N,
16.5%); νmax(KBr)/cmϪ1 1730 and 1715; δH(CDCl3) 3.29 (3 H, s),
3.68 (3 H, s), 4.05 (3 H, s), 5.88 (1 H, s), 6.80 (1 H, s), 7.27–7.31
(1 H, m) and 7.35–7.40 (4 H, m); δC(CDCl3) 34.6 (q), 51.9 (q),
52.5 (q), 76.0 (d), 106.7 (s, 3JC,H 9.4, 3JC,H 5.9), 124.6 (d), 127.4
(d), 128.4 (2 × d), 128.6 (2 × d), 133.0 (s), 134.3 (s), 136.1 (s),
137.8 (s), 165.6 (s) and 167.1 (s).
(E)-8b: Mp 145–147 ЊC (Found: C, 57.2; H, 4.6; N, 14.0.
C19H18N4O6 requires C, 57.3; H, 4.55; N, 14.1%); νmax(KBr)/
cmϪ1 1735, 1720 and 1690; δH(CDCl3) 3.31 (3 H, s), 3.66 (3 H,
s), 3.83 (3 H, s), 4.48 (3 H, s), 6.79 (1 H, s) and 7.31–7.43 (5 H,
m); δC(CDCl3) 42.1 (q), 51.1 (q), 52.0 (q), 52.6 (q), 87.5 (s),
3
107.6 (s, JC,H 9.8), 126.8 (d), 127.6 (2 × d), 128.1 (d), 130.7
(2 × d), 133.1 (s), 133.2 (s), 140.8 (s), 148.5 (s), 163.1 (s), 164.9
(s) and 166.1 (s).
(Z)-8b: Mp 234–235 ЊC (Found: C, 56.9; H, 4.5; N, 13.8.
C19H18N4O6 requires C, 57.3; H, 4.55; N, 14.1%); νmax(KBr)/
cmϪ1 1750, 1715 and 1695; δH(CDCl3) 3.18 (3 H, s), 3.72 (3 H,
s), 3.73 (3 H, s), 4.57 (3 H, s), 6.65 (1 H, s), 7.32–7.36 (2 H, m)
and 7.39–7.42 (3 H, m); δC(CDCl3) 42.5 (q), 51.2 (q), 51.7 (q),
3
52.2 (q), 91.4 (s), 109.2 (s, JC,H 6.8), 111.8 (d), 127.2 (2 × d),
[(E)-7b]: Yield 0.16 g (40%), mp 147–149 ЊC (Found: C,
57.45; H, 4.7; N, 14.0. C19H18N4O6 requires C, 57.3; H, 4.55; N,
14.1%); νmax(KBr)/cmϪ1 1735 and 1720; δH[(CD3)2SO] 3.28 (3 H,
s), 3.57 (3 H, s), 3.66 (3 H, s), 4.38 (3 H, s), 6.80 (1 H, s), 7.22–
7.24 (2 H, m) and 7.34–7.39 (3 H, m); δC[(CD3)2SO] 37.1 (q),
128.4 (d), 130.5 (2 × d), 131.8 (s), 137.4 (s), 142.5 (s), 148.9 (s),
162.3 (s), 165.3 (s) and 166.1 (s).
5-Benzoyl-1,6-dimethyl-1H-pyrrolo[1,2-d]tetrazole 3i
3
A solution of the 1H-pyrrolotetrazole 1b (0.27 g, 2 mmol) and
benzoic anhydride (0.90 g, 4 mmol) in diethyl ether (10 cm3) was
allowed to stand at room temperature for 12 h. After evapor-
ation of the solvent the residue was dissolved in the minimum
amount of chloroform; addition of diethyl ether–light petrol-
eum (1 : 1) caused precipitation of the product which was
collected by filtration and recrystallised from chloroform. Yield
0.16 g (33%), mp 170–171 ЊC (Found: C, 64.8; H, 5.05; N, 23.5.
C13H12N4O requires C, 65.0; H, 5.0; N, 23.3%); νmax(KBr)/cmϪ1
3125 and 1610; δH(CDCl3) 2.23 (3 H, s), 4.05 (3 H, s), 5.64 (1 H,
s), 7.42–7.53 (3 H, m) and 7.63–7.66 (2 H, m); δC(CDCl3) 15.8
(q), 34.6 (q), 81.3 (d), 116.7 (s), 128.20 (2 × d), 128.22 (2 × d),
131.0 (d), 136.3 (s), 140.3 (s), 141.4 (s) and 183.6 (s).
50.7 (q), 52.0 (q), 52.6 (q), 84.6 (s), 108.7 (s, JC,H 10.1), 127.5
(2 × d), 127.8 (d), 128.6 (d), 130.2 (2 × d), 131.0 (s), 131.9 (s),
132.9 (s), 135.6 (s), 162.1 (s), 164.5 (s) and 165.2 (s).
Reaction of the 2H-pyrrolotetrazoles 2c and 2h with DMAD.
General procedure
To a solution of 2c or 2h (1 mmol) in methanol (20 cm3), pre-
pared by gentle warming, was added at room temperature the
reagent DMAD (0.57 g, 4 mmol). The mixture was stirred at
20 ЊC for 1 h (2c) or 8 h (2h) [or heated under reflux for 1 h (2h)]
and then allowed to stand at 0–5 ЊC for 12 h. Isolation of
products occurred as detailed below.
In the case of 2c, 0.16 g orange to red dimethyl (2-methyl-6-
phenyl-2H-pyrrolo[1,2-d]tetrazol-5-yl)fumarate (E)-4d,‡ mp
168–170 ЊC, was filtered off and a second crop (0.02 g) was
obtained from the concentrated filtrate (total yield 53%).
Crystallisation from dichloromethane–light petroleum gave a
mixture of (E)-4d, mp as above, and yellow dimethyl (2-methyl-
6-phenyl-2H-pyrrolo[1,2-d]tetrazol-5-yl)maleate (Z)-4d,‡ mp
135–139 ЊC, which was in turn separated by picking out the
pertinent crystals. Recrystallisation of these materials was
effected with chloroform–diethyl ether [(E)-4d; both rapid
precipitation and filtration] or methanol [(Z)-4d].
In the case of 2h, 0.05 g pale yellow dimethyl (7-methoxy-
carbonyl-2-methyl-6-phenyl-2H-pyrrolo[1,2-d]tetrazol-5-yl)-
maleate (Z)-8b,‡ mp 232–234 ЊC, was filtered off. The concen-
trated filtrate crystallised on standing at room temperature
within 2 d to afford, after addition of diethyl ether and cooling
at 0–5 ЊC for 12 h, 0.27 g deep yellow dimethyl (7-methoxy-
carbonyl-2-methyl-6-phenyl-2H-pyrrolo[1,2-d]tetrazol-5-yl)-
fumarate (E)-8b,‡ mp 140 ЊC, which was collected by filtration
(total yield 80%). Recrystallisation was effected with dichloro-
methane–diethyl ether [(E)-8b] or methanol [(Z)-8b].
1-Methyl-N,6-diphenyl-1H-pyrrolo[1,2-d]tetrazole-5-carb-
oxamide 3j
A solution of the 1H-pyrrolotetrazole 1c (0.40 g, 2 mmol) and
phenyl isocyanate (0.36 g, 3 mmol) in anhydrous dichloro-
methane (5 cm3) was stirred at room temperature for 2 d. The
mixture was concentrated and the residue briefly heated under
reflux with ethanol (5 cm3) whereupon crystals of the product
separated which were thoroughly washed with ethanol. Yield
0.24 g (38%), mp 156–158 ЊC (Found: C, 68.1; H, 4.7; N, 22.0.
C18H15N5O requires C, 68.1; H, 4.8; N, 22.1%); νmax(KBr)/cmϪ1
3385 and 1660; δH(90 MHz; CDCl3) 4.04 (3 H, s), 5.74 (1 H, s),
6.97–7.72 (10 H, m) and 8.33 (1 H, br).
Substituted 5,7-dibromo- and 5-bromo-1H-/2H-pyrrolotetrazoles
5, 6, 8f. General procedure
Bromine [0.64 g, 4 mmol (for 5); 0.74 g, 4.6 mmol (for 6, 8f)],
dissolved in chloroform (5 cm3), was added with stirring and ice
cooling to a solution of the pyrrolotetrazole 1c, 2c or 2h
(2 mmol) in the same solvent (5 cm3). After 30 min the mixture
was shaken with aqueous sodium carbonate (5%; 10 cm3) until
the solid disappeared. The product was isolated by concen-
tration of the organic layer and recrystallised from chloro-
form–light petroleum (5) or dichloromethane–light petroleum
(6, 8f).
(E)-4d: Mp 171–172 ЊC (Found: C, 59.4; H, 4.8; N, 16.2.
C17H16N4O4 requires C, 60.0; H, 4.7; N, 16.5%); νmax(KBr)/cmϪ1
‡ The IUPAC name for the parent structure of 4d and 8b is 1H-
pyrrolo[1,2-d]tetrazol-2-ium-1-ide.
J. Chem. Soc., Perkin Trans. 1, 2001, 729–735
733

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5: Yield 0.33 g (46%), mp 112–114 ЊC (Found: C, 37.2; H,
2.2; N, 15.7. C11H8Br2N4 requires C, 37.1; H, 2.3; N, 15.7%);
δH(CDCl3) 4.16 (3 H, s), 7.38–7.42 (1 H, m) and 7.45–7.54
(4 H, m); δC[(CD3)2SO] 35.0 (q), 59.6 (s), 78.7 (s), 128.1
(d), 128.5 (2 × d), 129.8 (2 × d), 130.9 (s), 131.1 (s) and
131.5 (s).
6: Yield 0.48 g (67%), mp 143–144 ЊC (Found: C, 36.9; H, 2.3;
N, 15.6. C11H8Br2N4 requires C, 37.1; H, 2.3; N, 15.7%);
δH(CDCl3) 4.40 (3 H, s), 7.38–7.42 (1 H, m), 7.45–7.49 (2 H, m)
and 7.56–7.59 (2 H, m); δC(CDCl3) 42.0 (q), 64.3 (s), 75.3 (s),
128.1 (d), 128.2 (2 × d), 130.2 (2 × d), 132.2 (s), 134.0 (s) and
144.0 (s).
8f: Yield 0.60 g (90%), mp 225 ЊC (Found: C, 46.5; H, 3.4;
N, 16.5. C13H11BrN4O2 requires C, 46.6; H, 3.3; N, 16.7%);
νmax(KBr)/cmϪ1 1687; δH(CDCl3) 3.80 (3 H, s), 4.50 (3 H, s) and
7.40–7.51 (5 H, m); δC(CDCl3) 42.2 (q), 51.1 (q), 81.3 (s), 87.5
(s), 127.7 (2 × d), 128.2 (d), 130.5 (2 × d), 132.2 (s), 138.0 (s),
147.5 (s) and 162.6 (s).
at room temperature for 15–30 min and then neutralised with
8 M NH3. The products 7d,e and 11a–c were filtered off
and washed with water, while 12a,b,e,f were extracted with
dichloromethane. Recrystallisation was effected with chloro-
form (7e), chloroform–diethyl ether (7d), dichloromethane–
diethyl ether (12a,f), methanol (11c) or methanol–diethyl
ether (11a,b, 12b,e).—In ref. 2, preparation of 11c failed
(cf. note 4).
7d: Yield 0.38 g (71%), mp 144–147 ЊC (lit.,2 141–143 ЊC)
(Found: C, 57.8; H, 4.0; N, 25.9. C13H11N5O2 requires C, 58.0;
H, 4.1; N, 26.0%); νmax(KBr)/cmϪ1 1650; δH(CDCl3) 2.11 (3 H,
s), 4.60 (3 H, s), 7.54–7.61 (3 H, m) and 7.74–7.76 (2 H, m);
δC(CDCl3) 29.6 (q), 38.3 (q), 103.7 (s), 128.5 (2 × d), 130.1 (d),
130.6 (s), 131.0 (2 × d), 138.2 (s), 147.3 (s), 149.9 (s) and 193.0
(s).
7e: Yield 0.45 g (79%), mp 138–140 ЊC (lit.,2 138–140 ЊC)
(Found: C, 54.9; H, 3.95; N, 24.5. C13H11N5O3 requires C, 54.7;
H, 3.9; N, 24.55%); for νmax/cmϪ1, δH and δC, see ref. 2.
11a: Yield 0.23 g (51%), mp 138–139 ЊC (lit.,2 138–139 ЊC)
(Found: C, 58.0; H, 3.7; N, 31.0. C11H9N5O requires C, 58.15;
H, 4.0; N, 30.8%); for νmax/cmϪ1, δH, δC and λmax/nm, see ref. 2.—
15N-11a (having C15NO group; cf. ref. 2): δC[(CD3)2SO] 33.9 (q),
34.7 (s, 1JN,C 81.0, 3JC,H 17.5), 118.3 (d, 3JN,C 1.7), 120.4 (s, 2JN,C
Substituted 5-(phenylazo)- and 7-(phenylazo)-1H-/2H-pyrrolo-
tetrazoles 3e, 4e, 7c, 8c, 9b. General procedure
To the respective pyrrolotetrazole 1 or 2 (2 mmol), dissolved in
acetic acid (10.0 g), was added at 0 ЊC a freshly prepared solu-
tion of benzenediazonium chloride (2.5–3 mmol; from equi-
molar amounts of aniline and sodium nitrite in 5–6 M HCl).
The mixture was stirred at room temperature for 15 min (in the
case of 1h and 2h for 1 h), then diluted with water (50 cm3) and
neutralised with sodium carbonate. The product was separated
by extraction with dichloromethane and recrystallised from
chloroform–diethyl ether (3e, 7c, 9b) or dichloromethane–
diethyl ether (4e, 8c), in the latter two cases after chromato-
graphy on silica gel [chloroform–ethyl acetate (ca. 2 : 1) as
eluent].
3
2.1), 126.8 (2 × d), 129.2 (2 × d), 130.7 (d), 133.8 (s, JN,C 0.8)
and 150.7 (s).
11b: Yield 0.39 g (67%), mp 144–146 ЊC (lit.,2 144–146 ЊC)
(Found: C, 66.3; H, 3.8; N, 24.2. C16H11N5O requires C, 66.4; H,
3.8; N, 24.2%); νmax(KBr)/cmϪ1 2305; δH[(CD3)2SO] 7.47 (1 H,
s), 7.52–7.53 (3 H, m) and 7.70–7.77 (7 H, m); δC[(CD3)2SO]
118.1 (d), 122.0 (s), 125.4 (2 × d), 126.8 (2 × d), 129.3 (2 × d),
130.1 (2 × d), 130.8 (d), 130.9 (d), 133.0 (s), 133.7 (s) and 150.3
(s) [C of CNO group not observed (cf. ref. 18)].
11c: Yield 0.11 g (33%), mp 114–115 ЊC (Found: C, 43.8; H,
4.3; N, 43.0. C6H7N5O requires C, 43.6; H, 4.3; N, 42.4%);
νmax(KBr)/cmϪ1 2290; δH[(CD3)2SO] 2.29 (3 H, d, J 1.6), 4.08
(3 H, s) and 7.34 (1 H, q, J 1.6); δC[(CD3)2SO] 22.7 (q), 33.6 (q),
118.6 (s), 120.2 (d) and 150.3 (s) [C of CNO group not observed
(cf. ref. 18)].
12a: Yield 0.42 g (92%), mp 97–99 ЊC (Found: C, 58.0; H, 3.8;
N, 30.9. C11H9N5O requires C, 58.15; H, 4.0; N, 30.8%);
νmax(KBr)/cmϪ1 2305; δH(CDCl3) 4.45 (3 H, s), 7.45–7.50 (3 H,
m), 7.57 (1 H, s) and 7.65–7.68 (2 H, m); δC(CDCl3) 39.9 (q),
119.3 (s), 123.0 (d), 126.3 (2 × d), 129.2 (2 × d), 130.2 (d), 134.4
(s) and 161.9 (s) [C of CNO group not observed (cf. ref. 18)];
λmax(TFA)/nm 400 (log ε/dm3 molϪ1 cmϪ1 3.55) and 263
(4.14).
12b: Yield 0.45 g (78%), mp 132–133 ЊC (Found: C, 66.4; H,
3.85; N, 24.2. C16H11N5O requires C, 66.4; H, 3.8; N, 24.2%);
νmax(KBr)/cmϪ1 2297; δH(CDCl3) 7.45–7.54 (4 H, m), 7.57–7.61
(2 H, m), 7.68 (1 H, s), 7.69–7.72 (2 H, m) and 8.25–8.27 (2 H,
m); δC(CDCl3) 119.90 (2 × d), 119.91 (s), 122.8 (d), 126.4
(2 × d), 129.2 (2 × d), 129.8 (2 × d), 130.1 (d), 130.3 (d), 134.2
(s), 136.5 (s) and 161.8 (s) [C of CNO group not observed
(cf. ref. 18)].
12e: Yield 0.32 g (48%), mp 110–111 ЊC (Found: C, 65.25; H,
4.0; N, 20.8. C18H13N5O2 requires C, 65.25; H, 4.0; N, 21.1%);
νmax(KBr)/cmϪ1 2284 and 1701; δH(CDCl3) 2.26 (3 H, s), 7.45–
7.51 (5 H, m), 7.53–7.61 (3 H, m) and 8.21–8.23 (2 H, m) [8d:
2.50 (integral < 5% of s at 2.26)]; δC(CDCl3) 31.4 (q), 119.2 (s),
120.1 (2 × d), 128.6 (2 × d), 129.4 (2 × d), 129.9 (2 × d), 130.4
(d), 130.7 (d), 133.7 (s), 136.4 (s), 138.3 (s), 160.9 (s) and 199.6
(s) [C of CNO group not observed (cf. ref. 18)].
3e: Yield 0.49 g (81%), mp 169–171 ЊC (lit.,2 168–170 ЊC)
(Found: C, 67.6; H, 4.6; N, 27.9. C17H14N6 requires C, 67.5; H,
4.7; N, 27.8%); for δH and δC, see ref. 2.
4e: Yield 0.47 g (78%), mp 142–144 ЊC (Found: C, 67.6; H,
4.6; N, 27.8. C17H14N6 requires C, 67.5; H, 4.7; N, 27.8%);
δH(CDCl3) 4.37 (3 H, s), 6.43 (1 H, s), 7.21–7.28 (1 H, m), 7.36–
7.48 (5 H, m), 7.83–7.85 (2 H, m) and 8.00–8.02 (2 H, m);
δC(CDCl3) 41.8 (q), 85.2 (d), 121.6 (2 × d), 125.7 (s), 127.8 (d),
128.3 (d), 128.4 (2 × d), 128.9 (2 × d), 129.7 (2 × d), 134.0 (s),
140.5 (s), 148.7 (s) and 154.4 (s).
7c: Yield 0.46 g (64%), mp 240–242 ЊC (lit.,2 240–242 ЊC)
(Found: C, 63.4; H, 4.4; N, 23.3. C19H16N6O2 requires C, 63.3;
H, 4.5; N, 23.3%); νmax(KBr)/cmϪ1 1710; δH[(CD3)2SO] 3.71
(3 H, s), 4.42 (3 H, s), 7.37–7.41 (1 H, m), 7.47–7.49 (5 H, m)
and 7.60–7.64 (4 H, m).
8c: Yield 0.50 g (69%), mp 238–240 ЊC (Found: C, 63.4; H,
4.4; N, 22.9. C19H16N6O2 requires C, 63.3; H, 4.5; N, 23.3%);
νmax(KBr)/cmϪ1 1709; δH(CDCl3) 3.87 (3 H, s), 4.58 (3 H, s),
7.29–7.42 (1 H, m), 7.46–7.52 (5 H, m) and 7.73–7.76 (4 H, m);
δC(CDCl3) 42.4 (q), 51.4 (q), 90.2 (s), 122.0 (2 × d), 127.3
(2 × d), 128.2 (s), 128.7 (d), 129.0 (2 × d), 129.3 (d), 131.4 (s),
131.9 (2 × d), 142.6 (s), 149.3 (s), 153.7 (s) and 162.7 (s).
9b: Yield 0.39 g (62%), mp 148–150 ЊC (Found: C, 68.1; H,
5.15; N, 26.3. C18H16N6 requires C, 68.3; H, 5.1; N, 26.6%);
δH(CDCl3) 2.59 (3 H, s), 4.51 (3 H, s), 7.22–7.26 (1 H, m), 7.34–
7.39 (3 H, m), 7.44–7.48 (2 H, m) and 7.59–7.62 (4 H, m);
δC(CDCl3) 9.6 (q), 38.2 (q), 110.6 (s), 114.4 (s), 121.1 (2 × d),
125.1 (s), 127.1 (d), 127.9 (d), 128.0 (2 × d), 128.9 (2 × d), 129.7
(s), 131.0 (2 × d), 133.1 (s) and 153.4 (s).
12f: Yield 0.31 g (54%), mp 112–113 ЊC (Found: C, 54.5; H,
3.8; N, 24.3. C13H11N5O3 requires C, 54.7; H, 3.9; N, 24.55%);
νmax(KBr)/cmϪ1 2291, 2254 and 1732; δH(CDCl3) 3.69 (3 H, s),
4.44 (3 H, s) and 7.44–7.49 (5 H, m) [8e: 3.88, 4.59 (integrals ca.
5% of s at 3.69 and 4.44, respectively)]; δC(CDCl3) 40.0 (q), 53.1
(q), 121.2 (s), 127.8 (2 × d), 129.1 (2 × d), 130.3 (s), 130.4 (d),
134.4 (s), 160.7 (s) and 165.2 (s) [C of CNO group not observed
(cf. ref. 18)].
Substituted 5-nitroso-1H-pyrrolotetrazoles 7d,e and substituted
3-(1H-/2H-tetrazol-5-yl)acrylonitrile oxides 11a–c, 12a,b,e,f.
General procedure
To a solution of the respective pyrrolotetrazole 1 or 2 (2 mmol)
in acetic acid (10.0 g) was added at 0 ЊC sodium nitrite (0.28 g,
4 mmol) in a small amount of water. The mixture was stirred
734
J. Chem. Soc., Perkin Trans. 1, 2001, 729–735

View Article Online
Substituted dimethyl 3-[2-(1H-/2H-tetrazol-5-yl)vinyl]isoxazole-
4,5-dicarboxylates 13a,f, 14a. General procedure
Acknowledgement
Assistance in performing the AM1 calculations by Dr L. Preu
of this Institute is gratefully acknowledged.
To a suspension of the nitrile oxide 11a (0.11 g, 0.5 mmol) or
12a (0.45 g, 2 mmol) in methanol (10 and 40 cm3, respectively)
or of the 1H-pyrrolotetrazole 7e (0.14 g, 0.5 mmol) in toluene
(10 cm3) was added dimethyl acetylenedicarboxylate (DMAD;
11a, 7e: 0.14 g, 1 mmol; 12a: 0.57 g, 4 mmol). The mixture was
heated under reflux for 0.5 h (11a, 12a) or 2 h (7e). Evaporation
of the solvent and addition of diethyl ether caused precipitation
of the product which was collected by filtration and recrystal-
lised from methanol (13a), chloroform–diethyl ether (13f) or
dichloromethane–light petroleum [14a; after preceding purifi-
cation on silica gel using chloroform–diethyl ether–ethyl acetate
(6 : 1 : 2) as eluent].
References
1 Part 1. D. Moderhack, D. Decker and B. Holtmann, J. Chem. Soc.,
Perkin Trans. 1, 2001, DOI: 10.1039/b007873p.
2 A few results on 1H-pyrrolotetrazoles (1) described herein have been
published in preliminary form: D. Moderhack and D. Decker,
Heterocycles, 1994, 37, 683; see also: D. Moderhack and D. Decker,
14th International Congress of Heterocyclic Chemistry, Antwerp,
1993, Abstracts of Papers, PO 3-211.
3 Overview: J. Elguero, R. M. Claramunt and A. J. H. Summers,
Adv. Heterocycl. Chem., 1978, 22, 183; for material not included,
see refs. 4a–f.
13a: Yield 0.17 g (92%), mp 161–162 ЊC (lit.,2 161–162 ЊC)
(Found: C, 55.2; H, 4.0; N, 18.95. C17H15N5O5 requires C, 55.3;
H, 4.1; N, 19.0%); for νmax/cmϪ1, δH and δC, see ref. 2.
4 (a) F. S. Babichev, G. P. Kutrov and M. Yu. Kornilov, Ukr. Khim.
Zh. (Russ. Ed.), 1968, 34, 1020; (b) F. S. Babichev, Nguyen Thi and
Nguyen Phonh, Ukr. Khim. Zh. (Russ. Ed.), 1969, 35, 932; (c) L. M.
Alekseeva, G. G. Dvoryantseva, I. V. Persianova, Yu. N. Sheinker,
R. M. Palei and P. M. Kochergin, Khim. Geterotsikl. Soedin., 1972,
492, 1132; L. M. Alekseeva, G. G. Dvoryantseva, I. V. Persianova,
Yu. N. Sheinker, R. M. Palei and P. M. Kochergin, Chem.
Heterocycl. Compd. (USSR), 1972, 8, 449, 1023; (d) F. S. Babichev,
V. A. Kovtunenko, M. Yu. Kornilov and L. I. Savranskii, Ukr. Khim.
Zh. (Russ. Ed.), 1973, 39, 581; (e) V. A. Kovtunenko and F. S.
Babichev, Ukr. Khim. Zh. (Russ. Ed.), 1975, 41, 927; ( f ) L. M.
Alekseeva, G. G. Dvoryantseva, Yu. N. Sheinker, A. A. Druzhinina,
R. M. Palei and P. M. Kochergin, Khim. Geterotsikl. Soedin., 1976,
70; L. M. Alekseeva, G. G. Dvoryantseva, Yu. N. Sheinker, A. A.
Druzhinina, R. M. Palei and P. M. Kochergin, Chem. Heterocycl.
Compd. (USSR), 1976, 12, 64.
5 Exceptions are rare, e.g.: (a) O. Ceder and B. Beijer, Tetrahedron,
1972, 28, 4352; (b) J. C. Brindley, D. G. Gillon and G. D. Meakins,
J. Chem. Soc., Perkin Trans. 1, 1986, 1255.
6 (a) M. Yu. Kornilov, G. G. Dyadyusha and F. S. Babichev, Khim.
Geterotsikl. Soedin., 1968, 905; M. Yu. Kornilov, G. G. Dyadyusha
and F. S. Babichev, Chem. Heterocycl. Compd. (USSR), 1968, 4,
654; (b) L. I. Savranskii, V. A. Kovtunenko and F. S. Babichev,
Khim. Geterotsikl. Soedin., 1974, 261; L. I. Savranskii, V. A.
Kovtunenko and F. S. Babichev, Chem. Heterocycl. Compd. (USSR),
1974, 20, 230.
13f: Yield 0.10 g (47%), mp 129–131 ЊC (lit.,2 129–131 ЊC)
(Found: C, 53.4; H, 4.1; N, 16.4. C19H17N5O7 requires C, 53.4;
H, 4.0; N, 16.4%); νmax(KBr)/cmϪ1 1746 and 1728; δH(CDCl3)
3.62 (3 H, s), 3.66 (3 H, s), 3.94 (3 H, s), 4.02 (3 H, s), 7.34–7.36
(2 H, m) and 7.40–7.48 (3 H, m); δC(CDCl3) 34.2 (q), 52.7 (q),
53.0 (q), 53.6 (q), 116.0 (s), 120.7 (s), 128.5 (2 × d), 128.8
(2 × d), 130.6 (d), 134.8 (s), 145.8 (s), 151.1 (s), 155.9 (s), 159.1
(s), 160.8 (s), 160.9 (s) and 164.0 (s).
14a: Yield 0.29 g (39%), mp 78–79 ЊC (Found: C, 55.2; H, 4.2;
N, 18.5. C17H15N5O5 requires C, 55.3; H, 4.1; N, 19.0%);
νmax(KBr)/cmϪ1 1753 and 1717; δH(CDCl3) 3.59 (3 H, s), 4.00
(3 H, s), 4.19 (3 H, s) and 7.35–7.45 (6 H, m); δC(CDCl3) 39.4
(q), 52.4 (q), 53.5 (q), 116.2 (s), 118.0 (d), 126.7 (2 × d), 128.9
(2 × d), 129.4 (d), 134.4 (s), 137.3 (s), 156.8 (s), 159.9 (s), 160.90
(s), 160.94 (s) and 162.1 (s).
Substituted dimethyl 3-[2-(1H-/2H-tetrazol-5-yl)vinyl]pyrazole-
4,5-dicarboxylates 13d, 14d. General procedure
A stirred mixture of the pyrrolotetrazole 3e or 4e (0.30 g, 1
mmol) and DMAD (0.57 g, 4 mmol) in toluene (20 cm3) was
heated under reflux for 24 h (3e) or kept at 80 ЊC for 2.5 h (4e)
whereupon the solvent was evaporated. In the case of 13d, the
residue was chromatographed on silica gel [chloroform–ethyl
acetate (4 : 1) as eluent] and the product crystallised from
chloroform–diethyl ether. 14d was isolated by dissolving the
residue in a small amount of dichloromethane, followed by
addition of diethyl ether, purification of the precipitate on silica
gel [chloroform–ethyl acetate (5 : 3) as eluent] and recrystallis-
ation from dichloromethane–diethyl ether.
7 W. D. Ollis, S. P. Stanforth and C. A. Ramsden, J. Chem. Soc., Perkin
Trans. 1, 1989, 957.
8 B. Holtmann, Dissertation, Technische Universität Braunschweig
(Germany), 1998.
9 Resembling the conditions for acetylation of the generally less
reactive 1H-pyrrolo[1,2-b][1,2,4]triazole system (I; a = N, b = CR,
c = NR): F. S. Babichev and V. A. Kovtunenko, Ukr. Khim. Zh.
(Russ. Ed.), 1975, 41, 181.
10 D. T. Decker, Dissertation, Technische Universität Braunschweig
(Germany), 1996.
11 Overview: V. A. Ostrovskii and A. Koren, Heterocycles, 2000, 53,
1421.
13d: Yield 0.34 g (76%), mp 174–176 ЊC (lit.,2 174–176 ЊC)
(Found: C, 61.9; H, 4.8; N, 18.7. C23H20N6O4 requires C, 62.15;
H, 4.5; N, 18.9%); for νmax/cmϪ1, δH and δC, see ref. 2 (solvent
quoted with δH to be corrected into CDCl3).
12 D. Moderhack and B. Holtmann, J. Prakt. Chem., 2000, 342, 591.
13 R. A. Jones and J. Sepulveda Arques, Tetrahedron, 1981, 37, 1597.
14 C. A. Ramsden, Tetrahedron, 1977, 33, 3203; C. A. Ramsden, in:
Comprehensive Heterocyclic Chemistry, eds. A. R. Katritzky and
C. W. Rees, Pergamon, Oxford, 1984, vol. 6, p. 1027.
14d: Yield 0.33 g (74%), mp 98–101 ЊC (Found: C, 62.1; H,
4.6; N, 18.8. C23H20N6O4 requires C, 62.15; H, 4.5; N, 18.9%);
νmax(KBr)/cmϪ1 1742 and 1720; δH(CDCl3) 3.55 (3 H, s), 3.89
(3 H, s), 4.19 (3 H, s), 7.33–7.38 (4 H, m), 7.39–7.47 (3 H, m)
and 7.50–7.55 (4 H, m); δC(CDCl3) 39.2 (q), 51.6 (q), 53.4 (q),
114.9 (s), 116.6 (d), 124.1 (2 × d), 126.9 (2 × d), 128.5 (2 × d),
128.7 (d), 129.0 (d), 129.3 (2 × d), 137.8 (s), 139.0 (s), 139.10 (s),
139.12 (s), 150.5 (s), 161.3 (s), 162.0 (s) and 163.0 (s).
15 Cf. R. C. Storr, in: 1,3-Dipolar Cycloaddition Chemistry, ed. A.
Padwa, Wiley, New York, 1984, vol. 2, p. 169.
16 J. M. Kane, J. Org. Chem., 1980, 45, 5396; see also S. Kanemasa,
S. Ikeda, H. Shimoharada and S. Kajigaeshi, Chem. Lett., 1982,
1533.
17 D. Moderhack and D.-O. Bode, J. Chem. Soc., Perkin Trans. 1, 1992,
1483.
18 M. Christl, J. P. Warren, B. L. Hawkins and J. D. Roberts, J. Am.
Chem. Soc., 1973, 95, 4392.
J. Chem. Soc., Perkin Trans. 1, 2001, 729–735
735