Oxidative addition of N-aminophthalimide and 3-amino-2-methylquinazolin- 4(3H)-one to conjugated azocyclopentenes and azocyclohexenes

Article abstract of DOI:10.1023/B:COHC.0000044572.81905.92

The oxidation of N-aminophthalimide and 3-amino-2-methylquinazolin-4(3H)- one in the presence of conjugated azocyclopentenes, azocyclohexenes, and 3-arylazocyclohexen-2-ones gives adducts at the carbon-carbon double bond corresponding to C-azoaziridines a

Full text of DOI:10.1023/B:COHC.0000044572.81905.92

Chemistry of Heterocyclic Compounds, Vol. 40, No. 7, 2004
OXIDATIVE ADDITION OF N-AMINO-
PHTHALIMIDE AND 3-AMINO-2-METHYL-
QUINAZOLIN-4(3H)-ONE TO CONJUGATED
AZOCYCLOPENTENES AND AZOCYCLOHEXENES
S. M. Buchaka1, M. A. Kuznetsov1, and J. G. Schantl2
The oxidation of N-aminophthalimide and 3-amino-2-methylquinazolin-4(3H)-one in the presence of
conjugated azocyclopentenes, azocyclohexenes, and 3-arylazocyclohexen-2-ones gives adducts at the
carbon-carbon double bond corresponding to C-azoaziridines and/or bicyclic 2H-1,2,3-triazoles.
Keywords: C-azoaziridines, 1-azocycloalkenes, 3-azocycloalken-2-ones, 3-amino-2-methylquinazolin-
4(3H)-one, N-aminophthalimide, 2H-1,2,3-triazoles, oxidative aminoaziridination.
The oxidation of a series of N-amino heterocycles related to N-aminophthalimide using lead tetraacetate
in the presence of a compound with a carbon-carbon double bond gives N-aminoaziridine derivatives or the
aminoazimine valence isomers of triaziridines [1, 2] with azo compounds. Non-conjugated γ,δ-unsaturated
alkylazoalkenes react with the system N-aminophthalimide – Pb(OAc)4 at the azo group only [3] but with
conjugated phenylazoalkenes and 1-isopropylazocycloalkenes to give adducts at the C=C bond (the
corresponding C-azoaziridines) and also, quite unexpectedly, 2H-1,2,3-triazoles and 1,2-dicarbonyl compound
dihydrazones [3-5]. The formation of the two latter types of compound has not previously been reported in the
reactions with olefines or in reactions with azo compounds and is clearly due to the specific conjugated
azoalkene system.
In this case the composition of the products of the oxidative addition of N-aminophthalimide to
conjugated azocycloalkenes strongly depends, at first glance, on small changes in the structure of the substrate.
Whereas in the reaction of the systems N-aminophthalimide – Pb(OAc)4 with 1-isopropylazocyclopentene,
1-isopropylazocyclohexene, and 1-phenylazocyclohexene we have separated only the bicyclic C-azoaziridines,
the single product of the reaction with 1-phenylazocyclopentene is 2-phenyl-2,4,5,6-tetrahydrocyclopenta-
[d][1,2,3]triazole [3-5] in 70% yield.
In order to reveal the factors which determine the course of the oxidative addition of N-amino
heterocycles to conjugated azocycloalkenes we have carried out the oxidation of N-aminophthalimide (PiNNH2)
and the related 3-amino-2-methylquinazolin-4(3H)-one (MeQNNH2) using lead tetraacetate in the presence of a
series of conjugated azocyclopentenes 1a,b and azocyclohexenes 1c-j, in which we have varied the nature of the
substituent on the azo group and the C=C bond.
__________________________________________________________________________________________
1
St. Petersburg State University, St. Petersburg 198504, Russia; e-mail: mak@org.chem.lgu.spb.su.
2
Institute for Organic Chemistry, Innsbruck University, Innsbruck A-6020, Austria; e-mail:
Joachim.Schantl@uibk.ac.at. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1043-1051,
July, 2004. Original article submitted May 27, 2004.
0009-3122/04/4007-0895©2004 Springer Science+Business Media, Inc.
895

R
N
R
R
NHet
N
HetN–NH2
Pb(OAc)4
HetN–NH2
Pb(OAc)4
N
N
N
N
N
N
–Pb(OAc)2
–2AcOH
–HetNH
–Pb(OAc)2
–2AcOH
( )n
1a–g
( )n
( )n
2c,d,f,g HetN = PiN
4a–c,e
3c,d,f,g HetN = MeQN
O
O
N
MeQN–
PiN–
N
N
Me
O
1–4 a, b n = 1; c–g n = 2; a, c R = Ph, b, d R = p-O2NC6H4; e R = p-MeOC6H4;
OAc
f R = i-Pr,
g R =
In addition to the compounds 1a,c,f already introduced into the reaction with N-aminophthalimide we
have taken arylazocycloalkenes with acceptor 1b,d and donor 1e substituents in the aromatic ring. The
1-cyclohexylazocyclohexanol acetate 1g was selected as a sterically hindered azoalkene. In addition, we
considered it useful to introduce an acceptor group at the C=C bond (substrates 1h-j) since, in the case of the
oxidative aminoaziridination of olefines, such a structural modification generally increases the yield of the
adduct [1].
PiN
R
R
N
N
N
N
N
PiNNH2
Pb(OAc)4
O
O
–Pb(OAc)2
–2AcOH
R'
R'
R'
2h–j
R'
1h–j
1, 2 h R = Ph, R' = H; i R = p-O2NC6H4, R' = H; j R = Ph, R' = Me
The reactions were carried out with an equimolar ratio of reagents with the addition, in turn, of small
portions of the corresponding N-amino heterocycle and Pb(OAc)4 to a cooled solution (-20 to -30°C) of the
azocycloalkene 1 in methylene chloride with a small excess of potassium carbonate. Separation of the reaction
mixture was carried out by column chromatography on silica gel. As a result, for both N-amino heterocycles
with the majority of 1-azocyclohexenes 1c,d,f,g and all of the 3-azocyclohexen-2-ones 1h-j, the bicyclic
aziridine adducts 2 and 3 at the carbon-carbon double bond were obtained in yields from 10 to 57%. The
separation of the mixture of products with the azocyclopentenes 1a,b and 4-(cyclohexen-1-ylazo)anisole (1e)
gave the bicyclic 1,2,3-triazoles 4a,b,e. In none of the given reactions were there recorded adducts at the azo
group or dihydrazones of the 1,2-dicarbonyl compounds.
In addition to the azoaziridines 2, 3 or triazoles 4 there are always present in the reaction mixtures
phthalimide or 2-methylquinazolin-4(3H)-one (the desamination products of the starting N-amino heterocycles).
Their formation is typical of the oxidative reactions of N-aminophthalimide and related compounds [6, 7] and
always accompanies the oxidative addition at the multiple bond or the unsaturated pair of electrons. Hence the
yield of these desamination products can serve as a measure of the "inertness" of the substrate. However, the
896

formation of the 2H-triazoles 4 are considered as an exception since with either mechanism the phthalimide or 2-
methylquinazolin-4(3H)-one must separate only after the reaction with the azoalkene and here it is a main and
not a side product of the reaction.
The composition of the bicyclic 1,2,3-triazoles 4 and the majority of the azoaziridines 2, 3 were
confirmed from elemental analytical data, their structure from 1H and 13C NMR spectroscopy, and in the case of
the azoaziridines their mass spectra (in which the molecular ion peaks could be detected). The assignment of
signals in the NMR spectra was made on the basis of a spectroscopic comparison of the entire series of
compounds prepared and also from literature data with the use of additive schemes [3-5, 8, 9].
Certain azo-7-azabicyclo[4.1.0]heptanes proved to be quite unstable in CDCl3 solution hence to monitor
1
13
the state of the samples we recorded their H NMR spectra both before and after the recording of the C NMR
spectra. The low stability of the azoaziridines complicates carrying out their elemental analysis and also
recording their mass spectra. Hence in the EI mass spectrum of the 6-(4-nitrophenyl)azo-7-phthalimido-7-
azabicyclo[4.1.0]heptan-2-one (2i) recorded under standard conditions with direct introduction of the sample the
molecular ion peak is absent. This is related to the fact that, with a comparatively slow heating of the sample, it
decomposes well before its vaporization. The molecular ion peak for the azoaziridine 2i could be recorded only
with rapid heating of the sample above 400°C, however the intensity is low in this case. In both mass spectra the
base peaks are signals for the decomposition products of the azoaziridine.
A typical feature of N-aminoaziridine derivatives is the inversion (slow on the NMR time scale) of the
endocyclic nitrogen atom [8], which often leads to the appearance of signals for two invertomers in their spectra.
In the NMR spectra of the N-phthalimidoaziridines 2 only one set of signals is seen and signs of slow dynamic
processes are absent and thus point to their existence in a single, more stable form. The position of the signals of
the aziridine protons of the syn and anti invertomers are usually markedly different [8], but for all of the azo-7-
azabicyclo[4.1.0]heptanes 2 they lie in quite a narrow range (3.70-4.25 ppm) hence it can be assumed that all
these azoaziridines can be assigned to a single series of stereoisomers. Since the effective bulk of the azo group
is less than the tetramethylene chain of the bicyclic system these are more likely the invertomers with a syn
positioning of the azo group and the phthalimide substitutent (Z-invertomers) (cf. [4, 5]).
Confirmation of this comes from the anomalously high field signal for the CH3COO proton group
1
(1.63 ppm) in the H NMR spectrum of the adduct 2g which lies far from the usual limits for its chemical shift
range (1.9-2.2 ppm; in the starting azo compound 1g it is at 2.11 ppm). Its position can only be explained by the
acetoxy group falling in the area of magnetic shielding by the phthalimide group. Optimization of the geometry
of the different conformers of the E- and Z-invertomers of the adduct 2g by the method of molecular mechanics
(AMBER force field) and the semi-empirical methods AM1 and PM3 have shown that this is only possible for a
syn positioning of the phthalimide substituent and the azo group.
It might be expected that when crossing from the phthalimidoaziridines 2 to the compounds of series 3
with the more sterically demanding 2-methyl-4-oxoquinazolinyl substituent the Z-invertomer would also be
1
more thermodynamically stable. However, in the H NMR spectra of the adducts 3c,d,f with 3-amino-2-
methylquinazolin-4(3H)-one, there are clear signs of a slowing of the dynamic processes on the NMR time scale
and even the appearance of a second form, clearly seen in the spectra of the isopropylazoaziridine 3f. Thus the
signals of the aziridine proton, the methyl group, and the aromatic H-5 proton signal of the heterocyclic fragment
are markedly broadened. Moreover, the intensity of the signal for the aziridine proton at ∼4 ppm is slightly
reduced and along with this there is present an additional broad signal in the range 3.0-3.4 ppm.
The observed picture can be explained by the appearance in the NMR spectra of the aminoaziridines 3 of
hindered rotation about the N–N bond. Since the van der Waals radius of the methyl group is significantly larger
than the oxygen atom and substituents in the six-membered ring of the oxoquinazolinyl radical is placed
markedly closer to the aziridine fragment than the carbonyl groups of the five membered phthalimide ring, the
barrier to rotation about the N–N bond of the asymmetric oxoquinazolinyl substituent can be so high that
evidence for hindered rotation and even signals for the separate rotamers might be observed.
897

1
A notable feature of the H NMR spectra of the azoaziridines 2f [3] and 3f is the diastereotopism of the
1
methyl groups of the isopropyl fragment and, in the H NMR spectra of the phthalimidoaziridine 2g, a pairwise
diastereotopism of the oppositely placed C(2',6') and C(3',5') cyclic substituents is observed.
The number of signals in the NMR spectra of the bicyclic 2H-triazoles 4 and also the nature of the
multiplets in the proton spectra point to the magnetic equivalence of the oppositely placed atoms in the molecule.
This agrees with the structure 4 proposed by us (local symmetry C2v) and fully excludes their structure as the
isomeric 1H-triazoles.
With the exception of the adduct of 1-isopropylazocyclohexene with 3-amino-2-methylquinazolin-
4(3H)-one 3f (which is a pale, greenish oil) the remaining azoaziridines are colored (orange, yellow, or
greenish), crystalline materials which are readily soluble in polar organic solvents. Their stability depends
strongly on the nature of the substituent on the azo group. Hence the azoaziridines with an acceptor substituent
on the azo group decompose slowly, even when they are stored at room temperature. The compounds 2d and 2i
with a p-nitrophenyl substituent are particular unstable and rapidly decompose in CDCl3 solution to a mixture of
phthalimide and the bicyclic triazole 4d or 4i respectively. At the same time, the C-isopropylazoaziridines 2f, 3f
are unchanged in chloroform solution, even when gently heated over several days.
In this connection, it should be noted that in the 1H NMR spectrum of the mixture of reaction products of
3-amino-2-methylquinazolin-4(3H)-one with 4-(cyclopenten-1-ylazo)-1-nitrobenzene 1b before its separation on
a silica gel column there is seen a broadened triplet at 3.93 ppm which is absent in the spectra of all of the
compounds separated on the column. It cannot be ruled out that this signal corresponds to a proton of the
azoaziridine 3b which decomposes on silica gel to the 1,2,3-triazole 4b. The low stability of the proposed azo-6-
azabicyclo[3.1.0]hexane 3b with a 4-nitrophenyl substituent on the azo group is in good agreement with the
dependence noted above. Also in agreement we had previously been able to separate and characterize the
corresponding 1-isopropylazo-6-azabicyclo[3.1.0[hexane [3] from the reaction of N-aminophthalimide with
1-isopropylazocyclopentene.
By studying the effect of the structure of the reagents on the course of the oxidative addition of
N-aminophthalimide and 3-amino-2-methylquinazolin-4(3H)-one to the conjugated azocycloalkenes 1a-j it can
immediately be seen that both N-amino heterocycles react very similarly, although the yields of the adducts with
the N-aminophthalimide are usually a little higher. This is possibly due simply to the greater steric bulk of the
3-amino-2-methylquinazolin-4(3H)-one. The change from the arylazocyclohexenes 1c,d to the corresponding
arylazocyclohexenones 1h-j has comparatively little effect on the preparative yields of the C-azoaziridines 2. At
the same time, the yield and composition of the reaction products depends on the substituent on the azo group
and the size of the carbocycle in the azocycloalkene.
The addition to 4-(cyclohexen-1-ylazo)anisole 1e clearly occurs poorly since almost all is recovered
from the reaction with N-aminophthalimide and with both N-amino heterocycles the
2-(4-methoxyphenyl)triazole 4e is produced in low yield. A similar low yield of the adduct 2g occurs with the
acetate 1g, in which a bulky tertiary substituent is found on the azo group. The reason for this seems purely
steric. In the reactions with azocyclopentenes we more often separate the 2H-triazoles and with the
azocyclohexenes the corresponding C-azoaziridines.
In summary, we have shown that the formation not only of azoaziridines but also of 1,2,3-triazoles
occurs generally in the series of conjugated azocyclohexenes and azocyclopentenes. We consider that,
independently of the size of the ring olefine fragment, the oxidative addition of the N-amino heterocyclic
compound to the conjugated azocycloalkene occurs at the carbon-carbon double bond to give azoaziridines.
Formation of the bicyclic 2H-1,2,3-triazoles is the result of secondary reactions. A study of the possible
preparation of bicyclic 1,2,3-triazoles by the decomposition of azoaziridines will be the subject of our next
paper.
898

EXPERIMENTAL
1H and 13C NMR spectra were recorded on Varian Gemini 2000 (200 and 50 MHz) and Bruker DPX-300
(300 and 75 MHz) instruments using CDCl3 solvent. The internal standard was the residual proton signal for the
solvent at 7.25 ppm or carbon signal at 77.0 ppm. DEPT Spectra were used for assignment of the carbon atom
signals. Mass spectra were obtained on Finnigan MAT 95 and MX-1303 mass spectrometers. Electron impact
ionization was used with an ionization energy of 70 eV and FAB (Cs source, 20 kV 0.2 µA) in a 3-nitrobenzyl
alcohol matrix. Elemental analysis was carried out on a Hewlett-Packard HP-185B C,H,N automatic analyzer.
Melting points were measured on a Boetius type heating stage with a VEB Analytik PHMK 05 direct reading
device at an accuracy of 0.2°C. The composition of the reaction mixtures and their separated fractions together
with the purity of the individual components were monitored by TLC on Macherey-Nagel Polygram sil G/UV254
and Alugram sil G/UV254 plates.
The conjugated azocycloalkenes used in this work were synthesized by known methods or on their basis
[10-15].
Oxidative Addition of N-Amino Heterocycles to Azocycloalkenes. (General Method).
N-Aminophthalimide (162 mg, 1 mmol) [16] (or 175 mg of 3-amino-2-methylquinazolin-4(3H)-one [17]) and
lead tetraacetate (520 mg, 1 mmol) (containing ∼15% acetic acid) were added alternately and in small portions
over 30 min to a suspension of potassium carbonate (966 mg, 7 mmol (690 mg, 5 mmol)) in anhydrous
methylene chloride (50 ml) containing the azo compound (1 mmol) with vigorous stirring and cooling to -20 to
-30°C. The reaction mixture was held for a further 20 min at -20 to -30°C, then heated to 12-16°C, and filtered
through a 1.5-20 cm layer of silica gel. The viscous precipitate of inorganic salts was washed with methylene
chloride to a colorless filtrate. Solvent was removed at reduced temperature in vacuo using a water pump and the
oily residue was separated on a silica gel column (40-63 µm) using hexane (or petroleum ether)–ether (5:1) as
eluent with a gradual increase in the fraction of the latter.
Addition of N-Aminophthalimide to 1-Nitro-4-(cyclohexen-1-ylazo)benzene (1d) (0.5 mmol) to give
the starting azo compound 1d (44 mg, 38%), phthalimide (24 mg, 33%), and 112 mg (57%, 93% based on
recovered starting azo compound) of 1-(4-nitrophenyl)azo-7-phthalimido-7-azabicyclo[4.1.0]heptane (2d) as
bright yellow crystals; mp 109.8-110.3°C, Rf 0.15 (petroleum ether–ether, 5:1). Using TLC and NMR
1
spectroscopy, the aziridine was found to decompose rapidly in CDCl3 solution. H NMR spectrum, δ, ppm
(J, Hz): 1.30-1.75 (4H, m, H-3,4); 2.04-2.28 (2H, m, H-5); 2.49 (1H, m, H-2); 2.93 (1H, m, H-2); 3.91 (1H, dd,
13
J = 5.3, J = 1.3, H-6); 7.53 (2H, d, J = 9.2, Ar); 7.65-7.77 (4H, m, PiN); 8.18 (2H, d, J = 9.2, Ar). C NMR
spectrum, δ, ppm: 19.9 and 20.2 (C(3,4)); 23.3 and 23.5 (C(2,5)); 52.0 (C(6)); 74.1 (C(1)); 122.8, 123.0 (PiN, C(3,6)
and Ar, C(2,6)); 124.6 (Ar, C(3,5)); 130.5 (PiN, C(1,2)); 134.1 (PiN, C(4,5)); 148.5 (Ar, C(1)); 155.0 (Ar, C(4)); 165.0
(PiN, C=O). Mass spectrum (FAB), m/z (I, %): 393 (22), 392 (M++ 1) (54), 391 (M+) (33), 327 (30), 308 (25),
307 (100), 289 (60), 281 (42), 267 (25), 245 (85), 244 (40), 221 (27), 207 (43).
Addition of N-Aminophthalimide to 4-(Cyclohexen-1-ylazo)anisole (1e) (1.6 mmol) to give the
starting azo compound 1e (191 mg, 55%), phthalimide (206 mg, 89%), and 192 mg of an oily residue which,
from NMR spectroscopic data, is a mixture of the starting azo compounds 1e and 2-(4-methoxyphenyl)-4,5,6,7-
tetrahydro-2H-benzo-1,2,3-triazole (4e) in the molar ratio 5.4: 1. 1H NMR spectrum, δ, ppm (J, Hz): signals for
the 4-(cyclohexen-1-ylazo)anisole 1e: 1.70-1.78 (4H, m, H-4,5); 2.40-2.50 (4H, m, H-3,6); 3.85 (3H, s, CH3O);
6.88 (1H, t, H-2); 6.95 (2H, d, J = 9, Ar, H-3,5); 7.72 (2H, d, J = 9, Ar, H-2,6); triazole signals: 1.90-1.95 (4H,
m, H-5,6); 2.84-2.88 (4H, m, H-4,7); 3.84 (3H, s, CH3O); 6.95 (2H, d, J = 9, Ar, H-3,5); 7.92 (2H, d, J = 9, Ar,
H-2,6). 13C NMR spectrum, δ, ppm: azo compound 1e signals: 22.1 and 22.4 (C(4,5)); 22.8 (C(3)); 26.3 (C(6)); 55.5
(MeO); 114.1 (Ar, C(3,5)); 123.9 (Ar, C(2,6)); 139.9 (C(2)); 147.1 (Ar, C(1)); 155.0 (Ar, C(4)), 161.1 (C(1)): triazole
4a signals: 21.9 (C(5,6)); 23.1 (C(4,7)); 55.5 (CH3O); 114.3 (Ar, C(3,5)); 119.7 (Ar, C(2,6)); 145.1 (C(3a,7a) and Ar,
C(1)); 158.7 (Ar, C(4)).
899

Addition of N-Aminophthalimide to 1-(1-Cyclohexenylazo)cyclohexanol Acetate (1g) (3.5 mmol) to
give the starting azo compound 1g (356 mg, 41%) and 1-(1-acetoxycyclohexyl)azo-7-phthalimido-7-
1
azabicyclo[4.1.0]heptane 2g (146 mg, 10%) as yellow crystals; mp 114-117°C. H NMR spectrum, δ, ppm
(J, Hz): 1.19-1.82 (m, H-2',3,3',4,4'5',6'); 1.63 (s, MeCOO) and 1.99-2.13 (m, H-2,5) overall 19H; 2.33 (1H, m,
13
H-5); 2.60 (1H, m, H-2); 3.73 (1H, d, J = 4.9, H-6); 7.63-7.75 (4H, m, PiN). C NMR spectrum, δ, ppm: 19.9
and 20.1 (C(3,4)); 21.2 (AcO); 22.9 and 23.3 (C(2,5)); 21.8, 21.9, 24.9, 32.6, and 32.8 (C(2',3',4',5',6')); 49.5 (C(6)); 71.7
(C(1)); 102.4 (C(1')); 122.6 (PiN, C(3,6)); 130.7 (PiN, C(1,2)); 133.7 (PiN, C(4,5)); 164.9 (PiN, C=O); 168.9 (AcO,
C=O). Mass spectrum (EI), m/z (I, %); 410 [M+] (12), 368 (16), 350 (4), 325 (35), 299 (17), 267 (17), 264 (14),
248 (100), 222 (99), 207 (39), 179 (33), 167 (31), 154 (96), 10 (89 ), 109 (86), 104 (20), Found, %: C 64.67; H
6.35; N 13.43. C22H26N4O4. Calculated, %: C 64.38; H 6.39; N 13.65.
Later fractions contained phthalimide (145 mg, 28%).
Addition of N-Aminophthalimide to 3-Phenylazocyclohexen-2-one (1h) (2.4 mmol) to give the
starting compound 1h (311 mg, 65%), phthalimide (198 mg, 56%), and 268 mg (31%, 88% based on recovered
starting material) of 6-phenylazo-7-phthalimido-7-azabicyclo[4.1.0]heptan-2-one (2h) as yellow crystals with
mp 172°C. 1H NMR spectrum, δ, ppm (J, Hz): 1.86-1.95 (1H, m, H-4); 2.09-2.30 (2H, m, H-3,4); 2.61-2.76 (3H,
m, H-3,5); 4.23 (1H, s, H-1); 7.34-7.40 (3H, m, Ph, H-3,4,5); 7.47-7.50 (2H, m, Ph, H-2,6); 7.67-7.79 (4H, m,
13
PiN). C NMR spectrum δ, ppm: 17.6 (C(4)); 23.2 (C(3)); 36.8 (C(5)); 54.3 (C(1)); 74.5 (C(6)); 122.4 and 123.2
(PiN, C(3,6) and Ph, C(2,6)); 129.0 (Ph, C(3,5)); 130.3 (PiN, C(1,2)); 131.4 (Ph, C(4)); 134.1 (PiN, C(4,5)); 151.6 (Ph,
C(1)); 164.2 (PiN, C=O); 201.1 (C(2)).
Addition of N-Aminophthalimide to 3-(4-Nitrophenyl)azocyclohexen-2-one (1i) (2.3 mmol).
Several fractions of the filtrate with change in intensity of the solution color were collected when filtering
through a layer of silica gel. The latter colorless fraction contained only phthalimide (77 mg). The remaining
fractions were combined and the solvent was distilled off in vacuo. The oily residue (849 mg) was triturated
with a minimum amount of ether until a precipitate appeared and this was filtered off (phthalimide 27 mg). The
filtrate was evaporated. Repeat of this procedure gave a further 56 mg of phthalimide (overall yield of
phthalimide 160 mg (47%)). According to 1H NMR spectroscopic analysis, the oily residue after evaporation of
the filtrate (671 mg) was a mixture of the starting azo compound 1i and the aziridine 2i in the molar ratio of
∼1.8:1 (346 mg (62%) of 1i and 317 mg (34%, 88% based on the recovered starting azo compound) of 2i and
also contained traces of phthalimide. It was dissolved in a minimum amount of methylene chloride, hexane was
added to solution turbidity, and the mixture was left in the cold for several hours. The precipitate was filtered
off (starting azo compound 1i) and the filtrate was evaporated (206 mg, a mixture of the starting azo compounds
1i and the aziridine 2i in the molar ratio 1: 4 according to 1H NMR spectroscopy). Repeat of this procedure gave
6-(4-nitrophenyl)azo-7-phthalimido-7-azabicyclo[4.1.0]heptan-2-one 2i (141 mg, 15%) as orange crystals.
1H NMR spectrum, δ, ppm (J, Hz): 1.88-1.93 (1H, m, H-4); 2.14-2.31 (3H, m, H-3,4); 2.64-2.65 (2H, m, H-5);
4.24 (1H, s, H-1); 7.61 (2H, d, J = 8.2, Ar, H-2,6); 7.70-7.80 (4H, m, PiN); 8.22 (2H, d, J = 9.2, Ar, H-3,5).
13C NMR spectrum, δ, ppm: 17.3 (C(4)); 23.1 (C(3)); 36.7 (C(5)); 54.9 (C(1)); 75.3 (C(6)); 123.0 and 123.3 (PiN,
C(3,6) and Ar, C(2,6)); 124.7 (Ar, C(3,5)); 130.1 (PiN, C(1,2)); 134.4 (PiN, C(4,5)); 148.9 (Ar, C(1)); 154.6 (Ar, C(4));
164.2 (PiN, C=O); 200.3 (C(2)). Mass spectrum (EI) obtained with rapid heating above 400°C, m/z (I, %): 405
[M+] (3), 366 (37), 349 (35), 319 (28), 276 (39), 259 (43), 258 (60), 216 (100), 162 (83), 148 (52), 147 (83), 130
(44), 122 (79), 104 (78), 93 (78), 92 (79). In the mass spectrum obtained under the standard conditions of
plotting the main peaks were m/z 258 and 147 corresponding to the molecular ion peaks of the triazole 4i and
phthalimide. The molecular ion peak of the azoaziridine 2i is located only with rapid sample heating above
400°C.
Addition of N-Aminophthalimide to 5,5-Dimethyl-3-phenylazocyclohex-2-enone(1j) (3.5 mmol) to
give compound 1j (437 mg, 55%), phthalimide (167 mg, 33%), and 595 mg (44%, 97% based on recovered
starting azo compound) of 4,4-dimethyl-6-phenylazo-7-phthalimido-7-azabicyclo[4.1.0]heptan-2-one (2j) as
1
yellow crystals with mp 113°C (decomp.). H NMR spectrum, δ, ppm (J, Hz): 0.90 (3H, s, CH3); 1.16 (H, s,
CH3); 2.07 (1H, d, J = 13.3, H-3); 2.21 (1H, d, J = 14.8, H-5); 2.70 (1H, d, J = 13.8, H-3); 3.22 (1H, d,
900

J = 14.3, H-5); 4.13 (1H, s, H-1); 7.33-7.35 (3H, m, Ph, H-3,4,5); 7.46-7.48 (2H, d, J = 7.2, Ph, H-2,6);
7.67-7.79 (4H, m, PiN). 13C NMR spectrum, δ, ppm: 26.9 (CH3); 30.4 (CH3); 35.2 (C(4)); 35.9 (C(3)); 50.0 (C(5));
54.0 (C(1)); 76.1 (C(6)); 122.5 and 123.2 (PiN, C(3,6) and Ph, C(2,6)); 129.0 (Ph, C(3,5)); 130.2 (PiN, C(1,2)); 131.4
(Ph, C(4)); 134.1 (PiN, C(4,5)); 151.3 (Ph, C(1)); 164.2 (PiN, C=O); 202.4 (C(2)). Found, %: C 67.94; H 4.71;
N 13.04. C22H20N4O3. Calculated, %: C 68.03; H 5.19; N 14.42.
Addition of 3-Amino-2-methylquinazolin-4(3H)-one to Cyclopenten-1-ylazobenzene (1a) (5 mmol).
The oily residue (692 mg) was dissolved in a minimum amount of ether and the precipitate formed was filtered
off (336 mg (42%) of the quinazolinone). The filtrate was evaporated on a rotary evaporator to give 2-phenyl-
2,4,5,6-tetrahydrocyclopenta-1,2,3-triazole 4a (344 mg, 37%) as white crystals with mp 62°C (lit. mp 62-64°C
[4, 5]). The 1H and 13C NMR spectra for the compound obtained agreed with data in [4, 5].
Addition of 3-Amino-2-methylquinazolin-4(3H)-one to 1-Nitro-4-(cyclopenten-1-ylazo)benzene
(1b) (0.6 mmol). Several fractions of the filtrate with change in intensity of the solution color were collected
when filtering through a layer of silica gel. The latter colorless fraction contained only 2-methylquinazolin-
4(3H)-one (53 mg). The remaining fractions were combined and the solvent distilled off in vacuo. The 1H NMR
spectrum of the mixture obtained showed a characteristic triplet for the aziridine proton at 3.93 ppm. The oily
residue (183 mg) was chromatographed of a silica gel column (20 g) using petroleum ether–methylene chloride
(4:1), gradually increasing its polarity to 1: 1 to give the starting azo compound 1b (20 mg, 15%) and
2-(4-nitrophenyl)-2,4,5,6-tetrahydrocyclopenta-1,2,3-triazole 4b (120 mg, 87%) as yellowish crystals with
mp 227-229°C (decomp.) and Rf 0.63 (ether). 1H NMR spectrum, δ, ppm (J, Hz): 2.58 (2H, q, J = 7.6, H-5); 2.87
13
(4H, t, J = 7.6, H-4,6); 8.09 (2H, d, J = 9.3, Ar, H-2,6); 8.28 (2H, d, J = 9.3, Ar, H-3,5). C NMR spectrum,
δ, ppm: 22.1 (C(4,6)); 28.7 (C(5)); 117.9 (Ar, C(2,6)); 125.2 (Ar, C(3,5)); 144.6 and 145.3 (Ar, C(1,4)), 159.0 (C(3a,6a)).
Found, %: C 57.61; H 4.48; N 23.39. C11H10N4O2. Calculated, %: C 57.39; H 4.35; N 24.35.
Later fractions contained 2-methylquinazolin-4(3H)-one (27 mg) (overall yield 80 mg (82%)).
Addition of 3-Amino-2-methylquinazolin-4(3H)-one to Cyclohexen-1-ylazobenzene (1c) (5 mmol)
to give the starting azo compound 1c (200 mg, 22%), 2-phenyl-4,5,6,7-tetrahydro-2H-benzotriazole 4c (12 mg,
1
1%) as white crystals with mp 70°C. H NMR spectrum, δ, ppm (J, Hz): 1.85-1.90 (4H, m, H-5,6); 2.78-2.82
13
(4H, m, H-4,7); 7.25 (1H, t, Ph, H-4); 7.42 (2H, t, Ph,, H-3,5); 7.96 (2H, d, Ph, H-2,6). C NMR spectrum, δ,
ppm: 21.9 (C5,6); 23.1 (C4,7); 118.3 (Ph, C2,6); 126.5 (Ph, C4); 129.2 (Ph, C3,5); 140.1 (Ph, C1); 145.7 (C3a,7a)]
together with 1.209 g of a mixture of the aziridine 3c and 2-methylquinazolin-4(3H)-one. The last fraction was
triturated with a small amount of a low polarity mixture of cold petroleum ether and ether. The crystals formed
were filtered off, the filtrate was evaporated on a rotary evaporator, and the residue was recrystallized from
methanol. The yield of 2-methyl-3-(1-phenylazo-7-azabicyclo[4.1.0]hept-7-yl)quinazolin-4(3H)-one (3c) was
653 mg (37%, 47% based on recovered starting azo compound) as yellow needles with mp 98-101°C. 1H NMR
spectrum, δ, ppm (J, Hz): 1.50-1.76 (4H, m, H-3,4); 1.97-2.21 (2H, m, H-5); 2.38 (3H, s, CH3); 2.62-2.70 (1H,
m, H-2); 2.94-3.01 (1H, m, H-2); 3.20 broad signal and 3.98 (d, J = 4.1) overall 1H, H-6; 7.26-7.46 (6H, m, Ph
and MeQN, H-6); 7.57-7.72 (2H, m, MeQN, H-7,8); 8.24 (1H, d, J = 8, MeQN, H-5). 13C NMR spectrum,
δ, ppm: 19.8, 20.5, 23.2, 23.6 (C(2,3,4,5)); 22.6 (MeQN, Me); 53.0 (C(6)); 76.6 (C(1)); 121.4 (C(4a)); 122.1 (Ph,
C(2,6)); 126.0, 126.1, 126.4 (MeQN, C(5,6,8)); 128.8 (Ph, C(3,5)); 131.2 (Ph, C(4)); 133.5 (MeQN, C(7)); 145.9 (C(8a));
151.4 (Ph, C(1)); 154.0 (MeQN, C(2)); 160.1 (MeQN, C(4)). Found, %: C 70.24; H 5.96; N 19.91. C21H21N5O.
Calculated, %: C 70.20; H 5.85; N 19.50.
The yield of the 2-methylquinazolin-4(3H)-one was 365 mg (45%).
Addition of 3-Amino-2-methylquinazolin-4(3H)-one to 1-Nitro-4-(cyclohexen-1-ylazo)benzene (1d)
(2 mmol) to give the starting azo compound 1d (54 mg, 12%) and 2-methyl-3-(1-(4-nitrophenyl)azo-7-
azabicyclo[4.1.0]hept-7-yl)quinazolin-4(3H)-one 3d (364 mg, 45%, 51% based on recovered starting azo
1
compound) as yellow crystals with mp 180.4-181.1°C. H NMR spectrum, δ, ppm (J, Hz): 1.47-1.82 (4H, m,
H-3,4); 2.04-2.24 (2H, m, H-5); 2.35 (3H, br. s, MeQN, CH3); 2.62-2.74 (1H, m, H-2); 3.00 (1H, ddd, J = 14.6,
J = 8, J = 6, H-2); 3.39 br. s and 4.15 br. s (1H, H-6); 7.40-7.48 (3H, m, Ar, H-2,6 and MeQN, H-6); 7.60 (1H,
901

d, J = 8, MeQN, H-8); 7.72 (1H, t, J = 7.8, MeQN, H-7); 8.15-8.18 (3H, m, Ar, H-3,5 and MeQN, H-5).
13C NMR spectrum, δ, ppm: 19.7 and 20.4 (C(3,4)); 22.7 (MeQN, CH3); 23.2 and 23.5 (C(2,5)); 54.2 (C(6)); 76.0
(C(1)); 122.9 (C(4a), Ar, C(2,6)); 124.7 br. signal, 126.3 br. signal, 126.4 and 126.7 (Ar, C(3,5) and MeQN, C(5,6,8));
133.9 (MeQN, C(7)); 146.0 (C(8a)); 148.1 (Ar, C(1)); 154.3 and 155.2 (Ar, C(4) and MeQN, C(2)); 160.1 (MeQN,
C(4)). Mass spectrum (FAB), m/z (I, %): 405 [M+] (84), 369 (74), 338 (48), 307 (65), 289 (52), 282 (32), 245
(100). Found, %: C 62.47; H 5.20; N 19.86. C21H20N6O3. Calculated, %: C 62.37; H 4.99; N 20.78.
Later fractions contained 2-methylquinazolin-4(3H)-one (99 mg, 31%).
Addition of 3-Amino-2-methylquinazolin-4(3H)-one to 4-(Cyclohexen-1-ylazo)benzene (1e)
(2 mmol) to give the starting azo compound 1e (42 mg, 10%), 2-(4-methoxyphenyl)-4,5,6,7-tetrahydro-2H-
1,2,3-triazole 4e (30 mg, 7%), 110 mg of a mixture of several compounds with similar retention times using a
1
mixture of petroleum ether–ether (5: 1) (for which the H NMR spectrum showed no signals in the range
3-5 ppm), and the quinazolinone (100 mg, 31%).
Compound 4e. 1H NMR spectrum, δ, ppm (J, Hz): 1.89 (4H, m, H-5,6); 2.80 (4H, m, H-4,7); 3.84 (3H,
13
s, MeO); 6.95 (2H, d, J = 9, Ar, H=3,5); 7.89 (2H, m J = 9, Ar, H-2,6). C NMR spectrum: 21.8 (C(5,6)); 23.1
(C(4,7)); 55.5 (MeO); 114.3 (Ar, C(3,5)); 119.8 (Ar, C(2,6)); 145.1 (C(3a,7a) and Ar, C(1)); 158.4 (Ar, C(4)).
Addition of 3-Amino-2-methylquinazolin-4(3H)-one to 1-Isopropylazocyclohexene (1f) (4 mmol) to
give the starting azo compound 1f (46 mg, 7%) and 3-(1-isopropylazo-7-azabicyclo[4.1.0]hept-7-yl)-2-
methylquinazolin-4(3H)-one 3f (628 mg, 48%, 52% based on recovered starting azo compound) as a greenish
oil. 1H NMR spectrum, δ, ppm (J, Hz): 1.05 (d, J = 6.8) and 1.06 (d, J = 6.6), 6H, i-Pr, 2CH3; 1.30-1.60 (4H, m,
H-3,4); 1.92-2.09 (2H, m, H-5); 2.34 s and 2.40 s (3H, MeQN, CH3); 2.43-2.67 (2H, m, H-2); 3.59 (1H, sept,
J = 6.6, i-Pr, CH); 3.05 br. s and 3.85 (1H, d, J = 4.2, H-6); 7.23 (1H, t, J = 7.2, MeQN, H-6); 7.40-7.55 (2H,
m, MeQN, H-7,8); 8.10 (d, J = 7.2) and 8.01-8.06 m (1H, MeQN, H-5). 13C NMR spectrum, δ, ppm: signals for
the main rotamer: 19.7 (i-Pr, 2CH3); 19.6 and 20.2 (C(3,4)); 22.6 (MeQN, CH3); 22.8 (C(5)); 23.2 (C(2)); 50.9 (C(6));
67.9 (i-Pr, CH); 74.5 (C(1)); 121.3 (C(4a)); 125.7, 125.9, 126.2 (MeQN, C(5,6,8)); 133.2 (MeQN, C(7)); 145.8 (C(8a));
153.9 (MeQN, C(2)); 159.8 (MeQN, C(4)): signals for the minor rotamer: 20.9 (MeQN, Me); 126.1, 127.8, 128.1
(MeQN, C(5,6,8)); 136.0 (MeQN, C(7)); 146.0 (C(8a)).
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