Cycloaddition reactions of 2,4-diphenyl-1,3-diazabuta-1,3-dienes with isocyanates and isothiocyanates

Article abstract of DOI:10.1016/S0040-4020(03)01124-4

The cycloaddition reactions of 1-p-tolyl and 1-benzyl- 2,4-diphenyl-1,3-diazabuta-1,3-dienes with a variety of aryl and alkyl isocyanate and isothiocyanate are described. The reaction mechanism is also discussed.

Full text of DOI:10.1016/S0040-4020(03)01124-4

Tetrahedron 59 (2003) 7397–7402
Cycloaddition reactions of 2,4-diphenyl-1,3-diazabuta-1,3-dienes
with isocyanates and isothiocyanates
*
Giorgio Abbiati, Alessandro Cirrincione de Carvalho and Elisabetta Rossi
`
Istituto di Chimica Organica “Alessandro Marchesini”, Universita degli Studi di Milano, Via Venezian 21, I-20133 Milan, Italy
Received 15 May 2003; revised 24 June 2003; accepted 17 July 2003
Abstract—The cycloaddition reactions of 1-p-tolyl and 1-benzyl- 2,4-diphenyl-1,3-diazabuta-1,3-dienes with a variety of aryl and alkyl
isocyanate and isothiocyanate are described. The reaction mechanism is also discussed.
q 2003 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
In the last decades the cycloaddition reactions of 1,3-
diazabuta-1,3-dienes represented a useful tool for the
synthesis of a wide variety of four, five and six member
nitrogen-containing heterocycles.1 The involvement of
these azadienes in cycloaddition reactions with isocya-
nides,2 phosphoric compounds,3 the Simmons–Smith
reagent,4 acetylenes,5 enamines,6 sulfenes,7 oxazolinones,8
acrylates,9 the Reformatsky reagent,10 nitriles11 and a-
nitrostyrenes,12 have been reported. Nevertheless the
cycloaddition reactions of 1,3-diazabuta-1,3-dienes with
ketenes represent the most studied application of 1,3-
diazabutadienes in heterocyclic synthesis,13 leading up to a
wide variety of azetidinones and pyrimidinones. Recently in
our laboratories we investigated the reactions of 2,4-
diphenyl-1,3-diazabuta-1,3-dienes 1a and 1b with mono
and disubstituted ketenes14 and the thermal and photo-
chemical transformations of the [2þ2] cycloadduct into the
corresponding [4þ2] adduct.15 We also extended our study
to the cycloaddition reactions of 1-benzyl-2,4-diphenyl-1,3-
diazabuta-1,3-diene 1b with some chiral ketenes leading up
to optically active azetidinones.16 In connection with our
ongoing interest in this research area, we widened our study
to cycloaddition reactions of 2,4-diphenyl-1,3-diazabuta-
1,3-dienes 1a and 1b with isocyanates17 and isothiocya-
nates.18 In the literature there are only a few reports of the
reactions of simple acyclic azadienes and they mainly
involve 4,4-disubstituted azadienes11a,19 or 2,4-heterosub-
stituted azadienes.20 On the contrary azadienes 1a and 1b
are marked out by the monosubstitution on C-4 and by the
all-carbon substitutions on the diene chain.
We tested the reactivity of the 1,3-diaza-1,3-butadienes 1a-
b with arylisocyanates 2a-c, benzylisocyanate 2d, alkyliso-
cyanates 2e,f, arylisothiocyanates 2g,h and benzylisothio-
cyanate 2i. In the first stage of the study the reactions were
performed in a sealed tube under nitrogen atmosphere by
addition of the appropriate heteroallene 2a–i (2 equiv.) to a
stirred solution of 1,3-diaza-1,3-diene 1a or 1b (1 equiv.) in
dry benzene and in the presence of few crystals of
hydroquinone to avoid heterocumulene polymerisation
(Method A). The reactions of azadiene 1a were performed
at 80–1108C while 1b reacted at lower temperatures. After
usual work up, the reaction mixtures were purified by flash
chromatography over silica gel or by crystallisation. The
structures were assigned on the basis of analytical and
spectral data.
As summarised in Table 1 the reactions of the azadiene 1a,
bearing a p-tolyl group on N-1 with arylisocyanates 2a-c
gave rise to the 3,4-dihydro-1H-[1,3,5]triazin-2-ones 3a-c in
satisfactory yields; the presence of an electron withdrawing
group on the isocyanate moiety positively affected the
reaction, increasing the yields and reducing the reaction
times (Table 1, entries 1–3). The reaction with benzyliso-
cyanate 2d resulted in the isolation of a modest amount of
triazin-2-one 3d besides the N-substituted 3,4-dihydroquin-
azoline 4d (Table 1, entry 4). This trend was emphasized in
the reactions of 1a with alkylisocyanates 3e,f yielding the
N-substituted 3,4-dihydroquinazolines 4e,f as the sole
isolated products (Table 1, entries 5 and 6). Finally no
reaction was observed between 1a and the isothiocyanates
2g,h and the 3,4-dihydroquinazoline 5 was the exclusive
detected product (Table 1, entries 7–8).
Keywords: 1,3-diazabuta-1,3-dienes; isocyanates; isothiocyanates; [4þ2]
cycloaddition; triazin-2-ones; triazin-2-thiones.
*
The reactions performed with 1,3-diaza-1,3-butadiene 1b,
bearing a benzyl group on N-1, and heteroallenes 2a-i
Corresponding author. Tel.: þ39-2-50314474; fax: þ39-2-50314476;
e-mail: giorgio.abbiati@unimi.it
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4020(03)01124-4

7398
G. Abbiati et al. / Tetrahedron 59 (2003) 7397–7402
Table 1. Reactions of 1a with 2a-h (Method A)
Entry
Compound
R
X
Yield (%)
Time (h)
Temperature (8C)
3
4
5
1
2
3
4
5
6
7
8
2a
Ph–
m-Cl–Ph–
p-CH3–Ph–SO2–
Ph–CH2–
O
O
O
O
O
O
S
68
84
91
39
–
–
–
–
–
–
–
60
78
63
–
–
–
–
–
–
–
77
82
31
5
1
24
25
75
24
22
80
110
80
110
100
100
80
2b
2c
2d
2e
2f
c-C6H11
–
CH3CH2CH2–
p-NO2–Ph–
Ph–
2g
2h
S
–
80
resulted in the isolation of the [4þ2] cycloaddition reaction
products, the triazin-2-ones/thiones 6a-i besides a variable
amount of the 1,2-dihydro-1,3,5-triazine 7 as by-product
(Table 2).
dienes is dominated by pronounced charge alternation and
high electron deficiency. On the basis of perturbation theory
the N-1 is placed in a more favorable position of the diene
system and with respect to N-3 is much prone to act as
nucleophile.13c On the other hand the reactivity of
isocyanates and isothiocyanates can be well understood by
considering both electronic and steric effect of the groups
attached to the nitrogen atom; the reactions of hetero-
cumulenes with nitrogen nucleophile involve the attack on
the central carbon of iso(thio)cyanate; consequently, in
absence of steric hindrance any electron-withdrawing group
linked to the NCO/NCS moiety amplifies the positive
charge on carbon atom increasing the reactivity toward
nucleophiles; on the contrary, the opposite effect is shown
when an electron-donating group is attached to NCO/NCS
cluster.22
The behavior of azadiene 1b in the reactions with the aryl
and benzyl isocyanates 2a–d was closely related to those
observed for 1a (Table 2, entries 1–4). In contrast, 1b was
able to react with the alkyl isocyanates 2e,f affording the
3,4-dihydro-1H-[1,3,5]triazin-2-ones 6e,f in low yields
beside a considerable amount of triazine 7 (Table 2, entries
5 and 6). Moreover, the reaction of 1b with the
isothiocyanates 2g–i gave the corresponding 3,4-dihydro-
1H-[1,3,5]triazin-2-thiones 6g–i in moderate yields (Table
2, entries 7–9). In all performed reactions the use of an
excess of heteroallene did not give any adduct arising from
the reaction of two molecules of iso(thio)cyanate with one
molecule of diene, such as has been reported.21
On the basis of these considerations and in analogy with the
reactions of azadienes 1a,b with ketenes14 the proposed
mechanism for the reaction between 1a,b and the iso
It is well known that the chemistry of 1,3-diazabuta-1,3-
Table 2. Reactions of 1b with 2a-i (Method A)
Entry
Compounds
R
X
Yield (%)
Time (h)
Temperature
(8C)
6
7
1
2
3
4
5
6
7
8
9
2a, 6a
2b, 6b
2c, 6c
2d, 6d
2e, 6e
2f, 6f
2g, 6g
2h, 6h
2i, 6i
Ph–
m-Cl–Ph–
p-CH3–Ph–SO2–
Ph–CH2–
O
O
O
O
O
O
S
72
76
82
42
15
17
52
42
35
13
–
–
19
48
56
18
23
10
26
20
5
24
72
72
48
96
120
25
25
25
25
25
25
25
60
60
c-C6H11
–
CH3CH2CH2–
p-NO2–Ph–
Ph–
S
S
Ph–CH2–

G. Abbiati et al. / Tetrahedron 59 (2003) 7397–7402
7399
Nevertheless the quinazoline 5 did not react with isothio-
cyanate 2g–h which are unreactive under these reaction
conditions.25
On the other hand, in the reactions between 1b and
heteroallenes, the formation of 1,2-dihydro-1,3,5-triazine
7 (formally derived from two molecules of azadiene 1b) was
competitive with the cycloaddition reaction (Table 2, entries
1, 4–7); the mechanism of formation of 7 was widely
discussed in a previous paper.26
Scheme 1.
The lower reactivity of 1a with respect to 1b is probably
related to the poor nucleophilicity of the N-1 in the fully
conjugated system 1a and to the steric hindrance exerted by
the phenyl group directly linked to the N-1 atom in 1a. The
reactive center in 1b is less hindered by the insertion of a
methylene spacer between N-1 and the phenyl group.
Moreover the presence of a methylene group in 1b decrease
the conjugation and increase the nucleophilicity of the
system.
(thio)cyanates 2a–i is a two-step process. As previously
reported for cyclic azadienes,23 the first step involves the
nucleophilic attack of the N-1 of the azadiene on the central
carbon atom of heterocumulene followed by the intramo-
lecular attack of the C-4 of the diene system on the nitrogen
atom of the heteroallene to afford six member heterocycles 3
or 6 (Scheme 1). It is worthy to note that, whereas 1b reacts
with ketenes giving rise to [2þ2] cycloaddition products,14
the reactions of 1b with iso(thio)cyanates did not afford any
[2þ2] cycloaddition product and the hypothetical diazeti-
dinone/thione 8 was never detected or isolated (Scheme 1).
With the aim to improve the yields and avoid or minimize
the formation of by-products we performed some new
experiments for the reactions that failed or gave low yields
by the way of method A. Thus, the reactions of 1a with
2d,f,g and 1b with 2d–f,i were carried out without solvent
by stirring a mixture of 100 mg of azadiene 1 and 1 mL of
the appropriate heterocumulene 2 at 25–1228C (Method B).
The obtained results are reported in Table 3.
In the reactions of 1a with alkylisocyanates 2d–f the
formation of the N-substituted 3,4-dihydroquinazolines
4d–f (Table 1, entries 4–6) can be explained as conse-
quence of the competitive sequential thermal 6p electro-
cyclic ring closure/[1,5] sigmatropic hydrogen shift of
azadiene 1a to give 3,4-dihydroquinazoline 5,24 followed by
nucleophilic addition to isocyanate 2d–f (Scheme 2).
By this way, it was possible to improve the yields of reaction
of the azadiene 1a with benzylisocyanate 2d from 39 to 61%
Scheme 2.
Table 3. Reactions of 1a and 1b with 2d-g,i (Method B)
Entry
Compound
Compound
Time (h)
Temperature (8C)
Products
Yield (%)
Gain (%)a
By-products
Yield (%)
3/6
4/5/7
1
2
3
4
5
6
7
1a
1a
1a
1b
1b
1b
1b
2d
2f
2g
2d
2e
2f
44
48
72
48
72
48
72
25
25–60
122b
25
40
25
3d
–
–
6d
6e
6f
6i
61
–
–
64
46
43
54
þ56
–
–
þ52
þ206
þ153
þ54
4d
4f
5
7
7
tr.
91
68
tr.
tr.
tr.
tr.
7
7
2i
60
a
Calculated as: (yield method B2yield method A)£100/yield method A.
The reaction was performed in melted p-nitrophenylisothiocyanate 2g.
b

7400
G. Abbiati et al. / Tetrahedron 59 (2003) 7397–7402
(Table 3, entry 1) whereas also in these new reaction
conditions and even at high temperatures, each attempt to
react 1a with alkylisocyanate 2f and isothiocyanate 2g
failed (Table 3, entries 2–3). On the other hand the yields of
cycloaddition reactions of 1b with all iso(thio)cyanates
(2d–f,i) tested were increased with a gain from 52 to 206%
(Table 3, entries 4–7).
Method B. In a sealed tube, under a nitrogen atmosphere, 1a
or 1b (0.200 g, 0.67 mmol) was added to the appropriate
heteroallene 2 (2 mL) in the presence of few crystals of
hydroquinone. The reaction mixture was stirred at 25–
1228C for 44–72 h until no more starting azadiene was
detectable by TLC. When liquid, the excess of hetero-
allene was removed by distillation at reduced pressure.
The crude product was purified by flash chromatography
over silica gel column (for yields, times and temperatures
see Table 3).
The presented study allowed us to confirm the good
reactivity of the ready available 2,4-diphenyl-1,3-diaza-
buta-1,3-dienes 1a and 1b toward heteroallenes. As a result,
we have shown that the [4þ2] cycloaddition reactions of 1a
and 1b with isocyanates and isothiocyanates led in
satisfactory yields to a great variety of 3,4-dihydro-1H-
[1,3,5]triazin-2-ones and 3,4-dihydro-1H-[1,3,5]triazin-2-
thiones.
3.2.1. 3,4,6-Triphenyl-1-p-tolyl-3,4-dihydro-1H-
[1,3,5]triazin-2-one (3a). Crystallised from methanol.
White solid. Mp: 1448C. IR (KBr) n¼1699, 1636 cm21
.
1H NMR: d¼2.24 (s, 3H, CH3), 6.46 (s, 1H, CH), 6.96 (m, 4H,
arom.), 7.12–7.62 (m, 15H, arom.) ppm. 13C NMR: d¼21.1,
77.1, 125.7, 126.2, 126.5, 127.9, 128.6, 128.8, 129.0, 129.1,
129.2, 129.3, 129.9, 134.2, 134.9, 137.3, 140.1, 14.0.4, 152.1,
155.3 ppm. C28H23N3O (417.50): calcd C 80.55, H 5.55, N
10.06; found C 80.67, H 5.58, N 10.10.
3. Experimental
3.1. General details
3.2.2. 3-(3-Chlorophenyl)-4,6-diphenyl-1-p-tolyl-3,4-
dihydro-1H-[1,3,5]triazin-2-one (3b). Eluent for chroma-
tography: PE/EtOAc (8:2). Pale yellow solid. Mp: 738C. IR
(KBr) n¼1698, 1645 cm21. 1H NMR: d¼2.24 (s, 3H, CH3),
6.23 (s, 1H, CH), 6.91 (d, 3J¼8.4 Hz, 2H, arom., AA0 part of
an AA0BB0 system), 6.98 (d, 3J¼8.4 Hz, 2H, arom., BB0 part
All chemicals and solvents are commercially available and
were used after distillation or treatment with drying agents.
Merck silica gel 60 F254 thin-layer plates were employed for
thin layer chromatography (TLC). Merck silica gel (230–
400 mesh) was employed for flash column chromatography.
Melting points, measured with a Stuart Scientific SMP3
apparatus, are uncorrected. Infrared spectra were recorded
on a FT-IR Perkin–Elmer Spectrum One spectrophotometer
using KBr tablets. Proton NMR spectra were recorded at
room temperature in CDCl3, on Varian-Gemini 200 at
200 MHz, with residual chloroform as the internal reference
(dH¼7.27 ppm). 13C NMR spectra were recorded at room
temperature in CDCl3, on the same spectrometer, at
50.3 MHz, with the central peak of chloroform as the
internal reference (dC¼77.3 ppm). The APT or DEPT
sequences were used to distinguish the methine and methyl
carbon signals from those due to methylene and quaternary
carbons. Two-dimensional NMR experiments (NOESY)
were used, where appropriate, to aid in the assignment of
signals in the proton spectra. Azadienes 1a,b were prepared
according to described method.12 The isocyanates 2a–f and
isothiocyanate 2g–j were purchased from standard chemi-
cal suppliers. The 6-Methyl-2,4-diphenyl-3,4-dihydro-quin-
azoline 524 and the 1,2-dihydro-1,3,5-triazine 726 are known
compounds. ‘PE’ refers to the fraction of petroleum ether
with boiling point of 40–608C. ‘EtOAc’ means ethyl
acetate. TEA means triethylamine.
of an AA0BB0 system), 7.16–7.60 (m, 14H, arom.) ppm. 13
C
NMR: d¼21.1, 76.8, 123.5, 126.1, 126.5, 126.6, 126.9,
127.8, 127.9, 128.2, 128.7, 128.8, 129.2, 130.0, 134.5,
134.6, 137.5, 139.0, 139.6, 141.5, 151.9, 155.3 ppm.
C28H22ClN3O (451.95): calcd C 74.41, H 4.91, N 9.30;
found C 74.31, H 4.90, N 9.34.
3.2.3. 4,6-Diphenyl-3-(toluene-4-sulfonyl)-1-p-tolyl-3,4-
dihydro-1H-[1,3,5]triazin-2-one (3c). Crystallised from
diisopropyl ether. White crystals. Mp: 145–1498C. IR
(KBr) n¼1715, 1645, 1326, 1171 cm21. 1H NMR: d¼2.21
3
(s, 3H, CH3), 2.37 (s, 3H, CH3), 6.85 (d, J¼8.1 Hz, 2H,
arom., AA0 part of an AA0BB0 system), 6.87 (d, 3J¼8.1 Hz,
2H, arom., BB0 part of an AA0BB0 system), 7.11 (s, 1H, CH),
7.17 (m, 4H, arom.), 7.27 (m, 3H, arom.), 7.36 (m, 4H,
arom.), 7.64 (d, 3J¼8.4 Hz, 2H, arom.), 7.88 (m, 1H,
arom.) ppm. 13C NMR: d¼21.2, 21.7, 73.5, 126.4, 128.0,
128.5, 129.0, 129.2, 129.4, 129.9, 130.1, 131.4, 133.4,
133.7, 135.0, 135.5, 138.1, 138.6, 144.9, 149.4, 154.2 ppm.
C29H25N3O3S (495.59): calcd C 70.28, H 5.08, N 8.48;
found C 70.40, H 5.02, N 8.45.
3.2.4. 3-Benzyl-4,6-diphenyl-1-p-tolyl-3,4-dihydro-1H-
[1,3,5]triazin-2-one (3d). Eluent for chromatography: PE/
TEA (8:2). White solid. Mp: 140–1438C. IR (KBr) n¼1692,
3.2. Reactions of azadienes 1 with heteroallenes 2
1648 cm21
.
1H NMR: d¼2.27 (s, 3H, CH3), 3.90 (d,
Method A. In a sealed tube, under a nitrogen atmosphere,
the appropriate heteroallene 2 (1.34 mmol) was added to a
solution of 1a or 1b (0.200 g, 0.67 mmol) in dry benzene
(5 mL) in the presence of few crystals of hydroquinone. The
reaction mixture was stirred at 25–1108C for 1–120 h until
no more starting azadiene was detectable by TLC. The
solvent was then removed in vacuum. The crude product
was purified by crystallisation or by flash chromatography
over silica gel column (for yields, times and temperatures
see Tables 1 and 2).
2J¼15.4 Hz, 1H, CH2), 5.37 (d, 2J¼15.4 Hz, 1H, CH2), 6.01
(s, 1H, CH), 7.01 (m, 4H, arom.), 7.14–7.50 (m, 15H,
arom.) ppm. 13C NMR: d¼21.1, 48.4, 74.2, 126.5, 127.8,
127.9, 128.4, 128.7, 128.8, 128.9, 129.0, 129.1, 129.2,
129.6, 134.6, 135.2, 136.3, 137.3, 139.7, 153.1, 154.5 ppm.
C29H25N3O (431.53): calcd C 80.72, H 5.84, N 9.74; found
C 80.60, H 5.86, N 9.77.
3.2.5. 6-Methyl-2,4-diphenyl-4H-quinazoline-3-carboxylic
acid benzylamide (4d). Eluent for chromatography: PE/TEA

G. Abbiati et al. / Tetrahedron 59 (2003) 7397–7402
7401
(8:2). White crystals. Mp: 150–1568C. IR (KBr) n¼3256,
1659, 1541 cm21. 1H NMR: d¼2.40 (s, 3H, CH3), 4.19 (dd,
3.2.10. 1-Benzyl-4,6-diphenyl-3-(toluene-4-sulfonyl)-3,4-
dihydro-1H-[1,3,5]triazin-2-one (6c). Eluent for chroma-
tography: PE/EtOAc (9:1). Yellow solid. Mp: 139–1418C.
3
2
2J¼14.5 Hz, J¼4.7 Hz, 1H, CH2), 4.27 (dd, J¼14.5 Hz,
3J¼5.9 Hz,1H,CH2),4.49(bm,1H,NH, exchangewithD2O),
6.70 (s, 1H, H4), 6.77 (m, 2H, arom.), 7.06 (s, 1H, H5), 7.10–
7.50 (m, 13H, arom.), 7.60 (m, 2H, arom.) ppm. 13C NMR:
d¼21.5, 45.6, 56.4, 125.6, 127.4, 127.5, 127.6, 127.9, 128.1,
128.5, 128.7, 128.8, 129.2, 129.7, 131.3, 135.9, 137.6, 137.7,
139.8, 140.9, 150.7, 154.9, 156.8 ppm. C29H25N3O (431.53):
calcd C 80.72, H 5.84, N 9.74; found C 80.72, H 5.82, N 9.76.
IR (KBr) n¼1690, 1632, 1360, 1180 cm21
.
1H NMR:
2
d¼2.46 (s, 1H, CH3), 4.37 (d, J¼15.4 Hz, 1H, CH2), 5.13
(d, 2J¼15.4 Hz, 1H, CH2), 6.42 (d, 3J¼7.3 Hz, 2H, arom.),
3
3
6.94 (dd, J¼7.3, 7.7 Hz, 2H, arom.), 7.06 (d, J¼7.3 Hz,
1H, arom.), 7.12 (s, 1H, CH), 7.22–7.52 (m, 11H, arom.),
3
7.84 (d, J¼8.4 Hz, 2H, arom) ppm. 13C NMR: d¼21.8,
48.1, 72.7, 126.3, 127.5, 127.7, 128.3, 128.4, 128.6, 128.8,
129.2, 129.4, 130.6, 133.2, 135.7, 135.8, 138.4, 145.1,
149.9, 155.4 ppm (one signal obscured). C29H25N3O3S
(495.59): calcd C 70.28, H 5.08, N 8.48; found C 70.38,
H 5.04, N 8.45.
3.2.6. 6-Methyl-2,4-diphenyl-4H-quinazoline-3-car-
boxylic acid cyclohexylmethylamide (4e). Eluent for
chromatography: PE/EtOAc (8:2). White crystals. Mp:
1458C. IR (KBr) n¼3292, 1654, 1543 cm21
.
1H NMR:
d¼0.70–2.80 (m, 10H, CH2 cyclohexyl), 2.39 (s, 3H, CH3),
3.51 (m, 1H, CH cyclohexyl), 4.17 (bd, 3J¼8.2 Hz, 1H, NH,
exchange with D2O), 6.64 (s, 1H, H4), 7.05 (s, 1H, H5),
7.20–7.59 (m, 10H, arom.), 7.61 (m, 2H, arom.) ppm. 13C
NMR: d¼21.4, 24.4, 24.5, 25.4, 32.1, 33.1, 49.9, 55.9,
125.3, 127.2, 127.5, 127.8, 127.9, 128.3, 128.6, 128.9,
129.4, 131.1, 135.9, 137.3, 139.7, 141.1, 150.8, 153.8 ppm.
C29H31N3O (437.58): calcd C 79.60, H 7.14, N 9.60; found
C 79.68, H 7.16, N 9.55.
3.2.11. 1,3-Dibenzyl-4,6-diphenyl-3,4-dihydro-1H-
[1,3,5]triazin-2-one (6d). Eluent for chromatography: PE/
EtOAc (95:5). White solid. Mp: 138–1408C. IR (KBr)
1
2
n¼1682, 1654 cm21. H NMR: d¼3.81 (d, J¼15.4 Hz,
1H, CH2), 4.59 (d, 2J¼15.4 Hz, 1H, CH2), 5.23 (d,
2J¼15.4 Hz, 1H, CH2), 5.39 (d, 2J¼15.4 Hz, 1H, CH2),
5.91 (s, 1H, CH), 6.80 (m, 2H, arom.), 7.11–7.50 (m, 18H,
arom.) ppm. 13C NMR: d¼43.3, 74.0, 126.6, 127.4, 127.8,
127.9, 128.1, 128.3, 128.4, 128.5, 128.6, 128.7, 128.8,
130.1, 134.4, 136.4, 137.6, 139.4, 153.4, 155.4 ppm.
C29H25N3O (431.53): calcd C 80.72, H 5.84, N 9.74;
found C 80.82, H 5.85, N 9.74.
3.2.7. 6-Methyl-2,4-diphenyl-4H-quinazoline-3-car-
boxylic acid propylamide (4f). Eluent for chromatography:
PE/EtOAc (9:1). White crystals. Mp: 1568C. IR (KBr)
n¼3270, 1658, 1542 cm21
.
1H NMR: d¼0.54 (t,
3.2.12. 1-Benzyl-3-cyclohexylmethyl-4,6-diphenyl-3,4-
dihydro-1H-[1,3,5]triazin-2-one (6e). Eluent for chroma-
tography: PE/EtOAc (95:5). White solid. Mp: 1298C. IR
3J¼7.5 Hz, 3H, CH3–CH2–CH2), 1.14 (sexs., J¼7.5 Hz,
2H, CH3–CH2–CH2), 2.90 (m, 1H, CH3–CH2–CH2), 3.10
(m, 1H, CH3–CH2–CH2), 4.25 (bm, 1H, NH, exchange
with D2O), 6.65 (s, 1H, H4), 7.05 (s, 1H, H5), 7.20–7.50 (m,
10H, arom.), 7.64 (m, 2H, arom.) ppm. 13C NMR: d¼11.8,
21.2, 22.4, 40.4, 56.0, 125.3, 127.2, 127.7, 127.9, 128.3,
128.6, 128.9, 129.4, 131.2, 131.3, 135.7, 137.4, 139.7,
140.9, 150.7, 154.7 ppm. C25H25N3O (383.49): calcd C
78.30, H 6.57, N 10.96; found C 78.52, H 6.54, N 10.92.
3
1
(KBr) n¼1671, 1647 cm21. H NMR: d¼0.90–2.01 (m,
10H, CH2 cyclohexyl), 4.27 (m, 1H, CH cyclohexyl), 4.42
2
(d, 2J¼14.7 Hz, 1H, CH2), 5.19 (d, J¼14.7 Hz, 1H, CH2),
6.04 (s, 1H, CH), 6.78 (m, 2H, arom.), 7.02–7.46 (m, 13H,
arom.) ppm. 13C NMR: d¼25.5, 26.0, 26.1, 31.1, 31.5, 48.6,
49.4, 55.4, 126.4, 127.5, 128.2, 128.4, 128.5, 128.6, 128.8,
128.9, 130.7, 137.3, 141.1, 152.9, 157.0 ppm (one signal
obscured). C29H31N3O (437.58): calcd C 79.60, H 7.14, N
9.60; found C 79.52, H 7.18, N 9.63.
3.2.8. 1-Benzyl-3,4,6-triphenyl-3,4-dihydro-1H-
[1,3,5]triazin-2-one (6a). Eluent for chromatography: PE/
TEA (9:1). White solid. Mp: 127–1298C. IR (KBr) n¼1678,
3.2.13. 1-Benzyl-4,6-diphenyl-3-propyl-3,4-dihydro-1H-
[1,3,5]triazin-2-one (6f). Eluent for chromatography: PE/
TEA (95:5). Yellow solid. Mp: 129–1338C. IR (KBr)
1
2
1659, 1595 cm21. H NMR: d¼4.49 (d, J¼15.0 Hz, 1H,
CH2), 5.29 (d, 2J¼15.0 Hz, 1H, CH2), 6.34 (s, 1H, CH), 6.90
(d, 3J¼8.1 Hz, 2H, arom.), 7.10–7.51 (m, 18H, arom.) ppm.
13C NMR: d¼48.4, 76.2, 125.1, 126.2, 126.3, 127.3, 128.1,
128.3, 128.5, 128.7, 128.8, 129.1, 130.3, 133.7, 137.1,
139.9, 140.5, 152.7, 155.9 ppm (one signal obscured).
C28H23N3O (417.50): calcd C 80.55, H 5.55, N 10.06;
found C 80.29, H 5.52, N 10.09.
1
3
n¼1681, 1526 cm21. H NMR: d¼0.94 (t, J¼7.3 Hz, 3H,
CH3–CH2–CH2), 1.66 (m, 2H, CH3–CH2–CH2), 2.85 (m,
1H, CH3–CH2–CH2), 3.85 (m, 1H, CH3–CH2–CH2), 4.49
(d, 2J¼15.0 Hz, 1H, CH2), 5.19 (d, J¼15.0 Hz, 1H, CH2),
2
5.96 (s, 1H, CH), 6.78 (m, 2H, arom.), 7.02–7.50 (m, 13H,
arom.) ppm. 13C NMR: d¼11.4, 21.2, 47.6, 48.0, 74.9,
126.3, 127.3, 128.3, 128.6, 128.8, 129.3, 134.4, 137.7,
140.1, 153.2, 155.7 ppm (two signals obscured).
C25H25N3O (383.49): calcd C 78.30, H 6.57, N 10.96;
found C 78.42, H 6.59, N 11.00.
3.2.9. 1-Benzyl-3-(3-chlorophenyl)-4,6-diphenyl-3,4-
dihydro-1H-[1,3,5]triazin-2-one (6b). Eluent for chroma-
tography: PE/TEA (95:5). White solid. Mp: 132–1348C. IR
1
(KBr) n¼1689, 1645, 1591 cm21. H NMR: d¼4.49 (d,
2J¼15.0 Hz, 1H, CH2), 5.27 (d, 2J¼15.0 Hz, 1H, CH2), 6.33
(s, 1H, CH), 6.67 (d, 3J¼7.0 Hz, 2H, arom.), 7.00–7.50 (m,
17H, arom.) ppm. 13C NMR: d¼48.5, 76.2, 122.8, 125.2,
126.2, 126.3, 127.4, 128.0, 128.3, 128.5, 128.7, 128.9,
129.9, 130.4, 133.8, 134.5, 136.9, 139.4, 141.6, 152.5,
155.9 ppm (one signal obscured). C28H22ClN3O (451.95):
calcd C 74.41, H 4.91, N 9.30; found C 74.30, H 4.89, N
9.33.
3.2.14. 1-Benzyl-3-(4-nitro-phenyl)-4,6-diphenyl-3,4-
dihydro-1H-[1,3,5]triazin-2-thione (6g). Eluent for chro-
matography: PE/TEA (95:5). Yellow solid. Mp: 144–
1488C. IR (KBr) n¼1645, 1363 cm21. 1H NMR: d¼4.77 (d,
2J¼15.0 Hz, 1H, CH2), 6.08 (d, 2J¼15.0 Hz, 1H, CH2), 6.34
3
(s, 1H, CH), 6.48 (d, J¼7.0 Hz, 2H, arom.), 6.94 (m, 2H,
arom.), 7.09 (m, 1H, arom.), 7.30–7.49 (m, 8H, arom.), 7.59
(d, J¼9.2 Hz, 2H, arom., AA part of an AA BB system),
0
0
0
3

7402
G. Abbiati et al. / Tetrahedron 59 (2003) 7397–7402
8.23 (d, 3J¼9.2 Hz, 2H, arom., BB0 part of an AA0BB0
system) ppm. 13C NMR: d¼53.5, 76.9, 124.6, 126.5, 127.4,
128.0, 128.2, 128.5, 128.7, 129.0, 129.1, 130.8, 133.5,
135.9, 138.2, 146.2, 149.4, 154.4, 180.8 ppm (one signal
obscured). C28H22N4O2S (478.57): calcd C 70.27, H 4.63, N
11.71; found C 70.39, H 4.66, N 11.70.
Kaerlein, C. P. Chem. Ztg. 1984, 108, 209–210. (b) Burger,
K.; Huber, E.; Kahl, T.; Partscht, H.; Ganzer, M. Synthesis
1988, 44–49. (c) Burger, K.; Penninger, S. Synthesis 1978,
524–526.
12. (a) Sharma, A. K.; Mazumdar, S. N.; Mahajan, M. P.
Tetrahedron Lett. 1993, 34, 7961–7964. (b) Sharma, A. K.;
Mazumdar, S. N.; Mahajan, M. P. J. Chem. Soc., Perkin Trans.
1 1997, 3065–3070. (c) Sharma, A. K.; Hundal, G.; Obrai, S.;
Mahajan, M. P. J. Chem. Soc., Perkin Trans. 1 1999, 615–619.
13. (a) Matsuda, I.; Yamamoto, S.; Ishii, Y. J. Chem. Soc., Perkin
Trans. 1 1976, 1528–1532. (b) Mazumdar, S. N.; Ibnusaud, I.;
Mahajan, M. P. Tetrahedron Lett. 1986, 27, 5875–5876. (c)
3.2.15. 1-Benzyl-3,4,6-triphenyl-3,4-dihydro-1H-
[1,3,5]triazin-2-thione (6h). Eluent for chromatography:
PE/EtOAc (95:5). White solid. Mp: 1468C. IR (KBr)
1
2
n¼1641, 1363 cm21. H NMR: d¼4.75 (d, J¼15.0 Hz,
1H, CH2), 6.17 (d, 2J¼15.0 Hz, 1H, CH2), 6.32 (s, 1H, CH),
3
˝
Luthardt, P.; Wurthwein, E. U. Tetrahedron Lett. 1988, 29,
6.25 (d, J¼7.0 Hz, 2H, arom.), 6.97 (m, 2H, arom.), 7.10
(m, 1H, arom.), 7.29–7.45 (m, 15H, arom.) ppm. 13C NMR:
d¼53.6, 77.4, 126.8, 127.4, 127.7, 128.1, 128.3, 128.5,
128.7, 128.8, 129.0, 129.3, 129.5, 130.6, 134.1, 13.6, 139.0,
144.3, 154.5, 180.9 ppm. C28H23N3S (433.57): calcd C
77.57, H 5.35, N 9.69; found C 77.68, H 5.38, N 9.64.
921–924. (d) Ibnusaud, I.; Padma Malar, E. J.; Sundaram, N.
Tetrahedron Lett. 1990, 31, 7357–7358. (e) Singh, S. P.;
Mahajan, A. R.; Prajapati, D.; Sandhu, J. S. Synthesis 1991,
1026–1028. (f) Mazumdar, S. N.; Mahajan, M. P. Tetrahedron
1991, 47, 1473–1484. (g) Mazumdar, S. N.; Mukherjee, S.;
Sharma, A. K.; Sengupta, D.; Mahajan, M. P. Tetrahedron
1994, 50, 7579–7587. (h) Dey, P. D.; Sharma, A. K.; Rai,
S. N.; Mahajan, M. P. Tetrahedron 1995, 51, 7459–7468. (i)
Sharma, A. K.; Mahajan, M. P. Heterocycles 1995, 40,
787–800. (j) Sharma, A. K.; Mahajan, M. P. Tetrahedron
1997, 40, 13841–13854. (k) Dey, P. D.; Sharma, A. K.;
Bharatam, P. V.; Mahajan, M. P. Tetrahedron 1997, 40,
13829–13840. (l) Sharma, A. K.; Jayakumar, S.; Mahajan,
M. P. Tetrahedron Lett. 1998, 39, 7205–7208. (m) Mukherjee,
S.; Mazumdar, S. N.; Sharma, A. K.; Mahajan, M. P.
Heterocycles 1998, 47, 933–950. (n) Landreau, C.; Deniaud,
D.; Reliquet, F.; Reliquet, A.; Meslin, J. C. Heterocycles 2000,
53, 2667–2678. (o) Arai, S.; Sakurai, T.; Asakura, H.; Fuma,
S.; Shioiri, T.; Aoyama, T. Heterocycles 2001, 2283, 2288. (p)
Sharma, A. K.; Jayakumar, S.; Hundal, M. S.; Mahajan, M. P.
J. Chem. Soc., Perkin Trans. 1 2002, 6, 774–784.
14. Rossi, E.; Abbiati, G.; Pini, E. Tetrahedron 1997, 53,
14107–14114.
3.2.16. 1,3-Dibenzyl-4,6-diphenyl-3,4-dihydro-1H-
[1,3,5]triazin-2-thione (6i). Eluent for chromatography:
PE/EtOAc (95:5). Yellowish oil. IR (KBr) n¼1643,
1
2
1371 cm21. H NMR: d¼4.36 (d, J¼15.0 Hz, 1H, CH2),
2
2
4.71 (d, J¼15.0 Hz, 1H, CH2), 6.10 (d, J¼15.0 Hz, 1H,
CH2), 6.12 (s, 1H, CH), 6.32 (d, 2J¼15.0 Hz, 1H, CH2), 6.53
3
(d, J¼7.0 Hz, 2H, arom.), 6.92 (m, 2H, arom.), 7.08 (m,
1H, arom.), 7.22–7.44 (m, 15H, arom.) ppm. 13C NMR:
d¼53.9, 55.7, 73.3, 126.4, 127.3, 128.0, 128.1, 128.2, 128.3,
128.6, 128.7, 128.8, 129.0, 129.1, 130.5, 134.1, 135.7,
136.9, 138.7, 154.9, 180.9 ppm. C29H25N3S (447.60): calcd
C 77.82, H 5.63, N 9.39; found C 77.74, H 5.66, N 9.44.
References
1. For some recent reviews see: (a) Jayakumar, S.; Ishar, M. P. S.;
Mahajan, M. P. Tetrahedron 2002, 58, 379–471. (b)
Barluenga, J.; Tomas, M. Synthesis of Heterocycles from
Azadienes. In Advances in Heterocyclic Chemistry. Katritzky,
A. R., Ed.; Academic: New York, 1993; pp 60–80. (c) Boger,
D. L. Tetrahedron 1983, 39, 2869–2939.
15. Rossi, E.; Abbiati, G.; Pini, E. Tetrahedron 1999, 55,
6961–9670.
16. Abbiati, G.; Rossi, E. Tetrahedron 2001, 57, 7205–7212.
17. For a recent review see: Ozaki, S. Chem. Rev. 1972, 72,
457–496.
18. For a recent review see: Mukerjee, A. K.; Ashare, R. Chem.
Rev. 1991, 91, 1–24.
2. Morel, G.; Marchand, E.; Fouvaud, A.; Toupet, L. J. Org.
Chem. 1989, 54, 1185–1191.
19. Burger, K.; Wassmuth, U.; Forster, B.; Penninger, S.
Z. Naturforsch. B Anorg. Chem. Org. Chem. 1984, 39,
1442–1452.
3. Burger, K.; Penninger, S. Synthesis 1978, 526–528.
4. Jayakumar, S.; Ishar, M. P. S.; Mahajan, M. P. Tetrahedron
Lett. 1998, 39, 6557–6560.
20. (a) Barluenga, J.; Tomas, M.; Ballesteros, A.; Lopez, L. A.
Synthesis 1989, 3, 228–229. (b) Dalla Croce, P.; Ferraccioli,
R.; La Rosa, C. Heterocycles 1997, 45, 1309–1318. (c)
Landreau, C.; Deniaud, D.; Reliquet, A.; Reliquet, F.; Meslin,
J. C. J. Heterocycl. Chem. 2001, 38, 93–98.
5. Padma Malar, E. J.; Sundaram, N. Tetrahedron Lett. 1990, 31,
7357–7358.
`
6. (a) Barluenga, J.; Tomas, M.; Ballestreros, A.; Lopez, L. A.
Tetrahedron Lett. 1989, 30, 4573–4576. (b) Barluenga, J.;
`
Tomas, M.; Ballestreros, A.; Lopez, L. A. Heterocycles 1994,
37, 1109–1120.
21. Bartman, W. Chem. Ber. 1967, 100, 2938–2945.
22. Arnold, R. G.; Nelson, J. A.; Verbanc, J. J. Chem. Rev. 1957,
57, 47–76.
7. (a) Mazumdar, S. N.; Sharma, M.; Mahajan, M. P. Tetra-
hedron Lett. 1987, 28, 2641–2642. (b) Friot, C.; Reliquet, A.;
Reliquet, F.; Meslin, J. C. Synthesis 2000, 695–703.
8. Sain, B.; Singh, S. P.; Sandhu, S. Tetrahedron Lett. 1991, 38,
5151–5152.
23. Abdel-Rahman, M. A. Synth. Commun. 1993, 23, 1427–1436.
24. Rossi, E.; Celentano, G.; Stradi, R.; Strada, A. Tetrahedron
Lett. 1990, 31, 903–906. (b) Rossi, E.; Calabrese, D.; Farma,
F. Tetrahedron 1991, 47, 5819–5834.
9. Sain, B.; Singh, S. P.; Sandhu, S. Tetrahedron 1992, 48,
4567–4578.
25. Tennant, G. In Comprensive Organic Chemistry. Barton, D.,
Ollis, W. D., Eds.; Pergamon: Oxford, 1979; pp 513–527.
26. Rossi, E.; Abbiati, G.; Nava, D. Heterocycles 1999, 51,
1401–1407.
10. Mazumdar, S. N.; Mahajan, M. P. Tetrahedron Lett. 1990, 31,
4215–4218.
11. (a) Burger, K.; Partscht, H.; Huber, E.; Gieren, A.; Hubner, T.;