Heterocyclization of functionalized heterocumulenes with C,N- and C,O-binucleophiles: VI. Synthesis of carbofused 2,3-dihydro-1,3-oxazin-4-ones and 3,4-dihydro-1,3-oxazin-2-ones

Article abstract of DOI:10.1134/S1070428007020170

Condensations of 1-phenyl-2,2,2-trifluoro-1-chloroethyl isocyanate and 1-chlorobenzyl isocyanate with cyclic 1,3-diketones yield respectively carbofused 2,3-dihydro-1,3-oxazin-4-ones and 3,4-dihydro-1,3-oxazin-2-ones.

Full text of DOI:10.1134/S1070428007020170

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2007, Vol. 43, No. 2, pp. 256−262. © Pleiades Publishing, Ltd. 2007.
Original Russian Text © M.B. Vovk, V.A. Sukach, N.G. Chubaruk, A.N. Chernega, A.V. Bol’but , 2007, published in Zhurnal Organicheskoi Khimii,
2007, Vol. 43, No. 2, pp. 264−270.
Heterocyclization of Functionalized Heterocumulenes
with C,N- and C,O-Binucleophiles: VI.* Synthesis of Carbofused
2,3-Dihydro-1,3-oxazin-4-ones and 3,4-Dihydro-1,3-oxazin-2-ones
M. B. Vovk, V. A. Sukach, N. G. Chubaruk,A. N. Chernega, andA. V. Bol’but
Institute of Organic Chemistry, National Academy of Sciences of the Ukraine, Kiev, 02094 Ukraine
e-mail: mvovk@i.com.ua
Received July 18, 2005
Abstract—Condensations of 1-phenyl-2,2,2-trifluoro-1-chloroethyl isocyanate and 1-chlorobenzyl isocyanate with
cyclic 1,3-diketones yield respectively carbofused 2,3-dihydro-1,3-oxazin-4-ones and 3,4-dihydro-1,3-oxazin-2-ones.
DOI: 10.1134/S1070428007020170
case an isomerization was observed of N-alkylidene-
carbamates into 1-aryloxyalkyl isocyanates that under-
went cyclization into 2,3-dihydrobenz[1,3]oxazin-4-ones.
In event of more electron-donor dialkylamino group no
thermal rearrangement occurred with the corresponding
N-alkylidenecarbamates, and isomeric 3,4-dihydro-
benz[1,3]oxazin-2-ones were obtained. We established
also that dimedone (5,5-dimethylcyclohexane-1,3-dione)
cleanly reacted both with isocyanates I [7] and their ana-
logs, N-(1-aryl-2,2,2-trifluoro-1-chloro)-ethyl-N’-aryl-
carbodiimides [8] in the presence of triethylamine giving
respectively carbofused 2,3-dihydro-1,3-oxazin-4-ones and
their 4-arylimino derivatives. Therewith the target prod-
ucts form along essentially different pathways, indicating
the importance of the nature of the 1,3-bielectrophilic re-
agent.
1-Aryl-2,2,2-trifluoro-1-chloroethyl isocyanates I that
we have investigated systematically for the last 25 years
exhibit pronounced bielectrophilic properties and are
capable to undergo cyclocondensation with various
binucleophilic reagents forming partially hydrogenated
heterocyclic systems. The high regioselectivity of these
processes combined with the possibility to monitor their
course using 19F NMR spectra show that compounds I
can be convenient synthetic equivalents of the 1,3-hetero-
diene synthon [–C=N–C=O]2+ [2]. At the same time
much less attention was paid to simpler in structure and
more available 1-chlorobenzylisocyanates II [3] appar-
ently due to their high reactivity and consequently to low
selectivity in condensations with binucleophiles.
Aiming at synthesis of new derivatives of 1,3-oxazines
we investigated in more detail cyclocondensation of two
types of 1-chloroalkyl isocyanates, 1-phenyl-2,2,2-tri-
fluoro-1-chloroethyl isocyanate (III), and 1-chlorobenzyl
isocyanates IVa–IVf with cyclic 1,3-diketones Va–Vc.
The published approaches to preparation of 3,4-dihydro-
1,3-oxazin-2-ones include reactions of vinyl isocyanate
with dimedone [9], of chlorosulfonyl isocyanate with
α,β-unsaturated ketones [10], and also of N-alkoxy-
carbonyliminium salts with propargyltrimethylsilane [11].
The examples of the synthesis of the regioisomeric het-
erocyclic system, 2,3-dihydro-1,3-oxazin-4-one, are lim-
We formerly developed a new approach to the syn-
thesis of fused 1,3-oxazine systems based on applying
[–C=N–C=O]2+ + [–C=C–O]2– synthon model of build-
ing up the oxazine ring. It was shown by an example of
reaction between compounds I and 3-alkoxyphenols [4,
5] and 3-dialkylaminophenols [6] that the structure of
compounds obtained depended essentially on the nature
of the nucleophilic component. In particular, in the former
* For communication V see [1].
256

HETEROCYCLIZATION OF FUNCTIONALIZED HETEROCUMULENES
257
Scheme 1.
IV,Ar = Ph (a), 2-FC6H4 (b), 3-BrC6H4 (c), 4-ClC6H4 (d), 4-BrC6H4 (e), 4-NO2C6H4 (f); V, VI, R = H (a), Me (b), R,R = (CH2)5 (c);
VII, R = H,Ar = Ph (a), 3-BrC6H4 (b); R = Me,Ar = Ph (c), 2-FC6H4 (d), 3-BrC6H4 (e), 4-ClC6H4 (f), 4-BrC6H4 (g), 4-NO2C6H4 (h);
R,R = (CH2)5,Ar = 2-FC6H4 (i), 4-ClC6H4 (j).
ited to reactions of Schiff bases with 2-diazo-1,3-cyclo-
pentane-dione [12] and Meldrum’s acid derivatives [13].
pounds of B type where further carbamoylation of the
hydroxy group of enol resulted in oxazines VIIa–VIIj.
Taking into consideration the data of previous studies in
the field of the chemistry of 1-func-tionalized isocyan-
ates [2] it is presumable that isocyanates IVa–IVf most
likely reacted with nonionized enols of diketones Va–Vc
in the tautomeric N-benzylidenecarba-moyl chloride form
leading to carbamoyl chlorides of C type. The latter are
able to easily eliminate nydrogen chloride converting into
intermediates of B type (Scheme 2).
It was established that isocyanate I reacted with
cyclohexanediones Va–Vc in toluene only in the pres-
ence of an organic base giving in high yields 2,3-dihydro-
1,3-oxazin-4-ones VIa–VIc. On the contrary, 1-chloro-
benzyl isocyanates IVa–IVf reacted with diketones Va–
Vc in toluene at room temperature without organic base
and in 73–84% yield formed regioisomeric 3,4-dihydro-
1,3-oxazin-2-ones VIIa–VIIj (Scheme 1). This reaction
is among the first successful examples of applying com-
pounds IV in heterocyclization.
The structure of regioisomeric 1,3-oxazin-4-ones VIa–
VIc and 1,3-oxazin-2-ones VIIa–VIIj was exactly proved
by a complex physicochemical investigation. The IR spec-
tra of the synthesizes dihydrooxazinones turned out to be
Obviously the different behavior of 1-chloroalkyl iso-
cyanates (III) and compounds IVa–IVf demonstrates
the crucial distinctions in the electrophilic character of
these reagents. The reaction of isocyanate III with 1,3-di-
ketones Va–Vc started exclusively in the presence in the
reaction mixture of an organic base (triethylamine) as-
sisting in formation of anion of the 1,3-dicarbonyl com-
pound, whose carbon atom suffered later the isocyanate
group attack. N-akylidene intermediate A formed under-
went fast cyclization inti compound VIa–VIc. More elec-
trophilic 1-chlorobenzyl isocyanates IVa–IVf possessing
pronounced alkylating properties give intermediate com-
Scheme 2.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 2 2007

VOVK et al.
258
VIa–VIc appeared at 89–90 ppm as a quartet with a con-
2
stant JC–F 32–33 Hz. The unambiguous proof of com-
pounds VII structure was obtained by X-ray crystallog-
raphy by an example of chlorophenyl derivative VIIj. The
general view of molecule VIIj is presented on Fig.1.*
°
The main bond lengths (A) and bond angles (deg) are
as follows: O1–C1 1.395 (2), O1–C2 1.372 (2), O2–C1
1.198 (2), O3–C5 1.229 (2), N1–C1 1.335 (2), N1–C4 1.462
(2), N1–H1 0.88 (2), C2–C3 1.337 (2), C2–C8 1.492 (3),
C3–C4 1.505 (2), C3–C5 1.459 (3), C4–C9 1.521 (2), C4–
H2 0.965 (18), C5–C6 1.504 (3), C6–C7 1.540 (3), C7–C8
1.538 (3); C1O1C2121.12 (14), C1N1C4128.45 (16),
C1N1H1114.0 (14), C4N1H1116.5 (13), O1C1O2117.37
(17), O1C1N1116.03 (16), O2C1N1126.59 (18),
O1C2C3122.48 (16), O1C2C8111.93 (14), C3C2C8125.58
(17), C2C3C4121.64 (16), C2C3C5119.68 (16),
C4C3C5118.68 (15), N1C4C3108.60 (14), N1C4C9110.66
(15), C3C4C9112.75 (14), N1C4H2107.6 (10),
C3C4H2108.6 (10), C9C4H2108.4 (10), O3C5C3 121.15
(16), O3C5C6122.08 (17), C3C5C6116.75 (16),
C5C6C7113.80 (15), C6C7C8107.94 (16), C2C8C7113.36
(15). The central bicyclic system O1N1C1–8 is essentially
nonplanar: the deviations of atoms from the least-mean-
Fig. 1. General view of molecule of 4-(4-chlorophenyl)-4,8-
dihydrospiro(1,3-benzoxazine-7,1'-cyclohexane)-2,5(3H,6H)-
dione (VIIj).
sufficiently characteristic for their unambiguous attribu-
tion to a definite structural type. In the spectra of com-
pounds VIa–VIc amide fragment gave rise to absorption
bands at 1720–1730 cm–1 whereas the absorption band
of the carbamate carbonyl in the spectra of compounds
VIIa–VIIjappeared at 1765–1780 cm–1 [6]. In the 1H NMR
spectra of 3,4-dihydrooxazin-2-ones VIIa–VIIj singlets
from protons belonging to groups CH and NH were ob-
served in the regions 5.08–5.26 and 8.57–8.78 ppm re-
spectively. In the 19F NMR spectra of oxazines VIa–
VIc the fluorine atoms of the trifluoromethyl group ap-
peared in the region from –80.7 to –80.8 ppm indicating
the presence in the structure of the molecule of an
°
squares plane reach 0.406 A. Therewith the heterocycle
°
O1N1C1–4 is planar within 0.074 A, whereas the cyclic
system C2,3,5–8 exists in a conformation of a notably flat-
tened semiboat (modified Cremer−Pople parameters [14]
are S 0.19, ψ 29.7, θ 66.3 deg). Due to steric factors the
benzene ring C9–14 is virtually normal to the central bicy-
clic system (the corresponding dihedral angle amounts to
82.9 deg). The cyclohexane substituent has a common
chair conformation. The N1 atom has a trigonal plane
configuration of its bonds (the sum of the bond angles at
this atom is 359.0 deg). The conjugation between the
unshared electron pair of this atom and the π-system of
C1=O1 bond caused significant shortening of the formally
oxyaminal fragment [O–C(CF3)Ph–NH] [5]. In the 13
C
NMR spectra the signals of C4 atoms in the spectra of
compounds VIIa–VIIj were located in the region 49–52
ppm, and the signals belonging to C2 atoms of compounds
°
ordinary N1–C1 bond [1.335(2) A] compared to the val-
°
ues 1.43–1.45 A, characteristic of a pure ordinary bond
N(sp2)-C(sp2) [15, 16]. In the crystal the molecules of
compound VIIj are joined into an infinite chain by inter-
...
molecular hydrogen bonds N1–H1 O3 [N1–H1 0.88(2),
°
...
...
N1 O3 3.030(2), H1 O3 2.20(2) A, N1H1O3156(1) deg]
(Fig. 2).
Oxazin-2-ones VII contain a vinilog O-acylcarbamine
fragment possessing two electrophilic sites: C2 and C8a
atoms. At the attack on the C2 atom by nucleophiles like
ammonia or primary amines the opening of the oxazine
* The numbering of atoms is different from that used in the name of
the compound.
Fig. 2. Crystal packing of 4-(4-chlorophenyl)-4,8-dihydro-
spiro(1,3-benzoxazine-7,1'-cyclohexane)-2,5(3H,6H)-dione
(VIIj). The intermolecular hydrogen bond N –H O is
1
1
...
3
shown by a dotted line.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 2 2007

HETEROCYCLIZATION OF FUNCTIONALIZED HETEROCUMULENES
259
Scheme 2.
IX, R = 4-ClC6H4 (a), 4-MeOC6H4 (b); X, R = H,Ar = Ph (a), 4-ClC6H4 (b).
ring is expected to occur giving intermediates of D type
that are also intermediates in the synthesis of dihydro-
pyrimidinones VIII by Biginelli reaction [17]. We found,
that in no case after heating oxazines VII in ethanol with
free bases like ammonia, benzylamine or anisidine the
corresponding dihydropyrimidones of VIII type were iso-
lated. At the use of ammonium acetate or an aromatic
amine in the presence of 1 equiv of acetic acid we de-
tected by GC-MS procedure the formation of 3-arylamino-
5,5-di-methylcyclohex-2-en-1-ones IXa and IXb, and
hexa-hydroacridine-1,8-diones Xa and Xb that were also
isolated from the reaction mixture and identified in an
individual state. The scheme of these compounds forma-
tion contains at least two alternatives of transformations.
Presumably first the amino group attacks C2 atom, but
under the conditions of the process the arising intermedi-
ate D does not undergo cyclization into compounds of
VIII type and decomposes with elimination either of
urea (path a) or N-benzylideneurea (path b) giving as a
result compounds IXa and IXb, Xa and Xb (Scheme 3).
matic four-circle diffractometer Enraf-Nonius CAD-4
(CuKα-radiation, λ 1.54178 A, the ratio of scanning rates
°
2θ/ω 1.2, θmax. 60 deg, spherical segment 0 ≤ h ≤ 14, 0 ≤
k ≤ 8, –19 ≤ l ≤ 18). 2851 reflections were collected.
Crystals of compound VIIj monoclinic, a 12.722(4),
°
°
b 7.932(4), c 16.925(6) A, β 97.75(3) deg, V 1692.3 A3,
M 271.3, Z 4, dcalc 1.36 g/cm3, μ 21.4 cm–1, F(000) 570.6,
space group P21/C (N 14). The structure was solved by
the direct method and refined by the least-mean-squares
method in full-matrix anisotropic approximation using soft-
ware CRYSTALS [18]. Refining was performed with
the use of 2153 reflections with I > 3σ(I) (297 refined
parameters, 7.2 reflection per parameter). All hydrogen
atoms were revealed from the difference synthesis and
refined isotropically. The refining was performed apply-
ing the weight Chebyshev scheme [19] containing 5 pa-
rameters: 4.16, –2.29, 1.98, –0.74, and –0.87. The final
values of divergence factors are R 0.040 and RW 0.041,
GOF 0.991. The residual electron density from the dif-
°
ference Fourier series was 0.18 and –0.26 ε/A3. The
EXPERIMENTAL
extinction in the crystal was estimated by azimuthal scan-
ning [20]. The complete set of X-ray crystallographic data
for compound VIIj are deposited in the Cambridge Struc-
tural Database (CCDC 277102).
X-ray crystallographic investigation of a single crystal
of compound VIIj having spherical form, diameter 0.43
mm, was carried out at room temperature on an auto-
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VOVK et al.
260
IR spectra were recorded on a spectrophotometer
124.55 q (CF3, J 285 Hz), 127.27, 129.21, 131.27, 134.13
(Carom), 158.18, 177.55, 192.05 (C8a, C4, C5). 19F NMR
spectrum, δ, ppm: –80.81. Found, %:
C 63.05; H 5.25; N 3.60. C20H20F3NO3. Calculated, %:
C 63.32; H 5.31; N 3.69.
UR-20 from KBr pellets. 1H, 13C, and 19F NMR spectra
in DMSO-d6 were registered on a spectrometer Varian-
Gemini (299.95, 75.4, 282.2 MHz respectively), internal
references TMS (1H, 13C) and CCl3F (19F). 1-Phenyl-
2,2,2-trifluoro-1-chloroethyl isocyanate (III) and 1-
chlorobenzyl isocyanates IVa–IVf were prepared by pro-
cedures [21] and [3] respectively.
4-Aryl-4,6,7,8-tetrahydro-2H-1,3-benzoxazine-
2,5(3H)-diones VIIa–VIIj. To a solution of 5 mmol of
isocyanate IVa–IVf in 20 ml of anhydrous toluene was
added 5 mmol of diketone Va–Vc, and the mixture was
stirred for 24 h at room temperature. The separated pre-
cipitate was filtered off and recrystallized from a mixture
ethyl acetate–hexane, 2:1.
2-Aryl-2-trifluoromethyl-7,8-dihydrobenz-2H-
1,3-oxazine-4,5(3H,6H)-diones VIa–VIc. To a solu-
tion of 1.17 g (5 mmol) of isocyanate III in 20 ml of
anhydrous toluene was added 5 mmol of diketone Va–
Vc, and then at stirring was added within 1 h 0.7 ml
(5 mmol) of triethylamine in 10 ml of anhydrous toluene.
The reaction mixture was stirred for 4 h, the separated
precipitate was filtered off, washed with water, dried, and
recrystallized from ethanol.
4-Phenyl-4,6,7,8-tetrahydro-2H-1,3-benzoxa-
zine-2,5(3H)-dione (VIIa). Yield 73%, mp 150–152°C.
IR spectrum, cm–1: 3320 (NH), 1770, 1720, 1680 (C=O).
1H NMR spectrum, δ, ppm: 2.01 m (2H, CH2), 2.30 m
(2H, CH2), 2.60 m (2H, CH2), 5.09 s (1H, CH), 7.27 m
(5Harom), 8.62 s (1H, NH). 13C NMR spectrum, δ, ppm:
20.41, 26.78, 36.59 (3CH2), 52.32 (CH), 112.86 (C4a),
127.17, 128.26, 129.05, 142.79 (Carom), 147.97, 166.92,
195.47 (C8a, C2, C4). Found, %: C 68.99; H 5.33; N 5.71.
C14H13NO3. Calculated, %: C 69.12; H 5.39; N 5.76.
2-Trifluoromethyl-2-phenyl-7,8-dihydro-2H-1,3-
benzoxazine-4,5(3H,6H)-dione (VIa). Yield 71%,
mp 160–162°C. IR spectrum, cm–1: 3200, 3100 (NH),
1730 (C=O). 1H NMR spectrum, δ, ppm: 1.91 m (2Haliph),
2.17 m (1Haliph), 2.26 m (1Haliph), 2.71 m (2Haliph),
7.49 m (3Harom), 7.62 m (2Harom), 9.85 C (1H, NH).
13C NMR spectrum, δ, ppm: 19.46, 28.59, 37.94 (3CH2),
89.78 q (C2, J 32.5 Hz), 109.83 (C4a), 121.93 q (CF3,
J 285 Hz), 127.15, 129.33, 131.26, 133.97 (Carom), 158.23,
179.18, 192.27 (C8a, C4, C5). 19F NMR spectrum, δ, ppm:
–80.73. Found, %: C 57.61; H 3.80; N 4.62.
C15H12F3NO3. Calculated, %: C 57.88; H 3.89; N 4.50.
4-(3-Bromophenyl)-4,6,7,8-tetrahydro-2H-1,3-
benzoxazine-2,5(3H)-dione (VIIb).Yield 75%, mp 151–
153°C. IR spectrum, cm–1: 3330 (NH), 1770, 1730, 1680
(C=O). 1H NMR spectrum, δ, ppm: 2.01 m (2H, CH2),
2.32 m (2H, CH2), 2.61 m (2H, CH2), 5.11 s (1H, CH),
7.28 m (2Harom), 7.43 m (2Harom), 8.66 s (1H, NH).
13C NMR spectrum, δ, ppm: 20.35, 26.82, 36.55 (3CH2),
51.96 (CH), 112.12 (C4a), 122.12, 126.21, 130.20, 131.17,
131.36, 145.36 (Carom), 147.66, 167.33, 195.52 (C8a, C2,
C4). Found, %: C 52.32; H 3.81; N 4.28. C14H12BrNO3.
Calculated, %: C 52.20; H 3.75; N 4.35.
7,7-Dimethyl-2-trifluoromethyl-2-phenyl-7,8-
dihydro-2H-1,3-benzoxazine-4,5(3H,6H)-dione
(VIb). Yield 82%, mp 158–160°C [7]. IR spectrum, cm–1:
1
3210, 3100 (NH), 1730 (C=O). H NMR spectrum, δ,
ppm: 13C NMR spectrum, δ, ppm: 27.17, 27.37 (2CH3),
31.55 (C7), 41.06 (CH2), 51.32 (CH2), 88.99 q (C2,
J 32 Hz), 108.50 (C4a), 122.05 q (CF3, J 284 Hz), 126.76,
128.79, 130.79, 133.60 (Carom), 157.76, 177.34, 191.80
(C8a, C4, C5). 19F NMR spectrum, δ, ppm: –80.78. Found,
%: C 60.37; H 4.83; N 4.02. C17H16F3NO3. Calculated,
%: C 60.18; H 4.75; N 4.13.
7,7-Dimethyl-4-phenyl-4,6,7,8-tetrahydro-2H-
1,3-benzoxazine-2,5(3H)-dione (VIIc). Yield 82%,
mp 209–211°C. IR spectrum, cm–1: 3330 (NH), 1765,
1
1730, 1680 (C=O). H NMR spectrum, δ, ppm: 0.98 s
(3H, CH3), 1.08 s (3H, CH3), 2.20 m (2H, CH2), 2.49 m
(2H, CH2), 5.08 s (1H, CH), 7.25 m (3Harom), 7.30 m
(2Harom), 8.64 s (1H, NH). 13C NMR spectrum, δ, ppm:
27.50, 28.72 (2CH3), 32.62, 40.04 (2CH2), 50.32 (C7),
52.43 (CH), 111.85 (C4a), 127.17, 128.29, 129.05, 142.77
(Carom), 147.96, 164.95, 195.23 (C8a, C2, C4). Found, %:
C 71.20; H 6.44; N 5.03. C16H17NO3. Calculated, %:
C 70.83; H 6.32; N 5.16.
2-Trifluoromethyl-2-phenyl-7,8-dihydrospiro-
(1,3-benzoxazine-7,1'-cyclohexane)-4,5(3H,6H)-
dione (VIc). Yield 77%, mp 195–197°C. IR spectrum,
cm–1: 3210 (NH), 1725 (C=O). 1H NMR spectrum, δ,
ppm: 1.20–1.44 m (10Haliph), 2.12 d (1H, CHAHΒ, J 16.2
Hz), 2.30 d (1H, CHAHΒ, J 16.2 Hz), 2.74 m (2H, CH2),
7.49 m (3Harom), 7.61 m (2Harom), 9.90 C (1H, NH).
13C NMR spectrum, δ, ppm: 21.32, 25.95, 34.94, 35.45,
36.25, 50.05 (Caliph), 88.95 q (C2, J 33 Hz), 109.23 (C4a),
7,7-Dimethyl-4-(2-fluorophenyl)-4,6,7,8-tetra-
hydro-2H-1,3-benzoxazine-2,5(3H)-dione (VIId).
Yield 77%, mp 198–200°C. IR spectrum, cm–1: 3320
1
(NH), 1770, 1735, 1670 (C=O). H NMR spectrum, δ,
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HETEROCYCLIZATION OF FUNCTIONALIZED HETEROCUMULENES
261
79%, mp 120–122°C. IR spectrum, cm–1: 3330 (NH),
1770, 1680 (C=O). H NMR spectrum, δ, ppm: 0.98 s
ppm: 0.98 s (3H, CH3), 1.08 s (3H, CH3), 2.11 d (1H,
CHAH , J 16.0 Hz), 2.21 d (1H, CHAH , J 16.0 Hz),
2.49 m (2H, CH2), 5.25 s (1H, CH), 7.14 m (2Harom),
7.29 m (2Harom), 8.60 s (1H, NH). 13C NMR spectrum,
δ, ppm: 27.21, 28.82 (2CH3), 32.60, 40.02 (2CH2), 48.47
(C7), 50.25 (CH), 109.98 (C4a), 116.15, 124.94, 129.19,
130.47, 130.55, 147.64 (Carom), 159.74, 165.11, 195.12
(C8a, C2, C4). Found, %: C 66.21; H 5.52; N 4.92.
C16H16FNO3. Calculated, %: C 66.43; H 5.57; N 4.84.
Β
Β
1
(3H, CH3), 1.09 s (3H, CH3), 2.15 d (1H, CHAHΒ,
J 16.4 Hz), 2.23 d (1H, CHAHΒ, J 16.4 Hz), 2.49 m (2H,
CH2), 5.26 s (1H, CH), 7.55 d (2H, Harom, J 8.6 Hz),
8.19 d (2H, Harom, J 8.6 Hz), 8.78 s (1H, NH). 13C NMR
spectrum, δ, ppm: 27.58, 28.61 (2CH3), 32.62, 40.01
(2CH2), 50.22 (C7), 52.21 (CH), 110.85 (C4a), 124.29,
128.83, 147.51 (Carom), 147.72, 165.08, 195.23 (C8a, C2,
C4). Found, %: C 60.54; H 4.97; N 8.83. C16H16N2O5.
Calculated, %: C 60.76; H 5.10; N 8.86.
4-(3-Bromophenyl)-7,7-dimethyl-4,6,7,8-tetra-
hydro-2H-1,3-benzoxazine-2,5(3H)-dione (VIIe).
Yield 81%, mp 163–165°C. IR spectrum, cm–1: 3330
4-(2-Fluorophenyl)-4,8-dihydrospiro(1,3-
benzoxazine-7,1'-cyclohexane)-2,5(3H,6H)-dione
(VIIi). Yield 79%, mp 120–122°C. IR spectrum, cm–1:
3340 (NH), 1775, 1740, 1670 (C=O). 1H NMR spectrum,
δ, ppm: 1.28–1.40 m (10Haliph), 2.24 m (2H, CH2),
2.49 m (2H, CH2), 5.24 s (1H, CH), 7.14 m (2Harom),
7.28 m (2Harom), 8.57 s (1H, NH). 13C NMR spectrum,
δ, ppm: 21.45, 26.10, 35.20, 36.87, 37.74, 48.21 (Caliph),
48.43 (CH), 109.99 (C4a), 116.16, 124.95, 129.10, 130.40,
130.47, 147.67 (Carom), 159.73, 164.71, 194.89 (C8a, C2,
C4). Found, %: C 69.51; H 6.15; N 4.20. C19H20FNO3.
Calculated, %: C 69.29; H 6.12; N 4.25.
1
(NH), 1770, 1720, 1680 (C=O). H NMR spectrum, δ,
ppm: 0.99 s (3H, CH3), 1.08 s (3H, CH3), 2.17 d (1H,
CHAHΒ, J 16.4 Hz), 2.21 d (1H, CHAHΒ, J 16.4 Hz),
2.48 m (2H, CH2), 5.08 s (1H, CH), 7.28 m (2Harom),
7.40 m (2Harom), 8.66 s (1H, NH). 13C NMR spectrum,
δ, ppm: 27.56, 28.62 (2CH3), 32.66, 40.02 (2CH2), 50.26
(C7), 52.08 (CH), 111.09 (C4a), 122.09, 126.23, 130.24,
131.21, 131.41, 145.32 (Carom), 147.64, 165.85, 195.32
(C8a, C2, C4). Found, %: C 55.20; H 4.69; N 4.03.
C16H16BrNO3. Calculated, %: C 54.87; H 4.61; N 4.00.
7,7-Dimethyl-4-(4-chlorophenyl)-4,6,7,8-tetra-
hydro-2H-1,3-benzoxazine-2,5(3H)-dione (VIIf).
Yield 84%, mp 191–193°C. IR spectrum, cm–1: 3330
4-(4-Chlorophenyl)-4,8-dihydrospiro(1,3-
benzoxazine-7,1'-cyclohexane)-2,5(3H,6H)-dione
(VIIj). Yield 79%, mp 158–160°C. IR spectrum, cm–1:
3330 (NH), 1770, 1720, 1680 (C=O). 1H NMR spectrum,
δ, ppm: 1.29–1.50 m (10Haliph), 2.54 m (4H, 2CH2),
5.10 s (1H, CH), 7.28 d (2H, Harom, J 8.8 Hz), 7.35 d (2H,
Harom, J 8.8 Hz), 8.65 s (1H, NH). 13C NMR spectrum,
δ, ppm: 21.47, 21.52, 35.31, 35.59, 36.67, 37.75, 48.26
(Caliph), 51.98 (CH), 111.40 (C4a), 128.66, 129.18, 132.85,
141.71 (Carom), 147.76, 164.69, 195.01 (C8a, C2, C4). Found,
%: C 66.33; H 5.86; N 3.92. C19H20ClNO3. Calculated,
%: C 65.99; H 5.83; N 4.05.
1
(NH), 1770, 1720, 1680 (C=O). H NMR spectrum, δ,
ppm: 0.98 s (3H, CH3), 1.08 s (3H, CH3), 2.15 d (1H,
CHAHΒ, J 16.2 Hz), 2.21 d (1H, CHAHΒ, J 16.2 Hz),
2.49 m (2H, CH2), 5.10 s (1H, CH), 7.27 d (2H, Harom
,
J 8.7 Hz), 7.33 d (2H, Harom, J 8.7 Hz), 8.67 s (1H, NH).
13C NMR spectrum, δ, ppm: 27.04, 28.14 (2CH3), 32.09,
39.50 (2CH2), 49.76 (C7), 51.47 (CH), 110.87 (C4a),
128.52, 128.67, 132.34, 141.22 (Carom), 147.22, 164.56,
194.75 (C8a, C2, C4). Found, %: C 62.94; H 5.33; N 4.48.
C16H16ClNO3. Calculated, %: C 62.85; H 5.27; N 4.58.
4-(4-Bromophenyl)-7,7-dimethyl-4,6,7,8-tetra-
hydro-2H-1,3-benzoxazine-2,5(3H)-dione (VIIg).
Yield 80%, mp 195–196°C. IR spectrum, cm–1: 3320
3-Arylamino-5,5-dimethyl-2-cyclohexen-1-ones
IXa and IXb. To a solution of 1.35 g (5 mmol) of com-
pound VIIc in 30 ml of ethanol was added 10 mmol of an
appropriate substituted aniline, 0.6 ml (10 mmol) of ace-
tic acid, and the mixture was boiled for 10 h. The reac-
tion mixture was diluted with 60 ml of water, the sepa-
rated precipitate was filtered off, dried, and recrystal-
lized from a mixture ethyl acetate–hexane, 1:1.
1
(NH), 1765, 1720, 1680 (C=O). H NMR spectrum, δ,
ppm: 0.98 s (3H, CH3), 1.08 s (3H, CH3), 2.15 d (1H,
CHAHΒ, J 16.4 Hz), 2.21 d (1H, CHAHΒ, J 16.4 Hz),
2.49 m (2H, CH2), 5.09 s (1H, CH), 7.22 d (2H, Harom
,
J 8.8 Hz), 7.50 d (2H, Harom, J 8.8 Hz), 8.66 s (1H, NH).
13C NMR spectrum, δ, ppm: 27.58, 28.65 (2CH3), 32.60,
40.06 (2CH2), 50.30 (C7), 52.05 (CH), 111.36 (C4a),
121.38, 129.37, 131.95, 142.15 (Carom), 147.72, 165.08,
195.23 (C8a, C2, C4). Found, %: C 54.68; H 4.65; N 3.87.
C16H16BrNO3. Calculated, %: C 54.87; H 4.61; N 4.00.
5,5-Dimethyl-3-(4-chlorophenylamino)-2-cyclo-
hexen-1-one (IXa). Yield 34%, mp 205–207°C [22].
5,5-Dimethyl-3-(4-methoxyphenylamino)-2-
cyclohexen-1-one (IXb). Yield 30%, mp 186–188°C
[22].
7,7-Dimethyl-4-(4-nitrophenyl)-4,6,7,8-tetra-hy-
dro-2H-1,3-benzoxazine-2,5(3H)-dione (VIIh). Yield
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 2 2007

VOVK et al.
262
9-Aryl-3,3,6,6-tetramethyl-3,4,6,7,9,10-
9. Prager, R.H. and Were, S.T., Aust. J. Chem., 1991, vol. 44,
p. 1635.
10. Claub, K., Friedrich, H.-J., and Jensen, H., Lieb. Ann., 1974,
p. 561.
11. Esch, P.M., Hiemstra, H., and Speckamp, W.N., Tetrahe-
dron, 1992, vol. 48, p. 3445.
12. Stetter, H. and Kiehs, K., Chem. Ber., 1965, vol. 98, p. 2099.
13. Yamamoto, Y., Watanabe, Y., and Ohnishi, S., Chem. Pharm.
Bull., 1987, vol. 35, p. 1860.
14. Zefirov, N.S. and Palyulin, V.A., Dokl. Akad.Nauk SSSR,
1980, vol. 252, p. 111.
15. Burke-Laing, M. and Laing, M., Acta Cryst. B, 1976, vol. 32,
p. 3216.
16. Allen, F.H., Kennard, O., Watson, D.G., Brammer, L., Or-
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1987, p. 51.
hexahydro-1,8(2H,5H)-acridinediones Xa and Xb.
To a solution of 5 mmol of compound VIIc or VIIf in 30
ml of ethanol was added 1.54 g (20 mmol) of ammonium
acetate, and the mixture was boiled for 10 h. The reac-
tion mixture was diluted with 60 ml of water, the sepa-
rated precipitate was filtered off, dried, and recrystal-
lized from a mixture ethanol–water, 2:1.
3,3,6,6-Tetramethyl-9-phenyl-3,4,6,7,9,10-
hexahydro-1,8(2H,5H)-acridinedione (Xa). Yield
38%, mp 290–292°C [23].
3,3,6,6-Tetramethyl-9-(4-chlorophenyl)-
3,4,6,7,9,10-γεqCahydro-1,8(2H,5H)-acridinedione
(Xb). Yield 40%, mp 298–300°C [23].
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