Reactions of 4-oxo-1,3-benzoxazinium perchlorates with sodium borohydride

Article abstract of DOI:10.1134/S1070363209070184

Reduction of 4-oxo-1,3-benzoxazinium perchlorates with sodium borohydride depending on the structure of starting salt and the reaction conditions leads to different products. 2-Alkyl- and 2-phenylsubstituted salts react with sodium borohydride to give 2,3

Full text of DOI:10.1134/S1070363209070184

ISSN 1070-3632, Russian Journal of General Chemistry, 2009, Vol. 79, No. 7, pp. 1509–1512. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © N.I. Vikrishchuk, Yu.I. Ryabukhin, A.D. Vikrishchuk, 2009, published in Zhurnal Obshchei Khimii, 2009, Vol. 79, No. 7, pp. 1152–
1155.
Reactions of 4-Oxo-1,3-Benzoxazinium Perchlorates
with Sodium Borohydride
N. I. Vikrishchuka, Yu. I. Ryabukhinb, and A. D. Vikrishchukc
a Southern Federal University, ul. Zorge 7, Rostov-on-Don, 344090 Russia
e-mail: natvi2004@mail.ru
b Astrakhan State Technical University, Astrakhan, Russia
c Southern Scientific Center of Russian Academy of Sciences, Rostov-on-Don, Russia
Received January 22, 2009
Abstract—Reduction of 4-oxo-1,3-benzoxazinium perchlorates with sodium borohydride depending on the
structure of starting salt and the reaction conditions leads to different products. 2-Alkyl- and 2-
phenylsubstituted salts react with sodium borohydride to give 2,3-dihydro-4-oxo-1,3-benzoxazines. 2-
Arylvinyl- and 2-heterylvinyl-substituted perchlorates either form 4-oxo-1,3-benzoxazines or undergo
hydrogenation to aryl- or heterylethyldihydrobenzoxazinones.
DOI: 10.1134/S1070363209070184
Substances of 4-oxo-1,3-benzoxazine series exhibit
interesting biological activity. In detail, among the
derivatives of 4-oxo-1,3-benzoxazines are found
compounds posessing the antiichemic action [1].
conditions. When methoxyphenyl- and indolylvinyl
substituted perchlorates IIIa, IIIb are involved in the
reaction no formation of 2,3-dihydro-4-oxo-1,3-
benzoxazines of the type II takes place at room
temperature as well as on boil. The only process
observed is deprotonation of salts leading to formation
of 4-oxo-1,3-benzoxazines IVa, IVb.
With the purpose of searching new potentially
biologically active compounds we have involved 4-
oxo-1,3-benzoxazinium perchlorates Ia, b, IIIa–IIIf
[2] in the reaction with sodium borohydride. It occured
that in the case of 2-alkyl- and 2-phenylsubstituted 4-
oxo-1,3-benzoxazinium salts Ia, Ib C=O group does
not react with sodium borohydride in acetonitrile, and
the reduction proceeds at the electronodeficient
position 2 of heteroring with formation of 2,3-dihydro-
4-oxo-1,3-benzoxazines IIa, IIb.
O
O
NaBH4
NH
N
ClO4−
R
+
O
O
R
IVа, IVb
IIIа, IIIb
O
O
R = 4-CH3OC6H4 (а); indol-3-yl (b).
NaBH4
NH
NH
R
ClO4−
+
H
It is connected probably with low solubility of
benzoxazines IVa, IVb in acetonitrile that prevents
further hydrogenation.
O
R
O
II
I
R = CH3 (а), Ph (b).
When perchlorates IIIc–IIIe are reacted with
NaBH4 instead of the expected aryl- and heterylvinyl-
dihydrobenzoxazinones analogous to II were isolated
aryl- and heterylethylbenzoxazinones Vc–Ve. In this
case hydrogenation proceeds at the position 2 of
heteroring as well as at the double bond of substituent.
2-Arylvinyl- and 2-heterylvinyl substituted 4-oxo-
1,3-benzoxazinium perchlorates III prepared ac-
cording to [3, 4] react with NaBH4 ambiguously
depending on their structure and the reaction
1509

1510
VIKRISHCHUK et al.
O
O
O
NaBH4, 30−35oC
NH
NH
ClO4−
R
+
CH3CN
R
O
Vc−Ve
IIIc−IIIe
R = thienyl (c), Ph (d), 4-F-C6H4 (e).
Such unusual reaction pathway may be explained
probably by activation of C=C bond of the substituent
with the adjacent electronodeficient carbon atom in the
position 2 of heteroring of perchlorates III or corres-
ponding benzoxazinones IV.
range 3200–3167 cm–1 and at 3086 cm–1 is caused by
the symmetric and asymmetric bond vibrations of NH
group. IR spectra contain also the band of high
intensity at 1690–1687 cm–1 attributed to C=O group
and two strong bands of aromatic absorption at 1620–
1
1587 cm–1. H NMR spectra of these compounds are
Reaction of perchlorate IIIf with NaBH4 proceed-
ing at 20–23ºC yields arylvinyl benzoxazinone IVf
while at 30–35ºC arylethyl-substtituted dihydrobenzo-
xazinone Ve is formed.
also characteristic. The triplet at 2.1–2.2 ppm and the
multiplet at 2.6–3.1 ppm relate to β- and α-methylene
protons of substituent. The triplet of methine proton at
5.2 ppm and the singlet of NH proton at 8.7 ppm
together with the signals of aromatic protons tell in
favor of formation of 2-arylethyl- and 2-heterylethyl-
dihydrobenzoxazinones.
The composition and structure of the compounds
obtained were confirmed by elemental analysis data
and the IR and NMR spectroscopy. In the IR spectra of
benzoxazinones IV the absorption band of high
intensity at 1693–1680 cm–1 belonging to C=O group
is observed. Two strong bands at 1660–1590 cm–1
EXPERIMENTAL
1H NMR spectra were taken on a Varian Unity 250
(250 MHz) spectrometer in DMSO-d6. IR spectra were
recorded on a Specord IR-75 spectrometer in vaseline
oil. Elemental analysis was carried out on an automatic
Perkin-Elmer 2400 CHN-analyzer.
1
relate to C=C and C=N bonds. In H NMR spectra of
these compounds AB-system of the CH=CH protons is
observed at 6.7–8.4 ppm, and the multiplet of aromatic
protons is located in the range 6.75–8.2 ppm.
Presence of two characteristic absorption bands in
the IR spectra of dihydrobenzoxazinones Vc–Vf in the
Perchlorates I, III were prepared according to [2–4].
O
N
O
NaBH4, 20−23oC
NH
ClO4−
+
CH3CN
O
O
OMe
OMe
OMe
OMe
IVf
IIIf
O
NaBH4, 30−35oC
NH
CH3CN
O
OMe
OMe
Vf
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 7 2009

REACTIONS OF 4-OXO-1,3-BENZOXAZINIUM PERCHLORATES
1511
(3H, OCH3), 6.75-8.12 m (9H, ArH, CH=CH). Found,
%: C 79.95; H 4.81; N 4.46. C18H15NO4. Calculated,
%: C 69.89; H 4.89; N 4.53.
2-Methyl-2,3-dihydro-4-oxo-1,3-benzoxazine (IIa).
To a suspension of 2.61 g of perchlorate Ia in 20 ml of
acetonitrile 0.65 g of sodium borohydride was added
slowly. The reaction mixture was handled at room
temperature for 20 h. After that 150 ml of water were
added, and the precipitate formed was filtered off.
Yield 68%, colorless crystals, mp 145ºC (from
aqueous methanol). IR spectrum, ν, cm–1: 3175 and
3080 (NH), 1696 (C=O), 1613 and 1582 (C=Carom). 1H
NMR spectrum, δ, ppm (J, Hz): 1.65 d (3H, CH3,
J 5.61 Hz), 5.41 q (1H, CH), 6.85–7.45 m (4H, ArH),
8.81 d (1H, NH). Found, %: C 66.45; H 5.31; N 8.67.
C9H9NO2. Calculated, %: C 66.26; H 5.52; N 8.59.
2-[2-(2-Thienyl)ethyl]-2,3-dihydro-4-oxo-1,3-benz-
oxazine (Vc). To a suspension of 3.85 g of perchlorate
IIIc in 22 ml of acetonitrile 0.72 g of sodium boro-
hydride was added slowly to avoid foaming at 30–
35ºC. The reaction mixture was handled at 30ºC for
15 h. After that 50 ml of cold water was added, and the
precipitate formed was filtered off and crystallized
from propanol-2. Brown crystalline powder was ob-
tained, mp 140–142ºC, yield 1.59 g (50%). IR
spectrum, ν, cm–1: 3160 and 3086 (NH), 1687 (C=O),
1625, 1620 (C=Carom). 1H NMR spectrum δ, ppm: 2.21 t
(2H, CH2), 2.91–3.12 m (2H, CH2), 5.25 t (1H, 2-CH),
6.91–7.91 m (7H, ArH), 8.72 s (1H, NH). Found, %: C
64.80, H 5.11, N 5.35, S 11.10. C14H13NO2S.
Calculated, %: C 64.84, H 5.05, N 5.40, S 11.02.
2-Phenyl-2,3-dihydro-4-oxo-1,3-benzoxazine (IIb).
This compound was prepared analogously, yield 55%,
colorless crystals, mp 168-169&ºC. IR spectrum, ν,
cm–1: 3180 and 3078 (NH), 1688 (C=O), 1611 and
1579 (C=Carom). Found, %: C 74.45; H 4.91; N 6.37.
C14H11NO2. Calculated, %: C 74.67; H 4.89; N 6.22.
2-(2-Phenylethyl)-2,3-dihydro-4-oxo-1,3-benzoxa-
zine (Vd) was obtained analogously. White crystals,
mp 141–143ºC (from octane), yield 52%. IR spectrum,
ν, cm–1: 3167 and 3086 (NH), 1687 (C=O), 1607 and
2-[2-(4-Methoxyphenyl)vinyl]-4-oxo-1,3-benzoxa-
zine (IVa). To a suspension of 2.14 g of perchlorate
IIIa in 12 ml of acetonitrile 0.38 g of finely pulverized
NaBH4 was added slowly (to avoi foaming) at room
temperature or at 35ºC. The reaction mixture was left
for 10 h and then treated with 50 ml of cold water. The
crystals formed were filtered off and crystallized from
butanol. Yellow crystals with mp 210ºC were
obtained, yield 0.71 g (40%). IR spectrum, ν, cm–1:
1680 (C=O), 1620 and 1590 (C=C and C=N). 1H NMR
spectrum, δ, ppm (J, Hz): 3.85 s (3H, OCH3), 6.78 d
(1H, CH, J 15.1 Hz), 6.98 d (2H, ArH, J 9.2 Hz), 7.48–
8.08 m (7H, ArH, CH). Found, %: C 71.95; H 4.81; N
5.20. C16H13NO3. Calculated, %: C 71.90; H 4.90; N
5.24.
1
1587 (C=Carom). H NMR spectrum, δ, ppm: 2.12 t
(2H, CH2), 2.71–3.12 m (2H, CH2), 5.21 t (1H, 2-CH),
6.81–7.51 m (8H, ArH), 7.82 d (1H, ArH), 8.71 s (1H,
NH). Found, %: C 75.75; H 5.88; N 5.26. C16H15NO2.
Calculated, %: C 75.87; H 5.97; N 5.53.
2-[2-(4-Fluorophenyl)ethyl]-2,3-dihydro-4-oxo-1,3-
benzoxazine (Ve) was obtained analogously to
compound Vc. Colorless crystals, mp 135–137ºC
(from propanol-2), yield 47%. IR spectrum, ν, cm–1:
3200 and 3086 (NH), 1690 (C=O), 1600 and 1590
1
(C=Carom). H NMR spectrum, δ, ppm (J, Hz): 2.11 t
(2H, CH2), 2.71–2.92 m (2H, CH2), 5.21 t (1H, 2-CH),
6.81–7.42 m (7H, ArH), 7.81 d (1H, ArH, J 6.2 Hz),
8.71 s (1H, NH). Found, %: C 69.70; H 5.17; F 6.20; N
5.50. C15H13FNO2. Calculated, %: C 69.76; H 5.07; F
6.20; N 5.42.
2-[2-(1H-Indol-3-yl)vinyl]-4-oxo-1,3-benzoxazine
(IVb) was obtained analogously and crystallized from
butanol. Yellow crystals, mp 305ºC, yield 42%. IR
spectrum, ν, cm–1: 3273 (NH), 1693 (C=O), 1880 and
1
1620 (C=C and C=N). H NMR spectrum, δ, ppm
2-[2-(3,4-Dimethoxyphenyl)ethyl]-2,3-dihydro-4-
oxo-1,3-benzoxazine (Vf) was prepared analogously
to compound Vc. Colorless crystals, mp 140ºC (from
butanol), yield 52%. IR spectrum, ν, cm–1: 3160 and
(J, Hz): 6.71 d (1H, CH, J 6.3 Hz), 7.11-8.22 m (9H,
ArH), 8.41 d (1H, CH, J 6.3 Hz), 12.12 s (1H, NH).
Found, %: C 74.90; H 4.31; N 9.90. C18H12N2O2.
Calculated, %: C 74.99; H 4.20; N 9.97.
1
3086 (NH), 1680 (C=O), 1620 (C=Carom). H NMR
spectrum, δ, ppm: 2.11 t (2H, CH2), 2.61–2.91 m (2H,
CH2), 3.71 s (3H, OCH3), 3.85 s (3H, OCH3), 5.21 t
(1H, 2-CH), 6.71–7.12 m (5H, ArH), 7.41–7.92 m (2H,
ArH), 8.17 s (1H, NH). Found, %: C 69.32; H 7.10; N
4.26. C18H19NO4. Calculated, %: C 69.28; H 7.04; N
4.25.
2-[2-(3,4-Dimethoxyphenyl)vinyl]-4-oxo-1,3-benzoxa-
zine (IVf) was obtained analogously to compound IVa
at 20–23ºC. Yellow crystals, mp 305ºC (from iso-
butanol), yield 48%. IR spectrum, ν, cm–1: 1690
(C=O), 1660 and 1620 (C=C and C=N), H NMR
spectrum, δ, ppm (J, Hz): 3.82 s (3H, OCH3), 3.91 s
1
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VIKRISHCHUK et al.
3. Ryabukhin, Yu.I., Mezheritskii, V.V., Karpenko, V.D.,
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