General procedure for the synthesis of spirocyclic 3-hydroxy- and 3-oxotetrahydrofurans containing carbo- and heterocyclic fragments

Article abstract of DOI:10.1134/S1070428011070207

Reactions of cyclopentanone, cyclohexanone, N-substituted pyrrolidin-3-one and piperidin-4-one, and tetrahydropyran-4-one with allyl bromide in the presence of zinc and ammonium chloride gave the corresponding geminal hydroxy allyl derivatives. Treatment of the latter with sodium periodate in the presence of sodium metabisulfite resulted in their oxidative cyclization with formation of oxa spirocyclic alcohols containing carbo- and heterocyclic fragments. Swern oxidation of the spiro alcohols afforded the corresponding ketones which were characterized as 2,4-dinitrophenylhydrazones. Pleiades Publishing, Ltd., 2011.

Full text of DOI:10.1134/S1070428011070207

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 7, pp. 1091–1096. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © A.I. Moskalenko, S.L. Belopukhov, A.A. Ivlev, V.I. Boev, 2011, published in Zhurnal Organicheskoi Khimii, 2011, Vol. 47, No. 7,
pp. 1073–1077.
General Procedure for the Synthesis of Spirocyclic
3
-Hydroxy- and 3-Oxotetrahydrofurans Containing Carbo-
and Heterocyclic Fragments
A. I. Moskalenko, S. L. Belopukhov, A. A. Ivlev, and V. I. Boev
Lipetsk State Pedagogical University, ul. Lenina 42, Lipetsk, 398020 Russia
e-mail: kaf_himii@lspu.lipetsk.ru
Received July 14, 2010
Abstract—Reactions of cyclopentanone, cyclohexanone, N-substituted pyrrolidin-3-one and piperidin-4-one,
and tetrahydropyran-4-one with allyl bromide in the presence of zinc and ammonium chloride gave the corre-
sponding geminal hydroxy allyl derivatives. Treatment of the latter with sodium periodate in the presence of
sodium metabisulfite resulted in their oxidative cyclization with formation of oxa spirocyclic alcohols
containing carbo- and heterocyclic fragments. Swern oxidation of the spiro alcohols afforded the corresponding
ketones which were characterized as 2,4-dinitrophenylhydrazones.
DOI: 10.1134/S1070428011070207
Spirocyclic derivatives of tetrahydrofuran attract
interest as potential biologically active substances. For
example, compounds I and II were isolated from
plants [1, 2], in particular from tea [3]. 8-Methyl-1-
oxa-8-azaspiro[4.5]decan-3-one, 2,8-dimethyl-1-oxa-
particular mercury(II) salts [5], lead(IV) acetate [8],
and selenium(II) compounds [9], or expensive rhodium
catalysts [11] were used, which may also be regarded
as disadvantages.
Taking into account the above stated and the results
of our previous studies [12] on new heterocyclic spiro
compounds, the goal of the present work was to
develop a general procedure for the synthesis of spiro-
cyclic 3-hydroxy- and 3-oxotetrahydrofuran deriva-
tives containing carbo- and heterocyclic fragments.
Interest in such compounds is determined by broad
potential of their application in preparative organic
synthesis due to the presence of functional groups. As
starting compounds we used accessible carbo- and
heterocyclic ketones, cyclopentanone (IIIa), cyclo-
hexanone (IIIb), tert-butyl 3-oxopyrrolidine-1-carbox-
ylate (IIIc), tert-butyl 3-oxopiperidine-1-carboxylate
(IIId), tert-butyl-4-oxopiperidine-1-carboxylate (IIIe),
and tetrahydropyran-4-one (IIIf). Ketones IIIa–IIIf
fairly readily reacted with allyl bromide in the pres-
ence of zinc dust in tetrahydrofuran–saturated aqueous
ammonium chloride over a period of 10–12 h at room
temperature under vigorous stirring (TLC monitoring).
As a result, the corresponding geminal allyl hydroxy
derivatives IVa–IVf were formed in almost quantita-
tive yield (Scheme 1); their structure was confirmed
8
-azaspiro[4.5]decan-3-one and their derivatives were
reported to act as muscarinic cholinomimetics [4], i.e.,
their activity is analogous to that of such medical
agents as Aceclidine and Pilocarpine.
Me
Me
Me
O
O
Me
I
H
Me
Me
H
N
HO
Me
H
Me
H
O
HO
H
H
HO
II
Known methods for the synthesis of oxaspiro-
nonane and oxaspirodecane systems [4–11] are quite
specific and tedious, whereas the overall yields of
target products VIa and VIb do not exceed 20%.
Moreover, in some cases highly toxic reagents, in
1
by elemental analyses, and IR, H NMR, and mass
spectra.
1
091

1
092
MOSKALENKO et al.
Scheme 1.
H C
2
HO
O
O
BrCH
2
CH=CH
2
2
, Zn
NaIO
t-BuOH–H O
, Na S O
4 2 2 3
(
)n
HO
( )n
X
( )n
X
( )n
X
NH Cl, H O–THF
[O]
4
2
O
O
X
IIIa–IIId
IVa–IVd
Va–Vd
OH
VIa–VId
O
CH2
O
HO
O
O
BrCH CH=CH , Zn
NaIO , Na S O
4 2 2 3
2
2
NH Cl, H O–THF
t-BuOH–H O
[O]
4
2
2
X
X
X
X
IIIe, IIIf
IVe, IVf
Ve, Vf
VIe, VIf
2
X = CH (a, b), t-BuOCON (c, d, e), O (f); n = 1 (a, c), 2 (b, d).
The IR spectra of IVa–IVf contained absorption
bands in the regions 3500–3480 and 1605–1617 cm
was oxidation according to Swern [14], which ensured
82–97% yield of compounds VIa–VIf. Other oxidants,
e.g., pyridinium chlorochromate [15] (yield of VIa and
VIb 45–52%), turned out to be less effective. The IR
spectra of VIa–VIf contained a new strong absorption
–
1
due to stretching vibrations of the O–H and C=C
1
bonds, respectively. In the H NMR spectra of IVa–
IVf, multiplet signals typical of allyl group were
–
1
observed at δ 2.15–2.30 (2H, CH ), 5.05–5.20 (2H,
band in the region 1760–1728 cm due to stretching
vibrations of the ketone carbonyl group. In the
2
CH=CH ), and 5.85–5.95 ppm (1H, CH=CH ).
2
2
1
H NMR spectra of VIa–VIf singlets at δ 2.32–2.44
The key step in the synthesis of oxaspirocyclic
systems from alcohols IVa–IVf may be oxidative
cyclization which is generally [13] characterized by
low selectivity and poor yield. The results of our
experiments showed that the optimal and most general
conditions for oxidative cyclization of compounds
IVa–IVf include treatment with sodium periodate in
the presence of sodium metabisulfite in aqueous tert-
butyl alcohol at 50°C (10–12 h) and subsequent stir-
ring for 10 h at room temperature. After chromato-
graphic purification, the yields of spirocyclic alcohols
Va–Vf were 45–50%, and the tert-butoxycarbonyl
(
CH C=O) and 3.96–3.98 ppm (OCH C=O) were ob-
2
2
served. The presence of a carbonyl group in com-
pounds VIa–VIf was confirmed by the reaction with
2
,4-dinitrophenylhydrazine which quantitatively af-
forded the corresponding crystalline 2,4-dinitrophenyl-
hydrazones VIIa–VIIf with sharp melting points.
EXPERIMENTAL
The IR spectra were recorded in KBr on a Specord
1
7
5IR spectrometer. The H NMR spectra were meas-
ured on a Bruker DPX-400 instrument at 400 MHz
(
Boc) protecting group remained unchanged.
from solutions in CDCl using hexamethyldisiloxane
3
Compounds Va–Vf displayed in the IR spectra
as internal reference. The mass spectra (atmospheric
pressure chemical ionization) were obtained on
a Thermo Finnigan Surveyor MSQ GC–MS system
(USA). The progress of reactions was monitored by
TLC on Silufol UV-254 plates using hexane–ethyl
acetate (1 : 1 by volume) as eluent. Silicagel 60
(Merck) was used for column chromatography.
–
1
absorption bands in the region 3478–3445 cm due to
stretching vibrations of the hydroxy group. The IR
spectra of Vc–Ve also contained absorption bands at
–
1
1
695–1690 cm , which belong to stretching vibrations
of the ester carbonyl group. The OH proton resonated
1
in the H NMR spectra of Va–Vf at δ 4.42–4.83 ppm,
the CHOH proton gave a multiplet at δ 3.78–4.04 ppm,
and the doublet at δ 3.28–3.57 ppm was assigned to
protons in the methylene group neighboring to the
endocyclic oxygen atom.
1
-Allylcyclopentan-1-ol (IVa). Zinc dust, 13 g
0.2 mol), was slowly added under vigorous stirring to
a mixture of 8.4 g (0.1 mol) of cyclopentanone (IIIa),
0.25 g (0.25 mol) of allyl bromide, 30 ml of THF, and
(
3
The structure of alcohols Va–Vf was also con-
firmed by their oxidation into the corresponding
ketones VIa–VIf (Scheme 1). Here, the most effective
100 ml of a saturated aqueous solution of ammonium
chloride in such a way that the temperature did not
exceed 40°C. The mixture was then stirred for 10 h at
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 7 2011

GENERAL PROCEDURE FOR THE SYNTHESIS OF SPIROCYCLIC 3-HYDROXY- ...
1093
room temperature, 100 ml of 10% aqueous sulfuric
acid was added, the mixture was filtered, the organic
phase was separated, and the aqueous phase was satu-
rated with sodium chloride and extracted with diethyl
ether. The extracts were combined with the organic
phase and dried over anhydrous sodium sulfate, and
the solvent was distilled off under reduced pressure.
Yield 11.4 g (90%), light yellow liquid. IR spectrum, ν,
CH NCH ), 5.18 m (2H, CH=CH ), 5.93 m (1H,
2
2
2
+
CH=CH ). Mass spectrum, m/z: 228 [M + H] , 171
2
+
+
[M – 57 + H] , 127 [M – 101 + H] . Found, %:
C 63.61; H 9.43; N 6.02. C H NO . Calculated, %:
1
2
21
3
C 63.44; H 9.25; N 6.17. M 227.
Compounds IVd and IVe were synthesized in
a similar way.
–
1
1
tert-Butyl 3-allyl-3-hydroxypiperidine-1-carbox-
ylate (IVd). Yield 98%, light yellow oily liquid. IR
cm : 3500 (OH), 1617 (C=C). H NMR spectrum, δ,
ppm: 1.58–1.65 m (4H, CH ), 1.81–1.87 m (4H, CH ),
2
2
–
1
spectrum, ν, cm : 3480 (OH), 1690 (C=O), 1608
2
.15 d (2H, 1-CH ), 3.16 s (1H, OH), 5.05 m (2H,
2
1
(
C=C). H NMR spectrum, δ, ppm: 1.48 s (9H, t-Bu),
CH=CH ), 5.85 m (1H, CH=CH ). Mass spectrum:
2
2
+
1
3
.54–1.78 m (4H, CH ), 2.27 m (3H, 3-CH , OH),
m/z 127 [M + H] . Found, %: C 76.28; H 11.18.
C H O. Calculated, %: C 76.19; H 11.11. M 126.
2
2
.03 d and 3.68 m (2H each, NCH ), 5.18 m (2H,
2
8
14
CH=CH ), 5.91 m (1H, CH=CH ). Mass spectrum,
2
2
Compounds IVb and IVf were synthesized in
a similar way.
+
+
m/z: 242 [M + H] , 185 [M – 57 + H] , 141 [M – 101 +
H] . Found, %: C 64.45; H 9.28; N 5.63. C H NO .
+
13
23
3
1
-Allylcyclohexan-1-ol (IVb). Yield 96%, light
Calculated, %: C 64.73; H 9.54; N 5.81. M 241.
–
1
yellow liquid. IR spectrum, ν, cm : 3496 (OH), 1612
C=C). H NMR spectrum, δ, ppm: 1.43–1.54 m (6H,
1
tert-Butyl 4-allyl-4-hydroxypiperidine-1-carbox-
ylate (IVe). Yield 100%, colorless oily liquid. IR spec-
(
CH ), 1.68–1.79 m (4H, CH ), 2.21 d (2H, 1-CH ),
2
2
2
–
1
trum, ν, cm : 3486 (OH), 1692 (C=O), 1610 (C=C).
3
.24 s (1H, OH), 5.06 m (2H, CH=CH ), 5.87 m (1H,
2
1
+
H NMR spectrum, δ, ppm: 1.39 s (9H, t-Bu), 1.45–
CH=CH ). Mass spectrum: m/z [M + 1] 141. Found,
2
1
.62 m (4H, CH ), 2.16 d (2H, 4-CH ), 2.28 s (1H,
%
: C 77.38; H 11.26. C H O. Calculated, %: C 77.14;
2
2
9
16
OH), 3.04 m and 3.64 m (2H each, NCH ), 5.08 m
H 11.43. M 140.
2
(
2H, CH=CH ), 5.88 m (1H, CH=CH ). Mass spec-
2
2
4
-Allyltetrahydropyran-4-ol (IVf). Yield 98%,
+
+
–
1
trum, m/z: 242 [M + H] , 185 [M – 57 + H] , 141
[M – 101 + H] . Found, %: C 64.68; H 9.41; N 5.56.
colorless liquid. IR spectrum, ν, cm : 3496 (OH),
615 (C=C). H NMR spectrum, δ, ppm: 1.42–1.53 m
+
1
1
C H NO . Calculated, %: C 64.73; H 9.54; N 5.81.
1
3
23
3
(
3H, CH , OH), 1.73 m (2H, CH ), 2.25 d (2H, 4-CH ),
2
2
2
M 241.
3
5
.80 m (4H, CH OCH ), 5.19 m (2H, CH=CH ),
2 2 2
.88 m (1H, CH=CH ). Mass spectrum: m/z 143
1-Oxaspiro[4.4]nonan-3-ol (Va). A solution of
2
+
[M + H] . Found, %: C 67.43; H 9.75. C H O . Calcu-
19 g (0.1 mol) of Na S O in 80 ml of water was added
8
14
2
2
2
5
lated, %: C 67.61; H 9.86. M 142.
dropwise over a period of 2 h to a mixture of 12.6 g
(
0.1 mol) of compound IVa, 21.4 g (0.1 mol) of NaIO4,
tert-Butyl 3-allyl-3-hydroxypyrrolidine-1-car-
boxylate (IVc). Zinc dust, 13 g (0.2 mol), was slowly
added under vigorous stirring to a mixture of 18.5 g
1
50 ml of tert-butyl alcohol, and 50 ml of water under
stirring at 50°C. The mixture was stirred for 10 h at
0°C and for 10 h at room temperature, the dark brown
5
(
(
0.1 mol) of tert-butyl 3-oxopyrrolidine-1-carboxylate
IIIc), 30.25 g (0.25 mol) of allyl bromide, 50 ml of
organic layer was separated, and the aqueous phase
was saturated with sodium chloride and extracted with
ethyl acetate. The extracts were combined with the
organic phase and washed with a saturated aqueous
solution of sodium thiosulfate, the resulting colorless
solution was dried over anhydrous sodium sulfate, the
solvent was removed under reduced pressure, and the
oily residue was purified by column chromatography
on silica gel using ethyl acetate–hexane (2:1) as
eluent. Yield 6.8 g (48%), colorless oily liquid. IR
spectrum: ν 3478 cm (OH). H NMR spectrum, δ,
ppm: 1.51–1.63 m (4H, CH ), 1.75–1.84 m (4H, CH ),
1.92 d (2H, CH ), 3.28 d (2H, OCH ), 3.87 m (1H,
CHO), 4.45 s (1H, OH). Found, %: C 67.52; H 9.73.
C H O . Calculated, %: C 67.61; H 9.86.
THF, and 100 ml of a saturated aqueous solution of
ammonium chloride in such a way that the temperature
did not exceed 40°C. The mixture was stirred for 12 h
at room temperature (TLC monitoring), 100 ml of
1
0% aqueous sulfuric acid was added, the mixture was
filtered, the organic phase was separated, and the
aqueous phase was extracted with ethyl acetate. The
extracts were combined with the organic phase and
dried over anhydrous sodium sulfate, and the solvent
was distilled off under reduced pressure. Yield 22.5 g
–
1
1
–
1
(
3
99%), light yellow oily liquid. IR spectrum, ν, cm :
2
2
1
486 (OH), 1689 (C=O), 1605 (C=C). H NMR spec-
trum, δ, ppm: 1.43 s (9H, t-Bu), 1.88 m (2H, CH2),
.25 d (2H, 3-CH ), 3.28 s (1H, OH), 3.51 d (4H,
2
2
2
2
8
14
2
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 7 2011

1
094
MOSKALENKO et al.
%: C 60.42; H 8.76; N 5.28. C H NO . Calculated,
Compounds Vb and Vf were synthesized in a simi-
1
3
23
4
lar way.
%: C 60.70; H 8.95; N 5.45. M 257.
1
-Oxaspiro[4.5]decan-3-ol (Vb). Yield 50%,
tert-Butyl 3-hydroxy-1-oxa-8-azaspiro[4.5]-
decane-8-carboxylate (Ve). Yield 48%, thick yellow–
–
1
colorless oily liquid. IR spectrum, ν, cm : 3464 (OH).
H NMR spectrum, δ, ppm: 1.41–1.52 m (6H, CH2),
.61–1.73 m (4H, CH ), 2.01 d (2H, CH ), 3.34 d (2H,
OCH ), 3.83 m (1H, CHO), 4.42 s (1H, OH). Found,
: C 69.13; H 10.73. C H O . Calculated, %:
C 69.23; H 10.26.
1
–1
brown oily liquid. IR spectrum, ν, cm : 3486 (OH),
1
1
1692 (C=O). H NMR spectrum, δ, ppm: 1.39 s (9H,
2
2
2
t-Bu), 1.42–1.84 m (6H, CH ), 322–3.40 m (4H,
2
%
NCH , CH O), 3.56–3.79 m (2H, NCH ), 4.30 m (1H,
9
16
2
2
2
2
CHO), 4.73 s (1H, OH). Mass spectrum, m/z: 258 [M +
+
+
+
H] , 201 [M – 57 + H] , 158 [M – 101 + H] . Found,
%: C 60.43; H 8.54; N 5.41. C H NO . Calculated,
1
,8-Dioxaspiro[4.5]decan-3-ol (Vf). Yield 46%,
–
1
colorless oily liquid. IR spectrum: ν 3475 cm (OH).
H NMR spectrum, δ, ppm: 1.18–2.08 m (6H, CH2),
13 23
4
1
%: C 60.70; H 8.95; N 5.45. M 257.
3
.37 s (1H, OH), 3.62–4.50 m (7H, CH O, CHO).
2
1-Oxaspiro[4.4]nonan-3-one (VIa). a. Dimethyl
sulfoxide, 58.5 g (0.75 mol), was added at –70°C to
a solution of 47.6 g (0.375 mol) of oxalyl chloride in
300 ml of anhydrous methylene chloride, the mixture
was stirred for 0.5 h, and a solution of 42.6 g (0.3 mol)
of compound Va in 200 ml of anhydrous methylene
chloride was added at –70°C. The mixture was stirred
for 1 h, 80.8 g (0.8 mol) of triethylamine in 300 ml of
methylene chloride was added, and the mixture was
stirred for 0.5 h at –70°C and for 10 h at room tem-
perature. The dark organic solution was washed with
two portions of 20% aqueous citric acid, dried over
anhydrous sodium sulfate, and evaporated, and the
residue was distilled under reduced pressure. Yield
36.1 g (86%), bp 68–70°C (1 mm). IR spectrum:
Found, %: C 60.58; H 8.73. C H O . Calculated, %:
C 60.76; H 8.86.
8
14
3
tert-Butyl 3-hydroxy-1-oxa-7-azaspiro[4.4]-
nonane-7-carboxylate (Vc). A solution of 19 g
(
0.1 mol) of Na S O in 80 ml of water was added over
2 2 5
a period of 1 h to a mixture of 22.7 g (0.1 mol) of
compound IVc, 21.4 g (0.1 mol) of NaIO , 150 ml of
tert-butyl alcohol, and 50 ml of water under stirring at
5
1
was separated, and the aqueous layer was extracted
with ethyl acetate. The extracts were combined with
the organic phase and washed with a saturated aqueous
solution of sodium thiosulfate, the resulting colorless
solution was dried over anhydrous sodium sulfate, the
solvent was distilled off under reduced pressure, and
the oily residue was purified by column chromatog-
raphy on silica gel using acetone as eluent. Yield
4
0°C. The mixture was stirred for 12 h at 50°C and for
0 h at room temperature, the dark brown organic layer
–
1
1
ν 1756 cm (C=O). H NMR spectrum, δ, ppm: 1.48–
1.62 m (4H, CH ), 1.73–1.85 m (4H, CH ), 2.32 s (2H,
2
2
CH C=O), 3.96 s (2H, OCH ). Found, %: C 68.42;
2
2
H 8.24. C H O . Calculated, %: C 68.57; H 8.57.
8
12
2
1
0.9 g (45%), thick yellow–brown oily liquid. IR spec-
b. Pyridinium chlorochromate, 21.6 g (0.1 mol),
was added to a solution of 14.2 g (0.1 mol) of com-
pound Va in 150 ml of anhydrous methylene chloride,
the mixture was stirred for 20 h at room temperature
and filtered through a 3-cm layer of Celite, the sorbent
was washed with 150 ml of methylene chloride, the
solution was evaporated, and the residue was distilled
under reduced pressure. Yield 6.3 g (45%).
–
1
1
trum, ν, cm : 3445 (OH), 1690 (C=O). H NMR spec-
trum, δ, ppm: 1.42 s (9H, t-Bu), 1.86 m (2H, CH2),
2
3
OH). Mass spectrum, m/z: 244 [M + H] , 187 [M –
5
.02 d (2H, CH ), 3.31 s and 3.52 s (2H each, NCH ),
2
2
.57 d (2H, CH O), 4.02 m (1H, CHO), 4.83 s (1H,
2
+
+
+
7 + H] , 143 [M – 101 + H] . Found, %: C 59.48;
H 8.54; N 5.63. C H NO . Calculated, %: C 59.26;
1
2
21
4
H 8.64; N 5.76. M 243.
Compounds Vd and Ve were synthesized in a simi-
lar way.
Compounds VIb and VIf were synthesized in
a similar way.
1
-Oxaspiro[4.5]decan-3-one (VIb). Yield 87%,
tert-Butyl 3-hydroxy-1-oxa-7-azaspiro[4.5]-
decane-7-carboxylate (Vd). Yield 47%, thick light
–
1
bp 79–82°C (1 mm). IR spectrum: ν 1760 cm (C=O).
H NMR spectrum, δ, ppm: 1.36–1.70 m (10H, CH2),
2.30 s (2H, CH C=O), 3.98 s (2H, OCH ). Found, %:
C 69.95; H 9.18. C H O . Calculated, %: C 70.13;
1
–
1
brown oily liquid. IR spectrum, ν, cm : 3478 (OH),
1
2
2
1
692 (C=O). H NMR spectrum, δ, ppm: 1.44 s (9H,
9
14
2
t-Bu), 1.63–1.80 m (4H, CH ), 2.01 d (2H, CH ), 3.15–
2
2
H 9.09.
3
.45 m (4H, NCH , CH O), 3.80–4.01 m (3H, NCH ,
2 2 2
CHO), 4.50 s (1H, OH). Mass spectrum, m/z: 258 [M +
H] , 201 [M – 57 + H] , 158 [M – 101 + H] . Found,
1,8-Dioxaspiro[4.5]decan-3-one (VIf). Yield 83%,
bp 84–86°C (1 mm), colorless oily liquid. IR spec-
+
+
+
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GENERAL PROCEDURE FOR THE SYNTHESIS OF SPIROCYCLIC 3-HYDROXY- ...
1095
–
1
1
trum: ν 1758 cm (C=O). H NMR spectrum, δ, ppm:
1
3
%
0.1 ml of concentrated hydrochloric acid, and 12 ml of
ethanol was heated for 1 h under reflux. The mixture
was cooled, diluted with 60 ml of water, and left to
stand for 12 h in a refrigerator at 5–6°C. The precip-
itate was filtered off and recrystallized from ethanol.
.16–1.79 m (4H, CH ), 2.59 s (2H, CH C=O), 3.61–
.78 m (4H, CH O), 3.92 s (2H, OCH C=O). Found,
2 2
: C 61.38; H 7.45. C H O . Calculated, %: C 61.54;
2 2
8 12 3
H 7.69.
tert-Butyl 3-oxo-1-oxa-7-azaspiro[4.4]nonane-
-carboxylate (VIc). Dimethyl sulfoxide, 21.8 g
0.28 mol), was added at –70°C to a solution of 17.9 g
0.14 mol) of oxalyl chloride in 100 ml of anhydrous
methylene chloride, the mixture was stirred for 0.5 h,
a solution of 24.3 g (0.1 mol) of compound Vc in
Compound VIIa. Yield 97%, mp 118–120°C. IR
–
1
7
(
(
spectrum, ν, cm : 3385 (NH); 1628 (C=N); 1531,
1350 (NO ). Found, %: C 52.31; H 4.87; N 17.64.
. Calculated, %: C 52.50; H 5.00; N 17.50.
Compound VIIb. Yield 98%, mp 132–134°C. IR
2
C H N O
14 16 4 5
–
1
spectrum, ν, cm : 3387 (NH); 1625 (C=N); 1532,
348 (NO ). Found, %: C 53.71; H 5.27; N 16.84.
8
–
(
0 ml of anhydrous methylene chloride was added at
70°C, the mixture was stirred for 1 h, 31.4 g
1
2
C H N O . Calculated, %: C 53.89; H 5.39; N 16.77.
1
5
18
4
5
0.31 mol) of triethylamine in 100 ml of methylene
chloride was added, and the mixture was stirred for
.5 h at –70°C and for 15 h at room temperature. The
dark organic solution was washed with two portions of
0% aqueous citric acid and dried over anhydrous
Compound VIIc. Yield 96%, mp 136–137°C. IR
–1
spectrum, ν, cm : 3405 (NH); 1691 (C=O); 1620
C=N); 1531, 1352 (NO ). Found, %: C 51.16; H 5.32;
0
(
2
N 16.48. C H N O . Calculated, %: C 51.31; H 5.46;
1
8
23
5
7
2
N 16.63.
sodium sulfate, and the solvent was distilled off under
reduced pressure. Yield 23.4 g (97%), mp 71–72°C
Compound VIId. Yield 97%, mp 139–140°C. IR
–
1
–
1
spectrum, ν, cm : 3402 (NH); 1690 (C=O); 1622
(C=N); 1534, 1349 (NO ). Found, %: C 52.36; H 5.64;
N 15.97. C H N O . Calculated, %: C 52.41; H 5.75;
(
(
1
from hexane). IR spectrum, ν, cm : 1730, 1691
1
2
C=O). H NMR spectrum, δ, ppm: 1.42 s (9H, t-Bu),
1
9
25
5
7
.92–2.13 m (2H, CH ), 2.50 s (2H, CH C=O), 3.31 m
2 2
N 16.09.
and 3.51 m (2H each, NCH ), 3.98 s (2H, OCH ).
2
2
+
Compound VIIe. Yield 98%, mp 148–149°C. IR
Mass spectrum: m/z 142 [M – 101 + H] . Found, %:
–
1
spectrum, ν, cm : 3402 (NH); 1692 (C=O); 1618
C=N); 1532, 1348 (NO ). Found, %: C 52.58; H 5.71;
C 59.68; H 7.63; N 5.66. C H NO . Calculated, %:
1
2
19
4
(
2
C 59.75; H 7.88; N 5.81. M 241.
N 16.25. C H N O . Calculated, %: C 52.41; H 5.75;
1
9
25
5
7
Compounds VId and VIe were synthesized in
a similar way.
N 16.09.
Compound VIIf. Yield 96%, mp 127–128°C. IR
tert-Butyl 3-oxo-1-oxa-7-azaspiro[4.5]decane-7-
carboxylate (VId). Yield 96%, thick yellow–brown
–1
spectrum, ν, cm : 3396 (NH); 1619 (C=N); 1532,
1
350 (NO ). Found, %: C 49.81; H 4.65; N 16.53.
–
1
2
oily liquid. IR spectrum, ν, cm : 1735, 1691 (C=O).
C H N O . Calculated, %: C 50.00; H 4.76; N 16.67.
1
14 16
4
6
H NMR spectrum, δ, ppm: 1.41 s (9H, t-Bu), 1.80 m
(
4H, CH ), 2.30 m (2H, CH C=O), 3.35 m (4H,
2 2
REFERENCES
NCH ), 4.01 s (2H, OCH ). Mass spectrum: m/z 156
[
C H NO . Calculated, %: C 61.18; H 8.24; N 5.49.
M 255.
2
2
+
1
2
3
4
. Ina, K. and Sakato, Y., Tetrahedron Lett., 1968, vol. 9,
M – 101 + H] . Found, %: C 60.87; H 8.31; N 5.24.
p. 2777.
1
3
21
4
. Sashida, Y., Mimaki, H., and Shimomura, H., Chem.
Lett., 1989, vol. 18, p. 897.
. Sato, A. and Mishima, H., Tetrahedron Lett., 1969,
tert-Butyl 3-oxo-1-oxa-8-azaspiro[4.5]decane-8-
carboxylate (VIe). Yield 97%, mp 65–66°C (from
vol. 10, p. 1803.
–
1
hexane). IR spectrum, ν, cm : 1738, 1692 (C=O).
. Wu, E.S.C., Griffith, R.C., Loch, J.T., III, Kover, A.,
Murray, R.J., Mullen, G.B., Blosser, J.C., Machul-
skis, A.C., and McCreedy, S.A., J. Med. Chem., 1995,
vol. 38, p. 1558.
. Colonge, D., Bull. Soc. Chim. Fr., 1958, p. 211.
. Picard, P. and Moulines, J., Bull. Soc. Chim. Fr., 1974,
1
H NMR spectrum, δ, ppm: 1.40 s (9H, t-Bu), 1.54–
1
3
.73 m (4H, CH ), 2.42 s (2H, CH C=O), 3.31 m and
2 2
.45 m (2H each, NCH ), 3.99 s (2H, OCH ). Mass
2
2
+
spectrum: m/z 156 [M – 101 + H] . Found, %: C 61.09;
H 8.17; N 5.28. C H NO . Calculated, %: C 61.18;
H 8.24; N 5.49. M 255.
5
6
1
3
21
4
p. 2889.
2
,4-Dinitrophenylhydrazones VIIa–VIIf (general
7. Marx, J.N., Tetrahedron, 1975, vol. 31, p. 1251.
procedure). A mixture of equimolar amounts (2 mmol)
of ketone VIa–VIf and 2,4-dinitrophenylhydrazine,
8. Nakatani, Y. and Yamanishi, T., Tetrahedron Lett., 1969,
vol. 10, p. 1995.
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. Middleton, D., Simpkins, N., Begley, M., and Ter-
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Compounds. Akanes, Alkenes, Alkynes, and Arenes,
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1
0. Okimoto, Y., Kikuchi, D., Sakaguchi, S., and Ishii, Y.,
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1. Keith, J. and Teymour, T., Tetrahedron, 2001, vol. 57,
14. Mancuso, A.J. and Swern, D., Synthesis, 1981, p. 165;
Mancuso, A.J., Swern, D., Kozikowski, A.P., and
Stein, P.D., J. Org. Chem., 1984, vol. 49, p. 2305.
1
p. 2427.
1
2. Moskalenko, A.I. and Boev, V.I., Russ. J. Org. Chem.,
15. Corey, E.J. and Suggs, J.W., Tetrahedron Lett., 1975,
2
009, vol. 45, p. 1018.
vol. 16, p. 2647.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 7 2011