Synthesis of novel spiro compounds using anthrone and pyrazole-5-thione moieties: A Michael addition approach

Article abstract of DOI:10.3184/030823407X237821

Novel routes for the synthesis of spiro derivatives anthrone have been designed using a Michael addition reaction followed by a Dieckmann condensation and Thorpe-Ziegler cyclisation. Bis-Michael addition of pyrazole-5-thione with 1,5-diarylpenta-1,4-dien-3-one gave directly a spiro derivative of pyrazole-5-thione. An enol lactone was synthesised by using mono Michael addition on dimedone, followed by hydrolysis and condensation.

Full text of DOI:10.3184/030823407X237821

468 RESEARCH PAPER
AUGUST, 468–471
JOURNAL OF CHEMICAL RESEARCH 2007
Synthesis of novel spiro compounds using anthrone and pyrazole-
5-thione moieties: a Michael addition approach
Madhukar S. Chande*, Rahul R. Khanwelkar and Pravin A. Barve
Department of Chemistry, The Institute of Science, 15 Madam Cama Road, Mumbai 400 032, India
Novel routes for the synthesis of spiro derivatives anthrone have been designed using a Michael addition reaction
followed by a Dieckmann condensation and Thorpe–Ziegler cyclisation. Bis-Michael addition of pyrazole-5-thione
with 1,5-diarylpenta-1,4-dien-3-one gave directly a spiro derivative of pyrazole-5-thione. An enol lactone was
synthesised by using mono Michael addition on dimedone, followed by hydrolysis and condensation.
Keywords: Michael addition, spiro compounds, anthrone, pyrazole-5-thione, dimedone
Michael addition is one of the oldest well-known reactions,
which involves the formation of a carbon–carbon bond and
has found extensive applications in organic synthesis.1 The
reaction, usually carried out in basic conditions, deals with
the addition of compounds containing active methylene group
(donors) to activated π systems (acceptors). More recently,
the use of organometallics2 and ionic liquids3 has gained
considerable importance to carry out this reaction, since it
leads to products with high enantioselectivity.
Over the past decade, we have reported some exciting
synthetic strategies for the synthesis of this exclusive class of
compounds.4 Recently, we have been actively exploring the
Michael addition reaction on heterocyclic and carbocyclic
systems bearing active methine5 and methylene6 groups.
We have successfully employed the Michael adducts as key
intermediates for the synthesis of some interesting spiro
compounds. Thus, continuing our work along this line, we
report here the reaction of anthrone 1, pyrazole-5-thiones 8
and dimedone 11 as Michael donors for the synthesis of novel
spirocyclohexanone derivatives, which would further broaden
the utility and scope of this reaction.
of anthracenol have been investigated in conjunction with 9-
substituted anthracenes.8a,8b Spiro compounds using anthrone
are less reported in the literature10 and using Michael
addition reaction has not been observed. Hence we decided
to utilise bis-Michael adducts for the synthesis of novel spiro
derivatives of anthrone.
The Michael addition of 1 with Michael acceptors such
as methyl acrylate 2 and acrylonitrile 5 proceeded smoothly
leading to diadducts. Thus diadduct 3 were obtained by
interaction of 1 with two equivalents of methyl acrylate 2 and
catalytic amount of benzyltrimethylammonium hydroxide
(triton B) in 1,4 dioxan at 60°C. The existence of a carbonyl
peak at 184.6 ppm and tetrahedral carbon at 46.4 ppm in 13C
NMR spectrum of Michael diadduct 3 ruled out the possibility
of the mono-Michael adducts, O-alkylated diadducts
and Diels–Alder reaction products, and confirmed the
regioselectivity of Michael addition. Dieckmann condensation
of 3 in presence of sodium methoxide in methanol directly
afforded the corresponding novel spirocyclohexanone
derivative of anthrone 4, which was confirmed on the basis
of spectral analysis showing presence of two carbonyl peaks
at 187.0 and 214.5 ppm, of two carbonyl groups (Scheme 1,
route i).
The study of the Michael addition on 1 was further extended
to acrylonitrile 5. Under similar reaction experimental
conditions Michael diadduct 6 was obtained in excellent
yield. The IR spectrum displayed a sharp band at 2244 cm-1
due to nitrile group. Michael diadduct 6 on Thorpe–Ziegler
cyclisation afforded desired spirocycloimino derivative 7.
The spirocyclohexanone derivative of anthrone 4 was obtained
by hydrolysis and decarboxylation of the compound 7.
Results and discussions
Anthrone and anthracenol are typical examples of keto-enol
isomerisation in solution.7 Anthracenol ion generated from
the deprotonation of anthrone by base leads to a consecutive
double Michael addition.8 In the presence of ZnCl2 1,4-
conjugated addition of anthrone with a,b-unsaturated ketones/
esters proceeds to give mono-Michael adducts.9 In addition
to the Michael addition of anthrone, Diels–Alder reactions
O
O
COOMe
2
(a)
route i
1
(b)
O
H3COOC
COOCH 3
(a)
CN
3
route ii
5
O
O
(d)
O
(c)
4
CN
NC
CN
NH
7
6
Scheme 1 (a) Triton B/1,4- dioxan/60°C; (b) NaOMe/MeOH/reflux; (c) Na/toluene/reflux; and (d) HBr/acetic acid/reflux.
* Correspondent. Email: mschande@yahoo.com
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JOURNAL OF CHEMICAL RESEARCH 2007 469
H3C
Ph
Therefore an alternative, unambiguous and independent
method for the synthesis of compounds 4 has been established
(Scheme 1, route ii).
H3C
Ph
N
N
HM
HM
N
S
N
S
HM
HM
HX
HX
In continuation to our work on the synthesis of novel
spirocyclohexanone using 1,5-diarylpenta-1,4-dien-3-one
as a Michael acceptor and their stereochemical studies,6a, 6d
we now report the synthesis of novel spirocyclohexanone
derivative of pyrazole-5-thiones 8 using 1,5-diarylpenta-
1,4-dien-3-one 9 and their steriochemical study. Pyrazole-5-
thiones 8 was prepared in good yield using microwave-assisted
reaction of pyrazole-5-ones with Lawessons reagent, using
methodology developed in our group.6e Spirocyclohexanone
10 was synthesised in a single step by Bis-Michael addition
of pyrazole-5-thione 8 with 1,5-diarylpenta-1,4-dien-3-one 9
in presence of sodamide in dry DMF at 10–15°C in moderate
yield (Scheme 2). Cyclohexanones and spirocyclohexanones
have been extensively studied for their stereochemistry.11
Spirocyclohexanone 10 can exhibit either symmetric I or
antisymmetric II form (Fig. 1). In 10a, HA exhibited a doublet
of doublets at 4.32 (dd, J = 4 Hz, 12 Hz), while HM and HX
exhibited triplet and doublet of doublets at the region 3.87
(t, J = 13 Hz) and 3.50 (dd, J = 4 Hz, 12 Hz) respectively.
The coupling constants of HA are in agreement with those
of axial–axial and axial–equatorial H–H couplings of a
cyclohexane chair conformation. This confirmed the axial
orientation for HA and that the aryl substituents are in an
equatorial orientation as shown in I (Fig. 1) and not in an
axial–equatorial orientation as shown in II (Fig. 1). This was
further confirmed by the 13C NMR spectrum which highlighted
the symmetry in the molecule, which could only occur when
the aryl substituents are disposed in equatorial orientations
as shown in I (Fig. 1) Hence, only the cis 1,3–diequatorial
isomer of 10 I (Fig. 1) had been produced, selectively, and in
moderate yield.
Ph
HA
O
HA
O
HA
HX
HX
HA
Ph
II
I
Fig. 1 10a
The reaction sequence shown in Scheme 3 illustrates the
usefulness of mono Michael adduct of dimedone 12 and
13, for the synthesis of enol lactone 15. Enol lactone is an
important functionalised substructure found in the skeletons of
neoflavonoid and coumarin family which often shows a variety
of interesting biological and pharmaceutical activities.12
Although many synthetic routes have been developed for the
construction of enol lactones, the effective synthetic reactions
are quite limited.13 Hence, we report here a very simple and
efficient method for the synthesis of enol lactone. Dimedone
is in toutomeric form with its enol form at equilibrium. Due
to the presence of methylene group between two keto groups,
it is well known nucleophile. When dimedone is treated with
Michael acceptors, generally both mono and bis-Michael
adducts were obtained.16 We report here a very simple method
for the regioselective synthesis of mono Michael adduct.
Monoalkyl derivatives of dimedone 12 and 13 were prepared
in high yields by Michael addition of 11 to methyl acrylate 2
and acrylonitrile 5 in presence of catalytic amount of sodamide
in dry DMF at 10–15°C. Formation of the bis-Michael adduct
was not observed even with 3 mol equivalence of the Michael
acceptor, increment in amount of base or increase in reaction
time and temperature.
Compound 12 was prepared by stirring dimedone 11, methyl
acrylate 2, and NaNH2, in dry DMF at 10–15°C. The presence
of a triplet for the two methylene protons at d 2.58 and two
singlets for methoxy and hydroxyl protons at d 3.75 and 9.35
respectively in the 1H NMR, and presence of olefin carbon at
113.2 ppm in 13C NMR, clearly indicated the formation of a
mono-Michael adduct regioselectively over the other Michael
adducts. Compound 12 was then hydrolysed using base
hydrolysis to give the keto-acid derivative 14. Cyclisation of
14 by refluxing it in acetic anhydride gave the expected enol
lactone 15 in moderate yield (Scheme 3, route i).
R
R
Me
S
Me
N
N
N
( a )
Ph
N
S
+
O
O
Ph
8
R
R
Under similar experimental conditions, when Michael
addition of 11 was extended to acrylonitrile 5, the mono
adduct 13 was obtained in excellent yield. The IR spectrum
displayed a sharp band at 2250 cm-1 due to the nitrile group.
9a R' = H
10a R = H (65%)
10b R = Cl (62%)
9b R' = Cl
Scheme 2 (a) NaNH2/DMF/10–15°C.
O
O
COOMe
2
(a)
COOMe
OH
O
12
11
CN
(a)
(b)
5
O
O
O
(c)
(b)
CN
OH
COOH
OH
14
O
O
13
15
Scheme 3 (a) NaNH2/DMF/10–15°C; (b) NaOH/H2O/reflux; (c) Acetic anhydride/reflux.
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470 JOURNAL OF CHEMICAL RESEARCH 2007
144.4–128.0 (12 x aromatic carbons), 118.1 (–CN), 38.4, 38.2, 26.0,
(2 x –CH2), 36.3 (spiro carbon), 24.9 (–CH).
Base hydrolysis of 13 gave expected acid derivative 14 in
good yield, which on cyclisation furnished the desired enol
lactone 15 (Scheme 3, route ii).
Spiro[anthracene-9,1'-cyclohexane]-4', 10-dione (4) from (7):
Compound 7 (1.5 g, 5 mmol) was placed in 25 ml glacial acetic
acid. To this 10 ml of hydrobromic acid in acetic acid was added.
The reaction mixture was refluxed for 4 h. From reaction mixture
solvent was removed by distillation and remaining solid contents
were poured onto crushed ice to yield the yellow coloured compound
4. It was filtered, washed with water, vacuum dried and recrystallised
from benzene/pet ether to afford pure compound 4 (1.04 g, 85%).
M.p. 205°C.
Conclusion
We have explored the scope and utility of Michael addition
reaction for the synthesis of novel spiro/enol lactone
derivatives of anthrone, pyrazol-5-thones, and dimedone
using mono and bis-Michael adducts.
1-methyl-3,6,10-triphenyl-4-thioxo-2,3-diazaspiro[5.4]dec-1-en-
8-one (10a): Compound 8 (0.95 g, 5 mmol) and sodamide (0.39 g,
10 mmol) were stirred in DMF (20 ml.) at 10–15°C for 10 min.
To this 1,5-diphenylpenta-1,4-dien-3-one 9a (1.17 g, 5 mmol)
was added. The reaction mixture was then stirred for 4 h at room
temperature. This reaction mixture was then poured onto crushed ice
and acidified using aqueous 2N HCl to pH 2–3. The obtained crude
compound 10a was filtered, washed with water and recrystallised
from aqueous methanol (1.36 g, 65%). M.p. 92°C. (Found: C 76.30%,
H 5.60%, N 6.49%, S 7.39% C27H24N2OS requires C 76.38%,
H 5.70%, N 6.60, S 7.55%). IR (cm-1) 1695, 1598. dH 7.72–7.07 (m,
5H, aromatic-H), 4.32 (dd, J = 4 Hz, 12 Hz, 2HA), 3.87 (t, J = 13,
2HM), 3.50 (dd, J = 4 Hz, 12 Hz, 2HX), 2.43 (s, 3H, –CH3). dC 216.5
(C=O), 149.4 (C=S), 139.3 (C=N), 139.0, 128.8, 128.4, 127.9, 127.6,
127.2, 125.5, 125.0 (18 x aromatic C), 109.4 (spiro carbon), 55.1
(–CH), 48.3 (–CH2), 13.5 (–CH3). m/z (ESI) 424 (M+).
Experimental
Melting points were taken in open capillaries and are uncorrected.
1H NMR and 13C NMR spectra were recorded on Bruker AMX 500
series (500 MHz) spectrometer at 25°C. IR spectra were recorded
on Perkin-Elmer 257-FTIR 1600 series spectrometer using KBr
discs. Mass spectra were recorded on Shimadzu QP 2010 GCMS
instrument. Elemental analysis was recorded on Thermo-Quest 11112
series instrument.
Methyl-3-[9-(2-methoxycarbonyl ethyl)-10-oxo-9-10-dihydro-
anthracene-9-yl]propionate (3): Anthrone 1 (0.97 g, 5 mmol)
and catalytic amount of Triton B were stirred in 15 ml. of 1–4
dioxane at room temperature. To this methyl acrylate 2 (0.86 g,
10 mmol) was added dropwise during 3 min. This reaction mixture
was stirred at 60°C for 1.5 h and then allowed to stand for overnight
at room temperature. The reaction mixture was poured onto crushed
ice and acidified using aqueous 2N HCl to pH 2–3. Separated buff
coloured solid was filtered off, washed with water, vacuum dried
and recrystallised from benzene/pet ether to obtain white crystals of
compound 3 (1.85 g, 90%). M.p. 117°C (lit.8a 116–118°C). (Found:
C 72.10%, H 6.08%. C22H22O5 requires C 72.12%, H 6.05%.).
IR (cm-1) 1736, 1668. dH 7.51–8.40 (m, 8 H, aromatic protons), 3.42
(s, 6H, 2 x –OCH3), 2.61 (t, 4H, 2 x –CH2), 1.57 (t, 4H, 2 x –CH2).
dC 184.6, 174.7 (2 x C=O), 146.4–127.5 (12 x aromatic carbons),
53.1 (2 x –OCH3), 46.4 (tetrahedral carbon), 41.4, 30.7 (2 x –CH2).
Spiro[anthracene-9,1'-cyclohexane]-4', 10-dione (4) from (3):
To the stirred solution of methanol (25 ml.) containing sodium metal
(0.12 g, 5 mmol) compound 3 (1.83 g, 5 mmol.) was added at room
temperature. The reaction mixture was then refluxed for about 4 h.
It was then poured onto the crushed ice and acidified using aqueous
2N HCl to pH 2–3. A yellow coloured product was obtained, it was
then filtered, washed with water, vacuum dried and recrystallised
from benzene/pet ether to afford pure compound 4 (1.11 g, 80%).
M.p. 205°C. (Found: C 82.60%, H 5.88%. C19H16O2 requires C
82.58%, H 5.84%.). IR (cm-1) 1727, 1658. dH 7.21–8.42 (m, 8 H,
aromatic protons), 2.03 (t, 4H, 2 x –CH2), 1.47 (t, 4H, 2 x –CH2).
1-methyl-6,10-bis(4-chlorophenyl)-3-phenyl-4-thioxo-2,3-
diazaspiro[5.4]dec-1-en-8-one (10b): Compound 10b was similarly
prepared by reacting 8 with 1,5- di (4'-chlorophenyl)penta-1,4-dien-
3-one 9b (yield 62%, m.p. 170°C). (Found: C 65.63%, H 4.32%,
N 5.52%, S 6.34%, Cl 14.20% C27H22Cl2N2OS requires C 65.72%,
H 4.49%, N 5.68, S 6.50%, Cl 14.37%). IR (cm-1) 1704, 1597.
d
H 7.37–7.15 (m, 13H, aromatic H), 3.95 (dd, J = 4 Hz, 12 Hz, 2HA),
3.48 (t, J = 13, 2HM), 2.73 (dd, J = 4 Hz, 12 Hz, 2HX), 2.16 (s, 3H,
–CH3), dC 210.9 (C=O), 152.4 (C=S), 143.4 (C=N), 134.8, 130.4,
128.9, 128.8, 128.5, 128.4, 128.2, 125.4 (aromatic C), 106.7 (spiro
carbon), 63.7 (–CH), 43.0 (–CH2), 18.7 (–CH3). m/z (ESI) 492 (M+).
Methyl
3-[2-Hydroxy-4,4-dimethyl-6-oxocyclohex-1-enyl]
propionate (12): Dimedone 11 (0.7 g, 5 mmol) was added to the stirred
solution of sodamide (catalytic amount) in DMF (15 ml) at 10–15°C.
To this, methyl acrylate 2 (0.48 g, 5.5 mmol) was added dropwise
for 3 min. This reaction mixture was then stirred for 2 h at room
temperature. The reaction mixture was then poured onto the crushed
ice and acidified using aqueous 2N HCl to pH 2–3. The separated
compound 12 was filtered, washed with water and recrystallised
from methanol/water to afford pure crystalline white compound 12,
which was air-dried (1.02 g, 90%). M.p. 119°C. (Found: C 63.55%,
H 7.90% C12H18O4 requires C 63.70%, H 8.02%). IR (cm-1) 1735.
d
C 214.5, 187.0 (2 x C=O), 134.1–127.0 (12 x aromatic carbons),
42.1 (spiro carbon), 38.6, 12.0 (4 x –CH2).
dH 9.35 (s, 1H, –OH) (D2O exchangeable), 3.75(s, 3H, –OCH3), 2.58
(10-Oxo-10H-anthracene-9,9-diyl)dipropionitrile (6): Anthrone 1
(0.97 g, 5 mmol) and catalytic amount of Triton B were stirred in
15 ml. of 1–4 dioxane at room temperature. To this, acrylonitrile 5
(0.53 g, 10 mmol) was added dropwise during 3 min. This reaction
mixture was kept stirring at 60°C for 1.5 h and then allowed to stand
for overnight at room temperature. The reaction mixture was poured
onto crushed ice and acidified using aqueous 2N HCl to pH 2–3.
The obtained pale yellow coloured solid was filtered off, washed with
water and vacuum dried and recrystallised from benzene/pet ether to
give white crystals of compound 6 (1.41 g, 94%). M.p. 215°C (lit.8a
213–215°C). (Found: C 79.78%, H 5.08%, N 9.17% C20H16N2O
requires C 79.98%, H 5.37%, N 9.33%.). IR (cm-1) 2244, 1662.
(t, 4H, 2 x –CH2), 2.38 (s, 2H, –CH2), 2.21 (s, 2H, –CH2), 1.05 (s,
6H, 2 x –CH3). dC 198.3, 171.5 (2 x C=O), 171.3 (C=C–OH), 113.2
(C=C–OH), 50.7 (–OCH3), 32.9 (tetrahedral carbon), 28.1 (2 x –
CH3), 42.8, 31.3, 16.3 (4 x –CH2).
3-(2-Hydroxy-4,4-dimethyl-6-oxocyclohex-1-enyl)propionic acid
(14) from (12): Compound 12 (1.13 g, 5 mmol) was refluxed in water
(25 ml) containing NaOH (0.5 g) for 2 h. The reaction mixture was
poured onto crushed ice and acidified using aqueous 2N HCl to pH
2–3. Separated product was filtered, washed with water, vacuum dried
and recrystallised from methanol/water to afford crystalline colourless
compound 14 (0.90 g, 85%). M.p. 140°C. (Found: C 62.21%,
H 7.49% C11H16O4 requires C 62.25%, H 7.60%). IR (cm-1) 1706.
dH 10.90–10.10 (br. 2H, –COOH and –OH) (D2O exchangeable),
2.42 (s, 2H, –CH2), 2.38 (t, 2H, –CH2), 2.29 (s, 2H, –CH2), 2.14
(t, 2H, –CH2), 0.97 (s, 6H, 2 x –CH3). dC 198.3 (C=O; ketone), 174.6
(C=O; acid), 153.1 (C=C–OH), 111.9 (C=C–OH), 50.7 (–OCH3),
32.6 (tetrahedral carbon), 37.0, 31.6,17.5 (4 x –CH2), 28.0 (2 x –
CH3). m/z (ESI) 212 (M+).
3-(2-Hydroxy-4,4-dimethyl-6-oxocyclohex-1-enyl)propionitrile
(13): Dimedone 11 (0.7 g, 5 mmol) was added to the stirred solution
of sodamide (catalytic amount) in DMF (15 ml) at 10–15°C. To this
acrylonitrile 5 (0.30 g, 5.5 mmol.) was added dropwise for 3 min.
A reaction mixture was then stirred for 2 h at room temperature.
The reaction mixture was then poured onto the crushed ice and
acidified using aqueous 2N HCl to pH 2–3. Separated solid was
filtered, washed with water, vacuum dried and recrystallised from
methanol/water to afford crystalline white compound 13 (0.87 g,
90%). M.p. 150°C (lit.14a 150–151°C). (Found: C 68.20%, H 7.75%,
N 7.12% C11H15NO2 requires C 68.37%, H 7.82%, N 7.25%).
d
H 8.45–7.52 (m, 8 H, aromatic protons), 2.63 (t, 4H, 2 x –CH2), 1.57
(t, 4H, 2 x –CH2).
4'-imino-10-oxospiro[anthracene-9,1'-cyclohexane]-3-carbo-
nitrile (7): Compound 6 (1.5 g, 5 mmol) was dissolved in 25 ml
toluene. To this, pulverised sodium (0.12 g, 5 mmol) was then
added. The reaction mixture was refluxed for 8 h. To this reaction
mixture, a little methanol was added to react with the unreacted
sodium metal. From the reaction mixture, solvent was removed by
vacuum distillation and the remaining solid contents were poured
onto crushed ice and acidified using aqueous 2N HCl to pH 2–3.
The dark coloured solid obtained was then filtered, washed with water,
vacuum dried, and recrystallised from benzene/pet ether to afford
pure compound 7 (1.11 g, 74%). M.p. 246°C. (Found: C 79.80%,
H 5.11%, N 9.18% C20H16N2O requires C 79.98%, H 5.37%,
N 9.33%.). IR (cm-1) 2252, 1668. dH 8.32–7.18 (m, 8 H, aromatic
protons), 7.90 (br, 1H, –NH) (D2O exchangeable), 2.53 (m, 1H, –
CH), 2.33–1.96 (m, 6H, 3 x –CH2). dC 187.0 (C=O), 164.5 (C=NH),
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JOURNAL OF CHEMICAL RESEARCH 2007 471
IR (cm-1) 3418, 2959, 2250, 1707. dH 9.40 (br, 1H, –OH), 2.72 (m,
4H, 2 x –CH2), 2.39 (s, 2H, –CH2), 2.22 (s, 2H, –CH2), 1.10 (s, 6H,
2 x –CH3).
3-(2-Hydroxy-4,4-dimethyl-6-oxocyclohex-1-enyl)propionic acid
(14) from (13): Compound 13 (0.97 g, 5 mmol) was refluxed in water
(25 ml.) containing NaOH (0.5 g) for 2 h. The reaction mixture was
then poured onto the crushed ice and acidified using aqueous 2N HCl
to pH 2–3. Separated solid was filtered, washed with water, vacuum
dried and recrystallised from methanol/water to afford crystalline
white compound 14 (0.88 g, 85%). M.p. 140°C.
Indian J. Chem., 1999, 38(B), 218; (f). M.S. Chande and S.K. Balel,
Indian J. Chem., 1996, 35(B), 377; (g) M.S. Chande, J.D. Bhandari and
A.S. Karyekar, Indian J. Chem., 1995, 34(B), 990; (h) M.S. Chande and
N.M. Paingankar, Indian J Chem., 1995, 34(B), 603.
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(a) M.S. Chande and R.R. Khanwelkar, Tet. Lett., 2005, 46, 7787;
(b) M.S. Chande, R.S. Verma, P.A. Barve, R.R. Khanwelkar,
R.B. Vaidya and K.B. Ajaikumar, Eur. J. Med. Chem., 2005, 40, 1143;
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345; (e) M.S. Chande, P.A. Barve and V. Suryanarayan, J. Heterocyclic
Chem, (In press).
5
6
7,7-Dimethyl-3,4,7,8-tetrahydro-2H-chromene-2,5(6H)-dione(15):
The keto-acid 14 (1.06 g, 5 mmol) was refluxed in freshly distilled
acetic anhydride (25 ml.) under nitrogen atmosphere at 150°C. After
2 h, anhydrous sodium acetate (catalytic amount) was added. Boiling
was continued for another 2 h. The acetic anhydride was removed
by distillation and to remaining material, diethyl ether was added. It
was washed with dilute sodium carbonate solution twice followed
by water. The ether layer was then dried by using sodium sulfate,
and on evaporation gave a white product (0.63 g, 65%). M.p. 56°C
(lit.15 56–58°C). (Found: C 62.87%, H 7.14% C11H14O3 requires C
68.02%, H 7.26%). IR (cm-1) 1782, 1655. dH 2.72 (m, 2H, –CH2),
2.62 (s, 2H, –CH2), 2.28 (s, 2H, –CH2), 2.20 (m, 2H, –CH2), 1.11 (s,
6H, 2 x –CH3).
7
8
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9
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Received 7 July 2007; accepted 31 July 2007
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