An efficient regioselective synthesis of functionalized biphenyls via sequential reactions of aromatic aldehydes and β-keto esters or ketones

Article abstract of DOI:10.1016/j.tetlet.2009.02.001

Knoevenagel/Michael/Aldol reactions of aromatic aldehydes and β-keto esters/ketones in a sequential manner yielded intermediate cyclohexanones in good yields. The latter, on oxidative aromatization with iodine, afforded functionalized biphenyls with at le

Full text of DOI:10.1016/j.tetlet.2009.02.001

Tetrahedron Letters 50 (2009) 1812–1816
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An efficient regioselective synthesis of functionalized biphenyls via sequential
reactions of aromatic aldehydes and b-keto esters or ketones
*
Anindra Sharma, Jyoti Pandey, R. P. Tripathi
Medicinal and Process Chemistry Division, Central Drug Research Institute, Lucknow 226 001, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Knoevenagel/Michael/Aldol reactions of aromatic aldehydes and b-keto esters/ketones in a sequential
manner yielded intermediate cyclohexanones in good yields. The latter, on oxidative aromatization with
iodine, afforded functionalized biphenyls with at least one phenolic hydroxyl in moderate to good yields.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 2 December 2008
Revised 29 January 2009
Accepted 2 February 2009
Available online 5 February 2009
Keywords:
Polysubstituted benzenes
Aldol reactions
Michael additions
Knoevenagel reaction
Regioselective
Hydroxylated biphenyls
The phenyl group and polysubstituted benzenes are key
structures of great utility in synthetic and natural product
chemistry, medicinal chemistry and material sciences. Hydrox-
ylated biphenyl derivatives occur in a large number of natu-
atives17 and [4+2] annulation strategy from the Baylis–Hillman
reaction.18 Within
short span of time four different ap-
a
proaches were reported for the synthesis of biphenyls starting
from Baylis–Hillman adducts.19 Keeping in view the above
points, we were prompted to synthesize functionalized biphe-
nyls, starting from b-keto carbonyl compounds and aromatic
aldehydes. These may serve as starting material for the synthe-
sis of antitubercular agents in our ongoing programme. Our
method of preparation is simple and economical as no special
apparatus or chemical is required and is also devoid of any
toxic byproducts during the reaction.
The reaction of a mixture of benzaldehyde and pentane-2,4-
dione in the presence of piperidine (20 mol %) resulted in an inter-
mediate cyclohexanone derivative 1a in good yields (Scheme 1).
Compound 1a was a diastereoisomeric mixture as evident from
its spectral data (1H and 13C NMR) and used altogether in the next
step. In order to screen the suitability of the base used for cyclo-
hexanone preparation, we have carried out the above-mentioned
rally
occurring
compounds,
such
as
vancomycin,
biphenomycin and ellagitannins.1 Therefore, the preparation of
polysubstituted aromatics in general and biphenyls in particu-
lar has been a fascinating area in organic syntheses.2 Classical
approaches are based on aromatic substitution, which intro-
duces a substituent to the benzene ring. Synthetic methodolo-
gies based on this route have been developed including
electrophilic3 or nucleophilic substitutions4, coupling reactions5
catalyzed by transition metals and metallation–functionalization
reactions.6 However, these approaches have some drawbacks
from the viewpoint of atom economy7 or environmental con-
cern. The methods that construct the aromatic backbone from
acyclic precursors have received growing interest recently due
to their short synthetic steps and selective nature.8 These gen-
eral features are common in the most useful benzannulation
reactions involving different inter- and intramolecular cycliza-
tions, cycloadditions and benzannulation reactions,9–16 synthesis
of acetophenones and methyl benzoates via the reaction of 1,3-
dinitroalkanes with 2-ene-1,4-dione or 2-ene-4-oxo ester deriv-
O
O
CHO
O
O
Catalyst
H3C
OH
CH3
+
CH3
O
CH3
1a
* Corresponding author. Tel.: +91 0522 2612411; fax: +91 522 26124305.
E-mail address: rpt.cdri@gmail.com (R.P. Tripathi).
Scheme 1.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.02.001

A. Sharma et al. / Tetrahedron Letters 50 (2009) 1812–1816
1813
Table 1
O
O
O
OH
R
Synthesis of intermediate cyclohexanone derivative 1a under the influence of various
catalysts
R
Iodine/MeOH
R
OH
CH3
CH3
Base
Mol (%)
Reaction time (h)
Yield (%)
O
R
O
Piperidine
DABCO
DBU
Et3N
K2CO3
20
20
20
20
20
20
10
12
12
15
15
16
80
70
63
62
40
56
1b-1k
2b-2k
Scheme 3.
Pyrrolidine
Structural elucidation of all the biphenyls so obtained was
carried out by their detailed spectroscopic analysis.22 The posi-
tion of different substituents in the biphenyls (2b–k) was further
confirmed by the NOESY experiment with one such compound
(Fig. 2, 2c), which shows the interaction of the C-5 proton of
the penta-substituted benzene ring with the adjacent methyl
protons of the same ring and no interaction with protons of
the other aromatic ring. This clearly indicates the closeness of
the C-5 proton to the methyl group at C-6 of the penta-substi-
tuted benzene ring.
A plausible mechanism for the formation of cyclohexanone
derivatives during the reaction of aldehyde and b-keto ester or
ketone has already been reported by Enders et al.21 It involves
the Knoevenagel condensation of an aldehyde with b-keto ester
or ketone to give a Knoevenagel product (A), which undergoes
reaction with different organic and inorganic bases and the results
are shown in Table 1.
Using the above reaction conditions (Table 1, entry 1), other
compounds of the series viz. 1b–k were similarly prepared from
respective aldehydes and b-keto compounds as diastereoisomeric
mixtures and were used as such for the next step of oxidative aro-
matization. It is important to mention here that the reaction of b-
keto carbonyl compounds and aromatic aldehydes which results in
most of these intermediate cyclohexanone derivatives has also
been reported21 earlier, and the compounds were fully character-
ized by spectroscopic techniques.20
The cyclohexanone derivative (1a) thus obtained was subjected
to oxidative aromatization with iodine in methanol to give the
biphenyl derivative (2a) in moderate yields (55%) (Scheme 2). A
number of other reagents were also explored to carry out oxidative
aromatization to the respective biphenyl derivative 2a (Table 2).
However, only iodine/methanol and DABCO/DMF gave the desired
results. While a combination of I2 in methanol afforded the maxi-
mum yield (55%), DABCO in DMF gave only a 50% yield of the com-
pound in either the presence or the absence of oxygen. Therefore,
only the iodine/ methanol combination was used for oxidative aro-
matization with other substrates.
HO
O
O
O
CH3
H3C
CH3
O
B
CHO
+
O
O
O
CH3
R'
O
C
CH3
O
A
To see the scope of this method, different aromatic aldehydes
and b-keto compounds were successfully used to get the interme-
diate cyclohexanone derivatives (1b–k) as diastereoisomeric mix-
tures which in turn were oxidized with iodine separately to give
their respective biphenyl derivatives (2b–k) (Scheme 3). The re-
sults are depicted in Table 3.
H2O
OH
O
O
O
O
O
H
CH2
-H2O
O
Me
Me
OH
CH3
CH3
O
O
O
F
D
E
I2
O
OH
O
H
OH
O
OH
I2
H
Ar
O
O
O
OH
Me
I
-HI
oxidative reagents
Table 2
H3C
H3C
Me
I
OH
H
O
Me
O
CH3
CH3
CH3
I
O
O
CH3
O
H
G
I
1a
2a
-HI
OH
Scheme 2.
O
Table 2
Optimization of the reaction condition for the conversion of 1a to 2a
Me
O
Entry
Conditions
% Yield
J
1
2
3
4
5
6
7
8
9
DDQ(1.0 equiv), benzene, 80–120 °C, 24 h
DDQ(5.0 equiv), toluene, 120–140 °C, 24 h
DBU(10 mol %), THF, 80–100 °C, 72 h
DBU(3.0 equiv), DMF, 120–140 °C, 12 h
DABCO(5.0 equiv), DMF, 120–140 °C, 12 h
I2, toluene, 120–140 °C, 16 h
I2, isopropanol, 80–120 °C, 16 h
I2, propanol, 80–120 °C, 14 h
I2, ethanol, 80–120 °C, 14 h
No reaction
No reaction
No reaction
20%
50%
20%
No reaction
30%
20% and trans-
esterification product
55%
O
H
O
OH
OH
H3C
Me
Me
H
O
N
O
G
N
DABCO
10
I2, methanol, 80–120 °C, 12 h
Figure 1.

1814
A. Sharma et al. / Tetrahedron Letters 50 (2009) 1812–1816
Table 3
Synthesis of biphenyls via sequential reactions of different aromatic aldehydes and b-keto esters or ketones
Entry
Aromatic aldehyde
b-Keto compound
Cyclohexanone
% Yield
Biphenyl derivatives
OH
Reaction time (h)
% Yield
55
O
O
O
CHO
OH
CH3
O
O
O
O
O
O
O
O
1
82
12
O
2a
O
1a
O
O
O
OH
CHO
OH
2
3
4
5
61
75
72
69
12
11
12
14
55
55
55
40
CH3
Br
Cl
O
Br
Cl
O
2b
Br
1b
O
O
O
OH
CHO
OH
CH3
O
O
Cl
2c
1c
O
O
O
OH
CHO
OH
CH3
PhH2CO
O
PhH2CO
O
OCH2Ph
CHO
2d
1d
O
O
O
OH
H3CO
H3CO
OH
CH3
O
O
O
O
H3CO
H3CO
O
OCH3
O
OCH3
2e
1e
O
O
O
OH
H3CO
H3CO
CHO
CHO
OH
CH3
6
7
75
66
14
14
45
45
O
OCH3
O
OCH3
2f
1f
O
O
O
OH
EtO
EtO
OH
CH3
O
O
EtO
O
OEt
O
OEt
2g
1g
O
O
O
OH
CHO
Cl
H3CO
H3CO
Cl
OH
O
O
8
65
14
45
CH3
H3CO
O
OCH3
O
OCH3
Cl
2h
1h
O
O
O
OH
CHO
EtO
EtO
Cl
OH
O
O
9
10
11
69
70
75
14
14
12
50
40
60
CH3
EtO
O
OEt
O
2i
OEt
OH
Cl
Cl
1i
O
O
O
CHO
H3CO
Br
H3CO
O
O
OH
CH3
H3CO
O
OCH3
O
OCH3
Br
Br
1j
2j
O
O
OH
O
CHO
Cl
Cl
OH
CH3
Cl
O
O
O
O
1k
2k

A. Sharma et al. / Tetrahedron Letters 50 (2009) 1812–1816
1815
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a Michael addition of an active methylene compound via its enol
form (B) to give an intermediate (C). The latter undergoes intra-
molecular aldol condensation in the presence of a base via enol
(D) to give an intermediate cyclized aldol product (E), which, on
dehydration, results in a cyclohexenone derivative (F), which ex-
ists as a tautomeric mixture with a predominance of the enol
form (G) in the presence of iodine. Dehydration and enolization
are facilitated by iodine as it acts as a Lewis acid. Dehydration in
such compounds with iodine in methanol or other solvents is
well known.23,24 Finally, the removal of hydroiodic acid from
intermediate (I) mediated by iodine results in the desired biphe-
nyl derivatives (Fig. 1a). The final site of aromatization is also
possible in the presence of the base, which may abstract a pro-
ton from carbon adjacent to the carbonyl carbon in intermediate
G followed by rearrangement to more stable biphenyl derivatives
(Fig. 1b).
In summary, we have developed a simple method for the prep-
aration of functionalized biphenyls via domino Knoevenagel, Mi-
chael and Aldol reactions, followed by the oxidation of the
intermediate cyclohexanone with iodine. The compounds are ob-
tained in moderate yields. The application of these compounds in
the designing of new biologically important molecules is
underway.
17. Ballini, R.; Barboni, L.; Fiorini, D.; Giarlo, G.; Palmieri, A. Chem. Commun. 2005,
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Kim, T. H.; Kim, J. N. Bull. Korean Chem. Soc. 2003, 24, 999–1001.
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Reson. Chem. 2005, 43, 430–434.
21. Enders, D.; Müller, S.; Demir, A. S. Tetrahedron Lett. 1988, 29, 6437–6440.
22. Typical procedure for the synthesis of biphenyls and their physical data: To a
magnetically stirred solution of b keto compound (6.07 ml, 59.0 mmol) and
benzaldehyde (3.0 ml, 29.5 mmol) in ethanol (5.0 mL), piperidine (0.583 ml,
5.9 mmol) was added, and the reaction mixture was stirred at ambient
temperature. The stirring continued till the disappearance of aldehyde; the
reaction mixture was filtered and the solid so obtained was washed with
ethanol followed by water and n-hexane sequentially to get cyclized product
1a as a colourless powder which was dried under a vacuum. The latter (1a,
1.0 g, 3.70 mmol) was undergoing oxidation with I2 (1.88 g, 7.40 mmol) in
MeOH under refluxing conditions. After refluxing at 70 °C for the given time
(Table 3), the reaction mixture was evaporated under reduced pressure. The
residue was extracted with ethylacetate and water followed by washing with a
saturated sol. of sodium thiosulfate. The ethyl acetate layer was dried over
sodium sulfate (Na2SO4) and concentrated under reduced pressure. The crude
product was purified by column chromatography over SiO2 (60–120 mesh)
using EtOAc/n-hexane (2:8) as eluent to give the desired biphenyl (2a) as a
Acknowledgements
This is CDRI communication No. 7552. The authors thank DRDO,
DBT and CSIR (New Delhi) for financial assistance. Anindra and Jyo-
ti are thankful to CSIR, New Delhi, for a JRF and a SRF, respectively.
We also thank the SAIF staff for providing the spectral data and
microanalysis.
light yellow solid. Mp 90–91 °C. IR (KBr): mmax = 3436, 3019, 2363, 1693, 1631.
1H NMR (200 MHz, CDCl3 + CCl4): d 11.73 (s, 1H, OH), 7.45–7.42 (m, 3H, ArH),
7.30–7.26 (m, 2H, ArH), 6.85 (s, 1H, ArH), 2.26 (s, 3H, CH3), 1.71 and 1.70 (two
s, 6H, COCH3). 13C NMR (50 MHz, CDCl3 + CCl4): d 206.5, 206.1 (2CO), 161.6,
141.2, 139.9, 139.5, 135.9 (5ArC), 130.6, 129.3, 129.2 (5ArCH), 119.8 (ArC),
119.4 (ArCH), 32.1 and 31.7 (2COCH3), 20.5 (CH3). MS (ESMS): m/z: 269 [M+H]+.
Elemental Anal. Calcd for C17H16O3: C, 76.10; H, 6.01. Found: C, 76.08; H, 6.00.
Supplementary data
Compound 2b: Light yellow solid. Mp 131–132 °C. IR (KBr): mmax = 3779, 3345,
2922, 2143, 1592. 1H NMR (200 MHz, CDCl3 + CCl4): d 11.72 (s, 1H, OH), 7.61 (d,
2H, J = 8.4 Hz, ArH), 7.18 (d, 2H, J = 8.4 Hz, ArH), 6.87 (s, 1H, ArH), 2.25 (s, 3H,
CH3), 1.78 and 1.75 (two s, 6H, COCH3). 13C NMR (50 MHz, CDCl3 + CCl4,): d
205.9, 205.8 (2CO), 161.7, 141.2, 138.3, 135.9 (5ArC), 132.5, 132.2 (4ArCH),
123.9 (ArC), 119.8 (ArCH), 119.6 (ArC), 32.3 and 32.0 (2COCH3), 20.4 (CH3). MS
(ESI+): m/z: 348 [M+H]+. Elemental Anal. Calcd for C17H15BrO3: C, 58.81; H,
4.35. Found: C, 58.79; H, 4.37. Compound 2c: Light yellow solid. Mp 140–
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2009.02.001.
References and notes
1. (a) Nicolaou, K. C.; Boddy, C. N. C.; Brase, S.; Winssinger, N. Angew. Chem., Int.
Ed. 1999, 38, 2096–2152; (b) Hubbard, B. K.; Walsh, C. T. Angew. Chem., Int. Ed.
2003, 42, 730–765; (c) Schimana, J.; Gebhardt, K.; Holtzel, A.; Schmid, D. G.;
Sussmuth, R.; Muller, J.; Pukall, R.; Fiedler, H. P. J. Antibiot. 2002, 55, 565–570;
(d) Ezaki, M.; Iwami, M.; Yamashita, M.; Komori, T.; Umehara, K.; Imanaka, H.
Appl. Environ. Microbial. 1992, 58, 3879–3882; (e) Quideau, S.; Feldman, K. S.
Chem. Rev. 1996, 96, 475–503; (f) Feldman, K. S. Phytochemistry 2005, 66, 1984–
2000.
142 °C. IR (KBr): m
max = 3852, 3430, 3020, 2924, 2361, 1685, 1634, 1596 1H
NMR (200 MHz, CDCl3 + CCl4): d 11.72 (s, 1H, OH), 7.45 (d, 2H, J = 8.4 Hz, ArH),
7.25 (d, 2H, J = 8.4 Hz, ArH), 6.86 (s, 1H, ArH), 2.25 (s, 3H, CH3), 1.78 and 1.74
(two s, 6H, COCH3). 13C NMR (50 MHz, CDCl3 + CCl4): d 206.1, 206.0 (2CO),
161.7, 141.3, 138.4, 137.8, 136.0, 135.8 (6ArC), 131.9, 129.5, 119.8 (5ArCH),
109.9 (ArC), 32.3, 32.0 (2COCH3), 20.4 (CH3).. MS (ESI+): m/z: 303.5 [M+H]+;
Elemental Anal. Calcd for C17H15ClO3: C, 67.44; H, 4.99. Found: C, 67.42; H,
5.00. Compound 2d: White solid. Mp 134–136 °C. IR (KBr): mmax = 3427, 3021,
2. Astrue, D. In Modern Arene Chemistry; Wiley-VCH: Weinheim, Germany, 2002.
3. (a) Olah, G.. In Friedel–Crafts and Related Reactions; Wiley Interscience: New
York, 1963; Vols. I–IV; (b) Pearson, D. E.; Buehler, C. A. Synthesis 1972, 533–542.
4. (a) Smith, M. B.; March, J. Advanced Organic Chemistry, 5th ed.; Wiley-
Interscience: New York, 2001. Chapter 13; (b) Buncel, E.; Dust, J. M.; Terrier,
F. Chem. Rev. 1995, 95, 2261–2280.
2923, 2363, 1632. 1H NMR (200 MHz, CDCl3 + CCl4): d 11.69 (s, 1H, OH), 7.45–
7.33 (m, 5H, ArH), 7.20 (d, 2H, J = 8.6 Hz, ArH,), 7.04 (d, 2H, J = 8.6 Hz, ArH), 6.83
(s, 1H, ArH), 5.10 (s, 2H, OCH2), 2.25 (s, 3H, CH3), 1.74 (s, 6H, 2COCH3). 13C NMR
(50 MHz, CDCl3 + CCl4): d 206.7, 206.5 (2CO), 161.6, 159.8, 141.3, 139.8, 136.6,
136.0, 131.7, 120.1 (6ArC), 131.8, 129.0, 128.6, 127.9 (7ArCH), 120.1 (ArC),

1816
A. Sharma et al. / Tetrahedron Letters 50 (2009) 1812–1816
119.1, 115.7 (3ArCH), 32.1, 31.8 (2COCH3), 20.5 (CH3). MS (ESI+): m/z: 375
[M+H]+. Elemental Anal. Calcd for C17H15ClO5: C, 61.00; H, 4.52. Found: C,
59.98; H, 4.54. Compound 2i: Light yellow oil. IR (neat): max = 3781, 3410,
[M+H]+. Elemental Anal. Calcd for C24H22O4: C, 76.99; H, 5.92. Found: C, 76.97;
m
H, 5.93. Compound 2e: Light yellow solid. Mp 135–136 °C. IR (KBr):
m
3021, 2360, 1721, 1663, 1599. 1H NMR (200 MHz, CDCl3 + CCl4): d 11.17 (s, 1H,
OH), 7.31 (d, 2H, J = 10.0 Hz, ArH), 7.14 (d, 2H, J = 10.0 Hz, ArH), 6.87 (s, 1H,
ArH), 4.00–3.85 (m, 4H, OCH2), 2.33 (s, 3H, CH3), 0.94 (t, 3H, J = 7.2 Hz, CH3),
0.76 (t, 3H, J = 7.2 Hz, CH3). 13C NMR (50 MHz, CDCl3 + CCl4): d 170.2, 168.1
(2CO), 162.3, 141.9, 140.5, 138.7, 133.1 (6ArC), 130.0 (2ArCH), 128.1(ArC),
127.3, 118.6 (3ArCH), 109.8 (ArC), 61.1, 60.8, (2OCH2), 20.0, 13.7, 12.9, (3CH3).
MS (ESMS): m/z: 363.5 [M+H]+. Elemental Anal. Calcd for C19H19ClO5: C, 62.90;
H, 5.28. Found: C, 62.88; H, 5.29. Compound 2j: Light yellow solid. Mp 95–
max = 3781, 3697, 3410, 3021, 2929, 2359, 1725, 1666, 1595. 1H NMR
(200 MHz, CDCl3 + CCl4): d 11.03 (s, 1H, OH), 7.85–7.75 (m, 3H, ArH), 7.60 (s,
1H, ArH), 7.49–7.47 (m, 2H, ArH), 7.46–7.29 (m, 2H, ArH), 6.91 (s, 1H, ArH),
3.32 and 3.23 (two s, 3H, OCH3), 2.37 (s, 3H, CH3). 13C NMR (50 MHz,
CDCl3 + CCl4): d 171.2, 169.1 (2CO), 162.7, 142.4, 142.3, 138.2, 133.1, 132.6,
128.4 (7ArC), 128.3, 127.9, 127.8, 126.9, 126.7, 126.4, 126.3, 118.8 (8ArCH),
110.4 (ArC), 52.0, 51.8 (2OCH3), 20.6 (CH3). MS (ESI+): m/z: 351 [M+H]+.
Elemental Anal. Calcd for C21H18O5: C, 71.99; H, 5.18. Found: C, 71.96; H, 5.19.
96 °C. IR (KBr): m
max = 3781, 3407, 3021, 2361, 1726 1599. 1H NMR (200 MHz,
Compound 2f: Light yellow oil. IR (neat):
m
max = 3692, 3389, 3021, 2360, 1724,
CDCl3 + CCl4): d = 10.97 (s, 1H, OH), 7.46 (d, 2H, J = 8.4 Hz, ArH), 7.03 (d, 2H,
J = 8.4 Hz, ArH), 6.85 (s, 1H, ArH), 3.45 and 3.40 (two s, 3H, OCH3), 2.31 (s, 3H,
CH3). 13C NMR (50 MHz, CDCl3 + CCl4): d 170.9, 168.7 (2CO), 162.7, 142.4,
141.0, 139.5, (4ArC), 130.7, 130.5, (4ArCH), 128.3, 121.5(2ArC), 119.0 (ArCH),
110.1 (ArC), 52.1, 51.9 (2OCH3), 20.5(CH3). MS (ESI+): m/z: 380 [M+H]+.
Elemental Anal. Calcd for C17H15BrO5: C, 53.85; H, 3.99. Found: C, 53.84; H,
1667, 1578. 1H NMR (200 MHz, CDCl3 + CCl4): d 10.97 (s, 1H, OH), 7.31–7.26
(m, 3H, ArH), 7.15–7.11 (m, 2H, ArH), 6.86 (s, 1H, ArH), 3.40 and 3.37 (two s,
6H, OCH3), 2.33 (s, 3H, CH3). 13C NMR (50 MHz, CDCl3 + CCl4): d 171.2, 169.2
(2CO), 162.4, 142.6, 142.2, 140.5 (5ArC), 128.7, 127.6, 127.3, 118.6 (6ArCH),
110.4 (ArC), 52.0, 51.9 (2OCH3), 20.5 (CH3). MS (ESI+): m/z: 301 [M+H]+.
Elemental Anal. Calcd for C17H16O5: C, 67.99; H, 5.37. Found: C, 67.97; H, 5.39.
4.00. Compound 2k: Light yellow solid. Mp 104–106 °C. IR (KBr): mmax = 3450,
Compound 2g: Light yellow solid. Mp 101–102 °C. IR (KBr):
m
max = 3782, 3021,
3020, 2924, 2359, 1631, 1523. 1H NMR (200 MHz, CDCl3 + CCl4): d 12.50 (s, 1H,
OH), 7.46–7.26 (m, 4H, ArH), 6.88 (s, 1H, ArH), 2.25 (s, 3H, CH3), 1.84 and 1.78
(two s, 6H, COCH3). 13C NMR (50 MHz, CDCl3 + CCl4): d 205.3, 205.2 (2CO),
162.9, 141.8, 138.3, 136.6, 135.9, 134.6 (6ArC), 133.0, 130.9, 130.4, 127.7, 120.8
(5ArCH), 118.7 (ArC), 31.6, 31.2 (2COCH3), 20.6 (CH3). MS (ESI+): m/z: 303.5
[M+H]+; Elemental Anal. Calcd for C17H15ClO3: C, 67.44; H, 4.99. Found: C,
67.42; H, 5.00.Intermediate G: (Fig. 1a): Light yellow solid. Mp 75–80 °C. IR
2360, 1723, 1664, 1596. 1H NMR (200 MHz, CDCl3 + CCl4): d 11.11 (s, 1H, OH),
7.30–7.27 (m, 3H, ArH), 7.18–7.13 (m, 2H, ArH), 6.86 (s, 1H, ArH), 3.96–3.80 (m,
4H, OCH2), 2.34 (s, 3H, CH3), 0.90 and 0.71 (two t, J = 7.2 Hz, 3H, CH3,). 13C NMR
(50 MHz, CDCl3 + CCl4): d 170.8, 168.7 (2CO), 162.5, 142.3, 142.0, 140.8 (4ArC),
129.0 (2ArCH), 128.6 (ArC), 127.5, 127.2, 118.6 (4ArCH), 110.5 (ArC), 61.2, 61.0
(2OCH2), 20.5 (CH3), 14.0, 13.3 (2CH3). MS (ESI+): m/z: 329 [M+H]+. Elemental
Anal. Calcd for C19H20O5: C, 69.50; H, 6.14. Found: C, 69.47; H, 6.15. Compound
(KBr):
m
max = 3626, 3020, 2925, 2361, 1521, 1425. 1H NMR (200 MHz,
2h: Light yellow oil. IR (neat):
m
max = 3781, 3425, 3020, 2360, 1724, 1607. 1H
CDCl3 + CCl4): d 16.2 (s, 1H, OH), 7.42–7.09 (m, 4H, ArH), 6.14 (s, 1H, H-5),
4.76 (s, 1H, H-2), 3.22 (s, 1H, H-1), 2.36 (s, 3H, CH3), 1.84 and 1.83 (two s, 6H,
COCH3). MS (ESI+): m/z: 305 [M+H]+; Elemental Anal. Calcd for C17H15ClO3: C,
67.00; H, 5.62. Found: C, 67.42; H, 5.00.
NMR (200 MHz, CDCl3 + CCl4): d 11.02 (s, 1H, OH), 7.32 (d, 2H, J = 10.0 Hz, ArH),
7.11 (d, 2H, J = 10.0 Hz, ArH), 6.87 (s, 1H, ArH), 3.45 and 3.42 (s, 3H, OCH3), 2.32
(s, 3H, CH3). 13C NMR (50 MHz, CDCl3 + CCl4): d 171.0, 168.9 (2CO), 162.6,
142.4, 141.1, 138.9, 133.5 (5ArC), 130.1(2ArCH), 128.5 (ArC), 127.8, 119.0
(3ArCH), 110.2 (ArC), 52.2, 52.0 (2OCH3), 20.5 (CH3). MS (ESI+): m/z: 335.5
23. Stavber, G.; Zupan, M.; Stavber, S. Tetrahedron Lett. 2006, 47, 8463–8466.
24. Reeve, W.; Doherty, R. M. J. Org. Chem. 1975, 40, 1662–1664.