New synthesis of 3-methoxy-4-substituted pyrazole derivatives

Article abstract of DOI:10.1016/j.tetlet.2005.11.072

A simple and efficient protocol for the synthesis of 3-methoxy-4- arylmethylene- and 3-methoxy-4-heteroarylmethylenepyrazoles has been developed. These derivatives are obtained in one step from alcohols 3 or 8a-b.

Full text of DOI:10.1016/j.tetlet.2005.11.072

Tetrahedron
Letters
Tetrahedron Letters 47 (2006) 817–820
New synthesis of 3-methoxy-4-substituted pyrazole derivatives
*
´
Bertrand Cottineau, Jacques Chenault and Gerald Guillaumet
Institut de Chimie Organique et Analytique, UMR CNRS 6005, Universite´ d’Orle´ans, BP 6759, 45067 Orle´ans Cedex 2, France
Received 8 March 2005; revised 13 November 2005; accepted 15 November 2005
Abstract—A simple and efficient protocol for the synthesis of 3-methoxy-4-arylmethylene- and 3-methoxy-4-heteroarylmethylene-
pyrazoles has been developed. These derivatives are obtained in one step from alcohols 3 or 8a–b.
Ó 2005 Elsevier Ltd. All rights reserved.
The pyrazole moiety is present in a wide variety of bio-
logically active compounds.1 Among them, Kess et al.
have described a number of 3-hydroxy-4-benzylpyraz-
oles (Fig. 1), which represent a new class of antidiabetic
compounds.2 These pyrazoles seem to act as inhibitors
of glucose renal reabsorption. The authors have descri-
bed a wide number of derivatives with good hypogly-
cemic activities. In all cases, their syntheses proceeded
in low yield from b-ketoesters (Fig. 1).
In order to examine the formation of carbocation 1 we
decided to react pyrazolylmethanol 3 with nucleophilic
species, such as an alcohol and a thiol.
Reactions were carried out with a catalytic quantity of
camphorsulfonic acid using either dichloromethane or
the alcohol as a solvent. This resulted in the formation
of ether or thioether 4a–h in moderate to excellent yields
(Scheme 2, Table 1).5
In the last few years, we have been interested in the reac-
tivity and the biological activity of ethyl 3-hydroxy-1H-
pyrazole-4-carboxylate. During these studies, reactions
on N1, O3 and C5 positions and the in vivo hypoglyce-
mic activity of these derivatives have been described.3 In
the present letter, we show a new and efficient synthesis
of 4-arylmethylenepyrazole and 4-heteroarylmethylene-
pyrazole derivatives. The methodology employed was
based on a Friedel–Crafts-type reaction between carbo-
cation 1 and aromatic species (Scheme 1). We postulated
that this intermediate could be easily obtained by dehy-
dration of alcohol 3,4 compound synthesized in quanti-
tative yield by reduction of the ester function of pyrazole
2.3
During these reactions, bispyrazolylmethane 5 was
obtained as a by-product (Table 1). According to the
synthesis of bisbenzopyrazolylalkane described by Miki
and collaborators,6 we have proposed the following
autocondensation mechanism. In acidic conditions, dehy-
dration of pyrazolylmethanol 3 forms the intermediate 1
Me
Me
N
+
N
N
N
ArH
MeO
MeO
CH
2
Ar
1
Scheme 1. Reaction investigated for the synthesis of 4-benzyl-
pyrazoles.
R
N
N
RO
R
Me
Me
Me
b
N
N
a
N
N
N
N
MeO
MeO
MeO
Figure 1. Structure of hypoglycemic pyrazoles.
COOEt
2
ZR
OH
4a-h
3
Scheme 2. Reagents and conditions: (a) LiAlH4 (2 equiv), THF, rt,
2 h, 99%. (b) 4a–c ROH (solvent), CSA (0.1 equiv), rt, 1 h 4d–h RZH
(3 equiv), CSA (0.1 equiv), CH2Cl2, rt, 1 h.
Keywords: Pyrazole; Benzylpyrazole; Friedel–Crafts.
*
Corresponding author. Tel.: +33 2 38 41 73 54; fax: +33 2 38 41 72
81; e-mail: gerald.guillaumet@univ-orleans.fr
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.11.072

818
B. Cottineau et al. / Tetrahedron Letters 47 (2006) 817–820
Table 2. Synthesis of 3-methoxy-4-substituted pyrazoles 6a–i
Table 1. Synthesis of ethers and thioether 4a–h
Yield (%)a
RXH
Solvent
Compound
4 (%)a
5 (%)a
ArH
Compound
Me
EtOH
iPrOH
tBuOH
EtOH
iPrOH
tBuOH
4a
4b
4c
100
100
90
0
0
0
OMe
N
MeO
N
OMe
OMe
50
OH
CH2Cl2
4d
71
25
MeO
MeO
MeO
OMe
OMe
6a
MeO
MeO
Me
O
Me
CH2Cl2
CH2Cl2
4e
4f
50
60
46
34
OH
OH
Me
O
N
N
64
71
50
75
80
85
78
60
Cl
MeO
6b
6c
CH2Cl2
CH2Cl2
4g
4h
73
80
23
13
OH
Me
EtSH
N
OH
N
OH
OH
a Isolated yield.
MeO
which reacts with another alcohol to give, after loss of
formaldehyde, pyrazole 5 (Scheme 3).
Me
OH
MeO
N
MeO
N
MeO
Me
After optimizing the conditions for the formation of car-
bocation 1, we investigated its reaction with aromatic
and heteroaromatic species. To avoid the formation of
bispyrazolylmethane 5, reactions were carried out by
adding pyrazolylmethanol 3 very slowly to a solution
of the aromatic and a catalytic quantity of camphorsul-
fonic acid in dichloromethane. These reactions produced
pyrazoles 6a–i7 in yields varying from 50% to 80%
(Scheme 4, Table 2). Structure of these derivatives was
assigned based on NMR (1D and 2D). For pyrazoles
6a–d, the multiplicity of protons of phenyl rings indi-
cates the substitution position. For compounds 6f–i,
NOESY experiments were needed, these show a correla-
tion between the CH2 and H30 which confirms the sub-
stitution on C2 position of the heterocycle.
OMe
6d
MeO
N
N
N
H
N
H
MeO
6e
Me
N
N
N
H
N
MeO
6f
H
Me
N
N
N
N
Me
MeO
Me
Me
6g
Me
N
+
N
N
N
Me
MeO
MeO
+
N
O
O
1
CH2
N
HO
3
O
MeO
6h
Me
Me
+
N
N
Me
N
N
Me
N
N
N
MeO
MeO
OH
OMe
N
N
OH
O
O
5
H
OMe
MeO
6i
N
Me
a Isolated yield.
Scheme 3. Mechanism of the autocondensation of pyrazolylmethanol
3.
This reaction is compatible with activated benzene
derivatives and neutral oxygen and nitrogen heteroaro-
matic species. In the case of less activated benzene deriv-
atives, such as anisole and toluene, this reaction yielded
pyrazole 5.
Me
Me
N
N
N
N
a
MeO
MeO
Ar
6a-i
OH
To further diversify our synthetic library, we extended
this reaction to substituted pyrazolylmethanol. Alcohols
8a and 8b8 were synthesized in good yields by the addi-
tion of organolithium species to aldehyde 7 (Scheme 5).9
3
Scheme 4. Reagents and conditions: (a) ArH (3 equiv), CSA
(0.1 equiv), CH2Cl2, rt, 30 min.

B. Cottineau et al. / Tetrahedron Letters 47 (2006) 817–820
819
3. (a) Cottineau, B.; Chenault, J. Synlett 2002, 769; (b)
Cottineau, B.; Toto, P.; Marot, C.; Pipaud, A.; Chenault,
J. Bioorg. Med. Chem. Lett. 2002, 12, 2105.
Me
Me
N
N
N N
a
MeO
MeO
4. Synthesis of compound 3: To a stirred suspension of
LiAlH4 (4.1 g, 108.4 mmol) in 30 mL of dry THF, cooled
to 0 °C, was added slowly a solution of compound 2 (10 g,
54.2 mmol) in 50 mL of dry THF. The reaction mixture
was stirred for 2 h at rt and cooled to 0 °C. Then, 4.1 mL
of water, 4.1 mL of 15% NaOH solution and 12.3 mL of
water were added successively. The resulting mixture was
stirred for 1 h at rt and filtered off on Celite. The filtrate
was dried over MgSO4 and concentrated under vacuum
to give a colourless oil (7.6 g, 99%). 1H NMR (250
MHz, CDCl3) d 3.55 (s, 3H); 3.75 (s, 3H); 4.25 (s, 2H);
6.95 (s, 1H). 13C NMR (63 MHz, CDCl3) d 38.7, 56.2,
58.2, 105.4, 131.4, 161.3. MS: 143 5[M+H]+. IR (NaCl)
CHO
OH
7
3
Me
Me
N
N
N
N
c
b
MeO
MeO
R = Ph, Bu
R
Ar
9a-d
R
OH
8a-b
Scheme 5. Reagents and conditions: (a) MnO2 (10 equiv), CHCl3, 20 h,
rt, 99%. (b) RLi (2.5 equiv), THF, ꢀ30 °C, 3 h, (8a: R = Ph 87%; 8b:
R = Bu 83%). (c) ArH (3 equiv), CSA (0.1 equiv), CH2Cl2, rt, 30 min.
3100 cmꢀ1
.
Table 3. Synthesis of pyrazoles 9a–d
5. (a) Synthesis of compounds 4a–c, general procedure: To a
stirred solution of CSA (23 mg, 0.1 mmol) in 5 mL of
alcohol was added pyrazole 3 (140 mg, 1 mmol). The
resulting mixture was stirred at rt for 1 h, then 15 mL of a
saturated NaHCO3 solution and 15 mL of CH2Cl2 were
added. The organic layer was separated, dried over
MgSO4 and concentrated under vacuum to give a colour-
less oil. Synthesis of compounds 4d–h, general procedure:
To a stirred solution of CSA (23 mg, 0.1 mmol) and
alcohol or thiol (3 mmol) in 5 mL of CH2Cl2 was added
pyrazole 3 (140 mg, 1 mmol). The resulting mixture was
stirred at rt for 1 h, then 15 mL of a saturated NaHCO3
solution and 15 mL of CH2Cl2 were added. The organic
layer was separated, dried over MgSO4 and concentrated
under vacuum to give a colourless oil.
R
ArH
Compound
Yield (%)a
Me
OMe
N
MeO
N
OMe
Ph
68
MeO
MeO
OMe
Ph
MeO
9a
Me
N
N
Ph
Bu
Bu
83
67
86
N
H
N
H
MeO
Ph
9b
Me
1
(b) Spectral data for compounds 4a–h. Compound 4a: H
NMR (250 MHz, CDCl3) d 1.15 (t, J = 6.8 Hz, 3H); 3.44
(q, J = 6.8 Hz, 2H); 3.65 (s, 3H); 3.85 (s, 3H); 4.21 (s, 2H);
7.11 (s, 1H). 13C NMR (63 MHz, CDCl3) d 15.5; 39.2; 56.4;
61.5; 65.5; 102.7; 132.0; 162.0. MS: 172 [M+H]+. Com-
pound 4b: 1H NMR (250 MHz, CDCl3) d 1.12 (d,
J = 6.2 Hz, 2H); 3.55–3.68 (m, 4H); 3.85 (s, 3H); 4.21 (s,
2H); 7.11 (s, 1H). 13C NMR (63 MHz, CDCl3) d 21.9; 38.5;
55.9; 58.4; 70.0; 102.6; 131.3; 161.3. MS: 185 [M+H]+.
Compound 4c: 1H NMR (250 MHz, CDCl3) d 1.23 (s, 9H);
3.66 (s, 3H); 3.87 (s, 3H); 4.18 (s, 2H); 7.12 (s,1H). 13C
NMR (63 MHz, CDCl3) d 29.3; 40.4; 54.8; 57.7; 74.7;
OMe
N
MeO
N
OMe
MeO
MeO
OMe
Bu
MeO
9c
Me
N
N
N
H
N
H
MeO
Bu
1
105.1; 132.9; 162.8. MS: 199 [M+H]+. Compound 4d: H
9d
a Isolated yield.
NMR (250 MHz, CDCl3) d 2.39 (t, J = 2.35 Hz, 1H); 3.62
(s, 3H); 3.82 (s, 3H); 4.04 (d, J = 2.35 Hz, 2H); 4.29 (s, 2H);
7.11 (s, 1H). 13C NMR (63 MHz, CDCl3) d 37.6; 54.9; 55.1;
58.8; 73.1; 78.6; 99.8; 130.7; 160.6. MS: 181 [M+H]+.
Compound 4e: 1H NMR (250 MHz, CDCl3) d 1.37 (s, 3H);
1.44 (s, 3H); 3.59 (dd, J = 5.0 and 11.6 Hz, 1H); 3.65–3.80
(m, 5H); 3.90 (s, 3H); 4.05 (dd, J = 6.6, 8.2 Hz, 1H); 4.20–
4.25 (m, 1H); 4.28 (s, 2H); 7.17 (s, 1H). 13C NMR
(63 MHz, CDCl3) d 23.7; 25.2; 37.3; 54.6; 58.5; 61.5; 64.3;
74.7; 100.7; 107.8; 130.3; 160.3. MS: 257 [M+H]+. Com-
pound 4f: 1H NMR (250 MHz, CDCl3) d 1.57–1.81 (m,
4H); 3.38 (t, J = 6.1 Hz, 2H); 3.46 (d, J = 6.5 Hz, 2H); 3.63
(s, 3H); 3.83 (s, 3H); 4.18 (s, 2H); 7.08 (s, 1H). 13C NMR
(63 MHz, CDCl3) d 29.0; 31.5; 40.9; 47.0; 58.1; 63.3; 70.7;
104.2; 133.6; 163.7. MS: 232–234 [M+H]+. Compound 4g:
1H NMR (250 MHz, CDCl3) d 1.40–1.80 (m, 4H); 3.65 (s,
3H); 3.86 (s, 3H); 3.90–4.00 (m, 1H); 4.18 (s, 2H); 7.11 (s,
1H). 13C NMR (63 MHz, CDCl3) d 24.0; 33.0; 39.3; 56.6;
59.8; 80.8; 103.2; 132.0; 162.1. MS: 211 [M+H]+. Com-
pound 4h: 1H NMR (250 MHz, CDCl3) d 1.23 (t,
J = 7.3 Hz, 3H); 2.48 (q, J = 7.3 Hz, 2H); 3.47 (s, 2H);
3.68 (s, 3H); 3.88 (s, 3H); 7.06 (s, 1H). 13C NMR(63 MHz,
CDCl3) d 14.6; 23.0; 25.7; 39.0; 56.3; 102.2; 130.8; 161.4.
MS: 187 [M+H]+.
As this aldehyde could not be obtained by the reduction
of ester 2, this was carried out in quantitative yield by
the reaction of alcohol 3 with MnO2. Reactions of these
alcohols with aromatic and heteroaromatic species in
the same conditions as described before gave the 4-
substituted pyrazoles 9a–d in good yields (Table 3).10
In summary, we have developed a new and efficient syn-
thesis of 3-methoxy-4-substituted pyrazoles 4, 6 and 9.
These derivatives are synthesized in mild conditions
starting from alcohols 3 and 8a–b.
References and notes
1. Elguero, J.; Goya, P.; Jagerovic, N.; Silva, A. M. S.
Targets Heterocycl. Syst. 2002, 6, 52.
2. Kees, K. L.; Fitzgerald, J. J., Jr.; Steiner, K. E.; Mattes, J.
F.; Mihan, B.; Tosi, T.; Mondoro, D.; McCaleb, M. L. J.
Med. Chem. 1996, 39, 3920.

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B. Cottineau et al. / Tetrahedron Letters 47 (2006) 817–820
6. (a) Miki, Y.; Tomii, O.; Nakao, H.; Kubo, M.; Hachiken,
8. (a) Synthesis of alcohols 8a–b, general procedure: Under
nitrogen, to a stirred solution of compound 7 (1.4 g,
10 mmol) in 30 mL of dry THF, was added at ꢀ30 °C the
organolithium (30 mmol). The resulting mixture was
stirred at ꢀ30 °C for 3 h then 30 mL of water was added.
After extraction with ethyl acetate, the organic layer was
dried over MgSO4 and concentrated under vacuum. Then,
the residue was purified by flash chromatography on silica
H.; Takemura, S.; Ikeda, M. J. Heterocycl. Chem. 1988,
25, 327; (b) Miki, Y.; Nakamura, N.; Hachiken, H.;
Takemura, S. J. Heterocycl. Chem. 1989, 26, 1739.
7. (a) Synthesis of compounds 6a–i, general procedure: To a
stirred solution of CSA (23 mg, 0.1 mmol) and the
aromatic (3 mmol) in 5 mL of CH2Cl2 was added slowly
(1 h) pyrazole 3 (140 mg, 1 mmol) in 5 mL of CH2Cl2.
The resulting mixture was stirred at rt for 1 h, then
15 mL of a saturated NaHCO3 solution and 15 mL of
CH2Cl2 were added. The organic layer was separated,
dried over MgSO4 and concentrated under vacuum.
Compounds were purified by column chromatography on
silica gel; (b) Spectral data for compounds 6a–i. Com-
gel to give
a colourless oil; (b) Spectral data for
compounds 8a–b. Compound 8a: 1H NMR (250 MHz,
CDCl3) d 3.56 (s, 3H); 3.61 (s, 3H); 5.31 (s, 1H); 6.84 (s,
1H); 7.23–7.42 (m, 5H). 13C NMR (63 MHz, CDCl3) d
38.9; 56.2; 73.9; 107.6; 126.5; 127.2; 128.3; 130.6; 142.5;
161.0. MS: 219 [M+H]+. Compound 8b: 1H NMR
(250 MHz, CDCl3) d 0.80 (t, J = 6.9 Hz, 3H); 1.13–1.37
(m, 4H); 1.52–1.83 (m, 2H); 3.64 (s, 3H); 3.81 (s, 3H); 4.10
(t, J = 6.9 Hz, 1H); 7.0 (s, 1H). 13C NMR (63 MHz,
CDCl3) d 14.1; 22.6; 28.2; 36.1; 38.9; 56.1; 72.1; 106.8;
129.8; 161.5. MS: 199 [M+H]+.
1
pound 6a: (white solid) mp: 118 °C H NMR (250 MHz,
CDCl3) d 3.55 (s, 5H); 3.75 (s, 6H); 3.77 (s, 3H); 3.90 (s,
3H); 6.64 (s, 2H); 6.88 (s, 1H). 13C NMR (63 MHz,
CDCl3) d 15.5; 39.0; 55.4; 56.0; 56.4; 91.2; 105.3; 110.3;
130.5; 158.9; 159.7; 161.2. MS: 293 [M+H]+. Compound
6b: (colourless oil) 1H NMR (250 MHz, CDCl3) d 3.56
(s, 2H); 3.63 (s, 3H); 3.75 (s, 3H); 3.78 (s, 3H); 3.89 (s,
3H); 6.38 (dd, J = 2.4 Hz, 8.1 Hz, 1H); 6.42 (d,
J = 2.4 Hz, 1H); 6.81 (s, 1H); 7.0 (d, J = 8.1 Hz, 1H).
13C NMR (63 MHz, CDCl3) d 20.7; 37.6; 55.2; 55.0; 97.4;
102.8; 103.2; 120.9; 128.8; 129.6; 156.9; 158.2; 160.3. MS:
9. Synthesis of aldehyde 7. To a stirred solution of alcholol 3
(1.4 g, 10 mmol) in 40 mL of CHCl3 was added MnO2
(8.9 g, 100 mmol). The resulting mixture was stirred at rt
for 20 h and filtered off, the filtrate was dried over MgSO4
and concentrated under vacuum to give a slighly yellow
1
solid (140 mg, 99%). H NMR (250 MHz, CDCl3) d 3.74
1
263 [M+H]+. Compound 6c: (white solid) mp: 102 °C H
(s, 3H); 3.94 (s, 3H); 7.64 (s, 1H); 9.67 (s, 1H). 13C NMR
NMR (250 MHz, CDCl3) d 3.60 (s, 2H); 3.66 (s, 3H);
3.92 (s, 3H); 6.77 (d, J = 8.3 Hz, 2H); 6.86 (s, 1H); 7.07
(d, J = 8.3 Hz, 2H); 8.53 (s, 1H). 13C NMR (63 MHz,
CDCl3) d 27.8; 38.9; 56.8; 55.0; 106.0; 115.8; 129.8; 131.4;
132.7; 155.3; 161.6. MS: 219 [M+H]+ IR (KBr) 3000–
3300 cmꢀ1. Compound 6d: (white solid) mp: 180 °C 1H
NMR (250 MHz, CDCl3) d 3.51 (s, 3H); 3.65 (s, 8H);
3.75 (s, 3H); 6.04 (s, 2H); 6.71 (s, 1H); 8.28 (s, 1H). 13C
NMR (63 MHz, CDCl3) d 27.8; 39.2; 55.7; 56.4; 91.2;
105.3; 110.3; 130.5; 155.9; 158.7; 161.2. MS: 279
[M+H]+. IR (KBr) 3000–3300 cmꢀ1. Compound 6e:
(white solid) mp<40 °C 1H NMR (250 MHz, CDCl3) d
3.57 (s, 3H); 3.78 (s, 2H); 3.93 (s, 3H); 6.78 (s, 1H); 6.90
(s, 1H); 7.00–7.15 (m, 2H); 7.27 (d, J = 7.5 Hz, 1H); 7.56
(d, J = 7.5 Hz, 1H); 8.23 (s, 1H). 13C NMR (63 MHz,
CDCl3) d 16.2; 36.8; 54.3; 102.8; 109.3; 113.5; 117.2;
120.0; 125.4; 128.8; 134.6; 159.3. MS: 242 [M+H]+. IR
(KBr) 3300 cmꢀ1. Compound 6f: (white solid) mp<40 °C
1H NMR (250 MHz, CDCl3) d 3.67 (s, 3H); 3.96 (s, 3H);
5.95 (m, 1H); 6.11 (m, 1H); 6.66 (m, 1H); 6.93 (s, 1H);
8.53 (s, 1H). 13C NMR (63 MHz, CDCl3) d 20.1; 38.0;
55.6; 102.4; 104.3; 107.2; 116.0; 129.7; 130.6; 160.4. MS:
192 [M+H]+. IR (KBr) 3333 cmꢀ1. Compound 6g: (white
(63 MHz, CDCl3) d 40.3; 56.6; 109.6; 134.4; 164.0; 183.2
MS: 141 [M+H]+. IR (KBr) 1734 cmꢀ1
.
10. (a) Synthesis of compounds 9a–d, general procedure: To a
stirred solution of CSA (0.1 mmol) and the aromatic
(3 mmol) in 5 mL of CH2Cl2 was added slowly (1 h)
pyrazole 8 (1 mmol) in 5 mL of CH2Cl2. The resulting
mixture was stirred at rt for 1 h, then 15 mL of a saturated
NaHCO3 solution and 15 mL of CH2Cl2 were added. The
organic layer was separated, dried over MgSO4 and
concentrated under vacuum. Compounds were purified
by column chromatography on silica gel.
(b) Spectral data for compounds 9a–d. Compound 9a:
(white solid) mp: 78 °C 1H NMR (250 MHz, CDCl3) d
3.58 (s, 6H); 3.65 (s, 3H); 3.75 (s, 3H); 3.84 (s, 3H); 5.84 (s,
1H); 6.13 (s, 2H); 6.99 (s, 1H); 7.08–7.15 (m, 5H). 13C
NMR (63 MHz, CDCl3) d 32.9; 38.8; 55.2; 55.9; 56.2; 91.9;
106.4; 114.8; 124.8; 127.5; 132.1; 144.9; 158.8; 159.8; 161.6.
MS: 369 [M+H]+. Compound 9b: (white solid) mp: 92 °C
1H NMR (250 MHz, CDCl3) d 3.63 (s, 3H); 3.85 (s, 3H);
5.44 (s, 1H); 6.67–6.69 (m, 1H); 6.71 (s, 1H); 6.95–7.02 (m,
1H); 7.11–7.34 (m, 8H); 7.97 (s, 1H). 13C NMR (63 MHz,
CDCl3) d 37.2; 39.0; 56.3; 108.5; 111.1; 119.4; 120.0; 122.1;
123.2; 126.2; 126.9; 128.3; 128.4; 131.4; 136.9; 144.1; 160.9.
MS: 318 [M+H]+ IR (KBr) 3315 cmꢀ1. Compound 9c:
1
solid) mp: 90 °C H NMR (250 MHz, CDCl3) d 3.51 (s,
1
3H); 3.62 (s, 2H), 3.68 (s, 3H); 3.94 (s, 3H); 5.89 (m, 1H);
6.05 (m, 1H); 6.55 (m, 1H); 6.82 (s, 1H). 13C NMR
(63 MHz, CDCl3) d 19.9; 34.0; 39.2; 56.5; 103.3; 106.8;
106.9; 121.7; 131.0; 132.2; 161.3. MS: 206 [M+H]+.
Compound 6h: (colourless oil) 1H NMR (250 MHz,
CDCl3) d 3.68 (s, 5H); 3.89 (s, 3H); 5.98 (m, 1H); 6.25
(m, 1H); 6.98 (s, 1H); 7.28 (m, 1H). 13C NMR (63 MHz,
CDCl3) d 20.5; 38.1; 55.4; 100.5; 104.5; 109.5; 129.8;
140.3; 153.8; 160.5. MS: 193 [M+H]+. Compound 6i:
(colourless oil) 1H NMR (250 MHz, CDCl3) d 3.63 (s,
2H); 3.65 (s, 3H); 3.86 (s, 3H); 4.50 (s, 2H); 5.88 (d,
J = 3.1 Hz, 1H); 6.12 (d, J = 3.1 Hz, 1H); 6.98 (s, 1H).
13C NMR (63 MHz, CDCl3) d 21.7; 39.1; 56.5; 57.7;
101.4; 106.4; 108.9; 131.1; 153.1; 155.0; 161.5. MS: 223
(white solid) mp: 52 °C H NMR (250 MHz, CCl3) d 0.82
(t, J = 6.9 Hz, 3H); 1.10–1.31 (m, 4H); 1.85–2.12 (m, 2H);
3.63 (s, 3H); 3.77 (s, 9H); 3.86 (s, 3H); 4.41 (dd, J = 6.9,
9.42 Hz, 1H); 6.13 (s, 2H); 6.96 (s, 1H). 13C NMR
(63 MHz, CDCl3) d 14.1; 22.7; 28.5; 30.5; 33.2; 38.7; 55.1;
55.8; 56.2; 91.5; 109.3; 113.7; 130.6; 159.2; 159.3; 161.2.
MS: 349 [M+H]+. Compound 9d: (white solid) mp: 45 °C
1H NMR (250 MHz, CDCl3) d 0.83–0.88 (m, 3H); 1.25–
1.35 (m, 4H); 1.93–2.05 (m, 2H); 3.59 (s, 3H); 3.91 (s, 3H);
4.03 (t, J = 7.7 Hz, 1H); 6.82 (s, 1H); 6.96 (d, J = 2.5 Hz,
1H); 7.03–7.17 (m, 2H); 7.28 (d, J = 7.8 Hz, 1H); 7.59 (d,
J = 7.85 Hz, 1H); 8.26 (s, 1H). 13C NMR (63 MHz,
CDCl3) d 14.1; 22.7; 30.3; 31.1; 35.6; 38.7; 56.2; 109.8;
111.2; 119.0; 119.6; 120.1; 121.1; 126.9; 129.9; 136.6; 161.1.
[M+H]+. IR (KBr) 3150 cmꢀ1
.
MS: 298 [M+H]+. IR (KBr) 3305 cmꢀ1
.