On the synthesis of dimethoxybenzyl cinnamates, monomers for electron transfer polymers

TETRAHEDRON

Pergamon

Tetrahedron 57 82001) 4889±4901

On the synthesis of dimethoxybenzyl cinnamates,

monomers for electron transfer polymers

a

Christophe Waterlot, Bruno Hasiak, Daniel Couturier and Benoõt Rigo

a

b,p

Ã

a

Â Â Â

Laboratoire d'Ingenierie Moleculaire, Universite des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq Cedex, France

Â

Â Â

Laboratoire d'Ingenierie Moleculaire, Ecole des Hautes Etudes Industrielles, 13 rue de Toul, 59046 Lille, France

b

Â

Received 16 January 2001; revised 26 March 2001; accepted 10 April 2001

AbstractÐAn economical way to obtain new monomers, precursors of electron transfer polymers, is described. These monomers were

obtained by a Heck reaction between amino or halogeno-2,5-dimethoxydiarylmethane and methylacrylate. Different routes for the ionic

reduction of various acetophenones to the corresponding diarylmethanes were studied. The yields and the nature of the by-products was

1. Introduction

easy reaction workup^2,5since the products of reaction can be

isolated by ®ltration of the resin. These polymeric reagents

always require the preparation of macromolecular back-

bone⁶or tedious modi®cation of a commercial one.^1,5,7

Particularly, electron transfer polymers 8ETP) were

obtained by addition of redox functionalities to a preformed

Insoluble polymers are an important class of reagents

developed for the halogenation,¹oxidation,²hydrogenation³

or reduction⁴of organic compounds. Their usefulness arises

from the ability to recycle the spent polymer³and from an

Scheme 1.

Keywords: acylation; reduction; vinylation; electron transfer polymer.

Corresponding author. Tel.: 133-3-28-38-48-58; fax: 1 33-3-28-38-48-59; e-mail: rigo@hei.fr

p

PII: S0040-4020801)00417-3

4890

C. Waterlot et al. / Tetrahedron 57 02001) 4889±4901

Scheme 2.

Scheme 3. Reagents and conditions: 8i) NaBH₄, CF₃CO₂H, CH₂Cl₂, 2 58C; 8ii) Et₃SiH, CF₃CO₂H, CCl₄, 558C; 8iii) Et₃SiH, CF₃SO₃H, CH₂Cl₂, 2 58C.

chloromethylated resin.⁸It was observed that the results

obtained with these resins are closely related to the number

of redox functions on the polymer matrix.⁹

2. Results and discussion

2.1. Preliminary reactions

On the other hand, starting from the polymer backbone, four

steps are necessary to synthesize the new material with only

60±80% of grafted redox functions.^8,9Therefore, there is a

need for new methods giving maximal density of redox

functionalities. We prepared polymers 1 with one hydro-

quinone group per monomeric unit.¹⁰In this paper, the

preparation of monomers 2 and of their precursors 3 as

well as the structure of some by-products obtained during

these syntheses are described 8Scheme 1).

The Friedel±Crafts alkylation of 1,4-dimethoxybenzene 5

with chloromethyl substituted benzenes or chloromethyl-

styrene was ®rst studied as a way to diarylmethanes 2 or

3. Under these conditions 8ZnCl₂/CH₂Cl₂^8aor montmorillo-

nite K₁₀/ZnCl₂/CCl₄¹¹), a mixture of compounds was

obtained. Other reactions leading to diarylmethanes were

then investigated.

Reduction of diarylcarbinols 7 can yield such compounds.

Table 1. Acylation then reduction of p-dimethoxybenzene 5

Entry

X

Method B

AlCl₃/MeNO₂4 8%)^a

Method C

NaBH₄/MeOH 7 8%)^a

Method D

NaBH₄/CF₃CO₂3 8%)^a,b

Method E

Et₃SiH/CF₃CO₂H 3 8%)^a,c

Method F

Et₃SiH/CF₃SO₃H 3 8%)^a,d

1

Cl

90

93

47

80

84

2Br

3

4

85

86

85

92

53

80

90

I

88

89

90

89

92

93

CH₃

NO₂

5

a

Isolated yields.

b

c

d

The ratio alcohol/NaBH₄/CF₃CO₂H was 1/5/35.

The ratio alcohol/Et₃SiH/CF₃CO₂H was 1/2/10.

The ratio alcohol/Et₃SiH/CF₃SO₃H was 1/1.2/0.3.

C. Waterlot et al. / Tetrahedron 57 02001) 4889±4901

4891

Scheme 4.

We tried to obtain these carbinols via Grignard reaction. In

that way, the reaction of 4-chlorobenzaldehyde, chosen as a

model compound, with Grignard reagent 6 gives a mixture

of 7a 861%) and of ketone 4a 815%)^12±148Scheme 2).

Reaction with NaBH₄and tri¯uoroacetic acid¹⁹provide a

complex mixture whose main product 3 8XCl, Br) was

isolated only in average yields 8Table 1, method D). On

the other hand, triethylsilane and tri¯uoroacetic acid²⁰or

tri¯ic acid²¹produce compounds 3 in good yield 8Scheme

3, Table 1, methods E and F).

2.2. Three steps synthesis of diarylmethanes 3

Since the previous methods cannot lead to diarylmethanes 2,

3 with good yields, a multisteps sequence 8Scheme 3) start-

ing from acid chlorides 8 was used. Substituents of 8

8XCl, Br, I, CH₃, NO₂) were chosen because their modi-

®cations can lead to ethylenic compounds 2. Friedel±Crafts

reaction of 1,4-dimethoxybenzene 5¹⁵with yttrium tri¯ate

as catalyst¹⁶gives 67% of 4b 8XBr) but yields of benzo-

phenones 4 higher than 85% were always obtained with

AlCl₃in nitromethane¹⁷8Table 1, method B). Reduction

of ketones 4 by NaBH₄in methanol gives benzhydrols 7

in very good yields 8Table 1, method C). Three methods

for the ionic reduction¹⁸of diarylcarbinols 7 were tried.

2.3. Two steps synthesis of diarylmethanes 3

The route described above was interesting because of the

high yields obtained, but had the drawback of three sepa-

rated steps for going from dimethoxybenzene 5 to diaryl-

methane 3. Thus the one-step ionic reduction of ketones 4 to

compound 3 was examined 8Scheme 4, Table 2). Reaction

of benzophenone with NaBH₄/CF₃CO₂H has been

described¹⁹but, when this method was used with compound

4, the diarylmethanes formed 3 were not stable in the reac-

tion medium, giving by-products 10 and 12 8Fig. 1) in a time

dependent amount 8compare Table 2, entries 1 and 2 or 3

Table 2. Reduction of benzophenones 4 to diphenylmethanes 3

Entry Method

X

Ratio^a

Hydride

Acid

Solvent Temp 88C) Time 8h)

X

3 8%)^b9 8%)^b10 8%)^b11 8%)^b12 8%)^b

1

2G

3

4

5

6

7

8

9

10

11

12I

13

14

15

16

17

18

19

20

21

22

23

24

25

26

27

28

G

Cl

1:10:70 NaBH₄

CF₃CO₂H CH₂Cl₂

CF₃CO₂H CCl₄

CF₃SO₃H CH₂Cl₂

25

2

25

2

12

Cl

61

39

40^c

17

c

Cl

1:10:70 NaBH

Br

Cl

Br

Cl

Br

CH₃

NO₂

Cl

5

44

Cl

63

310^c

47

4

G

H

I

1:10:70 NaBH₄

Br

c

18

Br

38^c

1:3:10

1:2:15

1:10:6

Et

Et₃SiH

₃SiH

55

25

2

6

1

Cl

Br

Cl

Br

CH₃

NO₂

Cl

Br

Cl

Br

I

CH₃

Cl

Br

83

82

100

84^c

90^c

81

2

15

22

17

18

21

Cl

1:10:6

1.5

56

11

I

J

K

L

Br

Cl

Br

I

1:10:6

Et₃SiH

1.5

0.75

6

200

5

7

5

480

5

6

1:2.2:0.3 Et₃SiH

84^c

83^c

95^c

89^c

92^c

43^c

CH₃1:2.2:0.3 Et₃SiH

Cl

Br

1:2.2:1 Et₃SiH

AlCl₃

CH₃NO₂

NO₂1:2.2:1.1 Et₃SiH

NO₂

Cl

15^c

7

Cl

Br

I

Cl

NO₂

1:3.5:15 PMHS

1:3:0.3 PMHS

1:3:1.1 PMHS

CF₃SO₃H CH₃NO₂

CF₃SO₃H CH₂Cl₂

53^d

c

48

Cl

707

25

2

25

2

Cl

Br

7

89^c

85^c

c

I

85

AlCl₃

CH₃NO₂

CH₂Cl₂

Cl

9^c,e

c

40

Cl

75

25

NO₂

79^c

a

Refers to the ratio ketone 4/hydride/acid.

Yields were determined by H NMR or HPLC.

Isolated yields.

47% of recovered ketone.

20% of recovered ketone and 71% of compound 13 8Fig. 1) was isolated.

b

c

d

e

1

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C. Waterlot et al. / Tetrahedron 57 02001) 4889±4901

Figure 1.

and 4). Other conditions for the ionic reduction of ketones 4

were then tried; triethylsilane, in the presence of tri¯uoro-

acetic acid^18,22gave the best yield of diphenylmethanes 3

when the ratio ketone/Et₃SiH/CF₃CO₂H was changed from

1/3/10 to 1/2/5 8compare Table 2, entries 5 and 7 or 6 and 8).

using triethylsilane with tri¯ic acid,²¹the formation of by-

products 9, 10, 12 was time dependent 8compare Table 2,

entries 11 and 12) and was suppressed when the reaction

was performed for 45 min while the ratio ketone/hydride/

acid was varied from 1/10/6²¹to 1/2.2/0.3. Almost quanti-

tative yields of 3a and 3b 8XCl, Br, Table 2, entries 18 and

19) were also obtained by using AlCl₃as the acid,²³but for

Other acids were also tested for these ionic reductions. By

Scheme 5.

Table 3. Acylation/reduction of p-dimethoxybenzene 5

Entry

Method

X

Hydride

Solvent

Ratio^a

Time 8h) Reaction 1

Time 8h) Reaction 2

3 Isolated 8%)

1

2

3

4

5

6

7

8

M

N

O

P

Cl

Et₃SiH

EtSiH

CH₃NO₂

CH₂Cl₂

C₆H₅NO₂

1:3

1:2.2

1:3

1:3.5

1:3

1

290

292

2

1275

40

1275

1277

1270

6

Br

NO₂

Cl

Br

I

CH₃

NO₂

Cl

3

Et₃SiH

PMHS

43^b

70^c

1.5

1

9

10

11

70

7^d

1:3

960

a

Refers to the ratio of the hydride vs benzophenones 4.

Compounds 9 815%) and 12 815%) were isolated.

10% of by-product 9 was isolated.

b

c

d

50% of ketone 4 and 34% of 13 were also isolated.

C. Waterlot et al. / Tetrahedron 57 02001) 4889±4901

4893

Scheme 6.

Table 4. Synthesis of monomer 2

Entry

Method

X

R⁰

Et

Pd8OAc)

Et

Catalyst/`L'

Solvent

nBu₃N

DMF

2 8%) Isolated

1

2Q

3

4

5

6

7

8

9

Q

Br

R

S

T

U

Cl

Pd8OAc)₂/PPh₃

₂/PPh₃

0

2

Et

Br

I

7

Pd8OAc)₂/PPh₃

MK₁₀±Pd±Cu

37

73

75

16

93

85

70

Et

I

Me

Et

Br

I

NH₂

DMF

CH₃CO₂H

Me

3e 8XNO₂, Table 2, entry 20) by products 9 and 12 8Fig. 1)

were also formed and the yield of 3e was only 43%.

time, benzophenone 4 and demethylated ketone 13 8Table

3, entry 11, Fig. 1) were mainly obtained.

Analogs results were observed when polymethylhydrosil-

oxane 8PMHS)²⁴was used as the hydride, best yields

being obtained by reducing the amount of tri¯ic acid

8compare Table 2, entries 22 and 23). With this acid, as

well as with AlCl₃, best yields were obtained using methyl-

ene chloride as the solvent 8compare Table 2, entries 21 and

22 or 26 and 27). Noteworthy also is the demethylation

observed in the PMHS/AlCl₃/CH₃NO₂reaction, giving

phenol 13 871%) 8Table 2, entry 26). Not surprisingly, the

reaction time was greater by using PMHS instead of Et₃SiH.

2.5. Synthesis of monomers 2

The next step of the work was the synthesis of acrylates 2 by

using a Heck reaction 8Scheme 6). No condensation

occurred between acrylic esters and diphenylmethanes 3

substituted by a Cl atom 8Table 4, entry 1). Whatever the

catalyst used, the yields were low when a Br was the leaving

group 8Table 4, entries 2, 3 and 6). The best results were

obtained by using 3 8XI) with Pd8OAc)₂or Pd/Cu²⁶

25

modi®ed montmorillonite K10 8MK10±Pd±Cu). Note-

worthy, the newly described²⁷reaction of an arylamino

compound and acrylic ester with MK10±Pd±Cu as the cata-

lyst, led to a good yield of monomer 2 8Table 4, entry 9). As

for 3 8XNH₂), it was obtained by reduction of 3 8XNO₂)

by NaBH₄/Pd 8Scheme 7).

2.4. One pot synthesis of diarylmethanes 3

Given the good results obtained by using AlCl₃as well for

the acylation of p-dimethoxybenzene 5 8Table 1, method A)

as for the reduction of benzophenones 4 8Table 2, entries

18±20 and 26±27), this acid was chosen for one-pot acyl-

ation/reduction²³of compound 5 8Scheme 5). The best

yields of diarylmethanes 3 8XCl, Br) were obtained by

performing the reaction in nitromethane and using triethyl-

silane as the reducing agent 8Table 3, entries 1 and 2). The

formation of by-products 9 and 12 observed in these con-

ditions for XNO₂was suppressed when PMHS²⁴was used

in dichloromethane 8Table 3, entries 3 and 10), and medium

yields were obtained for all the substituents tested. With

nitrobenzene as solvent, even after a very long reaction

2.6. Structure and synthesis of by-products

Formation of by-products during Friedel±Crafts reac-

tion^28,29or during the ionic reduction of ketones^18,30or benz-

hydrols^19,31frequently occurred. In our work, by-products

9±12 were obtained 8Fig. 1). Their structure were deter-

mined by elemental analysis, mass spectra and from the

symmetry of their NMR spectra for compounds 9, 10, 12.

The structure of dimer 11a was obtained from the NOESY

and HETCOR correlations 8Fig. 2).

Scheme 7.

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C. Waterlot et al. / Tetrahedron 57 02001) 4889±4901

Figure 2. Main NOESY and long-range HETCOR correlations for compound 11a.

Scheme 8.

Scheme 9.

Table 5. Synthesis of by-products 12

Treatment of diarylmethane 3b in the same conditions as for

the ionic reductions 8CF₃SO₃H, Et₃SiH, CH₂Cl₂) lead to the

formation of 3.5% of products 9b and 12b 8Scheme 8). This

result allowed to know that the by-products are formed from

the decomposition of the diarylmethanes as well as from the

dimerization of diarylmethanols. Synthesis of triarylmethanes

Entry

X

14 8%)

12 8%)

68

1

2Br

3

Cl

85

NO₂

90

67

93

63

C. Waterlot et al. / Tetrahedron 57 02001) 4889±4901

4895

12 from chloride 14 yields another proof of their structure:

treatment of diarylcarbinols 7 with chlorotrimethylsilane

lead to benzhydryl chlorides 14³²whose the Friedel±Crafts

reaction with p-dimethoxybenzene 5 yields compounds 12

8Scheme 9, Table 5).

compound 4d, using 4-bromobenzoyl chloride. Yield 90%,

mp 818C; IR 8KBr): 3085, 2835, 1665, 1580, 1490, 1220,

1

1030, 845, 715 cm²¹; H NMR 8CDCl₃): d 3.63 8s, 3H),

3.76 8s, 3H), 6.90 8m, 3H), 7.00 8d, J9.0 Hz, 2H), 7.65

8d, J9.0 Hz, 2H); ¹³C NMR 8CDCl₃): d 55.8, 56.2, 113.0,

114.4, 117.8, 128.1, 128.8, 131.3, 131.5, 136.5, 151.4,

153.5, 195.1.

3. Conclusion

4.2.3. 2-04⁰-Chlorobenzoyl)-1,4-dimethoxybenzene 4a

0XCl). This compound was obtained in the same way as

compound 4d, using 4-chlorobenzoyl chloride. Yield 85%,

mp 658C; IR 8KBr): 3090, 2830, 1665, 1580, 1495, 1220,

Various diarylmethanes are synthesized by reduction of the

corresponding benzophenones with hydrides and acids,

leading precursor 2 of electron transfer polymers in good

global yield. From an economic point of view, the syntheses

of diarylmethanes 3 by one-step reactions performed with

AlCl₃then PMHS in CH₂Cl₂are particularly inexpensive

and are very interesting for an industrial use.

1

1050, 845, 715 cm²¹; H NMR 8CDCl₃): d 3.65 8s, 3H),

3.77 8s, 3H), 6.90 8d, J8.8 Hz, 1H), 6.928d, J2.6 Hz,

1H), 7.00 8dd, J8.8, 2.6 Hz, 1H), 7.39 8d, J8.5 Hz,

2H), 7.75 8d, J8.5 Hz, 2H); ¹³C NMR 8CDCl₃): d 55.8,

56.2, 113.0, 114.5, 117.8, 128.5, 128.8, 131.1, 136.1, 139.3,

151.4, 153.6, 194.9.

4. Experimental

4.1. Materials

4.2.4. 2,5-Dimethoxy-1-04⁰-iodobenzoyl)benzene 4c 0XI).

This compound was obtained in the same way as compound

4d, using 4-iodobenzoyl chloride. Yield 86%, mp 908C; IR

8KBr): 3080, 2835, 1665, 1580, 1495, 1220, 1045, 845,

Melting points were determined with a Metler FP1 appa-

ratus and are uncorrected. All reactions were monitored by

HPLC using acetonitrile±water 860:40) as a mobile phase

under reversed phase conditions. Thin-layer chromato-

graphies were carried out on Merck F-254 silica glass plates.

Column chromatographies were performed on silica gel

8Merck, 70±230 mesh). Mass spectra were obtained on a

Nermag R-10-10H spectrometer. Data are reported in the

form m/z. Infrared spectra were recorded in KBr on a

BruÈcker IFS48 Fourier transform spectrophotometer.

NMR spectra were run on a BruÈcker AC300 spectrometer,

at 300 MHz for ¹H and 75 MHz for ¹³C, using CDCl₃as the

solvent and TMS as an internal reference. Chemical shifts

8d) are given in ppm; mutiplicities are indicated by s

8singlet), d 8doublet), dd 8double±doublet), m 8multiplet).

Elemental analyses were performed by the `Service Central

de Microanalyses' of CNRS, in Vernaison, France.

1

460 cm²¹; H NMR 8CDCl₃): d 3.64 8s, 3H), 3.77 8s, 3H),

6.90 8m, 2H), 7.00 8dd, J9.0, 3.0 Hz, 1H), 7.50 8d, J

8.3 Hz, 2H), 7.60 8d, J8.3 Hz, 2H); ¹³C NMR 8CDCl₃):

d 55.9, 56.2, 101.0, 113.0, 114.5, 117.8, 128.7, 131.1, 137.0,

137.5, 151.5, 153.5, 195.5.

4.2.5. 2,5-Dimethoxy-1-04⁰-nitrobenzoyl)benzene 4e 0X

NO₂). This compound was obtained in the same way as

compound 4d, using 4-nitrobenzoyl chloride. Yield 85%,

mp 1368C; IR 8KBr): 2985, 2840, 1660, 1605, 1525, 1495,

1

1450, 1350, 1220, 1045, 835 cm²¹; H NMR 8CDCl₃): d

3.60 8s, 3H), 3.79 8s, 3H), 6.928d, J8.9 Hz, 1H), 7.00 8d,

J3.1 Hz, 1H), 7.07 8dd, J8.9, 3.1 Hz, 1H), 7.90 8d, J

8.9 Hz, 2H), 8.20 8d, J8.9 Hz, 2H); ¹³C NMR 8CDCl₃): d

55.9, 56.0, 113.1, 114.7, 119.1, 123.4, 127.7, 130.2, 143.0,

150.2, 151.8, 153.7, 194.5.

4.3. Preparation of substituted benzhydrols 7

4.2. Preparation of substituted benzophenones 4

4.3.1. 4⁰-Chloro-2,5-dimethoxybenzhydrol 7a 0XCl)

0Method A). Magnesium turnings 87 g, 39 mmol) in dry

THF 810 mL) were activated by a small piece of iodine,

with stirring and heating until the color of iodine dis-

appeared. 1-Bromo-2,5-dimethoxybenzene 81 g, 4.6 mmol)

was added to the suspension of activated magnesium and the

mixture was heated to 508C. Next, a solution of 1-bromo-

2,5-dimethoxybenzene 84 g, 18.4 mmol) in dry THF

820 mL) was added dropwise to the stirred mixture over

15 min while keeping under re¯ux condition. The stirring

at re¯ux was further continued for 4 h. A solution of

4-chlorobenzaldehyde 83.2g, 23 mmol) in THF 810 mL)

was added at 08C. The temperature was gradually allowed

to warm to 558C for 4 h. The reaction mixture was poured

into aqueous NH₄Cl 8200 mL) and extracted with diethyl

ether 82£30 mL). The organic phases were dried over

Na₂SO₄and concentrated to give a crude product 85.1 g,

80%), which was crystallized form petroleum ether to

give the 2,5-dimethoxy-1-84⁰-chlorobenzoyl)benzene 4a

8XCl) 815%) and 7a 83.9 g, 61%) as a colorless oil: IR

8KBr pellets): 3420, 3005, 2835, 1590, 1500, 1450, 1275,

4.2.1. 2,5-Dimethoxy-1-04⁰-methylbenzoyl)benzene 4d

0XCH₃) 0Method B). A mixture of 1,4-dimethoxyben-

zene 85 g, 36.2mmol) and aluminum chloride 86.8 g,

50 mmol) in nitromethane 820 mL) was stirred at 108C

until complete dissolution of the Lewis acid. A solution of

4-methylbenzoyl chloride 85.6 g, 36.2mmol) in nitro-

methane 810 mL) was added dropwise and the reaction

mixture was stirred at room temperature for 60 min. The

mixture was diluted with 0.5 M HCl 850 mL) and extracted

with dichloromethane 82£20 mL). The organic layer was

dried and concentrated under vacuum to give 4d 89.3 g,

83%) as a white solid, mp 638C; IR 8KBr): 2995, 2955,

2830, 1665, 1610, 1585, 1495, 1465, 1450, 1225, 1050,

1

805 cm²¹; H NMR 8CDCl₃): d 2.39 8s, 3H), 3.65 8s, 3H),

3.76 8s, 3H), 6.85 8m, 3H), 7.22 8d, J7.2Hz, 2H), 7.728d,

J7.2Hz, 2H); ¹³C NMR 8CDCl₃): d 21.7, 55.8, 56.3,

113.1, 114.4, 117.0, 129.0, 129.8, 130.0, 135.0, 143.9,

151.3, 153.4, 195.8.

4.2.2. 2-04⁰-Bromobenzoyl)-1,4-dimethoxybenzene 4b

0XBr). This compound was obtained in the same way as

4896

C. Waterlot et al. / Tetrahedron 57 02001) 4889±4901

1

1215, 1045, 710 cm²¹; H NMR 8CDCl₃): d 3.24 8s, 1H),

3.73 8s, 6H), 5.95 8s, 1H), 6.80 8m, 3H), 7,27 8m, 4H); ¹³H

NMR 8CDCl₃): d 55.7, 55.9, 71.6, 111.9, 112.9, 114.0,

127.9, 128.3, 132.6, 132.9, 141.7, 150.7, 153.8.

4.4. Preparation of the substituted diarylmethanes 3

from benzhydrols 7

4.4.1. 2,5-Dimethoxy-1-04⁰-methylbenzyl)benzene 3d 0X

CH₃) 0Method E). Triethylsilane 84.9 mL, 31.0 mmol) was

added 8syringe) at room temperature, to a stirred solution of

compound 7d 84 g, 15.5 mmol) and tri¯uoroacetic acid

811.9 mL, 155 mmol) in carbon tetrachloride 830 mL). The

reaction was then stirred at 558C for 5 h. After washing the

mixture with a solution of 1 M NaOH 850 mL), the organic

layer was dried over Na₂SO₄and concentrated under

vacuum to give 3d 83.4 g, 89%) as a white solid, mp

388C; IR 8KBr): 3005, 2955, 2830, 1605, 1505,1460,

4.3.2. 2,5-Dimethoxy-4⁰-nitrobenzhydrol 7e 0XNO₂)

0Method C). Sodium borohydride 80.48 g, 12.5 mol) was

added at 258C, over a period of 10 min, to a solution of

compound 4e 83 g, 10.4 mmol) in methanol 820 mL). The

reaction mixture was stirred for 90 min at room temperature.

After removing the methanol, diethyl ether 810 mL) was

added and the organic phase was washed with a solution

of 1 M HCl. The aqueous phases were extracted with diethyl

ether 83£10 mL). After drying the organic phases over

CaCl₂and evaporating the solvents, the benzhydrol was

obtained as an oil which crystallized in a petroleum ether

and diethyl ether mixture to give 7e 82.7 g, 90%) as a white

solid, mp 888C 8petroleum ether/diethyl ether); IR 8KBr):

3515, 3005, 2830, 1595, 1510, 1450, 1345, 1280, 1225,

1

1440, 1220, 1045, 805 cm²¹; H NMR 8CDCl₃): d 2.38 8s,

3H), 3.77 8s, 3H), 3.83 8s, 3H), 3.99 8s, 2H), 6.74 8dd, J8.6,

3.0 Hz, 1H), 6.78 8d, J3.0 Hz, 1H), 6.85 8d, J8.6 Hz,

1H), 7.13 8m, 4H); ¹³C NMR 8CDCl₃): d 21.1, 35.6, 55.6,

56.1, 111.2, 111.4, 116.9, 128.9, 129.1, 131.4, 135.7, 137.7,

151.7, 153.6.

1045, 815 cm²¹; H NMR 8CDCl₃): d 3.528s, 1H), 3.71

1

4.4.2. 2-04⁰-Bromobenzyl)-1,4-dimethoxybenzene 3b

0XBr) 0Method F). Tri¯ic acid 81.4 g, 9.34 mmol) was

added 8syringe) to a stirred solution of compound 7b

810 g, 31.1 mmol) in dichloromethane 880 mL). A solution

of triethylsilane 89.02g, 77.9 mmol) in dry dichloromethane

820 mL) was added dropwise. After 45 min, the mixture was

poured into cold 858C) saturated sodium hydrogen carbonate

solution 8100 mL) and extracted with dichloromethane

83£30 mL). The organic layer was dried with magnesium

sulfate, and evaporated to give 3b 88.5 g, 90%) as a white

solid, mp 498C 8petroleum ether/diethyl ether); IR 8KBr):

2995, 2940, 1830, 1595, 1495, 1450, 1430, 1225, 1045, 800,

8s, 3H), 3.728s, 3H), 6.028s, 1H), 6.77 8m, 2H), 6.84 8d,

J2.4 Hz, 1H), 7.51 8d, J8.4 Hz, 2H), 8.09 8d, J8.4 Hz,

2H); ¹³C NMR 8CDCl₃): d 55.6, 55.8, 70.8, 111.8, 113.2,

113.7, 123.3, 127.1, 131.9, 147.1, 150.5, 151.0, 153.8.

4.3.3. 4⁰-Chloro-2,5-dimethoxybenzhydrol 7a 0XCl).

This compound was obtained in the same way as compound

7e, using 2-84⁰-chlorobenzoyl)-1,4-dimethoxybenzene. The

compound 7a was isolated as a white solid 893%), mp 658C,

with the same physical properties as the compound obtained

following the method A.

1

710 cm²¹; H NMR 8CDCl₃): d 3.75 8s, 3H), 3.77 8s, 3H),

4.3.4. 4⁰-Bromo-2,5-dimethoxybenzhydrol 7b 0XBr).

This compound was obtained in the same way as compound

7e, using 2-84⁰-bromobenzoyl)-1,4-dimethoxybenzene.

Yield 92%, mp 708C; IR 8KBr): 3300, 3000, 2830, 1585,

3.91 8s, 2H), 6.68 8d, J2.9 Hz, 1H), 6.76 8dd, J8.8,

2.9 Hz, 1H), 6.82 8d, J8.8 Hz, 1H), 7.11 8d, J8.3 Hz,

2H), 7.40 8d, J8.3 Hz, 2H); ¹³C NMR 8CDCl₃): d 35.6,

55.7, 56.0, 111.4, 116.9, 119.7, 130.2, 130.7, 131.3, 139.9,

151.6, 153.3; Anal. Calcd for C₁₅H₁₅BrO₂: C, 58.65; H,

4.92; O, 10.42. Found: C, 58.57; H, 4.93; O, 10.45.

;

1500, 1455, 1270, 1235, 1040, 700 cm²^{1 1}H NMR

8CDCl₃): d 3.128s, 1H), 3.71 8s, 3H), 3.728s, 3H), 5.93

8s, 1H), 6.78 8m, 2H), 6.85 8d, J2.3 Hz, 1H), 7.24 8d, J

8.4 Hz, 2H), 7.41 8d, J8.4 Hz, 2H); ¹³C NMR 8CDCl₃): d

55.7, 55.9, 71.6, 111.9, 112.9, 113.9, 121.0, 128.3, 131.2,

132.6, 142.3, 150.7, 153.7.

4.5. Preparation of the substituted diarylmethanes 3

from benzophenones 4

4.3.5. 2,5-Dimethoxy-4⁰-iodobenzhydrol 7c 0XI). This

compound was obtained following the method B, using

2,5-dimethoxy-1-84⁰-iodobenzoyl)benzene. Yield 88%, IR

8KBr): 3305, 2995, 2835, 1580, 1500, 1450, 1270, 1230,

4.5.1. 2-04⁰-Bromobenzyl)-1,4-dimethoxybenzene 3b 0X

Br) 0Method I). Tri¯ic acid 81.4 g, 9.34 mmol) was added

8syringe) to a stirred solution of compound 4b 810 g,

31.1 mmol) in dichloromethane 880 mL). A solution of

triethylsilane 89.02g, 77.9 mmol) in dry dichloromethane

820 mL) was added dropwise. An exothermic reaction

took place while the temperature was maintained at 208C

in a water bath. After 45 min, the mixture was poured into

cold 858C) saturated sodium hydrogen carbonate solution

8100 mL) and extracted with dichloromethane 83£30 mL).

The organic layer was dried with magnesium sulfate, and

evaporated to give 3b 87.9 g, 83%) as a white solid with

the same physical properties than the product obtained

following the method F.

1

1045, 525 cm²¹; H NMR 8CDCl₃): d 3.15 8s, 1H), 3.63

8s, 6H), 5.83 8s, 1H), 6.68 8m, 2H), 6.75 8d, J2.3 Hz,

1H), 7.13 8d, J7.6 Hz, 2H), 7.54 8d, J7.6 Hz, 2H); ¹³C

NMR 8CDCl₃): d 55.7, 55.9, 71.6, 92.7, 111.8, 112.9, 113.9,

121.0, 128.6, 132.5, 137.2, 143.0, 150.7, 153.7.

4.3.6. 2,5-Dimethoxy-4⁰-methylbenzhydrol 7d 0XCH₃).

This compound was obtained following the method B, using

2,5-dimethoxy-1-84⁰-methylbenzoyl)benzene. Yield 89%,

mp 458C; IR 8KBr): 3470, 3005, 2940, 2830, 1605, 1495,

1460, 1280, 1210, 1030 cm²¹; ¹H NMR 8CDCl₃): d 2.37 8s,

3H), 3.45 8s, 1H), 3.74 8s, 3H), 3.76 8s, 3H), 6.028s, 1H),

6.80 8m, 2H), 6.98 8d, J2.3 Hz, 1H), 7.16 8d, J8.4 Hz,

2H), 7.32 8d, J8.4 Hz, 2H); ¹³C NMR 8CDCl₃): d 21.2,

55.7, 56.0, 71.7, 111.9, 112.7, 113.9, 126.6, 128.9, 133.5,

136.8, 140.5, 150.9, 153.8.

4.5.2. 2-04⁰-Chlorobenzyl)-1,4-dimethoxybenzene 3a 0X

Cl). This compound was obtained following the method E,

using 2-84⁰chlorobenzoyl)-1,4-dimethoxybenzene. Yield

84%, mp 418C; IR 8KBr): 3000, 2945, 2830, 1590, 1495,

1460, 1435, 1220, 1045, 805, 710 cm²¹; ¹H NMR 8CDCl₃):

C. Waterlot et al. / Tetrahedron 57 02001) 4889±4901

4897

d 3.74 8s, 3H), 3.76 8s, 3H), 3.91 8s, 2H), 6.66 8d, J3.0 Hz,

1H), 6.73 8dd, J8.8, 3.0 Hz, 1H), 6.80 8d, J8.8 Hz, 1H),

7.14 8d, J8.5 Hz, 2H), 7.20 8d, J8.5 Hz, 2H); ¹³C NMR

8CDCl₃): d 35.5, 55.6, 56.0, 111.4, 116.8, 128.3, 130.2,

130.3, 131.6, 139.1, 151.6, 153.5; Anal. Calcd for

C₁₅H₁₅ClO₂: C, 68.57; H, 5.75; O, 12.18. Found: C, 68.60;

H, 5.71; O, 12.20.

2H), 7.14 8d, J8.3 Hz, 2H), 7.20 8d, J8.3 Hz, 2H), 7.23

8d, J8.3 Hz, 2H); ¹³C NMR 8CDCl₃): d 35.4, 43.0, 55.6,

56.1, 56.5, 56.6, 110.8, 111.9, 113.5, 114.1, 117.2, 127.8,

128.1, 128.3, 130.3, 130.5, 130.8, 131.6, 133.5, 139.6,

142.3, 151.1, 151.2, 151.7, 153.3; m/z 526 8for ³⁷Cl, ³⁵Cl,

MH¹, 9.3), 525 8for ³⁷Cl, ³⁵Cl, M¹, 22.8), 524 8for ³⁵Cl,

MH¹, 65.9), 523 8for ³⁵Cl, M¹, 29.0), 522 8for ³⁵Cl, M^1z,

100); Anal. Calcd for C₃₀H₂₈Cl₂O₂: C, 68.84; H, 5.39; O,

12.23. Found: C, 68.69; H, 5.41; O, 12.40. Compound 9a

was obtained as a white solid, mp 1408C 8heptane/diethyl

ether); IR 8KBr): 2985, 2935, 2830, 1590, 1500, 1465, 1410,

4.5.3. 2,5-Dimethoxy-1-04⁰-iodobenzyl)benzene 3c 0XI).

This compound was obtained in the same way as compound

3b, using 2,5-dimethoxy-1-84⁰-iodobenzoyl)benzene. Yield

95%, mp 608C; IR 8KBr): 2995, 2935, 2825, 1585, 1500,

1450, 1430, 1225, 1050, 795, 525 cm²¹; ¹H NMR 8CDCl₃):

d 3.74 8s, 3H), 3.76 8s, 3H), 3.89 8s, 2H), 6.66 8d, J2.8 Hz,

1H), 6.74 8d, J8.8, 2.8 Hz, 1H), 6.80 8d, J8.8 Hz, 1H),

6.98 8d, J8.2Hz, 2H), 7.60 8d, J8.2Hz, 2H); ¹³C NMR

8CDCl₃): d 35.7, 55.7, 56.0, 91.4, 111.4, 116.9, 130.5,

131.0, 137.3, 140.9, 152.1, 153.8.

1

1220, 1040, 870, 735 cm²¹; H NMR 8CDCl₃): d 3.70 8s,

6H), 3.90 8s, 4H), 6.55 8s, 2H), 7.13 8d, J8.3 Hz, 4H), 7.21

8d, J8.3 Hz, 4H); ¹³C NMR 8CDCl₃): d 35.4, 56.1, 113.1,

127.8, 128.4, 130.1, 131.6, 139.5, 151.2; m/z 390 8for ³⁷Cl,

M¹, 11.2), 389 8for ³⁷Cl, ³⁵Cl, MH¹, 15.3), 388 8for ³⁷Cl,

³⁵Cl, M¹, 66.4), 387 8for ³⁵Cl, MH¹, 24.1), 386 8for ³⁵Cl,

M¹, 100); Anal. Calcd for C₂₂H₂₀Cl₂O₂: C, 68.23; H, 5.20;

O, 8.26. Found: C, 68.44; H, 5.29; O, 8.42.

4.5.4. 2-04⁰-Bromobenzyl)-1,4-dimethoxybenzene 3b 0X

Br) 0Method G). To a stirred solution of 2-84⁰-bromo-

benzoyl)-1,4-dimethoxybenzene 84.0 g, 12.5 mmol) and

tri¯uoroacetic acid 867 mL, 872mmol) in dichloromethane

880 mL) was slowly added sodium borohydride pellets

84.74 g, 125 mmol). The reaction mixture was stirred at

room temperature for 18 h. After washing the mixture

with a solution of 1 M NaOH 8100 mL), the organic layer

was dried over CaCl₂and concentrated under vacuum to

give 3b and 11b 8XBr). The crude mixture was crystal-

lized from petroleum ether and diethyl ether giving ®rst 3b

81.8 g, 47%) with the same physical properties that the

product obtained following the method F and 11b 82.91 g,

38%) as a white solid, mp 848C 8petroleum ether/diethyl

ether); IR 8KBr): 2995, 2945, 2830, 1590, 1500, 1450,

4.5.6. 2,5-Dimethoxy-1-04⁰-methylbenzyl)benzene 3d 0X

CH₃) 0Method H). Triethylsilane 86.2mL, 39.0 mmol) was

added 8syringe) at room temperature, to a stirred solution of

compound 4d 85 g, 19.5 mmol) and tri¯uoroacetic acid

822.5 mL, 0.29 mol) in carbon tetrachloride 840 mL). The

reaction was then stirred at 558C for 6 h. After washing the

mixture with a solution of 1 M NaOH 850 mL), the organic

layer was dried over CaCl₂and concentrated under vacuum

to give 3d 84.0 g, 84%) with the same physical properties

that the product obtained following the method E.

4.5.7. 2,5-Dimethoxy-1-04⁰-nitrobenzyl)benzene 3e 0X

NO₂). This compound was obtained following the same

procedure in the same way as 3d, using 2,5-dimethoxy-1-

84⁰-nitrobenzoyl)benzene. Yield 90%, mp 708C; IR 8KBr):

3005, 2935, 2835, 1600, 1510, 1465, 1440, 1345, 1215,

1

1215, 1045, 795, 720 cm²¹; H NMR 8CDCl₃): d 3.53 8s,

3H), 3.57 8s, 3H), 3.63 8s, 3H), 3.67 8s, 3H), 3.87 8s, 2H),

6.01 8s, 1H), 6.31 8s, 1H), 6.41 8d, J3.0 Hz, 1H), 6.59 8s,

1H), 6.728dd, J8.8, 3.0 Hz, 1H), 6.79 8d, J8.8 Hz, 1H),

6.93 8d, J8.3 Hz, 2H), 7.09 8d, J8.8 Hz, 2H), 7.34 8d,

J8.8 Hz, 2H), 7.37 8d, J8.3 Hz, 2H); ¹³C NMR 8CDCl₃):

d 35.4, 43.1, 55.5, 56.1, 56.4, 56.6, 110.7, 111.9, 113.5,

114.0, 117.1, 119.6, 119.7, 127.7, 130.6, 130.9, 131.0,

131.3, 133.4, 140.1, 142.8, 151.1, 151.2, 151.6, 153.3; m/z

615 8for ⁸¹Br, ⁷⁹Br, MH¹, 15.5%), 614 8for ⁸¹Br, ⁷⁹Br, M¹,

51.6%), 613 8for ⁷⁹Br, MH¹, 41.0%), 6128for ⁷⁹Br, M¹,

100%); Anal. Calcd for C₃₀H₂₈Br₂O₂: C, 58.84; H, 4.61;

O, 10.45. Found: C, 58.64; H, 4.76; O, 10.26.

1

1035, 810 cm²¹; H NMR 8CDCl₃): d 3.73 8s, 3H), 3.74

8s, 3H), 4.00 8s, 2H), 6.68 8d, J2.9 Hz, 1H), 6.75 8dd, J

8.8, 2.9 Hz, 1H), 6.80 8d, J8.8 Hz, 1H), 7.33 8d, J8.7 Hz,

2H), 8.08 8d, J8.7 Hz, 2H); ¹³C NMR 8CDCl₃): d 36.3,

55.7, 55.9, 111.5, 111.9, 117.0, 123.5, 128.8, 129.5, 146.4,

148.9, 151.5, 153.6.

4.5.8. 2,5-Dimethoxy-1-04⁰-nitrobenzyl)benzene 3e 0X

NO₂) 0Method J). Triethylsilane 86.1 mL, 38.5 mmol)

was added 8syringe) at room temperature, to a stirred solu-

tion of compound 4e 85 g, 17.4 mmol) and aluminum

chloride 82.6 g, 19.2 mmol) in nitromethane 840 mL). The

reaction mixture was stirred at room temperature for 90 min.

After washing the mixture with a solution of 1 M HCl

850 mL), the organic layer was dried over CaCl₂and

concentrated under vacuum. The crude mixture was washed

in a ®rst time with petroleum ether to give 9e 8XNO₂)

80.5 g, 15%) as a brown solid, mp 194±1958C; IR 8KBr):

2995, 2935, 2835, 1595, 1515, 1460, 1345, 1220, 1035,

4.5.5. 2-04⁰-Chlorobenzyl)-1,4-dimethoxybenzene 3a 0X

Cl). This compound was obtained following the same pro-

cedure in the same way as 3b, using 2-84⁰-chlorobenzoyl)-

1,4-dimethoxybenzene and stirring the reaction mixture for

44 h instead of 18 h. After recrystallization from petroleum

ether and diethyl ether, three compounds were isolated: 3a

81.0 g, 31%) with the same physical properties that the

product obtained following the method I, 11a 82.6 g, 40%)

and 9a 8XCl) 80.5 g, 10%). Compound 11a was obtained

as a white solid, mp 908C 8petroleum ether/diethyl ether); IR

8KBr): 3005, 2945, 2830, 1590, 1500, 1215, 1045, 795,

1

835 cm²¹; H NMR 8CDCl₃): d 3.64 8s, 6H), 3.97 8s, 4H),

6.61 8s, 2H), 7.28 8d, J8.6 Hz, 4H), 8.05 8d, J8.6 Hz,

4H); ¹³C NMR 8CDCl₃): d 36.2, 55.9, 113.7, 123.6, 126.9,

139.4, 146.3, 148.8, 151.5; Anal. Calcd for C₂₂H₂₀N₂O₆: C,

64.70; H, 4.94; N, 6.86. Found: C, 64.82; H, 5.21; N, 6.55.

The ®rst residue was washed with acetone to give 12e

8XNO₂) 80.53 g, 15%) as a yellow solid, mp 598C; IR

8KBr): 2995, 2940, 2840, 1595, 1510, 1495, 1345, 1215,

1

730 cm²¹; H NMR 8CDCl₃): d 3.54 8s, 3H), 3.57 8s, 3H),

3.64 8s, 3H), 3.67 8s, 3H), 3.89 8s, 2H), 6.07 8s, 1H), 6.35 8s,

1H), 6.428d, J3.0 Hz, 1H), 6.59 8s, 1H), 6.728dd, J8.8,

3.0 Hz, 1H), 6.80 8d, J8.8 Hz, 1H), 6.99 8d, J8.3 Hz,

4898

C. Waterlot et al. / Tetrahedron 57 02001) 4889±4901

1050, 825 cm²¹; ¹H NMR 8CDCl₃): d 3.64 8s, 6H), 3.66 8s,

6H), 6.18 8s, 1H), 6.36 8d, J2.9 Hz, 2H), 6.74 8dd, J8.8,

2.9 Hz, 2H), 6.81 8d, J8.8 Hz, 2H), 7.20 8d, J8.5 Hz,

2H), 8.09 8d, J8.5 Hz, 2H); ¹³C NMR 8CDCl₃): d 43.8,

55.6, 56.3, 111.3, 111.8, 117.3, 123.3, 129.9, 132.0, 146.2,

151.5, 152.0, 153.5; Anal. Calcd for C₂₃H₂₃NO₆: C, 67.47;

H, 5.66; N, 3.42. Found: C, 67.14; H, 5.51; N, 3.57. The

second residue was concentrated under vacuum yielding 3e

with the same physical properties that the product obtained

following the method I.

3426, 3005, 2940, 2840, 1675, 1590, 1490, 1225, 1040,

1

825, 710 cm²¹; H NMR 8CDCl₃): d 3.70 8s, 3H), 7.00 8d,

J3.1 Hz, 1H), 7.16 8dd, J8.4, 3.1 Hz, 1H), 6.81 8d, J

8.4 Hz, 1H), 7.48 8d, J8.6 Hz, 2H), 7.66 8d, J8.6 Hz,

2H), 11.4 8s, 1H); ¹³C NMR 8CDCl₃): d 55.9, 115.8,

118.5, 119.4, 128.7, 130.1, 137.3, 138.4, 151.5, 157.4,

199.8.

When the reaction mixture was performed in dichloro-

methane 810 mL) for 40 h, compound 3a was obtained

83.6 g, 75%) without any side products.

4.5.9. 2-04⁰-Bromobenzyl)-1,4-dimethoxybenzene 3b 0X

Br). This compound was obtained following the method J,

using 2-84⁰-bromobenzoyl)-1,4-dimethoxybenzene. The

compound 3b was isolated as a white solid 885%) with the

same physical properties that the product obtained follow-

ing the method F.

4.5.14. 2,5-Dimethoxy-1-04⁰-nitrobenzyl)benzene 3e 0X

NO₂). This compound was obtained following the same

procedure, using 2,5-dimethoxy-1-84⁰-nitrobenzoyl)ben-

zene. The compound 3e was isolated as a yellow solid

879%) with the same physical properties than the product

obtained following the method I.

4.5.10. 2-04⁰-Bromobenzyl)-1,4-dimethoxybenzene 3b

0XBr) 0Method K). Tri¯ic acid 80.27 mL, 4.8 mmol)

was added dropwise 8syringe) to a stirred solution of

compound 4b 85.1 g, 16 mmol) and polymethylhydrosilox-

ane 82.9 mL, 48 mmol) in dichloromethane 820 mL). The

reaction mixture was stirred at room temperature for 7 h.

After ®ltering the mixture on silica gel and washing the

residue with a solution of 1 M NaOH 850 mL), the aqueous

layer was extracted with dichloromethane 82£20 mL), dried

over CaCl₂and concentrated under vacuum. The residue

was washed with a mixture of diethyl ether/heptane 87/3)

yielding 3b 84.2g, 85%) as a white solid with the same

physical properties that the product obtained following the

method F.

4.6. One step synthesis of diarylmethanes

4.6.1. 2-04⁰-Chlorobenzyl)-1,4-dimethoxybenzene 3a 0X

Cl) 0Method M). A mixture of 1,4-dimethoxybenzene 83 g,

21.7 mmol) and aluminum chloride 84.1 g, 30.4 mmol) in

nitromethane 830 mL) was stirred at 108C for 5 min. A solu-

tion of p-chlorobenzoyl chloride 82.76 mL g, 21.7 mmol) in

dichloromethane 810 mL) was added dropwise 85 min) and

the reaction mixture was stirred at room temperature for

90 min. A solution of triethylsilane 86.5 mL, 65.1 mmol)

in dichloromethane 810 mL) was then added and the mixture

was stirred at room temperature for 2h. After washing the

mixture with a solution of 1 M HCl 850 mL), the organic

layer was extracted with dichloromethane 82£20 mL), dried

over CaCl₂and concentrated under vacuum giving 3a

85.2g, 90%) as a white solid with the same physical proper-

ties than the product obtained following the method I.

4.5.11. 2-04⁰-Chlorobenzyl)-1,4-dimethoxybenzene 3a

0XCl). This compound was obtained following the same

procedure, using 2-84⁰-chlorobenzoyl)-1,4-dimethoxy-

benzene. The compound 3a was isolated as a white solid

889%) with the same physical properties than the product

obtained following the method I.

4.6.2. 2-04⁰-Chlorobenzyl)-1,4-dimethoxybenzene 3a 0X

Cl) 0Method O). A mixture of 1,4-dimethoxybenzene 83 g,

22.0 mmol) and aluminum chloride 84.1 g, 30.0 mmol) in

dichloromethane 830 mL) was stirred at 108C for 10 min.

A solution of p-chlorobenzoyl chloride 82.80 mL, 22.0

mmol) in dichloromethane 810 mL) was added dropwise

and the reaction mixture was stirred at room temperature

for 90 min. The mixture was cooled down 108C and a solu-

tion of polymethylhydrosiloxane 84.0 mL, 65.0 mmol) in

dichloromethane 810 mL) was slowly added 85 min). The

mixture was stirred at room temperature for 12h, then

®ltered on silica gel and washed with a solution of 1 M

HCl 850 mL). The organic layer was extracted with

dichloromethane 82£20 mL), dried over CaCl₂and concen-

trated under vacuum to give an oil which was crystallized

from a mixture of diethyl ether/petroleum ether yielding 3a

84.3 g, 75%) as a white solid with the same physical proper-

ties than the product obtained following the method I.

4.5.12. 2,5-Dimethoxy-1-04⁰-iodobenzyl)benzene 3c 0X

I). This compound was obtained following the same pro-

cedure, using 2,5-dimethoxy-1-84⁰-iodobenzoyl)benzene.

The compound 3c was isolated as a white solid 885%)

with the same physical properties than the product obtained

following the method I.

4.5.13. 2-04⁰-Chlorobenzyl)-1,4-dimethoxybenzene 3a

0XCl) 0Method L). Polymethylhydrosiloxane 83.2mL,

54 mmol) was added 8syringe) at room temperature, to a

stirred solution of compound 4a 85 g, 18 mmol) and alu-

minum chloride 82.8 g, 21 mmol) in nitromethane 810

mL). The reaction mixture was stirred at room temperature

for 20 days. After ®ltering the mixture on silica gel and

washing the residue with a solution of 1 M HCl 850 mL),

the organic layer was extracted with dichloromethane

82£20 mL), dried over CaCl₂and concentrated under

vacuum. The crude was washed with a mixture of diethyl

ether/heptane 87/3) yielding 3a 80.4 g, 9%) as a white solid

with the same physical properties that the compound

obtained following the method I and 13a 8XCl) puri®ed

by column chromatography 8petroleum ether/diethyl ether

7/3) 83.4 g, 71%) as a yellow solid, mp 828C; IR 8KBr):

4.6.3. 2-04⁰-Aminobenzyl)-1,4-dimethoxybenzene 3f 0X

NH₂). Under N₂atmosphere, a solution of 2,5-dimethoxy-1-

84⁰-nitrobenzyl)benzene 3e 85 g, 19.3 mmol) in methanol

830 mL) was poured into a suspension of 10% palladium

on charcoal 80.2g) in methanol 820 mL). Sodium boro-

hydride 81.5 g, 40.5 mmol) was slowly added and the

mixture was stirred at room temperature for 60 min. The

C. Waterlot et al. / Tetrahedron 57 02001) 4889±4901

4899

reaction mixture was acidi®ed by 2M HCl 850 mL), neutra-

4.8. Preparation of benzhydryl chlorides 14

lized by 1 M NaOH 825 mL). Methanol was removed under

reduced pressure and the aqueous phase was extracted by

dichloromethane 82£20 mL). The combined organic layers

were dried over MgSO₄then evaporated. The resulting solid

was recristallized from a mixture of water and ethanol 87:3,

70 mL) yielding compound 3f 84.2g, 90%) as a white solid;

IR 8KBr): 3440, 3385, 3220, 2925, 2835, 1625, 1505, 1445,

1280 cm²¹; ¹H NMR 8CDCl₃): d 3.55 8s, 2H), 3.73 8s, 3H),

3.78 8s, 3H), 3.87 8s, 2H), 6.61 8d, J8.7 Hz, 2H), 6.69 8dd,

J8.9, 3.0 Hz, 1H), 6.73 8d, J3.0 Hz, 1H), 6.80 8d, J

8.9 Hz, 1H), 7.03 8d, J8.7 Hz, 2H); ¹³C NMR 8CDCl₃):

d 35.1, 55.6, 56.1, 111.0, 111.4, 115.3, 111.7, 129.8, 130.7,

141.8, 144.3, 151.7, 153.5.

4.8.1. 4⁰-Chloro-2,5-dimethoxybenzhydryl chloride 14a

0XCl). Chlorotrimethylsilane 86.6 mL, 36.9 mmol) was

added 8syringe) to a solution of 4⁰-chloro-2,5-dimethoxy-

benzhydrol 87a) 85 g, 18.0 mmol) in dichloromethane 810

mL). The mixture was stirred at 58C for 25 min, then

concentrated under vacuum. The crude product was diluted

with dichloromethane 820 mL), then washed with a aqueous

1 M Na₂CO₃. The organic layer was dried over CaCl₂and

concentrated to give 14a 85.2g, 97%) as a brown oil; IR

8KBr pellets): 3000, 2940, 2835, 1585, 1500, 1465, 1225,

1050, 830 cm²¹; ¹H NMR 8CDCl₃): d 3.59 8s, 3H), 3.61 8s,

3H), 6.43 8s, 1H), 6.66 8m, 2H), 7.02 8d, J2.6 Hz, 1H),

7.14 8d, J8.9 Hz, 2H), 7.25 8d, J8.9 Hz, 2H); ¹³C NMR

8CDCl₃): d 55.7, 56.2, 57.4, 111.9, 113.9, 115.0, 128.5,

129.1, 130.0, 133.8, 140.0, 150.0, 153.6. Anal. Calcd for

C₁₅H₁₄Cl₂O₂: C, 60.62; H, 4.75; O, 10.77. Found: C,

60.45; H, 4.78; O, 10.82.

4.7. Preparation of monomer 2

4.7.1. Ethyl 4-02,5-dimethoxybenzyl)cinnamate 2 0R⁰

Et) 0Method R). A solution of ethyl acrylate 82.8 g,

28.2 mmol) in n-tributylamine 82mL) was slowly added

to a mixture of compound 3c 85 g, 14.1 mmol), triphenyl-

phosphine 80.07 g, 0.28 mmol) and palladium diacetate

80.03 g, 0.14 mmol) in n-tributylamine 83 mL). The mixture

was heated at 1058C for 2h. After cooling the reaction

mixture, the catalyst was collected and the organic phase

was stirred with 50 mL of water for 15 min. The aqueous

layer was extracted with dichloromethane 830 mL), dried

over CaCl₂and concentrated under vacuum. The brown

solid was recrystallized from a mixture of petroleum

ether/diethyl ether to give the monomer 2 83.4 g, 73%) as

a white solid; IR 8KBr): 2995, 2835, 1710, 1600, 1505,

4.8.2. 4⁰-Bromo-2,5-dimethoxybenzhydryl chloride 14b

0XBr). This compound was obtained following the same

procedure in the same way as 14a, using 4⁰-bromo-2,5-

dimethoxybenzhydrol 87b). Yield 97%, mp 558C; IR

8KBr): 3000, 2940, 2835, 1585, 1500, 1465, 1225, 1050,

1

830, 700 cm²¹; H NMR 8CDCl₃): d 3.77 8s, 6H), 6.53 8s,

1H), 6.97 8m, 2H), 7.12 8d, J2.2 Hz, 1H), 7.32 8d, J

8.5 Hz, 2H), 7.46 8d, J8.5 Hz, 2H); ¹³C NMR 8CDCl₃):

d 55.8, 56.2, 57.4, 111.9, 113.9, 115.0, 121.8, 129.4, 131.1,

139.9, 140.2, 150.1, 153.7. Anal. Calcd for C₁₅H₁₄BrClO₂:

C, 52.74; H, 4.13; Cl, 10.38; O, 9.37. Found: C, 52.65; H,

4.15; Cl, 10.45; O, 9.20.

1

1425, 1320, 1230, 1165, 1015 cm²¹; H NMR 8CDCl₃): d

1.17 8t, 3H), 3.67 8s, 3H), 3.71 8s, 3H), 3.90 8s, 2H), 4.20 8q,

2H), 6.34 8d, J16.0 Hz, 1H), 6.628d, J2.9 Hz, 1H), 6.68

8dd, J8.8, 3.0 Hz, 1H), 6.75 8d, J8,8 Hz, 1H), 7.18 8d,

J8.1 Hz, 2H), 7.38 8d, J8.1 Hz, 2H), 7.61 8d, J16.0 Hz,

1H); ¹³C NMR 8CDCl₃): d 14.2, 35.8, 55.5, 55.8, 60.2,

111.2, 111.3, 116.7, 117.1, 128.0, 129.2, 130.0, 132.0,

143.4, 144.4, 151.5, 153.4, 167.0.

4.8.3. 2,5-Dimethoxy-4⁰-nitrobenzhydryl chloride 14e 0X

NO₂). This compound was obtained following the same

procedure in the same way as 14a, using 2,5-dimethoxy-

4⁰-nitrobenzhydrol 87e). Yield 93%; IR 8KBr): 3090,

2940, 2835, 1610, 1595, 1450, 1460, 1350, 1210, 1110,

1

1035, 820 cm²¹; H NMR 8CDCl₃): d 3.69 8s, 3H), 3.70

8s, 3H), 6.49 8s, 1H), 6.75 8m, 2H), 7.00 8d, J2.2 Hz,

1H), 7.51 8d, J8.8 Hz, 2H), 8.08 8d, J8.8 Hz, 2H); ¹³C

NMR 8CDCl₃): d 55.8, 56.1, 56.8, 111.9, 114.2, 114.9,

123.6, 128.5, 129.5, 147.6, 148.2, 150.0, 153.9. Anal.

Calcd for C₁₅H₁₄ClNO₄: C, 58.55; H, 4.59; N, 4.55; O,

20.80. Found: C, 58.42; H, 4.61; N, 4.49; O, 20.75.

4.7.2. Methyl 4-02,5-dimethoxybenzyl)cinnamate 2 0R⁰

Me) 0Method T). A solution of methyl acrylate 87.4 g,

84.7 mmol) in dimethylformamide 850 mL) was slowly

added to a mixture of compound 3c 815 g, 42.4 mmol),

potassium carbonate 815.8 g, 114.3 mmol) and catalyst

K₁₀±Pd±Cu²⁶81.5 g) in dimethylformamide 850 mL). The

mixture was re¯uxed for 2h. The catalyst was collected and

the cooled reaction mixture was stirred with 100 mL of

water for 15 min. The aqueous layer was extracted with

dichloromethane 850 mL), dried over CaCl₂and concen-

trated under vacuum. The brown solid was recrystallized

from a mixture of petroleum ether/diethyl ether to give

the monomer 2 812.3 g, 93%) as a white solid, mp 838C;

IR 8KBr): 2995, 2835, 1710, 1600, 1500, 1430, 1320, 1230,

1170, 1020 cm²¹; ¹H NMR 8CDCl₃): d 3.728s, 3H), 3.76 8s,

3H), 3.79 8s, 3H), 3.95 8s, 2H), 6.38 8d, J16.1 Hz, 1H),

6.66 8d, J3.0 Hz, 1H), 6.728dd, J8.8 Hz, J3.0 Hz, 1H),

6.79 8d, J8.8 Hz, 1H), 7.22 8d, J8.1 Hz, 2H), 7.42 8d, J

8.1 Hz, 2H), 7.66 8d, J16.1 Hz, 1H); ¹³C NMR 8CDCl₃): d

4.9. Preparation of triarylmethanes 12

4.9.1. 1-[4⁰-Chlorobenzyl)02,5-dimethoxyphenyl)]-2,5-

dimethoxybenzene 12a 0XCl). To a stirred solution of

p-dimethoxybenzene 89.2g, 67.3 mmol) and aluminum

chloride 80.9 g, 6.73 mmol) in dichloromethane 8180 mL)

was added a solution of chloride 14a 8XCl) 82g,

6.73 mmol) in dichloromethane 820 mL). The mixture was

stirred at room temperature for 15 min and washed with a

solution of 0.5 M HCl 8100 mL). The organic layer was

dried over CaCl₂and concentrated under vacuum. The resi-

due was washed with petroleum ether, then puri®ed by

column chromatography 8silica gel 100 g, petroleum ether/

diethyl ether9/1) to give 12a 81.8 g, 67%) as a white solid.

R_f: 0.20, mp 828C; IR 8KBr): 3000, 2950, 2835, 1595, 1495,

36.1, 51.7, 55.7, 56.0, 111.5, 116.9, 128.2, 128.4, 130.2,

1

132.1, 143.7, 144.9, 151.7, 153.6, 167.7; m/z 3128M

,

1

100); Anal. Calcd for C₁₉H₂₀O₄: C, 73.06; H, 6.45. Found:

C, 72.92; H, 6.29.

1455, 1220, 1110, 1045, 715 cm²¹; H NMR 8CDCl₃): d

3.64 8s, 6H), 3.68 8s, 6H), 6.128s, 1H), 6.428d, J3.0 Hz,

4900

C. Waterlot et al. / Tetrahedron 57 02001) 4889±4901

7. 8a) Clarke, S. D.; Harrison, C. R.; Hodge, P. Tetrahedron Lett.

1980, 21, 1375±1378. 8b) Chang, Y. H.; Ford, W. T. J. Org.

Chem. 1981, 46, 3756±3758. 8c) Zupan, M.; Pollak, A.

J. Chem. Soc. Chem. Comm. 1975, 715±716.

2H), 6.73 8dd, J8.8, 3.0 Hz, 2H), 6.81 8d, J8.8 Hz, 2H),

7.028d, J8.4 Hz, 2H), 7.22 8d, J8.4 Hz, 2H); ¹³C NMR

8CDCl₃): d 43.0, 55.5, 56.4, 110.8, 111.9, 117.2, 128.2,

130.6, 131.6, 133.2, 142.1, 151.6, 153.3; m/z 400 8for

³⁷Cl, M¹, 37.3), 398 8for ³⁵Cl, M¹, 100); Anal. Calcd for

C₂₃H₂₃ClO₄: C, 69.26; H, 5.81; O, 16.04. Found: C, 69.17;

H, 5.82; O, 15.79.

8. 8a) Kun, K. A. J. Polym. Sci. 1965, 3, 1833±1843. 8b) Kun,

K. A. J. Polym. Sci. 1966, 4, 847±857.

9. Kun, K. A.; Kunin, R. J. Polym. Sci. 1966, 4, 859±868.

10. Waterlot, C.; Couturier, D.; Hasiak, B. J. Appl. Polym. Sci.

2001, 80, 223±229.

4.9.2. 1-[4⁰-Bromobenzyl)02,5-dimethoxyphenyl)]-2,5-di-

methoxybenzene 12b 0XBr). This compound was

obtained following the same procedure in the same way as

12a, using 4⁰-bromo-2,5-dimethoxybenzydryl chloride.

Yield 68%, R_f: 0.13, mp 898C; IR 8KBr): 2995, 2945,

11. 8a) Cornelis, A.; Lazlo, P. Synlett 1994, 155±159. 8b) Clark,

J. H.; Kybett, R. P.; McQuaries, D. J.; Barlow, S. J. J. Chem.

Soc. Chem. Comm. 1989, 1353±1354. 8c) Cornelis, A.; Dony,

C.; Lazlo, P.; Nsunda, K. M. Tetrahedron Lett. 1991, 32,

2901±2902.

1

2830, 1590, 1495, 1450, 1215, 1100, 1045, 725 cm²¹; H

NMR 8CDCl₃): d 3.63 8s, 6H), 3.66 8s, 6H), 6.07 8s, 1H),

6.38 8d, J3.0 Hz, 2H), 6.71 8dd, J8.8, 3.0 Hz, 2H), 6.79

8d, J8.8 Hz, 2H), 6.94 8d, J8.3 Hz, 2H), 7.35 8d, J

8.3 Hz, 2H); ¹³C NMR 8CDCl₃): d 43.2, 55.6, 56.5, 110.9,

111.9, 117.2, 119.8, 131.0, 131.1, 133.3, 142.7, 151.6,

153.4; m/z 445 8for ⁸¹Br, MH¹, 24.7), 444 8for ⁸¹Br, M¹,

94.3), 443 8for ⁷⁹Br, MH¹, 25.9), 442 8for ⁷⁹Br, M¹, 100)

364 8for ⁸¹Br, MH¹2Br, 100); Anal. Calcd for C₂₃H₂₃BrO₄:

C, 62.31; H, 5.23; O, 14.44. Found: C, 62.22; H, 5.24; O,

14.36.

12. The formation of ketones during Grignard reaction of aryl

aldehydes has already been observed,¹³and is not due to a

disproportionation of the benzhydrol.¹⁴

13. 8a) Bourry, A.; Pitard, P.; Rigo, B.; Sanz, G.; Couturier, D.;

J. Heterocycl. Chem., submitted to publication. 8b) Kas, C. L.;

Yen, S. Y.; Chern, J. W.; Kas, S. Y. Tetrahedron Lett. 2000,

41, 2207±2210.

14. 8a) Gautret, P.; El Ghammati, S.; Legrand, A.; Couturier, D.;

Rigo, B. Synth. Comm. 1996, 26, 707±713. 8b) Waterlot, C.;

Couturier, D.; Debacker, M.; Rigo, B. Can. J. Chem. 2000, 78,

1242±1246.

4.9.3. 2,5-Dimethoxy-1-[02,5-dimethoxyphenyl)04⁰-nitro-

benzyl)]benzene 12e 0XNO₂). This compound was

obtained following the same procedure in the same way as

12a, using 4⁰-nitro-2,5-dimethoxybenzydryl chloride. Yield

63%, R_f: 0.11, mp 598C; IR 8KBr): 2995, 2940, 2840, 1595,

15. 8a) Kauffman, H.; Grombach, A. Beilstein 1905, 17, 794±797.

8b) Philbin, E. M.; Swirski, J.; Wheeler, T. S. J. Chem. Soc.

1956, 4455±4558.

16. Kawada, A.; Mitamura, S.; Kobayashi, Y. Synlett 1994, 545±

546.

1510, 1495, 1345, 1215, 1050, 825 cm²¹

;

¹H NMR

17. Olah, G. A. In Friedel±Crafts and Related Reactions: General

Aspect I, Wiley: New York, 1963; pp 296±307.

18. 8a) Kursanov, D. N.; Parnes, Z. N.; Loim, N. M. Synthesis

1974, 23, 633±651. 8b) Mayr, H.; Dogan, B. Tetrahedron

1997, 38, 1013±1016.

8CDCl₃): d 3.64 8s, 6H), 3.66 8s, 6H), 6.18 8s, 1H), 6.36

8d, J2.9 Hz, 2H), 6.74 8dd, J8.8, 2.9 Hz, 2H), 6.81 8d,

J8.8 Hz, 2H), 7.20 8d, J8.5 Hz, 2H), 8.09 8d, J8.5 Hz,

2H); ¹³C NMR 8CDCl₃): d 43.8, 55.6, 56.3, 111.3, 111.8,

117.3, 123.3, 129.9, 132.0, 146.2, 151.5, 152.0, 153.5; m/z

410 8MH¹, 27.0), 409 8M¹, 100); Anal. Calcd for

C₂₃H₂₃NO₆: C, 67.47; H, 5.66; N, 3.42. Found: C, 67.14;

H, 5.51; N, 3.57.

19. Gribble, G. W.; Leese, R. M. Synthesis 1977, 172±176.

20. Carey, F. A.; Tremper, H. S. J. Am. Chem. Soc. 1968, 90,

2578±2583.

21. Olah, G. A.; Arvanaghi, M.; Ohannesian, L. Synthesis 1986,

770±772.

22. 8a) Kursanov, D. N.; Parnes, Z. N.; Bassova, G. I.; Loim,

N. M.; Pdanovich, V. I. Tetrahedron 1967, 23, 2235±2242.

8b) West, C. T.; Donnelly, S. J.; Kooistra, D. A.; Doyle, M. P.

J. Org. Chem. 1973, 38, 2675±2681.

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Article Doi

On the synthesis of dimethoxybenzyl cinnamates, monomers for electron transfer polymers

DOI: 10.1016/S0040-4020(01)00417-3

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