Original formation of benzyl benzoates by TDAE strategy

Article abstract of DOI:10.1016/j.tetlet.2007.12.011

We report herein an original photoinduced electron transfer reaction between an aromatic aldehyde and TDAE in the presence of chloromethyl-dimethoxybenzenes. Thus, the reaction of 1-chloromethyl-2,5-dimethoxy-3,4,6-trimethylbenzene (1), dichlorides 4 and

Full text of DOI:10.1016/j.tetlet.2007.12.011

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 1016–1020
Original formation of benzyl benzoates by TDAE strategy
a
a
b
a,
*
´
Ouassila Amiri-Attou , Thierry Terme , Maurice Medebielle , Patrice Vanelle
a Laboratoire de Chimie Organique Pharmaceutique LCOP, UMR CNRS 6517, Universite´ de la Me´diterrane´e, Faculte´ de Pharmacie,
27 Bd Jean Moulin, 13385 Marseille Cedex 05, France
b
`
`
´
´
´
´
´
Laboratoire Synthese, Electrosynthese et Reactivite des Composes Organiques Fluores (SERCOF), Institut de Chimie et Biochimie Moleculaires
et Supramole´culaires (ICBMS), Universite´ Claude Bernard Lyon 1 (UCBL), UMR 5246 CNRS—UCBL—INSA—CPE,
43 Bd du 11 novembre 1918, F-69622 Villeurbanne, France
Received 26 September 2007; revised 30 November 2007; accepted 4 December 2007
Available online 8 December 2007
Dedicated to the memory of Dr. Jean-Pierre Finet
Abstract
We report herein an original photoinduced electron transfer reaction between an aromatic aldehyde and TDAE in the presence of
chloromethyl-dimethoxybenzenes. Thus, the reaction of 1-chloromethyl-2,5-dimethoxy-3,4,6-trimethylbenzene (1), dichlorides 4 and 5
with a series of aromatic aldehydes, in the presence of TDAE and under light catalysis, gave the corresponding benzyl benzoates.
Ó 2007 Elsevier Ltd. All rights reserved.
Keywords: TDAE; Aromatic aldehydes; Benzyl benzoates; Electron transfer
Quinones are a large class of compounds with diverse
biological activities. They are found in many animal and
plant cells and are widely used as anticancer,1 antibacterial2
or antimalarial3 drugs as well as fungicides.4 Quinones rep-
resent a class of organic compounds possessing rich and
fascinating chemistry. Many of them are important thera-
peutic agents, quite often they serve as auxiliaries in
organic synthesis and in the dye industry.5
Tetrakis(dimethylamino)ethylene (TDAE) is a reducing
agent, which reacts with halogenated derivatives to gener-
ate an anion under mild conditions via a single electron
transfer (SET).8 According to this strategy, we have
recently developed many reactions between nitrobenzylic
substrates and a series of electrophiles such as aldehydes,
ketones, a-keto-esters, a-ketolactams and ketomalonates
leading to the corresponding alcohol adducts.9
Electron transfer reactions are intensively studied in
chemistry and the photochemical approach of reactions
of this type has become familiar to most organic chemists
as the result of a better understanding of primary pro-
cesses.6 Photoinduced electron transfer (PET) reactions
between a carbonyl derivative considered as an acceptor
and an amine considered as a donor have received consid-
erable attention since the pioneering studies on photo-
reduction of aromatic ketones with tertiary amines.7
In our research program directed toward the develop-
ment of original synthetic methods using TDAE methodo-
logy in medicinal chemistry and the preparation of new
potentially bioactive compounds as anticancer agents,9,10
we envisaged to prepare novel quinonic derivatives, from
the reaction of dimethoxybenzene precursors and TDAE,
in the presence of aldehydes. We report herein the prepara-
tion of 1-chloromethyl-2,5-dimethoxy-3,4,6-trimethyl-
benzene (1) and studied its reactivity with aromatic
aldehydes in the presence of TDAE.
After the two-step synthesis of chloride 1 from 2,3,5-tri-
methyl-1,4-hydroquinone by methylation, using dimethyl-
sulfate and chloromethylation according to Thomson
*
Corresponding author. Tel.: +33 4 91 83 55 80; fax: +33 4 91 79 46 77.
E-mail address: patrice.vanelle@pharmacie.univ-mrs.fr (P. Vanelle).
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.12.011

O. Amiri-Attou et al. / Tetrahedron Letters 49 (2008) 1016–1020
1017
O
H
No reaction
OCH3
CH3
CH3
CH3
Cl
1) TDAE, DMF
-20 ºC
OCH3
2) rt, 48 h
NO2
CH3
CH3
CH3
hν
OCH3
NO2
2a
O
1
O
OCH3
3a
Scheme 1. Reaction of chloride 1 and aromatic aldehyde 2a.
Table 1
to investigate the impact of light on this reaction. The
beneficial effect of light in TDAE mediated nucleophilic
perfluoroalkylation of aldehydes and ketones has been
previously demonstrated by one of us.8a,f
Influence of experimental conditions in the reaction of 1 and 2a in the
presence of TDAE
Entrya Solvent
TDAE
(equiv)
Benzaldehyde 2a
(equiv)
Yield 3a
(%)
Under light irradiation and inert atmosphere, the reac-
tion of chloride 1 with 4-nitrobenzaldehyde 2a in the pres-
ence of TDAE at À20 °C for 1 h, followed by 48 h at room
temperature furnishes the 2,5-dimethoxy-3,4,6-trimethyl-
benzyl 4-nitrobenzoate 3a (Scheme 1). To optimize the
formation of this unexpected ester derivative 3a, we have
studied the influence of solvent (DMF, THF, CH3CN),
the concentration of TDAE (0–3 equiv) and 4-nitrobenzal-
dehyde 2a (1–4 equiv) as shown in Table 1.
This study shows the importance of DMF as the solvent
and the sensitivity of this reaction to an excess of 4-nitro-
benzaldehyde 2a (3 equiv) and TDAE (1.5 equiv). The best
yield (82%) was obtained under light irradiation and inert
atmosphere, by using 3 equiv of 4-nitrobenzaldehyde 2a
and 1 equiv of chloride 1 in the presence of 1.5 equiv of
TDAE at À20 °C for 1 h, followed by 48 h at room temper-
ature and under light irradiation (Table 1, Entry 5). After
2 h only 42% of benzyl benzoate 3a was isolated.
To explain the formation of this unexpected ester deriv-
ative 3a, we have developed a mechanistic study. Firstly,
contrary to the classical TDAE activation of chloride deriv-
atives, which develops a red color, in this reaction an
original green color appears when the TDAE and the
4-nitrobenzaldehyde 2a get in contact. Thus, we have con-
sidered that the initiation step was a possible photoinduced
electron transfer between TDAE and 4-nitrobenzaldehyde
2a, we have replaced TDAE by a known electron donor
used in many synthetic PET reactions, that is, triethylamine
1
2
3
4
5
6
7
8
9
DMF
1
0
0.5
1
1.5
3
1.5
1.5
1.5
1.5
3
3
3
3
3
3
1
2
4
3
3
0
0
DMFb
DMFb
DMFb
DMFb
DMFb
DMFb
DMFb
DMFb
THFb
40
57
82
c
—
40
45
45
64
50
10
11
a
CH3CNb 1.5
All the reactions are performed using 1 equiv of 1.
Under light irradiation.
Only untractable tarry matters were formed.
b
c
procedure, a preliminary study in classical TDAE condi-
tions was considered (Scheme 1).11
Treated under classical conditions,9,10 that is, under
inert atmosphere, with 3 equiv of 4-nitrobenzaldehyde 2a
in the presence of TDAE at À20 °C for 1 h, followed by
2 or 48 h at room temperature, chloride 1 was recovered
unchanged. This result could be explained by the absence
of reduction of chloride 1 due to its particularly high reduc-
tion potential (E = À2.42 V vs SCE).
The importance of light in electron transfer reactions,
allowing to favor the reduction of chloride 1 or to realize
an hypothetic photoinduced electron transfer between aro-
matic aldehyde as an acceptor and TDAE as donor, led us
O
OCH3
O2N
CH3
CH3
CH3
O
Cl
O2
OCH3
1
O
H
O
H
O
H
OCH3
OCH3
NO2
CH3
CH3
CH3
O
TDAE, hν
OCH3
CH3
CH3
CH3
O
Cl
O2
3a
NO2
NO2
NO2
OCH3
1
2a
2a
OCH3
CH3
NO2
CH3
CH3
O
H
OCH3
Scheme 2. Mechanism formation of ester 3a.

1018
O. Amiri-Attou et al. / Tetrahedron Letters 49 (2008) 1016–1020
Table 2
Table 3
Reaction of chloride 1 and aromatic aldehydes 2a–g
Cyclic voltammetry study of benzaldehydes
Aromatic aldehyde
R
Ester derivative Yield (%)
Aromatic aldehyde
Epc1
(V vs SCE)
Epc2
(V vs SCE)
Yield 3
(%)
4-Nitrobenzaldehyde
4-Cyanobenzaldehyde
3-Nitrobenzaldehyde
2-Nitrobenzaldehyde
4-Bromobenzaldehyde
Benzaldehyde
4-NO2
4-CN
3-NO2
2-NO2
4-Br
3a
3b
3c
3d
3e
3f
82
40
40
4
14
58
10
4-Nitrobenzaldehyde
4-Cyanobenzaldehyde
3-Nitrobenzaldehyde
4-Bromobenzaldehyde
Benzaldehyde
À0.87
À1.35
À0.97
À1.76
À1.95
À0.52
À2.30
À1.43
À2.40
À2.21
82
40
40
14
58
10
0
4-H
2,4-Dinitrobenzaldehyde 2-NO2; 4-NO2 3g
2,4-Dinitrobenzaldehyde
4-Chlorobenzaldehyde
À0.99
All the reactions are performed using 3 equiv of aromatic aldehydes 2a–g,
1 equiv of chloride 1 and 1.5 equiv of TDAE in anhydrous DMF under
light irradiation and inert atmosphere (N2) at À20 °C for 1 h, followed by
48 h at room temperature.
1 (Scheme 2). However, the 4-nitrobenzoic acid was never
isolated in all these reactions despite the modifications of
the experimental protocol and the study of the reaction
of 4-nitrobenzaldehyde 2a and TDAE, which furnishes
only resins. The absence of confirmation of 4-nitrobenzoic
acid as an intermediate led us to propose an alternative
pathway to explain the formation of ester 3a. Moreover,
it was not possible to trap the putative benzylic radical
neither by methylacrylate15 nor with TEMPO.16
(Et3N).12 With 4-nitrobenzaldehyde 2a, the use of triethyl-
amine and light catalysis furnished the corresponding ester
although in lower yield, 37% versus 82% using TDAE; no
reaction was observed in the absence of light catalysis. This
result shows that the primary step is indeed an electron
transfer between TDAE and the aldehyde, and that TDAE
is a better electron donor than Et3N.
This reactivity has been generalized with various aro-
matic aldehydes but this reaction was only observed with
aromatic aldehydes presented in Table 2 (Scheme 3).17
No reactivity has been observed with other aromatic alde-
hydes (4-chloro, 4-fluoro, 4-trifluoromethyl, 2-bromo, etc.).
To determine if the aldehydes may act or not as electron
transfer reagents, some of them have been studied by cyclic
voltammetry in DMF as a solvent with NBu4PF6 as a sup-
porting electrolyte (Table 3). Aromatic aldehydes 2a, 2c,
and 2f were the easiest to reduce in the series, and they
usually gave two reduction steps; the first one was attrib-
uted to the formation of a stable ketyl radical anion
(Epc1 = À0.52 to À0.87 V vs SCE) and the second one
(Epc2 = À0.99 to À2.21 V vs SCE) to the formation of a
stable dianion. 4-Cyanobenzaldehyde 2b was also a good
electron acceptor giving a stable radical anion close to
À1.35 V versus SCE. Other aldehydes 2d, 2e, and 2g gave
only one irreversible reduction step (unstable radical anion;
Epc1 = À1.76 to À2.30 V vs SCE) with 4-chlorobenzalde-
hyde being the most difficult (Epc1 = À2.30 V vs SCE).
Yields of the benzoate derivatives 3 seem to be correlated
to the ability of these aldehydes to form stable radical
anions at relatively low reduction potentials, with the excep-
tion of aldehydes 2e and 2f.
An oxidation step proceeding via a possible radical
mechanism seems to be probable to explain the final forma-
tion of ester derivative 3a.13 The use of freshly degassed
DMF (N2 bubbling for 2 h) in classical experimental condi-
tions in the reaction of 1 with aldehyde 2a decreases the
yield of ester 3a (33% vs 82%). These results suggest the
possible role of molecular oxygen. This suggestion seems
to be confirmed by the reaction of chloride 1, aldehyde
2a and Et3N under atmospheric dioxygen, which gives an
increase in yield (57% vs 37% under inert atmosphere).
However, under similar conditions (under atmospheric
dioxygen) the use of TDAE as electron donor did not per-
mit us to isolate the expected ester 3a, probably due to the
instability of TDAE in the presence of dioxygen.14
To a better understanding of the formation of ester 3a,
we have considered a possible oxidation of benzaldehyde to
a carboxylic species, which reacts with chloride 1. This
hypothesis seems confirm by the reaction of 4-nitrobenzoic
acid and chloride 1 in the presence of TDAE which fur-
nishes ester 3a in 71% yield with or without light catalysis.
No reaction was observed in the absence of TDAE. These
two reactions show the basic properties of TDAE to form a
carboxylate anion and the possibility of the latter to react
with chloride 1.
To generalize this original reactivity to other dimethoxy-
benzene derivatives, we have prepared two new dichloride
derivatives 4 and 518 (E = À2.41 V vs SCE for 4 and
À2.17 V vs SCE for 5) and studied their reactivity in the
same experimental conditions (under light catalysis) pre-
All these data led us to consider that under light cataly-
sis, 4-nitrobenzaldehyde 2a would be activated by TDAE
to form a ketyl radical-anion followed by an oxidation step
to form 4-nitrobenzoate anion, which reacts with substrate
O
H
OCH3
OCH3
R
CH3
CH3
CH3
CH3
CH3
CH3
Cl
1) TDAE, DMF,
-20 ºC, hν
O
2) rt, 48 h
R
O
OCH3
OCH3
2a-g
3a-g
1
Scheme 3. Reaction of chloride 1 and aromatic aldehydes 2a–g under light irradiation.

O. Amiri-Attou et al. / Tetrahedron Letters 49 (2008) 1016–1020
1019
NO2
O
H
OCH3
OCH3
OCH3
CH3
CH3
CH3
CH3
Cl
Cl
1) TDAE, DMF, -20 ºC, hν
O
O
NO2
6a 55%
2) rt, 48 h
OCH3 O
NO2
2a
4
O
NO2
O
H
OCH3
OCH3
OCH3
Cl
Cl
O
O
O
1) TDAE, DMF, -20 ºC, hν
7a 28%
NO2
2) rt, 48 h
OCH3
O
2a
NO2
5
Scheme 4. Reaction of dichlorides 4, 5 and aromatic aldehyde 2a under light catalysis.
OCH3
OCH3
O
R
R
´
O. Piva (Universite Claude Bernard Lyon 1, ICBMS) for
useful suggestions.
CH3
CH3
CH3
CH3
CH3
CH3
CAN
O
O
CH3CN
O
O
O
References and notes
3a R = 4-NO2
3b R = 4-CN
3c R = 3-NO2
8a 70 %
8b 61 %
8c 66 %
1. (a) Arcamone, F. Cancer Res. 1985, 45, 5995–5999; (b) Moore, H. W.
Science 1977, 197, 527–532; (c) Lin, A. J.; Cosby, L. A.; Shansky, C.
W.; Sartorelli, A. C. J. Med. Chem. 1972, 15, 1247–1252.
2. (a) Lana, E. J. L.; Carazza, F.; Takahashi, A. J. Agric. Food Chem.
2006, 54, 2053–2056; (b) Drewes, S. E.; Khan, F.; van Vuuren, S. F.;
Viljoen, A. M. Phytochemistry 2005, 66, 1812–1816.
3. Eyong, K. O.; Folefoc, G. N.; Kuete, V.; Beng, V. P.; Krohn, K.;
Hussain, H.; Nkengfack, A. E.; Saeftel, M.; Sarite, S. R.; Hoerauf, A.
Phytochemistry 2006, 67, 605–609.
4. Bernini, R.; Mincione, E.; Barontini, M.; Fabrizi, G.; Pasqualetti, M.;
Tempesta, S. Tetrahedron 2006, 62, 7733–7737.
5. Gallagher, P. T. Contemp. Org. Synth. 1996, 3, 433–446.
6. (a) Fox, M. A.; Chanon, M. Photoinduced Electron Transfer; Elsevier:
Amsterdam, 1988; (b) Julliard, M.; Chanon, M. Chem. Rev. 1983, 83,
425–506.
Scheme 5. Preparation of benzoquinones 8a–c by oxidation of the
corresponding dimethoxybenzene derivatives 3a–c.
sented with 4-nitrobenzaldehyde 2a. The dichlorides 4 and
5 furnished the corresponding diester derivatives 6a or 7a
in, respectively, 55% and 28% yields (Scheme 4).19 Finally
the obtained dimethoxybenzene, 3a–c were oxidized into
the corresponding benzoquinones 8a–c using Cerium
Ammonium Nitrate (CAN) in acetonitrile (Scheme 5).20
In conclusion, we have presented herein a photoinduced
electron transfer reaction between an aromatic aldehyde
and TDAE and its original application in dimethoxy-
benzene series leading to unexpected ester derivatives. This
reactivity has been generalized to other dimethoxybenzene
dichlorides and some products have been oxidized to the
corresponding benzoquinones. The mechanistic study
seems to indicate a TDAE-light activation of the benzalde-
hyde derivatives to form ketyl radical anion via a photoin-
duced electron transfer followed by an oxidation step.
However, further experiments are necessary to confirm
the oxidation step and the proposed mechanism. The gen-
eralization of the reaction of dichlorides with other benzal-
dehydes is under active investigation.
7. (a) Cossy, J.; Pete, J.-P. In Advances in Electron Transfer Chemistry;
Mariano, P. S., Ed.; JAI: Greenwich, CT, 1996; Vol. 5, p 141; (b)
Yoon, U. C.; Mariano, P. S.; Givens, R. S.; Atwater, B. W., III. In
Advances in Electron Transfer Chemistry; Mariano, P. S., Ed.; JAI:
Greenwich, CT, 1994; Vol. 4, p 117; (c) Kavarnos, G. J.; Turro, N. J.
Chem. Rev. 1986, 86, 401–449.
´
8. (a) Pooput, C.; Medebielle, M.; Dolbier, W. R., Jr. J. Org. Chem.
2006, 71, 3564–3568; (b) Pooput, C.; Me´debielle, M.; Dolbier, W. R.,
´
Jr. Org. Lett. 2004, 6, 301–303; (c) Medebielle, M.; Kato, K.; Dolbier,
W. R., Jr. Tetrahedron Lett. 2003, 44, 7871–7873; (d) Takechi, N.;
´
Ait-Mohand, S.; Medebielle, M.; Dolbier, W. R., Jr. Tetrahedron
´
Lett. 2002, 43, 4317–4319; (e) Takechi, N.; Ait-Mohand, S.; Mede-
bielle, M.; Dolbier, W. R., Jr. Org. Lett. 2002, 4, 4671–4672; (f) Ait-
´
Mohand, S.; Takechi, N.; Medebielle, M.; Dolbier, W. R., Jr. Org.
´
Lett. 2001, 3, 4271–4273; (g) Medebielle, M.; Keirouz, R.; Okada, E.;
´
Ashida, T. Synlett 2001, 821–823; (h) Dolbier, W. R., Jr.; Medebielle,
M.; Ait-Mohand, S. Tetrahedron Lett. 2001, 42, 4811–4814; (i)
Acknowledgments
´
Burkholder, C. R.; Dolbier, W. R., Jr.; Medebielle, M. J. Org. Chem.
1998, 63, 5385–5394.
9. (a) Amiri-Attou, O.; Terme, T.; Vanelle, P. Molecules 2005, 10, 545–
This work was supported by the Centre National de la
Recherche Scientifique. We express our thanks to V.
´
´
551; (b) Giuglio-Tonolo, G.; Terme, T.; Medebielle, M.; Vanelle, P.
1
Remusat for H and 13C NMR spectra recording and to
Tetrahedron Lett. 2004, 45, 5121–5124; (c) Giuglio-Tonolo, G.;

1020
O. Amiri-Attou et al. / Tetrahedron Letters 49 (2008) 1016–1020
´
Terme, T.; Medebielle, M.; Vanelle, P. Tetrahedron Lett. 2003, 44,
6433–6435.
observed in this experiment. Anal. Calcd for C19H21NO6: C, 63.50; H,
5.89; N, 3.90. Found: C, 63.34; H, 6.06; N, 3.89. Compound 3d: white
solid; 1H NMR (CDCl3, 200 MHz) d 2.22 (s, 3H); 2.24 (s, 3H); 2.31 (s,
3H); 3.68 (s, 3H); 3.72 (s, 3H); 5.50 (s, 2H); 7.75 (m, 2H); 8.20 (m,
2H). Compound 3e: white solid; mp 109 °C, 1H NMR (CDCl3,
200 MHz) d 2.21 (s, 3H); 2.24 (s, 3H); 2.29 (s, 3H); 3.68 (s, 3H); 3.71
(s, 3H); 5.43 (s, 2H); 7.54 (d, J = 8.6 Hz, 2H); 7.88 (d, J = 8.6 Hz,
2H). Compound 3f: white solid; mp 70 °C, 1H NMR (CDCl3,
200 MHz) d 2.22 (s, 3H); 2.24 (s, 3H); 2.31 (s, 3H); 3.68 (s, 3H); 3.72
(s, 3H); 5.45 (s, 2H); 7.42 (m, 2H); 7.54 (m, 1H); 8.03 (m, 2H). 13C
NMR (CDCl3, 50 MHz) d 11.9 (CH3); 12.6 (CH3); 12.9 (CH3); 59.6
(CH2); 60.0 (OCH3); 61.8 (OCH3); 125.0 (C); 128.1 (C); 129.0
(2 Â CH); 129.2 (C); 129.3 (2 Â CH); 129.8 (C); 131.8 (C); 133.5 (CH);
152.8 (C); 153.8 (C); 165.9 (C). Anal. Calcd for C19H22O4: C, 72.59;
H, 7.05. Found: C, 72.51; H, 7.26. Compound 3g: brown solid; mp
106 °C, 1H NMR (CDCl3, 200 MHz) d 2.16 (s, 3H); 2.21 (s, 3H); 2.24
(s, 3H); 3.75 (s, 3H); 3.81 (s, 3H); 5.44 (s, 2H); 6.79 (s, 1H); 8.23 (d,
J = 9.2 Hz, 2H).
10. (a) Montana, M.; Terme, T.; Vanelle, P. Tetrahedron Lett. 2006, 47,
6573–6576; (b) Montana, M.; Terme, T.; Vanelle, P. Tetrahedron Lett.
2005, 46, 8373–8376.
11. (a) Syper, L.; Kloc, K.; Mlochovsky, J. Tetrahedron 1980, 36, 123–
129; (b) Thomson, R. H. J. Chem. Soc. 1953, 1196–1199.
12. Cossy, J.; Bellotti, D. Tetrahedron 2006, 62, 6459–6470.
13. See for relevant examples: (a) Bjorsvik, H.-R.; Liguori, L.; Minisci, F.
Org. Process. Res. Dev. 2001, 5, 136–140; (b) Lawrence, N. J.;
Lamarche, O.; Thurrab, N. Chem. Commun. 1999, 689–690; (c)
Russell, G. A.; Bemis, A. G. J. Am. Chem. Soc. 1966, 88, 5491; (d)
Russell, G. A.; Janzen, E. G.; Becker, H.-D.; Smentowsky, F. J. Am.
Chem. Soc. 1962, 84, 2652.
14. Fletcher, A. N.; Heller, C. A. J. Phys. Chem. 1967, 71, 1507–1518.
15. (a) Nishiyama, Y.; Kobayashi, A. Tetrahedron Lett. 2006, 47, 5565–
5567; (b) Nishiyama, Y.; Kawabata, H.; Kobayashi, A.; Nishino, T.;
Sonoda, N. Tetrahedron Lett. 2005, 46, 867–869.
16. Terme, T.; Beziane, A.; Vanelle, P. Lett. Org. Chem. 2005, 2, 367–
370.
17. General procedure for the reaction of 1-(chloromethyl)-2,5-di-
18. Terme, T.; Maldonado, J.; Crozet, M. P.; Vanelle, P. Synth. Commun.
2001, 31, 3877–3883.
1
19. Compound 6a: white solid; mp 196 °C, H NMR (CDCl3, 200 MHz)
methoxy-3,4,6-trimethylbenzene
1
and aromatic aldehydes 2a–g,
d 2.29 (s, 6H); 3.77 (s, 6H); 5.57 (s, 4H); 8.06 (m, 8H). 13C NMR
(CDCl3, 50 MHz) d 13.2 (2 Â CH3); 60.1 (2 Â CH2); 62.0 (2 Â OCH3);
123.5 (4 Â CH); 126.1 (2 Â C); 130.6 (4 Â CH); 133.6 (2 Â C); 135.2
(2 Â C); 150.5 (2 Â C); 154.6 (2 Â C); 164.3 (2 Â C). Anal. Calcd for
using TDAE. Into a two-necked flask equipped with a silica gel
drying tube and a nitrogen inlet was added, under nitrogen and
irradiated by fluorescent lamps (2 Â 60 W) at À20 °C, 8 mL of
anhydrous DMF solution of 1-(chloromethyl)-2,5-dimethoxy-3,4,6-
trimethyl-benzene 1 (0.4 g, 1.74 mmol) and aromatic aldehydes 2a–g
(5.22 mmol). The solution was stirred and maintained at this
temperature for 30 min and then was added dropwise (via a syringe)
the TDAE (0.39 g, 2.61 mmol). A green color immediately developed
with the formation of a white fine precipitate. The solution was
vigorously stirred at À20 °C for 1 h and then warmed up to room
temperature for 48 h under light irradiation. After this time TLC
analysis (dichloromethane) clearly showed that compound 1 was
totally consumed. The black-green turbid solution was filtered (to
remove the octamethyl-oxamidinium dichloride) and hydrolyzed with
80 mL of H2O. The aqueous solution was extracted with chloroform
(3 Â 40 mL) and the combined organic layers were washed with H2O
(3 Â 40 mL) and dried over MgSO4. Evaporation of the solvent left
black oil as crude product. Purification by silica gel chromatography
(dichloromethane) and recrystallization from ethanol gave the corres-
ponding esters. New products: Compound 3a: yellow solid; mp
131 °C, 1H NMR (CDCl3, 200 MHz) d 2.22 (s, 3H); 2.24 (s, 3H); 2.31
(s, 3H); 3.68 (s, 3H); 3.72 (s, 3H); 5.50 (s, 2H); 8.20 (d, J = 9.2 Hz,
2H); 8.23 (d, J = 9.2 Hz, 2H). 13C NMR (CDCl3, 50 MHz) d 12.1
(CH3); 12.7 (CH3); 13.1 (CH3); 60.2 (OCH3); 60.9 (CH2); 62.0
(OCH3); 123.5 (2 Â CH); 124.4 (C); 128.6 (C); 129.5 (C); 130.7
(2 Â CH); 132.6 (C); 135.6 (C); 150.5 (C); 153.2 (C); 154.2 (C); 164.7
(C). Anal. Calcd for C19H21NO6: C, 63.50; H, 5.89; N, 3.90. Found:
C, 63.23; H, 5.57; N, 4.01. Compound 3b: white solid; mp 147 °C, 1H
NMR (CDCl3, 200 MHz) d 2.21 (s, 3H); 2.24 (s, 3H); 2.29 (s, 3H);
3.68 (s, 3H); 3.71 (s, 3H); 5.48 (s, 2H); 7.71 (d, J = 8.6 Hz, 2H); 8.11
(d, J = 8.6 Hz, 2H). 13C NMR (CDCl3, 50 MHz) d 12.2 (CH3); 12.7
(CH3); 13.1 (CH3); 60.2 (OCH3); 60.8 (CH2); 62.0 (OCH3); 116.4 (C);
117.9 (C); 124.5 (C); 128.6 (C); 129.5 (C); 130.1 (2 Â CH); 132.2
(2 Â CH); 132.6 (C); 134.1 (C); 153.2 (C); 154.2 (C); 165.0 (C). Anal.
Calcd for C20H21NO4: C, 70.78; H, 6.24; N, 4.13. Found: C, 70.83; H,
6.19; N, 4.10. Compound 3c: yellow solid; mp 98 °C, 1H NMR
(CDCl3, 200 MHz) d 2.22 (s, 3H); 2.25 (s, 3H); 2.31 (s, 3H); 3.69 (s,
3H); 3.73 (s, 3H); 5.51 (s, 2H); 7.62 (m, 1H); 8.37 (m, 2H); 8.82 (m,
1H). 13C NMR (CDCl3, 50 MHz) d 12.1 (CH3); 12.7 (CH3); 13.0
(CH3); 60.2 (OCH3); 60.9 (CH2); 62.0 (OCH3); 124.4 (C); 124.6 (CH);
127.3 (CH); 128.6 (C); 129.5 (C); 129.6 (CH); 132.0 (C); 132.6 (C);
135.3 (CH); 153.2 (C); 154.2 (C); 164.5 (C); the C-nitro was not
C
26H24N2O10: C, 59.54; H, 4.61; N, 5.34. Found: C, 59.38; H, 4.56; N,
5.26. Compound 7a: yellow solid; mp 238 °C, 1H NMR (CDCl3,
200 MHz) d 3.85 (s, 6H); 5.45 (s, 4H); 7.02 (s, 2H); 8.25 (m, 8H). 13C
NMR (CDCl3, 50 MHz) d 56.3 (2 Â OCH3); 62.9 (2 Â CH2); 113.3
(2 Â CH); 123.5 (4 Â CH); 124.8 (2 Â C); 130.8 (4 Â CH); 135.7
(2 Â C); 150.6 (2 Â C); 151.7 (2 Â C); 164.6 (2 Â C). Anal. Calcd for
C24H20N2O10: C, 58.07; H, 4.06; N, 5.64. Found: C, 58.36; H, 4.28; N,
5.01.
20. General procedure for the oxidation: To a solution of benzyl benzoate
(0.10 g, 27 mmol) in acetonitrile (1 mL) was added dropwise a
mixture of CAN (0.40 g, 67.5 mmol) in water (0.5 mL). The reaction
mixture was stirred for 12 h at room temperature and was quenched
with water (30 mL). The aqueous solution was extracted with
dichloromethane (3 Â 20 mL), and the combined organic layers were
dried over MgSO4 and the solvent was removed under vacuum.
Purification by silica gel chromatography (dichloromethane) and
recrystallization from diethylether gave the corresponding benzo-
quinones. Compound 8a: orange solid; mp 97 °C, 1H NMR (CDCl3,
200 MHz) d 2.07 (s, 6H); 2.20 (s, 3H); 5.33 (s, 2H); 8.16 (d,
J = 9.1 Hz, 2H); 8.27 (d, J = 9.1 Hz, 2H). 13C NMR (CDCl3,
50 MHz) d 12.4 (CH3); 12.5 (CH3); 12.6 (CH3); 58.6 (CH2); 123.6
(2 Â CH); 130.9 (2 Â CH); 135.0 (C); 136.1 (C); 140.8 (C); 141.3 (C);
145.2 (C); 150.7 (C); 164.3 (C); 185.6 (C); 187.2 (C). Anal. Calcd for
C
17H15NO6: C, 62.00; H, 4.59; N, 4.25. Found: C, 61.70; H, 4.89; N,
4.26. Compound 8b: orange solid; mp 125 °C, 1H NMR (CDCl3,
200 MHz) d 2.06 (s, 6H); 2.18 (s, 3H); 5.30 (s, 2H); 7.72 (d,
J = 8.6 Hz, 2H); 8.09 (d, J = 8.6 Hz, 2H). 13C NMR (CDCl3,
50 MHz) d 12.4 (CH3); 12.5 (CH3); 12.6 (CH3); 58.5 (CH2); 116.7
(C); 117.8 (C); 127.5 (C); 130.2 (2 Â CH); 132.2 (2 Â CH); 133.5 (C);
136.2 (C); 140.8 (C); 141.3 (C); 145.2 (C); 164.5 (C); 185.6 (C). Anal.
Calcd for C18H15NO4: C, 69.89; H, 4.89; N, 4.50. Found: C, 69.32;
H, 4.94; N, 4.50. Compound 8c: yellow solid; mp 182 °C, 1H NMR
(CDCl3, 200 MHz) d 2.06 (s, 6H); 2.18 (s, 3H); 5.28 (s, 2H); 7.45 (m,
3H); 7.98 (m, 1H). 13C NMR (CDCl3, 50 MHz) d 12.4 (2 Â CH3);
12.5 (CH3); 57.7 (CH2); 128.4 (2 Â CH); 129.7 (2 Â CH); 133.2 (C);
136.8 (C); 140.8 (C); 141.1 (C); 144.9 (C); 166.2 (C); 185.7 (C); 187.4
(C); the C-nitro was not observed in this experiment. Anal. Calcd
for C17H15NO6: C, 62.00; H, 4.59; N, 4.25. Found: C, 61.86; H,
4.35; N, 4.18.