Synthesis of functionally substituted benzaldehydes

Article abstract of DOI:10.1134/S0012500817100019

A new method of synthesis of functionally substituted benzaldehydes by catalytic debromometoxylation of dibromomethylarenes with benzaldehyde dimethyl acetal has been suggested. Anhydrous zinc chloride has been used as a catalyst. Being soft Lewis acid, it formed no strong complex with aldehyde group and other functional groups. The initial acetal has been readily recovered by the treatment of benzaldehyde isolated from the reaction mixture with trimethyl orthoformate.

Full text of DOI:10.1134/S0012500817100019

ISSN 0012-5008, Doklady Chemistry, 2017, Vol. 476, Part 2, pp. 227–229. © Pleiades Publishing, Ltd., 2017.
Original Russian Text © M.B. Gazizov, S.Yu. Ivanova, Sh.N. Ibragimov, R.A. Khairullin, R.F. Karimova, K.S. Gazizova, I.S. Antipin, 2017, published in Doklady Akademii Nauk,
2017, Vol. 476, No. 5, pp. 527–529.
CHEMISTRY
Synthesis of Functionally Substituted Benzaldehydes
a,
a
a
a
a
M. B. Gazizov *, S. Yu. Ivanova , Sh. N. Ibragimov , R. A. Khairullin , R. F. Karimova ,
a
b
K. S. Gazizova , and Corresponding Member of the RAS I. S. Antipin
Received June 22, 2017
Abstract—A new method of synthesis of functionally substituted benzaldehydes by catalytic debromometox-
ylation of dibromomethylarenes with benzaldehyde dimethyl acetal has been suggested. Anhydrous zinc chlo-
ride has been used as a catalyst. Being soft Lewis acid, it formed no strong complex with aldehyde group and
other functional groups. The initial acetal has been readily recovered by the treatment of benzaldehyde iso-
lated from the reaction mixture with trimethyl orthoformate.
DOI: 10.1134/S0012500817100019
We have recently shown [1, 2] that dihalomethyl-
Acetal groups in dibromide Ib and 4-(dime-
arenes react with methyl esters of P(IV) acids to form thoxymethyl)benzaldehyde IIIb participate in debro-
aromatic aldehydes and phosphorus acid anhydrides. momethoxylation to give terephthalic aldehyde IIIa as
However, the reaction requires high temperature the major reaction product. Compound IIIb was
1
(
160–180°C) and expensive methyl esters of P(IV) detected only by H NMR and chromatography.
acids. In recent decade, two promising methods have Moreover, since compound Ib contains both dibro-
been proposed for the synthesis of aromatic monoal- momethyl and acetal groups, we expected the pres-
dehydes from dihalomethylarenes: heating of a mix- ence of intermolecular interaction between them.
ture of the latter with a large excess of dimethyl sulfox- Indeed, the addition of catalytic amounts of ZnCl to
2
ide [3] of pyridine [4] at 70–120°C for 1–18 h followed
by treatment of reaction mixture with water. However,
the isolation of individual aldehydes is a laborious pro-
cess.
compound Ib caused the formation of terephthalic
aldehyde IIIa in 96% yield.
In general case (Scheme 3), the reaction of tetra-
bromide Ie with benzaldehyde dimethyl acetal II
depending on reagent ratio can result in formation of
three aldehydes: monoaldehyde Ia, dialdehyde IIIa,
and benzaldehyde IV, while tetrabromide Ie could
react incompletely.
The aim of this work is to develop a new method for
preparing functionally substituted aromatic aldehydes
by the catalytic debromomethoxylation of dibro-
momethylarenes with benzaldehyde dimethyl acetal.
We propose for the first time to synthesize func-
tionally substituted aromatic aldehydes by the catalytic
debromometoxylation of dibromomethylarenes I with
benzaldehyde dimethyl acetal II (Scheme 1).
1
At the reagent ratio Ie : II = 1.0 : 2.1, the H NMR
spectrum of the reaction mixture showed no reso-
nance signal at 6.61 ppm corresponding to the proton
of the dibromomethyl group. We isolated terephthalic
aldehyde IIIa in 90% yield.
Zinc chloride was used as a catalyst, it is a soft
Lewis acid, which forms no strong complex with alde-
hyde and other functional groups. We found in prelim-
inary experiments that the reaction of compounds I
and II without a catalyst occurs only at 220°C. When
With the aim to use this reaction for the prepara-
tion of 4-(dibromomethyl)benzaldehyde Ia—a prom-
ising heterofunctional compound for organic synthe-
sis—synthesized by us for the first time [5], we reacted
compounds Ie and II in different ratios.
1
2
0 mol % of ZnCl is used, the reaction completes after
2
h at 50°C and after 1 h at 80°C. The reaction was
1
conducted in isooctane or benzene or in the absence
According to H NMR, the reaction mixture con-
of a solvent. The reaction does not affect methoxycar- tained no tetrabromide Ie at the 1.0 : 1.5 ratio. Com-
bonyl and carbonyl groups (Scheme 2).
pounds Ia and IIIa were isolated in individual state by
column chromatography (benzene as an eluent, silica
gel as a sorbent) in 11 and 64% yield, respectively.
Thus, in the absence of tetrabromide Ie, tereph-
thalic aldehyde IIIa is the major reaction product; i.e.,
a
Kazan State Technological University, Kazan,
20015 Tatarstan, Russia
Kazan Federal University, Kazan, 420008 Tatarstan, Russia the second dibromomethyl group of compound Ie is
e-mail: mukattisg@mail.ru
4
b
*
involved in the reaction to give target compound Ia in
27
2

2
28
GAZIZOV et al.
CHBr2
X + PhCH(OMe)2
CHO
1
0 mol % ZnCl2
X + PhCHO
−2MeBr
I
II
III
IV
I, III: X = 4-CHO (a), 4-CH(OMe) (b),
2
4-COOMe (c), 3-OCOMe (d)
Scheme 1.
ZnCl2, 50°C
4
-Br CHC H CH(OMe)
4-OCHC H CHO + 2MeBr
6 4
2
6
4
2
Ib
IIIa
Scheme 2.
4
-Br CHC H CHBr + PhCH(OMe)
2 6 4 2 2
Ie
II
10 mol % ZnCl2
4
-Br CHC H CHO + 4-OCHC H CHO + PhCHO
2
6
4
6
4
Ia
IIIa
IV
Scheme 3.
low yield. We isolated unchanged initial tetrabromide Ie (mp 115–116°C [6]). Benzaldehyde IV (3.86 mmol,
in 18% yield at 1 : 1 ratio. The yields of individual com- 28%) was isolated from the mother liquor.
pounds Ia, IIIa, and IV isolated by column chroma-
tography toward reacted tetrabromide Ie were 23, 53,
and 41%, respectively. Thus, the yield of target prod-
uct Ia increased twofold at this ratio of the initial
reagents. Initial acetal II was readily regenerated by
the treatment of benzaldehyde formed in the reaction
with trimethyl orthoformate.
Stage (b). A mixture of 7 mmol of tetrabromide Ie,
1
5 mmol of acetal II, and 0.7 mmol of zinc chloride in
5
mL of isooctane was heated at 50°C for 2.5 h. The
isooctane solution was decanted, the residue was addi-
tionally extracted with 10 mL of isooctane. Com-
pound IIIa (6.34 mmol, 89%) was isolated from the
combined isooctane solutions. Benzaldehyde IV
Thus, we have developed for the first time the (4.05 mmol, 29%) was isolated from the mother
method of synthesis of functionalized aromatic alde- liquor.
hydes by catalytic debromomethoxylation of dibro-
momethylarenes with benzaldehyde dimethyl acetal.
Stage (c). A mixture of 7 mmol of tetrabromide Ie,
1
5
5 mmol of acetal II, and 0.7 mmol of zinc chloride in
mL of isooctane was heated at 80°C for 1 h. Com-
pound IIIa (6.42 mmol, 90%) was isolated from the
isooctane solution. Benzaldehyde IV (3.77 mmol,
EXPERIMENTAL
1
H NMR spectra were recorded on a Tesla BS 567 A 28%) was isolated from the mother liquor.
and a Bruker AVANCE 400WB radiospectrometers
operating at 100 and 400.13 MHz, respectively, in
CDCl . Chemical shifts are reported relative to
Stage (d). Ratio 1.0 : 1.5. A mixture of 7 mmol of
tetrabromide Ie, 11 mmol of acetal II, and 0.7 mmol of
zinc chloride in 5 mL of isooctane was heated at 80°C
3
tetramethylsilane using residual protons of the deuter- for 1 h. Compound IIIa (3.73 mmol, 53%) was iso-
ated solvent as a reference.
lated from the isooctane solution. Benzaldehyde IV
(
6.22 mmol, 55%), compound Ia (0.79 mmol, 11%),
Reaction of 1,4-bis(dibromomethyl)benzene (Ie)
with benzaldehyde dimethyl acetal (II). Stage (a).
Reagent ratio is 1.0 : 2.1. A mixture of 7 mmol of tetra-
bromide Ie, 15 mmol of acetal II, and 0.7 mmol of
zinc chloride was heated at 50°C for 2 h. Extraction
with isooctane afforded 5.97 mmol (84%) of com- bromide Ie, 7 mmol of acetal II, and 0.7 mmol of zinc
pound IIIa as colorless crystals with mp 115–116°C chloride in 10 mL of benzene was heated at 80°C for 1 h.
and additional compound IIIa (0.82 mmol, 11%) were
isolated from the residue by column chromatography
(
benzene as an eluent, silica gel as a sorbent).
Stage (e). Ratio 1 : 1. A mixture of 7 mmol of tetra-
DOKLADY CHEMISTRY
Vol. 476
Part 2
2017

SYNTHESIS OF FUNCTIONALLY SUBSTITUTED BENZALDEHYDES
229
The solution was concentrated in a vacuum and sub- 3-Formylphenyl acetate (IIId). A mixture of
jected to column chromatography (benzene as an elu- 6.5 mmol of compound Id, 6.8 mmol of acetal II, and
ent, silica gel as a sorbent) to give 1.33 mmol (23%) of 0.65 mmol of zinc chloride was heated at 80°C for 2 h.
compound Ia and 3.13 mmol (53%) of compound Column chromatography (benzene : diethyl ether =
IIIa, whose yields were calculated toward reacted 19 : 1 as an eluent, silica gel as a sorbent) afforded
tetrabromide Ie, and 2.83 mmol (41%) of compound IV. 2.01 mmol (30%) of compound IIId as an oil [8] and
1
Reaction of 4-(dibromomethyl)benzaldehyde (Ia) 1.89 mmol (29%) of benzaldehyde IV. H NMR
with acetal II. A mixture of 3.6 mmol of compound Ia, (CDCl
, δ, ppm): 2.42 (s, 3H, CH
), 7.47–8.13 (m,
3
3
3
.8 mmol of acetal II, and 0.36 mmol of zinc chloride 4H, C H ), 10.08 (s, 1H, CHO).
6 4
in 5 mL of isooctane was heated at 80°C for 1 h. Com-
pound IIIa (2.99 mmol, 83%) was isolated from the
isooctane solution. Benzaldehyde IV (1.98 mmol,
ACKNOWLEDGMENTS
5
5%) was obtained from the mother liquor.
Reaction of 1-(dibromomethyl)-4-(dimethoxy-
This work was supported by the Ministry of Educa-
tion and Science of the Russian Federation (project
no. 4.5348.2017/8.9 as a part of State Contract).
methyl)benzene (Ib) with acetal II. A mixture of
3
.1 mmol of compound Ib, 3.3 mmol of acetal II, and
.31 mmol of zinc chloride was heated at 50°C for 1.5 h.
0
Compound IIIa (1.12 mmol, 36%) was isolated by
extraction with isooctane. Fractions containing
REFERENCES
1
2
3
4
5
. Gazizov, M.B., Kachalova, T.N., Karimova, R.F.,
Khairullin, R.A., and Sinyashin, O.G., Russ. J. Gen.
Chem., 1997, vol. 67, no. 12, pp. 1942–1943.
. Gazizov, M.B., Kachalova, T.N., Karimova, R.F., and
Sinyashin, O.G., Dokl. Chem., 1998, vol. 359, nos. 4–6,
pp. 71–73.
0
.94 mmol (30%) of benzaldehyde IV, 0.45 mmol
(
15%) of dialdehyde IIIa, and a fraction composed of
compounds II and IIIb identified by chromatography
on a Sorbfil PTLC-AF-A-UV high-performance plate
(
Labtekh, Russia, benzene as an eluent) were isolated
from the mother liquor by chromatography (benzene :
diethyl ether = 19 : 1 as an eluent, silica gel as a sor-
bent).
. Li, W., Li, J., DeVincentis, D., and Mansour, T.S., Tet-
rahedron Lett., 2004, vol. 45, pp. 1071–1074. doi
10.1016/j.tetlet.2003.11.072
Transformation of 1-(dibromomethyl)-4-(dime-
thoxymethyl)benzene (I) in dialdehyde (IIIa) under the
action of catalytic amounts of zinc chloride. A mixture
of 3.4 mmol of compound Ib and 0.34 mmol of zinc
chloride was heated at 50°C for 1 h. Compound IIIa
. Augustine, J.K., Naik, Y.A., Mandal, A.B., Chow-
dappa, N., and Praveen, V.B., Tetrahedron, 2008,
vol. 64, pp. 688–695.
. Gazizov, M.B., Ivanova, S.Yu., Bagauva, L.R., Kari-
mova, A.A., Ibragimov, Sh.N., and Musin, R.Z., Russ.
J. Gen. Chem., 2015, vol. 85, no. 9, pp. 2209–2211.
(
3.28 mmol, 96%) was isolated by extraction with
isooctane.
6
. Snell, J. and Weisberger, A., in Organic Syntheses, Col-
Methyl 4-formylbenzoate (IIIc). A mixture of
.2 mmol of compound Ic, 3.4 mmol of acetal II, and
.32 mmol of zinc chloride was heated at 50°C for 2 h
lective Volume 3, Wiley, 1955.
3
0
7
. Kyung, D.K., Young, Y., Hyo, J.J., Ham, M.J.,
Ki, L.K., Ah, N.K., Oyunerdene, D., Gyoo, S.P., and
Seok, C.K., Bull. Korean Chem. Soc., 2012, vol. 33,
no. 12, pp. 4275–4276.
and at 80°C for 2 h. Compound IIIc (2.62 mmol,
8
2%) was isolated by extraction with isooctane, mp
1
5
9−61°C (mp 63−65°C [7]). H NMR (CDCl , δ,
3
8
. Sudipta, R.R., Samaresh, C.S., and Swadhin, K.M.,
Org. Chem., 2014, vol. 79, pp. 9150–9160. doi
10.1021/jo501505j
ppm): 3.97 (s, 3H, OCH ), 7.94 d and 8.19 d (4H,
3
3
C H , J 8.4 Hz), 10.10 (s, 1H, CHO). Benzalde-
6
4
HH
hyde IV (0.94 mmol, 29%) was isolated from the
mother liquor.
Translated by I. Kudryavtsev
DOKLADY CHEMISTRY Vol. 476 Part 2 2017