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Gazizov et al.
(76%) of compound 2a, colorless crystals, m.p. 53 °C (cf. Ref. 12:
m.p. 53 °C), b.p. 107 °C (0.1 Torr) (cf. Ref. 12: b.p. 138—139 °C
(9 Torr)). The samples obtained by methods A and B are identical.
C. A mixture of 4ꢀ(dibromomethyl)benzaldehyde (1e) (1.00 g,
3.6 mmol), CH(OMe)3 (1.53 g, 14.4 mmol), and zinc chloride
(0.05 g, 0.36 mmol) was heated at 80 °C for 2 h. The volatiles
were removed in vacuo and the residue was extracted with hot
isooctane to give 0.80 g (99%) of compound 2a, colorless crysꢀ
tals. The physicochemical properties of the sample are coinꢀ
cide with those given above.
tion mixture with isooctane afforded 0.34 g (81%) of compound
2c, colorless oil (cf. Ref. 8, 10). 1H NMR (CDCl3), δ: 3.21 (s, 6 H,
OMe); 3.84 (s, 3 H, COOMe); 5.35 (s, 1 H, CHO2); 7.43, 7.94
(both s, 2 H each, C6H4, 3JH,H = 8.2 Hz). 13C NMR (CDCl3),
δ: 51.9 (COOMe); 52.2 (OMe); 101.8 (CHO2); 126.8, 127.0,
129.5, 129.5 (CHAr); 130.1, 142.8 (CAr); 166.3 (CO).
Reaction of methyl 4ꢀ(dibromomethyl)benzoate (1b) with triꢀ
ethyl orthoformate. A mixture of compound 1b (1.50 g, 4.9 mmol),
triethyl orthoformate (1.90 g, 12.8 mmol), and zinc chloride
(0.07 g, 0.49 mmol) was heated at 80 °C for 4 h. Extraction of
the reaction mixture with isooctane afforded 0.87 g of an insepꢀ
arable mixture of methyl 4ꢀ(diethoxymethyl)benzoate (2d) and
ethyl 4ꢀ(diethoxymethyl)benzenecarboxylate (2e) in a ratio of
1.7 : 1.0.
3ꢀ(Dimethoxymethyl)phenyl acetate (2f). A mixture of 3ꢀ(diꢀ
bromomethyl)phenyl acetate (1d) (2.48 g, 8 mmol), trimethyl
orthoformate (3.40 g, 32 mmol), and zinc chloride (0.10 g,
0.8 mmol) was heated at 50 °C for 1 h. 1H NMR spectrum
contained weak signal of the aldehyde group (δ 10.03), thereꢀ
fore CH(OMe)3 (2.55 g, 24 mmol) was additionally added and
heating at 50 °C was continued for 2 h. Removal of the volatiles
in vacuo and extraction of the residue with isooctane afforded
0.50 g (30%) of compound 2f, colorless oil. 1H NMR (CDCl3),
δ: 2.35 (s, 3 H, COMe); 3.38 (s, 6 H, OMe); 5.51 (s, 1 H,
CHO2); 7.12—7.46 (m, 4 H, C6H4). 13C NMR (CDCl3), δ:
20.9 (COMe); 52.0 (OMe); 101.6 (CHO2); 120.2, 121.5, 124.1,
127.1, 127.5, 129.9, 139.8 (C6H4); 168.7 (CO). Found (%):
C, 62.63; H, 6.59. C11H14O4. Calculated (%): C, 62.86; H, 6.67.
D. A mixture of compound 1e (0.25 g, 0.9 mmol), CH(OMe)3
(0.38 g, 3.6 mmol), and zinc chloride (0.01 g, 0.09 mmol) was
1
kept at room temperature for 24 h. H NMR spectrum of the
reaction mixture (CDCl3), δ: 3.26 (s, OMe acetal and ortho
ester); 4.89 (s, 1 H, CHO3); 5.38 (s, 2 H, CHO2); 7.39 (s, 4 H,
C6H4); 3.71 (s, 3 H, OMe); 8.01 (s, 1 H, HC(O)O). Removal of
the volatiles in vacuo afforded 0.19 g (95%) of diacetal 2a,
colorless crystals. The sample was identical to the products
obtained by the other methods.
E. Independent synthesis. A mixture of 4ꢀ(dimethoxymethyl)ꢀ
benzaldehyde (3) (0.32 g, 1.8 mmol), CH(OMe)3 (0.38 g,
3.6 mmol), and zinc chloride (0.02 g, 0.18 mmol) was heated at
80 °C for 2 h. The volatiles were removed in vacuo and the
residue was extracted with hot isooctane to give 0.40 g (98%) of
compound 2a, colorless crystals. Physicochemical and spectral
properties of the sample are identical with those given above.
1,4ꢀBis(diethoxymethyl)benzene (2b). A. A mixture of 1,4ꢀbisꢀ
(dibromomethyl)benzene (1d) (15.00 g, 35.5 mmol), triethyl
orthoformate (22.10 g, 149.1 mmol), and zinc chloride (0.48 g,
3.55 mmol) was heated at 80 °C for 4.5 h. Vacuum distillation
of the reaction mixture afforded 6.80 g (68%) of compound 2b,
colorless liquid, b.p. 119—120 °C (0.1 Torr) (cf. Ref. 11: b.p.
107—108 °C (0.001 Torr)). 1H NMR (CDCl3), δ: 1.17 (t, 12 H,
OCH2Me, 3JH,H = 7.0 Hz); 3.49 (q, 8 H, OCH2, 3JH,H = 7.0 Hz);
5.44 (s, 2 H, CHO2); 7.37 (s, 4 H, C6H4).
B. A mixture of 4ꢀ(dibromomethyl)benzaldehyde (1e) (1.00 g,
3.6 mmol), triethyl orthoformate (2.13 g, 14.4 mmol), and zinc
chloride (0.05 g, 0.36 mmol) was heated at 80 °C for 2 h. Reꢀ
moval of the volatiles in vacuo and extraction of the residue
with hot isooctane afforded 0.99 g (98%) of 1,4ꢀbis(diethoxyꢀ
methyl)benzene (2b), colorless liquid. The samples obtained by
methods A and B are identical.
This work was financially supported by the Ministry
of Education and Science of the Russian Federation
(Project No. 4.5348.2017/8.9 in the framework of the
basic part of the State Assignment).
References
1. WeygandꢀHilgetag, Organischꢀchemische Experimentierꢀ
kunst, J. A. Barth, Leipzig, 1964, 1142 pp.
2. D. Barton, W. D. Ollis, Comprehensive Organic Chemistry.
The Synthesis and Reactions of Organic Compounds, Vol. 1,
Stereochemistry, Hydrocarbons, Halo Compounds, Oxygen
Compounds, Ed. J. F. Stoddart, Pergamon Press, Oxford—
New York—Toronto—Sydney—Paris—Frankfurt, 1979.
3. J. March, Advanced Organic Chemistry. Reactions, Mechaꢀ
nisms and Structure, John Wiley and Sons, New York, 1992,
387 pp.
4. L. A. Yanovskaya, S. S. Yufit, V. F. Kucherov, Khimiya
atsetalei [Chemistry of Acetals], Nauka, Moscow, 1975,
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5. R. B. Moffett, Org. Synth., 1963, Coll. Vol. 4, 427.
6. K. Schank, Chem. Ber., 1967, 100, 2292.
7. G. Cavallini, J. Med. Chem., 1964, 7, 255; DOI: 10.1021/
jm00333a003.
8. A. Clerici, N. Pastori, O. Porta, Tetrahedron, 1998, 54,
15679; DOI: 10.1016/S0040ꢀ4020(98)00982ꢀX.
9. H. Nao, K. Kiyoshi, S. Tsuneo, S. Hisashi, Synlett, 2004,
1074; DOI: 10.1055/sꢀ2004ꢀ820038.
10. C. Wiles, P. Watts, S. J. Haswell, Tetrahedron, 2005, 61,
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C. A mixture of 4ꢀ(dibromomethyl)benzaldehyde 1e (0.25 g,
0.9 mmol), CH(OEt)3 (0.53 g, 3.6 mmol), and zinc chloride
(0.01 g, 0.09 mmol) was kept at room temperature for 24 h.
1H NMR (CDCl3) spectrum of the reaction mixture contained
resonances for the protons of the starting compound at δ 6.71
(s, 1 H, CHBr2) and 9.94 (s, 1 H, CHO). These signals disꢀ
1
appeared 24 h after the additional reaction time and H NMR
spectrum showed signals of diacetal 2b at δ 5.40 (s, 2 H,
2 CHO2) and 7.34 (s, 4 H, C6H4), ethyl formate at δ 4.09 (q, 2 H,
OCH2, 3JH,H = 7.0 Hz) and 7.91 (s, 1 H, HC(O)O), and excess
CH(OEt)3 at δ 5.01 (s, 1 H, CHO3); the signals of the ethoxy
groups of diacetal and ortho ester overlapped. Removal of the
volatiles in vacuo afforded diacetal 2b, colorless liquid. Physicoꢀ
chemical and spectral properties of the sample are identical
with those given above.
Methyl 4ꢀ(dimethoxymethyl)benzoate (2c). A mixture of
methyl 4ꢀ(dibromomethyl)benzoate (1b) (0.63 g, 2 mmol), triꢀ
methyl orthoformate (0.85 g, 8 mmol), and zinc chloride (0.03 g,
0.2 mmol) was heated at 80 °C for 2 h. Extraction of the reacꢀ