Alkylation of NH-, OH-, and SH-acids in the presence of potassium carbonate: 1. Functionalization of chloromethyl group of alkoxy-substituted aromatic aldehydes

Article abstract of DOI:10.1007/s11172-015-0875-9

An easily scalable, economocal, and more safe method for the preparation of 3-chloromethyl-4-methoxybenzaldehyde was developed. The latter was subjected to reactions with NH-, OH-, and SH-acids in the presence of potassium carbonate to obtain new aromatic aldehydes in high yields.

Full text of DOI:10.1007/s11172-015-0875-9

Russian Chemical Bulletin, International Edition, Vol. 64, No. 2, pp. 395—404, February, 2015
395
Alkylation of NHꢀ, OHꢀ, and SHꢀacids in the presence of potassium carbonate
1. Functionalization of chloromethyl group of alkoxyꢀsubstituted aromatic aldehydes
D. S. Khachatryan,a A. L. Razinov,a A. V. Kolotaev,a S. K. Belus´,a and K. R. Matevosyanb
aLabor Red Banner order Federal State Unitary Enterprise
"Research Institute of Chemical Reactants and Ultrapure Compounds (IREA)",
3 Bogorodskii val, 107076 Moscow, Russian Federation.
Eꢀmail: derenikꢀs@yandex.ru
bD. I. Mendeleev University of Chemical Technology of Russia,
9 Miusskaya pl., 125047 Moscow, Russian Federation
An easily scalable, economocal, and more safe method for the preparation of 3ꢀchloroꢀ
methylꢀ4ꢀmethoxybenzaldehyde was developed. The latter was subjected to reactions with
NHꢀ, OHꢀ, and SHꢀacids in the presence of potassium carbonate to obtain new aromatic
aldehydes in high yields.
Key words: 3ꢀchloromethylꢀ4ꢀmethoxybenzaldehyde, NHꢀ, OHꢀ, and SHꢀacids, alkylaꢀ
tion, potassium carbonate, aromatic aldehydes.
The importance of aromatic aldehydes in the construcꢀ
tion of biologically active molecules is of common knowꢀ
ledge. Their heterocyclization reaction was used to obtain
symmetrically substituted porphyrins,1—4 carbolines,5—10
dihydroquinazolones,11—17 tetrahydropyrimidinones,18—21
and xanthines.22—25
tating properties. We developed a convenient procedure
for its synthesis which uses paraform aldehyde in concenꢀ
trated hydrochloric acid without additional reagents and
solvents. A multiple use of the mother liquor of the hydroꢀ
chloric acid solution gave a possibility to increase the yield
1
of the target product to 99% (according to the H NMR
From a plethora of methods for the preparation of
polyfunctional aromatic aldehydes,26,27 we have chosen
the chloromethylation reaction28—30 of 4ꢀmethoxybenzꢀ
aldehyde (anisic aldehyde (1a)) with subsequent replaceꢀ
ment of the chlorine atom with different Oꢀ, Nꢀ, and
Sꢀnucleophiles (Scheme 1). This gave us a possibility to
obtain a wide range of substituted aromatic aldehydes from
simple and inexpensive reactants. This choice is also exꢀ
plained by the suggestion that the introduction of an
alkoxyphenyl group in an organic molecule can impart
a certain biological activity to this molecule.31
data, the purity of the product was >95%) and make the
process of lowꢀwaste. A decrease in the amount of operaꢀ
tions of the technological process allowed us to improve
safety conditions.
Other 4ꢀalkoxybenzaldehydes (for example, 1b,c) can
be also involved in such transformations. The thus obꢀ
tained 3ꢀchloromethyl derivatives 2a—c readily undergo
hydrolyzation upon reflux with 2% aqueous solution of
sodium hydrogen carbonate, leading to 3ꢀhydroxymethylꢀ
benzaldehydes 3a—c in high yields (see Scheme 1, Table 1).
Based on our experience on alkylation of CHꢀacids,32—35
we have chosen potassium carbonate as a base for the
substitution of chlorine with different nucleophiles
(phenols, secondary amines, thiols). The solvents were
ethanol, acetonitrile, and DMF, in which the starting
nucleophiles are soluble, whereas the final products are
isolated in the solid state.
Scheme 1
The reaction of morpholine with 3ꢀchloromethylꢀ4ꢀ
methoxybenzaldehyde (2a) upon reflux in ethanol gave
rise to 4ꢀmethoxyꢀ3ꢀmorpholinomethylbenzaldehyde (4a)
in 91% yield and more than 97% purity. Other amino
derivatives were also synthesized in high yields (82—95%)
(Scheme 2, Table 2).
R = Me (a), Et (b), Pr (c)
It is necessary to avoid a direct contact with 3ꢀchloroꢀ
methylꢀ4ꢀmethoxybenzaldehyde (2a) because of its irriꢀ
When phenols in an alcohol were used as nucleophiles,
up to 10% of 3ꢀethoxymethyl derivatives were formed
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 0395—0404, February, 2015.
1066ꢀ5285/15/6402ꢀ0395 © 2015 Springer Science+Business Media, Inc.

396
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 2, February, 2015
Khachatryan et al.
Scheme 2
4: NR1R2
=
(a),
(b),
(c),
(d),
(e),
(f)*,
(g),
(h),
(i),
(j),
(k)
5: Ar =
(a),
(h),
(a),
(b),
(c),
(d),
(e),
(f),
(g),
(i),
(j),
(k),
(l),
(m)
6: R3
=
(b),
(c),
(d),
(e),
(f),
(g)
* As a hydrochloride.

Functionalized benzaldehydes
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 2, February, 2015
397
Table 1. Yields, melting points, elemental analysis data, and 1H NMR spectra (in DMSOꢀd6) of aldehydes 2a—c and 3a—c
Comꢀ Yield
pound (%)
M.p./C
Found
Calculated
Molecular
formula
1H NMR,  (J/Hz)
(%)
H
C
2a
2b
99
98
56—58
75—76
58.61
58.23
5.16
5.43
C9H9ClO2
3.96 (s, 3 H, C(9)H3); 4.78 (s, 2 H, C(8)H2); 7.27 (d, 1 H,
C(5)HAr, J = 8.3); 7.93 (d, 1 H, C(2)HAr, J = 2.1); 7.95—7.97
(m, 1 H, C(6)HAr); 9.88 (s, 1 H, C(7)HO)
1.38 (t, 3 H, C(9)H3, J = 6.9); 4.23 (q, 2 H, C(8)H2, J = 6.9);
4.77 (s, 2 H, C(10)H2); 7.24 (d, 1 H, C(5)HAr, J = 8.5);
7.92 (dd, 1 H, C(6)HAr, J = 8.5, J = 2.1); 7.96 (d, 1 H,
C(2)HAr, J = 2.1); 9.88 (s, 1 H, C(7)HO)
60.31
60.45
5.63
5.54
C10H11ClO2
2c
3a
3b
3c
95
83
90
81
47—48
55—56.5
58ꢀ59
62.01
62.11
6.26
6.12
C11H13ClO2
C9H10O3
0.99 (t, 3 H, C(11)H3, J = 6.9); 1.70—1.85 (m, 2 H, C(10)H);
4.10 (t, 2 H, C(9)H3, J = 6.9); 5.11 (s, 2 H, C(8)H2); 7.21
(d, 1 H, C(5)HAr, J = 8.4); 7.80 (s, 1 H, C(2)HAr); 7.87
(d, 1 H, C(6)HAr, J = 8.4); 9.87 (s, 1 H, C(7)HO)
3.89 (s, 3 H, C(9)H3); 4.52 (s, 2 H, C(8)H2); 5.23 (br.s,
1 H, ОН); 7.16 (d, 1 H, C(5)HAr, J = 8.4); 7.83 (dd, 1 H,
C(6)HAr, J = 8.4, J = 2.2); 7.92—7.95 (m, 1 H, C(2)HAr);
9.89 (s, 3 H, C(7)HO)
1.36 (t, 3 H, C(10)H3); 4.16 (q, 2 H, C(9)H2); 4.52 (s, 2 H,
C(8)H2); 5.22 (s, 1 H, ОН); 7.14 (d, 1 H, C(5)HAr, J = 8.4);
7.80 (dd, 1 H, C(6)HAr, J = 8.4, J = 2.0); 7.92—7.95
(m, 1 H, C(2)HAr); 9.88 (s, 1 H, C(7)HO)
65.32
65.05
6.44
6.06
66.85
66.65
6.58
6.71
C10H12O3
C11H14O3
45ꢀ46
68.25
68.04
7.54
7.22
1.00 (t, 3 H, C(11)H3, J = 6.9); 1.69—1.83 (m, 2 H, C(10)H);
4.09 (t, 2 H, C(9)H2, J = 6.9); 4.53 (s, 2 H, C(8)H2); 5.21 (t,
1 H, OH); 7.12 (d, 1 H, C(5)HAr, J = 8.4); 7.80 (d, 1 H, C(6)HAr
J = 8.4); 7.93 (s, 1 H, C(2)HAr); 9.88 (s, 1 H, C(7)HO)
,
Table 2. Yields, melting points, elemental analysis data, and 1H NMR spectra (in DMSOꢀd6) of aldehydes 4a—k, 5a—m, and 6a—g
Comꢀ Yield M.p./C
pound (%)
Found
Calculated
Molecular
formula
1H NMR,  (J/Hz)
(%)
C
H
N
S
4a
4b
91 77.5—78
89 88—88.5
66.21 7.11
66.36 7.28
5.87
5.95
—
C13H17NO3
2.39 (t, 4 H, C(10)H2, J = 4.6); 3.50 (s, 2 H, C(9)H2);
3.59 (t, 4 H, C(11)H2, J = 4.6); 3.92 (s, 3 H, C(8)H3);
7.19 (d, 1 H, C(5)HAr, J = 8.3); 7.82 (d, 1 H, C(2)HAr
J = 2.2); 7.84—7.88 (m, 1 H, C(6)HAr);
,
9.88 (s, 1 H, C(7)HO)
76.69 6.64
76.84 6.81
4.78
4.98
—
C18H19NO2
1.96 (m, 2 H, C(11)H2, J = 6.0); 2.76 (t, 2 H, C(12)H2,
J = 6.0); 3.37 (t, 2 H, C(10)H2, J = 6.0); 3.96 (s, 3 H,
C(8)H3); 4.41 (s, 2 H, C(9)H2); 6.23 (d, 1 H, CHAr
,
J = 7.8); 6.46 (t, 1 H, CHAr, J = 8.3); 6.84 (t, 1 H,
CHAr, J = 8.3); 6.91 (d, 1 H, CHAr, J = 7.8); 7.25 (d,
1 H, C(5)HAr, J = 8.5); 7.55 (d, 1 H, C(2)HAr, J = 2.0);
7.85 (dd, 1 H, C(6)HAr, J = 8.5, J = 2.0);
9.80 (s, 1 H, C(7)HO)
4c
4d
92 80—80.5
70.41 7.02
70.56 7.10
8.11
8.23
—
—
C20H24N2O3
2.56 (br.s, 4 H, C(10)H2); 2.98 (br.s, 4 H, C(11)H2);
3.57 (s, 2 H, C(9)H2); 3.76 (s, 3 H, C(18)H3); 3.91 (s,
3 H, C(8)H3); 6.82—6.98 (m, 4 H, CHAr); 7.21 (d, 1 H,
C(5)HAr, J = 8.4); 7.85 (dd, 1 H, C(6)HAr, J = 8.4,
J = 2.0); 7.89 (d, 1 H, C(2)HAr, J = 2.0);
9.89 (s, 1 H, C(7)HO)
82 71.5—72
64.57 7.74
64.72 7.97 10.06
9.89
C15H22N2O3
2.39 (t, 2 H, C(12)H2, J = 6.3); 2.33—2.49 (m, 8 H,
C(10)H2, C(11)H2); 3.48 (t, 2 H, C(13)H2, J = 6.3);
3.49 (s, 2 H, C(9)H2); 3.89 (s, 3 H, C(8)H3); 4.40
(br.s, 1 H, OH); 7.18 (d, 1 H, C(5)HAr, J = 8.2);
7.79—7.87 (m, 2 H, CHAr); 9.87 (s, 1 H, C(7)HO)
(to be continued)

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Khachatryan et al.
Table 2 (continued)
Comꢀ Yield M.p./C
pound (%)
Found
Calculated
Molecular
formula
1H NMR,  (J/Hz)
(%)
C
H
N
S
4e
4f
90 87—87.5
69.31 6.34
69.49 6.44
8.40
8.53
—
C19H21FN2O2 2.55 (t, 4 H, C(11)H2, J = 4.8); 3.09 (t, 4 H, C(10)H2,
J = 4.8); 3.57 (s, 2 H, C(9)H2); 3.91 (s, 3 H, C(8)H3);
6.89—6.97 (m, 2 H, C(14)HAr); 6.98—7.08 (m, 2 H,
C(13)HAr); 7.21 (d, 1 H, C(5)HAr, J = 8.5); 7.85 (dd,
1 H, C(6)HAr, J = 8.5, J = 2.1); 7.89 (d, 1 H, C(2)HAr
J = 2.1); 9.89 (s, 1 H, C(7)HO)
,
87 202—203 54.97 5.23
54.89 5.09
6.82
6.74
—
—
C19H21Cl3N2O2 3.07—3.50 (m, 6 H, CH2); 3.78—3.92 (m, 2 H, CH2);
3.97 (s, 3 H, C(8)H2); 4.40 (br.s, 2 H, C(9)H2); 6.97
(dd, 1 H, C(17)HAr, J = 8.9, J = 2.7); 7.21 (d, 1 H,
C(13)HAr, J = 2.1); 7.35 (d, 1 H, C(5)HAr, J = 8.6);
7.44 (d, 1 H, C(16)HAr, J = 8.9); 8.08 (dd, 1 H,
C(6)HAr, J = 8.6, J = 1.8); 8.17 (d, 1 H, C(2)HAr
J = 1.8); 9.90 (s, 1 H, C(7)HO); 11.06 (N+H)
,
4g
93 178.5—179 70.87 6.43
70.98 6.55
8.46
8.55
C20H22N2O3
1.67—1.91 (m, 2 H, CH2); 2.27—2.47 (m, 2 H, CH2);
2.40 (br.s, 1 H, CH); 2.73—2.98 (m, 2 H, CH2); 3.01
(br.s, 1 H, CH); 3.45 (s, 2 H, C(9)H2); 3.65—3.95
(m, 2 H, CH2); 3.81 (s, 3 H, C(8)H3); 6.05 (dd, 1 H,
C(13)HAr, J = 6.9, J = 1.3); 6.27 (dd, 1 H, C(15)HAr
,
J = 9.0, J = 1.3); 7.12 (d, 1 H, C(5)HAr, J = 8.5); 7.29
(d, 1 H, C(2)HAr, J = 2.1); 7.34 (dd, 1 H, C(14)HAr
J = 9.0, J = 6.9); 7.73 (dd, 1 H, C(6)HAr, J = 8.5,
J = 2.1); 9.60 (s, 1 H, C(7)HO)
,
4h
88 88—88.5
69.32 6.21
69.49 6.44
8.38
8.53
—
C19H21FN2O2 2.58 (t, 4 H, C(10)H2, J = 4.6); 3.03 (t, 4 H, C(11)H2,
J = 4.6); 3.58 (s, 2 H, C(9)H2); 3.91 (s, 3 H, C(8)H3);
6.90—7.16 (m, 4 H, CHAr); 7.21 (d, 1 H, C(5)HAr
,
J = 8.5); 7.85 (dd, 1 H, C(6)HAr, J = 8.5, J = 2.0);
7.90 (d, 1 H, C(2)HAr, J = 2.0); 9.89 (s, 1 H, C(7)HO)
4i
4j
95 129—130 54.98 4.12 16.01
55.17 4.24 16.08
—
—
C12H11N3O4
3.93 (s, 3 H, C(8)H3); 5.43 (s, 2 H, C(9)H2); 7.26 (d,
1 H, C(5)HAr, J = 8.5); 7.65 (d, 1 H, C(2)HAr, J = 2.1);
7.94 (dd, 1 H, C(6)HAr, J = 8.5, J = 2.1); 8.27 (s, 1 H,
C(10)H); 8.95 (s, 1 H, C(12)H); 9.85 (s, 1 H, C(7)HO)
85 123.5—124 51.92 4.49
52.03 4.68
8.51
8.67
C14H15BrN2O2 2.09 (s, 3 H, C(13)H3); 2.21 (s, 3 H, C(14)H3); 3.94
(s, 3 H, C(8)H3); 5.22 (s, 2 H, C(9)H2); 7.25 (d, 1 H,
C(5)HAr, J = 8.5); 7.29 (d, 1 H, C(2)HAr, J = 2.1);
7.89 (dd, 1 H, C(6)HAr, J = 8.5, J = 2.1);
9.82 (s, 1 H, C(7)HO)
4k
94 140.5—141 58.03 5.12 14.29
58.13 5.23 14.52
—
C14H15N3O4
2.37 (s, 3 H, C(14)H3); 2.63 (s, 3 H, C(13)H3); 3.93
(s, 3 H, C(8)H3); 5.31 (s, 2 H, C(9)H2); 7.26 (d, 1 H,
C(5)HAr, J = 8.5); 7.52 (d, 1 H, C(2)HAr, J = 1.9);
7.92 (dd, 1 H, C(6)HAr, J = 8.5, J = 1.9);
9.85 (s, 1 H, C(7)HO)
5a
5b
5c
96 49—49.5
93 85.5—86
89 76.5—78
69.08 4.89
69.22 5.03
—
—
—
—
—
—
C15H13FO3
C15H13ClO3
C19H21ClO3
3.94 (s, 3 H, C(8)H3); 5.09 (s, 2 H, C(9)H2); 6.99—7.07,
7.08—7.18 (both m, 2 H each, CHAr); 7.25—7.31 (m, 1 H,
CHAr); 7.90—7.97 (m, 2 H, CHAr);
9.89 (s, 1 H, C(7)HO)
64.99 4.58
65.11 4.74
3.94 (s, 3 H, C(8)H3); 5.11 (s, 2 H, C(9)H2);
7.01—7.08, 7.25—7.30 (both m, 2 H each, CHAr);
7.31—7.37 (m, 1 H, CHAr); 7.91—7.96
(m, 2 H, CHAr); 9.88 (s, 1 H, C(7)HO)
68.47 6.29
68.57 6.36
1.15 (d, 6 H, C(18)H3, J = 6.9); 2.28 (s, 3 H, C(16)H3);
3.22 (m, 1 H, C(17)H); 3.94 (s, 3 H, C(8)H3); 5.11 (s,
2 H, C(9)H2); 7.06 (br.s, 1 H, C(15)HAr); 7.16 (br.s,
1 H, C(12)HAr); 7.28 (d, 1 H, C(5)HAr, J = 8.4);
7.90—8.00 (m, 2 H, CHAr); 9.89 (s, 1 H, C(7)HO)
(to be continued)

Functionalized benzaldehydes
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 2, February, 2015
399
Table 2 (continued)
Comꢀ Yield M.p./C
pound (%)
Found
Calculated
Molecular
formula
1H NMR,  (J/Hz)
(%)
C
H
N
S
5d
85
88—90
70.02 6.34
70.16 6.48
—
—
C20H22O5
0.96 (d, 6 H, C(17)H3, J = 6.6); 2.00 (m, 1 H, C(16)H,
J = 6.6); 3.95 (s, 3 H, C(8)H3); 4.02 (d, 2 H, C(15)H2,
J = 6.6); 5.20 (s, 2 H, C(9)H2); 7.11—7.18 (m, 2 H,
CHAr); 7.26—7.32 (m, 1 H, CHAr); 7.90—7.98
(m, 4 H, CHAr); 9.89 (s, 1 H, C(7)HO)
5e
5f
97 114—114.5 61.02 3.98
61.13 4.10
—
—
—
—
C15H12ClFO3 3.94 (s, 3 H, C(8)H3); 5.12 (s, 2 H, C(9)H2); 6.99—7.07
(m, 1 H, CHAr); 7.25—7.40 (m, 3 H, CHAr); 7.91—7.98
(m, 2 H, CHAr); 9.89 (s, 1 H, C(7)HO)
87
39—40
70.45 5.79
70.57 5.92
C16H16O4
C15H13BrO3
C19H22O3
3.69 (s, 3 H, C(16)H3); 3.94 (s, 3 H, C(8)H3); 5.04
(s, 2 H, C(9)H2); 6.82—6.99 (m, 4 H, CHAr); 7.26 (d,
1 H, CHAr, J = 8.7); 7.88—7.96 (m, 2 H, CHAr);
9.88 (s, 1 H, C(7)HO)
5g
5h
5i
96 92—92.5
87 73—73.5
55.91 3.96
56.09 4.08
—
—
—
—
—
—
3.94 (s, 3 H, C(8)H3); 5.11 (s, 2 H, C(9)H2); 6.96—7.04
(m, 2 H, CHAr); 7.25—7.31 (m, 1 H, CHAr); 7.42—7.50,
7.90—7.97 (both m, 2 H each, CHAr);
9.88 (s, 1 H, C(7)HO)
76.31 7.33
76.48 7.43
1.25 (s, 9 H, C(15)H3); 3.95 (s, 3 H, C(8)H3); 5.08 (s,
2 H, C(9)H2); 6.89—6.96 (m, 2 H, CHAr); 7.24—7.34
(m, 3 H, CHAr); 7.89—7.96 (m, 2 H, CHAr);
9.89 (s, 1 H, C(7)HO)
97 119—121 62.60 4.42 4.71
62.72 4.56 4.88
C15H13NO5
C16H15ClO3
3.94 (s, 3 H, C(8)H3); 5.30 (s, 2 H, C(9)H2); 7.11—7.19
(m, 1 H, CHAr); 7.29 (d, 1 H, CHAr, J = 8.7); 7.46 (d,
1 H, CHAr, J = 8.0); 7.62—7.71 (m, 1 H, CHAr);
7.87—8.01 (m, 3 H, CHAr); 9.88 (s, 1 H, C(7)HO)
5j
91 99.5—100 65.92 5.08
66.09 5.20
—
2.30 (s, 3 H, C(16)H3); 3.94 (s, 3 H, C(8)H3); 5.09 (s,
2 H, C(9)H2); 6.87 (dd, 1 H, CHAr, J = 8.7, J = 3.0);
7.06 (d, 1 H, CHAr, J = 3.0); 7.25—7.33, 7.91—7.97
(both m, 2 H each, CHAr); 9.89 (s, 1 H, C(7)HO)
5k
5l
90
88—90
64.58 4.19
64.75 4.35
—
—
—
—
C15H12F2O3
C21H24O3
3.94 (s, 3 H, C(8)H3); 5.16 (s, 2 H, C(9)H2); 6.96—7.06
(m, 1 H, CHAr); 7.22—7.36 (m, 3 H, CHAr); 7.92—7.98
(m, 2 H, CHAr); 9.89 (s, 1 H, C(7)HO)
94 69—69.5
77.56 7.33
77.75 7.46
1.20—1.50, 1.65—1.85 (both m, 5 H each, CH2); 2.97 (m,
1 H, CH); 3.95 (s, 3 H, C(8)H3); 5.11 (s, 2 H, C(9)H2);
6.88—6.95, 6.99—7.04 (both m, 1 H each, CHAr);
7.11—7.21 (m, 2 H, CHAr); 7.25—7.32, 7.90—7.97,
7.99—8.03 (all m, 1 H each, CHAr);
9.89 (s, 1 H, C(7)HO)
5m
87 104—104.5 74.82 6.18
74.98 6.29
—
—
C16H16O3
2.22 (s, 3 H, C(16)H3); 3.95 (s, 3 H, C(8)H3); 5.11 (s,
2 H, C(9)H2); 6.86 (t, 1 H, CHAr, J = 7.0); 6.98 (d,
1 H, CHAr, J = 7.8); 7.11—7.19 (m, 2 H, CHAr); 7.28
(d, 1 H, C(5)HAr, J = 8.5); 7.93 (dd, 1 H, C(6)HAr
J = 8.5, J = 2.0); 7.97 (d, 1 H, C(2)HAr, J = 2.0);
9.89 (s, 1 H, C(7)HO)
,
6a
6b
79
65—67
59.29 5.14 10.42 12.08 C13H14N2O2S 3.38 (s, 3 H, C(13)H3); 3.89 (s, 3 H, C(8)H3); 4.16 (s,
59.52 5.38 10.68 12.20
2 H, C(9)H2); 6.95 (d, 1 H, CHIm, J = 1.1); 7.19 (d,
1 H, C(5)HAr, J = 8.5); 7.20 (d, 1 H, CHIm, J = 1.1);
7.55 (d, 1 H, C(2)HAr, J = 2.1); 7.84 (dd, 1 H, CHAr
J = 8.5, J = 2.1); 9.78 (s, 1 H, C(7)HO)
,
89 73.5—75
60.85 4.06 4.33 20.28 C16H13NO2S2 3.95 (s, 3 H, C(8)H3); 4.65 (s, 2 H, C(9)H2); 7.25 (d,
60.93 4.15 4.44 20.33
1 H, CHAr, J = 8.5); 7.32—7.40, 7.43—7.51 (both m,
1 H each, CHAr); 7.86—7.93, 7.96—8.06 (both m,
2 H each, CHAr); 9.84 (s, 1 H, C(7)HO)
(to be continued)

400
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 2, February, 2015
Khachatryan et al.
Table 2 (continued)
Comꢀ Yield M.p./C
pound (%)
Found
Calculated
Molecular
formula
1H NMR,  (J/Hz)
(%)
C
H
N
S
6c
6d
6e
6f
87 114—114.5 64.00 4.16 4.44 10.63 C16H13NO3S
64.19 4.38 4.68 10.71
3.95 (s, 3 H, C(8)H3); 4.62 (s, 2 H, C(9)H2); 7.26 (d,
1 H, C(5)HAr, J = 8.5); 7.28—7.38 (m, 2 H, C(13)HAr
C(14)HAr); 7.60—7.70 (m, 2 H, C(12)HAr, C(15)HAr);
7.90 (dd, 1 H, C(6)HAr, J = 8.5, J = 2.1); 8.03 (d,
1 H, C(2)HAr, J = 2.1); 9.85 (s, 1 H, C(7)HO)
,
85
41—43
72.99 7.31
73.13 7.36
—
9.62
9.76
C20H24O2S
1.16 (s, 9 H, C(18)H3); 2.24 (s, 3 H, C(16)H3); 3.87 (s,
3 H, C(8)H3); 4.13 (s, 2 H, C(9)H2); 7.08—7.12 (m,
3 H, CHAr); 7.18 (d, 1 H, C(5)HAr, J = 8.5); 7.65 (d,
1 H, C(2)HAr, J = 2.1); 7.82 (dd, 1 H, C(6)HAr
J = 8.5, J = 2.1); 9.78 (s, 1 H, C(7)HO)
,
96 171—171.5 64.17 4.65 9.14 10.57 C16H14N2O2S 3.93 (s, 3 H, C(8)H3); 4.57 (s, 2 H, C(9)H2); 7.07—7.14
64.41 4.73 9.39 10.74
(m, 2 H, C(12)HAr, C(13)HAr); 7.23 (d, 1 H, C(5)HAr,
J = 8.5); 7.40—7.47 (m, 2 H, C(11)HAr, C(14)HAr); 7.86
(dd, 1 H, C(5)HAr, J = 8.5, J = 2.1); 7.96 (d, 1 H,
C(3)HAr, J = 2.1); 9.81 (s, 1 H, C(7)HO)
86
89
81—82
92—94
64.72 5.03 5.37 12.22 C14H13NO2S
64.84 5.05 5.40 12.37
4.43 (s, 2 H, C(9)H2); 7.10—7.14 (m, 1 H, C(13)HPy);
7.22 (d, 1 H, C(5)HAr, J = 8.5); 7.29 (dt, 1 H,
C(11)HPy, J = 8.0, J = 1.0); 7.59—7.67 (m, 1 H,
C(12)HPy); 7.84 (dd, 1 H, C(6)HAr, J = 8.5, J = 2.1);
7.91 (d, 1 H, C(2)HAr, J = 2.1); 8.45—8.49 (m, 1 H,
C(14)HPy); 9.82 (s, 1 H, C(7)HO)
6g
54.41 4.42 10.39 12.01 C12H12N2O3S 2.67 (s, 3 H, C(12)H3); 3.93 (s, 3 H, C(8)H3); 4.52 (s,
54.53 4.58 10.60 12.13
2 H, C(9)H2); 7.25 (d, 1 H, C(5)HAr, J = 8.3);
7.86—7.94 (m, 2 H, CHAr); 9.84 (s, 1 H, C(7)HO)
together with the major 3ꢀaryloxymethylꢀ4ꢀmethoxybenzꢀ
aldehydes. To avoid this side reaction, we studied alkylaꢀ
tion of 4ꢀfluorophenol with chloride 2a (see Scheme 2)
upon reflux in different solvents (Table 3).
incoming nucleophile from the other side ( from 3.45
in the case of cytisine to 5.45 in the case of nitropyrꢀ
azole, see Table 2). Similar phenomenon is observed
The solvent system DMF—acetonitrile = (1 : 9)—(2 : 8)
was found to be optimal not only for the case of phenols
(85—95% yields), but also for that of thiols (see Scheme 2).
This procedure was also used for the preparation of other
aldehydes 8a,b, 9—12 (Scheme 3, Table 4).
Table 3. Alkylation of 4ꢀfluorophenol with chloride 2a in various
solvents
Solvent

T/C
ta/h
Yieldb (%)
The structures of all the synthesized aldehydes were
characterized by 1H NMR spectra, their composition was
confirmed by elemental analysis. 13C NMR, IR, and mass
spectra were also recorded for some samples.
The 1H NMR spectra of compounds 2—6 exhibit sigꢀ
nals characteristic of the aromatic protons of 3,4ꢀdisubstiꢀ
tuted benzaldehydes (see Tables 1 and 2).
method 1 method 2
DMF
Benzene
Toluene
MeCN
DMF—MeCNd
36.7 90—100
5
20c
20c
20
7
92
71
77
94
96
78
—
—
81
82
2.28
2.38
36.2
—
80
110
80
80—85
a Reaction duration, TLC monitoring of the reaction progress.
b In method 1, the product was isolated by evaporation of the
solvent on a rotary evaporator with subsequent treatment of the
reaction mixture with water; in method 2, the product was isoꢀ
lated by the dilution of the reaction mixture with water with
subsequent extraction of the product with dichloromethane.
c The reaction did not reach completion (TLC showed the presꢀ
ence of 2a). To isolate the pure product the residue was addiꢀ
tionally treated with 50% aqueous ethanol.
Interestingly, if chemical shifts for protons H(5) in
benzaldehyde do not virtually change ( 7.2—7.3)
(see Table 2), the chemical shifts for protons H(2) and
H(6) vary within a wide range ( 7.2—8.2) depending
on the electronꢀwithdrawing properties of substituꢀ
ent CH2X after substitution of chlorine in the CH2Cl group.
The nature of this substituent also greatly affects chemiꢀ
cal shift of the methylene group directly bonded to
the aromatic ring of the aldehyde from one side and to the
d The best results were obtained for the ratios (1 : 9)—(2 : 8).

Functionalized benzaldehydes
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 2, February, 2015
401
Scheme 3
Ar = 2ꢀO2NC6H4 (8a), 4ꢀO2Nꢀ3ꢀMeC6H3 (8b)
Table 4. Yields, melting points, elemental analysis data, and 1H NMR spectra (in DMSOꢀd6) of compounds 8a,b and 9—12
Comꢀ Yield
pound (%)
M.p.
/C
Found
Calculated
Molecular
formula
1H NMR,  (J/Hz)
(%)
C
H
N
8a
8b
77
83
130
110
58.28 3.59 5.62
58.30 3.67 5.67
C12H9NO5
C13H15NO5
5.42 (s, 2 H, C(7)H2); 6.89 (d, 1 H, C(9)H, J = 3.5); 7.13—7.21
(m, 1 H, CHAr); 7.49—7.56 (m, 2 H, CHAr, C(10)H);
7.64—7.72 (m, 1 H, CHAr); 7.89 (dd, 1 H, CHAr, J = 8.0,
J = 1.6); 9.60 (s, 1 H, C(12)H)
2.55 (s, 3 H, C(7)H); 5.35 (s, 2 H, C(8)H); 6.92 (d, 1 H,
C(10)H, J = 3.5); 7.10 (dd, 1 H, C(5)HAr, J = 9.1, J = 2.7);
7.17 (d, 1 H, C(3)HAr, J = 2.7); 7.54 (d, 1 H, C(11)H, J = 3.5);
8.06 (d, 1 H, C(6)HAr, J = 9.1); 9.61 (s, 1 H, C(13)H)
1.34 (t, 3 H, C(9)H3, J = 6.9); 4.12 (q, 2 H, C(8)H2,
J = 6.9); 7.27 (d, 1 H, CHAr, J = 8.3); 7.37—7.45,
59.72 4.13 5.29
59.77 4.24 5.36
9
91
86
81—81.5 66.02 5.13
66.10 5.20
—
C16H15ClO3
C10H11NO4
7.49—7.63 (both m, 3 H eaсh, CHAr); 9.84 (s, 1 H, C(7)H)
3.86 (s, 3 H, C(10)H3); 4.59 (s, 2 H, C(8)H2); 7.05 (d, 1 H,
10
158
57.29 5.19 6.52
57.41 5.30 6.70
CHAr, J = 8.3); 7.39 (br.s, 2 H, NH2); 7.42 (d, 1 H, CHAr
J = 1.9); 7.53 (dd, 1 H, C(6)HAr, J = 8.3, J = 1.9);
9.85 (s, 1 H, C(7)H)
,
11
12
93
94
62
74.22 5.73
74.36 5.82
—
C15H14O3
3.84 (s, 3 H, C(8)H3); 5.22 (s, 2 H, C(9)H2); 7.27 (d, 1 H,
CHAr, J = 8.2); 7.31—7.49 (m, 6 H, CHAr);
7.54 (m, 1 H, CHAr); 9.84 (s, 1 H, C(7)H)
136—137 53.34 3.33 4.65 C13H10BrNO2 5.37 (s, 2 H, C(8)H); 7.30 (d, 1 H, C(3)HAr, J = 8.6);
53.45 3.45 4.79
7.33—7.39 (m, 1 H, C(11)HPy); 7.63 (d, 1 H, C(13)HPy, J = 7.8);
7.76—7.80 (m, 1 H, C(4)HAr); 7.82 (d, 1 H, C(6)HAr, J = 2.8);
7.86 (td, 1 H, C(12)HPy, J = 7.8, J = 1.8); 8.56—8.61 (m, 1 H,
C(10)HPy); 10.38 (s, 1 H, C(7)HO)

402
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Khachatryan et al.
131.21 (C(6)Ar), 131.44 (C(1)Ar), 160.17 (C(4)Ar), 191.57 (CHO).
IR (KBr), /cm–1: 3399—3205 (OH assoc.), 2985—2724 (C—H),
1681 (C=O), 1602 (CAr—C), 1492—1436 (CH3, CH2), 1260
(C—O—C), 1041 (C—O—C).
for analogous methylene protons in compounds 8—12
(see Table 4).
In conclusion, we developed convenient preparative
procedures for the preparation of a wide range of benzꢀ
aldehydes. The use of potassium carbonate as a base allowꢀ
ed us to regioselectively and in high yield conduct nucleoꢀ
philic substitution of chlorine in the intermediate 4ꢀalkoxyꢀ
3ꢀchloromethylbenzaldehydes with the preservation of the
aldehyde function.
3ꢀAminomethylꢀ4ꢀmethoxybenzaldehydes 4a—k (general proꢀ
cedure). A mixture of 3ꢀchloromethylꢀ4ꢀmethoxybenzaldehyde
(1.85 g, 0.010 mol), the corresponding secondary amine
(0.011 mol), and potassium carbonate (2.00 g, 0.0145 mol) in
ethanol (20 mL) was refluxed for 3—5 h with stirring (TLC monꢀ
itoring). After evaporation of ethanol, the residue was treated
with water, a precipitate formed was filtered off, washed with
40% aqueous ethanol, and dried in air. In the case of aldehyde 4f,
an oil obtained after treatment of the residue with water was
dissolved in 4 M solution of a mixture of dioxane—HCl and a preꢀ
cipitate of hydrochloride 4f was filtered off and dried in vacuo.
Yields and physicochemical characteristics of aldehydes 4a—k
are given in Table 2.
4ꢀMethoxyꢀ3ꢀ[(6ꢀoxoꢀ7,11ꢀdiazatricyclo[7.3.1.02,7]tridecaꢀ
2,4ꢀdienꢀ11ꢀyl)methyl]benzaldehyde (4g). MS (EI, 70 eV), m/z
(Irel (%)): 338 [M]+ (20), 149 [3ꢀCHOꢀ6ꢀMeOꢀBn]+ (100).
13C NMR (DMSOꢀd6), : 25.09 (C(20)), 27.54 (C(18)), 34.58
(C(11)), 49.65 (C(17)), 54.35 (C(10)), 55.86 (C(8)), 59.71 (C(9)),
59.78 (C(19)), 103.77 (C(13)), 111.13 (C(5)Ar), 115.28 (C(15)),
126.72 (C(3)Ar), 128.96 (C(1)Ar), 129.07 (C(2)Ar), 130.93 (C(6)Ar),
138.77 (C(14)), 152.00 (C(12)), 162.05 (C(16)), 162.19 (C(4)Ar),
190.92 (CHO). IR (KBr), /cm–1: 3057 (CAr—H), 2944—2710
(C—H), 1685 (C=O of aldehyde), 1644 (C=O of ketone), 1604
(CAr—C), 1562—1543 (C—N), 1434 (CH3, CH2), 1256 (C—O—C),
1023 (C—O—C).
4ꢀMethoxyꢀ3ꢀ[(4ꢀnitroꢀ1Hꢀpyrazolꢀ1ꢀyl)methyl]benzaldeꢀ
hyde (4i). MS (EI, 70 eV), m/z (Irel (%)): 261 [M]+ (20), 230
[M – MeO]+ (90). 13C NMR (DMSOꢀd6), : 50.99 (C(9)), 56.31
(OCH3), 111.53 (C(5)Ar), 124.36 (C(3)Ar), 129.30 (C(1)Ar),
130.15 (C(2)Ar), 131.08 (C(12)), 133.09 (C(10)), 134.88 (C(11)),
135.92 (C(6)Ar), 161.74 (C(4)Ar), 191.25 (CHO). IR (KBr),
/cm–1: 3136 (C—H pyrazole), 2951—2752 (C—H), 1678 (C=O),
1605 (C=N, CAr—C), 1501 (C—N=O), 1315 (NO2), 1268
(C—O—C), 1122 (C—N), 1019 (C—O—C).
3ꢀAryloxymethylꢀ (5a—m) and 3ꢀhetarylthiomethylꢀ4ꢀmethꢀ
oxybenzaldehydes (6a—g) (general procedure). A mixture of
3ꢀchloromethylꢀ4ꢀmethoxybenzaldehyde (2a) (1.85 g, 0.01 mol),
the corresponding phenol or thiol (0.011 mol), and potassium
carbonate (2.00 g, 0.0145 mol) in a mixture of acetonitrile—
DMF (20 mL, from 9 : 1 to 8 : 2, v/v) was refluxed for 5—7 h with
stirring (TLC monitoring). After evaporation of the solvents, the
residue was treated with water, a precipitate formed was filtered
off, washed with 40% aqueous ethanol, and dried in air. Yields
and physicochemical characteristics of aldehydes 5a—m and 6a—g
are given in Table 2.
Experimental
Reaction progress and purity of aldehydes 2—12 were moniꢀ
tored by TLC on Silufol UVꢀ254 plates, eluent chloroform—
methanol (8 : 2), visualization under UV light and in iodine
vapors. 1H and 13C NMR spectra were recorded on a Bruker
AVANCE III NanoBay spectrometer (300 MHz) in the deuterium
stabilization mode, thermostabilization 25 C, internal standard
Me4Si. Elemental composition was determined on a Eurovector
EuroEA 3000 CHNSꢀanalyzer. IR spectra were obtained on
a Bruker Vertex 70 IR Fourierꢀtransform spectrometer in KBr
pellets (16 scans, resolution 4 cm–1). Mass spectra (EI) were
recorded on a GLCꢀMS spectrometric system based on a Khroꢀ
matek Crystal 5000.2 gas chromatograph with a Thermo ISQ mass
spectrometric detector, a TRꢀ5MS quartz capillary column, carꢀ
rier gas helium, energy of ionizing electrons 70 eV, temperature
of the source of ions 200 C. Melting points were measured on
a standard PTP instrument with certified thermometers.
4ꢀAlkoxyꢀ3ꢀchloromethylbenzaldehydes 2a—c (general proꢀ
cedure). A mixture of 4ꢀalkoxybenzaldehyde (0.10 mol), paraformꢀ
aldehyde (4.00 g, 0.133 mol), and concentrated hydrochloric
acid (100 g, d = 1.19 g cm–3) was stirred for 3 h at 70—80 C with
a simultaneous bubbling of hydrogen chloride (30—40 mL min–1).
After cooling, the crystals formed were separated and dried in
air. The mother liquors were reused in the next syntheses (the
cycles were repeated thrice without considerable changes in the
quality of the product). Total yields and physicochemical charꢀ
acteristics of aldehydes 2a—c are given in Table 1.
3ꢀChloromethylꢀ4ꢀethoxybenzaldehyde (2b). MS (EI, 70 eV),
m/z (Irel (%)): 200 (30), 198 [M]+ (90), 163 [M – Cl]+ (98), 135
[M – Cl – C2H4]+ (100). 13C NMR (DMSOꢀd6), : 14.39
(OCH2CH3), 41.05 (CH2Cl), 64.38 (OCH2CH3), 112.31 (C(5)Ar),
126.36 (C(3)Ar), 129.13 (C(1)Ar), 131.40 (C(6)Ar), 133.12 (C(2)Ar),
161.29 (C(4)Ar), 191.12 (CHO). IR (KBr), /cm–1: 3041 (CAr—H),
2979—2740 (C—H), 1683 (C=O), 1597 (CAr—H), 1473—1392
(CH2, CH3), 1268 (C—O—C), 1039 (C—O—C), 809 (C—Cl).
4ꢀAlkoxyꢀ3ꢀhydroxymethylbenzaldehydes 3a—c (general proꢀ
cedure). A mixture of the corresponding chloromethyl derivative
2a—c (0.01 mol) and a 2% aqueous solution of sodium hydrogen
carbonate (100 mL) was refluxed for 3—4 h with stirring (TLC
monitoring). After cooling of the reaction mixture, the white
crystals formed were filtered off and dried in air. Yields and
physicochemical characteristics of products 3a—c are given in
Table 1.
Isobutyl 4ꢀ(5ꢀformylꢀ2ꢀmethoxybenzyloxy)benzoate (5d). MS
(EI, 70 eV), m/z (Irel (%)): 342 [M]+ (2), 149 [3ꢀCHOꢀ6ꢀMeOꢀBn]+
(100). 13C NMR (DMSOꢀd6), : 18.92 (C(17), C(17´)), 27.41
(C(16)), 56.22 (C(8)), 64.48 (C(9)), 70.06 (C(15)), 111.37
(C(5)Ar), 114.72 (C(11), C(11´)), 122.38 (C(13)), 125.14 (C(3)Ar),
129.30 (C(1)Ar), 129.50 (C(2)Ar), 131.21 (C(12), C(12´)), 132.65
(C(6)Ar), 161.73 (C(4)Ar), 162.10 (C(10)), 165.30 (C(14)), 191.33
(CHO). IR (KBr), /cm–1: 2955—2710 (C—H), 1709 (C=O
ether), 1689 (C=O), 1606 (CAr—H), 1471—1441 (CH2, CH3),
1275 (C—O), 1176 (CH(CH3)2), 1038 (C—O—C).
4ꢀEthoxyꢀ3ꢀhydroxymethylbenzaldehyde (3b). MS (EI, 70 eV),
m/z (Irel (%)): 180 [M]+ (70), 151 [M – CHO]+ (60), 134
[M – H2O – C2H4]+ (84), 106 [PhCHO] (100). 13C NMR
(DMSOꢀd6), : 14.46 (OCH2CH3), 57.47 (CH2OH), 63.83
(OCH2CH3), 110.98 (C(5)Ar), 127.16 (C(2)Ar), 129.04 (C(3)Ar),
3ꢀ(2ꢀCyclohexylphenoxymethyl)ꢀ4ꢀmethoxybenzaldehyde (5l).
MS (EI, 70 eV), m/z (Irel (%)): 324 [M]+ (2), 149 [3ꢀCHOꢀ6ꢀ

Functionalized benzaldehydes
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 2, February, 2015
403
MeOꢀBn]+ (100). IR (KBr), /cm–1: 3067 (CAr—H), 2926—2730
(C—H), 1690 (C=O), 1603 (CAr—C), 1498—1453 (CH3, CH2),
1255 (C—O—C), 1024 (C—O—C).
[M – Bn]+ (82). 13C NMR (DMSOꢀd6), : 55.61 (C(10)), 67.22
(C(8)), 109.99 (C(2)Ar), 112.76 (C(5)Ar), 125.59 (C(6)Ar), 130.21
(C(1)Ar), 149.32 (C(3)Ar), 152.69 (C(4)Ar), 169.15 (C(9)), 191.40
(CHO). IR (KBr), /cm–1: 3458 (NH free), 3167 (NH bonded),
3078—3010 (CAr—H), 2917—2723 (C—H), 1717 (C=O of
amide), 1682 (C=O), 1587—1508 (NH), 1470—1426 (CH3,
CH2), 1264 (C—O—C), 1023 (C—O—C).
4ꢀBenzyloxyꢀ3ꢀmethoxybenzaldehyde (11). MS (EI, 70 eV), m/z
(Irel (%)): 242 [M]+ (30), 91 [Bn]+ (100). 13C NMR (DMSOꢀd6),
: 55.54 (C(8)), 70.00 (C(9)), 109.72 (C(13)Ar), 112.59 (C(5)Ar),
125.86 (C(2)Ar), 127.95 (C(11)Ar, C(11´)Ar), 128.08 (C(6)Ar),
128.48 (C(12)Ar, C(12´)Ar), 129.80 (C(1)Ar), 136.29 (C(10)Ar),
149.39 (C(3)Ar), 153.15 (C(4)Ar), 191.33 (CHO). IR (KBr),
/cm–1: 3060—3012 (CAr—H), 2948—2761 (C—H), 1676 (C=O),
1596 (CAr—C), 1465—1425 (CH3, CH2), 1261 (C—O—C), 1031
(C—O—C).
5ꢀBenzyloxyꢀ2ꢀbromopyridineꢀ4ꢀcarbaldehyde (12). MS (EI,
70 eV), m/z (Irel (%)): 293, 291 [M]+ (2), 264 (20), 262 [M – CHO]+
(20), 92 [2ꢀPyꢀCH2]+ (100). 13C NMR (DMSOꢀd6), : 71.08
(C(8)), 112.87 (C(5)Ar), 116.84 (C(3)Ar), 121.68 (C(13)Ar), 123.15
(C(11)Ar), 126.04 (C(1)Ar), 130.15 (C(6)Ar), 137.14 (C(12)Ar),
138.36 (C(4)Ar), 149.14 (C(10)Ar), 155.73 (C(9)Ar), 159.36
(C(2)Ar), 188.12 (CHO). IR (KBr), /cm–1: 3075—3048 (CAr—H),
2879 (C—H), 1681 (C=O), 1590 (CAr—H), 1482—1431 (CH2,
CH3), 1287 (C—O—C), 1030 (C—O—C, C—Br).
3ꢀ[(1,3ꢀBenzoxazolꢀ2ꢀyl)thiomethyl]ꢀ4ꢀmethoxybenzaldeꢀ
hyde (6c). MS (EI, 70 eV), m/z (Irel (%)): 299 [M]+ (10), 149
[3ꢀCHOꢀ6ꢀMeOꢀBn]+ (100). 13C NMR (DMSOꢀd6), : 30.74
(C(9)), 56.38 (C(8)), 110.18 (C(12)), 111.48 (C(5)Ar), 118.31
(C(15)), 124.35 (C(14)), 124.64 (C(13)), 125.15 (C(3)Ar), 129.20
(C(1)Ar), 130.82 (C(2)Ar), 132.71 (C(6)Ar), 141.19 (C(14)), 151.28
(C(11)), 162.05 (C(4)Ar), 163.85 (C(10)), 191.22 (CHO). IR
(KBr), /cm–1: 3030 (CAr—H), 2972—2759 (C—H), 1686 (C=O),
1600 (C=N), 1502 (oxazole), 1452 (CH3, CH2), 1399 (oxazole),
1262 (C—O—C), 1020 (C—O—C), 739 (oxazole).
3ꢀ[(5ꢀMethylꢀ1,3,4ꢀoxadiazolꢀ2ꢀyl)thiomethyl]ꢀ4ꢀmethoxyꢀ
benzaldehyde (6g). MS (EI, 70 eV), m/z (Irel (%)): 280 [M]+ (20),
206 (30), 149 [3ꢀCHOꢀ6ꢀMeOꢀBn]+ (100). 13C NMR (DMSOꢀd6),
: 15.20 (C(12)), 32.45 (C(9)), 56.31 (C(8)), 111.47 (C(5)Ar),
125.28 (C(3)Ar), 129.17 (C(1)Ar), 130.76 (C(2)Ar), 132.67 (C(6)Ar),
162.05 (C(11)), 164.35 (C(4)), 165.79 (C(10)), 191.22 (CHO).
IR (KBr), /cm–1: 3035 (CAr—H), 2942—2710 (C—H), 1690
(C=O), 1598 (CAr—C), 1496—1469 (CH2, CH3), 1380 (S—CH2),
1261 (C—O—C), 1019 (C—O—C), 822 (thiadiazole).
5ꢀAryloxymethylfurfurals 8a,b (general procedure). A mixꢀ
ture of 5ꢀchloromethylfurfural36 (0.010 mol), the corresponding
phenol (0.011 mol), and potassium carbonate (2.00 g, 0.0145 mol)
in a mixture of acetonitrile—DMF (20 mL, 9 : 1, v/v) was reꢀ
fluxed for 5—6 h with stirring (TLC monitoring). After evaporaꢀ
tion of the solvents, the residue was treated with water, a precipꢀ
itate formed was filtered off, washed with 30% aqueous methaꢀ
nol, and dried in air. Yields and physicochemical characteristics
of aldehydes 8a,b are given in Table 4.
5ꢀ[(3ꢀMethylꢀ4ꢀnitrophenoxy)methyl]ꢀ2ꢀfurancarbaldehyde
(8b). MS (EI, 70 eV), m/z (Irel (%)): 261 [M]+ (2), 109 [5ꢀCHOꢀ
furylꢀ2ꢀCH2]+ (100). 13C NMR (DMSOꢀd6), : 20.61 (C(7)),
62.11 (C(8)), 113.06 (C(3)Ar), 113.24 (C(10)), 118.22 (C(5)Ar),
123.67 (C(11)), 127.26 (C(6)Ar), 136.39 (C(2)Ar), 142.23 (C(1)Ar),
152.58 (C(12)), 155.18 (C(9)), 161.05 (C(4)Ar), 178.54 (CHO).
IR (KBr), /cm–1: 3112 (C—H of furan), 2869 (C—H), 1678
(C=O), 1606—1588 (C=C), 1504 (C—N=O), 1490—1459 (CH3,
CH2), 1333 (NO2), 1249 (C—O—C), 1192—1074 (furan), 1025
(C—O—C).
Aldehydes 9—12 (general procedure). A mixture of the correꢀ
sponding halide (0.010 mol), hydroxybenzaldehyde (0.011 mol),
and potassium carbonate (2.00 g, 0.0145 mol) in a mixture of
acetonitrile—DMF (20 mL, 8 : 2, v/v) was refluxed for 5—7 h
with stirring (TLC monitoring). After evaporation of the solꢀ
vents, the residue was treated with water, a precipitate formed
was filtered off, washed with 30% aqueous methanol, and dried
in air. Yields and physicochemical characteristics of aldeꢀ
hydes 9—12 are given in Table 4.
4ꢀ(2ꢀChlorobenzyloxy)ꢀ3ꢀethoxybenzaldehyde (9). MS (EI,
70 eV), m/z (Irel (%)): 290 [M]+ (6), 127 (30), 125 [2ꢀClꢀBn]+ (100).
13C NMR (DMSOꢀd6), : 14.54 (C(9)), 64.00 (C(10)), 67.56 (C(8)),
111.33 (C(2)Ar), 113.11 (C(5)Ar), 125.58 (C(6)Ar), 127.41 (C(15)Ar),
129.41 (C(13)Ar), 129.89 (C(16)Ar), 129.97 (C(14)Ar), 130.13
(C(1)Ar), 132.51 (C(12)Ar), 133.81 (C(11)), 148.62 (C(3)Ar),
153.04 (C(4)Ar), 191.41 (CHO). IR (KBr), /cm–1: 3073 (CAr—H),
2981—2707 (C—H), 1692 (C=O), 1588 (CAr—C), 1476—1430
(CH3, CH2), 1266 (C—O—C), 1124 (C—Cl), 1039 (C—O—C).
2ꢀ(4ꢀFormylꢀ2ꢀmethoxyphenoxy)acetamide (10). MS (EI,
70 eV), m/z (Irel (%)): 209 [M]+ (100), 165 [M – Ph]+ (76), 151
The authors are grateful to Prof. M. A. Yurovskaya for
the help in the discussion of the work results and compilaꢀ
tion of this paper.
This work was financially supported by the Ministry of
Education and Science of the Russian Federation (Agreeꢀ
ment on Grant No. 14.576.21.0044 from 05.08.14, the
Federal Target Program "Research and Development on
Priority Directions of Scientific and Technological Comꢀ
plex of Russia for the years 2014—2020", a unique identiꢀ
fication RFMEFI57614X0044).
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Received September 8, 2014;
in revised form October 30, 2014