Synthesis of salicylaldehydes bearing bulky substituents in the positions 3 and 5

Article abstract of DOI:10.1007/s11172-007-0170-5

Reaction of 2,4-disubstituted phenols with paraformaldehyde in the presence of SnCl₄ and 2,6-lutidine afforded a number of new salicylaldehydes, containing bulky substituents (tert-butyl, 1-phenylethyl, 1-(4-tert- butylphenyl)ethyl, α-cumyl, and trityl) in the positions 3 and 5.

Full text of DOI:10.1007/s11172-007-0170-5

Russian Chemical Bulletin, International Edition, Vol. 56, No. 6, pp. 1125—1129, June, 2007
1125
Synthesis of salicylaldehydes
bearing bulky substituents in the positions 3 and 5*
а
b
а
A. I. Kochnev,а I. I. Oleynik,а I. V. Oleynik, S. S. Ivanchev, and G. A. Tolstikov
ꢀ
аN. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry,
Siberian Branch of the Russian Academy of Sciences,
9 prosp. Akad. Lavrent´eva, 630090 Novosibirsk, Russian Federation.
Fax: +7 (383) 330 9524. Eꢀmail: oleynik@nioch.nsc.ru
bSt. Petersburg Division, G. K. Boreskov Institute of Catalysis,
Siberian Branch of the Russian Academy of Sciences,
6 Birzhevoi proezd, 199004 St. Petersburg, Russian Federation
Reaction of 2,4ꢀdisubstituted phenols with paraformaldehyde in the presence of SnCl4 and
2,6ꢀlutidine afforded a number of new salicylaldehydes, containing bulky substituents (tertꢀbutyl,
1ꢀphenylethyl, 1ꢀ(4ꢀtertꢀbutylphenyl)ethyl, αꢀcumyl, and trityl) in the positions 3 and 5.
Key words: formylation, phenols, salicylaldehydes, styrenes, alkylation, ligands.
The group IV transition metal chelate complexes with
salicylaldehyde Nꢀarylimines (so called "phenoxyimine"
complexes) show a high activity in the polymerization of
olefins.1
taining the corresponding substituents in the positions 2
and 4. Classic methods for the synthesis of oꢀhydroxyꢀ
benzaldehydes comprise the Reimer—Tiemann4 and the
Duff5 reactions, including a modification of the latter.6 In
the Reimer—Tiemann formylation, оꢀhydroxybenzaldeꢀ
hyde is chemoselectively formed, however, the yield does
not exceed 30%. The yields of aldehydes are higher in the
Duff formylation (~40—50%), and although the regioꢀ
selectivity of the process is generally lower, it is reasonꢀ
able to use this method for the 2,4ꢀdisubstituted phenols.7
The formylation of phenols upon their treatment with
paraformaldehyde in the presence of SnCl4 as a catalyst8
or upon sequential treatment with EtMgBr and paraformꢀ
aldehyde in the presence of HMPA is also described.9
The yields of benzaldehydes are close in these cases, beꢀ
ing 40—80%; however, the latter method has obvious
technological disadvantages.
Attempted formylation of 1ꢀ(phenyl)ethylꢀ, 1ꢀ(4ꢀtertꢀ
butylphenyl)ethylꢀ, and αꢀcumylꢀsubstituted phenols
1a—k with the use of SnCl4 (see Ref. 8) showed an imperꢀ
fection of the described procedure, consisting in a reꢀ
markable resinification of the reaction mixture and, as a
result, in a complication of the isolation of the target
product. We have found that the extent of decomposition
can be notably decreased by changing the order of addiꢀ
tion of reagents (2,6ꢀlutidine, SnCl4, and, finally, paraꢀ
formaldehyde should be added to a phenol) and by higher
diluting of the reaction mixture. After formylation of subꢀ
stituted phenols 1a—q under the described conditions,
the corresponding aldehydes 2a—k were isolated in
good yields (51—86%); relatively low yields of aldeꢀ
hydes were observed for pꢀtritylphenols 1l—o; in case of
Variation of the ligand structure enables one to reguꢀ
late sterical hindrance and electron density at an active
center of the catalyst and thus affect activity of the cataꢀ
lytic system, which can lead to a change of the mechaꢀ
nism of polymerization.2 A bulky substituent in the posiꢀ
tion 3 of the ligand ensures a high activity of the catalyst,
since it provides higher distance between a complex catꢀ
ion and a coꢀcatalyst anion and retards an electrophilic
attack of a coꢀcatalyst (the Lewis acids) on the phenoxide
oxygen. At the same time, a bulky substituent at the imine
nitrogen atom, making an access of a monomer to the
active center limited, decreases activity of the catalyst.3
A question about characteristic effects of substituents in
the position 5 of the ligand remains open, since the correꢀ
sponding complexes with various substituents were not
widely studied.
In the present work, we obtained of a number of
salicylaldehydes with various combinations of bulky subꢀ
stituents (tertꢀbutyl, 1ꢀphenylethyl, 1ꢀ(4ꢀtertꢀbutylpheꢀ
nyl)ethyl, αꢀcumyl (2ꢀphenylpropꢀ2ꢀyl), and trityl) in the
positions 3 and 5 to ensure their availability for the synꢀ
thesis of the corresponding aryl imine ligands in the
group IV transition metal complexes.
A general approach to the synthesis of such salicylꢀ
aldehydes consists in the formylation of phenols, conꢀ
* Dedicated to the memory of Academician N. N. Vorozhtsov
on the 100th anniversary of his birth.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1084—1088, June, 2007.
1066ꢀ5285/07/5606ꢀ1125 © 2007 Springer Science+Business Media, Inc.

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Kochnev et al.
оꢀtritylphenols 1p,q, we failed to isolate the correspondꢀ
ing aldehydes 2p,q in pure form (Scheme 1).
vibrations of the С=О group, is observed in the region
1641—1649 cm–1
.
Phenols 1a—k, used in the synthesis of aldehydes,
were obtained by the modification of a known method10
comprising alkylation of phenols (phenol, pꢀcresol, and
оꢀ or pꢀtertꢀbutylphenol) with styrenes (styrene, 4ꢀtertꢀ
butylstyrene, and αꢀmethylstyrene) in the presence of aluꢀ
minum phenoxide. Thus phenol 1a was obtained from
оꢀtertꢀbutylphenol and αꢀmethylstyrene in 85% yield (earꢀ
lier,11 phenol 1a was synthesized in the presence of TsOH
in 65% yield). Reactions of phenol, pꢀcresol, and pꢀtertꢀ
butylphenol with styrene, 4ꢀtertꢀbutylstyrene, and
αꢀmethylstyrene lead to the corresponding 2,4ꢀdisubstiꢀ
tuted derivatives 1b—k in 40—90% yields. pꢀTritylphenols
1l—o were obtained in good yields by reaction of triꢀ
phenylmethanol with 2ꢀtertꢀbutylꢀ, 2ꢀ(1ꢀphenylethyl)ꢀ,
2ꢀ[1ꢀ(4ꢀtertꢀbutylphenyl)ethyl]ꢀ, and 2ꢀcumylphenols in
the presence of acetic and sulfuric acids.12
оꢀTritylphenols 1p,q were synthesized by a known
method13 from pꢀcresol or pꢀtertꢀbutylphenol and chloroꢀ
triphenylmethane upon treatment with sodium metal in
79 and 35% yields, respectively.
In the conclusion, salicylaldehydes, containing
tertꢀbutyl, 1ꢀphenylethyl, 1ꢀ(4ꢀtertꢀbutylphenyl)ethyl, and
αꢀcumyl groups in the positions 3 and 5, can be obtained
in good yields by formylation of the corresponding phenols
with paraformaldehyde in the presence of SnCl4 and
2,6ꢀlutidine. Tritylꢀsubstituted analogs can be synthesized
in good yields by treatment of tritylꢀsubstituted phenols
with hexamethylenetetramine in trifluoroacetic acid.
Scheme 1
A. CH2O, SnCl4, 2,6ꢀlutidine. B. Hexamethylenetetramine,
CF3COOH.
2
R1
R2
Yield (%)
a
b
c
d
e
f
But
Me(Ph)CH
Me(Ph)CH
Me(Ph)CH
Me2(Ph)C
Н
Me
55 (A)
57 (A)
73 (A)
But
Н
Me
But
86 (A), 70 (B)
61 (A)
Me(4ꢀButC6H4)CH
Me(4ꢀButC6H4)CH
Me(4ꢀButC6H4)CH
Me2(Ph)C
66 (A)
73 (A)
60 (A)
51 (A)
60 (A)
66 (A)
g
h
i
Н
Me2(Ph)C
Me
But
j
Me2(Ph)C
k
l
Me2(Ph)C
But
Me2(Ph)C
Ph3C
Ph3C
Ph3C
Ph3C
Me
46 (A), 74 (B)
25 (A), 77 (B)
32 (A), 80 (B)
40 (A), 68 (B)
52 (B)
m
n
o
p
Me(Ph)CH
Me(4ꢀButC6H4)CH
Me2(Ph)C
Ph3C
q
Ph3C
But
72 (B)
Experimental
We have found that an aldehyde group can be more
easily introduced into tritylꢀsubstituted phenols 1l—q by
the Duff method with the use of trifluoroacetic acid
(method B). Thus after formylation of оꢀtritylphenols 1p,q
by method B, pure aldehydes 2p,q were successfully isoꢀ
lated in 52 and 72% yields, respectively. In case of
pꢀtritylphenols 1l—o, the yields of aldehydes were higher
for method B than for method A. For 2ꢀ(1ꢀphenylethyl)ꢀ
4ꢀtertꢀbutylphenol (1d) the reverse result was observed
(see Scheme 1).
1
H NMR spectra were recorded on a Bruker WPꢀ200 SY
spectrometer (200 MHz) for solutions of compounds in CCl4 or
CDCl3. HMDS was used as the internal standard. IR spectra
were recorded on a Vector 22 spectrometer for the neat liquid
samples or in KBr pellets. The reaction progress and the purity
of synthesized compounds were monitored by TLC on Silufol
UVꢀ254 plates (eluent, chloroform). Silica gel 5—40 µ was used
for flashꢀchromatography14 (chloroform—hexane, 1 : 1, as the
eluent). Elemental analyses were performed on a Carlo Erba 1106
CHNꢀanalyzer. Molecular formulae of compounds obtained
were calculated from the highꢀresolution mass spectra recorded
on a Finnigan MAT 8200 spectrometer. Melting points were
determined between glass plates upon heating with the rate of
The structure and composition of all the earlier unꢀ
known aldehydes 2a,b,d—g,m—p were established on the
bases of analytical and spectral data (highꢀresolution mass
spectra, IR spectra, and 1H NMR spectra), the structures
of known aldehydes 2c,h—l,q were confirmed by the IR
1 deg min–1
.
2ꢀtertꢀButylꢀ4ꢀ(2ꢀphenylpropꢀ2ꢀyl)phenol (1a). A mixture of
phenol (1.20 g, 0.0128 mol) and aluminum powder (0.05 g,
0.0018 mol) was heated at 185—190 °С until a melt of aluminum
phenoxide was formed, 2ꢀtertꢀbutylphenol (62.50 g, 0.416 mol)
was added to this. The reaction mixture was cooled down to
130 °С, αꢀmethylstyrene (23.0 g, 0.195 mol) was added and this
was stirred for 4 h at 130 °С. After cooling down to ~20 °C, the
mixture was treated with 2 M aq. HCl (50 mL) and ether
(100 mL) was added to this. The etheral layer was separated and
the water layer was extracted with ether (3×50 mL). The comꢀ
1
1
and H NMR spectral data. For the H NMR spectra of
substituted salicylaldehydes 2a—q, a strong downfield shift
of a signal for the proton of the ОН group (δ 11.12—11.87)
in comparison to the starting phenols (δ 4.00—4.50) is
observed, which can be explained by the presence of
the intramolecular hydrogen bonds in aldehydes 2a—q.
In the IR spectra of the compounds obtained, a strong
absorption band, corresponding to the stretching

Salicylaldehydes bearing bulky substituents
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 6, June, 2007
1127
bined extracts were washed with water (2×50 mL) and brine
(30 mL), dried with anhydrous MgSO4 and the solvent was
evaporated. The residue was distilled in vacuo, a fraction with
b.p. 160—162 °С (4—5 Torr) was collected. The yield was 42.30 g
2ꢀ(2ꢀPhenylpropꢀ2ꢀyl)phenol (1h) and 2,4ꢀbis(2ꢀphenylpropꢀ
2ꢀyl)phenol (1k) were obtained from phenol and αꢀmethylstyrene
similarly to compound 1b and were separated by fractional disꢀ
tillation in vacuo. Compound 1h. The yield was 35%, b.p.
170—175 °С (12—13 Torr). 1H NMR (CCl4), δ: 1.65 (s, 6 H,
Me); 4.05 (s, 1 H, OH); 6.60—7.40 (m, 9 H, Н arom.). Comꢀ
pound 1k. The yield was 53%, b.p. 190—196 °С (0.5 Torr).
1H NMR (CCl4), δ: 1.57, 1.65 (both s, 6 H each, Me); 3.86 (s,
1 H, OH); 6.52 (d, H(6), J = 8 Hz); 6.88—7.30 (m, 12 H,
Н arom.) (cf. Ref. 10).
4ꢀMethylꢀ2ꢀ(2ꢀphenylpropꢀ2ꢀyl)phenol (1i) was obtained
from pꢀcresol and αꢀmethylstyrene similarly to compound 1b.
The yield was 90%, b.p. 186—187 °С (12—13 Torr). 1H NMR
(CCl4), δ: 1.62 (s, 6 H, Me); 2.30 (s, 3 H, 4ꢀMe); 3.82 (s, 1 H,
OH); 6.51 (d, H(6), J = 8 Hz); 6.74 (dd, H(5), J1 = 8 Hz, J2 =
2 Hz); 7.10—7.27 (m, 6 H, Н arom.) (cf. Ref. 11).
4ꢀtertꢀButylꢀ2ꢀ(2ꢀphenylpropꢀ2ꢀyl)phenol (1j) was obtained
from 4ꢀtertꢀbutylphenol and αꢀmethylstyrene similarly to comꢀ
pound 1b. The yield was 76%, b.p. 196—198 °С (12—13 Torr).
1H NMR (CCl4), δ: 1.32 (s, 9 H, 4ꢀBut); 1.64 (s, 6 H, Me); 3.90
(s, 1 H, OH); 6.51 (d, 1 Н, H(6), J = 8 Hz); 7.05 (dd, 1 Н, H(5),
J1 = 8 Hz, J2 = 2 Hz); 7.10—7.28 (m, 5 H, Н arom.); 7.35 (d,
1 Н, H(3), J = 8 Hz) (cf. Ref. 11).
2ꢀtertꢀButylꢀ4ꢀtritylphenol (1l). Triphenylmethanol (10 g,
0.038 mol) and 2ꢀtertꢀbutylphenol (15.9 g, 0.106 mol) were disꢀ
solved in glacial acetic acid (100 mL) under heating. After the
components were dissolved, the reaction mixture was stirred
at ~20 °C. When precipitate appeared, conc. H2SO4 (10 mL)
was added, resulting in turning the color of the solution to black.
After 30 min, a precipitate was formed, this was stirred for
another 1.5 h. The precipitate was filtered off and washed with
acetic acid (20 mL) and methanol (3×20 mL). The yield was
11.4 g (76%). 1H NMR ((CD3)2CO), δ: 1.24 (s, 9 H, 2ꢀBut);
3.00 (br.s, 1 H, OH); 6.72 (d, 1 Н, H(6), J = 8.5 Hz); 6.81 (dd,
1 Н, H(5), J1 = 9 Hz, J2 = 2.5 Hz); 7.10 (d, 1 Н, H(3), J =
2.5 Hz); 7.12—7.33 (m, 15 H, Н arom.) (cf. Ref. 12).
1
(91%). H NMR (CDCl3), δ: 1.41 (s, 9 H, 2ꢀBut); 1.71 (s, 6 H,
Me); 4.61 (s, 1 H, OH); 6.55 (d, 1 H, H(6), J = 8 Hz); 6.93 (dd,
1 H, H(5), J1 = 8 Hz, J2 = 2 Hz); 7.18—7.35 (m, 6 H, H arom.)
(cf. Ref. 11).
2ꢀ(1ꢀPhenylethyl)phenol (1b). A mixture of phenol (68.0 g,
0.723 mol) and aluminum powder (0.3 g, 0.0104 mol) was heated
at 180—185 °С until a melt of aluminum phenoxide was formed.
The reaction mixture was cooled down to 110 °С, styrene (30.0 g,
0.288 mol) was added and this was stirred for 3 h at 110 °С. Then
this was cooled down to ~20 °C, acidified with 2 M aq. HCl
(50 mL), and ether (100 mL) was added to this. The etheral
layer was separated and the water layer was extracted with ether
(3×50 mL). The combined extracts were washed with water
(2×50 mL) and brine (30 mL) and dried with anhydrous MgSO4
and the solvent was evaporated. The residue was distilled in vacuo,
a fraction with b.p. 178—180 °С (15—16 Torr) was collected.
The yield was 45.5 g (81%). 1H NMR (CDCl3), δ: 1.57 (d, 3 H,
Me, J = 7.5 Hz); 4.30 (q, 1 H, CH, J = 7.5 Hz); 4.42 (s, 1 H,
OH); 6.55 (d, 1 H, H(6), J = 8 Hz); 6.55 (t, 1 H, H(5), J =
8 Hz); 6.95—7.30 (m, 7 Н, H arom.) (cf. Ref. 15).
4ꢀMethylꢀ2ꢀ(1ꢀphenylethyl)phenol (1c) was obtained from
pꢀcresol and styrene similarly to compound 1b. The yield was
1
70%, b.p. 190—195 °С (12—13 Torr). H NMR (CCl4), δ: 1.53
(d, 3 H, Me, J = 7.5 Hz); 2.21 (s, 3 Н, 4ꢀMe); 4.22 (q, 1 H, CH,
J = 7.5 Hz); 4.44 (s, 1 H, OH); 6.38 (d, 1 H, H(6), J = 8 Hz);
6.73 (d, 1 H, H(5), J = 8 Hz); 6.73 (s, 1 H, H(3)); 6.95—7.30
(m, 5 Н, H arom.) (cf. Refs 16 and 17).
4ꢀtertꢀButylꢀ2ꢀ(1ꢀphenylethyl)phenol (1d) was obtained from
4ꢀtertꢀbutylphenol and styrene similarly to compound 1b. The
yield was 67%, b.p. 200—205 °С (12—13 Torr). HRMS, found:
m/z 254.1671 [M]+. C18H22О. Calculated: M = 254.1670.
1H NMR (CDCl3), δ: 1.25 (s, 9 Н, 4ꢀBut); 1.56 (d, 3 H, Me, J =
7.5 Hz); 4.25 (q, 1 H, CH, J = 7.5 Hz); 4.45 (s, 1 H, OH); 6.43
(d, 1 H, H(6), J = 8 Hz); 6.95 (d, 1 H, H(5), J = 8 Hz);
6.75—7.50 (m, 6 H, H arom.).
2ꢀ[1ꢀ(4ꢀtertꢀButylphenyl)ethyl]phenol (1e) was obtained from
phenol and 4ꢀtertꢀbutylstyrene similarly to compound 1b. The
yield was 77%, b.p. 165—168 °С (2—3 Torr). HRMS, found:
m/z 254.1671 [M]+. C18H22О. Calculated: M = 254.1670.
1H NMR (CDCl3), δ: 1.29 (s, 9 Н, 4ꢀBut); 1.62 (d, 3 H, Me, J =
7.5 Hz); 4.31 (q, 1 H, CH, J = 7.5 Hz); 4.64 (s, 1 H, OH);
6.70—7.40 (m, 8 Н, H arom.).
2ꢀ(1ꢀPhenylethyl)ꢀ4ꢀtritylphenol (1m) was obtained from
phenol 1b similarly to compound 1l. The yield was 55%, m.p.
162—163 °С. HRMS, found: m/z 440.2143 [M]+. C33H28О.
1
Calculated: M = 440.2140. H NMR (CDCl3), δ: 1.40 (d, 3 H,
Me, J = 7.5 Hz); 4.25 (q, 1 H, CH, J = 7.5 Hz); 4.50 (s, 1 H,
OH); 7.08—7.33 (m, 23 H, Н arom.).
2ꢀ[1ꢀ(4ꢀtertꢀButylphenyl)ethyl]ꢀ4ꢀtritylphenol (1n) was obꢀ
tained from phenol 1e similarly to compound 1l. The yield was
72%, m.p. 101—103 °С. HRMS, found: m/z 496.2770 [M]+.
C
37H36О. Calculated: M = 496.2766. 1H NMR (CDCl3), δ:
2ꢀ[1ꢀ(4ꢀtertꢀButylphenyl)ethyl]ꢀ4ꢀmethylphenol (1f) was obꢀ
tained from pꢀcresol and 4ꢀtertꢀbutylstyrene similarly to comꢀ
pound 1b. The yield was 75%, b.p. 155—160 °С (0.5 Torr).
HRMS, found: m/z 268.1829 [M]+. C19H24О. Calculated:
1.30 (s, 9 H, 4ꢀBut); 1.43 (d, 3 H, Me, J = 7.5 Hz); 4.35 (q, 1 H,
CH, J = 7.5 Hz); 4.82 (s, 1 H, OH); 6.90—7.30 (m, 23 H,
Н arom.).
2ꢀ(2ꢀPhenylpropꢀ2ꢀyl)ꢀ4ꢀtritylphenol (1o) was obtained from
phenol 1h similarly to compound 1l. The yield was 62%, m.p.
171—173 °С. HRMS, found: m/z 454.2292 [M]+. C34H30O.
1
M = 268.1827. H NMR (CDCl3), δ: 1.30 (s, 9 Н, 4ꢀBut); 1.62
(d, 3 H, Me, J = 7.5 Hz); 2.30 (s, 3 Н, 4ꢀMe); 4.28 (q, 1 H, CH,
J = 7.5 Hz); 4.50 (s, 1 H, OH); 6.60—7.50 (m, 7 Н, H arom.).
4ꢀtertꢀButylꢀ2ꢀ[1ꢀ(4ꢀtertꢀbutylphenyl)ethyl]phenol (1g) was
obtained from 4ꢀtertꢀbutylphenol and 4ꢀtertꢀbutylstyrene simiꢀ
larly to compound 1b. The yield was 74%, b.p. 182—187 °С
(0.5 Torr). HRMS, found: m/z 310.2298 [M]+. C22H30О. Calꢀ
culated: M = 310.2297. 1H NMR (CDCl3), δ: 1.29, 1.32 (both s,
9 Н each, 4ꢀBut); 1.64 (d, 3 H, Me, J = 7.5 Hz); 4.30 (q, 1 H,
CH, J = 7.5 Hz); 4.50 (s, 1 H, OH); 6.70 (d, 1 Н, H(3), J =
8.5 Hz); 7.10—7.40 (m, 6 H, Н arom.).
1
Calculated: M = 454.2297. H NMR (CDCl3), δ: 1.45 (s, 6 H,
Me); 4.20 (s, 1 H, OH); 6.55 (d, 1 Н, H(6), J = 8.5 Hz);
6.91—7.33 (m, 22 Н, H arom.).
4ꢀMethylꢀ2ꢀtritylphenol (1p). Sodium metal (1.1 g, 0.05 mol)
was added to pꢀcresol (39.0 g, 0.36 mol) at 100 °С with vigorous
stirring. Triphenylchloromethane (10.0 g, 0.036 mol) was added
to a formed melt of cresolate and this was heated for 3 h at
135—145 °С with vigorous stirring. After cooling down to ~20 °C,
the reaction mixture was treated with 7% aq. NaOH (100 mL)

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Kochnev et al.
and ether (100 mL). The etheral layer was separated and washed
with 7% aq. NaOH (5×80 mL), water (100 mL), and brine
(30 mL). The organic layer was separated, dried with anhydrous
Na2SO4, the solvent was evaporated, and the residue was recrysꢀ
tallized from ethanol. The yield was 10.00 g (79%), m.p.
184—185 °С. 1H NMR (CCl4), δ: 2.16 (s, 3 H, 4ꢀMe); 4.02
(s, 1 H, OH); 6.62 (d, 1 Н, H(6), J = 8 Hz); 6.68 (dd, 1 Н,
H(5), J = 8 Hz, J = 2 Hz); 7.08—7.30 (m, 16 H, Н arom.)
(cf. Ref. 13).
4ꢀtertꢀButylꢀ2ꢀtritylphenol (1q) was obtained from 4ꢀtertꢀ
butylphenol similarly to compound 1p. The yield was 35%.
1H NMR (CCl4), δ: 1.28 (s, 9 H, 4ꢀBut); 3.93 (s, 1 H, OH); 6.60
(d, 1 Н, H(6), J = 8 Hz); 6.68 (dd, 1 Н, H(5), J1 = 8 Hz, J2 =
2 Hz); 7.05—7.38 (m, 16 H, Н arom.) (cf. Ref. 12).
Synthesis of salicylaldehydes (general procedure А). Tin(IV)
chloride (0.59 mL, 0.005 mol) was added under argon to
a mixture of the corresponding 2,4ꢀdisubstituted phenol 1
(0.05 mol), toluene (50 mL), and 2,6ꢀlutidine (2.14 g, 0.02 mol).
The formed yellow suspension was stirred for 1 h at ~20 °C, then
paraformaldehyde (3.3 g, 0.110 mol) was added, and this was
heated for 8—16 h at 115—125 °С. The reaction mixture was
cooled down to ~20 °C, ether (40 mL) was added, and this was
acidified with 2 M aq. HCl until pH value of 2 was reached. The
organic layer was separated and the water layer was extracted
with ether (3×20 mL). The combined extracts were washed with
water (50 mL) and brine (30 mL), separated, and dried with
anhydrous Na2SO4. The solvents were evaporated and the resiꢀ
due was subjected to flashꢀchromatography. Finally the aldeꢀ
hydes were purified by recrystallization from methanol.
General procedure B. A mixture of the corresponding tritylꢀ
substituted phenol 1l—q (0.01 mol), hexamethylenetetramine
(2.80 g, 0.02 mol), and CF3COOH (10 mL) was heated for 4 h at
115—125 °С, cooled down to 75—80 °С, 33% aq. H2SO4 (15 mL)
was added to this, and the resulting mixture was heated for
1—2 h at 125—130 °С. After cooling down to ~20 °C, ethyl
acetate (20 mL) and water (30 mL) were added. The organic
layer was separated and the water layer was extracted with ethyl
acetate (3×10 mL). The combined extracts were washed with
water (50 mL) and brine (30 mL), separated, and dried with
anhydrous Na2SO4. The solvent was evaporated and the residue
was subjected to flashꢀchromatography. Finally the aldehydes
were purified by recrystallization from methanol.
M = 282.1620. IR, ν/cm–1: 1642 (C=О). 1H NMR (CDCl3), δ:
1.28 (s, 9 Н, 5ꢀBut); 1.62 (d, 3 H, Me, J = 7.5 Hz); 4.60 (q, 1 H,
CH, J = 7.5 Hz); 7.10—7.55 (m, 7 Н, H arom.); 9.85 (s, 1 H,
СHО); 11.25 (s, 1 H, OH).
3ꢀ[1ꢀ(4ꢀtertꢀButylphenyl)ethyl]ꢀ2ꢀhydroxybenzaldehyde (2e).
M.p. 80—81 °C. HRMS, found: m/z 282.1643 [M]+. C19H22O2.
Calculated: M = 282.1620. IR, ν/cm–1: 1641 (C=О). 1H NMR
(CDCl3), δ: 1.32 (s, 9 Н, 4ꢀBut); 1.65 (d, 3 H, Me, J = 7.5 Hz);
4.54 (q, 1 H, CH, J = 7.5 Hz); 6.95 (t, 1 H, H(5), J = 8 Hz);
7.10—7.35 (m, 4 Н, H arom.); 7.40 (d, 2 H, H arom., J = 8 Hz);
9.81 (s, 1 H, СHО); 11.45 (s, 1 H, OH).
3ꢀ[1ꢀ(4ꢀtertꢀButylphenyl)ethyl]ꢀ2ꢀhydroxyꢀ5ꢀmethylbenzalꢀ
dehyde (2f). M.p. 74—76 °С. HRMS, found: m/z 296.1773 [M]+.
C20H24O2. Calculated: M = 296.1776. IR, ν/cm–1: 1646 (C=О).
1H NMR (CDCl3), δ: 1.30 (s, 9 Н, 4ꢀBut); 1.62 (d, 3 H, Me, J =
7.5 Hz); 2.28 (s, 3 H, 5ꢀMe); 4.50 (q, 1 H, CH, J = 7.5 Hz);
7.00—7.35 (m, 6 H, Н arom.); 9.75 (s, 1 H, СHО); 11.51
(s, 1 H, OH).
5ꢀtertꢀButylꢀ3ꢀ[1ꢀ(4ꢀtertꢀbutylphenyl)ethyl]ꢀ2ꢀhydroxybenzꢀ
aldehyde (2g). Oil. HRMS, found: m/z 338.2251 [M]+. C23H30O2.
Calculated: M = 338.2246. IR, ν/cm–1: 1644 (C=О). 1H NMR
(CDCl3), δ: 1.28 (s, 9 Н, 4ꢀBut); 1.32 (s, 9 Н, 5ꢀBut); 1.62 (d,
3 H, Me, J = 7.5 Hz); 4.50 (q, 1 H, CH, J = 7.5 Hz); 7.00—7.30
(m, 6 H, Н arom.); 9.82 (s, 1 H, СHО); 11.54 (s, 1 H, OH).
2ꢀHydroxyꢀ3ꢀ(2ꢀphenylpropꢀ2ꢀyl)benzaldehyde (2h). M.p.
85—86 °С. IR, ν/cm–1: 1648 (C=О). 1H NMR (CDCl3), δ: 1.72
(s, 6 H, Me); 7.00—7.70 (m, 8 H, Н arom.); 9.81 (s, 1 Н, СНО);
11.34 (s, 1 Н, ОН) (cf. Ref. 18).
2ꢀHydroxyꢀ5ꢀmethylꢀ3ꢀ(2ꢀphenylpropꢀ2ꢀyl)benzaldehyde
(2i). M.p. 69—71 °С. IR, ν/cm–1: 1646 (C=О). 1H NMR (CCl4),
δ: 1.69 (s, 6 H, Me); 2.35 (s, 3 H, 5ꢀMe); 7.00—7.18 (m, 6 H,
Н arom.); 7.35 (s, 1 Н, Н(6)); 9.73 (s, 1 Н, СНО); 11.12 (s, 1 Н,
ОН) (cf. Ref. 19).
5ꢀtertꢀButylꢀ2ꢀhydroxyꢀ3ꢀ(2ꢀphenylpropꢀ2ꢀyl)benzaldehyde
(2j). M.p. 76—78 °С. IR, ν/cm–1: 1649 (C=О). 1H NMR (CCl4),
δ: 1.32 (s, 9 H, 5ꢀBut); 1.71 (s, 6 H, Me); 7.02—7.32 (m, 7 H,
Н arom.); 9.77 (s, 1 Н, СНО); 11.19 (s, 1 Н, ОН) (cf. Ref. 19).
3,5ꢀBis(2ꢀphenylpropꢀ2ꢀyl)ꢀ2ꢀhydroxybenzaldehyde (2k).
1
M.p. 79—80 °C. IR, ν/cm–1: 1643 (C=О). H NMR (CCl4), δ:
1.62, 1.67 (both s, 6 H each, Me); 6.98—7.26 (m, 11 H, Н arom.);
7.33 (s, 1 Н, Н(6)); 9.71 (s, 1 Н, СНО); 11.23 (s, 1 Н, ОН) (cf.
Ref. 20).
3ꢀtertꢀButylꢀ2ꢀhydroxyꢀ5ꢀ(2ꢀphenylpropꢀ2ꢀyl)benzaldehyde
(2a). M.p. 82—84 °C. HRMS, found: m/z 296.1772 [M]+.
C20H24O2. Calculated: M = 296.1776. IR, ν/cm–1: 1641 (C=О).
1H NMR (CCl4), δ: 1.32 (s, 9 H, 3ꢀBut); 1.65 (s, 6 H, Me);
7.05—7.28 (m, 7 H, Н arom.); 9.76 (s, 1 Н, СНО); 11.69
(s, 1 Н, ОН).
2ꢀHydroxyꢀ3ꢀ(1ꢀphenylethyl)benzaldehyde (2b). M.p.
78—79 °С. HRMS, found: m/z 226.0994 [M]+. C15H14O2. Calꢀ
culated: M = 226.0993. IR, ν/cm–1: 1645 (C=О). 1H NMR
(CDCl3), δ: 1.53 (d, 3 H, Me, J = 7.5 Hz); 4.55 (q, 1 H, CH, J =
7.5 Hz); 6.80—7.40 (m, 8 Н, H arom.); 9.78 (s, 1 Н, СHО);
11.30 (s, 1 Н, OH).
3ꢀtertꢀButylꢀ2ꢀhydroxyꢀ5ꢀtritylbenzaldehyde (2l). M.p.
190—192 °C. IR, ν/cm–1: 1647 (C=О). 1H NMR (CCl4), δ:
1.28 (s, 9 H, 3ꢀBut); 7.00—7.42 (m, 17 H, Н arom.); 9.66 (s,
1 Н, СНО); 11.81 (s, 1 Н, ОН) (cf. Ref. 19).
2ꢀHydroxyꢀ3ꢀ(1ꢀphenylethyl)ꢀ5ꢀtritylbenzaldehyde (2m).
M.p. 197—199 °C. HRMS, found: m/z 468.2087 [M]+.
C
34H28O2. Calculated: M = 468.2089. IR, ν/cm–1: 1644 (C=О).
1H NMR (CDCl3), δ: 1.57 (d, 3 H, Me, J = 7.5 Hz); 4.65 (q,
1 H, CH, J = 7.5 Hz); 6.90—7.50 (m, 22 H, Н arom.); 9.75 (s,
1 H, СHО); 11.10 (s, 1 H, OH).
3ꢀ[1ꢀ(4ꢀtertꢀButylphenyl)ethyl]ꢀ2ꢀhydroxyꢀ5ꢀtritylbenzaldeꢀ
hyde (2n). M.p. 225—226 °C. HRMS, found: m/z 524.2713 [M]+.
2ꢀHydroxyꢀ5ꢀmethylꢀ3ꢀ(1ꢀphenylethyl)benzaldehyde (2c).
C
38H36O2. Calculated: M = 524.2715. IR, ν/cm–1: 1646 (C=О).
1
M.p. 52—53 °С. IR, ν/cm–1: 1643 (C=О). H NMR (CDCl3),
1H NMR (CDCl3), δ: 1.28 (s, 9 Н, 4ꢀBut); 1.57 (d, 3 H, Me, J =
7.5 Hz); 4.65 (q, 1 H, CH, J = 7.5 Hz); 6.85—7.50 (m, 21 H,
Н arom.); 9.85 (s, 1 H, СHО); 11.21 (s, 1 H, OH).
δ: 1.60 (d, 3 H, Me, J = 7.5 Hz); 2.29 (s, 3 Н, 5ꢀMe); 4.55 (q,
1 H, CH, J = 7.5 Hz); 7.00—7.40 (m, 7 Н, H arom.); 9.81 (s,
1 H, СHО); 11.20 (s, 1 H, OH) (cf. Ref. 16).
5ꢀtertꢀButylꢀ2ꢀhydroxyꢀ3ꢀ(1ꢀphenylethyl)benzaldehyde (2d).
Oil. HRMS, found: m/z 282.1625 [M]+. C19H22O2. Calculated:
2ꢀHydroxyꢀ3ꢀ(2ꢀphenylpropꢀ2ꢀyl)ꢀ5ꢀtritylbenzaldehyde (2o).
M.p. 174—176 °C. HRMS, found: m/z 482.2253 [M]+.
C
35H30O2. Calculated: M = 482.2246. IR, ν/cm–1: 1647 (C=О).

Salicylaldehydes bearing bulky substituents
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 6, June, 2007
1129
1H NMR (CCl4), δ: 1.52 (s, 6 H, Me); 6.90—7.40 (m, 22 H,
Н arom.); 9.61 (s, 1 Н, СНО); 11.37 (s, 1 Н, ОН).
4. H. Wynberg, Chem. Rev., 1960, 60, 169; H. Wynberg and
E. W. Meijer, Org. React., 1982, 28, 1.
2ꢀHydroxyꢀ5ꢀmethylꢀ3ꢀtritylbenzaldehyde (2p). M.p.
152—153 °C. HRMS, found: m/z 378.1625 [M]+. C27H22O2.
5. L. N. Ferguson, Chem. Rev., 1946, 38, 230.
6. J. F. Larrow, E. N. Jacobsen, Y. Gao, Y. Hong, X. Nie, and
C. M. Zepp, J. Org. Chem., 1994, 59, 1939.
1
Calculated: M = 378.1625. IR, ν/cm–1: 1644 (C=О). H NMR
(CDCl3), δ: 2.25 (s, 3 H, 5ꢀMe); 7.10—7.35 (m, 17 H, Н arom.);
9.77 (s, 1 H, СHО); 11.06 (s, 1 H, OH).
5ꢀtertꢀButylꢀ2ꢀhydroxyꢀ3ꢀtritylbenzaldehyde (2q). M.p.
164—166 °C. IR, ν/cm–1: 1647 (C=О). 1H NMR (CDCl3), δ:
1.18 (s, 9 Н, 5ꢀBut); 6.95—7.60 (m, 17 H, Н arom.); 9.78 (s,
1 H, СHО); 11.08 (s, 1 H, OH) (cf. Ref. 21).
7. J. F. Larrow and E. N. Jacobsen, Org. Synth., 1998, 75, 1.
8. G. Casiraghi, G. Casnati, G. Puglia, G. Sartori, and
G. Terenghi, J. Chem. Soc., Perkin Trans. 1, 1980, 1862.
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G. Sartori, and R. Ungaro, J. Chem. Soc., Perkin Trans. 1,
1978, 318.
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38, 1163.
This work was financially supported by the Siberian
Branch of the Russian Academy of Sciences (Integrational
Project No. 4.6).
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Received March 14, 2007;
in revised form May 25, 2007