Synthesis of 4-(Dibromomethyl)benzaldehyde by Catalytic Debromophosphoryl- and Phosphonyloxylation of 1,4-Bis(dibromomethyl)benzene with Phosphorus(IV) Acid Methyl Esters and Its Properties

Article abstract of DOI:10.1134/S1070363218110014

A new procedure has been developed for the simultaneous preparation of terephthalaldehyde and 4-(dibromomethyl)benzaldehyde by catalytic debromophosphoryl- and phosphonyloxylation of 1,4-bis- (dibromomethyl)benzene with P(IV) acid methyl esters. The reaction of 4-(dibromomethyl)benzaldehyde with ortho esters in the presence of sulfuric acid gave the corresponding acetals, whereas in the presence of ZnCl₂ terephthalaldehyde bis-acetals were formed. 4-(Dibromomethyl)benzaldehyde and its acetal were converted to methyl 4-(dibromomethyl)- and 4-(dimethoxymethyl)benzoates which were phosphorylated by the action of chlorophosphines, as well as by successive treatment with phosphorus(III) chloride and P(III) esters.

Full text of DOI:10.1134/S1070363218110014

ISSN 1070-3632, Russian Journal of General Chemistry, 2018, Vol. 88, No. 11, pp. 2243–2250. © Pleiades Publishing, Ltd., 2018.
Original Russian Text © M.B. Gazizov, S.Yu. Ivanova, R.A. Khairullin, Yu.S. Kirillina, K.S. Gazizova, 2018, published in Zhurnal Obshchei Khimii, 2018,
Vol. 88, No. 11, pp. 1761–1769.
Dedicated to the 115th anniversary of B.A. Arbuzov’s birth
Synthesis of 4-(Dibromomethyl)benzaldehyde
by Catalytic Debromophosphoryl- and Phosphonyloxylation
of 1,4-Bis(dibromomethyl)benzene with Phosphorus(IV) Acid
Methyl Esters and Its Properties
M. B. Gazizova*, S. Yu. Ivanovaa, R. A. Khairullina, Yu. S. Kirillinaa, and K. S. Gazizovaa
a Kazan National Research Technological University, ul. K. Marksa 68, Kazan, Tatarstan, 420015 Russia
*e-mail: mukattisg@mail.ru
Received September 6, 2018
Abstract—A new procedure has been developed for the simultaneous preparation of terephthalaldehyde and
4-(dibromomethyl)benzaldehyde by catalytic debromophosphoryl- and phosphonyloxylation of 1,4-bis-
(dibromomethyl)benzene with P(IV) acid methyl esters. The reaction of 4-(dibromomethyl)benzaldehyde with
ortho esters in the presence of sulfuric acid gave the corresponding acetals, whereas in the presence of ZnCl2
terephthalaldehyde bis-acetals were formed. 4-(Dibromomethyl)benzaldehyde and its acetal were converted to
methyl 4-(dibromomethyl)- and 4-(dimethoxymethyl)benzoates which were phosphorylated by the action of
chlorophosphines, as well as by successive treatment with phosphorus(III) chloride and P(III) esters.
Keywords: 1,4-bis(dibromomethyl)benzene, four-coordinate phosphorus acid methyl esters, phosphorylation
DOI: 10.1134/S1070363218110014
We previously described a new reaction of dimethyl
phosphonates RP(O)(OMe)2 1 with benzylidene
halides 2, which afforded aromatic aldehydes and pyro
phosphorus compounds [R(MeO)P(O)]2 3 or [RP(O)O]3
4 [1, 2]. This reaction has recently been extended to a
compound containing two dibromomethyl groups, 1,4-
bis(dibromomethyl)benzene (5a) [3–5]. For this
purpose, dimethyl methylphosphonate (1a) and tri-
methyl phosphate (1b) were used. The thermally
induced reaction was carried our at 170–180°C, and
the products were terephthalaldehyde (6) and pre-
viously unknown 4-(dibromomethyl)benzaldehyde
(7a). It should be noted that, among isomeric (dibromo-
methyl)benzaldehydes 7a–7c, only 3-(dibromomethyl)-
benzaldehyde (7b) has been reported. It was syn-
thesized by reaction of 1,3-bis(dibromomethyl)-
benzene (5b) with N,N-dimethylformamide at a tem-
perature exceeding 140°C. However, neither experi-
mental details nor characteristics of the product were
given in [6]. We have developed a procedure ensuring
simultaneous synthesis of compounds 6 and 7a, the
isolated yield of 7a being 43% [3–5].
The main drawback of the noncatalytic version of
this reaction is elevated temperature. In order to reduce
the reaction temperature and shorten the reaction time
we tried Lewis acids such as AlCl3, FeCl3, and ZnCl2
to catalyze the process. Positive results were obtained
only with the use of ZnCl2; in this case, the reaction
temperature was reduced from 180 to 130°C, and the
reaction time was significantly shortened, from 8 to 3–
4 h. Compounds 7a and 6 were isolated by column
chromatography in 53.5 and 7.5% yield, respectively.
Thus, 4-(dibromomethyl)benzaldehyde described for
the first time by us in [3–5] can be obtained with the
best yield (53.5%) by the catalytic version of the
reaction with the use of trimethyl phosphate which is
the cheapest among P(IV) acid methyl esters.
In keeping with the mechanism of activation of low
reactive Csp3–Hlg bonds by Lewis acids [7], zinc
chloride is likely to react with bromine of one
dibromomethyl group with the formation of donor–
acceptor complex A (Scheme 1) which is transformed
to dipolar ion 8. The positively charged CH carbon
2243

2244
GAZIZOV et al.
Scheme 1.
+
−
4-Br2CHC6H4CHBr2 + ZnCl2
4-Br2CHC6H4CH(Br)−Br−ZnCl2
А
5a
4-Br2CHC6H4CHBr BrZnCl2
8
RP(O)(OMe)2
4-Br2CHC6H4CH(Br)OP(OMe)2R BrZnCl2
9
4-Br2CHC6H4CH(Br)OP(O)(OMe)R
4-Br2CHC6H4CHO + R(MeO)P(O)Br
−(MeBr + ZnCl2)
10
7a
11а, 11b
R = Me (а), OMe (b).
Scheme 2.
H+
+
4-Br2CHC6H4CHO + CH(OR)3
7a 12
[4-Br2CHC6H4CHOH] + CH(OR)3
14
4-Br2CHC6H4CH(OR)2 + HCOOR
−H+
R = Me (а), Et (b).
atom of 8 is then attacked by the phosphoryl oxygen
atom of phosphonic (phosphoric) acid ester. The
resulting quasiphosphonium salt 9 is converted to
labile phosphoryloxy derivative 10 according to the
second stage of the Michaelis–Arbuzov reaction, and
compound 10 at elevated temperature (130°C) decom-
poses into aldehyde 7a and bromophosphate 11a or
bromophosphonate 11b. Reactions of the latter with
the initial phosphorus ester (1) give rise to pyrophos-
phorus compounds 3 and 4.
When the reaction was catalyzed by zinc chloride,
the product was terephthalaldehyde bis-acetal 15 since
ZnCl2 is capable of activating not only the aldehyde
group but also low reactive C–Br bond (Scheme 3).
Excess ortho ester is necessary to avoid elimination of
alkyl bromide from the intermediate α-bromo ether
4-(RO)2CHC6H4CH(OR)Br (16).
Aldehyde 7a and acetal 13a were oxidized with
N-bromosuccinimide (NBS) (Scheme 4). Acetal 13a
was thus converted to the corresponding ester, methyl
4-(dibromomethyl)benzoate (17). Aldehyde 7a reacted
with NBS to give 4-(dibromomethyl)benzoyl bromide
(18) which was isolated in the pure state. Bromide 18
readily reacted with trimethyl orthoformate to afford,
depending on the reactant ratio, ester 17 (1:1) or 19
(1:5). Compound 19 was also obtained by
acetalization of geminal dibromide 17 with trimethyl
orthoformate in the presence of ZnCl2.
4-(Dibromomethyl)benzaldehyde (7a) is a hetero-
functional compounds and it can be used as
intermediate product for the synthesis of various poly-
functional organic compounds. Initially, we studied
acetalization of 7a with trialkyl orthoformates 12 in the
presence of both Brønsted (sulfuric acid) and Lewis
acids (zinc chloride). In the first case, the reaction
involved only the aldehyde group to produce the
corresponding acetals, 1-(dialkoxymethyl)-4-(dibromo-
methyl)benzenes 13a and 13b (Scheme 2). Presumably,
the ortho ester reacted directly with protonated
aldehyde 14.
Acetals 13 and 19 were used to synthesize new
organophosphorus compounds (Scheme 5). They were
readily phosphinylated with chlorophosphines 20 to
obtain compounds 23 and 24. The reaction is likely to
Scheme 3.
ZnCl2
4-(RO)2CHC6H4CH(OR)2 + 3HCOOR + 2RBr + CH(OR)3
4-Br2CHC6H4CHO + 4CH(OR)3
7а 12
15
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SYNTHESIS OF 4-(DIBROMOMETHYL)BENZALDEHYDE
2245
Scheme 4.
NBS, hν, CCl4
4-Br2CHC6H4CH(OMe)2
13a
4-Br2CHC6H4COOMe + MeBr
Δ
17 (99.5%)
1.4NBS, hν, CCl4
4-Br2CHC6H4CHO
4-Br2CHC6H4COBr
7а
18
1:1
2CH(OMe)3
4-Br2CHC6H4COOMe
CH(OMe)3 12a, ZnCl2
17
−HCOOMe
−MeBr
1:5
4-(MeO)2CHC6H4COOMe
−2HCOOMe
−2MeBr
19
Scheme 5.
4-XC6H4CH(OMe)2 + R2PCl
[R2POMe + 4-XC6H4CH(OMe)Cl]
13, 19
20
21, 22
4-XC6H4CH(OMe)P(O)R2
23, 24
−MeCl
X = 4-Br2CH (13, 21), COOMe (19, 22); X = CHBr2, R = Ph (23a), Et (23b); X = COOMe, R = Ph (24a), Et (24b).
involve intermediate formation of α-chloro ethers 21
and 22. The formation of the latter was confirmed
experimentally by reacting acetals 13 with PCl3 in the
cold (Scheme 6). The structure of 21 was proved by 1H
NMR, as well as by reaction with P(III) esters 25 (after
removal of excess PCl3 and alkyl phosphorodi-
chloridite from the reaction mixture).
aldehyde and 4-(dibromomethyl)benzaldehyde, which
allows significant reduction of the reaction temperature
and shortening of the reaction time. 4-(Dibromo-
methyl)benzaldehyde is a promising intermediate
product for organic synthesis, and it can be used to
obtain new polyfunctional organic compounds.
EXPERIMENTAL
Phosphoryl derivatives 23 were converted to new
benzaldehydes 26 containing a phosphorus atom in the
side chain (Scheme 7). Compounds 23 reacted with
pyridine to give solid dipyridinium salts 27, and
hydrolysis of the latter afforded aldehydes 26.
1
The H and 13C NMR spectra were recorded on
1
Tesla BS–567A (100 MHz for H) and Bruker Avance
400WB spectrometers (400.13 MHz for 1H and
13
31
100.61 MHz for C) using CDCl3 as solvent. The P
NMR spectra were recorded on a Bruker Avance
400WB instrument at 161.98 MHz. The mass spectra
In summary, we have developed a catalytic pro-
cedure for the simultaneous synthesis of terephthal-
Scheme 6.
4-Br2CHC6H4CH(OR1)2 + PCl3
[4-Br2CHC6H4CH(OR1)Cl]
−R1OPCl2
13
21
R22POR3
25
4-Br2CHC6H4CH(OR1)P(O)R22 + R3Cl
23
R1 = Me (21a), Et (21b); R1 = Me, R2 = Ph (23a), Et (23b), OMe (23c), OEt (23d); R1 = Et, R2 = Ph (23e), OMe (23f).
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GAZIZOV et al.
Scheme 7.
N+
N+
2Br−
4-Br2CHC6H4CH(OMe)P(O)R2 + 2Py
4-R2P(O)CH(OMe)C6H4CH
27
4-R2P(O)CH(OMe)C6H4CHO + [2PyHBr]
R = Ph (а), Et (b).
23
2H2O
were obtained on a Thermo Electron Corporation DFS
GC/MS instrument (Germany); electron impact,
70 eV; ion source temperature 250°C; SGE BPX5
capillary column, 50 cm×0.32 mm; carrier gas helium
(ion peaks corresponding to the most abundant
isotopes, in particular 79Br, are given below).
115–116°C [8] (the yields were calculated on the
reacted tetrabromide 5a).
c. Reactant ratio 1.0:2.1; in the presence of ZnCl2.
A mixture of 8.44 g (0.02 mol) of compound 5a, 5.21 g
(0.042 mol) of phosphonate 1a, and 0.27 g (0.002 mol)
of zinc chloride was heated for 4 h at 130°C. The
mixture was treated with hot isooctane (3×20 mL), the
solvent was removed from the extract, the residue was
dissolved in 40 mL of benzene, and the solution was
washed with water (3×20 mL), dried over MgSO4, and
concentrated under reduced pressure. The residue was
subjected to column chromatography using benzene as
eluent to isolate 2.62 g (47.1%) of 7a and 0.33 g
(12.3%) of 6.
Reaction of 1,4-bis(dibromomethyl)benzene (5a)
with dimethyl methylphosphonate (1a). a. Reactant
ratio 1:1. A mixture of 8.44 g (0.02 mol) of
tetrabromide 5a and 2.48 g (0.02 mol) of phosphonate
1a was heated for 8 h at 170°C on an oil bath.
The mixture was extracted with boiling isooctane
(3×20 mL) by heating each time for 20 min under
reflux and separating the isooctane solution by
decanting. After cooling, crystals of a mixture of 5a,
7a, and 6 precipitated. By column chromatography
with benzene as eluent we isolated 2.39 g (43%) of of
4-(dibromomethyl)benzaldehyde (7a) as colorless
crystals with mp 89–90°C. 1H NMR spectrum, δ, ppm:
Reaction of 1,4-bis(dibromomethyl)benzene (5a)
with trimethyl phosphate (1b). a. Reactant ratio
1.0:1.5. A mixture of 4.22 g (0.010 mol) of compound
5a and 2.10 g (0.015 mol) of ester 1b was heated for
5.5 h at 180°C. The mixture was extracted with hot
isooctane, the solvent was removed from the extract,
and the residue was subjected to column chromato-
graphy using benzene as eluent to isolate 1.17 g
(42.1%) of 7a and 0.32 g (23.9%) of 6.
6.66 s (1H, CHBr2), 7.73 d and 7.89 d (4H, C6H4, 3JHH
=
8.4 Hz), 10.02 s (1H, CHO). 13C NMR spectrum, δC,
ppm: 39.49 (CHBr2), 127.35 and 130.06 (CHarom),
137.04 and 147.39 (Carom), 191.11 (CHO). Mass
spectrum, m/z (Irel, %): 247 (0.13) [M – CHO]+, 197
(91.3) [M – Br]+, 168 (7.8) [M – CHO – Br]+, 89
(100.0) [C7H5]+, 63 (77.5) [C5H3]+, 50 (20.4) [C4H2]+.
Found, %: C 34.36; H 2.12; Br 57.41. C8H6Br2O.
Calculated, %: C 34.57; H 2.18; Br 57.50.
b. Reactant ratio 1.0:2.1; in the presence of ZnCl2.
A mixture of 4.22 g (0.01 mol) of tetrabromide 5a,
2.94 g (0.021 mol) of phosphate 1b, and 0.14 g
(0.001 mol) of zinc chloride was heated for 4 h at 130°C.
The mixture was extracted with hot isooctane, the
extract was washed with water, the solvent was
removed, and the residue was subjected to column
chromatography using benzene as eluent to isolate 0.06 g
(1.4%) of unreacted 5a, 1.47 g (53.5%) of 7a, and 0.10 g
(7.5%) of 6 (the yields were calculated on the reacted
tetrabromide 5a).
b. Reactant ratio 1:1; in the presence of ZnCl2. A
mixture of 8.44 g (0.02 mol) of tetrabromide 5a, 2.48 g
(0.02 mol) of phosphonate 1a, and 0.27 g (0.002 mol)
of anhydrous zinc chloride was heated for 3 h at 130°C.
Extraction with boiling isooctane, followed by column
chromatography with benzene as eluent, gave 0.97 g
(11.5%) of unreacted compound 5a, 2.23 g (45.3%) of
aldehyde 7a (mp 89–90°C), and 0.32 g (13.5%) of
terephthalaldehyde (6) as colorless crystals with mp
1-(Dibromomethyl)-4-(dimethoxymethyl)benzene
(13a). One drop of sulfuric acid was added to a
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SYNTHESIS OF 4-(DIBROMOMETHYL)BENZALDEHYDE
2247
mixture of 2.00 g (0.0072 mol) of compound 7a and
3.06 g (0.0288 mol) of trimethyl orthoformate (12a).
The reaction was accompanied by evolution of heat.
The mixture was left to stand for 24 h at room
temperature, and volatile components were removed
under reduced pressure. Yield 2.22 g (98%), colorless
oil. 1H NMR spectrum, δ, ppm: 3.28 s (6H, Me), 5.40 s
(1H, CHO2), 6.62 s (1H, CHBr2), 7.42 d and 7.55 d
methoxymethyl)benzene (13a) and 1.12 g (0.0063 mol)
of NBS in 10 mL of carbon tetrachloride was refluxed
for 1 h in an inert atmosphere under irradiation. The
precipitate of succinimide was filtered off, and the
solvent was removed to isolate 1.93 g (99.5%) of
compound 17 as colorless crystals with mp 70–71°C
1
(from pentane). H NMR spectrum, δ, ppm: 3.93 s
(3H, COOMe), 6.63 s (1H, CHBr2), 7.62 d and 8.03 d
3
3
(4H, C6H4, JHH = 8.4 Hz). 13C NMR spectrum, δC,
(4H, C6H4, JHH = 8.4 Hz). 13C NMR spectrum, δC,
ppm: 40.77 (CHBr2), 52.81 (OMe), 102.37 (CHO2),
126.48 and 127.11 (CHarom), 139.94 and 142.02 (Carom).
Mass spectrum, m/z (Irel, %): 247 (0.26) [M –
CH(OMe)2]+, 199 (96.5) [M – OMe – Me – Br]+, 168
(8.6) [M – CH(OMe)2 – Br]+, 89 (100.0) [C7H5]+, 63
(80.9) [C5H3]+, 50 (21.7) [C4H2]+. Found, %: C 36.84;
H 3.65; Br 49.21. C10H12Br2O2. Calculated, %: C
37.06; H 3.74; Br 49.32.
ppm: 39.55 (CHBr2), 52.24 (COOMe), 126.60 and
130.02 (CHarom), 131.33 and 146.06 (Carom), 165.65
(CO). Found, %: C 34.88; H 2.49; Br 51.81.
C9H8Br2O2. Calculated, %: C 35.06; H 2.60; Br 51.95.
4-(Dibromomethyl)benzoyl bromide (18) was syn-
thesized in a similar way from 5.00 g (0.018 mol) of
4-(dibromomethyl)benzaldehyde (7a) using 4.45 g
(0.025 mol) of NBS; reaction time 4 h. Yield 4.25 g
(66.1%), colorless crystals, mp 97–99°C (from CCl4).
1H NMR spectrum, δ, ppm: 6.63 s (1H, CHBr2), 7.70 d
1-(Dibromomethyl)-4-(diethoxymethyl)benzene
(13b) was synthesized in a similar way from 1.00 g
(0.0036 mol) of aldehyde 7a and 3.20 g (0.0216 mol)
of triethyl orthoformate (12b). Yield 1.23 g (97%),
3
and 8.10 d (4H, C6H4, JHH = 8.4 Hz). 13C NMR
spectrum, δC, ppm: 38.45 (CHBr2), 127.14 and 132.25
(CHarom); 126.74, 130.65, 135.92, and 148.44 (Carom);
164.06 (CO). Found, %: C 26.67; H 1.31; Br 67.12.
C8H5Br3O. Calculated, %: C 26.89; H 1.40; Br 67.23.
1
colorless oil. H NMR spectrum, δ, ppm: 1.23 t (6H,
3
3
CH2Me, JHH = 7.1 Hz), 3.54 q (4H, CH2Me, JHH
=
7.1 Hz), 5.50 s (1H, CHO2), 6.63 s (1H, CHBr2), 7.60
3
d and 7.69 d (4H, C6H4, JHH = 8.7 Hz). Found, %: C
Reaction of 4-(dibromomethyl)benzoyl bromide
(18) with trimethyl orthoformate (12a). a. Reactant
ratio 1:1. Ortho ester 12a, 0.30 g (0.00280 mol), and
zinc chloride, 0.04 g (0.00028 mol), were added to a
solution of 1.00 g (0.00280 mol) of compound 18 in
5 mL of chloroform, and the mixture was heated for
30 min at 50°C. Removal of the solvent and volatile
components under reduced pressure left 0.85 g
(98.8%) of methyl 4-(dibromomethyl)benzoate (17) as
colorless crystals with mp 70–71°C (from pentane).
40.71; H 4.43; Br 45.31. C12H16Br2O2. Calculated, %:
C 40.91; H 4.55; Br 45.45.
1,4-Bis(dimethoxymethyl)benzene (15a). A mixture
of 1.00 g (0.00360 mol) of compound 7a, 1.53 g
(0.01440 mol) of orthoeester 12a, and 0.05 g
(0.00036 mol) of zinc chloride was heated for 2 h at
80°C. Volatile components were removed under
reduced pressure, and the residue was extracted with
hot isooctane to isolate 0.80 g (98.8%) of 1,4-bis
(dimethoxymethyl)benzene (15a) as colorless crystals
b. Reactant ratio 1:5. A mixture of 3.00 g
(0.00840 mol) of compound 18, 4.46 g (0.04200 mol)
1
with mp 53°C [9]. H NMR spectrum, δ, ppm: 3.13 s
(12H, OMe), 5.23 s (2H, CHO2), 7.26 s (4H, C6H4).
13C NMR spectrum, δC, ppm: 52.08 (OMe), 102.32
(CHO2), 126.54 (CHarom), 138.07 (Carom).
of trimethyl orthoformate (12a), and 0.11
g
(0.00084 mol) of zinc chloride was heated for 10 h at
80°C. Volatile components were removed under
reduced pressure to leave 1.75 g (99.2%) of methyl
4-(dimethoxymethyl)benzoate (19) as colorless oil [11].
1,4-Bis(diethoxymethyl)benzene (15b) was syn-
thesized in a similar way from 1.00 g (0.00360 mol) of
aldehyde 7a, 2.13 g (0.01440 mol) of ortho ester 12b,
and 0.05 g (0.00036 mol) of zinc chloride. Yield 1.00 g
Methyl 4-(dimethoxymethyl)benzoate (19). A
mixture of 0.63 g (0.0020 mol) of compound 17,
0.85 g (0.0080 mol) of ortho ester 12a, and 0.03 g
(0.0002 mol) of zinc chloride was heated for 2 h at 80°C.
Volatile components were removed under reduced
pressure, and the residue was extracted with hot
isooctane to isolate 0.34 g (81%) of ester 19 as
1
(99%), colorless oil [10]. H NMR spectrum, δ, ppm:
3
1.17 t (12H, OCH2Me, JHH = 7.0 Hz), 3.49 q (8H,
3
OCH2, JHH = 7.0 Hz), 5.44 s (2H, CHO2), 7.37 s (4H,
C6H4).
Methyl 4-(dibromomethyl)benzoate (17). A solution
of 2.03 g (0.0063 mol) of 1-(dibromomethyl)-4-(di-
1
colorless oil [11]. H NMR spectrum, δ, ppm: 3.21 s
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GAZIZOV et al.
1
(6H, OMe), 3.84 s (3H, COOMe), 5.35 s (1H, CHO2),
7.43 d and 7.94 d (4H, C6H4, 3JHH = 8.2 Hz). 13C NMR
spectrum, δC, ppm: 51.90 (COOMe), 52.12 (OMe),
101.82 (CHO2), 126.79 and 129.46 (CHarom); 126.53,
130.14, 130.76, and 142.81 (Carom); 166.31 (CO).
isooctane). H NMR spectrum, δ, ppm: 1.15 t (3H,
3
OCH2Me, JHH = 7.2 Hz), 3.35 q and 3.57 q (2H,
3
2
OCH2Me, JHH = 7.2 Hz), 5.13 d (1H, PCH, JPH
=
13.2 Hz), 6.55 s (1H, CHBr2), 7.15–7.93 m (14H,
H
arom). 13C NMR spectrum, δC, ppm: 15.27 (OCH2Me),
2
40.53 (CHBr2), 66.99 d (OCH2Me, JPC = 11.2 Hz),
81.48 d (PCH, 1JPC = 86.4 Hz); 126.26, 127.74, 127.78,
127.88, 128.00, 128.27, 128.39, 131.72, 131.81, 131.91,
131.97, 132.50, 132.59 (CHarom); 129.07, 130.30,
131.31, 131.42, 136.22, 141.47 (Carom). 31P NMR spectrum
(CCl4): δP 26.9 ppm. Found, %: C 51.71; H 4.03; P 5.95.
C22H21Br2O2P. Calculated, %: C 51.99; H 4.17; P 6.10.
{[4-(Dibromomethyl)phenyl](methoxy)methyl}di-
phenylphosphine oxide (23a). 1-(Dibromomethyl)-4-
(dimethoxymethyl)benzene (13a), 2.02 g (0.0062 mol),
was added dropwise with stirring to a solution of 1.37 g
(0.0062 mol) of chloro(diphenyl)phosphine (20a) in
10 mL isooctane at such a rate that the temperature did
not exceed 30°C. The mixture was then refluxed for
1.5 h and left to stand for 24 h at room temperature.
The crystalline solid was filtered off and dried. Yield
2.45 g (80.1%), colorless crystals, mp 146–148°C
Methyl 4-[(diphenylphosphinyl)(methoxy)methyl]-
benzoate (24a). Methyl 4-(dimethoxymethyl)benzoate
(19), 1.76 g (0.0084 mol), was added dropwise with
stirring in inert atmosphere to a solution of 1.85 g
(0.0084 mol) of phosphine 20a in 3 mL of isooctane.
The reaction was accompanied by evolution of heat.
The mixture was refluxed for 2 h and left to stand for
24 h at room temperature. The solvent and volatile
components were removed under reduced pressure to
leave 2.93 g (91.8%) of compound 24a as thick oil. 1H
NMR spectrum, δ, ppm: 3.18 s (3H, OMe), 3.69 s (3H,
1
(from isooctane). H NMR spectrum, δ, ppm: 3.37 s
2
(3H, OMe), 5.02 d (1H, PCH, JPH = 13.3 Hz), 6.56 s
(1H, CHBr2), 7.15–8.05 m (14H, Harom). 13C NMR
spectrum, δC, ppm: 40.68 (CHBr2), 58.97 d (OMe, 2JPC =
1
12.5 Hz), 83.08 d (PCH, JPC = 86.5 Hz); 126.37,
128.09, 128.16, 128.51, 128.63, 131.68, 131.76, 132.20,
132.54, 132.62 (CHarom); 128.78, 128.76, 130.36,
130.87, 135.54, 141.67, 141.69 (Carom). 31P NMR spectrum
(CCl4): δP 28.2 ppm. Found, %: C 50.81; H 3.77; P 6.14.
C21H19Br2O2P. Calculated, %: C 51.04; H 3.88; P 6.27.
2
COOMe), 5.01 d (1H, PCH, JPH = 16.0 Hz), 7.03–
7.76 m (14H, Harom). 13C NMR spectrum, δC, ppm:
51.99 (COOMe), 58.93 d (OMe, 2JPC = 12.5 Hz), 83.07
1
{[4-(Dibromomethyl)phenyl](methoxy)methyl}di-
ethylphosphine oxide (23b) was synthesized from
0.80 g (0.0064 mol) of chloro(diethyl)phosphine (20b)
and 2.07 g (0.0064 mol) of compound 13a. Yield 2.01 g
(78.8%), colorless crystals, mp 147–149°C (from iso-
d (PCH, JPC = 86.4 Hz); 127.80, 127.84, 127.99,
128.11, 128.50, 128.61, 129.14, 131.73, 131.82, 132.23,
132.53, 132.62 (CHarom); 128.18, 128.31, 128.39,
129.47, 131.33, 131.43, 131.61, 138.72 (Carom); 166.62
31
(CO). P NMR spectrum (CCl4): δP 27.6 ppm. Found,
1
octane). H NMR spectrum, δ, ppm: 0.97 d.t and 1.26
%: C 69.25; H 5.41; P 8.08. C22H21O4P. Calculated, %:
C 69.47; H 5.53; P 8.16.
3
3
d.t (3H, PCH2Me, JHH = 7.6, JPH = 15.2 Hz), 1.43–
1.57 m (2H, PCH2Me), 1.81–1.89 m (2H, PCH2Me),
2
Methyl 4-[diethylphosphinyl(methoxy)methyl]
benzoate (24b) was synthesized in a similar way from
0.92 g (0.0074 mol) of phosphine 20b and 1.55 g
(0.0074 mol) of ester 19. Yield 2.01 g (95.7%), thick
3.41 s (3H, OMe), 4.61 d (1H, PCH, JPH = 13.2 Hz),
6.61 s (1H, CHBr2), 7.37 d and 7.56 d (4H, C6H4, 3JHH
=
13
7.6 Hz). C NMR spectrum, δC, ppm: 5.22 d and 5.48
2
d (PCH2Me, JPC = 5.5 Hz), 16.84 d and 18.15 d
1
1
oil. H NMR spectrum, δ, ppm: 0.86 d.t and 1.18 d.t
(PCH2Me, JPC = 65.4 Hz), 40.18 s (CHBr2), 59.15 d
3
3
(OMe, 3JPC = 11.6 Hz), 80.45 d (PCH, 1JPC = 78.3 Hz);
126.84, 126.96, 127.00 (CHarom); 135.95 and 141.71
(Carom). 31P NMR spectrum (CCl4): δP 50.8 ppm.
Found, %: C 38.96; H 4.71; Br 39.97; P 7.64.
C13H19Br2O2P. Calculated, %: C 39.21; H 4.82; Br
40.14; P 7.79.
(6H, PCH2Me, JHH = 8.0, JPH = 16.0 Hz), 1.42–1.50
m and 1.80–1.90 m (4H, PCH2Me), 3.30 s (3H, OMe),
3.80 s (3H, COOMe), 4.71 d (1H, PCH, 2JPH = 12.0 Hz),
7.39 d and 7.92 d (4H, C6H4, 3JHH = 8.0 Hz). 13C NMR
spectrum, δC, ppm: 5.14 d and 5.43 d (PCH2Me, 2JPC
=
5.0 Hz), 16.55 d and 17.79 d (PCH2Me, 1JPC = 65.4 Hz),
51.83 (COOMe), 59.13 d (OMe, 2JPC = 11.8 Hz), 80.41
1
d (PCH, JPC = 78.5 Hz), 126.77 and 129.35 (CHarom);
{[4-(Dibromomethyl)phenyl](ethoxy)methyl}di-
phenylphosphine oxide (23e) was synthesized in a
similar way from 1.32 g (0.006 mol) of phosphine 20a
and 2.11 g (0.006 mol) of acetal 13b. Yield 2.65 g
(86.9%), colorless crystals, mp 136–138°C (from
127.71, 129.29, 129.75, 129.92, 130.08, 139.08 (Carom);
31
165.98 (CO). P NMR spectrum (CCl4): δP 52.8 ppm.
Found, %: C 58.97; H 7.30; P 10.83. C14H21O4P.
Calculated, %: C 59.15; H 7.39; P 10.92.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 11 2018

SYNTHESIS OF 4-(DIBROMOMETHYL)BENZALDEHYDE
2249
1-[(Chloro)(methoxy)methyl]-4-(dibromomethyl)
benzene (21a). In order to remove HCl impurity,
10 mL of PCl3 was mixed with 0.75 g (0.0062 mol) of
N,N-dimethylaniline at room temperature, and the
mixture was distilled in a nitrogen atmosphere directly
into the reaction flask. A solution of 2.00 g (0.0062 mol)
of acetal 13a in 1 mL of carbon tetrachloride was
added dropwise to 1.70 g (0.0124 mol) of purified
PCl3, maintaining the temperature at –5 to 0°C. After
5 min, the mixture crystallized. Compound 21a is
thermally unstable, and it was identified without
additional purification after removal of the solvent and
volatile products in a high vacuum (0.05 mm) in the
21a and 1.03 g (0.0062 mol) of triethyl phosphite. The
product was isolated by column chromatography using
ethyl acetate–benzene (3:2) as eluent. Yield 0.80 g
(30%), colorless crystals, mp 64–66°C. 1H NMR spec-
3
trum, δ, ppm: 1.23 d.t (6H, OCH2Me, JHH = 6.8,
4JPH = 4.4 Hz), 3.38 s (3H, OMe), 3.95–4.07 m (4H,
2
OCH2Me), 4.48 d (1H, PCH, JPH = 16 Hz), 6.61 s
3
(1H, CHBr2), 7.40 d and 7.53 d (4H, C6H4, JHH
=
8.0 Hz). 13C NMR spectrum, δC, ppm: 16.47 d
(OCH2Me, JPC = 4.6 Hz), 40.30 (CHBr2), 58.97 d
3
(OMe, 2JPC = 14.2 Hz), 62.95 d and 63.14 d (OCH2Me,
2JPC = 6.8 Hz), 80.04 d (PCH, 1JPC = 168.0 Hz); 126.58,
128.01, 128.07 (CHarom); 126.45, 130.30, 136.54,
141.98 (Carom). 31P NMR spectrum (CCl4): δP 18.3 ppm.
Mass spectrum, m/z (Irel, %): 428 (0.15) [M]+, 293
(100.0) [M – P(O)(OEt)2 + 2H]+, 249 (19.6) [M –
CH(OMe)P(O)(OEt)2 + 2H]+, 212 (68.3) [M –
P(O)(OEt)2 – Br]+, 168 (26.8) [M – CHBr2 – 2OEt + H]+,
89 (31.8) [C7H5]+. Found, %: C 36.05; H 4.34; Br 37.01;
P 7.04. C13H19Br2O4P. Calculated, %: C 36.30; H 4.46;
Br 37.16; P 7.20.
1
cold. H NMR spectrum (5°C), δ, ppm: 3.68 s (3H,
OMe), 6.43 s (1H, CHCl), 6.62 s (1H, CHBr2), 7.42–
7.62 m (4H, C6H4).
1-[(Chloro)(ethoxy)methyl]-4-(dibromomethyl)-
benzene (21b) was synthesized in a similar way from
1.7 g (0.0124 mol) of PCl3 and 2.0 g (0.0057 mol) of
1
acetal 13b. H NMR spectrum (5°C), δ, ppm: 1.11–
1.65 m (3H, OCH2Me), 3.39–4.01 m and 4.01–4.62 m
(2H, OCH2Me), 6.45–6.83 m [2H, CHBr2, CH(OEt)Cl],
7.41–7.82 m (4H, C6H4).
Dimethyl [4-(dibromomethyl)phenyl](ethoxy)-
methylphosphonate (23f) was synthesized in a similar
way from 2.00 g (0.0057 mol) of compound 21b and
0.71 g (0.0057 mol) of trimethyl phosphite (12a). Yield
{[4-(Dibromomethyl)phenyl](methoxy)methyl}di-
phenylphosphine oxide (23a). Ethyl diphenylphos-
phinite, 0.87 g (0.0038 mol), was added dropwise to a
solution of 1.25 g (0.0038 mol) of compound 21a in
1 mL of diethyl ether on cooling to –5 to 5°C. The
mixture was left to stand for 24 h at room temperature,
and the solvent and volatile components were removed
under reduced pressure. Yield 1.44 g (76.6%), colorless
crystals, mp 146–148°C (from isooctane). The spectral
characteristics of samples of 23a synthesized by
different methods were identical.
1
1.91 g (80.6%), thick oil. H NMR spectrum, δ, ppm:
3
1.21 t (3H, OCH2Me, JHH = 7.0 Hz), 3.15–3.85 m
(2H, OCH2Me, partially overlapped by the POMe
signals), 3.62 d and 3.73 d (6H, POMe, 3JPH = 10.7 Hz),
4.60 d (1H, PCH, 2JPH = 16.4 Hz), 6.61 s (1H, CHBr2),
7.38 d and 7.53 d (4H, C6H4, 3JHH = 8.5 Hz). 31P NMR
spectrum (CCl4): δP 18.4 ppm. Found, %: C 34.43; H
4.02; P 7.31. C12H17Br2O4P. Calculated, %: C 34.64; H
4.13; P 7.44.
4-[(Diphenylphosphinyl(methoxy)methyl]benz-
aldehyde (26a). A mixture of 0.94 g (0.0019 mol) of
phosphine oxide 23a and 0.75 g (0.0095 mol) of
pyridine was heated for 2 h at 100°C. The mixture was
poured into 30 mL of ice-cold distilled water and
extracted with diethyl ether (3×10 mL). The combined
extracts were washed with water and dried over
Na2SO4, and the solvent was removed under reduced
pressure. Yield 0.33 g (49.6%), pale yellow crystals,
Dimethyl [4-(dibromomethyl)phenyl](methoxy)-
methylphosphonate (23c) was synthesized in a
similar way from 1.41 g (0.0043 mol) of compound
21a and 0.53 g (0.0043 mol) of trimethyl phosphite.
Yield 0.65 g (37.6%), colorless crystals, mp 95–96°C
1
(from isooctane). H NMR spectrum, δ, ppm: 3.40 s
3
(3H, CHOMe), 3.70 d and 3.67 d (6H, POMe, JPH
=
2
10.6 Hz), 4.49 d (1H, PCH, JPH = 16.0 Hz), 6.62 s
(1H, CHBr2), 7.15–7.70 m (4H, C6H4). 31P NMR
spectrum (CCl4): δP 18.3 ppm. Found, %: C 32.64; H
3.62; P 7.58. C11H15Br2O4P. Calculated, %: C 32.86; H
3.77; P 7.70.
1
mp 163–165°C (from hexane). H NMR spectrum, δ,
2
ppm: 3.36 s (3H, OMe), 5.11 d (1H, PCH, JPH
=
12.8 Hz), 7.34–7.92 m (14H, Harom), 9.96 s (1H, CHO).
3
13C NMR spectrum, δC, ppm: 59.12 d (OMe, JPC
=
12.1 Hz), 83.48 d (PCH, 1JPC = 85.2 Hz); 128.4, 128.06,
128.18, 128.33, 128.37, 128.55, 128.66, 129.43, 131.61,
131.69, 132.25, 132.45, 132.54 (CHarom); 127.87, 128.84,
Diethyl [4-(dibromomethyl)phenyl](methoxy)-
methylphosphonate (23d) was synthesized in a
similar way from 2.00 g (0.0062 mol) of compound
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 11 2018

2250
GAZIZOV et al.
130.98, 131.96, 136.12, 140.87 (Carom); 192.01 (CO). 31P
NMR spectrum (CCl4): δP 27.4 ppm. Found, %: C 71.78;
H 5.31; P 8.73. C21H19O3P. Calculated, %: C 72.00; H
5.43; P 8.86.
REFERENCES
1. Gazizov, M.B., Kachalova, T.N., Karimova, R.F.,
Khairullin, R.A., and Sinyashin, O.G., Russ. J. Gen.
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Karimova, A.A., Ibragimov, Sh.N., and Musin, R.Z.,
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4. Gazizov, M.B., Ivanova, S.Yu., Karimova, R.F.,
Bagauva, L.R., Gazizova, K.S., and Karimova, A.A.,
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doi 10.1007/s11172-016-1282-6
5. Gazizov, M.B., Ivanova, S.Yu., Bagauva, L.R.,
Khairullin, R.A., and Musin, R.Z., Tetrahedron Lett.,
2016, vol. 57, no. 2, p. 210. doi 10.1016/j.tetlet.2015.12.005
4-[Diethylphosphinyl(methoxy)methyl]benzal-
dehyde (26b) was synthesized in a similar way from
1.00 g (0.0025 mol) of phosphine oxide 23b and 0.99 g
(0.0125 mol) of pyridine. Yield 0.25 g (39.4%), yellow
1
oil. H NMR spectrum, δ, ppm: 0.94 d.t and 1.22 d.t
3
3
(3H, PCH2Me, JHH = 7.6, JPH = 15.2 Hz), 1.45–1.62
m and 1.81–1.89 m (4H, PCH2Me), 3.39 s (3H, OMe),
2
4.67 d (1H, PCH, JPH = 13.2 Hz), 7.55 d and 7.85 d
3
(4H, C6H4, JHH = 7.6 Hz), 9.95 s (1H, CHO). 13C
NMR spectrum, δC, ppm: 5.03 d and 5.24 d (PCH2Me,
1
2JPC = 5.0 Hz), 16.74 d and 18.12 d (PCH2Me, JPC
=
3
64.6 Hz), 59.12 d (OMe, JPC = 11.4 Hz), 80.51 d
(PCH, JPC = 76.9 Hz), 127.32 and 128.09 (CHarom);
1
126.60, 127.35, 135.97, 141.23 (Carom); 191.24 (CO).
31P NMR spectrum (CCl4): δP 51.2 ppm. Found, %: C
61.17; H 7.34; P 12.06. C13H19O3P. Calculated, %: C
61.42; H 7.48; P 12.20.
6. Bankston, D., Synthesis, 2004, no. 2, p. 283. doi
10.1055/s-2003-44390
7. March, J., Advanced Organic Chemistry. Reactions,
Mechanisms, and Structure, New York: Wiley, 1992, 4th ed.
8. Snell, J.M. and Weissberger, A., Org. Synth., 1940,
ACKNOWLEDGMENTS
vol. 20, p. 92. doi 10.15227/orgsyn.020.0092
9. Manabe, Y., Kitawaki, Y., Nagasaki, M., Fukase, K.,
Matsubara, H., Hino, Y., Fukuyama, T., and Ryu, I.,
Chem. Eur. J., 2014, vol. 20, no. 40, p. 12750. doi
10.1002/chem.201402303
10. Podgoršek, A., Stavber, S., Zupan, M., and Iskra, J.,
Tetrahedron, 2009, vol. 65, no. 22, p. 4429. doi
10.1016/j.tet.2009.03.034
This study was performed under financial support
by the Ministry of Education and Science of the
Russian Federation in the framework of the base part
of state assignment in the sphere of research activity
(project no. 4.5348.2017/8.9).
CONFLICT OF INTERESTS
11. Wiles, S., Watts, P., and Haswell, S.J., Tetrahedron,
2005, vol. 61, no. 22, p. 5209. doi 10.1016/
j.tet.2005.03.082
No conflict of interests was declared by the authors.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 11 2018