Products of reaction between tetrabromo-substituted ortho- and para-hydroxybenzoic acids and sodium nitrite in CH3COOH

Article abstract of DOI:10.1134/S1070428012080064

The reaction of 2,3,5,6-tetrabromo-4-hydroxybenzoic acid with a 10-fold excess of NaNO2 in the glacial acetic acid at 20°C affords tetrabromonitrosophenols whose further transformations under the reaction conditions leads to the formation of a mixture of 2,4,5,6-tetrabromo-p-quinone diazide and tetrabromo-p- and -o-nitrophenols in the molar ratio 37 : 2 : 1. Under similar conditions the 3,4,5,6-tetrabromo-2-hydroxybenzoic acid is converted into a mixture of 3,4,5,6-tetrabromo-o-quinone diazide with the same nitrophenols in the ratio 13 : 1 : 3. The reaction of sodium 2,3,5,6-tetrabromo-4-hydroxy-benzoate with NaNO2 in dilute acetic acid resulted in a quantitative yield of tetrabromo-p-quinone monooxime. Pleiades Publishing, Ltd., 2012.

Full text of DOI:10.1134/S1070428012080064

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 8, pp. 1062−1070. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © M.V. Fadin, I.V. Tarasova, V.A. Vasin, V.N. Shishkin, 2012, published in Zhurnal Organicheskoi Khimii, 2012, Vol. 48, No. 8,
pp. 1066−1074.
Products of Reaction between Tetrabromo-Substituted
ortho- and para-Hydroxybenzoic Acids
and Sodium Nitrite in CH3COOH
M. V. Fadin, I. V. Tarasova, V. A. Vasin, and V. N. Shishkin†
Ogarev Mordovian State University, Saransk, 430005 Russia
e-mail: orgchem@mrsu.ru
Received March 21, 2012
Abstract—The reaction of 2,3,5,6-tetrabromo-4-hydroxybenzoic acid with a 10-fold excess of NaNO2 in the
glacial acetic acid at 20°C affords tetrabromonitrosophenols whose further transformations under the reaction
conditions leads to the formation of a mixture of 2,4,5,6-tetrabromo-p-quinone diazide and tetrabromo-p- and
-o-nitrophenols in the molar ratio 37 : 2 : 1. Under similar conditions the 3,4,5,6-tetrabromo-2-hydroxybenzoic
acid is converted into a mixture of 3,4,5,6-tetrabromo-o-quinone diazide with the same nitrophenols in the ratio
13 : 1 : 3. The reaction of sodium 2,3,5,6-tetrabromo-4-hydroxy-benzoate with NaNO2 in dilute acetic acid resulted
in a quantitative yield of tetrabromo-p-quinone monooxime.
DOI: 10.1134/S1070428012080064
It was established in [1] that dibromo-substituted
p- and o-hydroxybenzoic acids I and II and/or their
sodium salts reacted at 20°C with excess of NaNO2
in the glacial acetic acid giving products of oxida-
tive nitrosodecarboxylation, a mixture of isomeric
dibromo-p- and -o-nitrophenols III, IV. The reac-
tion proceeds along the mechanism of electrophilic
aromatic ipso-substitution involving the nitrosonium
cation generated from sodium nitrate by the action of
CH3COOH. The result of the reaction is due to the
intra- and intermolecular rearrangements of the inter-
mediate ipso-nitrosocomplexes.
OH
OH
OH
OH
COONa
Br
Br
NO2
Br
Br
Br
Br
Excess NaNO2
CH3COOH
Excess NaNO2
CH3COOH
+
NO2
COOX
Br
Br
Iа, Ib
III
IV
II
X = H (a), Na (b).
NaNO2 under various conditions.
Presuming that a similar rearrangement may be of a
general character in the reactions of nitrosodecarbox-
ylation of brominated hydroxybenzoic acids and that
the reactions proper are synthetically valuable for the
preparation of diverse difficultly available functional-
ized polybrominated derivatives we investigated the
transformations of tetrabromo-substituted p- and o-
hydroxybenzoic acids V, VI and some other brominated
Tetrabromo-substituted acids V, VI were prepared by
the bromination of dibromo-substituted acids I, II along
modified procedures [2, 3]: acids I, II were treated with
Br2 not in the 60% oleum at 30°C, but in the 40% oleum
at 35–40°C. This resulted in a considerable acceleration
of the bromodesulfonation of the intermediately formed
arenesulfonic acids, and the yield of the target products
increased. The bromination of acid Ia with Br2 in 30%
oleum at 40−45°C provided tribromo-substituted acid
hydroxybenzoic acids in acetic acid in the presence of
___________
† Deceased.
1062

PRODUCTS OF REACTION BETWEEN TETRABROMO-SUBSTITUTED
1063
VII in a 35% yield.
The main reaction products, crystalline quinone
diazides X, XI, were separated by filteration after al-
kalinizing the reaction mixtures with 10% solution of
Na2CO3. Isomeric nitrophenols VIII, IX were extracted
with ethyl ether from the mother liquors acidified with
dilute aqueous HCl till pH 1–2; these reaction products
were identified as mixtures by the data of IR and 13C
NMR spectra. The estimation of the relative content of
nitrophenols VIII, IX was performed using reference
signals of methoxy groups in the 1H NMR spectra of the
corresponding anisols obtained in a quantitative yield by
treating the mixtures of VIII, IX with dimethyl sulfate
in alkaline medium.
Tetrabromohydroxybenzoic acids V, VI compared
with dibromo-substituted analogs I, II proved to be
more active in the nitrosation reactions. For instance,
the reaction of acid V with the 10-fold molar excess of
NaNO2 in the glacial acetic acid at 20°C was completed
in 3 h. It resulted in a mixture containing products of the
oxidative nitrosodecarboxylation: nitrophenols VIII, IX,
and also tetrabromo-p-quinone diazide (X) in the molar
ratio 2 : 1 : 37 (the data of the material balance of the
reaction). The same nitrophenols VIII, IX in a mixture
with tetrabromo-o-quinone diazide (XI) in the molar ratio
1 : 3 : 13 formed under these conditions from isomer VI.
O
OH
OH
OH
Br
Br
Br
Br
Br
NO2
Br
Br
Br
Br
Br
Br
Br
Br
Br
Excess NaNO2
CH3COOH
+
+
Br
Br
COOH
NO2
N2
V
VIII
IX
X, 82%
O
OH
N2
Br
Br
Br
COOH
Br
Br
Excess NaNO2
CH3COOH
VIII
IX
+
+
Br
Br
Br
XI, 75%
VI
The structure of compounds X, XI was proved by their
spectral characteristics. In particular, in the IR spectra the
diazo group gives rise to a characteristic absorption band
at 2130 and 2136 cm–1 respectively, and the carbonyl
group, to the band of stretching vibrations at ~1681
cm–1. In the 13C NMR spectra the signals of the carbonyl
carbon atoms supporting the quinoid structure appear at
168.8 and 169.7 ppm respectively. The MALDI spectra
correspond to the empirical formula.
We used as initial compounds nitrophenols III, IV.
Their methylation with dimethyl sulfate in alkaline me-
dium provided dibromonitroanisoles XII, XIII. Next
stage of the nitro group reduction in compounds XII,
XIII aroused some troubles. We found that nitroanisole
XII could be reduced into anisidine XIV with the granu-
lated tin in concn. HCl. Similar approach to the synthesis
of anisidine XV was unsuccessful because of the low
yield and difficulties in the isolation of this oily product.
Therefore tetrabromoanisidine XVII was obtained in 67%
yield by the reduction of dibromonitroanisole XIII with
tin(II) chloride in a mixture of CH3COOH and concn.
HCl followed by the bromination of reaction product XV
without its isolation from the reaction mixture. The stages
of compound XIV bromination and anisidines XVI, XVII
deamination occurred without complications. As a result
the known tetrabromoanisoles XVIII, XIX were obtained
[4] whose nitration with fuming nitric acid (d 1.52 g cm—1)
in acetic anhydride furnished nitroanisoles XX, XXI. The
The more reliable identification of compounds VIII,
IX was obtained by the independent syntheses. To this
end we first attempted to reproduce the sequence of
procedures described in [4], however at the stage of
tetrabromohydroxybenzoic acids V, VI decarboxylation
by heating in N,N-dimethylaniline at 200°C intractable
mixtures of products were obtained, and we failed to
isolate therefrom the target products. Therefore taking
into account the existing published data we developed
a six-stage scheme of the synthesis of phenols VIII, IX.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 8 2012

FADIN et al.
NH2
1064
OCH3
NO2
NH2
Br2
[H]
(CH3O)2SO2
KOH
OCH3
III, IV
OCH3
CH3COOH
Br2
Br2
Br4
XII (4-NO2-2,6-Br2)
XIII (2-NO2-4,6-Br2)
XIV (4-OCH3-3,5-Br2)
XV (2-OCH3-3,5-Br2)
XVI (4-OCH3-2,3,5,6-Br4)
XVII (2-OCH3-3,4,5,6-Br4)
OCH3
OCH3
(1) NaNO2, H2SO4
(2) C2H5OH
HNO3
(CH3CO)2O
HBr
VIII, IX
NO2
H
CH3COOH
Br4
Br4
XX (4-NО2-2,3,5,6-Br4)
XXI (2-NО2-3,4,5,6-Br4)
XVIII (2,3,5,6-Br4)
XIX (2,3,4,5-Br4)
quinoid structure is supported by the presence in the IR
spectra of strong bands in the region 1635–1643 cm–1, and
in the 13C NMR spectra, of signals at 168–173 ppm belong-
ing to the carbon atom of the conjugated carbonyl group.
demethylation of nitroanisoles XX, XXI with a mixture
of glacial CH3COOH and concn. HBr (1 : 1) afforded
individual nitrophenols VIII, IX in 61–70% yield1 whose
constants were in agreement with the published data [4].
In interpreting the results obtained we proceed from
the electrophilic mechanism of the ipso-substitution in
the nitrosodecarboxylation of polybrominated hydroxy-
benzoic acids involving the nitrosonium acetate generated
in the reaction of NaNO2 with CH3COOH [7], which
leads to the formation of the corresponding brominated
nitrosophenol. We believe that the higher reactivity of
tetrabromohydroxybenzoic acids V, VI compared with
their dibromo-substituted analogs I, II is due to the ortho-
effect of bromine atoms. The carboxy group in these
compounds because of the steric repulsion is partially
displaced from the conjugation with the aromatic ring and
therefore does not deactivate the ring by the mesomeric
effect to the electrophilic attack.
We also established that the reaction of a water so-
lution of acid VI sodium salt and a five-fold excess of
NaNO2 in glacial acetic acid at 20°C resulted in the forma-
tion only of quinone diazide XI in 50% yield. In the same
conditions the sodium tetrabromohydroxybenzoate (V)
quantitatively converted into quinone monooxime XXII.
Similarly from sodium salts of 3-bromo-4-
hydroxybenzoic (XXIII) [5], dibromohydroxybenzoic
(Ia), and tribromohydroxybenzoic (VII) acids the
corresponding quinone monooximes XXIV–XXVI
were obtained in high yields. Compound XXIII does not
react with sodium nitrite in the glacial acetic acid, and
its isomer, 5-bromo-2-hydroxybenzoic acid (XXVII)
[6], same as acid II, does not react with NaNO2 either in
glacial or dilute acetic acid.
In event of tetrabromohydroxybenzoic acids V, VI the
formation of the diazo compound from the nitrosophenol
proves to be a prevailing process and parallel to it occurs
a side reaction of nitrosophenol oxidation into nitro-
phenol. We presume that the reason of these processes
consists in the fact that compared with the correspond-
ing dibromo analogs the tetrabromo-substituted nitroso
compounds XXVIII, XXIX because of the acceptor effect
of the large number of halogen atoms in the ring possess
a higher oxidative potential and are converted into nitro-
phenols only partially. The examples of diazo compounds
formation in the nitrosodecarboxylation of hydroxyben-
zoic acids were already described earlier [8–10]. In [11]
a mechanism was suggested of the transition of a nitroso
compound into a diazonium nitrate under the action of
The structure of quinone monooximes XXII, XXIV–
XXVI was confirmed by spectral data. For instance, the
O
OH
NaNO2
CH3COOH_H2O
Brn
Brn
NOH
XXII, XXIV_XXVI
COONa
Ia, V, VII, XXIII
n = 1_4.
____________
1 In [4] nitroanisoles XX, XXI were demethylated using BBr3 in
benzene; the yields of nitrophenols VIII, IX were 1.5 and 31%
respectively.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 8 2012

PRODUCTS OF REACTION BETWEEN TETRABROMO-SUBSTITUTED
1065
into nitrates of diazophenols A and B respectively, and
further at the treatment of the reaction mixtures with
Na2CO3 solution give quinone diazides X, XI.
nitrogen oxides. In this connection it is reasonable to
assume that nitrosophenols XXVIII, XXIX react with
nitrogen oxides, e.g., with NO, and are transformed first
OH
OH
Br
Br
Br
Na2CO3
10%
Br
Br
2 M NO
X
Br
Br
Br
N2+ NO3_
NO
XXVIII
A
OH
OH
N2+ NO_3
Br
NO
Br
Br
Br
Br
Br
10% Na2CO3
2 M NO
XI
Br
Br
XXIX
B
A qualitative confirmation of the formatation of di-
azophenol salts A and B at the nitrosodecarboxylation of
acids V, VI is the reaction of azocoupling proceeding at
the addition to the reaction mixture of the alkaline solu-
tion of β-naphthol resulting in the appearance of a dark
red precipitate.
It is possible analogously to rationalize the forma-
tion of compound VIII at the nitrosodecarboxylation of
tetrabromosalicilic acid (VI).
The rearrangements of the intermediate ipso-nitroso
complexes occur apparently through intramolecular
successive 1,2-shifts of bromine atoms via “bromonium”
transition states [12]. But the intermolecular exchange
of the ipso-nitroso complexes with the initial
tetrabromohydroxybenzoic acids cannot be ruled out.
A published analog of such process is the Reverdin
rearrangement [13, 14] observed at the nitration of
p-bromoanisole.
The formation of nitrophenol IX from acid V and of
nitrophenol VIII from acid VI in reaction carried out
in the glacial CH3COOH indicates the occurrence of
rearrangements in the ipso-nitroso complexes like at the
oxidative nitrosodecarboxylation of acid Ia and salt II.
Thus in keeping with the orientation effect of the
electron-donor hydroxy group the ipso-attack of the
nitrosonium cation on acid V occurs with respect to this
group both in the para- and ortho-positions giving an
ipso-nitroso complex C. The rearrangement of this com-
plex into ipso-bromo complex D and the decarboxylation
of the latter results in nitrosophenol XXIX that further
oxidates into nitrophenol IX.
One possible product among those generated by the
intermolecular rearrangement during the nitrosation of
tetrabromohydroxybenzoic acids V, VI might be penta-
bromophenol XXX, cf. [14]. We did not detect even trace
amounts of this compound among the products of nitroso-
decarboxylation. At the same time it was established that
the nitrosodebromination of phenol XXX occurred under
OH
OH
NO
Br
NO
Br
Br
Br
Br
[O]
XXIX
IX
_ CO2, _ H+
Br
COOH
Br
COOH
Br
D
C
identical conditions slower than the nitrosodecarboxyl-
ation of compounds V, VI. The relatively high conversion
(83%) was observed only after 5.5 h. The reaction prod-
ucts of compound XXX were the same nitrophenols VIII,
IX in the ratio 1.4 : 1 with a small impurity consisting of
two highly polar and well soluble compounds, presum-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 8 2012

FADIN et al.
1066
ably, dinitrophenols XXXI, XXXII. The main reaction
product, nitrophenol VIII, was isolated in an individual
state in 22% yield.
The intermediate compounds in the nitrosodebromina-
tion of phenol XXX like in the nitrosodecarboxylation of
acids V, VI are the same nitrosophenols XXVIII, XXIX
OH
OH
OH
NO2
Br
Br
Br
NO2
Br
Br
Br
O2N
Br
Excess NaNO2
CH3COOH
Br
Br
VIII
IX
+
+
+
NO2
Br
Br
XXX
XXXI
XXXII
and the strongest absorption bands are reported.
but their conversion into the final products proceeds
involving a stronger oxidant than HNO2 and nitrogen
oxides, namely, with a bromine cation liberated at the
electrophilic ipso-substitution.
The conditions of analytical TLC are as follows:
adsorbent Silufol UV-254, eluent hexane–acetone, 7 : 3,
development in iodine chamber or under UV irradiation.
The flash-chromatography was carried out using silica
gel Merk L 5/40 μ, eluent light petroleum ether–acetone,
2–9 : 1. Elemental analyses were performed on a CHN-
analyzer VarioMICRO.
The lack of the pentabromophenol in the reaction
mixtures during nitrosodecarboxylation of tetrabromo-
substituted hydroxybenzoic acids suggests that the rear-
rangement of the ipso-nitroso complexes most likely
occurs by the intramolecular mechanism.
Mass spectra MALDI were taken on an instrumentAu-
toflex II Bruker (resolution FWHM 18000) equipped with
a nitrogen laser with the operating wavelength 337 nm
and a time-of-flight analyzer operating in a reflectron
mode. Accelerating voltage 20 kV. The samples were
deposited on a sublayer of polished steel. The spectra
were registered in the positive ions mode. The resulting
spectrum was a sum of 300 spectra taken in various points
of the sample. 2,5-Dihydroxybenzoic acid (Acros, 99%)
and α-cyano-4-hydroxycinnamic acid (Acros, 99%) were
used as matrices.
The results of the nitrosation of compounds I, V,
VII, XXIII in dilute acetic acid may be ascribed to the
low solubility in the reaction mixture of the formed at
the ipso-nitrosodecarboxylation brominated p-nitros-
ophenols which undergo a fast rearrangement into the
corresponding more stable quinone monooximes XXII,
XXIV–XXVI that precipitate. Quinone monooximes
unlike nitrosophenols do not react with nitrogen oxides
and nitrous acid [15].
Thus the nitrosation of tetrabromohydroxybenzoic
V, VI and the other brominated hydroxybenzoic acids
in CH3COOH is a convenient method of the preparation
of previously unknown quinone diazides X, XI and p-
quinone monooximes XXII, XXIV–XXVI.
3-Bromo-4-hydroxybenzoic acid (XXIII) was ob-
tained in 76% yield by procedure [5], mp 176°C (aqueous
C2H5OH) (mp 175–178°C [5]). IR spectrum, ν, cm–1:
3301 br.m, 3078 w, 1677 v.s, 1581 m, 1377 m, 1299 v.s,
1249 s, 767 m. 1H NMR spectrum, δ, ppm: 6.98 d (1H,
H5, J 8.7 Hz), 7.76 d.d (1H, H6, J 2.3, 8.7 Hz), 7.99 d
(1H, H2, J 2.3 Hz), Harom; 11.04 br.s (2H, COOH, OH).
13C NMR spectrum, δ, ppm: 109.1, 116.0, 123.0, 130.5,
134.3, 158.2, 166.1 (COOH).
EXPERIMENTAL
1H and 13C NMR spectra were registered on a spec-
trometer JNM-ECX400 JEOL (400.1 and 100.6 MHz
respectively) from solutions of compounds in DMSO-d6
and in some cases, in CDCl3. The signals of residual pro-
tons and of carbon atoms of deuterated solvents served as
reference signals for measuring the chemical shifts.Aspe-
cial feature of 1H NMR spectra of some polybrominated
phenols and anisidines in DMSO-d6 is the absence of
proton signals from hydroxy and amino groups. IR spectra
were recorded on a Fourier spectrometer InfraLUM FT-02
from pellets with KBr. In the IR spectra 10 characteristic
5-Bromo-2-hydroxybenzoic acid (XXVII) was
obtained in 70% yield by procedure [6], mp 167°C
(aqueous C2H5OH) (mp 165–166°C [6]). IR spectrum,
ν, cm–1: 3248 w, 3063 m, 3034–2843 ser.br. bands,
1655 v.s, 1608 s, 1473 s, 1442 v.s, 1196 s, 825 s, 686
1
m, 628 m. H NMR spectrum, δ, ppm: 6.89 d (1H, H3,
J 8.7 Hz), 7.58 d.d (1H, H4, J 2.75, 8.7 Hz), 7.82 d (1H,
H6, J 2.75 Hz), Harom; 12.03 br.s (2H, COOH, OH).
13C NMR spectrum, δ, ppm: 109.8, 115.1, 119.6, 132.1,
137.9, 160.1, 170.5 (COOH).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 8 2012

PRODUCTS OF REACTION BETWEEN TETRABROMO-SUBSTITUTED
1067
3,5-Dibromo-4-hydroxybenzoic acid (Ia) was
obtained by procedure [16] in 81% yield, mp 200°C
(aqueous C2H5OH) (mp 202°C [16]). IR spectrum, ν,
cm–1: 3449 w, 3080 w, 2964–2519 ser.br.bands, 1693 v.s,
1587 w, 1562 w, 1421 w, 1304 s, 1277 s, 765 w, 744 w.
1H NMR spectrum, δ, ppm: 7.98 s (2H, H2,6, Harom).
13C NMR spectrum, δ, ppm: 111.3 (2C), 124.6 (1C), 133.4
(2C), 154.7 (1C), 164.9 (COOH).
slowly poured on ice. The separated precipitate was fil-
tered off, washed with water, and dried in air. The reac-
tion product was crystallized from aqueous ethanol with
activated carbon. Yield 4.46 g (35%), mp 224–225°C. IR
spectrum, ν, cm–1: 3464 m, 3078 w, 3036–2862 ser.br.
bands, 1709 v.s, 1566 m, 1358 s, 1296 s, 1192 s, 1095 m,
671 w. 1H NMR spectrum, δ, ppm: 7.91 s (1H, H5arom).
13C NMR spectrum, δ, ppm: 110.1, 117.5, 123.1, 128.2,
132.9, 154.3, 165.8 (COOH). Found, %: C 22.33; H 0.87.
C7H3Br3O3. Calculated, %: C 22.43; H 0.81.
3,5-Dibromo-2-hydroxybenzoic acid (II) was
obtained by procedure [17] in 87% yield, mp 201°C
(aqueous C2H5OH) (mp 204°C [17]). IR spectrum, ν,
cm–1: 3209 w, 3094 w, 3059 w, 3000–2515 ser.br. bands,
1662 v.s, 1597 w, 1427 s, 1300 s, 1226 v.s, 1180 s, 713 s.
1H NMR spectrum, δ, ppm: 7.84 d (1H, H4, J 2.29 Hz),
7.98 d (1H, H6, J 2.29 Hz), Harom; 10.53 br.s (2H, OH,
COOH). 13C, δ, ppm: 109.9, 111.7, 115.9, 131.7, 139.8,
157.1, 170.4 (COOH).
2,6-Dibromo-4-nitrophenol (III) was obtained
by procedure [18] in 92% yield, mp 143°C (aqueous
C2H5OH) (mp 144–145°C [18]). IR spectrum, ν, cm–1:
3365 m, 3079 w, 1573 m, 1512 v.s, 1463 s, 1323 v.s,
1230 s, 1128 s, 898 m, 742 s. 1H NMR spectrum, δ, ppm:
8.35 s (2H, Ha r om). 13C NMR spectrum, δ, ppm: 111.0
3, 5
(2C), 127.9 (2C), 140.0 (1C), 157.4 (1C).
Tetrabromohydroxybenzoic acids (V, VI). General
procedure. To a solution of 10 g (34 mmol) of hydroxy-
benzoic acid Ia or II in 40 ml of 40% oleum was added
dropwise at vigorous stirring within 0.5 h 3.2 ml (9.92
g, 62 mmol) of Br2 maintaining the temperature of the
reaction mixture at 35–40°C. The mixture was stirred at
this temperature for 4 h and was left overnight. Then it
was slowly poured on ice. The separated precipitate was
filtered off, washed with water, and crystallized from
aqueous ethanol with activated carbon.
4,6-Dibromo-2-nitrophenol (IV) was obtained by
procedure [19] in 90% yield, mp 112–113°C (aque-
ous C2H5OH) (mp 115°C [19]). IR spectrum, ν, cm–1:
3434 w, 3072 w, 1600 m, 1531 s, 1450 w, 1392 m,
1
1328 m, 1242 s, 1112 m. H NMR spectrum, δ, ppm:
8.06 d (1H, H5, J 2.29 Hz), 8.09 d (1H, H3, J 2.29 Hz),
Harom 13C NMR spectrum, δ, ppm: 108.3, 116.3, 126.9,
138.1, 139.8, 149.9.
Methylation of dibromonitrophenols III, IV.
General procedure. At 20°C equimolar amounts were
mixed of saturated ethanol solutions of nitrophenols III
or IV and KOH. The separated precipitate was filtered
off and dried in air. To boiling solution of 3 g (9 mmol)
of the obtained potassium salts in 30 ml of dry acetone
was added at stirring dropwise within 15 min 3 ml (4 g,
32 mmol) of dimethyl sulfate. The mixture was boiled
for 1 h more, then it was cooled to room temperature and
diluted with 70 ml of water. The separated precipitate
was filtered off and heated for 10 min with 50 ml of 10%
solution of KOH at 40–50°C. Insoluble in KOH the target
reaction product was filtered off, washed with water, and
crystallized from aqueous ethanol.
2,3,5,6-Tetrabromo-4-hydroxybenzoic acid (V).
Yield 65%, mp 227–228°C (mp 224°C[2]). IR spectrum,
ν, cm–1: 3528−2752 ser.br.bands, 1740 v.s, 1693 v.s, 1547
m, 1358 v.s, 1334 v.s, 1273 s, 1219 s, 1176 C, 640 m.
1H NMR spectrum, δ, ppm: 11.05 br.s (2H, COOH, OH).
13C NMR spectrum, δ, ppm: 115.6 (2C), 120.7 (2C), 133.5
(1C), 153.5 (1C), 166.5 (COOH).
3,4,5,6-Tetrabromo-2-hydroxybenzoic acid (VI).
Yield 70%, mp 235−236°C (mp 235−240°C [3]). IR spec-
trum, ν, cm–1: 3410 m, 3165–2746 ser.br.bands, 1709 v.s,
1701 v.s, 1558 s, 1358 m, 1273 s, 1203 m, 933 m, 671 m.
1H NMR spectrum, δ, ppm: 8.67 br.s (2H, COOH, OH).
13C NMR spectrum, δ, ppm: 116.5, 118.5, 120.5, 128.6,
129.1, 151.1, 165.8 (COOH).
2,6-Dibromo-4-nitroanisole (XII). Yield 84%,
mp 121°C (mp 123°C [20]). IR spectrum, ν, cm–1: 3082
w, 2955 v.w, 1516 s, 1458 m, 1412 m, 1346 v.s, 1265 m,
2,3,6-Tribromo-4-hydroxybenzoic acid (VII). To a
mixture of 10 g (34 mmol) of acid Ia and 80 ml of 30%
oleum at vigorous stirring was added dropwise within
0.5 h 3.2 ml (9.92 g, 62 mmol) of Br2 maintaining the
temperature of the water bath at 40−45°C. The stirring
at this temperature was continued for 4 h more, and the
reaction mixture was left overnight at 20°C. Then it was
1
1130 m, 972 s, 748 m. H NMR spectrum (CDCl3), δ,
ppm: 3.96 s (3H, OCH3), 8.40 s (2H, Ha r om). 13C NMR
3, 5
spectrum (CDCl3), δ, ppm: 61.0 (OCH3), 118.5 (2C),
128.1 (2C), 144.2 (1C), 159.7 (1C).
4,6-Dibromo-2-nitroanisole (XIII). Yield 77%,
mp 82°C (mp 80°C [21]). IR spectrum, ν, cm–1: 3078
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 8 2012

FADIN et al.
1068
2,3,5,6-Tetrabromoanisole (XVIII) was obtained by
diazotization of anisidine XVI with a subsequent reduc-
tion of the diazonium salt by procedure [23] in 50% yield,
mp 119°C (mp 117–118°C [23]). IR spectrum, ν, cm–1:
3082 w, 2978 w, 1585 w, 1531 s, 1388 s 1354 v.s, 1280 w,
1030 m, 1010 s, 945 m. 1H NMR spectrum (CDCl3), δ,
ppm: 3.87 s (3H, OCH3), 7.72 s (1H, H4arom). 13C (CDCl3),
δ, ppm: 60.5 (OCH3), 120.9 (2C), 124.9 (2C), 132.6 (1C),
156.6 (1C).
w, 2951 v.w, 1585 m, 1527 v.s, 1466 s, 1415 s, 1346 s,
1253 m, 976 s, 871 m. H NMR spectrum (CDCl3), δ,
ppm: 3.99 s (3H, OCH3), 7.88 d (2H, H5, J 2.29 Hz),
7.92 d (2H, H3, J 2.29 Hz), Harom 13C NMR spectrum
(CDCl3), δ, ppm: 62.8 (OCH3), 116.7, 120.8, 127.2,
140.0, 145.4, 150.1.
1
3,5-Dibromo-4-methoxyaniline (XIV).Amixture of
10 g (32 mmol) of nitroanisole XII, 11.5 g (97 mmol) of
granulated tin, and 75 ml of concn. HCl was maintained
for 1 h at 20°C, then the reaction mixture was heated on
a water bath at 70–80°C over 5 h with intermittent stir-
ring. The formed salt was filtered off, washed on the filter
with a little ice water and afterwards it was treated with 2
M solution of NaHCO3 till pH 6−7, and filtered. The ob-
tained precipitate was dispersed in 150 ml of acetone. The
mixture was filtered through a folded filter, the solvent
was evaporated in a vacuum, the residue was crystallized
from aqueous ethanol. Yield 6 g (67%), mp 69°C (mp
66°C [22]). IR spectrum, ν, cm–1: 3414 w, 3337 m, 3078
v.w, 2928 w, 1597 s, 1550 m, 1516 m, 1473 v.s, 1230 s,
987 s, 744 s. 1H NMR spectrum (CDCl3), δ, ppm: 3.62
2,3,4,5-Tetrabromoanisole (XIX) was obtained by
diazotization of anisidine XVII with a subsequent reduc-
tion of the diazonium salt by procedure [23] in 45% yield,
mp 141°C (mp 139–140°C [23]). IR spectrum, ν, cm–1:
2924 w, 1558 s, 1450 w, 1404 s, 1331 s, 1269 s, 1068 w,
1057 w, 1022 w, 844 w. 1H NMR spectrum (CDCl3), δ,
ppm: 3.88 s (3H, OCH3), 7.14 s (1H, H4arom). 13C NMR
spectrum (CDCl3), δ, ppm: 57.0 (OCH3), 115.2, 115.4,
119.3, 124.4, 129.6, 156.2.
Nitration of tetrabromoanisoles XVIII, XIX.
General procedure. To a solution of 1 g (2.35 mmol)
tetrabromoanisole XVIII or XIX in 50 ml of acetic an-
hydride was poured in one portion 20 ml of fuming nitric
acid (d 1.52 g/cm3). After 1.5 min the reaction mixture
was poured on ice. The separated precipitate was filtered
off, washed with water, and crystallized from aqueous
ethanol.
3, 5
br.s (2H, NH2), 3.78 s (3H, OCH3), 6.79 s (2H, Ha r om).
13C NMR spectrum (CDCl3), δ, ppm: 60.1 (OCH3), 118.1
(2C), 118.5 (2C), 144.3 (1C), 146.0 (1C).
3,4,5,6-Tetrabromo-2-methoxyaniline (XVII). To a
solution of 11.2 g (36 mmol) of dibromonitroanisole XIII
and 170 ml of glacial acetic acid was added in succession
53 g (280 mmol) of SnCl2 and 45 ml of concn. HCl. The
reaction mixture was heated for 6 h on a water bath at
70–80°C. Then to it was added dropwise 4.1 ml (12.67
g, 79.2 mmol) of Br2 in 30 ml of glacial acetic acid, and
the mixture was stirred for 1.5 h at 50°C, cooled to room
temperature and poured in water. The separated precipi-
tate was filtered off, dried in air, and crystallized from
light petroleum ether (bp 40–70°C). Yield 7.9 g (50%),
mp 110°C (mp 112°C [22]). IR spectrum, ν, cm–1: 3483
w, 3422 s, 2978 w, 1612 v.s, 1593 v.s, 1446 v.s, 1408 v.s,
1381 v.s, 1098 w, 999 v.s. 1H NMR spectrum (CDCl3), δ,
ppm: 3.81 s (3H, OCH3), 4.56 br.s (2H, NH2). 13C NMR
spectrum (CDCl3), δ, ppm: 59.5 (OCH3), 111.0, 114.5,
120.1, 123.7, 140.0, 143.7.
2,3,5,6-Tetrabromo-4-nitroanisole (XX). Yield 42%,
mp 155°C (mp 159°C [4]). IR spectrum, ν, cm–1: 2939
v.w, 1542 v.s, 1446 w, 1346 s, 1002 m, 744 v.w, 659
1
w, 621 w. H NMR spectrum (CDCl3), δ, ppm: 3.92 s
(3H, OCH3). 13C NMR spectrum (CDCl3), δ, ppm: 60.9
(OCH3), 116.9 (2C), 122.8 (2C), 149.8 (1C), 157.2 (1C).
Found, %: C 17.85; H 0.70; N 2.90. C7H3Br4NO3. Cal-
culated, %: C 17.94; H 0.65; N 2.99.
3,4,5,6-Tetrabromo-2-nitroanisole (XXI). Yield
50%, mp 110°C (mp 116°C [4]). IR spectrum, ν, cm–1:
2924 w, 1541 m, 1394 w, 1346 v.s, 1275 s, 1192 s.
1H NMR spectrum (CDCl3), δ, ppm: 3.94 s (3H, OCH3).
13C NMR spectrum (CDCl3), δ, ppm: 63.3 (OCH3), 115.9,
122.6, 125.5, 131.9, 147.1, 149.2. Found, %: C 17.80;
H 0.63; N 3.05. C7H3Br4NO3. Calculated, %: C 17.94;
H 0.65; N 2.99.
2,3,5,6-Tetrabromo-4-methoxyaniline (XVI) was
obtained by bromination of anisidine XIV by procedure
[23] in 70% yield, mp 143°C (mp 145–146°C[23]). IR
spectrum, ν, cm–1: 3414 w, 3310 m, 2939 w, 1670 m,
1446 s, 1404 v.s, 1307 m, 1014 s, 821 m, 640 m. 1H NMR
spectrum (CDCl3), δ, ppm: 3.80 s (3H, OCH3), 4.78 br.s
(2H, NH2). 13C NMR spectrum (CDCl3), δ, ppm: 60.7
(OCH3), 110.1 (2C), 120.9 (2C), 141.4 (1C), 146.9 (1C).
Demethylation of tetrabromonitroanisoles XX,
XXI. General procedure. Amixture of 1 g (2.1 mmol) of
nitroanisole XX or XXI, 15 ml of glacial CH3COOH, and
15 ml of concn. HBr was boiled for 6 h and left overnight
at room temperature.Afterwards the reaction mixture was
diluted with water to 130 ml. The separated precipitate
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 8 2012

PRODUCTS OF REACTION BETWEEN TETRABROMO-SUBSTITUTED
1069
was filtered off, washed with water, and heated with 50 ml
of 10% KOH solution for 10 min. The insoluble solid
was unreacted anisole XX or XXI that was filtered off.
The mother liquor was acidified with concn. HCl till pH
1–2. The reaction product was filtered off and purified
by crystallization from aqueous ethanol.
1099 s, 744 m, 636 m. 13C NMR spectrum (CDCl3), δ,
ppm: 122.1 (2C), 123.0 (2C), 138.3 (1C), 168.8 (1C).
MALDI spectrum: m/z 431.0315 [M]+. C6Br4N2O. Cal-
culated M 431.7511.
3,4,5,6-Tetrabromo-o-quinone diazide (XI). Yield
75%, mp 137–138°C (decomp.). IR spectrum, ν, cm–1:
2136 m, 1681 s, 1612 m, 1542 s, 1427 m, 1215 m, 1053 s,
702 w, 644 w. 13C NMR spectrum (CDCl3), δ, ppm: 111.4,
113.4, 126.3, 138.4, 140.5, 169.7. MALDI spectrum: m/z
432.3546 [M + H]+. C6Br4N2O. Calculated M 432.7511.
2,3,5,6-Tetrabromo-4-nitrophenol (VIII). Yield
70%, mp 186°C (decomp.) {mp 187°C (decomp.) [4]}.
IR spectrum, ν, cm–1: 3404 m, 1542 v.s, 1446 w, 1346 C,
1002 m, 744 v.w, 659 w, 621 w. 13C NMR spectrum, δ,
ppm: 115.9 (2C), 116.3 (2C), 145.4 (2C), 155.1 (2C).
Found, %: C 15.97; H 0.17; N 2.96. C6HBr4NO3. Cal-
culated, %: C 15.85; H 0.22; N 3.08.
Reaction of hydroxybenzoic acids I, V–VII, XXIII
with NaNO2 in dilute acetic acid. General procedure.
Hydroxybenzoic acid I, V–VII, XXIII was dissolved in
a minimum volume of ethanol and mixed with equimolar
amount of NaOH also dissolved in a minimum volume
of ethanol. The solvent was distilled off in a vacuum of
the water-jet pump. The salt obtained in a quantitative
yield was dried in air and was stored in a tightly stop-
pered weighing glass. In 70 ml of water was dissolved
at stirring 3 mmol of the sodium salt of hydroxybenzoic
acid I, V–VII, XXIII and 15 mmol of NaNO2. Then at
20°C was added dropwise within 1 h 10 ml of glacial
CH3COOH, and the mixture was stirred for 3 h. The
separated precipitate was filtered off, washed on the filter
with water till neutral washings. From acid VI by treat-
ing the precipitate along the above procedure quinone
diazide XI was obtained in 50% yield. In the other cases
the precipitate consisted of the corresponding p-quinone
monooxime XXII, XXIV–XXVI which after drying in
air was purified by crystallization from aqueous ethanol.
2,3,5,6-Tetrabromo-2-nitrophenol (IX). Yield 61%,
mp 196°C (mp 195°C [4]). IR spectrum, ν, cm–1: 3472 m,
1535 v.s, 1369 m, 1412 m, 1269 m, 941 w, 891 w. 13C NMR
spectrum, δ, ppm: 115.2, 118.1, 118.3, 130.7, 142.6, 147.1.
Found, %: C 15.78; H 0.26; N 3.06. C6HBr4NO3. Calcu-
lated, %: C 15.85; H 0.22; N 3.08.
Reactions of tetrabromohydroxybenzoic
acids V, VI with NaNO2 in glacial acetic acid.
General procedure. To a solution of 1.59 g (3.5 mmol)
of hydroxybenzoic acid V or VI in 50 ml of glacial
CH3COOH while stirring at 20°C was added by small
portions 2.42 g (35 mmol) of NaNO2 within 2 h. The reac-
tion mixture was stirred for 1 h more and poured into 200
ml of 10% solution of Na2CO3. The separated precipitate
was filtered off and dissolved in 30 ml of CH2Cl2. The
organic solution was washed with a saturated solution of
NaHCO3 (3 × 10 ml), with water, and dried with Na2SO4.
On removing the solvent in a vacuum of the water-jet
pump we obtained 0.89 g of light-yellow crystals of com-
pound X or 0.73 g of red-brown crystals of compound XI.
The mother liquor was acidified with concn. HCl till pH
1–2 and was diluted with water till 500 ml, then it was
extracted with ethyl ether (5 × 50 ml.) The combined ether
extracts were washed with water, dried with Na2SO4, the
solvent was evaporated. We obtained 0.08 g of a mixture
of tetrabromonitrophenols VIII, IX in a ratio 2:1 from
acid V and 0.20 g of the mixture in a ratio 1:3 from acid
VI. Compounds VIII, IXwere identified by methods
of TLC, IR and 13C NMR spectroscopy; their relative
2,3,5,6-Tetrabromo-p-quinone monooxime (XXII).
Yield 95%, mp 115–116°C (decomp.). IR spectrum, ν, cm–1:
3480 m, 1643 v.s, 1500 s, 1415 s, 1130 s, 868 m, 652 m.
13C NMR spectrum (CDCl3), δ, ppm: 124.5 (2C), 128.5
(2C), 151.8 (1C), 168.2 (C=O). MALDI spectrum: m/z
435.2561 [M + H]+. C6HBr4NO2. Calculated M 435.7517.
2-Bromo-p-quinone monooxime (XXIV). Yield
55%, mp 140–141°C (decomp.). IR spectrum, ν, cm–1:
3198 m, 3071 w, 1635 v.s, 1620 v.s, 1419 m, 1261 m,
1
1207 m, 1026 s, 871 m. H NMR spectrum, δ, ppm:
6.63 d (1H, H5, J 8.5 Hz), 7.54 d.d (1H, H6, J 2.3, 8.5 Hz),
8.11 d (1H, H2, J 2.3 Hz). 13C NMR spectrum, δ, ppm:
124.1, 128.0, 138.4, 145.5, 149.2, 168.3 (C=O). Found,
%: C 35.50; H 2.22; N 6.81. C6H4BrNO2. Calculated, %:
C 35.67; H 2.00; N 6.93.
1
content in the mixtures was determined by H NMR
spectroscopy after the quantitative conversion into the
corresponding nitroanisoles XX, XXI by the procedure
described above for compounds XII, XIII.
2,3,5,6-Tetrabromo-p-quinone diazide (X). Yield
82%, mp 132–133°C (decomp.). IR spectrum, ν, cm–1:
2130 v.s, 1682 m, 1604 v.s, 1535 s, 1388 m, 1280 s,
2,6-Dibromo-p-quinone monooxime (XXV). Yield
89%, mp 156–157°C (decomp.). IR spectrum, ν, cm–1:
3186 m, 3074 m, 1635 v.s, 1543 m, 1419 m, 1261 v.s,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 8 2012

FADIN et al.
1070
1057 m, 1014 m, 875 m, 717 m. 1H NMR spectrum, δ,
ppm: 8.05 s (2H, H2,6). 13C NMR spectrum, δ, ppm: 126.0
(2C), 133.4 (2C), 148.8 (1C), 173.1 (C=O). Found, %:
C 25.50; H 1.20; N 4.81. C6H3Br2NO2. Calculated, %:
C 25.65; H 1.08; N 4.99.
was subjected to column chromatography on silica gel
to give ~50 mg of yellow crystals, presumably, a mixture
of dinitrophenols XXXI, XXXII. 13C NMR spectrum,
δ, ppm: 105.3, 117.7, 119.1, 119.5, 139.8, 141.4, 145.6,
149.1, 153.6, 157.2. Found, %: C 16.95; H 0.11; N 6.48.
C6HBr3N2O5. Calculated, %: C 17.13; H 0.24; N 6.66.
2,3,6-Tribromo-p-quinone monooxime (XXVI).
Yield 93%, mp 120–121°C (decomp.). IR spectrum, ν,
cm–1: 3260 br.m, 3063 w, 1643 v.s, 1531 m, 1393 m,
1292 m, 1200 m, 1064 s, 906 m, 733 w. 1H NMR spec-
trum, δ, ppm: 8.26 s (1H, H5). 13C NMR spectrum, δ,
ppm: 126.3, 128.8, 134.7, 136.9, 147.1, 172.0 (C=O).
MALDI spectrum: m/z 357.1143 [M + H]+. C6H2Br3NO2.
Calculated M 357.8413.
REFERENCES
1. Shishkin, V.N. and Fadin, M.V., Zh. Org. Khim., 2008,
vol. 44, p. 697.
2. Pfanz, H. and Dorn, H., Arch. Pharm., 1956, vol. 289, p. 651.
3. Larkin, H.F., Stuart, A.P., and Twiss, D., J. Org. Chem.,
1940, vol. 62, p. 1237.
4. Harrison, C.R. and McOmie, J.F.W., J. Chem. Soc. C, 1966,
p. 997.
5. Tee, O.S., Iyengar, N.R., and Kraus, B., J. Org. Chem.,
1985, vol. 50, p. 973.
6. Hussey, A.S. and Wilk, I.J., J. Am. Chem. Soc., 1950,
vol. 72, p. 830.
7. Belyaev, E.Yu. and Gidaspov, B.V., Aromaticheskie nitro-
zosoedineniya (Aromatic Nitrocompounds), St. Petersburg:
Teza, 1996.
8. Tedder, J.M. and Theaker, G., J. Chem. Soc., 1959, p. 257.
9. Nemodruk,A.A., Zh. Obshch. Khim., 1958, vol. 28, p. 1082.
10. Nemodruk,A.A., Zh. Obshch. Khim., 1956, vol. 26, p. 3283.
11. Tedder, J.M., Tetrahedron, 1959, vol. 5, p. 288.
12. Jacquesy, J.-C. and Jouannetaud, M.-P., Tetrahedron Lett.,
1982, vol. 23, p. 1673.
13. Reverdin, F., Ber., 1896, vol. 29, p. 2595.
14. Perrin, C.L. and Skinner, G.A., J. Am. Chem. Soc., 1971,
vol. 93, p. 3389.
Pentabromophenol (XXX). a. To a mixture of 35 ml
(12.6 g, 687 mmol) of dry Br2 and 3 g (11.2 mmol) of
anhydrous AlBr3 was added dropwise within 16.28 g
(58.1 mmol) of anisole with intermittent stirring. The
reaction mixture was kept for 12 h more at 20°C, then
the excess bromine was distilled off, the solid product
was washed with 5% solution of Na2SO3 till complete
decoloration, and it was extracted with hot 10% NaOH
solution (6 × 50 ml). The hot solution was filtered through
a folded filter, the filtrate was neutralized with concn.
HCl to a weakly acidic reaction by an indicator paper.
The separated precipitate was filtered off, washed with
water on the filter, and dried in air. Yield 24.2 g (90%),
mp 223–224°C (CH3COOH) (mp 230°C [24]). IR spec-
trum, ν, cm–1: 3414 C, 1516 m, 1346 v.s, 1277, 1196 m,
933 w, 682 w. 13C NMR spectrum, δ, ppm: 115.6 (2C),
118.1 (1C), 127.4 (2C), 152.5 (1C). Found, %: C 14.62;
H 0.42. C6HBr5O. Calculated, %: C 14.75; H 0.21.
15. Nesmeyanov, A.N. and Ioffe, S.T., Zh. Obshch. Khim.,
1941, vol. 11, p. 393.
16. Robertson, W., J. Chem. Soc., 1902, vol. 81, p. 1482.
17. Earle, R.B. and Jackson, H.L., J. Am. Chem. Soc., 1906,
vol. 28, p. 111.
18. Sint. Org. prep., 1949, vol. 2, p. 185.
19. Guben, I., Metody organicheskoi khimii (Methods of Or-
ganic Chemistry), Leningrad: Goskhimizdat, 1949, vol. 4,
no. 1, p. 317.
20. Yamagishi, H., Matsumoto, K., Iwasaki, K., Miyazaki, T.,
Yokoshima, S., Tokuyama, H., and Fukuyama, T.,Synth.
Commun., 1984, vol. 10, p. 2369.
21. Kohn, M. and Krasso, O., J. Org. Chem., 1946, vol. 11,
p. 641.
b. Similarly phenetole was brominated. Yield 93%,
mp 224–225°C (CH3COOH).
Reaction of pentabromophenol (XXX) with NaNO2
in glacial acetic acid. To a solution of 1 g (2 mmol)
of pentabromophenol (XXX) in 150 ml of glacial
CH3COOH was added at stirring at 20°C with small
portions within 5.5 h 1.38 g (20 mmol) of NaNO2, and
the stirring was continued for 0.5 h more. The reaction
mixture was diluted with water to 500 ml. The separated
precipitate was filtered off and dried in air. This pre-
1
cipitate (0.7 g) according to the H NMR spectrum of
anisoles obtained from it consisted of unreacted penta-
bromophenol (XXX) and nitrophenols in a molar ratio
0.6 : 1.4 : 1.0. By means of flash-chromatography 0.2 g
(22%) of compound VIII was isolated in the individual
state. The filtrate was extracted with ethyl ether (5 ×
50 ml). The combined extracts were dried with Na2SO4
and evaporated. We obtained 0.18 g of solid residue that
22. Robertson, W., J. Chem. Soc., Perkin Trans., 1902, vol. 81,
p. 1475.
23. Shishkin, V.N., Tanaseichuk, B.S., Lapin, K.K., Ivkina,A.A.,
and Butin, K.P., Zh. Org. Khim., 1984, vol. 20, p. 2588.
24. Garman, J.A., Mamuzic, R.I., McDonald, R.B., Sands, J.L.,
and Thompson, G., Swiss Patent 647491, 1985; Ref. Zh.
Khim., 1985, 24N144P.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 8 2012