Synthesis of methyl 5(6)-(4-aminophenoxy)-and 5(6)-(2-aminophenoxy)-2- benzimidazolyl carbamates and their biological properties

Article abstract of DOI:10.1023/B:RUJO.0000010185.19571.76

A procedure was developed for preparation of methyl 5(6)-(4-aminophenoxy)- and 5(6)-(2-aminophenoxy)-2-benzimidazolyl carbamates by reaction of 3,4,4′-triaminodiphenyl or 3,4,2′-triaminodiphenyl ethers respectively with methyl cyanocarbamate in water solution in the presence of 7-10 molar excess of acetic acid. The helminthicidal properties, embryotoxicity, and overall toxicity of compounds obtained were estimated.

Full text of DOI:10.1023/B:RUJO.0000010185.19571.76

Russian Journal of Organic Chemistry, Vol. 39, No. 8, 2003, pp. 1154 1160. Translated from Zhurnal Organicheskoi Khimii, Vol. 39, No. 8, 2003,
pp. 1225 1231.
Original Russian Text Copyright
2003 by Pilyugin, Mikhailyuk, Kosareva, Chikisheva, Kiseleva, Kuznetsova, Vorobyeva, Klimakova.
Synthesis of Methyl 5(6)-(4-Aminophenoxy)-
and 5(6)-(2-Aminophenoxy)-2-benzimidazolyl Carbamates
and Their Biological Properties
V. S. Pilyugin, A. N. Mikhailyuk, V. M. Kosareva, G. E. Chikisheva, G. V. Kiseleva,
S. L. Kuznetsova, T. P. Vorobyeva, and E. V. Klimakova
Research Technological Institute of Herbicides and Plant Growth Control Compounds,
Academy of Sciences of Bashkortostan, Ufa, 450025 Russia
Received November 14, 2001
Abstract A procedure was developed for preparation of methyl 5(6)-(4-aminophenoxy)- and 5(6)-(2-
aminophenoxy)-2-benzimidazolyl carbamates by reaction of 3,4,4‘-triaminodiphenyl or 3,4,2‘-triaminodi-
phenyl ethers respectively with methyl cyanocarbamate in water solution in the presence of 7 10 molar
excess of acetic acid. The helminthicidal properties, embryotoxicity, and overall toxicity of compounds
obtained were estimated.
It is known [1] that 4 -acetylamino-3,4-diamino-
diphenyl ether (I) and 2 -acetylamino-3,4-diamino-
diphenyl ether (II), semiproducts at production of
3,4,4 -triaminodiphenyl (III) or 3,4,2 -triaminodi-
phenyl (IV) ethers and helminthicidal preparations
based thereon are obtained from sodium 4-acetyl-
amino-(V) or 2-acetylamino-(VI)phenolates by con-
densation with 2-nitro-5-chloroaniline in DMSO
(DMF) in the presence of anhydrous potassium
carbonate at heating. The synthesis of triaminodi-
phenyl ethers III and IV can be described by
Schemes 1 and 2.
(1)
(2)
In keeping with Scheme 1 diphenyl ether III is
obtained from a solution of 4-acetylamino-3,4-di-
aminodiphenyl ether I by boiling for 1 2 h in 5%
water solution of hydrochloric acid under a nitrogen
atmosphere.
Along the Scheme 2 were prepared both isomers of
triaminodiphenyl ethers III and IV [3].
We developed a preparation procedure for tri-
aminodiphenyl ethers III and IV by reaction of
1070-4280/03/3908-1154$25.00 2003 MAIK Nauka/Interperiodica

SYNTHESIS OF METHYL 5(6)-(4-AMINOPHENOXY)-...
1155
acetylaminophenol (V) with more accessible 4-nitro
and 2-nitochlorobenzenes respectively. The reaction
is carried out in DMF in the presence of anhydrous
potassium carbonate and furnishes 4-acetylamino-4 -
nitro- and 4-acetylamino-2 -nitrodiphenyl ethers re-
spectively. The 4-acetylamino-4 -nitro- and 4-acetyl-
amino-2 -nitrodiphenyl ethers obtained then undergo
nitration with the concn. HNO3 in chloroform or
acetic acid respectively, and the formed 4-acetyl-
amino-3,4 -dinitro-(I) and 4-acetylamino-3,2 -di-
nitrodiphenyl ethers are hydrolyzed by alkaline solu-
tion in 2-propanol. The isolated 4-amino-3,4 -dinitro-
and 4-amino-3,2 -dinitrodiphenyl ethers are reduced
with hydrazine hydrate in the presence of iron(III)
chloride and activated carbon in a mixture of ethylene
glycol and dioxane or in butanol affording triamino-
diphenyl ethers III and IV [4, 5].
It is known [7, 8] that preparation of derivatives at
the nitrogen atom in position 1 of the benzimidazole
ring provides a possibility to modify certain char-
acteristics of benzimidazolyl carbamates (solubility,
activity, biological availability etc.).
The presence of a free amino group in methyl
2-benzimidazolyl carbamates VII and VIII gives
additional opportunities for modifying these char-
acteristics by introducing various substituents to the
amino group.
Besides the procedures are known for replacement
an amino group on aromatic compounds by a hydro-
gen [9 11]. However this conversion can be feasible
only if a cheaper method would be developed for
production of methyl 2-benzimidazolyl carbamates
VII and VIII than the known procedures [1, 6].
These procedures were based on selective hydrolysis
at high temperature of methyl 5(6)-(4-acetylamino-
phenoxy)- and 5(6)-(2-acetylaminophenoxy)-2-benz-
imidazolyl carbamates in the presence of strong
mineral acids (hydrochloric, sulfuric or phosphoric
acids). The course of reaction here is not un-
ambiguous for the urethane group partially suffers
hydrolysis (Scheme 3).
The preparation procedures of methyl 5(6)-(4-
aminophenoxy)-2-benzimidazolyl carbamate (VII) and
methyl
5(6)-(2-aminophenoxy)-2-benzimidazolyl
carbamate (VIII) and their acetyl derivatives were
published in [1, 6], their high helminthicidal effici-
ency was shown but no data were mentioned concern-
ing the embryotropic activity and the theurapeutic
index.
(3)
Apparently in [1, 6] the synthesis of methyl 2-benz- for synthesis of methyl 2-benzimidazolyl carbamates
VII and VIII with the use as initial compounds more
easily available triaminodiphenyl ethers III and IV
is very urgent.
imidazolyl carbamates VII and VIII was purposefully
performed from triaminodiphenyl ethers III and IV.
The basicity of aniline is known [12] to exceed that of
1,2-phenylenediamine, and therefore the closure of
the benzimidazole ring may compete with addition
to the amino group of the aniline fragment of the
molecule (in positions 4 and 2) of the methyl cyano-
carbamate. Therefore the amino group requires pre-
liminary protection. However the synthesis of initial
monoacylated triaminodiphenyl ethers I and II has
significant drawbacks as compared to our method of
preparation of nonacylated triaminodiphenyl ethers
III and IV. Therefore the development of procedures
The reaction of 1,2-phenylenediamine with methyl
cyanocarbamate (a product obtained from calcium
cyanoamide and methyl chloroformate) resulting in
formation of the benzimidazole ring proceeds in
acid medium. The acid medium is necessary for
conversion of the calcium salt of methyl cyano-
carbamate into the active form. On the other hand,
1,2-phenylenediamine in acid medium can be present
in monoprotonated or diprotonated form depending
on the pH.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 8 2003

1156
PILYUGIN et al.
Therefore the medium should be moderately acidic
(pH 3.5 4.5) for the methyl cyanocarbamate should
be nonionized, and 1,2-phenylenediamine should not
lose all its nucleophilicity (Scheme 4).
(4)
In the molecules of triaminodiphenyl ethers III and
IV in contrast to 1,2-phenylenediamine three nucleo-
philic sites are present: the nitrogen of the aniline
fragment and the nitrogens of the 1,2-phenylenedi-
amine fragment. The selective preparation of methyl
2-benzimidazolyl carbamates VII and VIII requires
deactivation of the most basic nitrogen in the aniline
fragment.
We suggested that just in the acid medium the
strongest nucleophilic site could be completely
blocked providing it would be totally protonated.
Same as in the case of 1,2-phenylenediamine, the
triaminodiphenyl ethers III and IV can conserve
sufficient reactivity toward the methyl cyanocarb-
amate only if their molecules are monoprotonated
(Scheme 5).
(5)
It should be taken into account that the cyclization
of triaminodiphenyl ethers III and IV in the presence
of methyl cyanocarbamate occurs with ammonia
liberation; the latter can bind the acid necessary for
blocking the aniline nitrogen. Therefore it is neces-
sary to add acid into the reaction mixture during the
course of the process to maintain the optimum pH.
(7)
Triaminodiphenyl ethers III and IV are relatively
weak bases, and since the synthesis is carried out in
diluted acid water solutions the following equilibria
may exist between the different protonated forms of
the ethers (Schemes 6 and 7).
The equilibrium position depends not only on dilu-
tion but also on the strength of the acid used for
protonation. At the use of a strong acid, e.g., of
hydrochloric acid, at equimolar ratio of triaminodi-
phenyl ether acid the ethers would exist prevailingly
in form A; at the ratio 1: 2 the form B would
dominate.
At the use of weak acids, e.g., of acetic acid, the
reaction mixture would contain a lot of nonprotonated
forms of triaminodiphenyl ether (Scheme 6). At the
use of excess acetic acid the equilibrium almost would
not shift to B formation.
(6)
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 8 2003

SYNTHESIS OF METHYL 5(6)-(4-AMINOPHENOXY)-...
1157
(8)
Thus the preparation of methyl 2-benzimidazolyl
carbamates VII and VIII from the corresponding
triaminodiphenyl ethers III and IV requires the
application of weak acids, for instance, of acetic acid.
But the acid should be used in a large excess to avoid
the formation of a considerable amount of a side
product IX (Scheme 8).
The obtained by us methyl 2-benzimidazolyl carb-
amates VII and VIII were tested for helminthicidal
activity and embryotropic properties at the laboratory
of cattle therapy of the Skryabin Russian Central
Helminthology Institute. The tests confirmed the high
helminthicidal efficiency of benzimidazolyl carbamate
1
VII: It showed 100% efficiency at a dose 10mg kg ,
whereas benzimidazolyl carbamate VIII at a dose
20 mg kg was only to 70% efficient against gastro-
enteric strongyloidosis of sheep. However benzimid-
Actually we failed to find optimal preparation
conditions for methyl 2-benzimidazolyl carbamates
VII and VIII of good quality and in a high yield
when using hydrochloric acid. For instance, at excess
hydrochloric acid the rate of the reaction was low; on
the contrary, at small amount of the acid the conver-
sion of the initial ethers III or IV was fast but the
products contained many impurities. The side product
IX we succeeded to convert into the target compound
by prolonged boiling with hydrochloric acid, but the
process was accompanied by hydrolysis of the
urethane group in the benzimidazole part of the
molecule.
1
azolyl carbamate VII possesses strong embryotoxic
1
properties at the therapeutic dose 10 mg kg ;
embryotoxic properties of methyl ester VIII are
weakly pronounced. Besides benzimidazolyl carb-
amate VII possesses also a general toxicity, but benz-
imidazolyl carbamate VIII was nontoxic.
The tests demonstrated that the presence of a free
amino group in methyl 5(6)-(4-aminophenoxy)-(VII)
and 5(6)-(2-aminophenoxy)-2-benzimidazolyl carb-
amates (VIII) supplies them with unwanted biological
properties that should be removed either by deamina-
tion or by preparation of derivatives at the amino
group possessing necessary biological activity.
At the 3 5 molar excess of acetic acid with respect
to triaminodiphenyl ether III or IV the synthesis was
accompanied with formation of the side product IX.
Only at application of 7 10 molar excess of acetic
acid we succeeded in preparation of the target methyl
esters VII and VIII in high yield (80 85%) and with
trace impurities.
EXPERIMENTAL
Synthesis of 4-acetylamino-4 (2 )-nitrodiphenyl
ether. To 1.2 l of DMF at vigorous stirring was
added 339.2 g (2.24 mol) of 4-acetylaminophenol,
321.4 g (2.04 mol) of 4-nitrochlorobenzene or 2-nitro-
chlorobenzene, and 345 g (2.45 mol) of anhydrous
potassium carbonate. The reaction mixture was heated
to 145 150 C and was vigorously stirred at this
temperature for 8 10 h. The completion of reaction
was monitored by disappearance of nitrochloro-
benzene. If a residue of nitrochlorobenzene remained
in the reaction mixture, a small amount of 44% water
solution of sodium hydroxide was added thereto, and
the mixture was stirred for 1 h. After complete con-
In patent [1] where the preparation method is
described for methyl esters VII and VIII the methyl
5(6)-(4-aminophenoxy)-2-benzimidazolyl carbamate
(VII) is shown to be highly efficient helminthicide,
no worse than the most well-known preparation of
Hoehst Co. (Phenbendazole, Panakur). No data is
presented on the helminthicidal activity of methyl
5(6)-(2-aminophenoxy)-2-benzimidazolyl carbamate
(VIII), and the data on toxicity and embryotropic
properties of both benzimidazolyl carbamates VII and
VIII are also lacking.
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1158
PILYUGIN et al.
sumption of nitrochlorobenzene the reaction mixture
was poured into water, cooled to room temperature,
the precipitated 4-acetylamino-4 -nitrodiphenyl ether
or 4-acetylamino-2 -nitrodiphenyl ether was filtered
off, washed with 0.5 N alkali solution, with water,
and dried. 4-Acetylamino-4 -nitrodiphenyl ether and
4-acetylamino-2 -nitrodiphenyl ether were obtained in
93 and 95.6% yield respectively (518.1 and 533.4 g).
4-Acetylamino-2 -nitrodiphenyl ether: mp 128
129 C, Rf 0.30 (eluent benzene ethanol, 10:2).
Found, %: C 61.80; H 4.42; N 10.31. 4-Acetylamino-
4 -nitrodiphenyl ether: mp 153 154 C, Rf 0.36
(eluent benzene hexane, 3: 7). Found, %: C 61.78;
H 4.45; N 10.22. C14H12N2O4. Calculated, %:
C 61.76; H 4.44; N 10.29.
Synthesis of 4-amino-3,4 -dinitro- and 4-amino-
2 ,3-dinitrodiphenyl ethers. To 600 ml of 2-propan-
ol was added 123.9 g (0.39 ml) of 4-acetylamino-
3,4 -dinitrodiphenyl ether or 4-acetylamino-2 ,3-di-
nitrodiphenyl ether. The mixture was vigorously
stirred at 25 30 C, and gradually a solution of 16.5 g
(0.40 mol, 97%) of sodium hydroxide in 66 ml of
water was added thereto. Then the reaction mixture
was heated to 70 75 C, and it was vigorously stirred
at this temperature for 1.5 3.0 h. Then the reaction
mixture was poured into cold water, the separated
precipitate of 4-amino-3,4 -dinitrodiphenyl ether or
4-amino-2 ,3-dinitrodiphenyl ether was filtered off,
washed with water on the filter, and dried. 4-Amino-
2 ,3-dinitrodiphenyl ether (101,5 g) and 4-amino-
3,4 -dinitrodiphenyl ether (102.9 g) were obtained in
95 and 96.3% yield respectively. 4-Amino-3,4 -di-
nitrodiphenyl ether: mp 179 181 C, Rf 0.78 (eluent
benzene ethanol, 10:2). Found, %: C 52.30; H 3.21;
N 15.20. 4-Amino-2 ,3-dinitrodiphenyl ether: mp
162 163 C, Rf 0.53 (eluent benzene ethanol, 10:2).
Found, %: C 52.42; H 3.32; N 15.47. Calculated, %:
C 52.36; H 3.29; N 15.27.
Synthesis of 4-acetylamino-2 ,3-dinitrodiphenyl
ether. In 350 ml of acetic acid was added at stirring
163.2 g (0.60 mol) of 4-acetylamino-2 -nitrodiphenyl
ether. To the mixture was added 66 ml (0.70 mol) of
acetic anhydride, and then at vigorous stirring while
cooling with brine of temperature between +10 and
+15 C into the reactor was added dropwise within
40 50 min 77 ml (1.8 mol) of nitric acid (d
1
1.5 g ml , 90%). After addition the reaction mixture
Synthesis of 3,4,4 -triamino- and 2 ,3,4-tri-
aminodiphenyl ethers. The reduction of 4-amino-
2 ,3-dinitrodiphenyl and 4-amino-3,4 -dinitrodiphenyl
ethers was carried out in a glass four-neck reactor of
1 l capacity equipped with a stirrer, a thermometer,
a dropping funnel, and a reflux condenser connected
to a Dean-Stark trap. The trap was used when the
reaction was carried out in butanol. The required
temperature was maintained in the reactor by supply-
ing into the reactor jacket a heat carrier from an ultra-
thermostat.
was stirred for 20 25 min at 20 25 C, then heated to
40 45 C and vigorously stirred at this temperature
for 4 6 h more. The reaction progress was monitored
by TLC.
On disappearance from the reaction mixture of the
initial compound the content of the reactor was pour-
ed into cold water, the precipitate of 4-acetylamino-
2 ,3-dinitrodiphenyl ether was filtered off, thoroughly
washed on the filter with water, and dried. Yield of
dinitrodiphenyl ether 92% (175.1 g), mp 98 99 C,
Rf 0.56, of initial compound 0.30 (system benzene
ethanol, 10: 2). Found, %: C 53.05; H 3.52; N 13.28.
C14H11N3O6. Calculated, %: C 53.00; H 3.49;
N 13.24.
When the reaction was carried out in butanol the
water formed was removed from the reaction mixture
as an azeotrope with butanol and was collected in the
Dean-Stark trap where separation into a water and
butanol layers occurred. Together with water and
butanol hydrazine was also partially carried away and
in the trap it was distributed between the water and
organic layer. The water solution was removed into
a special receiver, and the alcoholic layer was
continuously returned into the reaction zone. The
hydrazine fraction lost with water is relatively small
and amounts to several percent.
Synthesis of 4-acetylamino-3,4 -dinitrodiphenyl
ether. To a suspension of 188.7 g (0.69 mol) of
4-acetylamino-4 -nitrodiphenyl ether in 950 ml of
chloroform was added 66 ml (0.7 mol) of acetic
anhydride and dropwise at 45 50 C 90 ml (2.1 mol)
1
of nitric acid (d 1.5 g ml ). The reaction mixture was
stirred at the same temperature for 6 h. Then 500 ml
of water was added, and the precipitate formed was
filtered off. We obtained 213 g (97%) of 4-acetyl-
amino-3,4 -dinitrodiphenyl ether, mp 121 123 C. Rf
0.7, of initial compound 0.36 (system benzene
ethanol, 10: 2). Found, %: C 52.98; H 3.46; N 13.30.
C14H11N3O6. Calculated, %: C 53.00; H 3.49;
N 13.24.
When the reduction was performed with hydrazine
hydrate to a solution of 63 g (0.216 mol) of 4-amino-
3,4 -dinitrodiphenyl ether in 210 ml of butanol was
added about 1.2 g (0.0045 mol) of FeCl3 6H2O
ground with 7.5 g of activated carbon. The mixture
was heated to 95 105 C (to boiling) for 30 min at
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 8 2003

SYNTHESIS OF METHYL 5(6)-(4-AMINOPHENOXY)-...
1159
passing through the reactor of a weak flow of nitro-
gen. Then at the same temperature within 4 6 h was
added dropwise 75 ml (1.5 mol) of hydrazine hydrate.
Thereafter the reaction mixture was heated at weak
reflux without stirring for 6 10 h till completion of
the reduction.
The analysis of mixtures of acetylaminophenol (or
aminophenol), nitrochlorobenzene, acetylaminonitro-
diphenyl ether, acetylaminodinitrodiphenyl ether, and
triaminodiphenyl ether was performed by HPLC on a
column with a reversed phase Rsil or Ultraspher ODS
in eluent system 65 vol% of methanol and 35 vol%
of water; to 1 l of this eluent was added 25 ml of 10%
solution of 18-crown-6 in methanol. The calculation
of chromatograms was performed by internal
normalization of peaks areas.
After completion of the reduction from the reaction
mixture was distilled in a vacuum in a nitrogen flow
the major part of butanol and the remnants of hydr-
azine. The residue was poured out from the reactor
into a cooled boiled water. After stirring from the
butanol water mixture slowly crystallized the tri-
aminodiphenyl ether which was washed with cold
water on the filter and then dried.
The analysis of crude methyl 5(6)-(4-aminophen-
oxy)- and 5(6)-(2-aminophenoxy)-2-benzimidazolyl
carbamates was carried out on liquid chromatograph
of Altex Co equipped with a pump of model 110, a
UV detector of model 153, a loop feeder of model
210 of 20 l volume, Hamilton microsyringes of
SNR type of 30, 50, and 100 l capacity, a stainless-
steel column 0.25 m long of internal diameter
4.6 mm.
The following reagents ratio are optimum for re-
duction in butanol: molar ratio of 4-amino-3,4 (2 ,3)-
dinitrodiphenyl ether to hydrazine (64 67%) is 1.0 :
(6.0 7.0), weight ratio of 4-amino-3,4 (2 ,3)-dinitro-
diphenyl ether to butanol is 1.0:(2.7 2.8). At these
conditions the yield of crude 3,4,4 -triamino- or
2 ,3,4-triaminodiphenyl ethers was 87 and 84%
respectively at content of the main product no less
than 95%.
The analysis of methyl 5(6)-(4-aminophenoxy)- or
5(6)-(2-aminophenoxy)-2-benzimidazolyl carbamates
in the reaction mixture was performed by TLC on
Silufol plates, visualization of spots by diazotization
and azocoupling with -naphthol. The other products
do not hamper the analysis.
3,4,4 -Triaminodiphenyl ether: mp 162 163 C, Rf
0.14, of initial compound 0.78 (system benzene
ethanol, 10: 1). Found, %: C 66.85; H 6.24; N 19.44.
C12H13N3O. Calculated, %: C 66.95; H 6.09;
N 19.52. 2 ,3,4-Triaminodiphenyl ether: mp 147
148 C, Rf 0,23, of initial compound 0.53. Found, %:
C 66.81; H 5.91; N 19.53.
The study was carried out under financial support
of the Russian Foundation for Basic Research (grant
no. 02-03-97911).
REFERENCES
Synthesis of methyl 5(6)-(4-aminophenoxy)- and
5(6)-(2-aminophenoxy)-2-benzimidazolyl
carb-
amates. To a suspension of 54 g (0.51 mol) of 77%
calcium cyanamide in 450 ml of distilled water at 38
41 C was added dropwise 49.9 g (40 ml, 0.52 mol)
of methyl chloroformate, the mixture was stirred for
1 h at this temperature, then filtered, and the residue
on the filter was washed with 60 ml of water. To a
solution of 58.1 g (0.27 mol) of 3,4,4 -triamino- or
2 -3,4-triaminodiphenyl ether in 200 ml of 2-propanol
and 110 ml of acetic acid was poured the above
obtained filtrate, and the mixture was boiled for 6 h.
We obtained 66.78 g (83%) of methyl 5(6)-(4-amino-
phenoxy)-2-benzimidazolyl carbamate. The yield of
methyl 5(6)-(2-aminophenoxy)-2-benzimidazolyl carb-
amate was 67.59 g (84%).
1. German Patent 2348104, 1973; Ref. Zh. Khim., 1975,
24O112.
2. Kosareva, V.M., Solonenko, I.G., Mikhailyuk, A.N.,
Sorokina, O.N., Demidov, N.V., and Volkova, G.N.,
USSR Inventor,s Certificate 1140433, 1983; Byull.
Izobr., 1985, no. 6.
3. Japan Patent 47-33333, 1972; Ref. Zh. Khim., 1973,
11N 146.
4. Pilyugin, V.C., Valitov, R.B., Kuznetsova, C.L.,
Kiseleva, G.V., Klimakova, E.V., Vorob,eva, T.P.,
and Sapozhnikov, Yu.E., Bash. Khim. Zh., 2000,
vol. 7, no. 4, p. 43.
5. Pilyugin, V.C., Kiseleva, G.V., Kuznetsova, C.L.,
and Chikisheva, G.E., Bash. Khim. Zh., 2001, vol. 8,
no. 1, p. 11.
6. Abuzar, S., Rao, K.V.B., Sharma, S., Gupta, S.,
and Katiyar, J.C., Indian J. Chem., 1985, vol. 24,
no. 2, p. 178.
Methyl 5(6)-(4-aminophenoxy)-2-benzimidazolyl
carbamate: mp 289 291 C (publ. mp 292 C, with a
flash [1]). Methyl 5(6)-(2-aminophenoxy)-2-benz-
imidazolyl carbamate: mp 272 274 C (publ. mp
276 C, with a flash [1]).
7. German Patent 2425704, 1975; Ref. Zh. Khim., 1976,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 8 2003

1160
17O140.
PILYUGIN et al.
11. Kornblum, N., Sintezy organicheskikh preparatov
(Organic Synthesis), Moscow: Inostr. Lit., 1952,
p. 203.
8. German Patent 2425705, 1975; Ref. Zh. Khim., 1976,
17O134.
9. Brewster, R.Q. and Roje, J.A., J. Am. Chem. Soc.,
1939, vol. 61, p. 2416.
10. Coleman, G.H. and Talbot, W.F., Organic Syntheses,
1943; Translated under the Title Sintezy organiche-
skikh preparatov, Moscow: Inostr. Lit., 1949.
12. Sergent, A.A., Konstanty ionizatsii kislot i osnovanii
(Ionization Constants of Acids and Bases), Moscow:
Khimiya, 1964, p. 138.
13. UK Patent 1239104, 1971; Ref. Zh. Khim., 1972,
2N 635.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 8 2003