Synthesis of N-adamantylated mononitro derivatives of aromatic amines in trifluoro- and dichloroacetic acids

Full text of DOI:10.1134/S1070363210030321

ISSN 1070-3632, Russian Journal of General Chemistry, 2010, Vol. 80, No. 3, pp. 545–547. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © V.G. Tsypin, V.A. Polukeev, 2010, published in Zhurnal Obshchei Khimii, 2010, Vol. 80, No. 3, pp. 517–518.
LETTERS
TO THE EDITOR
Synthesis of N-Adamantylated Mononitro Derivatives
of Aromatic Amines in Trifluoro- and Dichloroacetic Acids
V. G. Tsypin and V. A. Polukeevb
a
a
Federal State Unitary Enterprise “Russian Scientific Center Applied Chemistry”
pr. Dobrolyubova 14, St. Petersburg, 197198 Russia
phone: (812)4999849
fax: (812)3256648
E-mail: vgtsipin@yandex.ru
Closed Corporation “Vekton”
b
pr. Akad. Pavlova 12, St. Petersburg, 197376 Russia
phone: (812)3275095
fax: (812)3216777
e-mail: cyclic@peterlink.ru
Received September 17, 2009
DOI: 10.1134/S1070363210030321
We have studied earlier alkylation of nitro-
derivatives of aromatic amines with 1-adamantanol I
in sulfuric, phosphoric acids, acetic and phosphoric
acids mixture. It was shown that in some cases
reversible character of N-alkylation in strong protic
acids results in N-adamantylation products along with
C-substitution products in yields not exceeding 22% [1].
Therefore we thought that it is reasonable to study
the use of protic acids with lower acidity to increase
the selectivity and yield of the practically useful
adamantylation products.
It was reported [2] that the trifluoroacetic acid was
used as a medium and catalyst, and 1-(trifluoro-
acetoxy)adamantane II, as alkylating agent. The tri-
fluoroacetic acid was shown to be successfully applied
in the alkylation reactions with secondary and tertiary
alcohols of amides, ureas, nitrogen-containing hetero-
cycles, and some others compounds [3–5].
We showed that nitroanilines III–V react smoothly
with 1-(trifluoroacetoxy)adamantane II in trifluoro-
acetic acid to form predominantly the corresponding
N-alkylation products VI–VIII. The reaction with the
+
least basic 2-nitroaniline III (рK
–0.31, –0.26 [7,
ВН
8]) proceeds even at 18–20ºС and yields within 5 days
a mixture of N-(1-adamantyl)-2-nitroaniline VI and 4-
(
5
1-adamantyl)-2-nitroaniline IX in the ratio 94.3 to
1
.7 % (mass) respectively (by Н NMR). Recrystal-
lization from 80% aqueous 2-propanol provides
individual product VI in 58.7–61.4% yield. Any
conversion of 3-nitro- and 4-nitroanilines (IV, V)
+
(
рK
2.46 and 0.97, 1.00 respectively [7–9]) did not
ВН
occur in 3 days at this temperature. However, at 70–
5ºС compounds IV and V form only N-adamantyl
derivatives VII, VIII in yields of 73.9–75.1 and 86.8–
7.9 % respectively. C-Substituted products were not
formed.
7
8
Here we report on the study of the alkylation of 2-
The reactivity of substrates in the adamantylation
nitro-, 3-nitro- and 4-nitroanilines III–V with 1-(tri-
reaction decreases with the growth of the basicity of
the studied compounds. This reaction gives rise
predominantly to N-adamantylated products.
fluoroacetoxy)adamantane II. The acidity function рK
А
of trifluoroacetic acid, catalyst and medium, is 0.52
[
6]. Unlike 1-adamantanol I, the conversion of the
Therefore, the use of ester II as reagent and
trifluoroacetic acid as a medium and catalyst provides
a high reaction selectivity and good yields of the target
compounds VI–VIII.
start-ing ester II in trifluoroacetic acid does not result
in water formation, and as a consequence leads to no
changes in the medium acidity in the course of the
reaction.
5
45

5
46
TSYPIN, POLUKEEV
NH2
NO2
NH
NH2
NO2
Ad
+
Ad OC(O)CF
3
+
CF COOH
3
NO2
Ad
III
II
VI
IX
NH2
Ad NH
+
II
3
R COOH
R1
R1
R2
R2
VII, VIII
IV, V
Ad =
1
2
2
1
3
R = NO R = H (IV, VII); R = NO R = H (V, VIII); R = CF CHCl .
2
,
2,
3,
2
Aiming to extend a scope of protic acids for the
filtered off, washed with 2×100 ml of hot water (50–
55ºС), and dried. Compounds VII and VIII prepared
in trifluoroacetic acid do not require additional
purification. N-(1-Adamantyl)-2-nitroaniline VI was
purified by recrystallization from 80% aqueous solu-
tion of 2-propanol.
adamantylation reaction of highly basic amines, we
considered dichloroacetic acid having even lower
acidity (рK 1.33) [6]. 3-Nitroaniline IV reacts with 1-
А
(
trifluoroacetoxy)adamantane II in dichloroacetic acid
to give only N-(1-adamantyl)-3-nitroaniline VII. Yield
of the recrystalled product VII reaches 42.7%.
Reaction was carried out at 70–75ºС for 30 h using the
molar ratio ester II–acid 1 : 15. Therefore, the use of
dichloroacetic acid results in the acid-catalyzed
adamantylation of 3-nitroaniline IV, but leads to the
decrease in purity and yield of the target product.
Reaction of 3-nitroaniline IV with ester II in
dichloroacetic acid was performed as mentioned
above. The reaction temperature is 70–75ºС, reaction
time 30 h. The isolated crude product was recrystalled
from 80% aqueous solution of 2-propanol.
1
The Н NMR spectra and melting points of the
Reaction of nitroanilines III–V with 1-(trifluoro-
recrystalled products are consistent with those of the
acetoxy)adamantane (II). To a solution of 11.5 ml
1
samples obtained by procedure [1]. The Н NMR
(
0.15 mol) of trifluoroacetic acid were added in
spectra were recorded on a Bruker WM-400
succession 2.48 g (10 mmol) of ester II and 1.38 g
instrument using DMSO-d as solvent and ТМS as
6
(
10 mmol) of nitroaniline III–V. This mixture was
internal reference.
allowed to stand under stirring. The solvent excess was
removed in a vacuum. The residue was mixed with
1
-(Trifluoroacetoxy)adamantane II was obtained by
procedure [2]. Fraction with boiling temperature 91–
2ºС (7–8 mm Hg) was used.
2
0 ml of 2-propanol heated to 75–80ºС and poured
9
into 200 ml of water. The mixture was treated with
1
0% aqueous NaOH to рН 8, refluxed for 10–20 min,
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after alkalinizing and refluxing. The precipitate was
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 80 No. 3 2010

SYNTHESIS OF N-ADAMANTYLATED MONONITRO DERIVATIVES
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