One-pot N-acylation and N-alkylation of o-nitroaniline with saturated hydrocarbons in the presence of carbon monoxide

Article abstract of DOI:10.1016/j.mencom.2010.09.005

The first one-pot N-acylations and N-alkylations of o-nitroaniline with saturated hydrocarbons were performed in the presence of superelectrophiles; the role of CO in the alkylation with n-pentane is discussed.

Full text of DOI:10.1016/j.mencom.2010.09.005

Mendeleev
Communications
Mendeleev Commun., 2010, 20, 257–259
One-pot N-acylation and N-alkylation of o-nitroaniline
with saturated hydrocarbons in the presence of carbon monoxide
Irena S. Akhrem,* Dzhul’etta V. Avetisyan, Nikolai D. Kagramanov,
Pavel V. Petrovskii and Nadezhda E. Mysova
A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 119991 Moscow,
Russian Federation. Fax: +7 499 135 5085; e-mail: cmoc@ineos.ac.ru
DOI: 10.1016/j.mencom.2010.09.005
The first one-pot N-acylations and N-alkylations of o-nitroaniline with saturated hydrocarbons were performed in the presence of
superelectrophiles; the role of CO in the alkylation with n-pentane is discussed.
The selective syntheses of fine chemicals directly from alkanes
and cycloalkanes is an important problem of current organic
chemistry.1–4
Here, we report the N-acylation and N-alkylation of o-nitro-
aniline with n-pentane, cyclopentane (acylation only), norbornane,
trimethylenenorbornane (TMNB) and adamantane (AdH) with
or without CO in the presence of CX4·2AlBr3 (X = Br or Cl)
superelectrophiles (Scheme 1).
anilines are promising organic materials for nonlinear optics.10(b)–(d)
Nitroanilines are valuable precursors of anilines, which are
important intermediates in the preparation of dyes, pharma-
ceuticals, herbicides and pesticides.9,11
Here, the alkylation of nitroaniline with alkanes and cyclo-
alkanes, as well as nitroaniline acylation with n-pentane, endo-
TMNB and AdH, was performed for the first time. The acylation
of o-nitroaniline with cyclopentane and norbornane has been
briefly described previously.8 To perform acylation, o-nitroaniline
was added to an in situ generated acylium salt from RH and CO
in the presence of a superelectrophile CX4·2AlBr3 (X = Br or
Cl) in CH2Br2 (conditions for the generation of acylium salts
were specified elsewhere8), and the reactions were carried out
in an atmosphere of CO under the conditions shown in Table 1.
The structures of the products were proved by 1H and 13C NMR
spectroscopy and mass spectrometry (see Online Supplementary
Materials).
The simple and common methods of N-alkylation of amines
with saturated hydrocarbons have not been described. The tosyl-
amination of alkanes and cycloalkanes with tosylimidoiodo-
benzene, PhI=NTs, as the nitrene source catalyzed by Fe and Mn
porphyrins was ineffective and nonselective.5(a) More recently,
a similar approach with Cu- and, particularly, Ag-based catalysts
was found more successful. However, pentane and hexane
formed isomeric mixtures of corresponding R–NTs.5(b) The
synthesis of Ad'NH2 (Ad' is adamantyl or methyl adamantanes)
from Ad'H and NCl3 in the presence of promoted aluminum
halides was described.6(a),(b) The Ritter reaction was applied to
the preparation of amides from AdH and nitriles in the presence
of electrophiles.7 Recently, a new one-pot synthesis of amides
from amines, CO and saturated hydrocarbones has been reported.8
Nitroaniline was chosen as a model of a very weak N-nucleo-
phile, although its alkylation and acylation products (particularly,
with bi- and tricyclanes) may be interesting by themselves.
Aromatic amines are found in biologically natural products,
pharmaceuticals, dyes, materials with conductive and emissive
properties and ligands for transition-metal-catalyzed reactions.9
N-(1-Adamantyl)-2-nitroaniline is an intermediate in the syn-
thesis of 1,5-benzodiazepine, which is used as a gastrin and
cholecystokinin antagonist,10(a) while other N-adamantyl nitro-
Acylations of o-nitroaniline were carried out at temperatures
from –20 to +50 °C. The reactions proceeded selectively to
furnish a single product in 75–97% yield (with respect to E) for
cyclopentane, norbornane and endo-TMNB or only 27–30%
for pentane and AdH.
Nitroaniline probably enhances the stability of corresponding
acylium cations. Even at 35–50 °C, 60–75% yields of acylation
products were reached in the reactions of o-nitroaniline with
RCO+ generated from norbornane and cyclopentane. On the
contrary, in the absence of nitroaniline, the reactions of these
cycloalkanes with CO in the presence of CX4·2AlBr3 give
carbonyl-containing products in very poor yields, if at all, even
at 20 °C. To perform the alkylation, o-nitroaniline was added
to a reaction mixture containing CX4·2AlBr3 and a saturated
hydrocarbon. The alkylation temperature was varied from 0 to
50 °C. The yields of the alkylated products were 67–87%, except
for cyclopentane, which did not react at temperatures from –20
to 35 °C.
RH
RCO+
R+ + CO
Note that the previously described adamantylation of nitro-
substituted aromatic amines with 1-AdOH in protic acids was
shown to proceed inefficiently. For example, the reaction of
o-nitroaniline with 1-AdOH in H2SO4, gave N-adamantyl o-nitro-
aniline in ~13–19% yields for five to six days, while in a mixture
of H3PO4 and AcOH, both N- and C- alkylated products were
formed.6(c)
The selectivity and regioselectivity of both alkylation and
acylation reactions leading to the formation of the products con-
taining tert-pentyl, cyclopentyl, 2-norbornyl and 1-adamantyl
groups from n-pentane, cyclopentane, norbornane and AdH,
NO2
NH2
NO2
NHCOR
NO2
NHR
RH = n-pentane, cyclopentane, norbornane,
trimethylenenorbornane and adamantane
Scheme 1
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© 2010 Mendeleev Communications. All rights reserved.

Mendeleev Commun., 2010, 20, 257–259
Table 1 Alkylation and acylation of o-nitroaniline (I) with RH and the
{RH + CO} system in the presence of CBr4·2AlBr3 (E) in CH2Br2 solution.a
O2N
H2N
tert-C5H11CO+
Conditions for reactions
Product yield
(% on E)b
+
of RCO+ with I
Entry RH
20 °C, 12 h
CO 20 °C, 12 h
Alkylation
product
Acylation
product
T/°C t/h [I]:[E] CO
1
2
3
n-Pentane
–20 1.5 3:1
1:1
20 12 2:1
+
–
–
27
0
18
0
O2N
O2N
0
1
4 (R = Bu)
11 (R = C5H11
72
87
HN
tert-C5H11
HN
tert-C5H11
)
4
5
20 12 2:1
+
+
27
13
35
1
1
2:1
1:1
11%
+
72%
+
6
7
8
9
10
–20
0
+
–
–
+
+
0
0
0
0
0
50
0.5 1:1
O2N
O2N
0
0
35
4
2
1
1:1
1:1
1:1
97
60
BuHN
HN
tert-C5H11
11
12
13
14
15
0
0
35
35
50
1
2
1
1
1
1:1
1:1
1:1
1:1
1:1
–
–
–
+
+
47
81
44
—
—
4%
O
27%
75
65
Scheme 3
change in the reaction conditions (see entries 18 and 21 in
Table 1) led to nonselective alkylation resulting in three isomeric
alkylation products. Using different precursors of the trimethylene-
norbornyl cation in the Ritter reaction with acetonitrile initiated
by BF3 in liquid SO2, Bakke and Knudsen obtained amide (2,
R = NHCOMe) in 95% selectivity, while amides 3 were the
main products in similar reactions with other nitriles and electro-
philes.13 The formation of less stable isomers 2 (R = NHC6H4NO2,
NHCOMe) is probably due to both a large flexibility of the
trimethylenenorbornyl group and a low difference between the
stabilities of cations 1' and 2' (~4.8 kcal mol† compared with
the values of 9–12 kcal mol–1 for tertiary and secondary alkyl
cations14).
Surprisingly, the treatment of the in situ generated tert-C5H11CO+
with nitroaniline under CO atmosphere at 35 °C for 1 h or at 20 °C
for 12 h afforded an alkylation product, tert-C5H11NHC6H4NO2,
in 87 or 72% yield, respectively, while the yields of the expected
acylation product, tert-C5H11CONHC6H4NO2, were only 13–27%.
In the absence of CO, both reactions of nitroaniline with
n-pentane and tert-C5H11CO+ were inefficient and nonselective.
In other words, a high yield of the alkylation product with
n-pentane can be achieved if the acylium cation instead of alkane
is used as the precursor of the tert-amyl cation. Thus, the role of
CO, which, obviously, does not participate in the formation
of alkylation products, is very important. We believe that the
effect of CO consists in the maintaining low concentration of
the amyl cations in the media. As the result, the alkylation
of nitroaniline occurs, probably, rather than alkylation of con-
jugated olefins with the amyl cation resulting in the formation
of oligomers and fragmentation products. The presence of CO
may be important for other reactions with the participation of
cations that are prone to cracking.
16
17
Adamantane
0
0
1
4
1:1
2:1
–
+
75c
35
30
18
19
20
21
0
0
10
0
1
1
1
2
1:1
1:1
1:1
2:1
–
+
+
–
67
76
62
28d
aIn entries 13 and 20, E = CCl4·2AlBr3; [E] = 0.87–0.98 mol dm–3, except
for entry 15, where [E] = 0.34 mol dm–3. bAccording to GC data. cYield of
an isolated product. dA mixture of three isomers in a ratio of 1:1.4:2.7.
respectively, is obviously due to a highly preferable formation
of a single carbocationic species and the respective acylium cation
from these substrates under the employed conditions (similar
to the reported reactions4). An entirely different behaviour
was observed for TMNB. According to the previously reported
data,4(a),12 the exclusive formation of exo isomer 1 was observed
in case of o-nitroaniline acylation. On the contrary, exo isomer
2 was the product of o-nitroaniline alkylation. Under optimal
conditions (Table 1), both 1 and 2 were formed selectively.
7
7
10
10
5
5
4
4
6
6
9
9
1
1
2
2
3
3
8
8
HN
NO2
O
N
H
NO2
1
2
The order of stability for trimethylenenorbornyl cations was
reported13 to be 3' > 1' >> 2' (Scheme 3).
Thus, it should be expected that more stable tertiary cation 1'
rather than secondary one 2' would be accumulated in the
reaction medium; therefore, alkylation product 3 rather than
isomer 2 (R = NHC6H4NO2) should be produced. Note that a
Generally, the yields of the acylation products increase with
growing stabilities of corresponding acylium cations.15 Similarly,
the yields of the alkylated products increase with growing
stabilities of the corresponding carbocations. Scheme 4 shows a
reasonable correlation between the yields of acylation and alkyla-
tion products and stabilities (enthalpies) of the corresponding
acylium cations and carbocations. Cyclopentane generating the
less stable carbocation among the above listed displayed the
maximal activity in acylation and the absence of activity in
alkylation. The enthalpy of the norbornyl cation17 seems more
realistic than that presented by Steward.16 The former data shows
1'
2'
3'
R
R
†
3
2
The B3LYP/6-31** calculations by N. P. Gambaryan. Moscow, INEOS,
Scheme 2
unpublished data.
– 258 –

Mendeleev Commun., 2010, 20, 257–259
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0
47
67
75
16218
72 (CO)
15616
18816
176.617 No data
18216
ΔHexp
/
7
kcal mol–1
Increase of the carbocation stability
8
9
Scheme 4
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This work was supported by the Russian Foundation for Basic
Research (project no. 09-03-00194) and the RAS Presidium
Fund (Programme 18P).
Online Supplementary Materials
Supplementary data associated with this article can be found
in the online version at doi:10.1016/j.mencom.2010.09.005.
Received: 8th February 2010; Com. 10/3463
– 259 –