Alkanes and cycloalkanes in the one-pot synthesis of amides

Article abstract of DOI:10.1016/j.mencom.2007.09.010

Alkanes (or cycloalkanes) and CO in the presence of the superelectrophilic systems CX₄·2AlBr₃ (X = Cl, Br) have been used for the first time in the selective synthesis of amides from amines.

Full text of DOI:10.1016/j.mencom.2007.09.010

Mendeleev
Communications
Mendeleev Commun., 2007, 17, 279–280
Alkanes and cycloalkanes in the one-pot synthesis of amides
Irena S. Akhrem,* Dzhul’etta V. Avetisyan, Lyudmila V. Afanas’eva,
Sergei V. Vitt, Pavel V. Petrovskii, Nikolai D. Kagramanov and Alexander V. Orlinkov
A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 119991 Moscow,
Russian Federation. Fax: +7 495 135 5085; e-mail: cmoc@ineos.ac.ru
DOI: 10.1016/j.mencom.2007.09.010
Alkanes (or cycloalkanes) and CO in the presence of the superelectrophilic systems CX4·2AlBr3 (X = Cl, Br) have been used for
the first time in the selective synthesis of amides from amines.
1
The transformations of saturated hydrocarbons into valuable
chemicals are of considerable current interest.1–4 This work
presents the first one-pot synthesis of amides from amines
in the presence of the superelectrophilic systems CX4·2AlBr3
(X = Cl, Br). Amides are versatile building blocks or inter-
mediates for the synthesis of fine chemicals, including bio-
logically active compounds.5–7
Our approach was based on the use of new superelectrophilic
systems, which can effectively generate carbocations from
saturated hydrocarbons under very mild conditions.8
When the generation of carbocations occurs under a CO
atmosphere, acylium cations are formed.9 The one-pot acylation
of alcohols4,8 and aromatics, the acyldesilylation of tetraorgano-
silanes10 and THF ring opening11 by saturated hydrocarbons
and CO were previously reported.
Acylium salts were generated11 from alkanes and cycloalkanes
under a CO atmosphere in the presence of the superelectrophilic
complexes CX4·2AlBr3 (E). Then, an amine was introduced to
the in situ generated acylium salt. Both carbonylation of alkanes
and following N-acylation reactions should be carried out under
a CO atmosphere.†
When the procedure is strictly followed, only one isomer is
formed in each reaction (Scheme 1). Amides containing isopropyl,
tert-pentyl, cyclopentyl, 2-norbornyl and 1-adamantyl groups
are formed from propane, n-pentane, cyclopentane, norbornane
and adamantane, respectively.
The structures of amides were proved by H and 13C NMR
spectroscopy, GC, GC-MS and in some cases by elemental
analysis.‡ To the best of our knowledge, amides 3–5, 8, 11, 13,
14 and 15 are new compounds.
†
Conditions for the in situ generation of acylium salts (carbonylation
stage) under atmospheric pressure of CO.11 E = CX4·2AlBr3 in CH2X2
solution (X = Br, Cl; [AlBr3] = 0.46 g cm–3). [RH]:[E] molar ratio, tem-
perature and reaction time: for n-pentane or cyclopentane, 10:1, –20 °C,
1 h; for norbornane, (1–1.2):1, –20 °C, 1 h; for adamantane, 1:1, 0 °C,
3 h (in this case [AlBr3] = 0.04 g cm–3). Isopropylcarboxonium salt was
generated under propane/CO (3:2) gas atmosphere, P = 1 atm, –20 °C, 2 h.
Conditions for the acylation reactions. When the formation of an acylium
salt was over, an amine ([1–3]:[E]) was added to a reaction mixture at
the same temperature. Then, the temperature of the reaction mixture was
increased to 20 °C. After 0.5 h, diethyl ether was added to the reaction
mixture under cooling. The reactions of in situ generated RCO+ with
o-nitroaniline were carried out at 0 °C for 4 h (R = cyclopentyl) and at
35 °C for 1 h (R = C7H11, norbornyl). Then water was added dropwise.
After diethyl ether extraction, washing organic layer with water, drying
with MgSO4, products were analyzed by GC and GC–MS. For NMR
studies, diethyl ether and light products were removed from the extracts.
A typical procedure. At 0 °C under atmospheric pressure of CO, norbor-
nane (0.247 g, 2.58 mmol) was added to a stirred solution of tetrachloro-
methane (0.2 ml, 2.15 mmol), anhydrous CH2Br2 (2 ml) and aluminum
bromide (1.15 g, 4.3 mmol). The mixture was stirred for 2 h; then,
morpholine (2.5 ml, 2.60 mmol) was added under similar conditions.
After stirring for 30 min at 0 °C, diethyl ether was added to the reaction
mixture with cooling. Then, water was added dropwise. After diethyl
ether extraction, washing organic layer with water, drying with MgSO4,
products were analyzed by GC, GC–MS and NMR spectroscopy.
RCONEt2
For 14: yield, 72%; mp 84–85 °C (hexane); 1H NMR (600 MHz,
‡
RCO
RCO
N
N
COSY 1H-13C, CDCl3) d: 1.18 (13'CH), 1.24 (11'CH), 1.25 (13''CH) –
(1.17, m, 3H), 1.20 (14'CH) – (1.42, ddd, 1H, 2JHH 11.8 Hz, 3JHH 9.0 Hz,
3JHH 2.3 Hz), 1.48 (14''CH) – (1.53, tm, 1H, 2JHH 11.8 Hz), 1.50 (11''CH) –
(1.53, tm, 1H, 2JHH 12.0 Hz), 1.67 (15'CH) – (1.54, dm, 1H, 2JHH 12.0 Hz),
2.07 (12CH) – (22.29, m, 1H), 2.93 (15''CH) – (1.90, m, 1H, 2JHH 12.0 Hz),
2.18 (10CH), 2.93 (9CH) – (2.32, m, 2H), 3.20 (5CHax), 3.28 (5CHeq) –
(3.47, m, 2H), 3.46 (6CHax), 3.54 (6CHax) – (3.59, m, 2H), 3.53 (3CHeq),
3.55 (2CHax), 3.61 (3CHeq), 3.63 (2CHeq) – (3.65, m, 4H). 13C NMR
(150 MHz, CDCl3, JMODECHO) d: 28.46 (C14), 28.96 (C13), 34.30
(C15), 35.50 (C12), 36.26 (C11), 40.04 (C10), 41.65 (C5), 43.52 (C9),
45.43 (C3), 66.19 (C6), 66.50 (C2), 173.47 (C7). MS, m/z: 209 (M+, 27),
181 (M – C2H+4, 4), 180 (M – C2H+5, 15), 168 (6), 155 (5), 152 (1), 145
(11), 144 (93), 142 (2), 129 (5), 123 (C7H11CO+, 7), 122 (12), 114 (1), 113
(19), 111 (1), 96 (11), 95 (C7H+11, 100), 94 (4), 93 (12), 91 (3), 88 (17),
87 (10), 86 (C4H8NO+, 23), 85 (5), 81 (6), 80 (3), 79 (7), 78 (2), 77 (6),
72 (C4H8O+, 2), 70 (22), 69 (C5H+9, 3), 68 (4), 67 (30), 66 (9), 65 (7), 58
(2), 57 (17), 56 (18), 55 (30), 53 (9). Found (%): C, 68.91; H, 9.14;
N, 6.46. Calc. for C12H19O2N (209.282) (%): C, 68.86; H, 9.15; N, 6.69.
Characteristics for other new amides obtained will be reported elsewhere.
E+, CO
RH
RCO+
O
RCONH
N
X
RH = C3H8, n-C5H12 , cyclopentane, norbornane, adamantane
XH = H, NO2
Scheme 1
Various amines (aliphatic, cyclic and aromatic amines and,
in some cases, even nitroanilines) are readily acylated with
saturated hydrocarbons and CO in the presence of the above
superelectrophiles to give amides in good or moderate yields.
Amides 1–19 were prepared from alkanes (and cycloalkanes),
CO and amines (the yields are given based on GC data)
(Scheme 2).
– 279 –

Mendeleev Commun., 2007, 17, 279–280
In conclusion, the use of the polyhalomethane-based super-
O
O
O
electrophilic systems allows us to use saturated hydrocarbons
and CO as equivalents of acylium salts in the one-pot synthesis
of amides from amines. These reactions occur to selectively
give amides in high or moderate yields.
N
N
N
1 70%
2 69%
3 66%
This work was supported by the Russian Foundation for
Basic Research (project no. 06-03-32194).
O
O
O
N
N
NHPh
References
O
1
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4 80%
5 69%
6 54%
O
N
O
N
O
N
2
O
3
4
5
6
7
8
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7 77%
8 100%
9 40%
O
O
NHPh
NHC6H4-o-NO2
10 66%
11 100%
O
O
N
N
9
12 98%
13 96%
O8
O
11
10
3
6
10 I. S. Akhrem, I. M. Churilova, A. V. Orlinkov, L. V. Afanas’eva, S. V. Vitt
and P. V. Petrovskii, Izv. Akad. Nauk, Ser. Khim., 1998, 947 (Russ.
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4
9
2
14
7
N
NHC6H4-o-NO2
O1
13
12
15
5
11 I. S. Akhrem, D. V. Avetisyan, S. V. Vitt and P. V. Petrovskii, Mendeleev
14 72%
15 73%
Commun., 2005, 185.
O
O
N
N
16 77%
17 65%
O
O
N
NHPh
19 60%
O
18 48%
Scheme 2
Received: 9th March 2007; Com. 072887
– 280 –