Amberlyst-15 as a recyclable heterogeneous catalyst for synthesis of N-tert-butylamides via Ritter-type reaction

Article abstract of DOI:10.1016/j.cclet.2011.11.026

Highly efficient method for the preparation of N-tert-butylamides by reaction of nitriles with tert-butylacetate is described using Amberlyst-15 as a recyclable heterogeneous catalyst. Selective amidation of benzonitrile in the presence of acetonitrile was also achieved.

Full text of DOI:10.1016/j.cclet.2011.11.026

Available online at www.sciencedirect.com
Chinese Chemical Letters 23 (2012) 293–296
www.elsevier.com/locate/cclet
Amberlyst-15 as a recyclable heterogeneous catalyst for
synthesis of N-tert-butylamides via Ritter-type reaction
b
Masoud Mokhtary a, , Gholamreza Goodarzi
*
a Department of Chemistry, Rasht Branch, Islamic Azad University, Rasht, Iran
b Department of Chemistry, Amol Branch, Islamic Azad University, Amol, Iran
Received 6 October 2011
Available online 25 January 2012
Abstract
Highly efficient method for the preparation of N-tert-butylamides by reaction of nitriles with tert-butylacetate is described using
Amberlyst-15 as a recyclable heterogeneous catalyst. Selective amidation of benzonitrile in the presence of acetonitrile was also
achieved.
# 2011 Masoud Mokhtary. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Modified Ritter reaction; Amberlyst-15; Nitriles; tert-Butylacetate; N-tert-Butylamides
The application of polymer supports as reagent and catalyst has received special attention, due to easy work up of
reaction products and some selectivity which is undoubtedly attractive features of this methodology [1]. Ion exchange
resins are usually employed either as sulfonic acid cation exchangers in the hydrogen form or quaternary ammonium
anion exchangers in the hydroxide form in both aqueous and non-aqueous media. It is noteworthy that these reagents
are insoluble in reaction media and can be easily removed by simple filtration, therefore reducing the steps and
equipments required for catalyst removal. Furthermore these reagents can be handled easily without any danger to
personnel. The Ritter reaction makes possible the conversion of a group, capable of giving a relatively stable
carbonium ion, to a substituted amide by reaction with a nitrile in the presence of a strong acid like concentrated
sulfuric acid [2]. Several modifications have been attempted to improve Ritter reaction conditions. However, as an
alternative to sulfuric acid, other acid catalysts such as (CF3SO2)2O [3], BF3ꢀEt2O [4], Fe3+-Montmorillonite [5],
Mg(HSO4)2 [6], Bi(OTf)3 [7], CeCl3ꢀ7H2O/AcCl [8], P2O5/SiO2 [9] and Nafion [10] are employed in the Ritter
reaction. Ritter reaction using tert-butylacetate instead of alcohol was also reported to be catalyzed by sulfuric acid
[11,12], FeCl3ꢀ6H2O [13], ZnCl2/SiO2 [14], and I2 [15].
However, most of these methods suffer from at least one of the following disadvantage: vigorous reaction conditions,
strong protic and aqueous media, high cost and toxicity of the reagent, tedious work-up procedures, and instability and
hygroscopic nature of the reagent. Substantial investigations have been done to introduce novel supported catalysts
and chemical reagents. These include dispersing catalysts on inorganic supports such as metal oxide, alumina, silica, and
zeolite. There are a number of advantages in using polymer supported catalysts over the conventional catalysis. The
reactions can be performed under mild condition and purification of the product is simplified because of the use of an
* Corresponding author.
E-mail address: mmokhtary@iaurasht.ac.ir (M. Mokhtary).
1001-8417/$ – see front matter # 2011 Masoud Mokhtary. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2011.11.026

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M. Mokhtary, G. Goodarzi / Chinese Chemical Letters 23 (2012) 293–296
SO3H
P
R-CN
CH3CO2C(CH3)3
R-CONHC(CH3)3
+
70 oC/2-5h
Scheme 1.
insoluble solid support. Polymer supported catalysts can also be recycled after use [16]. Recently, Amberlyst-15 was
efficiently used as catalyst in variety of chemical reactions like: synthesis of 1,5-benzodiazepines [17], bis and tris (1H-
indol-3yl) methanes [18], b-acetamido ketones [19], regeneration of carbonyl compounds from oximes, hydrazones and
semicarbazones [20], preparation of quinoline derivatives [21], oxidation of benzyl alcohols catalyzed by isoamyl nitrate
[22] andsynthesis of alkyl/aryl/heterocyclicphosphonates [23]. In connectionwith ourresearchto develop applicationof
Ritter reaction for synthesis of polyamides [24], polyether amides [25] and amidation of benzhydrol and tertiary alcohols
with polyvinylpolypyrrolidone-boron trifluoride [26], herein, we found that Amberlyst-15 can be used for preparation of
N-tert-butylamide derivatives from tert-butylacetate via Ritter type reaction in good to excellent yields. This method
often leads to the development of eco-friendly protocols (Scheme 1).
Interestingly, this reagent not only gives good yields of the products but also Amberlyst-15 is easily regenerated and
can be reused several times.
Avariety of N-tert-butylamides were prepared from tert-butylacetate and the corresponding nitriles in the presence
of Amberlyst-15 in good yields (Table 1, entries 1–8). O-Tolunitrile shows low yield of corresponding amides
probably via steric hindrance of methyl group in ortho position of CN functional group (Table 1, entry 9). Aliphatic
nitriles were converted to the corresponding amides in moderate yields (Table 1, entries 10 and 11). Also, using of tert-
butanol and triphenyl methanol instead of tert-butylacetate lead to appropriate yield of corresponding amides (Table 1,
entry 12 and 13). It is worth mentioning that the corresponding amide in each case was isolated by simple filtration of
the catalyst followed by crystallization from the crude filtrate.
Additionally, competitive Amberlyst-15 catalyzed modified Ritter reaction of tert-butylacetate with equimolar
amounts of benzonitrile and acetonitrile leads to the selective formation of N-tert-butylbenzamide in good yield,
whereas acetonitrile remained unchanged (Scheme 2).
Mechanistically, we assume that the reaction likely proceeds via the protonation of tert-butylacetate by Amberlyst-
15 and facilitation of C–O cleavage by attacking of nitrile group to give the nitrilium cation which subsequently reacts
with water to furnish the desired amide (Scheme 3).
To check the reusability of the catalyst, it was employed the amidation of tert-butylacetate with benzonitrile five
cycles under the optimum conditions. In the first run 90% of N-tert-butylbenzamide was obtained. The catalyst powder
was recovered by filtration, washed with dichloromethane and immediately reused for amidation processes again,
taking into account the partial loss of catalyst during the recovery. After recycling five times, the catalytic activity of
Amberlyst-15 still remained at a high level (Table 2).
Cross-linked polystyrene tolerates well a broad range of reaction conditions, including treatment with weak
oxidants (ozone, DDQ), strong bases (LDA), and acids (HBr, TfOH). Strong oxidants at high temperatures and other
reagents which lead to a chemical modification of alkyl benzenes, however, not surprisingly, also attack polystyrene
[27]. In general, the maximum working temperature for acid resins is approximately 125 8C, so, Amberlyst-15 is
stable and decomposition not occurred in this reaction conditions.
In conclusion, we have developed a simple methodologyformodifiedRitter reaction using Amberlyst-15 as a recyclable
heterogonous catalyst, and represent effective catalytic activity for the amidation of tert-butylacetate with nitriles. This
catalyst can be recovered from reaction system and reused many times without significant loss of catalytic ability.
1. Experimental
All chemicals were purchased from Merck chemical company. Melting points were recorded on an electro thermal
melting point apparatus. The NMR spectra were recorded in CDCl3 with TMS as an internal standard on a Bruker
advance DRX 400 MHz spectrometer. IR spectra were determined on a SP-1100, P-UV-Com instrument. Purity
determination of the products was accomplished by TLC on silica gel poly gram SIL G/UV 254 plates. Products were
separated by simple filtration, and identified by comparison IR, and 1H NMR spectra, with those reported for authentic
samples.

M. Mokhtary, G. Goodarzi / Chinese Chemical Letters 23 (2012) 293–296
295
Table 1
Amidation of tert-butylacetate and tert-alcohol with nitriles using Amberlyst-15.
Entry
1
Substrate
Nitriles
Producta
Time/h
2
Yield %b
90
CONHtBu
CH3CO2C(CH3)3
CN
CONHtBu
2
3
4
CH3CO2C(CH3)3
CH3CO2C(CH3)3
CH3CO2C(CH3)3
2
4
5
92
76
87
CN
CN
CN
Cl
Cl
CONHtBu
HO
HO
CONHtBu
tBuNHOC
tBuNHOC
NC
NC
CONHtBu
5
6
CH3CO2C(CH3)3
CH3CO2C(CH3)3
5
2
85
84
CN
CN
CONHtBu
H3C
H3C
H3C
H3C
CONHtBu
7
8
CH3CO2C(CH3)3
CH3CO2C(CH3)3
2
3
92
25
CN
CH3
CH3
CN
CONHtBu
9
CH3CO2C(CH3)3
3
74
CONH tBu
ClCH2CONHtBu
CN
10
11
12
13
CH3CO2C(CH3)3
CH3CO2C(CH3)3
(CH3)3COH
ClCH2CN
NCCH2COOEt
CH3CN
3
3
3
3
48
56
76
85
tBuNHCOCH2COOEt
CH3CONHtBu
(Ph3)3COH
CH3CN
CH3CONHC(Ph)3
a
All the products were characterized by IR, 1H NMR spectra and comparison with authentic samples.
All yields refer to isolated products.
b
1.1. General procedure:
A solution of 3 mmol nitrile in 3 mmol tert-butylacetate or tert-butylalcohol was prepared. Amberlyst-15 (1 g) was
added to the solution and the reaction mixture was stirred for 2–5 h under 70 8C until TLC analysis showed that no nitrile
remained. The reaction mixture was filtered, and the solvent was evaporated on a rotatory evaporator under diminished
pressure. The solid residue was recrystallized from water to afford pure crystals of the proper amides in 48–92% yields.
N,N0-Di-tert-butylisophtalamide (entry 5): Yield 85%; mp: 204–207 8C. IR (KBr): 3272, 3068, 2969, 1639, 1548,
1
1307, 680 cmꢁ1. H NMR (400 MHz CDCl3): d 1.49 (s, 18H), 6 (br, s, 2H), 7.28–8.11 (m, 4H).
PhCONHC(CH3)3
+
CH3CONHC(CH3)3
(90%)
(0%)
P
SO3H
Ph-CN
+
CH3CN
tert-butylacetate
70 oC, 4h
Scheme 2.

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M. Mokhtary, G. Goodarzi / Chinese Chemical Letters 23 (2012) 293–296
+
OH
O
+
NC-R
SO3H
P
N
C(CH 3)3
R
N
O
C(CH 3)3
O
C(CH 3)3
H3C
H3C
-AcOH
+
H2O
-H
OH
C
O
C
C(CH 3)3
R
N
C(CH 3)3
R
H
Scheme 3.
Table 2
The recycling of Amberlyst-15 in the amidation of tert-butyl acetate to N-tert-butylbenzamide.
Cycle
1
2
3
4
5
Yield (%)a
90
88
86
85
84
a
Isolated yields.
N-tert-Butyl-3-methylbenzamide (entry 7): Yield 92%; mp: 96–97 8C. IR (KBr): 3382, 2962, 1643, 1529, 1447,
1
748 cmꢁ1. H NMR (400 MHz CDCl3): d 1.49 (s, 9H), 2.4 (s, 3H), 5.95 (br, s, 1H), 7.28–7.56 (m, 4H).
N-tert-Butylchloromethylacetamide (entry 10): Yield 48%; mp: 79–81 8C. IR (KBr): 3311, 2977, 1683, 1554, 1222,
1
673 cmꢁ1. H NMR (400 MHz CDCl3): d 1.40 (s, 9H), 3–96 (s, 2H), 6.38 (br, s, 1H).
N-tert-Butylmethylacetatoamide(entry 11): Yield 56%;mp: 90–93 8C; IR (KBr):2991, 2979, 1720, 1629, 1498, 1043,
736 cmꢁ1. 1H NMR (400 MHz, CDCl3): d 1.45 (s, 9H), 1.47 (t, 3H), 2.43(s, 2H), 4.54 (q, 2 H, J = 6.8) 11.25 (br, s, 1H).
Acknowledgment
We are grateful to Islamic Azad University of Rasht Branch for financial assistance of this work.
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