Perfluorinated sulfonic acid resin (Nafion-H) catalysed Ritter reaction of benzyl alcohols

Article abstract of DOI:10.3184/030823407X262436

Perfluorinated sulfonic acid resin (Nafion-H) catalyst found to be effective in promoting the Ritter reaction of benzyl alcohols with nitriles such as acetonitrile, acrylonitrile and benzonitrile to give the corresponding N-benzylamides.

Full text of DOI:10.3184/030823407X262436

JOURNAL OF CHEMICAL RESEARCH 2007
NOvEMbER, 641–643
RESEARCH PAPER 641
Perfluorinated sulfonic acid resin (Nafion-H) catalysed Ritter reaction of
benzyl alcohols
Takehiko Yamato*, Jian-yong Hu and Naoki Shinoda
Department of Applied Chemistry, Faculty of Science and Engineering, Saga University, Honjo-machi 1, Saga-shi, Saga 840-8502,
Japan
Perfluorinated sulfonic acid resin (Nafion-H) catalyst found to be effective in promoting the Ritter reaction of benzyl
alcohols with nitriles such as acetonitrile, acrylonitrile and benzonitrile to give the corresponding N-benzylamides.
Keywords: solid superacid, Nafion-H, Ritter reaction, benzyl alcohols, N-benzylamides
The application of polymer supported reagents in organic
synthesis such as acidic ion exchange resins and ionomer
membranes as strong acid catalysts is well-known.2 Nafion-
H,3 a perfluorinated sulfonic acid resin has been used as a
superacidic catalyst to carry out a variety of acid catalysed
transformations.
We have utilised Nafion-H as a versatile acid catalyst and
this has been reviewed.3 Thus, we have found that Nafion-
H catalyst is effective in a wide range of liquid and gas
phase systems, including electrophilic aromatic substitution
transalkylation, and condensation reactions.4
Nitrogen functionality can readily be introduced by the
Ritter reaction which involves treatment of alkenes or
alcohols with nitriles in the presence of sulfuric acid.5 The
mechanism involves electrophilic alkylation of nitriles.
Several modifications of the Ritter type reaction have
appeared in the literature6 which either start from alkyl halides
or alkanes to generate the potential electrophilic alkylation
species. It is often carried out with a large excess of protic
acid, such as concentrated sulfuric acid2 or trifluoromethane
sulfonic anhydride.5c Although these procedures are usually
very effective, the methodology is frequently tedious and the
reaction conditions are generally quite critical. The reaction
requires either prolonged periods of standing or elevated
temperatures for completion. In addition, the environmental
difficulties that arise from using a large excess of acid
are serious problems. Thus there is substantial interest in
developing an efficient and convenient procedure for the Ritter
reaction. Prompted by the strongly acidic nature of Nafion-H
catalyst, we now report the mild Nafion-H catalysed reactions
of benzyl alcohols with nitriles to obtain the corresponding
N-benzyl amides.
tube, the desired product, N-(4-methylbenzyl)acrylamide
(3b) was obtained in 39% yield along with 4-methylbenzyl
ether (4b) in 41% yield (Table 1). When the reaction time
was increased to 24 h and the temperature raised to 120°C
the yield of 3b increased to 75%. Product 3b was isolated
simply by filtering the hot reaction mixture and distilling
off the unreacted acrylonitrile. The reaction was very clean.
The amount of catalyst required, as a function of the amount
of 4-methylbenzyl alcohol (1b), was between 10 and 30 wt%.
Optimum yields of amide 3b were obtained with 30 wt% of
catalyst. The use of 10 wt% of catalyst gave lower yields.
Similar result was obtained in the reaction of benzyl alcohol
(1a) with acrylonitrile to afford N-benzylacrylamide (3a) in
56% yield.
The formation of 4-methylbenzyl ether (4b) can be
expected to be attributed to the self-condensation reaction
of 4-methylbenzyl alcohol (1b). In fact, treatment of 1b in
diethylene glycol dimethyl ether in the presence of Nafion-H
for 6 h under the conditions described above afforded 4-
methylbenzyl ether (4b) in quantitative yield. Thus comparing
the reaction products as shown in Table 1, runs
3
and 4, the 4-methylbenzyl cation generated from the
4-methylbenzyl ether (4b) might react with acrylonitrile
in
a Ritter reaction under these conditions to form
N-(4-methylbenzyl)acrylamide (3b). In fact, the reaction of
CH2OH
Nafion-H
+
CH2
CHCN
2
R
1a; R= H
CH2NHCOCH CH2
b; R= Me
R
CH2OCH2
+
R
Results and discussion
4a; R= H
b; R= Me
The attempted condensation reaction of 4-methylbenzyl
alcohol (1b) with 15 equiv. of acrylonitrile (2), performed
under refluxing for 36 h in the presence of 30 wt% Nafion-
H, failed. Only starting material was recovered. However,
when the reaction was performed at 100°C for 6 h in sealed
R
a; R= H
3
b; R= Me
Scheme 1
Table 1 Ritter reaction of benzyl alcohols 1 with acrylonitrile 2a
Run
Benzyl alcohol
Temp./°C
Time/h
Yield/%b
3
4
1
2
3
4
5
1b
1b
1b
1b
1a
100
100
120
120
120
6
24
6
24
24
39
49
43
41
36
38
<1
31
90 (75)c
67 (56)c
aReaction conditions: [Benzyl alcohol 1]/[acrylonitrile 2] = 1:15; Nafion-H: 30 wt%; bYields were determined by GLC analysis.
cIsolated yields are shown in parenthesis.
* Correspondent. E-mail: yamatot@cc.saga-u.ac.jp
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642 JOURNAL OF CHEMICAL RESEARCH 2007
as an internal reference. IR spectra were measured as Kbr pellets
on a Nippon Denshi JIR-AQ2OM spectrometer. Mass spectra
were obtained on a Nippon Denshi JMS-01SA-2 spectrometer at
75 ev using a direct-inlet system. GLC analysis were carried out by
Shimadzu gas chromatograph, GC-14A (conditions: Silicone Ov-1,
2 m; programmed temperature rise, 12°C/min; carrier gas nitrogen,
25 cm3/min.).
+
Me
CH2
CH2OCH2
CHCN
Me
2
4b
CH2NHCOCH CH2
Nafion-H (30 wt%)
Materials
120°C for 24 h
(73%)
Nafion-H catalyst was prepared from commercially available
(Du Pont) Nafion-K resin, as previously described.3
Me
3b
General procedure for the Nafion-H catalysed Ritter reaction of
nitriles with benzyl alcohols
Scheme 2
Typical procedure. A mixture of benzyl alcohol (1) (5 mmol) and
Nafion-H (200 mg, 30 wt%) in acrylonitrile (2) (4 g, 75 mmol)
was heated in the Pyrex sealed tube at 120°C till completion of the
reaction, as monitored by GLC analysis (Ov 101 column) (reaction
time listed in Table 1). The solid resin-sulfonic acid was then filtered
and the solvent evaporated. The crude product was washed with
a small amount of hexane (10 cm3) to give the respective amides.
The yields are given in Table 2.
N-Benzylacrylamide (3a) was obtained as a white solid, m.p. 110–
111°C (lit.8 m.p. 109–110°C); dH(CDCl3): 4.47 (2H, d, J = 5.4 Hz,
CH2), 5.68 (1H, d, J = 10 Hz, =CHa), 6.10 (1H, broad s, NH), 6.13
(1H, dd, J = 10, 14 Hz, CHc =CH2), 6.31 (1H, d, J = 14 Hz, =CHb),
7.2–7.4 (5H, m, ArH).
N-(4-Methylbenzyl)acrylamide (3b): White solid, m.p. 68–69°C
(lit.9 m.p. 68–69°C); dH(CDCl3): 2.31 (3H, s, Me), 4.46 (2H, d,
J = 5.4 Hz, CH2), 5.68 (1H, d, J = 10 Hz, =CHa), 5.90 (1H, broad s,
NH), 6.12 (1H, dd, J = 10, 14 Hz, CHc =CH2), 6.32 (1H, d, J = 14 Hz,
=CHb), 7.24 (2H, d, J = 8 Hz, ArH), 7.12–7.20 (4H, m, ArH).
N-Benzylacetamide (5a): White solid, m.p. 61–62°C (lit.5d
m.p. 60–62°C).
4-methyldibenzyl ether (4b) with acrylonitrile in the presence
of 30 wt% Nafion-H under the same conditions as those used
with 4-methylbenzyl alcohol (1b) afforded N-(4-methyl-
benzyl)acrylamide (3b) in 73% yield (Scheme 2).
As shown in Table 2, the present method gives good
yields, and the products are easily isolated. No acid-catalysed
polymerisation of acrylonitrile was observed under the
reaction conditions in contrast to the protic acid (CF3SO3H)
or Lewis acid Sc(OTf)2 catalysed Ritter reaction. Thus,
the Ritter reaction of 4-methylbenzyl alcohol (1b) with
acrylonitrile in the presence of CF3SO3H or Sc(OTf)2 afforded
N-(4-methylbenzyl)acrylamide (3b) in only 30 and 5%
yields, respectively, along with a large amount of intractable
mixture of products. Oi et al. reported7 the synthesis of
N-substituted acrylamide by the reaction of benzyl alcohol
with acrylonitrile in the presence of cationic palladium(II)
catalyst, Pd(CH3CN)2(PPh3)2](bF4)2. Reactive systems like
tert-butyl alcohol gave corresponding amides in 45% yield.
The reaction, however, did not occur with alcohols such as
benzyl alcohol or iso-propyl alcohol.
N-(4-Methylbenzyl)acetamide (5b): White solid, m.p. 114–116°C
(lit.5d m.p. 115–116°C).
N-(4-Methylbenzyl)benzamide (6a): White solid, m.p. 137–138°C
(lit.10 m.p. 137°C); dH(CDCl3): 2.34 (3H, s, Me), 3.60 (2H, s, CH2),
4.59 (2H, d, J = 5.4 Hz, CH2), 6.48 (1H, broad s, NH), 7.14–7.79
(9H, m, ArH).
N-(4-Methylbenzyl)-4-methylbenzamide (6b): White solid,
m.p. 165–166°C (lit.11 m.p. 164–166°C); dH(CDCl3): 2.34 (3H, s,
Me), 2.38 (3H, s, Me), 4.57 (2H, d, J = 5.4 Hz, CH2), 6.43 (1H, broad
s, NH), 7.01–7.7 (8H, m, ArH).
In conclusion, the major advantage in the above discussed
reactions with Nafion-H in the simple work-up procedure,
wherein the product is isolated by filtration of the catalyst
followed by evaporation. Furthermore, the ready regeneration
of the catalyst without the loss of catalytic activity offers an
advantage over previously reported methods.
Preparation of 4-methylbenzyl ether (4b)
A mixture of 4-methylbenzyl alcohol (6.1 g, 50 mmol) and NaH
(4.0 g, 100 mmol, 60%) in dry tetrahydrofuran (THF) (10 cm3) and
dimethylformamide (DMF) was heated at reflux for 1 h under N2.
Then a solution of 4-methylbenzyl chloride (7.1 g, 5.56 mmol) in
THF (10 cm3) was added at room temperature and the mixture heated
Experimental
1H NMR spectra were recorded at 300 MHz on a Nippon Denshi
JEOL FT-300 NMR spectrometer in deuteriochloroform with Me4Si
Table 2 Ritter reaction of benzyl alcohols with nitrilesa
Run
Benzyl alcohols
Nitriles
Product
Yield/%b
CH2NHCOMe
1
1a
CH3CN
5a (82)
CH2NHCOCH CH2
CH2NHCOMe
2
3
1a
1b
CH2 =CHCN
CH3CN
3a (56)
5b (86)
Me
Me
CH2NHCOCH CH2
CH2NHCO
4
1b
CH2 =CHCN
3b (75)
CN
5
6
1b
1b
6a (81)
6b (62)
Me
Me
Me
CH2NHCO
CN
Me
aReaction conditions: [benzyl alcohol 1]/[nitrile] = 1:15; Nafion-H 30 wt%. bIsolated yields are shown.
PAPER: 07/4877

JOURNAL OF CHEMICAL RESEARCH 2007 643
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under reflux for an additional 3 h. After cooling the reaction mixture
to room temperature, it was acidified with 1 N HCl (10 cm3) and
extracted with CH2Cl2 (100 cm3 ¥ 2). The combined extracts were
washed with water (50 cm3 ¥ 2), dried (Na2SO4) and condensed
under reduced pressure to give a colourless solid. Recrystallisation
from hexane afforded 4b (9.0 g, 80%) as colourless prisms, m.p. 61–
62°C (lit.12 m.p. 60–62°C); dH(CDCl3): 2.34 (6H, s, Me), 4.49 (4H, s,
CH2), 7.14 (2H, d, J = 8 Hz, ArH), 7.24 (2H, d, J = 8 Hz, ArH).
3
4
Nafion-H catalysed Ritter reaction of acrylonitrile (2) with
4-methylbenzyl ether (4b)
A mixture of 4-methylbenzyl ether (4b) (565 mg, 2.5 mmol) and
Nafion-H (30 wt%, 200 mg) in acrylonitrile (2) (4 g, 75 mmol) was
heated in the pyrex sealed tube at 120–125°C for 24 h. The solid
resin-sulfonic acid was then filtered and the solvent evaporated.
The crude product was washed with a small amount of hexane
(10 cm3) to give N-(4-methylbenzyl)acrylamide (3b) (640 mg, 73%)
as a white solid.
Sc(OTf)3 catalysed Ritter reaction of acrylonitrile (2) with 4-methyl-
benzyl alcohol (1b)
To a mixture of 4-methylbenzyl alcohol (1b) (610 mg, 5 mmol)
and acrylonitrile (2) (4 g, 75 mmol) was added Sc(OTf)3 (492 mg,
1 mmol) at room temperature. After the reaction mixture was stirred
at room temperature for 6 h, it was quenched with ice-water and
extracted with CH2Cl2 (10 cm3 ¥ 2). The combined extracts were
washed with water (5 cm3 ¥ 2), dried (Na2SO4) and condensed
under reduced pressure. The crude product was washed with a small
amount of hexane (5 cm3) to give N-(4-methylbenzyl)acrylamide (3b)
(44 mg, 5%) as a white solid.
5
6
Similarly, when the same reaction was carried out in the presence
of CF3SO3H, N-(4-methylbenzyl)acrylamide (3b) was obtained in
30% yield.
7
8
Regeneration of Nafion-H catalyst
The spent catalyst was washed several times with acetone and
deionised water, then it was dried at 105°C for 10 h. The activity of
the regenerated catalyst was the same as that of fresh catalyst.
9
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Received 10 October 2007; accepted 7 November 2007
10 Y.-J. Kang, H. –A. Chung, J. –J. Kim and Y. –J. Yoon, Synthesis, 2002,
Paper 07/4877
doi: 10.3184/030823407X262436
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1
Perfluorinated sulfonic acid resin (Nafion-H) catalysed organic synthesis,
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2
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