Temperature-controlled solvent-free selective synthesis of tert-butyl peresters or acids from benzyl cyanides in the presence of the TBHP/Cu(OAc)2 system

Article abstract of DOI:10.1039/c6ra27921j

Solvent-free room temperature synthesis of tert-butyl peresters was achieved via copper-catalyzed oxidative-coupling of benzyl cyanides with tert-butyl hydroperoxide in short reaction times. Various derivatives of tert-butyl peresters were synthesized by this pathway in good to excellent yields. Further investigation revealed that the above-mentioned protocol is effective for the synthesis of benzoic acid derivatives when the reaction is conducted at 80?°C, under the same reaction conditions.

Full text of DOI:10.1039/c6ra27921j

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Temperature-controlled solvent-free selective
synthesis of tert-butyl peresters or acids from
benzyl cyanides in the presence of the TBHP/
Cu(OAc)2 system†
Cite this: RSC Adv., 2017, 7, 7619
a
b
c
a
*
*
H. Hashemi, D. Saberi, S. Poorsadeghi and Kh. Niknam
Solvent-free room temperature synthesis of tert-butyl peresters was achieved via copper-catalyzed
oxidative-coupling of benzyl cyanides with tert-butyl hydroperoxide in short reaction times. Various
derivatives of tert-butyl peresters were synthesized by this pathway in good to excellent yields. Further
investigation revealed that the above-mentioned protocol is effective for the synthesis of benzoic acid
derivatives when the reaction is conducted at 80 ꢀC, under the same reaction conditions.
Received 8th December 2016
Accepted 2nd January 2017
DOI: 10.1039/c6ra27921j
www.rsc.org/advances
synthetic methods for tert-butyl peresters is interest. Here we
report a new synthetic pathway for the preparation of tert-butyl
Introduction
peresters via copper-catalyzed oxidative coupling of benzyl
cyanides with TBHP (Scheme 1, eqn (d), path I). Performing
under solvent-free conditions at room temperature in low
reaction times make interest this transformation. Moreover, we
found that when this reaction is conducted at 80 C, benzoic
acid derivatives will be predominant products (Scheme 1, eqn
(d), path II).
Providing new synthetic methods or promoting previously re-
ported ones is one of the main challenges to the synthetic
chemists. Many efforts have been made to achieve a variety as
well as green and eco-friendly synthetic pathways for important
and widely used organic compounds. In recent years, oxidative
coupling reactions in which two nucleophiles, in the presence
of an external oxidant, are coupled together have been devel-
oped.1 In this type of reaction, since only nucleophiles are used,
unlike traditional methods that involve either electrophiles or
nucleophiles, synthetic procedures will be more efficient and
waste production will be minimized.
ꢀ
tert-Butyl peresters are an important class of organic
compounds because of their participation in organic trans-
formations in particular as oxidants in oxidation reactions.2
Traditionally, tert-butyl peresters are prepared from carboxylic
acids or their analogous benzoyl chlorides with tert-butyl
hydroperoxide in the presence of base (Scheme 1, eqn (a)).3 In
2011, a distinguish methodology by high atom economy and
free of base was disclosed by Wan et al. for synthesis of tert-butyl
peresters.4 They reported on water Buꢀ4NI-catalyzed oxidative
coupling of aldehydes with TBHP at 40 C (Scheme 1, eqn (b)).
The same procedure has recently been reported by Wang et al.
in which alcohols is coupled with TBHP for synthesis of tert-
butyl peresters (Scheme 1, eqn (c)).5 Due to their importance as
well as the low number of reported procedures, development of
aDepartment of Chemistry, Faculty of Sciences, Persian Gulf University, Bushehr
75169, Iran. E-mail: niknam@pgu.ac.ir
bFisheries and Aquaculture Department, College of Agriculture and Natural Resources,
Persian Gulf University, Bushehr 75169, Iran. E-mail: saberi_d@pgu.ac.ir
cChemistry Department, Tarbiat Modares University, Tehran, Iran
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c6ra27921j
Scheme 1 Approaches for synthesis of tert-butyl peresters.
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carried out in the solvents such as H2O, CH3CN, DMF, EtOH,
and EtOAc, the efficiency was lower than that of solvent-free
conditions (Table 1, entries 15–19).
Results and discussion
Following the benzyl cyanide oxidation in the presence of
Cu(OAc)2/TBHP system, a unknown product was obtained in
40% yield that aer identication turned out to be tert-butyl
perbenzoate. As mentioned above, because of the gravity of this
class of compounds, efforts were made to raise efficiency by
changing the reaction conditions. The results are summarized
in Table 1. As can be seen in this table, the pre-starter reaction
was performed between benzyl cyanide (1 mmol) and TBHP (70
wt% in H2O, 1 mmol) in the presence of Cu(OAc)2 (10 mol%) as
catalyst under solvent-free conditions at room temperature.
Other copper salts such as CuCl2, CuCl, CuI, as well as TBAI also
worked for this reaction, albeit with lower yields (Table 1,
entries 2–5). Performance of FeCl2 for this transformation was
weaker than copper salts (Table 1, entry 6). Notably, NiCl2
showed no conversion (Table 1, entry 7). The experiment con-
ducted under catalyst-free conditions showed that the catalyst
has an important role in this reaction (Table 1, entry 8). Further
investigation revealed that the ratio between the reactants is
very important. The 1 : 4 ratio of benzyl cyanide to TBHP gave
the highest yield (Table 1, entries 9–12). By increasing the
amount of the catalyst to 20 mol%, the yield did not change,
while by reducing it to 5 mol%, efficiency was decreased with
50% (Table 1, entries 13 and 14). Then, the effect of solvents on
the reaction performance was evaluated. When the reaction was
As a last resort, the effect of temperature was studied and
some interesting results were obtained. As temperature rise to
ꢀ
80 C, the efficiency was sharply down, in return benzoic acid
was isolated with high efficiency (Table 1, entries 20 and 21).
However this also will be a new and effective procedure for
benzoic acid derivatives synthesis.
Aer optimization, in order to establish the scope of the
procedure, a wide range of benzyl cyanides were subjected to
the reaction conditions. The results are shown in Fig. 1. As seen
is this gure, various derivatives of benzyl cyanide bearing
halogen and electron-donating substituents, at different posi-
tion of aromatic ring, were converted to the corresponding tert-
butyl peresters in moderate to good yields (Fig. 1, 1a–j). 4-Cya-
nobenzyl cyanid was also successful in this transformation and
product 1k was obtained in 65% yield. 4-Nitrobenzyl cyanide
was failed to this reaction and the corresponding product was
formed in trace (Fig. 1, 1l). When 4-(methylthio)benzyl cyanide
was subjected to the reaction conditions, the desired perester
(Fig. 1, 1m) was obtained in 60% yield and sulde substituent
that is susceptible to oxidation to sulfoxide, remained intact.
Heteroaromatic and polycyclic cyanides, that is, thiophen-2-yl-
acetonitrile and naphthalen-2-yl-acetonitrile, also were
condensed into the corresponding tert-butyl peresters 1n and 1o
in high yields.
Table 1 The tests for achieving to the optimum conditionsa
Entry
Solvent
Catalyst (mol%)
TBHP (mmol)
Yieldb (%)
1
2
3
4
5
6
7
8
—
—
—
—
—
—
—
—
—
—
—
—
—
—
H2O
CH3CN
DMF
EtOH
EtOAc
—
Cu(OAc)2(10)
CuCl2(10)
CuCl(10)
CuI(10)
TBAI(10)
FeCl2(10)
NiCl2(10)
—
Cu(OAc)2(10)
Cu(OAc)2(10)
Cu(OAc)2(10)
Cu(OAc)2(10)
Cu(OAc)2(10)
Cu(OAc)2(10)
Cu(OAc)2(10)
Cu(OAc)2(10)
Cu(OAc)2(10)
Cu(OAc)2(10)
Cu(OAc)2(10)
Cu(OAc)2(10)
Cu(OAc)2(10)
1
1
1
1
1
1
1
1
2
3
4
6
4
4
4
4
4
4
4
4
4
40
30
35
37
20
10
—
—
60
70
80
80
80
50
50
50
5
9
10
11
12
13
14
15
16
17
18
19
20c
21d
30
30
40
5
—
a
Fig. 1 Substrate scope. Reaction conditions: benzyl cyanide deriva-
tives (1 mmol), TBHP (4 mmol), Cu(OAc)2 (10 mol%), r.t., reaction time:
5 h; the yields refer to the isolated pure products.
Benzyl cyanide (1 mmol), under air atmosphere at room temperature.
b
c
d
Isolated yield. At 50 ꢀC. The reaction was performed at 80 ꢀC and
benzoic acid was isolated as the main product in 85% yield.
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Moreover, 1,2-phenylenediacetonitrile was converted to the
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product 1p in which both benzylic groups have become to the
tert-butyl perester group. All the products 1a–p was identied by
1
elemental analysis and FTIR, H and 13C-NMR spectra.
As was considered above, when the model reaction was
ꢀ
conducted at 80 C, benzoic acid was obtained in 85% yield.
Therefore this protocol was extended for the synthesis of
benzoic acid derivatives. Optimized conditions for synthesis
of tert-butyl peresters were the best for acids so. And by
changing the amount of oxidant and catalysts, as well as
increasing the temperature to 100 ꢀC, the yield was not
improved. Worthy of note is that, when sodium hypochlorite
(NaOCl), di tert-butyl peroxide (DTBP), and m-chloro perben-
zoic acid (mCPBA) was used instead of TBHP, no acid was
formed and benzyl cyanide was isolated quantitative.
Aliphatic cyanides were not successful in this transformation.
In a typical experiment, when propionitrile was subjected to
the reaction conditions, the reaction was not performed. Fig. 2
shows the structures of acids synthesized by this method. As
can be seen in this gure, without depending on the type and
position of substitution, the acids were derived with the high
and neck-to-neck efficiency.
Scheme 2 Control experiments into the reaction mechanism.
From the viewpoint of reaction mechanism, since the benzyl
cyanide is prone to oxidation into the benzoyl cyanide in the
presence of TBHP,6 therefore reaction of benzoyl cyanide was
investigated under the same reaction conditions to obtain
a plausible mechanism (Scheme 2, eqn (1)). Formation of
perester 1a in high yield showed that benzoyl cyanide can be
impressive intermediate in this transformation. Moreover, the
sharp decrease of efficiency in the presence of TEMPO, a known
radical scavenger, revealed that radicals could be involved in the
reaction pathway (Scheme 2, eqn (2)). In addition, the presence
of free cyanide anion has been proven by the use of indicator
paper (see ESI†).6c–f
Based on the above results and related works,7 the mecha-
nism depicted in Scheme 3 is proposed for this transformation.
Initially, the copper(II) species donates an electron to TBHP to
generate a tert-butoxyl radical and a copper(III) species.7b The
latter abstracts an electron from another molecule of TBHP and
gives the original copper(II) species along with a tert-butyl peroxy
radical. The tert-butoxyl radical could then abstract a hydrogen
atom from the benzyl cyanide to generate the radical I which
couples with the tert-butyl peroxy radical, affording a perester
intermediate II. This intermediate can then be converted to the
benzoyl cyanide III with the loss of tert-butanol. Benzoyl cyanide
can be transformed to the corresponding tert-butyl perester,
tert-butyl benzoate, or acid via nucleophilic attack by tert-butyl
hydroperoxide, tert-butanol or water respectively. Worthy of
note is that tert-butyl benzoate was observed in some experi-
ments shown in Table 1.
Fig. 2 The structures of the synthesized acids. Reaction conditions:
benzyl cyanide derivatives (1 mmol), TBHP (4 mmol), Cu(OAc)2 (4
mol%), 80 ꢀC, reaction time: 5 h; the yields refers to the isolated pure
products.
Scheme 3 Proposed mechanism.
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Conclusions
In conclusion an effective and temperature-controlled protocol
was developed for the synthesis of tert-butyl peresters and
benzoic acids from benzyl cyanides in the presence of Cu/TBHP
catalytic system. Various derivatives of tert-butyl peresters were
synthesized in high yields under solvent-free conditions at
room temperature. Benzoic acids were prepared under the same
conditions with a slightly modied procedure, in which the
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Acknowledgements
We are thankful to Persian Gulf University Research Council for
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