Oxidation of benzyl halides to aldehydes and ketones with potassium nitrate catalyzed by phase-transfer catalyst in aqueous media

Article abstract of DOI:10.1080/00397910802323080

The catalytic oxidation of benzyl halides to aldehydes and ketones in aqueous media was studied under relatively mild reaction conditions by using phase-transfer catalyst combined with potassium nitrate and 10% aqueous potassium hydroxide solution. As a result, a simple high-yield procedure has been developed. Copyright Taylor & Francis Group, LLC.

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Oxidation of Benzyl Halides to
Aldehydes and Ketones with
Potassium Nitrate Catalyzed
by Phase-Transfer Catalyst in
Aqueous Media
Qifa Liu a , Ming Lu a , Feng Sun b , Jiang Li a
Yuebing Zhao a
&
a Chemical Engineering College, Nanjing University
of Science and Technology, Nanjing, China
b Nanjing Cosmos Chemical Co., Nanjing, China
Version of record first published: 31 Oct 2008.
To cite this article: Qifa Liu , Ming Lu , Feng Sun , Jiang Li & Yuebing Zhao (2008):
Oxidation of Benzyl Halides to Aldehydes and Ketones with Potassium Nitrate
Catalyzed by Phase-Transfer Catalyst in Aqueous Media, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry,
38:23, 4188-4197
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Synthetic Communications1, 38: 4188–4197, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802323080
Oxidation of Benzyl Halides to Aldehydes and
Ketones with Potassium Nitrate Catalyzed by
Phase-Transfer Catalyst in Aqueous Media
Qifa Liu,1 Ming Lu,1 Feng Sun,2 Jiang Li,1 and Yuebing Zhao1
1Chemical Engineering College, Nanjing University of Science
and Technology, Nanjing, China
2Nanjing Cosmos Chemical Co., Nanjing, China
Abstract: The catalytic oxidation of benzyl halides to aldehydes and ketones in
aqueous media was studied under relatively mild reaction conditions by using
phase-transfer catalyst combined with potassium nitrate and 10% aqueous potas-
sium hydroxide solution. As a result, a simple high-yield procedure has been
developed.
Keywords: Benzyl halide, oxidation, phase-transfer catalyst, potassium nitrate
INTRODUCTION
The oxidation of benzyl halides to the corresponding aldehydes and
ketones is widely recognized as one of the most fundamental transforma-
tions in both laboratory and industrial synthetic chemistry because the
aldehydes and ketones serve as important intermediates for the synthesis
of perfumery chemicals, pharmaceuticals, dyestuffs, agrochemicals, and
polymers.[1] Direct procedures for oxidizing benzyl halides to aldehydes
and ketones, in many cases, afford more convenient synthesis than the
oxidation of the corresponding alcohols.[2] Of these, two classic methods,
Received February 20, 2008.
Address correspondence to Ming Lu, Chemical Engineering College, Nanjing
University of Science and Technology, Nanjing 210094, China. E-mail:
luming302@126.com
4188

Oxidation of Benzyl Halides
4189
the Sommelet[3] and Hass–Bender[4] reactions, are the most straightforward
and commonly employed, and while each has some limitations, one or
other can almost always be satisfied for any given benzyl halide.[5] Other
procedures, such as the Kro¨hnke[6] and Kornblum[7] methods and oxida-
tions with different amine N-oxide,[8,9] N-alkoxypyridinium salts,[10,11]
NaIO4–DMF,[12] selenium compounds,[13] V2O5-H2O2,[14] IBX,[15] the
Masaki photooxidation,[16] and mercury[5] and bismuth[17] nitrate salts,
have all been developed with different degrees of success. Because of dete-
rioration of the environment, the introduction of environmentally benign
methods for oxidation of benzyl halides is still in demand.
Phase-transfer catalysis (PTC) is a versatile synthetic technique that
has been widely applied to intensify otherwise slow heterogeneous reac-
tions involving an organic substrate and an ionic reactant, either dis-
solved in water (liquid–liquid) or present in solid state (liquid–solid).[18]
In addition, PTC can make reaction conditions gentle, can effectively
avoid side reactions, can reduce consumption of organic solvent and
raw materials, and can enhance the efficiency of organic synthesis. At
present, PTC has been applied in various organic syntheses, such as elec-
trophilic substitution reaction, nucleophilic substitution reaction, oxida-
tion reaction, and hydrolysis.[19–21] We report here a new, economic,
and convenient method by which benzyl halides can be directly oxidized
to aldehydes and ketones with potassium nitrate (KNO3) catalyzed by
PTC without any organic solvents.
The oxidation of 4-isopropylbenzyl chloride (0.10 mol) was first car-
ried out by vigorously stirring the two-phase system (4-isopropylbenzyl
chloride and 15 mL H2O) at reflux temperature with KNO3 (0.11 mol).
The yield of 4-isopropylbenzaldehyde, 2a, was only 12% (Table 1,
entry 1) after 10 h. Using cetyltrimethylammonium bromide (CTAB,
1.1 mmol) as PTC under the same conditions, 2a was obtained in a higher
yield 57% (Table 1, entry 2). The colors of the reaction mixture varied
from colorless to yellow and a red-brown gas was observed as the reac-
tion proceeded. After addition of 0.11 mol of potassium hydroxide
(KOH) to the catalytic system, the yield of 2a increased to 71% (Table
1, entry 3) within 4 h. These results show that KOH can promote this
oxidation reaction to some extent. Considering that 2a may decompose
under the strongly basic conditions, we added 10% aqueous KOH
solution (60 mL, 0.11 mol) dropwise with a dropping funnel to keep the
pH value at 10–11 over the indicated time. The yields of 2a were signifi-
cantly increased. The results are shown in Table 1.
PTC and KOH must coexist in this oxidation system (Table 1, entries
4–6). The yield of 2a was raised to 92% in a shorter period (4 h) if both
CTAB and KOH were present in the reaction system (Table 1, entry 5).
CTAB was also crucial for achieving high yields of 2a because the yield

4190
Q. Liu et al.
Table 1. CTAB-catalyzed oxidation of 4-isopropylbenzyl chloride with KNO3 in
aqueous mediaa
Entry KNO3 (mol) CTAB (mmol) KOH (mol) Time (h) Yield (%)b
1
2
3
4
5
6
0.11
0.11
0.11
0.11d
0.11d
0.11d
10
10
4
4
4
12
57
71c
39
92
91
1.1
1.1
0.11
0.11
0.11
0.11
1.1
1.2
4
aReaction conditions: 4-isopropylbenzyl chloride (0.1 mol), H2O (15 mL),
reflux.
bIsolated yield.
cAbout 2 g cumenic acid (mp: 117–119 ꢀC, lit.[22] mp 118–120 ꢀC) was obtained
by acidifying the reaction aqueous solution with hydrochloric acid.
dAdded 10% KOH aqueous solution (60 mL, 0.1 mol) dropwise over the
indicated time with a dropping funnel.
Table 2. PTC-catalyzed oxidation of 4-isopropylbenzyl chloride with KNO3 in
aqueous mediaa
Phase-transfer catalyst
Time (h)
Yield (%)b
CTAB
TEAB
TBAB
DTAB
4
12
8
92
53
71
80
6
aReaction conditions: 4-isopropylbenzyl chloride (0.1 mol), KNO3 (0.11 mol),
H2O (15 mL), PTC (1.1 mmol); 10% KOH aqueous solution (60 mL, 0.11 mol)
added dropwise with a dropping funnel over 4 h, reflux.
bIsolated yield.

Oxidation of Benzyl Halides
4191
decreased to 39% in the absence of CTAB (Table 1, entry 4) but
increased to 92% in the presence of CTAB (1.1 mmol). Using 1.2 mmol
of CTAB, under the same conditions, the yield was not enhanced signif-
icantly. At lower temperatures such as 70 or 90ꢀC, this oxidation reac-
tion proceeded very slowly. Therefore, the optimal reaction conditions
were observed in Table 1, entry 5. Besides CTAB, we also tried to
use tetraethylammonium bromide (TEAB), tetrabutylammonium bro-
mide (TBAB), and dodecyltrimethylammonium bromide (DTAB) as
PTCs in this catalytic oxidation system. However, the yields were
merely 53%, 71%, and 80%, respectively (Table 2). The best PTC is
CTAB.
Various benzyl halides could also be converted to the correspond-
ing aldehydes=ketones under the same reaction conditions (Table 3).
The benzyl halides with electron-withdrawing groups could be more
easily oxidized to the corresponding aldehydes=ketones than those con-
taining electron-releasing ones. Thus, many aldehydes=ketones with
electron-releasing groups need longer reaction times to obtain higher
yields (Table 3). The substrates with a strong electron-withdrawing
nitro groups resulted in an intractable mixture (Table 3, entry 15),
and all efforts to isolate the resulting aldehydes from the mixture failed.
Further, the present catalytic oxidation system was not a good choice
for the oxidation of 4-methoxybenzyl halides and gave only 25%
isolated yield of 4-methoxybenzaldehyde with two by-products: 4-
methoxybenzyl alcohol (34%) and 4-methoxybenzoic acid (35%). No
aliphatic aldehydes could be produced through the oxidation of alipha-
tic halides under the same reaction conditions. The yield for oxidation
of benzyl bromide to aldehydes=ketones was slightly higher than that
for benzyl chloride (Table 3).
The oxidation mechanism in the present reaction system is well
documented in the literature.[5] Because the formation of benzyl nitrate
esters was observed in the reaction, we believe that benzyl halides were
first transported to the corresponding nitrate esters by treatment with
aqueous potassium nitrate solutions catalyzed by PTC and then transfor-
mation of the resulting nitrate ester into the corresponding aldehydes and
ketones under the synergism of PTC and KOH. To confirm this specula-
tion, we performed the reaction of 4-isopropylbenzyl chloride 1a
(0.1 mol) with potassium nitrate (0.11 mol) and 1.1 mmol of CTAB under
our catalytic system at reflux for 1.5 h and found that 16.0 g (82%) of
4-isopropylbenzyl nitrate ester 3a was indeed formed (Scheme 1). Elimi-
nation of nitrite acid from the resulting ester by KOH with the help of
CTAB gave the desire 4-isopropylbenzaldehyde. Based on these results,
we propose the plausible mechanism of the oxidation process shown
in Scheme 1.

4192

4193

4194
Q. Liu et al.
Scheme 1. Proposed mechanism for the oxidation of benzyl halides with KNO3
catalyzed by CTAB and KOH.
CONCLUSION
In conclusion, we have developed a new, economic, convenient, and
ecofriendly method for the preparation of aromatic aldehydes and ketones
from benzyl halides. Judging from the conditions employed, this oxidation
method showed has great prospects in industrial applications. Efforts to
elucidate the scope and limitations of this oxidation system are under way.
EXPERIMENTAL
Typical Reaction Procedures
To the reaction mixture of 4-isopropylbenzyl chloride (16.8 g, 0.1 mol),
KNO3 (11.1 g, 0.11 mol), CTAB (0.4 g, 1.1 mmol), and H2O (15 mL),
10% aqueous KOH solution (60 mL, 0.11 mol) was added dropwise with
a dropping funnel to keep the pH value at 10–11 over 4 h at reflux with
vigorous stirring. The reaction progress was monitored by GC Agilent
6890 with a FID and a DB-1701 column, 30 m ꢁ 0.25 mm i.d. At the
end of the experiment, the organic product was extracted with ether
(3 ꢁ 50 mL); washed with water to remove any traces of CTAB, KNO3,
and KOH; and dried over anhydrous Na2SO4. The solvent was removed,
and the residue was distilled under vacuum to give pure 4-isopropylben-
zaldehyde (bp: 86–87 ꢀC=5 mmHg, lit.[23] 41–42 ꢀC=1.20 mmHg) in 92%
1
yield identified by H NMR or its authentic sample.
Preparation of 4-Isopropylbenzyl Nitrate (3a)
A mixture of 4-isopropylbenzyl chloride (16.8 g, 0.1 mol), KNO3 (11.1 g,
0.11 mol), CTAB (0.4 g, 1.1 mmol), and H2O (15 mL) was heated to reflux

Oxidation of Benzyl Halides
4195
for 1.5 h. After the reaction mixture was cooled to room temperature, it
was extracted with ether (3 50 mL), washed with water to remove any
traces of CTAB and KNO3, and dried over anhydrous Na2SO4. The sol-
vent was removed, and the residue was distilled under vacuum to give
pure 4-isopropylbenzyl nitrate (3a, a colorless liquid, 16.0 g, 82%). Bp:
62–63 ꢀC=5 mmHg. 1H NMR (CDCl3, 300 MHz): d 1.24 (6H, d,
J ¼ 6.9 Hz, CH3), 2.87–2.97 (1H, m, CH), 5.39 (2H, s, CH2), 7.26 (2H,
d, J ¼ 8.1 Hz, Ar), 7.32 (2H, d, J ¼ 7.9 Hz, Ar). MS (m=z, %): 195 (Mþ,
68), 196 (Mþ þ1, 8), 180 (Mþ ꢁ15, 9), 149 (Mþ ꢁ46, 98), 133 (Mþ ꢁ62,
86), 119 (Mþ ꢁ76, 97), 105 (Mþ ꢁ90, 72), 91 (Mþ ꢁ104, 100), 79
(Mþ ꢁ116, 41). Elemental analysis: C, 61.53%; H, 6.71%, N, 7.18%; O,
24.58% calculated from C10H13NO3. Found: C, 61.55%; H, 6.71%; N,
7.16%; O, 24.52%.
Analytical Data of New Products
2-Isopropylbenzaldehyde (5)
Bp: 84–85 ꢀC=5 mm. 1H NMR (CDCl3, 300 MHz): d 1.28 (6H, d,
J ¼ 7.8 Hz, CH3), 2.98 (1H, m, CH), 7.44 (1H, dd, J ¼ 8.2, 8.2 Hz, Ar),
7.49 (1H, d, J ¼ 8.2 Hz, Ar), 7.82 (1H, d, J ¼ 8.2 Hz, Ar), 8.05 (1H, s,
Ar), 10.54 (1H, s, CHO). MS (m=z, %): 148 (Mþ, 67), 147 (Mþ ꢁ1,
11), 133 (Mþ ꢁ15, 100), 119 (Mþ ꢁ29, 30), 105 (Mþ ꢁ43, 68), 77
(Mþ ꢁ71, 29). Elemental analysis: C, 81.04%; H, 8.16%; O, 10.80%
calculated from C10H13NO3. Found: C, 80.94%; H, 8.15%; O, 10.83%.
4-tert-Butyl-2, 6-Dimethylbenzaldehyde (9)
Mp: 128–129 ꢀC, bp: 168–170 ꢀC=5 mmHg. 1H NMR (CDCl3, 500 MHz):
d 1.32 [9H, s, 4-C(CH3)3], 2.39 (6H, s, 2, 6-CH3), 7.12 (2H, s, 3,5-Ar-H),
10.59 (H, s, CHO). MS (m=z, %): 190 (Mþ, 45), 189 (Mþ ꢁ1, 58), 161
(Mþ ꢁ29, 12%), 147 (Mþ ꢁ43, 6.2), 133 (Mþ ꢁ57, 100), 119 (Mþ ꢁ71,
10), 91 (Mþ ꢁ101, 17), 77 (Mþ ꢁ113, 64). Elemental analysis: C,
82.06%; H, 9.53%; O, 8.41% calculated from C10H13NO3. Found: C,
81.98%; H, 9.52%; O, 8.56%.
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