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Chapter -8
Conversion of benzylic bromides to benzaldehydes
using sodium nitrate as an oxidant in water
8.1
Introduction
165
8.2
Experimental
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8.2.1 Experimental procedure for the synthesis of benzaldehyde
from benzyl bromide with sodium nitrate
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8.3
Results and discussion
169
8.4
Spectral data of aldehydes
175
8.5
Conclusion
179
8.6
References
180
164
Conversion of benzylic bromides to benzaldehydes
using sodium nitrate as an oxidant in water
8.1 Introduction
Aromatic aldehydes can be prepared by the direct introduction of
a formyl group onto an aromatic nucleus through reactions such as the
Gatterman-Koch reaction [1], the Reimer-Tiemann reaction [2] and
the Vilsmeier reaction [3]. Moreover, the formyl group can be
generated
from
an
appropriate
precursor
group
such
as
a
hydroxymethyl, an acid chloride, a halomethyl or a methyl group,
attached the aromatic ring. However, the preparation of aromatic
aldehydes from benzyl alcohols can be difficult, due to over-oxidation
to carboxylic acid under the reaction condition. To avoid this, many
synthetic methods have been described in literature. One of the most
important methods, because of its selectivity is the oxidation of
benzylic halides to benzaldehydes.
Benzylic halides can be prepared
easily through the photo-halogenation of aromatic methyl group [4] or
by Blanc chloromethylation reaction [5]. The benzylic bromides can
also be simply prepared in very good yield by two-phase electrolysis of
20-50% NaBr solution by in-situ generation of bromine, without using
toxic and costly brominating agents [6].
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The preparation of aromatic aldehydes from benzylic halides,
therefore, is an attractive route to aromatic aldehydes as it involves no
special conditions such as very high temperature, pressure and
proceeds smoothly without any special catalyst and several methods
have been developed to carry out this conversion. One such reaction is
the Sommelet reaction using hexamine as a reagent [7]. Reagents
that convert benzyl halides to benzaldehydes include 2-nitropropaneNaoEt
in
EtoH
p-nitrosodimethylaniline
[8],
and
mercury-ethanolic
water
(Krohnke
alkali
[9],
reaction)
[10],
NaIO4-DMF [11] and IBX [12]. Primary halides can also be oxidised to
aldehydes using trimethylamine oxide [13], 4—dimethylaminopyridineN-oxide [14], other amine oxides [15], pyridine N-oxide under
microwave irradiation [16], K2CrO4 in HMPA in the presence of a crown
ether [17] and MnO2 [18].
In the Kornblum reaction, benzyl halides are refluxed in DMSO
along with sodium bicarbonate to give the corresponding aldehydes
[19]. In this reaction, the nucleophilic oxyanion of DMSO attacks the
benzylic halide in an SN2 reaction and displaces the halide to form an
alkoxysulfonium salt. The base often abstracts a benzylic proton to
form the aldehyde. The reaction has recently been attempted under
microwave irradiation [20]. An efficient and convenient oxidation of
organic halides to carbonyl compounds by H2O2 in ethanol was studied
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by Tang et al. [21]. Substituted benzene 1,2-di carbaldehyde was
synthesized by the reaction of substituted 1,2-bis (dibromomethyl)
benzenes with fuming H2SO4, followed by hydrolysis.
Yield was
improved by introducing solid NaHCO3 into the reaction mixture before
hydrolysis and work up [22]. NaIO4 mediated selective oxidation of
benzylic alcohols were oxidized to carbonyl derivatives using water as
solvent was studied by Shaikh et al. and
benzaldehyde was
exclusively obtained in 79% yield with no formation of benzoic acid.
The benzylic bromides were oxidized with NaIO4, LiBr/H+ and
benzoic acid was obtained as product in high yield (71-89%). In this
case the reaction could not be stopped at the aldehyde stage itself.
The use of stoichiometric amount of NaIO4 (50 mol %) generally gave
poor yields of carboxylic acids. However, benzyl chloride was resistant
to undergo oxidation under the reaction conditions, probably because
of the higher bond strength of the C-Cl bond [23].
The major disadvantages of the above processes are the use of
costly reagents, high reaction times and lower conversion. Even
though HNO3 is very well established as an oxidant [24] its sodium
salt, NaNO3 which is easy to handle has very few report [25] for its
oxidising capacity.
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To explore the oxidising capacity of NaNO3 and to overcome the
above mentioned drawbacks, herein we describe the use of sodium
nitrate (20%) as an oxidising agent for the oxidation of benzylic
bromides to benzaldehydes (Scheme 8.1).
CH2OH
NaNO3
CH2Br
80 oC
R
CHO
NaNO3
120 oC
80 min
80 min R
R
R= H, Cl, Br, t-butyl, CH3, CH2Br, NO2
Scheme 8.1 Synthesis of benzaldehydes from benzyl bromides using
NaNO3
8.2 Experimental
8.2.1 Representative procedure for the synthesis of benzaldehyde
from benzyl bromide with sodium nitrate
To a 100 ml two-neck round-bottomed flask, fitted with a water
condenser, benzyl bromide (0.855 g, 5mmol), 25 ml of 20% sodium
nitrate solution were taken and the reaction mixture was stirred at
120 oC for 1 hour and 20 minutes. The reaction was monitored by
HPLC (Shimadzu) using methanol and water (80:20) as eluent. After
completion of reaction, the reaction mixture was cooled to room
temperature and aldehyde was extracted with diethyl ether. The
organic layer was separated, washed with cold water (3x30 ml), dried
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over Na2SO4, and evaporated under a vacuum to afford 0.459 g of
benzaldehyde(91% yield) as product along with 2% benzyl bromide
and 5% benzyl alcohol.
8.3 Results & discussion
Benzaldehyde was prepared in 91% yield from benzyl bromide
with 98% conversion at 120
o
C, in water without using an organic
solvent, whereas 81% of benzyl alcohol was obtained at a temperature
of 80
o
C in 80 minutes. This protocol demonstrates the direct
conversion of benzylic bromides into the corresponding benzaldehydes
in good yields with high conversion. The conversion of benzyl bromide
to benzaldehyde was taken as a model reaction for optimization. The
reaction was carried out at different temperatures with different
concentrations
of
sodium
nitrate
and
it
was
found
that
91%
benzaldehyde was formed as product at 120 oC, whilst benzyl alcohol,
an industrial important compound was formed in 81 % yield at 80 oC
with minor amount of aldehyde. Hence, the reaction temperature plays
a crucial role in the formation of different products. Among the other
nitrate salts used to oxidise the bromide to aldehyde, potassium
nitrate performs equally well, but the sodium nitrate is preferred due
to its low cost than the other salts. During the reaction, the reaction
mixture was stirred well with a stirring rate of 100 rpm.
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The reaction takes place in the following manner, which is
confirmed by the change of neutral pH of the initial reaction mixture
(sodium nitrate solution) to acidic (pH =2.3) at the end of the
reaction.
RCH2Br + NaNO3 -----Æ
RCHO
+ NaBr + HNO2
Under the optimised condition, various benzyl bromides were
reacted with 20% sodium nitrate solution at a temperature of 120 oC
to obtain the corresponding benzaldehydes (Table 8.1). In the present
scheme, we are not using any of the costly oxidising agents such as
manganese dioxide, peracid, periodate, IBX, and hydrogen peroxide
but the cheap NaNO3 was used in excess.
As the density of benzyl bromide is lower than aqueous sodium
nitrate solution (20%), two phases (organic and aqueous) exists at the
start of reaction and the reaction mixture becomes homogenous
during the course of reaction, due to better stirring with raise in
temperature. When the reaction is over, the phase separation occurs
as the reaction mixture attains room temperature. The phase
separation has the advantage of isolating the product by simple
extraction with organic solvent.
It was observed that the benzyl bromides of unsubstituted,
substituted with electron donating groups undergo the reaction in
shorter duration with maximum yield of benzaldehydes (entry 1,2),
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whilst the mild , strong electron withdrawing group substituted benzyl
bromides require two to five fold reaction time for the same conversion
to occur (entry 6,7) along with benzyl alcohol as side product. In all
the cases the conversions were > 95%. This process is carried out in
organic solvent free conditions and gives high conversion and yield.
The use of cheap NaNO3 reagent and water as solvent makes the
process economic and attractive.
In the conversion of benzylic bromides to benzylic alcohols, 20%
sodium nitrate solution is used as oxidant and the temperature of the
reaction mixture was maintained at 80
o
C for a specific time as
mentioned in the Table 8.2. Unsubstituted benzyl bromide gave 82%
benzyl alcohol and the other bromides substituted with electron
donating or electron withdrawing groups gave only 30-35 % benzyl
alcohols along with equal amount of aldehyde.
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Table 8.1 Distribution of products in the conversion of Benzylic
bromides with 20% sodium Nitrate as oxidant at 120 oC
S No
1
2
3
4
5
Reactant
CH2Br
Producta
CHO
CH2Br
CHO
CH3
CH3
CH2Br
CHO
CH2Br
CHO
C H 2 Br
CHO
CH2Br
CHO
Cl
Cl
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Time
(min)
80
Yieldb
(%)
91
90
88
90
86
445
84
120
75
6
7
8
CH2Br
CHO
Br
Br
CH2Br
CHO
NO2
NO2
CH2Br
CHO
CH2Br
9
CH2Br
CHO
CH3
CH2Br
80
480
50
180
51
120
70
145
68
CH2Br
Cl
10
150
Cl
CH3
CHO
a = The structures of the products were established from the spectral
data (1H NMR, FTIR) and by comparison with the authentic samples
through HPLC analysis.
b = isolated yield
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Table 8.2 Synthesis of benzyl alcohol from benzyl bromide with 20%
sodium Nitrate as oxidant at 80 oC
S No
1
2
3
Reactant
CH2Br
Product
CH2OH
CH2Br
CH2OH
CH3
CH3
CH2Br
CH2Br
CH2OH
Yield
(%)
81
90
30
120
35
300
33
120
32
CH2OH
4
CH3
CH3
CH2OH
CH2Br
5
Time
(min)
80
CH2Br
CH2OH
Cl
Cl
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8. 4 Spectral data of aldehydes
1.Benzaldehyde:IR(neat)3064,3031,2852,2820,2732,1654,1597,158
4,1455,1391,1167,828 cm-1. 1H NMR(400MHz, CDCl3): δ 9.90(s, 1H),
7.87-7.90(m,2H),
7.45- 7.67(m,3H).
2.4-Bromobenzaldehyde:IR(neat)
2920,2881,1689,1588,1289,1205,1154,1066,1009,811 cm-1. 1H NMR
(400MHz, CDCl3): δ 9.98(s, 1H),7.769(d,J=8.6 Hz,2H),7.69(d, J=8.6
Hz,2H).
3.4-Methylbenzaldehyde:IR(neat)
3082, 2969, 1712, 1607, 1538, 1344, 1293, 1196, 854 cm-1. 1H NMR
(400MHz, CDCl3): δ 10.1(s,1H),8.41(d,J=8.5 z,2H),8.08(d,J=8.5Hz, 2H).
4.Nitrobenzaldehyde:IR(neat)
3093,2978,2864,1713,1605,1540,1343,1294,1197,853 cm-1. 1H NMR
(400MHz, CDCl3): δ 10.3(s, 1H), 8.36 (d, J=8.5Hz,2H),8.07(d, J=8.5
Hz,2H).
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176
Figure 8.2 HPLC data of benzaldehyde obtained by oxidation of benzyl
bromide using 20% NaNO3.
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Figure 8.3 HPLC data of authentic benzaldehyde
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8.5 Conclusion
In summary, it has been demonstrated that the oxidation of
benzyl bromides at 120 oC to the corresponding benzaldehydes as
product in good yields (91%). sodium nitrate solution (20%) is used
under organic solvent free condition in shorter reaction time and
benzylic alcohols are formed as a major product (81% yield) at 80 oC.
This method avoids the usage of harmful organic solvent and water is
used as solvent. In the present method, the reaction occurs under mild
conditions with simple and clean workup.
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8.6 References
1. (a) Truce, W. E. Org. React. 1957, 9, 37; (b) Tanaka, M.; Fujiwara, M.;
Ando, H.
J. Org. Chem. 1995, 60, 2106.
2. Wynberg, N.; Meijer, E. W. Org. React. 1982, 28, 1.
3. Jutz, C. Adv. Org. Chem. 1976, 9, 225.
4. Poutsma, M. L.; Kochi, J. K. In Free-Radical; Wiley: New York, 1973; Vol.
2,
159.
5. Belen’Kii, L. I.; Vol’Kenshtein, Y. B.; Karmanova, I. B. Russ. Chem. Rev.
1977, 46, 891.
6.
Raju,
T.;
Kulangiappar,
K.;
Anbu
kulandainathan,
M.;
Muthukumaran, A. Tetrahedron Lett. 2005, 46, 7047.
7. Angyal, S. J. Org. React. 1954, 8, 197.
8. Hass, H. B.; Bender, M. L. J. Am. Chem. Soc. 1949, 71, 1767.
9. McKillop, A.; Ford, M. E. Synth. Commun. 1974, 4, 45.
10. Krohnke, F. Angew. Chem., Int. Ed. Engl. 1963, 2, 380.
11. Das, S.; Panigrahi, A. K.; Maikap, G. C. Tetrahedron Lett. 2003, 44,
1375.
12. Moorthy, J. N.; Singhal, N.; Senapati, K. Tetrahedron Lett. 2006, 47,
1757.
13. Franzen, V.; Otto, S. Chem. Ber. 1961, 94, 1360.
14. Mukaiyama, S.; Inanaga, J.; Yamaguchi, M. Bull. Chem. Soc. Jpn.
1981,
54, 2221.
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15. Suzuki, S.; Onishi, T.; Fujita, Y.; Misawa, H.; Otera, J. Bull.
Chem.Soc. Jpn. 1986, 59, 3287.
16. Barbry, D.; Champagne, P. Tetrahedron Lett. 1996, 37, 7725.
17. (a)Cardillo, G.; Orena, M.; Sandri, S. J. Chem. Soc., Chem.
Commun. 1976, 190;
(b) Cardillo, G.; Orena, M.; Sandri, S. Tetrahedron Lett.
1976,
17, 3985.
18. Goswami, S.; Jana, S.; Dey, S.; Adak, A.K. Chemistry Lett. 2005,
34, 194.
19. (a) Nace, H. R.; Monagle, J. J. J. Org. Chem. 1959, 24, 1792; (b)
Kornblum, N.; Jones, W. J.; Anderson, G. J. J. Am. Chem. Soc. 1959,
81, 4113.
20. Xu, G.; Wu, J. P.; Ai, X. M.; Yang, L. R. Chin. Chem. Lett. 2007, 18,
643.
21. Tang, J.; Zhu, J .;
Shen, Z.; and Zhang, Y. Tetrahedron Lett.
2007, 48, 1919.
22. Zhu Peter, C. Science in China series – B: Chemistry, 2007, 50,
249.
23. Shaikh, T.M.A.; Emmanuvel, L.; Sudalai, A. J. Org. Chem.2006,
71, 5043.
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24.(a) Joshi, S. R.; Kataria, K. L.; Sawwanth, B. S,; Joshi, J. B. Ind.
Eng.
Chem. Res. 2005, 44, 325. (b) Lee, J.; Lee, J. N.; Lee, J. M.
Bull. Korean Chem. soc. 2007, 26, 1300.
25. Putnam, M. E. U.S Patent, 1918. 1,272,522.
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