N-methyl morpholine chlorochromate: An efficient reagent for oxidation of primary and secondary alcohols to carbonyl compounds

Article abstract of DOI:10.1080/00397910802219502

Instantaneous generation of N-methyl morpholine chlorochromate (NMMCC) is an efficient reagent for oxidation of primary and secondary alcohols to the corresponding carbonyl compounds. The comparison of reaction time and product yield was studied with novel NMMCC and other chlorochromate reagents and shows that the presented method requires less reaction time with good yield at laboratory temperature. The synthesis of reagent, formation of toxic and hazardous chromylchloride have been avoided, and also use of NMMCC under microwave irradiation for oxidation leads to fast reaction time and success of the strategy. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910802219502

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N-Methyl Morpholine
Chlorochromate: An Efficient
Reagent for Oxidation of
Primary and Secondary
Alcohols to Carbonyl
Compounds
S. Chandrappa a , M. P. Sadashiva a & K. S. Rangappa
a
a Department of Studies in Chemistry, University of
Mysore, Manasagangotri, Mysore, India
Version of record first published: 09 Sep 2008
To cite this article: S. Chandrappa, M. P. Sadashiva & K. S. Rangappa (2008): N-
Methyl Morpholine Chlorochromate: An Efficient Reagent for Oxidation of Primary
and Secondary Alcohols to Carbonyl Compounds, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 38:15,
2638-2645
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Synthetic Communications1, 38: 2638–2645, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910802219502
N-Methyl Morpholine Chlorochromate: An
Efficient Reagent for Oxidation of Primary and
Secondary Alcohols to Carbonyl Compounds
S. Chandrappa, M. P. Sadashiva, and K. S. Rangappa
Department of Studies in Chemistry, University of Mysore, Manasagangotri,
Mysore, India
Abstract: Instantaneous generation of N-methyl morpholine chlorochromate
(NMMCC) is an efficient reagent for oxidation of primary and secondary alco-
hols to the corresponding carbonyl compounds. The comparison of reaction time
and product yield was studied with novel NMMCC and other chlorochromate
reagents and shows that the presented method requires less reaction time with
good yield at laboratory temperature. The synthesis of reagent, formation of toxic
and hazardous chromylchloride have been avoided, and also use of NMMCC
under microwave irradiation for oxidation leads to fast reaction time and success
of the strategy.
Keywords: Alcohols, carbonyl compounds, microwave irradiation, N-methyl
morpholine chlorochromate (NMMCC), oxidation
INTRODUCTION
Oxidation of alcohols to aldehydes or ketones is a ubiquitous transform-
ation in organic chemistry. Chromium and chromium trioxide complexes
are the mild reagents most extensively used for oxidation in the labora-
tory.[1–8] Unfortunately, most of them suffer at least from one of the
following disadvantages: high cost of preparation, long reaction time,
hygroscopisity, high acidity, instability, selectivity, and photosensitivity.
Various modifications of the procedure have been developed to minimize
Received February 15, 2008
Address corresponding to K. S. Rangappa, Department of Studies in Chemistry,
University of Mysore, Manasagangotri, Mysore 570006, India. E-mail: rangappaks@
gmail.com, rangappaks@chemistry.uni-mysore.ac.in
2638

N-Methyl Morpholine Chlorochromate
2639
these problems: (i) the reaction needs to be carried out at higher tempera-
ture (reflux temperature), (ii) loss of reagent yield (70–75%) at the
reagent synthesis step[9–12] because of high water solubility, and (iii) the
formation of chromyl chloride as side product, which is a very toxic
and hazardous compound.
Our present work deals with the instantaneous generation of a
novel N-methyl morpholine chlorochromate (NMMCC) reagent for
the oxidation of primary and secondary alcohols to the corresponding
carbonyl compounds in a single step, and the reaction is carried out at
room temperature (25 ꢀC). This reagent is efficient, and the formation
of toxic and hazardous chromyl chloride is avoided.
The practicality of microwave irradiation to enhance chemical-
reactions by increasing the reaction rates and formation of cleaner
products has been recognized. It is clear that synergic applications of
microwave-assisted technology allow rapid synthesis of biologically
significant molecules on that support.
RESULTS AND DISCUSSION
The comparative study of the rate of reaction and the product yield using
the conventional method (CM) with known chlorochromate reagents and
the present novel reagent (NMMCC) informed us that the proposed
reagent is efficient and consumes less time at laboratory temperature
with high yield (Table 1). Further, microwave technology shows fast
synthesis of the desired products with our new oxidation reagent.
Equimolar ratio of saturated hydrochloric acid in dry ether was
added slowly to the cold solution of N-methyl morpholine in dry chloro-
form with constant stirring. The solution was cooled to 0–5 ꢀC, and then
chromium trioxide was added portionwise. The reaction mixture was stir-
red for 10 min at the same temperature, followed by the addition of alco-
hol. Then the reaction mixture was stirred for 30–50 min at room
temperature (Scheme 1). In a similar fashion, the reaction was carried
out via microwave irradiation at 65 ꢀC and the reaction completed within
10 min (Table 1). The reaction was monitored by thin-layer chromato-
graphy (TLC). Upon completion, the reaction mass was filtered, and
the filtrate was evaporated under reduced pressure. The crude residue
was purified by a short-length silica-gel column. Finally, the pure product
1
was confirmed by H NMR, infra red (IR), and liquid chromatography
and mass spectra (LCMS) analysis.
In conclusion, we report a novel and efficient methodology for the
oxidation of aliphatic and aromatic alcohols to the corresponding car-
bonyl compounds. The mild, stable, inexpensive, and straightforward

2640
S. Chandrappa, M. P. Sadashiva, and K. S. Rangappa
Table 1. Oxidative comparison of reaction rates of alcohols with the presented
reagent (NMMCC) by conventional and microwave methods
Present method (NMMCC)
Time (min)
CM MW
50
Yield (%)
Compounds
R1
R2
CM
MW
99
3a
6
96
3b
3c
H
H
45
55
7
7
93
95
98
98
3d
H
50
5
90
99
3e
3f
H
H
50
45
5
6
90
92
96
96
3g
3h
H
H
48
45
7
6
91
93
98
98
3i
3j
H
H
50
45
6
5
95
90
99
97
Note. CM ¼ conventional method; MW ¼ microwave method.

N-Methyl Morpholine Chlorochromate
2641
Scheme 1. Reaction condition: (a) rt, 30–50 min; (b) MW (65 ꢀC), 5–10 min.
workup makes this method novel. In addition, this method does not
require a large amount of the reagent or long reaction time.
EXPERIMENTAL
General
Silica-gel column chromatography was performed using Merck 7734
silica gel (60–120 mesh) and Merck-made TLC plates (Merck F254).
IR spectra were recorded using a Jasco FTIR-4100 series instrument.
1H NMR spectra were recorded on a Shimadzu AMX 400-Bruker
400-MHz spectrometer using DMSO-d6 and CDCl3 as solvent and
TMS as internal standard (chemical shift in d ppm). Spin multiplets are
given as s (singlet), d (doublet), t (triplet), and m (multiplet). Microwave
using Biotase Initiator (TM2.0) and mass spectra were determined in an
ionization energy (EI) at 70 eV ionizing voltage.
Oxidation of benzhydrol to benzophenone (3a)
Equimolar ratio of saturated hydrochloric acid in dry ether (0.5 mL) was
added slowly to the cold solution of N-methyl morpholine (0.5 mL) in dry
chloroform with constant stirring. The solution was cooled to 0–5 ꢀC, and
then chromium trioxide (180 mg, 1.5 mmol) was added portionwise. The
reaction mixture was stirred for 10 min at the same temperature, and then
the reactant benzhydrol (150 mg, 1 mmol) was added and stirred at room
temperature for 30–50 min. The same reaction was done through a micro-
wave cavity at 65 ꢀC; the reaction completes in 6 min. The reaction was
monitored by thin-layer chromatography (TLC). The resulting crude
product was purified by a short-length silica-gel column (60–120 mesh)

2642
S. Chandrappa, M. P. Sadashiva, and K. S. Rangappa
using hexane–ethyl acetate (8:2) as an eluent. The reaction time and yield
of desired oxidation products are shown in Table 1.
The obtained pure product was in off-white crystalline solid (0.142 g,
96%). 1H NMR (d6-DMSO, 400 MHz): d 7.8 (m, 4H, Ar-H), 7.6 (m, 2H,
Ar-H), 7.5 (m, 4H, Ar-H). IR (KBr, cmꢁ1): 1651, 1594, 1446, 1318, 1277.
MS (ESI þ ion): m=z ¼ 183.2.
Oxidation of 4-methoxy benzyl alcohol to 4-methoxy
benzaldehyde (3b)
The typical synthetic method described above afforded 3b; the product
obtained was a colorless liquid (0.146 g, 93%) from 4-methoxy benzyl
alcohol 2b (0.16 g, 1.0 mmol).
1H NMR (DMSO-d6, 400 MHz): d 9.86 (s, 1H, Ar-CHO), 7.87 (t, 2H,
Ar-H, J ¼ 8 Hz), 7.12 (t, 2H, Ar-H, J ¼ 8 Hz), 3.85 (s, 3H, ꢁOCH3). IR
(Nujol, cmꢁ1): 1684, 1599, 1261, 1160, 833. MS (ESI þ ion): m=z ¼ 136.7.
Oxidation of 3-hydroxy benzyl alcohol to 3-hydroxy benzaldehyde (3c)
The typical synthetic method described above afforded 3c; the product
obtained was a colorless liquid (0.140 g, 95%), from 3-hydroxy benzyl
alcohol 2c (0.15 g, 1.0 mmol).
1H NMR (DMSO-d6, 400 MHz): d 10 (s, 1H, Ar-CHO), 9.93 (s, 1H,
Ar-OH), 7.42 (m, 1H, Ar-H), 7.3 (m, 1H, Ar-H), 7.25 (m, 1H, Ar-H), 7.1
(m, 1H, Ar-H). IR (Nujol, cmꢁ1): 1669, 1580, 1492, 1284, 1152, 782. MS
(ESI ꢁ ion): m=z ¼ 120.6.
Oxidation of 3-nitro benzyl alcohol to 3-nitro benzaldehyde (3d)
The typical synthetic method described above afforded 3d; the product
obtained was a pale yellow solid (0.130 g, 90%) from 3-hydroxy benzyl
alcohol 2d (0.15 g, 1.0 mmol).
1H NMR (DMSO-d6, 400 MHz): d 10.13 (s, 1H, Ar-CHO), 8.6
(m, 1H, Ar-H), 8.5 (m, 1H, Ar-H), 8.3 (m, 1H, Ar-H), 7.9 (t, 1H,
Ar-H, J ¼ 8.0 Hz). IR (KBr, cmꢁ1): 1705, 1560, 1350, 1200. MS (ESI þ ion):
m=z ¼ 151.1.
Oxidation of 4-fluoro benzyl alcohol to 4-fluoro benzaldehyde (3e)
The typical synthetic method described above afforded 3e; the product
obtained was a colorless liquid (0.270 g, 90%) from 4-fluoro benzyl

N-Methyl Morpholine Chlorochromate
2643
1
alcohol 2e (0.3 g, 1.0 mmol). H NMR (DMSO d6, 400 MHz): d 9.96 (s,
1H, Ar-CHO), 7.98 (m, 2H, Ar-H), 7.4 (m, 2H, Ar-H). IR (Nujol, cmꢁ1):
1698, 1597, 1506, 1232, 1150, 835, 598. MS (ESI þ ion): m=z ¼ 124.0.
Oxidation of 4-ethoxy benzyl alcohol to 4-Ethoxy benzaldehyde (3f)
The typical synthetic method described above afforded 3f; the product
obtained was a colorless liquid (0.184 g, 92%) from 4-ethoxy benzyl alco-
1
hol 2f (0.2 g, 1.0 mmol). H NMR (DMSO-d6, 400 MHz): d 9.85 (s, 1H,
Ar-CHO), 7.84 (d, 2H, Ar-H, J ¼ 8.0 z), 7.08 (d, 2H, Ar-H, J ¼ 8.0 z),
4.13 (q, 2H, ꢁOCH2), 1.35 (t, 2H, ꢁCH3). IR (Nujol, cmꢁ1): 1692,
1601, 1509, 1259, 1160, 1041, 834, 615. MS (ESI þ ion): m=z ¼ 150.7.
Oxidation of 4-chloro-3-nitro benzyl alcohol to 4-chloro-3-nitro
benzaldehyde (3g)
The typical synthetic method described above afforded 3g; the product
obtained was a colorless liquid (0.182 g, 91%) from 4-ethoxy benzyl alco-
1
hol 2g (0.2 g, 1.0 mmol). H NMR (DMSO-d6, 400 MHz): d 9.85 (s, 1H,
Ar-CHO), 7.84 (d, 2H, Ar-H, J ¼ 8.0 Hz), 7.08 (d, 2H, Ar-H,
J ¼ 8.0 Hz), 4.13 (q, 2H, ꢁOCH2), 1.35 (t, 2H, ꢁCH3). IR (Nujol, cmꢁ1):
): 1692, 1601, 1509, 1259, 1160, 1041, 834, 615. MS (ESI þ ion):
m=z ¼ 186.7.
Oxidation of 2-chloro-6-fluoro benzyl alcohol to 2-chloro-6-fluoro
benzaldehyde (3h)
The typical synthetic method described above afforded 3h; the product
obtained was an off-white crystalline solid (0.186 g, 93%) from
2-chloro-6-fluoro benzyl alcohol 2h (0.2 g, 1.0 mmol).
1H NMR (DMSO-d6, 400 MHz): d 10.3 (s, 1H, Ar-CHO), 7.75 (m,
1H, Ar-H), 7.52 (m, 1H, Ar-H), 7.46 (m, 1H, Ar-H). IR (KBr, cmꢁ1):
1703, 1600, 1454, 1248, 1192, 911, 790. MS (ESI ꢁ ion): m=z ¼ 156.7.
Oxidation of benzyl alcohol to benzaldehyde (3i)
The typical synthetic method described above afforded 3i; the product
obtained was a colorless liquid (0.140 g, 95%) from benzyl alcohol 2i
(0.15 g, 1.0 mmol).
1H NMR (DMSO-d6, 400 MHz): d 9.94 (s, 1H, Ar-CHO), 8–7.5 (m,
5H, Ar-H). IR (Nujol, cmꢁ1): 1702. MS (ESI þ ion): m=z ¼ 107.0.

2644
S. Chandrappa, M. P. Sadashiva, and K. S. Rangappa
Oxidation of 2-aminoethanol to 2-aminoacetaldehyde (3j)
The typical synthetic method described above afforded 3j; the product
obtained was a colorless liquid (0.180 g, 90%) from aminoethanol 2j
(0.2 g, 1.0 mmol).
1H NMR (CDCl3, 400 MHz): d 9.81 (s, 1H, ꢁCHO), 3.5–3.7 (m, 2H,
ꢁCH2), 2.9 (s, 2H, ꢁNH2). IR (Nujol, cmꢁ1): 3361, 1722.
ACKNOWLEDGMENT
The authors are grateful to University Grants Commission, New Delhi,
for financial support under UGC Project Order No. DV6=69=UGC=
2006-07, University Grant Commission (UGC)-SAP (Phase I) Project
Vide No. F. 540=10=DRS=2004–05 (SAP I) for IR data. The instruments
granted by the Department of Science and Technology-Fund for Impor-
tant of Science and Technology (DST-FIST) program to measure the
CHNS data are greatly acknowledged.
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N-Methyl Morpholine Chlorochromate
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