Hypervalent iodine(III)-mediated oxidation of aldoximes to N-acetoxy or N-hydroxy amides

Article abstract of DOI:10.1039/b917096k

Treatment of various aliphatic and aromatic aldoximes with the hypervalent iodine(iii) reagents (diacetoxyiodo)benzene (DIB) or Koser's reagent [hydroxy(tosyloxy)iodo]benzene (HTIB) gave, respectively, N-acetoxy or N-hydroxy amides in good yields rather t

Full text of DOI:10.1039/b917096k

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PAPER
www.rsc.org/obc | Organic & Biomolecular Chemistry
Hypervalent iodine(III)-mediated oxidation of aldoximes to N-acetoxy
or N-hydroxy amides†
Harisadhan Ghosh and Bhisma K. Patel*
Received 19th August 2009, Accepted 25th September 2009
First published as an Advance Article on the web 26th October 2009
DOI: 10.1039/b917096k
Treatment of various aliphatic and aromatic aldoximes with the hypervalent iodine(III) reagents
(diacetoxyiodo)benzene (DIB) or Koser’s reagent [hydroxy(tosyloxy)iodo]benzene (HTIB) gave,
respectively, N-acetoxy or N-hydroxy amides in good yields rather than the expected nitrile oxide
dimerised product oxadiazole-N-oxides reported to be formed with other oxidising and hypervalent
iodine reagents. The acetate or the hydroxyl group of DIB or HTIB attacks on the aryl/alkylnitrile
oxides formed in situ, which, upon intramolecular rearrangement, gave the expected N-acetoxy or
N-hydroxy amides.
success for the preparation of hydroxamic acids. The reported
Introduction
methods include amidation of esters using hydroxylamine,8
a
The importance of hypervalent iodine reagents in recent years is
reflected by the plethora of publications and reviews.1 Due to the
low toxicity, ready availability, easy handling, clean transformation
and above all, mild reaction conditions, hypervalent iodine
reagents have attracted a great deal of interest in modern synthetic
organic chemistry.1 The oxidising ability of non-metallic hyperva-
lent iodine reagents is similar to toxic metallic lead-, mercury- and
thallium-based reagents. Its mild oxidising properties have been
used for the oxidation of nitrogen-containing compounds such
nucleophilic displacement of carboxylates linked to an oxime
resin,9 amidation of carboxylic acids with hydroxylamine using
various coupling reagents,10 amidation of N-acyloxazolidinones
with hydroxylamines using samarium triflate,11 reaction of esters
with O-benzyl hydroxylamine12 and the Angelini–Rimini reaction
on a solid support,13 etc. Most of the reported methods use
strong basic conditions, complicated experimental procedures,
high reaction temperatures and tedious purification methods,
which limit their synthetic utility when applied on a large scale.
as oximes, hydrazones and acid hydrazides. Hypervalent iodine-
2b
mediated oxidative cleavage of ketoximes,2a hydrazones
and
Results and discussion
N¢,N¢-dialkylhydrazides2c to the parent ketone and acids/esters
have been studied. Unlike ketoxime, where the oxidation product is
regeneration of parent ketone,2a the oxidation product of aldoxime
is either regeneration of parent aldehyde or formation of nitrile
oxide, depending on the nature of the oxidising agent employed.2d,e
Nitrile oxides are valuable intermediates in organic synthesis.3
1,3-Dipolar cycloaddition reactions using nitrile oxides are ver-
satile methods for the preparation of synthetically useful interme-
diates such as isoxazolines and isoxazoles.4
Aromatic aldoximes are invariably oxidised to aryl nitrile
oxides with various oxidising agents such as NaOCl,3
Pb(OAc)4,14a NBS,14b 1-chlorobenzotriazole,14c MagtrieveTM
(CrO2),14d chloramine-T14e and PhICl2.14f However, aryl nitrile
oxides are not very stable and immediately dimerise to oxadiazole-
N-oxide derivatives. We have been interested in hypervalent
iodine-mediated oxidative desulfurization reactions.15 During the
course of (diacetoxyiodo)benzene (DIB)-mediated oxidation of
aromatic aldoximes, we observed the formation of N-acetoxy
benzamide (a) (Scheme 1). When the same reaction was performed
using Koser’s reagent [hydroxy(tosyloxy)iodo]benzene (HTIB),
the product obtained was N-hydroxy benzamide (b) (Scheme 1).
N-Acetoxy benzamides (O-acetyl hydroxamates) and O-tosyl
hydroxamates are important candidates for classical Lossen
rearrangements.5 Generally, the N-acetoxy amides are prepared
by the acylation of hydroxamic acids.6a,b Lately, the preparation of
O-acyl/O-benzoyl hydroxamates has been reported via a polymer-
supported reagent.6c The main drawback of these reported pro-
cedures is the formation of a mixture of O-acyl and N-acyl
hydroxamate, resulting in a low yield of the desired O-acylated
product.
The hydroxamic acid functionality is present in a number
of biologically active molecules with antibacterial, antifungal,
anti-inflammatory, anti-asthmatic, and anticancer properties.7
Several methods have been reported with varying degrees of
Scheme 1 Reaction of aldoximes with DIB or HTIB.
When benzaldehyde oxime (1) (1 equiv.) was reacted with
(diacetoxyiodo)benzene (DIB) (1.1 equiv.) in acetonitrile at 60 ◦C,
N-acetoxy benzamide (1a) was obtained in 78% isolated yield
rather than the expected benzonitrile oxide or its dimerised
product. This observation is in sharp contrast to the observation
Indian Institute of Technology Guwahati, Guwahati, 781 039, Assam, India.
E-mail: patel@iitg.ernet.in; Fax: +91 361-2690762; Tel: +91 361-2582307
† Electronic supplementary information (ESI) available: 1H and 13C NMR
spectra; X-ray structure for 9a. CCDC 744680. For ESI and crystallo-
graphic data in CIF or other electronic format see DOI: 10.1039/b917096k
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made by Das et al.,16a where in a CH2Cl2 medium and in the
absence of any alkenes, the nitrile oxide dimerised product is
speculated. The difference between the observation Das et al.16a
and ours is the use of different organic solvents. In order to
ascertain the role of the solvent, the reaction was carried out in
various organic solvents such as CH3CN, CHCl3, CH2Cl2, THF,
MeOH, toluene and DMSO. The isolated yields of (1a) after 2 h
were 78, 70, 58, 50, 51, 35 and ~7%, respectively. In the CH2Cl2
solvent, the product 1a was obtained in 58% isolated yield along
with a mixture of other side products. However, in THF, MeOH,
toluene and DMSO, the reaction gave an unclean reaction mixture.
Thus, CH3CN was found to be the most suitable solvent giving
good yield of N-acetoxy amide.
Although the starting aldoxime 1 was a diastereomeric (syn- and
anti-) mixture, both gave the same product N-acetoxy benzamide
(1a). Alkyl/aryl aldoxime, when treated with heavy metal oxidants
such as Pb(OAc)4,14a is reported to form nitrile oxide along with
other products. In this oxidation, the anti-aldoxime proceeds
via an iminoxy radical path, whereas the syn-aldoxime reacts in
concerted path giving nitrile oxide.14a A (diacetoxyiodo)benzene
(DIB)-mediated nitrile oxide formation from aldoxime has been
proposed by Das et al.16a According to this mechanism, the first
step is the nucleophilic displacement of one of the acetate groups of
DIB by an aldoxime oxygen. This is then followed by the formation
of intermediate (X), which, upon deprotonation, gives nitrile oxide
(Y) (Scheme 2). Nitrile oxide (Y), which is reported to be the
intermediate for this kind of reaction,16a,b is attacked by the in situ
liberated acetate ion from DIB, giving acylated intermediate (Z).
The intermediate (Z), upon intramolecular rearrangement, gave
the expected N-acetoxy arylamide. Alternatively, attack of nitrile
oxide (Y) by an acetic acid gives intermediate (K), which in turn
generates a tetrahedral intermediate (L) leading to the expected
N-acetoxy amide.
Scheme 3 Intermolecular nature of the mechanism.
When the DIB-mediated oxidation of aromatic aldoxime was
conducted in the presence of an activated alkene, methyl acry-
late, in dicloromethane, there was no formation of N-acetoxy
benzamide, but isoxazoline was isolated as the sole product an
observation consistent with the literature.16a It is also reported
that oxidation of aldoxime with iodosyl arene forms the dimerised
product of nitrile oxide, oxadiazole-N-oxide, which has been
isolated and well characterised.16b Therefore, it is clear that in the
absence of an activated alkene the dimerisation of the intermediate
nitrile oxide solely depends on the presence or absence of external
nucleophiles. In the presence of a suitable external nucleophiles,
such as acetate or hydroxy, the intermediate nitrile oxides undergo
oxidative rearrangement to produce the corresponding N-acetoxy
amides or N-hydroxy-amides without forming any dimerised
product.
Due to their immense synthetic importance of N-acetoxy amide,
we applied this strategy to various aldoxime for the construction of
N-acetoxy amide. Various aromatic aldoximes containing electron
donating groups (2–3) as well as electron withdrawing groups
(4–9) gave their corresponding N-acetoxy benzamide (2a–9a) in
good yields (Table 1) when reacted with DIB in acetonitrile at 60 ◦C
within 2 h. The structure of N-acetoxy-2,6-dichloro benzamide
(9a) has been confirmed by crystal X-ray crystallography (Fig. 1).
Fig. 1 ORTEP view of 9a with atom-numbering scheme.
Furthermore, the method was successfully extended to the
synthesis of a variety of aliphatic N-acetoxy amides (10a–13a)
from their corresponding aliphatic aldoximes (10–13). It was ob-
served that aliphatic aldoximes were more reactive than aromatic
aldoximes. For aliphatic aldoximes (10–13), complete conversion
took 30 min compared to 2 h for the aromatic aldoxime. Substrates
containing both electron donating as well as electron withdrawing
groups in the aromatic ring react efficiently (Table 1). In a compet-
ing reaction, when an equimolar mixture of 4-methylbenzaldehyde
oxime (2) and 4-nitrobenzaldehyde oxime (8) was reacted with
1 equiv. of DIB, the ratio of the acetoxy products 2a and 8a
formed after 2 h was 3 : 1. This demonstrates the faster reactivity
for the substrates with an electron donating group compared to
Scheme 2 Mechanism for the formation of N-acetoxy amides.
When the reaction was carried out in the presence of one
equivalent of propionic acid, N-acetoxy benzamide (1a) along
with N-propionyloxy benzamide (1c) were obtained in the ratio
60 : 40.17 The formation of N-propionyloxy benzamide (1c) proves
the intermolecular attack of acetate or propionate on benzonitrile
oxide (Scheme 3), thus ruling out the possibility of a radical-type
mechanism as has been proposed using Pb(OAc)4.14a
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Table 1 Preparation of N-acetoxy amidea
Productb
Table 1 (Contd.)
Substrate
Yield (%)c
Substrate
Productb
Yield (%)c
78
83
69
a Reactions were monitored by TLC. b Confirmed by IR, and 1H and 13
C
NMR. c Isolated yield. For aromatic substrates 1–9 the reaction time was
2 h, and for aliphatic substrates 10–13 the reaction time was 0.5 h.
the substrates with an electron withdrawing group. In a similar
competing reaction between an aliphatic aldoxime (11) and an
aromatic aldoxime (1), the ratio of the acetoxy product 11a and
1a formed after 2 h was 4 : 1, exhibiting the faster reactivity of the
aliphatic aldoxime compared to the aromatic aldoxime.
74
When another hypervalent iodine(III) reagent [hydroxy- (to-
syloxy)iodo]benzene (HTIB, Koser’s Reagent) was used as the
oxidising agent instead of DIB for the oxidation of ben-
zaldehyde oxime (1), N-hydroxybenzamide (1b) was isolated as
the sole product. Here, the –OH nucleophile (generated from
the reagent, HTIB) attacks the intermediate benzonitrile oxide
(Scheme 2), forming N-hydroxy benzamide (1b). This reaction
works better in a chloroform medium compared to an acetonitrile
medium.
81
77
Hydroxamic acids bearing various substituents on the aromatic
ring (1b–9b) can be efficiently prepared from the corresponding
benzaldehyde oximes (1–9), as shown in Table 2. Here again,
aliphatic aldoximes 10 and 12 were successfully converted to
their corresponding hydroxamic acids 10b and 12b in a shorter
time (30 min). Although quantitative conversion to hydroxamic
acids for both aromatic and aliphatic compounds from the parent
aldoximes were observed by GC/TLC, the isolated yields were
modest. This is because of the difficulties in separating the water
soluble product and byproduct p-toluenesulfonic acid (generated
from reagent HTIB). Several extraction and chromatographic
techniques were adopted but efficient separation could not be
achieved. The yield in the table refers to the pure isolated product
only. Similar purification difficulties were encountered by others
and have been overcome by attaching the reagent on a solid
support.13
69
76
79
86
Conclusion
75
61
In conclusion, the oxidation of both aromatic and aliphatic
aldoximes with hypervalent iodine(III) reagents DIB or HTIB
gave the corresponding N-acetoxy and N-hydroxy amides in good
yields, rather than the expected nitrile oxide dimerised products
oxadiazole-N-oxides reported with other oxidising agents. A
plausible mechanism for this transformation involves acetate
attack on the intermediate aryl/alkyl nitrile oxides, which, upon
rearrangement, gave the expected N-acetoxy amides. Thus, using
this approach, various N-acetoxy and N-hydroxy amides can be
prepared conveniently from their aldoximes.
66
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Table 2 Preparation of N-hydroxy amidesa
Productb
progress was monitored by TLC using Merck silica gel 60 F254
(0.25 mm) with detection by UV or iodine. Chromatography was
performed using Merck silica gel (60–120) mesh size with freshly
distilled solvents. Columns were typically packed as slurry and
equilibrated with the appropriate solvent system prior to use.
1H NMR (400 MHz) and 13C NMR (100 MHz) spectra were
recorded on a Varian FT-400 MHz instrument using TMS as an
internal standard. Data are presented as follows: chemical shift
(ppm), multiplicity (s = singlet, d = doublet, t = triplet, m =
multiplet, b = broad, coupling constant J (Hz). Elemental analyses
were carried out on a Perkin–Elmer 2400 automatic carbon,
hydrogen and nitrogen analyzer. Melting points were recorded
on Buchi B-545 melting point apparatus and are uncorrected. IR
spectra were recorded in KBr or neat on a Nicolet Impact 410
spectrophotometer. The crystal structure was recorded on Bruker
Smart APEX-II CCD diffractometer. Mass data were obtained
with a WATERS MS system, Q-tof premier and data analyzed
using Mass Lynx4.1.
Substrate
Yield (%)c
76
81
73
General experimental procedure
83
74
72
General procedure for preparation of N-acetoxy benzamide (1a)
from benzaldehyde oxime (1). DIB (708 mg, 2.2 mmol) was added
to a stirred solution of benzaldehyde oxime 1 (242 mg, 2 mmol)
in acetonitrile at room temperature, portion wise over a period
of 10 min. A white precipitate started to separate out during this
period. After the complete addition of DIB, the reaction mixture
was heated at 60 ◦C for 2 h (30 min for aliphatic substrates) and
conversion to the corresponding N-acetoxy benzamide 1a was
monitored by TLC. At the end of the reaction, the reaction mixture
becomes a clear solution. The organic layer was concentrated and
admixed with ethyl acetate (15 mL). The ethyl acetate layer was
washed with water (5 mL). The organic layer was dried over
anhydrous Na2SO4, concentrated under reduced pressure, and
purified through a short column of silica gel to afford the pure
product 1a.
70
General procedure for preparation of N-hydroxy-benzamide (1b)
from benzaldehyde oxime (1). HTIB (862 mg, 2.2 mmol) was
added to a stirred solution of benzaldehyde oxime 1 (242 mg,
2 mmol) in chloroform at room temperature, in portion wise
manner over a period of 10 min. After the complete addition
of HTIB, the reaction mixture was heated at 60 ◦C for 2 h (30 min
for aliphatic substrates), and conversion to the corresponding N-
hydroxy benzamide 1b was confirmed by TLC. The organic layer
was concentrated and admixed with ethyl acetate (15 mL). The
ethyl acetate layer was washed with 10% HCl water solution
(5 mL). The organic layer was dried over anhydrous Na2SO4,
concentrated under reduced pressure, and purified through a short
column of silica gel to afford the pure product 1b.
78
62
68
a Reactions were monitored by TLC. b Confirmed by IR, and 1H and 13
C
The identities of the known compounds 1a, 2a and 5a,6c 6a,18a
8a,6b 12a,14a 13a,18d 1b,9b 2b,17 4b and 5b18b 6b,18c 7b,9b 10b,12a and
12b13 were confirmed by comparison of their spectral data with the
reported ones. The physical and spectroscopic data of the others
synthesised compounds are given below.
NMR. c Isolated yield. For aromatic substrates 1–9 the reaction time was
2 h, and for aliphatic substrates 10–12 the reaction time was 0.5 h
Experimental
N-Acetoxy benzamide (1a)6c. mp: 126 ◦C; 1H NMR (400 MHz,
CDCl3): d (ppm) 2.29 (s, 3H), 7.46 (t, J = 7.2 Hz, 2H), 7.57 (t, J =
7.2 Hz, 1H), 7.82 (d, J = 7.6 Hz, 2H), 9.63 (br s, 1H); 13C NMR
(100 MHz, CDCl3): d (ppm) 18.5, 127.7, 128.9, 130.7, 132.9, 166.5,
General remarks
Unless otherwise stated, all reagents were purchased from com-
mercial sources and used without further purification. Reaction
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169.3; IR (KBr): 3151, 2961, 1793, 1650, 1531, 1366, 1198, 1021,
896, 695 cm-1. MS (ESI): 180.07 (MH+).
13C NMR (100 MHz, CDCl3 + DMSO-d6): d (ppm) 18.4, 123.5,
129.2, 136.9, 149.9, 163.6, 168.7; IR (KBr): 3154, 2971, 1795, 1660,
1603, 1524, 1352, 1297, 1187, 1107, 1029, 1012, 850, 725, 588 cm-1;
Elemental analysis: C9H8N2O5 (224.17) requires C, 48.22; H, 3.60;
N, 12.50. found: C, 48.25; H, 3.57; N, 12.47.
N-Acetoxy-4-methyl-benzamide (2a)6c. mp: 133–135 ◦C; 1H
NMR (400 MHz, CDCl3): d (ppm) 2.28 (s, 3H), 2.41 (s, 3H),
7.25 (d, J = 8.0 Hz, 2H), 7.71 (d, J = 8.0 Hz, 2H), 9.64 (br s, 1H);
13C NMR (100 MHz, CDCl3): d (ppm) 18.5, 21.7, 127.7, 127.9,
129.6, 143.6, 166.6, 169.4; IR (KBr): 3180, 2949, 2851, 1794, 1660,
1651, 1488, 1302, 1176, 1017, 906, 851, 753, 602 cm-1; Elemental
analysis: C10H11NO3 (193.20): calcd C, 62.17; H, 5.74; N, 7.25.
found: C, 62.15; H, 5.79; N, 7.24.
◦
1
N-Acetoxy-2,6-dichloro-benzamide (9a). mp: 162–164 C; H
NMR (400 MHz, CDCl3 + DMSO-d6): d (ppm) 2.26 (s, 3H), 7.35
(m, 5H), 12.19 (br s, 1H); 13C NMR (100 MHz, CDCl3 + DMSO-
d6): d (ppm) 18.1, 127.7, 131.2, 132.6, 133.0, 160.5, 167.8; IR
(KBr): 3149, 2995, 2809, 1798, 1661, 1524, 1434, 1191, 1026, 910,
792, 561 cm-1; Elemental analysis: C9H7Cl2NO3 (248.06) requires
C, 43.58, H, 2.84, N, 5.65. found: C, 43.59; H, 2.81; N, 5.63.
N-Acetoxy-2,5-dimethoxy-benzamide
(3a). Gummy;
1H
NMR (400 MHz, CDCl3): d (ppm) 2.22 (s, 3H), 3.74 (s, 3H), 3.89
(s, 3H), 6.87 (d, J = 8.8 Hz, 1H), 6.98 (dd, J1 = 3.2 Hz, J2 =
3.6 Hz, 1H), 7.62 (d, J = 3.2 Hz, 1H), 11.18 (br s, 1H); 13C NMR
(100 MHz, CDCl3): d (ppm) 18.5, 55.9, 56.9, 113.1, 115.5, 119.2,
120.6, 151.6, 154.1, 163.1, 168.6; IR (KBr): 3307, 2946, 2839,
1790, 1668, 1496, 1464, 1283, 1217, 1185, 1042, 815, 736 cm-1;
Elemental analysis: C11H13NO5 (239.23): calcd C, 55.23; H, 5.48;
N, 5.85. found: C, 55.23; H, 5.46; N, 5.84.
Cyclohexanecarboxylic acid acetoxy-amide (10a). mp: 85–
87 ◦C; 1H NMR (400 MHz, CDCl3): d (ppm) 1.27 (m, 3H), 1.53
(m, 2H), 1.69 (m, 1H), 1.82 (m, 5H), 2.23 (s, 3H), 9.08 (br s, 1H);
13C NMR (100 MHz, CDCl3): d (ppm) 18.4, 25.60, 25.63, 29.3,
42.3, 169.0, 174.6; IR (KBr): 3175, 2856, 1798, 1667, 1520, 1450,
1370, 1189, 1019, 961, 857, 761, 589 cm-1; Elemental analysis:
C9H15NO3 (185.22) requires C, 58.36, H, 8.16, N, 7.56. found: C,
58.38; H, 8.11; N, 7.52.
N-Acetoxy-2-chloro-benzamide (4a). mp: 99–101 ◦C; 1H
NMR (400 MHz, CDCl3): d (ppm) 2.29 (s, 3H), 7.36 (m, 1H),
7.44 (m, 2H), 7.71 (d, J = 7.2 Hz, 1H), 9.80 (br s, 1H); 13C NMR
(100 MHz, CDCl3): d (ppm) 18.4, 127.2, 130.5, 130.6, 131.2, 131.6,
132.5, 164.1, 168.6; IR (KBr): 3140, 2951, 2824, 1797, 1651, 1531,
1435, 1365, 1189, 1022, 901, 755, 638 cm-1; Elemental analysis:
C9H8ClNO3 (213.62): calcd C, 50.60; H, 3.77; N, 6.56. found: C,
50.61; H, 3.77; N, 6.50.
N-Acetoxy-butyramide (11a). Oily; 1H NMR (400 MHz,
CDCl3): d (ppm) 0.97 (t, 3H, J = 7.6 Hz), 1.69 (m, 2H), 2.20 (s,
3H), 2.22 (m, 2H), 10.37 (br s, 1H); 13C NMR (100 MHz, CDCl3):
d (ppm) 13.5, 13.9, 18.2, 18.7, 34.5, 168.7, 171.5; IR (KBr): 3196,
2878, 1797, 1669, 1505, 1464, 1369, 1181, 1029, 853, 748 cm-1;
Elemental analysis: C6H11NO3 (145.16) requires C, 49.65, H, 7.64,
N, 9.65. found: C, 49.61; H, 7.63; N, 9.68.
N-Acetoxy-3-chloro-benzamide (5a)6c. mp: 100–102 ◦C; 1H
NMR (400 MHz, CDCl3) d (ppm) 2.28 (s, 3H), 7.38 (t, J = 8.0 Hz,
1H), 7.53 (d, J = 7.6 Hz, 1H), 7.68 (d, J = 7.6 Hz, 1H), 7.80 (s,
1H), 9.90 (br s, 1H); 13C NMR (100 MHz, CDCl3): d (ppm) 18.5,
125.7, 127.9, 130.3, 132.4, 132.9, 135.2, 165.2, 169.2; IR (KBr):
3147, 2955, 2824, 1798, 1651, 1533, 1188, 1027, 915, 751 cm-1;
Elemental analysis: C9H8ClNO3 (213.62): calcd C, 50.60; H, 3.77;
N, 6.56. found: C, 50.58; H, 3.79; N, 6.53.
Heptanoic acid acetoxy-amide (12a)14a
.
mp: 80–82 ◦C; 1H
NMR (400 MHz, CDCl3): d (ppm) 0.88 (t, J = 6.4 Hz, 3H),
1.30 (m, 6H), 1.67 (m, 2H), 2.21 (s, 3H), 2.24 (m, 2H), 9.47 (br s,
1H); 13C NMR (100 MHz, CDCl3): d (ppm) 14.8, 18.4, 22.6, 25.3,
28.9, 31.6, 32.9, 168.9, 171.5; IR (KBr): 3156, 2859, 1791, 1658,
1533, 1418, 1378, 1192, 1042, 852, 565 cm-1; Elemental analysis:
C9H17NO3 (187.24) requires C, 57.73; H, 9.15; N, 7.48. found: C,
57.70; H, 9.18; N, 7.48.
N-Acetoxy-3-nitro-benzamide (6a)18a
.
mp: 146–148 ◦C; 1H
N-Acetoxy-3-phenyl-propionamide (13a)18d mp: 64–66 ◦C; 1H
.
NMR (400 MHz, CDCl3 + DMSO-d6): d (ppm) 2.29 (s, 3H),
7.68 (t, J = 8.0 Hz, 1H), 8.29 (d, J = 7.2 Hz, 1H), 8.39 (d, J =
7.2 Hz, 1H), 8.81 (s, 1H), 12.29 (br s, 1H); 13C NMR (100 MHz,
CDCl3 + DMSO-d6): d (ppm) 18.4, 122.7, 126.6, 129.7, 132.7,
134.1, 147.9, 163.0, 168.7; IR (KBr): 3148, 2958, 1798, 1661, 1524,
1352, 1185, 1027, 857, 844, 737, 680 cm-1; Elemental analysis:
C9H8N2O5 (224.17): calcd C, 48.22; H, 3.60; N, 12.50. found: C,
48.22; H, 3.63; N, 12.45.
NMR (400 MHz, CDCl3): d (ppm) 2.18 (s, 3H), 2.25 (t, J =
7.6 Hz, 2H), 2.99 (t, J = 7.6 Hz, 2H), 7.21 (m, 3H), 7.28 (m, 2H),
9.20 (br s, 1H); 13C NMR (100 MHz, CDCl3): d (ppm) 18.4, 31.2,
34.7, 126.7, 128.6, 128.8, 140.4, 168.9, 170.7; IR (KBr): 3148,
2961, 1790, 1667, 1497, 1453, 1368, 1176, 1063, 1017, 858, 747,
700, 560 cm-1; Elemental analysis: C11H13NO3 (207.23) requires C,
63.76; H, 6.32; N, 6.76. found: C, 63.75; H, 6.35; N, 6.71.
N-Hydroxy benzamide (1b)9b. mp: 124 ◦C; 1H NMR
(400 MHz, CDCl3 + DMSO-d6): d (ppm) 7.17 (m, 2H), 7.24
(t, J = 7.2 Hz, 1H), 7.57 (d, J = 8.0 Hz, 2H), 10.9 (br s, 1H);
13C NMR (100 MHz, CDCl3 + DMSO-d6): d (ppm) 126.8, 128.1,
131.1, 131.8, 165.2; IR (KBr): 3300, 2753, 1645, 1613, 1563, 1453,
1435, 1163, 1022, 898, 690 cm-1; MS (ESI): 138.06 (MH+).
N-Acetoxy-4-bromo-benzamide (7a). mp: 126–128 ◦C; 1H
NMR (400 MHz, CDCl3): d (ppm) 2.27 (s, 3H), 7.57 (d, J =
8.4 Hz, 2H), 7.66 (d, J = 8.4 Hz, 2H), 9.84 (br s, 1H); 13C NMR
(100 MHz, CDCl3): d (ppm) 18.5, 127.9, 129.2, 129.6, 132.3, 165.7,
169.3; IR (KBr): 3194, 2938, 1789, 1662, 1588, 1479, 1196, 1069,
1011, 909, 841, 750, 514 cm-1; Elemental analysis: C9H8BrNO3
(258.07): calcd C, 41.89; H, 3.12; N, 5.43. found: C, 41.92; H, 3.14;
N, 5.40.
◦
1
N-Hydroxy-4-methyl-benzamide (2b)17. mp: 145–147 C; H
NMR (400 MHz, CDCl3 + DMSO-d6) d (ppm) 2.37 (s, 3H),
7.21 (d, J = 7.6 Hz, 2H), 7.71 (d, J = 7.6 Hz, 2H), 8.72 (br s,
1H), 11.05 (br s, 1H); 13C NMR (100 MHz, CDCl3 + DMSO-d6):
d (ppm) 21.2, 127.2, 129.2, 141.8, 165.8; IR (KBr): 3296, 2760,
1648, 1565, 1508, 1374, 1309, 1161, 1037, 902, 839, 738, 538 cm-1;
N-Acetoxy-4-nitro-benzamide (8a)6b. mp: 189–191 ◦C; 1H
NMR (400 MHz, CDCl3 + DMSO-d6): d (ppm) 2.29 (s, 3H),
8.09 (d, J = 8.4 Hz, 2H), 8.28 (d, J = 8.4 Hz, 2H), 12.11 (br s, 1H);
388 | Org. Biomol. Chem., 2010, 8, 384–390
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Elemental analysis: C8H9NO2 (151.16): calcd C, 63.57; H, 6.00; N,
9.27. found: C, 63.52; H, 6.10; N, 9.20.
174.0; IR (KBr): 3296, 2852, 1632, 1541, 1449, 1142, 1060, 963,
808, 753, 663, 617 cm-1; Elemental analysis: C7H13NO2 (143.18)
requires C, 58.72; H, 9.15; N, 9.78. found: C, 58.77; H, 9.18; N,
9.76.
N-Hydroxy-2,5-dimethoxy-benzamide (3b). Gummy; 1H
NMR (400 MHz, CDCl3 + DMSO-d6): d (ppm) 3.80 (s, 3H),
3.92 (s, 3H), 6.90 (d, J = 9.2 Hz, 1H), 7.00 (dd, J1 = 3.2 Hz,
N-Hydroxyheptanamide (12b)13. mp: 72–74 ◦C; 1H NMR
(400 MHz, CDCl3): d (ppm) 0.84 (t, J = 6.0 Hz, 3H), 1.18
(m, 6H), 1.47 (m, 2H), 2.01 (m, 2H), 9.50 (br s, 1H);13C NMR
(100 MHz, CDCl3 + DMSO-d6): d (ppm) 14.1, 22.7, 25.7, 29.3,
29.8, 31.7, 171.7; IR (KBr): 3250, 2857, 1644, 1467, 1401, 1176,
1125, 1037, 1011, 816, 690, 615, 570 cm-1; Elemental analysis:
C7H15NO2 (145.20) requires C, 57.90; H, 10.41; N, 9.65. found: C,
57.93; H, 10.40; N, 9.61.
J2 = 2.8 Hz, 1H), 7.70 (d, J = 3.2 Hz, 1H), 10.50 (br s, 1H); 13
C
NMR (100 MHz, CDCl3 + DMSO-d6): d (ppm) 56.0, 56.6, 112.8,
115.2, 118.8, 119.8, 151.5, 154.0, 163.7; IR (KBr): 3305, 2944,
2837, 1645, 1607, 1495, 1282, 1218, 1179, 1043, 813, 735 cm-1;
Elemental analysis: C9H11NO4 (197.19): calcd C, 54.82; H, 5.62;
N, 7.10. found: C, 54.80; H, 5.57; N, 7.15.
2-Chloro-N-hydroxy-benzamide (4b)18b
.
mp: 150 ◦C; 1H NMR
Crystal data for 9a. C9H7Cl2NO3 M = 248.06, monoclinic,
(400 MHz, CDCl3 + DMSO-d6): d (ppm) 6.28 (br s, 1H), 7.30
(m, 1H), 7.38 (m, 2H), 7.49 (m, 1H), 10.50 (br s, 1H); 13C NMR
(100 MHz, CDCl3 + DMSO-d6): d (ppm) 126.6, 129.5, 129.8,
131.1, 131.4, 133.1, 164.3; IR (KBr): 3228, 1632, 1594, 1543,
1474, 1321, 1172, 907, 750, 724, 649 cm-1; Elemental analysis:
C7H6ClNO2 (171.58): calcd C, 49.00; H, 3.52; N, 8.16. found: C,
48.97; H, 3.51; N, 8.14.
˚
space group P21/c, a = 9.8316(4), b = 12.1236(5), c = 8.8033(3) A,
◦
3
˚
a = 90.00, b = 92.170(2), g = 90.00 , V = 1048.55(7) A , T =
˚
298(2) K, Z = 4, m(Mo-Ka) = 0.71073 A, colourless block, crystal
dimensions 0.50 ¥ 0.30 ¥ 0.20 mm, crystal density 1.571. Full
matrix least squares based on F2 gave R1 = 0.0299 and wR2 =
0.0753 for 1655 (I ≥ 2s(I)), GOF = 1.046 for 141 parameters.
CCDC 744680.†
◦
1
3-Chloro-N-hydroxy-benzamide (5b)18b
.
mp: 169–171 C; H
NMR (400 MHz, CDCl3 + DMSO-d6): d (ppm) 7.46 (m, 2H),
7.72 (d, J = 7.2 Hz, 1H), 7.80 (s, 1H); 13C NMR (100 MHz,
CDCl3 + DMSO-d6): d (ppm) 124.4, 126.1, 129.1, 130.1, 132.7,
133.2, 162.6; IR (KBr): 3295, 2758, 1655, 1621, 1564, 1474, 1173,
1047, 796, 747, 726, 673, 530 cm-1; Elemental analysis: C7H6ClNO2
(171.58): calcd C, 49.00; H, 3.52; N, 8.16. found: C, 49.08; H, 3.50;
N, 8.08.
Acknowledgements
B. K. P acknowledges support of this research from DST
New Delhi (SR/S1/OC-15/2006) and CSIR 01(2270)/08/EMR-
II. H.G thanks the CSIR for fellowships. Thanks are due to CIF
IIT Guwahati for NMR spectra, and DST-FIST for XRD facility.
N-Hydroxy-3-nitro-benzamide (6b)18c
.
mp: 142–144 ◦C; 1H
References
NMR (400 MHz, CDCl3 + DMSO-d6): d (ppm) 7.64 (t, J =
8.0 Hz, 1H), 8.23 (d, J = 8.00 Hz, 1H), 8.32 (d, J = 7.6 Hz,
1H), 8.75 (s, 1H), 11.67 (br s, 1H); 13C NMR (100 MHz, CDCl3 +
DMSO-d6): d (ppm) 122.1, 125.6, 129.5, 133.2, 133.7, 147.9, 162.6;
IR (KBr): 3375, 3178, 1670, 1656, 1619, 1521, 1350, 1172, 1035,
933, 715, 671 cm-1; Elemental analysis: C7H6N2O4 (182.14): calcd
C, 46.16; H, 3.32; N, 15.38. found: C, 46.18; H, 3.31; N, 15.27.
1 (a) T. Wirth, M. Ochiai, V. V. Zhdankin, G. F. Koser, H. Tohma and
Y. K i t a , Topics in Current Chemistry: Hypervalent Iodine Chemistry-
Modern Developments in Organic Synthesis, Spinger-Verlag, Berlin,
2002; (b) A. Varvoglis, Hypervalent Iodine in Organic Synthesis,
Academic Press, London, 1997; (c) P. Stang and V. V. Zhdankin, Chem.
Rev., 1996, 96, 1123; (d) A. Varvoglis, Tetrahedron, 1997, 53, 1179;
(e) V. V. Zhdankin and P. Stang, Chem. Rev., 2002, 102, 2523; (f) V. V.
Zhdankin and P. Stang, Chem. Rev., 2008, 108, 5299.
2 (a) R. M. Moriarty, O. Prakash and P. R. Vavilikolanu, Synth.
Commun., 1986, 16, 1247; (b) D. H. R. Barton, J. Cs. Jaszberenyi, W.
Liu and T. Shinada, Tetrahedron, 1996, 52, 14673; (c) P. G. M. Wuts and
M. P. Goble, Org. Lett., 2000, 2, 2139; (d) A. Ghorbani-Choghamarani,
L. Shiri and J. Zeinivand, Bull. Korean Chem. Soc., 2008, 29, 2496;
(e) F. P. Ballistreri, U. Chiacchio, A. Rescifina, G. Tomaselli and R. M.
Toscano, Molecules, 2008, 13, 1230.
3 C. Grundmann and J. M. Dean, J. Org. Chem., 1965, 30, 2809.
4 (a) A. P. Kozikowski, Acc. Chem. Res., 1984, 17, 410; (b) P. G. Baraldi,
A. Barco, S. Benetti, G. P. Pollini and D. Simoni, Synthesis, 1987,
857; (c) P. Cararnella and P. Grunanger, in: 1,3-Dipolar Cycloaddition
Chemistry, ed. A. Padwa, vol. 1, chapter 3, John Wiley & Sons, New
York, 1984; (d) B. A. Mendelsohn, S. Lee, S. Kim, F. Teyssier, V. S.
Aulakh and M. A. Ciufolini, Org. Lett., 2009, 11, 1539.
5 (a) L. Bauer and O. Exner, Angew. Chem., Int. Ed. Engl., 1974, 13,
376; (b) D. C. Berndt and W. J. Adams, J. Org. Chem., 1966, 31, 976;
(c) G. W. Adams, J. H. Bowie and R. N. Hayes, J. Chem. Soc., Perkin
Trans. 2, 1991, 689.
4-Bromo-N-hydroxy-benzamide (7b)9b. mp: 184–186 ◦C; 1H
NMR (400 MHz, CDCl3 + DMSO-d6): d (ppm) 3.10 (br s, 1H),
7.54 (d, J = 8.4 Hz, 2H), 7.73 (d, J = 8.4 Hz, 2H), 11.25 (br s, 1H);
13C NMR (100 MHz, CDCl3 + DMSO-d6): d (ppm) 125.3, 128.5,
129.5, 131.1, 163.7; IR (KBr): 3294, 3065, 2754, 1646, 1614, 1591,
1483, 1433, 1329, 1075, 843, 742, 525 cm-1; Elemental analysis:
C7H6BrNO2 (216.04): calcd C, 38.92; H, 2.80; N, 6.48. found: C,
38.85; H, 2.83; N, 6.46.
◦
1
2,6-Dichloro-N-hydroxybenzamide (9b). mp: 165–167 C; H
NMR (400 MHz, CDCl3 + DMSO-d6): d (ppm) 4.30 (br s, 1H),
7.32 (m, 4H), 10.79 (br s, 1H);13C NMR (100 MHz, CDCl3 +
DMSO-d6): d (ppm) 127.4, 130.5, 132.6, 133.4, 160.9; IR (KBr):
3227, 3031, 2905, 1630, 1580, 1524, 1433, 1310, 1194, 1098, 1025,
901, 804, 780, 467 cm-1; Elemental analysis: C7H5Cl2NO2 (206.03)
requires C, 40.81; H, 2.45; N, 6.80. found: C, 40.81; H, 2.41; N,
6.78.
6 (a) T. Okawara, Y. Kanazawa, T. Yamaski and M. Furukawa, Synthesis,
1987, 183and references cited therein; (b) Z. Zhang, Y. Yu and L. S.
Liebeskind, Org. Lett., 2008, 10, 3005; (c) A. S. Burungule, S. P. Bondge,
S. B. Munde, V. E. Bhingolikar and R. A. Mane, Synth. Commun., 2003,
33, 1923.
7 (a) G. Weber, Cancer Res., 1983, 43, 3466; (b) M. J. Miller, Chem. Rev.,
1989, 89, 1563.
8 (a) A. Mordini, G. Reginato, F. Russo and M. Taddei, Synthesis, 2007,
3201; (b) C. R. Hauser and W. B. Jr. Renfrow, Organic Synthesis, Wiley,
New York, 1943; Collect. vol. II, pp. 67–68.
◦
N-Hydroxycyclohexanecarboxamide (10b)12a
NMR (400 MHz, CDCl3): d (ppm) 1.25 (m, 3H), 1.47 (m, 2H),
1.69 (m, 1H), 1.80 (m, 4H), 2.08 (m, 1H), 8.37 (br s, 1H);13C NMR
(100 MHz, CDCl3 + DMSO-d6): d (ppm) 25.4, 28.6, 29.0, 41.7,
.
mp: 120 C; H
1
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9 (a) E. Thouin and W. Lubell, Tetrahedron Lett., 2000, 41, 457; (b) J.
Choi, J. G. Park and Y-P. Pang, Tetrahedron Lett., 2008, 49, 1103 .
10 (a) L. De Luca, G. Giacomelli and M. Taddei, J. Org. Chem., 2001, 66,
2534; (b) G. Giacomelli, A. Porcheddu and M. Salaris, Org. Lett.,
2003, 5, 2715; (c) A. Ech-Chahad, A. Minassi, L. Berton and G.
Appendino, Tetrahedron Lett., 2005, 46, 5113; (d) A. R. Katritzky, N.
Kirichenko and B. V. Rogovoy, Synthesis, 2003, 2777; (e) M. A. Bailen,
R. Chinchilla, D. J. Dodsworth and C. Na`jera, Tetrahedron Lett., 2001,
42, 5013; (f) A. S. Reddy, M. S. Kumar and G. R. Reddy, Tetrahedron
Lett., 2000, 41, 6285.
11 M. P. Sibi, H. Hasegawa and S. R. Ghorpade, Org. Lett., 2002, 4, 3343.
12 (a) M. C. Pirrung and G. H. L. Chau, J. Org. Chem., 1995, 60, 8084;
(b) A. Gissot, A. Volonterio and M. Zanda, J. Org. Chem., 2005, 70,
6925.
13 A. Porcheddu and G. Giacomelli, J. Org. Chem., 2006, 71, 7057.
14 (a) G. Just and K. Dahl, Tetrahedron Lett., 1968, 24, 5251; (b) C.
Grundmann and R. Richter, J. Org. Chem., 1968, 33, 476; (c) J. N.
Kim and E. K. Ryu, Synth. Commun., 1990, 20, 1373; (d) S. Bhosale, S.
Kurhade, U. V. Prasad, V. P. Palle and D. Bhuniya, Tetrahedron Lett.,
2009, 50, 3948; (e) A. Hassner and K. M. L. Rai, Synthesis, 1989,
57; (f) A. S. Radhakrishna, K. Sivaprakash and B. B. Singh, Synth.
Commun., 1991, 21, 1625.
15 (a) C. B. Singh, H. Ghosh, S. Murru and B. K. Patel, J. Org. Chem., 2008,
73, 2924; (b) H. Ghosh, R. Yella, J. Nath and B. K. Patel, Eur. J. Org.
Chem., 2008, 6189; (c) H. Ghosh, R. Yella, A. R. Ali, S. K. Sahoo and
B. K. Patel, Tetrahedron Lett., 2009, 50, 2407.
16 (a) B. Das, H. Holla, G. Mahender, J. Banerjee and M. Ravinder Reddy,
Tetrahedron Lett., 2004, 45, 7347; (b) S. Tanaka, M. Ito, K. Kishikawa,
S. Kohmoto and M. Yamamoto, Nippon Kagaku Kaishi, 2002, 3, 471.
17 The ratio of the two products (1a) and (1c) was determined by 1H
NMR. Spectral data of the mixture of products: N-acetoxy benzamide
(1a) + N-propionyloxy benzamide (1c) (60 : 40): 1H NMR (400 MHz,
CDCl3): d (ppm) 1.25 (t, J = 7.6 Hz, 1H), 2.28 (s, 3H), 2.57 (m, 2H),
7.43–8.16 (m, 10H), 9.76 (br s, 1H); IR (KBr): 3152, 2952, 2813, 1793,
1769, 1653, 1579, 1487, 1241, 1179, 1021, 897, 694 cm-1.
18 (a) A. Ashfaq, O. Pytela, J. Socha and M. Vecera, Collect. Czech. Chem.
Commun., 1976, 41, 3308; (b) D. Griffith, K. Krot, J. Comiskey, K. B.
Nolan and C. J. Marmion, Dalton Trans., 2008, 137; (c) C.-Y. Wei, P.
Yang, L.-H. Wang and L. Wang, Chinese J. Chem., 2002, 20, 453; (d) M.
Kawase, T. Kitamura and Y. Kikugawa, J. Org. Chem., 1989, 54, 3394.
390 | Org. Biomol. Chem., 2010, 8, 384–390
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