An efficient copper(II)-catalyzed direct access to primary amides from aldehydes under neat conditions

Article abstract of DOI:10.1016/j.tetlet.2012.01.029

A simple expeditious one-pot conversion of a wide assortment of aldehydes to corresponding primary amides in good to excellent yields has been accomplished employing hydroxylamine hydrochloride (1 mol equiv), sodium acetate (1.1 mol equiv), and copper sulfate pentahydrate (5 mol %) under neat conditions at 110 °C. The protocol based upon ligand-free copper (II)-catalysis avoids the use of relatively expensive late transition metal-based catalysts, and is performed under operationally simple conditions without any demanding procedure of isolation and purification of products.

Full text of DOI:10.1016/j.tetlet.2012.01.029

Tetrahedron Letters 53 (2012) 1413–1416
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
An efficient copper (II)-catalyzed direct access to primary amides
from aldehydes under neat conditions
⇑
Nemai C. Ganguly , Sushmita Roy, Pallab Mondal
Department of Chemistry, University of Kalyani, Kalyani 741235, WB, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A simple expeditious one-pot conversion of a wide assortment of aldehydes to corresponding primary
amides in good to excellent yields has been accomplished employing hydroxylamine hydrochloride
(1 mol equiv), sodium acetate (1.1 mol equiv), and copper sulfate pentahydrate (5 mol %) under neat con-
ditions at 110 °C. The protocol based upon ligand-free copper (II)-catalysis avoids the use of relatively
expensive late transition metal-based catalysts, and is performed under operationally simple conditions
without any demanding procedure of isolation and purification of products.
Received 11 November 2011
Revised 6 January 2012
Accepted 8 January 2012
Available online 13 January 2012
Keywords:
Aldehydes
Ó 2012 Elsevier Ltd. All rights reserved.
Primary amides
Copper sulfate pentahydrate
Sodium acetate
Hydroxylamine hydrochloride
Amide functionality is widely prevalent in pharmaceuticals and
drug candidates as well as various industrial materials including
detergents and lubricants.1 Amides are commonly prepared by
the reaction of activated carboxylic acid derivatives such as acid
chlorides, acid anhydrides, or esters with amines or direct coupling
of acids with amines assisted by carbodiimides/N,N0-dicarbonyldi-
imidazole.2 These methods are low in atom efficiency, often in-
volve potentially explosive molecules as catalysts and generate
substantial waste3 making their environmental profile unfavor-
able. This is the compelling reason for identifying atom-economi-
cal, safe, and efficient amide bond formation as a key thrust area
of green chemistry research.4 Mild, highly selective enzymatic
methods of hydrolysis of nitriles by nitrile hydrolases and lipase-
catalyzed amidation of acids and esters with ammonia represent
greener approaches but prohibitive isolation costs and applicabil-
ity to a limited range of substrates constitute serious drawbacks.5
The Beckmann rearrangement of ketoximes to secondary amides
under electrophilic catalysis of Lewis and Bronsted acids provides
efficient atom-economic access to secondary amides.6 Similar
isomerization of aldoximes to primary amides is ordinarily pre-
cluded due to poor migratory aptitude of hydrogen. To circumvent
this difficulty expensive late transition metal-based catalysts such
as those of Rh,7 Ru,8 Ir,9 Au–Ag,10 and Pd11 have been employed
which usually involve sequential dehydration of aldoximes to
nitriles and their controlled hydration to primary amides. Very
recently, utilization of indium and zinc salts12 for this purpose
has been also reported. We became interested in step-economic di-
rect conversion of aldehydes to primary amides avoiding isolation
of aldoximes. Available literature reports on CuII-catalyzed synthe-
sis of nitriles from aldoximes13,14 motivated us to explore one-pot
CuII-catalyzed conversion of aldehydes to primary amides. The suc-
cess of this endeavor primarily hinges upon identifying an appro-
priate Cu(II) salt as Lewis acid activator and finding out right
conditions that would favor dehydration of oxime to nitrile and
its facile concomitant hydration to amide rather than its cleavage
to parent aldehyde. To this end, copper sulfate pentahydrate was
considered an attractive candidate in view of its attenuated Lewis
acidity, ability to coordinate with oximic hydroxy group and
excellent performance as an alcohol dehydration catalyst.15 Herein,
we reveal a simple direct method of copper sulfate pentahydrate-
catalyzed conversion of aromatic aldehydes into primary amides
via aldoximes under neat conditions.
Exploratory experiments were carried out with piperonal (3,4-
methylenedioxybenzaldehyde) 1, a DOPA precursor, as a represen-
tative aromatic aldehyde. We chose piperonal as its oxime is
hydrolytically labile under Lewis acid-catalyzed conditions16 and,
therefore, expected to provide a good feel of mildness and selectiv-
ity of amide formation against competing deprotection process.
We screened a number of Cu(II)-salt catalysts such as CuSO4ꢀ5H2O,
Cu(OTf)2, Cu(NO3)2, Cu(OAc)2ꢀH2O, the results of which are exhib-
ited in Table 1. Initially, an equimolar mixture of piperonal (1),
hydroxylamine hydrochloride and fused sodium acetate together
with a catalytic amount of CuSO4ꢀ5H2O (10 mol %) was submitted
to reaction in refluxing toluene for 3 h to yield 3,4-methylenedi-
⇑
Corresponding author. Fax: +91 33 25828282.
E-mail address: nemai_g@yahoo.co.in (N.C. Ganguly).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2012.01.029

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N. C. Ganguly et al. / Tetrahedron Letters 53 (2012) 1413–1416
Table 1
Optimization experiments of Cu(II)-catalyzed conversion of aldehyde 1 to amide 1a.
O
NH2OH.HCl
CHO
O
O
NOH
O
O
O
O
(1 mol. equiv.)
NH2
Cu(II), base, 110 oC
1
1b
1a
Entry
Cu(II) salt (mol %)
Base (mol equiv)
Solvent
Reactiona time (h)
% Yieldb of
1a
1b
1
2
3
4
5
6
7
8
CuSO4ꢀ5H2O (10)
Cu(OTf)2 (10)
NaOAc (1)
NaOAc (1)
NaOH (1)
Et3N (1)
Na2CO3 (1)
K2CO3 (1)
NaOAc (1.1)
NaOAc (1.1)
NaOAc (2)
NaOAc (1.1)
NaOAc (1.1)
K2CO3 (1.1)
Na2CO3 (1.1)
NaOAc (1.1)
NaOAc (1.1)
NaOAc (1.1)
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
—
—
—
—
—
—
—
—
—
—
3
3
3
3
3
3
2
2
2
2
2
2
2
2
2
2
70
62
65
10
68
64
96
98
95
96
94
90
88
80
90
89
15
20
25
75
23
22
—
—
—
—
—
CuSO4.5H2O (10)
CuSO4ꢀ5H2O (10)
CuSO4ꢀ5H2O (10)
CuSO4ꢀ5H2O (10)
CuSO4ꢀ5H2O (10)
CuSO4ꢀ5H2O (5)
CuSO4ꢀ5H2O (5)
CuSO4 (5)
CuSO4ꢀ5H2O (5), MS 4 Å
CuSO4ꢀ5H2O (5)
CuSO4ꢀ5H2O (5)
Cu(OTf)2 (5)
9
10
11
12
13
14
15
16
—
—
5
—
Cu(NO3)2 (5)
Cu(OAc)2.H2O (5)
—
a
Reactions were performed on 1 mmolar scale.
Isolated yields after column chromatoghaphy.
b
oxybenzamide 1a as the major product (70%) accompanied with a
considerable amount of piperonal oxime 1b (entry 1). There was
further erosion in the selectivity of amide formation when copper
triflate replaced copper sulfate pentahydrate (entry 2). Sodium
hydroxide, triethylamine, anhydrous sodium carbonate, and potas-
sium carbonate were tried as bases to demask hydroxylamine from
its hydrochloride but only to deliver poorer results under identical
reaction conditions in terms of selectivity and yield of amide (en-
tries 3–6). The failure of triethylamine is presumably linked with
its ability to deactivate Cu(II)-catalyst by offering nucleophilic
nitrogen as an alternative coordination site. A serious synthetic
constraint of all these liquid phase experiments (entries 1–6) was
the persistent contamination of the desired amide with the
oxime 1b.
To circumvent this difficulty, we decided to explore solvent-free
variation of the reaction. To protect against the cleavage of oximes
triggered by protons released by hydrolysis of copper salts,15,17 it
was envisaged that mild basic conditions might be conducive
and this was bolstered by previous reports of base-assisted conver-
sions of aldoximes to nitriles.18 Gratifyingly, treatment of an equi-
molar mixture of 1, NH2OH.HCl together with a slight excess of
fused NaOAc (1.1 mol equiv) and 10 mol % of CuSO4ꢀ5H2O at
110 °C under neat conditions vastly biased the reaction in favor
of amide formation providing 1a exclusively in a 96% yield within
2 h (entry 7). Optimization of catalyst loading further revealed that
an impressive yield of 98% could be attained even with a lower cat-
alyst loading of 5 mol % (entry 8). Interestingly, anhydrous copper
sulfate, prepared by heating the pentahydrate at 200–300 °C under
reduced pressure, delivered similar excellent yield of amide. The
presence of dessicant, 4 Å molecular sieves did not alter the out-
come of the reaction significantly. The results clearly suggest that
‘external’ water released from the hydrated copper salt has no
important role in the reaction sequence. A few Cu(II)-salts such
as Cu(OTf)2, Cu(NO3)2, Cu(OAc)2ꢀH2O were tested for their efficacy
under identical solvent-free conditions (entry 14–16) but copper
sulfate pentahydrate showed best catalytic performance among
copper salts.
subjected to optimized reaction conditions and the results are
summarized in Table 2.
Table 2
Cu(II)-catalyzed conversion of aldehydes to primary amides under neat conditions
NH2OHꢀHCl ð1 mol equivÞ
NaOAc ð1:1 mol equivÞ
CusO4ꢀ5H2O ð5 mol%Þ; 110 ꢁC
RCHO
RCONH2
ƒƒƒƒƒƒƒƒƒƒƒƒƒ!
Entry
R
Timea/h
% Yield of amideb
1
2
3
4
5
6
7
8
3,4-(-OCH2O-)C6H3
C6H5
2-Cl C6H4
2
2
6
3
6
4
2
6
2
3
3
4
4
6
7
5
5
5
5
5
98
95
45
90
40
86
98
78c
97
95
98
96
98
70c
50
90
92
90
95
66
4-Cl C6H4
2-NO2 C6H4
4-NO2 C6H4
4-Me C6H4
4-OH C6H4
4-OMe C6H4
4-Allyloxy C6H4
4-Propargyloxy C6H4
4-Allyloxy,3-OMe C6H3
3-(2-Methylallyloxy) C6H4
4-OH,3-OMe C6H3
9-Anthracyl
2-Thiophenyl
2-Furyl
2-Styryl
C6H5CH2
(CH3)2CH
9
10
11
12
13
14
15
16
17
18
19
20
a
Reaction conditions: aldehyde (1 mmol), NH2OH.HCl (1 mmol), NaOAc
(1.1 mmol), CuSO4.5H2O (5 mol %), 110 °C, under air.
b
Isolated yield upon column chromatography over silica gel; the products were
characterized by spectral data (FTIR, 1H and 13C NMR and MS).
c
Varying amounts (10–20%) of unreacted aldehydes were isolated.
O
O
CuSO4.5H2O (5mol%)
NaOAc (10mol%)
OH
H
PhCH2NH2
+H2O
N
Ph
N
Ph
NH2
30%
Ph
NHCH2Ph
40%
-H2O
Ph
To assay the scope and generality of the protocol, a wide range
of aldehydes, mainly aromatic and heteroaromatic ones, were
Scheme 1. Synthesis of N-benzylbenzamide by traping benzonitrile with
benzylamine.

N. C. Ganguly et al. / Tetrahedron Letters 53 (2012) 1413–1416
1415
Table 3
Control experiments to assess the role of Cu(II)-catalysis in amide formation
O
CHO
O
O
NOH
O
O
CuSO4.5H20
neat, 110 oC
O
O
NH2
1
1b
1a
Entry
Cu(II) salt (mol %)
Additive (mol %)
Reactiona time (h)
% Yieldb of
1a
1
1
2
3
4
—
NaOAc (10)
NaOAc (10)
—
2
2
2
2
—
—
—
40
—
CuSO4ꢀ5H2O (5)
CuSO4ꢀ5H2O (5)
CuSO4ꢀ5H2O (5)
97
36
—
K+Na+ Tartrate(10)
a
Reactions were performed on 1 mmolar scale.
Isolated yields after column chromatoghaphy.
b
OH
N
pentahydrate (5 mol %) catalyzed reaction condition to yield
N-benzylbenzamide (40%) along with benzamide (Scheme 1).
To ascertain the role of Cu(II), piperonal oxime was treated with
NaOAc (10 mol %), with and without CuSO4ꢀ5H2O, in two separate
control experiments (entries 1, 2, Table 3). Non-formation of amide
without copper sulfate and its excellent yield (97%) in its presence
strongly suggest implication of Cu(II)-catalyst in the formation of
amide. When piperonal oxime was exposed to 5 mol % of
CuSO4ꢀ5H2O without NaOAc, substantial deoximation occurred
leading to concomitant formation of piperonal and the amide in
ca. 10:9 ratio (entry 3, Table 3). Literature precedents are available
on CuSO4-promoted deoximation for example acetophenone
oxime is cleaved to the ketone with 10 mol % CuSO4 in toluene
under reflux after 24 h.20 Removal of CuII by complexation with so-
dium potassium tartrate, resulted in the recovery of unreacted
oxime in almost quantitative yield further attesting to the essenti-
ality of Cu(II) catalyst (entry 4, Table 3).
O
OH
NH
H
Ar
NH2
Cu(II)
Ar
Ar
H
O
Cu(II)
H2O
N
H
O
H
Ar
Ar
Cu(II)
N
H
Ar
N
Ar
N
Cu(II)
Ar
NH
O
Cu(II)
OH
N
N
Ar
N
H
Ar
H
Ar
Cu(II)
H
N
Ar
OH
Scheme 2. Tentative catalytic cycle for the synthesis of primary amide using Cu(II)-
catalyst.
The strong propensity of oxime to bind with Cu(II) presumably
activates it toward dehydration to nitrile. Analogous mechanistic
scenario has been suggested for NiCl2ꢀ6H2O-catalyzed acylation
of amines with aldoximes.21 Aromatic nitriles have stronger pro-
pensity to hydration than their aliphatic counterparts.22 Therefore,
water released by the way of dehydration of oximes might possibly
hydrate nitriles strongly bound and activated to azaphilic Cu(II).
Another equally plausible mechanistic hypothesis is the involve-
ment of a second molecule of oxime as a surrogate of water for
delivery onto nitrile carbon in a Cu(II) complex that binds together
nitrile as well as oxime, as suggested in Rh-catalyzed ‘anhydrous
hydration’ of nitriles.23 A tentative catalytic cycle for the entire
reaction sequence is depicted below (Scheme 2).
In conclusion, the current ligand-free Cu(II)-catalyzed method
with low catalyst loading avoids use of strong bases under harsh
conditions; it has been carried out under air in solvent-free condi-
tions; it is operationally simple and uses organic solvent only in the
post-reaction stage for the isolation of product.24 No demanding or
solvent-intensive isolation and purification of product are involved
due to almost exclusive amide formation in most cases. The key
greener features combined with generality, cost effectiveness, high
selectivity, and efficiency make the present protocol synthetically
appealing.
Different aromatic moieties bearing deactivating para-nitro,
electron-releasing methoxy, allyloxy, propargyloxy, or electroneu-
tral methyl group could be accommodated to afford amides in
excellent yields (86–98%) (entries 6, 7, 9–13). The presence of
substituents ortho to the aldehyde group consistently lowered
yield and required extended reaction time (entries 3, 5). Steric
impediment to initial Cu (II) complex formation might be
responsible for this and it is further supported by sluggish and
incomplete conversion of sterically encumbered anthracene-9-
carbaldehyde to the corresponding amide (50%, 7 h) (entry 15).
The protocol has been successfully extended to heteroaromatic,
aliphatic, and aromatic aldehydes with extended conjugation
(entries 16–20). The stereochemical identity of the aldoxime
(E/Z) did not affect the outcome of the reaction. Interconversion
of the diastereoisomers under the conditions of the reaction is a
distinct possibility.
Remarkably, the present methodology did not work for ketoxi-
mes as well as oxime methyl ether thereby implying juxtaposition
of aldehydic hydrogen and oximic hydroxy group is essential for its
success. We separately prepared 4-chlorobenzonitrile following
literature procedure19 and subjected it to optimized reaction con-
ditions to afford the corresponding amide (94%) in 2 h. This obser-
vation is compatible with intermediacy of nitrile, although attempt
to isolate it in case of 4-chlorobenzaldoxime as substrate by stop-
ping the reaction short of completion after 1 h failed. However, we
could successfully intercept the putative benzonitrile intermediate
by reacting benzaldoxime with a primary amine, benzylamine hav-
ing fairly high boiling point (bp 182–185 °C) under copper sulfate
Acknowledgements
The authors (SR and PM) are thankful to UGC, New Delhi, India
and CSIR, New Delhi, India for financial assistance by way of re-
search fellowships. We are grateful to DST-FIST and UGC-SAP pro-
grammes for providing infrastructural facilities to the Department
of Chemistry, University of Kalyani.

1416
N. C. Ganguly et al. / Tetrahedron Letters 53 (2012) 1413–1416
was added CuSO4.5H2O (13 mg, 5 mol %) and the mixture was heated at 110 °C
References and notes
on an oil bath with thorough stirring for 2 h (TLC monitoring). After cooling the
reaction mixture, water (2 mL) was added to it to quench the reaction followed
by extraction with EtOAc (3 ꢂ 6 mL). The combined extract was washed with
brine (2 ꢂ 3 mL), dried (Na2SO4) and concentrated under reduced pressure. The
crude product so obtained was filtered through a short pad of silica gel (60–
120 mesh, Spectrochem, India) using EtOAc–n-hexane (1:1) as eluent to afford
3,4-methylenedioxybenzamide 1a as a white crystalline solid (161 mg, 98%),
mp 166–168 °C (lit 169 °C).10
1. Loudon, M. G. Organic Chemistry; Oxford University Press: New York, NY, 2002.
pp. 982–983.
2. For reviews of amide formation, see: (a) Valeur, E.; Bradley, M. Chem. Soc. Rev.
2009, 38, 606; (b) Montalbetti, C.; Falque, V. Tetrahedron 2005, 61, 10827.
3. Sheldon, R. A. Chemtech 1994, 38.
4. Constable, D. J. C.; Dunn, P. J.; Hayler, J. D.; Humphrey, G. R.; Leazer, J. L., Jr.;
Linderman, R. J.; Lorenz, K.; Manley, J.; Pearlman, B. A.; Wells, A.; Zaks, A.;
Zhang, T. Y. Green Chem. 2007, 9, 411.
5. (a) Wang, M.-X. Top. Catal. 2005, 35, 117; (b) Kumar, D.; Bhalla, T. C. Appl.
Microbial. Biotechnol. 2005, 68, 726.
6. (a) Ganguly, N. C.; Mondal, P. Synthesis 2010, 3705; (b) Gawley, R. E. Org. React.
1988, 35, 1; (c) Maruoka, K.; Yamamoto, H. In Comprehensive Organic Synthesis;
Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; pp 763–765. Vol. 6.
7. (a) Fujiwara, H.; Ogasawara, Y.; Yamaguchi, K.; Mizuno, N. Angew. Chem., Int. Ed.
2007, 46, 5202; (b) Kim, M.; Lee, J.; Lee, H.-Y.; Chang, S. Adv. Synth. Catal. 2009,
351, 1807.
8. Owston, N. A.; Parker, A. J.; Williams, J. M. Org. Lett. 2007, 9, 3599.
9. Owston, N. A.; Parker, A. J.; Williams, J. M. Org. Lett. 2007, 9, 73.
10. Ramon, R. S.; Bosson, J.; Diez-Gonzalez, S.; Marion, N.; Nolan, S. P. J. Org. Chem.
2010, 75, 1197.
11. Ali, M. A.; Punniyamurthy, T. Adv. Synth. Catal. 2010, 352, 288.
12. Kim, E. S.; Lee, H. S.; Kim, S. H.; Kim, J. N. Tetrahedron Lett. 2010, 51, 1589.
13. Jiang, N.; Ragauskas, A. J. Tetrahedron Lett. 2010, 51, 4479.
14. Attanasi, O.; Palna, P.; Serra-Zanetti, F. Synthesis 1983, 741.
15. Hofmann, R. V.; Bishop, R. D.; Fitch, P. N.; Hardeustein, R. J. Org. Chem. 1980, 45,
917.
Spectral data for selected products:
4-Allyloxybenzamide (entry 10): White solid; mp: 144–146 °C; IR (KBr): 3371,
3170, 1655, 1621, 1574, 1420, 1397, 1246, 1148, 1012, 939, 842 cmꢃ1 1H NMR
;
(400 MHz, CDCl3): d 7.79 (dd, J = 8, 1.6 Hz, 2H), 6.94 (d, J = 8.8 Hz, 2 H), 6.10–
6.02 (m, 1H), 6 (br s, 2H), 5.43 (dd, J = 17.2, 1.2 Hz, 1H), 5.32 (dd, J = 10.4,
1.2 Hz, 1H), 4.59 (dd, J = 2.4,1.6 Hz, 2H); 13C NMR (100 MHz, CDCl3): d 168.9,
161.6, 132.6, 129.3, 125.7, 118.2, 114.5, 68.9; LC–MS: m/z = 178 [M+1].
4-(Prop-2-ynyloxy)benzamide (entry 11): White solid; Mp: 120–122 °C; IR
(KBr): 3442, 3279, 3145, 1673, 1652, 1608, 1567, 1424, 1396, 1246, 1189,
1016, 855 cmꢃ1 1H NMR (300 MHz, DMSO-d6): d 7.81 (d, J = 8.7 Hz, 2H), 7.74
;
(br s, 1H), 7.19 (br s, 1H), 6.97 (d, J = 8.7 Hz, 2H), 4.81 (d, J = 2.1 Hz, 2H), 3.57 (d,
J = 2.1 Hz, 1H); 13C NMR (75 MHz, DMSO-d6): d 167.4, 159.5, 129.3, 127.3,
114.3, 78.9, 78.5, 55.6; LC–MS: m/z = 176 [M+1].
4-Allyloxy-3-methoxybenzamide (entry 12): White solid; Mp: 178–180 °C; IR
(KBr): 3367, 3169, 1646, 1619, 1578, 1426, 1381, 1278, 1260, 1151, 1124, 1010,
994, 874 cmꢃ1 1H NMR (300 MHz, DMSO-d6): d 7.81 (br s, 1 H), 7.42 (d,
;
J = 6.6 Hz, 2H), 7.15 (br s, 1H), 6.95 (d, J = 8.7 Hz, 1H), 6.06–5.93 (m, 1H), 5.35
(dd, J = 17.1, 1.8 Hz, 1H), 5.22 (d, J = 10.5 Hz, 1H), 4.56 (dd, J = 5.4, 1.2 Hz, 2H),
3.75 (s, 3H); 13C NMR (75 MHz, DMSO-d6): d 167.5, 150.2, 148.5, 133.6, 126.9,
120.7, 117.9, 112.4, 111.3, 68.9, 55.7; LC–MS: m/z = 208 [M+1].
16. (a) Hirano, M.; Ukawa, K.; Yakabe, S.; Clark, J. H.; Morimoto, T. Synthesis 1997,
858; (b) Ganguly, N. C.; Nayek, S.; Barik, S. K. Synth. Commun. 2009, 39, 4053.
17. Wabnitz, T. C.; Yu, J. Q.; Spencer, J. B. Chem. Eur. J. 2004, 10, 848.
18. (a) Saednya, A. Synthesis 1983, 748; (b) Saednya, A. Synthesis 1982, 190.
19. Chill, S. T.; Mebane, R. C. Synth. Commun. 2009, 39, 3601.
20. De, P.; Nonappa; Pandurangan, K.; Maitra, U.; Wailes, S. Org. Lett. 2007, 9, 2767.
21. Allen, C. L.; Davulcu, S.; Williams, J. M. J. Org. Lett. 2010, 12, 5096.
22. Kim, M.; Lee, J.; Lee, H.-Y.; Chang, S. Adv. Synth. Catal. 2009, 351, 1807.
23. Lee, J.; Kim, M.; Chang, S.; Lee, H.-Y. Org. Lett. 2009, 11, 5598.
24. Typical procedure for synthesis of primary amide 1a from aldehyde 1: To an
intimate mixture of neat piperonal 1 (150 mg, 1 mmol), NH2OH.HCl (69 mg,
1 mmol) and NaOAc (90 mg, 1.1 mmol) taken in a dried round bottomed flask
3-(2-Methylallyloxy)benzamide (entry 13): White solid; Mp: 108–110 °C; IR
(KBr): 3364, 3192, 3077, 1658, 1620, 1601, 1582, 1390, 1249, 1017, 895 cmꢃ1
;
1H NMR (300 MHz, DMSO-d6): d 7.9 (br s, 1H), 7.41 (d, J = 6.9 Hz, 2H), 7.3 (br s,
1H), 7.29 (t, J = 7.8 Hz, 1H), 7.05 (d, J = 8.4 Hz, 1H), 5.02 (s, 1H), 4.92 (s, 1H), 4.47
(s, 2H), 1.74 (s, 3H); 13C NMR (75 MHz, DMSO-d6): d 167.6, 158.2, 140.8, 135.8,
129.3, 119.9, 117.7, 113.7, 112.3, 71.0, 19.2; LC–MS: m/z = 192 [M+1].
Anthracene-9-carboxamide (entry 15): Brown solid; Mp: 206–208 °C; IR (KBr):
3426, 3168, 1668, 1650, 1605, 1426, 1387, 1314, 1275, 888 cmꢃ1 1H NMR
;
(300 MHz, DMSO-d6): d 8.6 (br s, 1H), 8.24 (br s, 1H), 8.09–8.02 (m, 5H), 7.99
(br s, 1H), 7.57–7.48 (m, 4H); 13C NMR (75 MHz, DMSO-d6): d 170.4, 133.8,
130.8, 128.4, 126.9, 126.4, 125.6, 125.5, 117.8; LC–MS: m/z = 222 [M+1].