Solvent-free, base-free microwave-mediated iridium-catalyzed N-alkylation of amides with alcohols

Article abstract of DOI:10.1055/s-0033-1340142

Solvent-free, base-free microwave-mediated (CpIrCl₂) ₂-catalyzed conditions for the N-alkylation of amides with alcohols have been developed. A series of primary and secondary alcohols have been shown to produce high yields of N-alkyl arylamides and N-alkyl alkylamides.

Full text of DOI:10.1055/s-0033-1340142

230▌
PAPER
paper
Solvent-Free, Base-Free Microwave-Mediated Iridium-Catalyzed N-Alkylation
of Amides with Alcohols
Iridium-Catalyzed N-Alkylation of Amides with Alcohols
Tushar D. Apsunde, Mark L. Trudell*
Department of Chemistry, University of New Orleans, New Orleans, LA 70148, USA
Fax +1(504)2806860; E-mail: mtrudell@uno.edu
Received: 20.09.2013; Accepted: 17.10.2013
to report the first solvent-free, base-free microwave-medi-
Abstract: Solvent-free, base-free microwave-mediated (Cp*IrCl2)2-
ated iridium-catalyzed N-alkylation of amides with both
catalyzed conditions for the N-alkylation of amides with alcohols
primary and secondary alcohols.
have been developed. A series of primary and secondary alcohols
have been shown to produce high yields of N-alkyl arylamides and
N-alkyl alkylamides.
As summarized in Table 1, our initial focus was aimed at
the optimization of the conditions for the solvent free N-
alkylation of benzamide (1a) with benzyl alcohol (2a) em-
Key words: alcohol, alkylation, amide, iridium
ploying microwave irradiation to heat the reaction mix-
ture. Initially we found that the solvent-free system (Table
1, entry 1) using one equivalent of alcohol and sodium ac-
etate (5 mol%) afforded a modest yield of the N-benzyl-
benzamide (3a). Use of K2CO3 offered a slight
improvement in yield while changing to a stronger base (t-
BuOK, entry 3) led to a diminished yield with only trace
amounts of product identified. Serendipitously, it was dis-
covered that if the base was omitted from the reactant
mixture, the reaction still gave N-alkylation products, al-
beit in low yield (entry 4). However, this result was en-
couraging since it revealed that a base was not essential to
the catalytic cycle in order to effect the N-alkylation of
amides. It was subsequently determined that by increasing
the quantity of the alcohol 2a to three equivalents (entry
6) and raising the reaction temperature to 160 °C (entry 8)
the yield of 3a (85%) under base-free conditions could be
significantly improved. It was determined that the sol-
vent-free, base-free microwave-mediated conditions fur-
nished amide yields equivalent to yields reported using
conventional methods.10
The N-substituted amide is an important functional group
found in natural products as well as in non-natural com-
pounds and materials. The N-substituted amide also plays
an important role in synthetic chemistry as a protecting
group for amines and carboxylic acid derivatives.1 There
have been a variety of reports that describe methods for
the preparation of N-substituted amides.2,3 Recently, tran-
sition metals have been used to catalyze the formation of
C–N bonds using alcohols as environmentally benign
equivalents of alkyl halides.4–7 These reactions work on
the hydrogen-borrowing concept, which involves genera-
tion of only water as a by-product. Previous reports on N-
alkylation of amides with alcohols have been shown that
high reaction temperatures (>180 °C) are required.8,9 The
first example of N-alkylation of amides with alcohols us-
ing an iridium complex was reported by Fujita co-work-
ers.10 This process required refluxing in toluene for 17
hours in the presence of a base. Subsequent studies by Xu
and co-workers had demonstrated that solvent-free condi-
tions could be employed for N-alkylation of amides with
primary alcohols using a variety of transition metal cata-
lyst systems (Rh, Ru, Ir).11 However, these systems typi-
cally required long reaction times and high reaction
temperatures. Williams and co-workers reported the use
of ruthenium catalysis under solvent-free microwave-
mediated conditions to effect N-alkylation of amides with
alcohols.12 However, despite the success of the metal-cat-
alyzed N-alkylation of amides, these reports were limited
to use of only primary alcohols as alkylation agents. Con-
sequently, there has remained a need for the development
of a suitable method with wide substrate tolerance that ex-
ploited solvent-free microwave-mediated conditions. Our
interest in iridium-based catalytic systems for the forma-
tion of C–N bonds prompted us to investigate the potential
application of iridium-catalyzed amide alkylation under
solvent-free and microwave conditions.13 Herein we wish
Further evaluation of the solvent-free, base-free micro-
wave-mediated conditions revealed that there was no im-
provement in yields with an increase of reaction
temperature above 160 °C (entry 9), while a decrease in
yield was observed with a reduction in catalyst loading
below 5 mol% (entries 10, 11). Having established opti-
mized conditions for the N-alkylation of benzamide (1a,
Table 1, entry 7) it was of interest to explore the scope and
limitations of the method.
As summarized in Table 2, substituted benzyl alcohols af-
forded good yields of the corresponding N-substituted
benzylamides 3b–h. Benzyl alcohols substituted with
electron-donating groups, electron-withdrawing groups,
and halogen were equally tolerant of the solvent-free,
base-free reaction conditions. Only the 4-nitrobenzyl al-
cohol (2f, Table 2, entry 6) failed to give a good yield of
the amide 3f, affording only an intractable mixture of ma-
terial. However, the poor yield obtained with 2f was con-
sistent with the sluggish reactivity previously reported for
the nitro derivative in other systems.14,15
SYNTHESIS 2014, 46, 0230–0234
Advanced online publication: 22.11.2013
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DOI: 10.1055/s-0033-1340142; Art ID: SS-2013-M0636-OP
© Georg Thieme Verlag Stuttgart · New York

PAPER
Iridium-Catalyzed N-Alkylation of Amides with Alcohols
231
Table 2 N-Alkylation of Amides with Primary Alcoholsa
Table 1 Optimization of Solvent-Free and Base-Free Microwave-
Mediated Conditions
O
O
R2OH 2
OH
R2
R1
NH2
R1
N
O
O
H
2a
(Cp*IrCl2)2
MW, 160 °C
3 h
1
3
N
NH2
H
(Cp*IrCl2)2
base, temp
MW, 3 h
Entry
R1 (Amide)
R2 (Alcohol)
3, Yield (%)b
1a
3a
Entry 2a (equiv)
(Cp*IrCl2)2 Base
(mol%)
Temp
(°C)
Yield
(%)a
1
Ph 1a
Bn 2a
3a, 85
3b, 85
2
Ph 1a
4-MeC6H4CH2 2b
1
1
1
1
1
2
3
3
3
3
3
3
5
NaOAc
160
160
160
140
140
140
150
160
165
160
160
40
51
<10
10
25
50
80
85
84
60
35
3
Ph 1a
4-MeOC6H4CH2 2c 3c, 72
4-MeSC6H4CH2 2d 3d, 75
2
5
K2CO3
4
Ph 1a
3
5
t-BuOK
5
Ph 1a
4-F3CC6H4CH2 2e
4-O2NC6H4CH2 2f
4-ClC6H4CH2 2g
4-BrC6H4CH2 2h
4-PhC6H4CH2 2i
Me(CH2)4 2j
Me(CH2)5 2k
Bn 2a
3e, 77
3f, IMc
3g, 65
3h, 68
3i, 60
4
5
–
–
–
–
-
6
Ph 1a
5
5
7
Ph 1a
6
5
8
Ph 1a
7
5
9
Ph 1a
8
5
10
11
12
13
14
15
16
Ph 1a
3j, 72
3k, 70
3l, 68
9
5
–
–
–
Ph 1a
10
11
2.5
1.25
Me 1b
4-MeC6H4 1c
4-MeOC6H4 1d
4-ClC6H4 1e
Bn 2a
3m, 76
3n, 75
3o, 70
3p, 78
a Isolated yield after flash chromatography.
Bn 2a
Bn 2a
In addition to benzyl alcohols, the primary alkanols, pen-
tan-1-ol (2j, entry 10) and hexan-1-ol (2k, entry 11) fur-
nished the N-alkyl amides 3j and 3k in 70% and 72%
yield, respectively. Acetamide (1b, entry 12) and the sub-
stituted benzamides (1c–f, entries 13–16) also gave good
yields of the corresponding N-benzylbenzamide deriva-
tives 3l–p under the solvent-free, base-free conditions.
3,5-(MeO)2C6H3 1f Bn 2a
a All reactions were carried out with amide (1 equiv), alcohol (3
equiv), and (Cp*IrCl2)2 (5 mol%) under microwave irrdiation at 160
°C for 3 h.
b Isolated yield after flash chromatography.
c IM: Intractable mixture.
The success of the solvent-free, base-free microwave-
mediated conditions with primary alcohols prompted a
further investigation of the suitability of the reaction con-
ditions for the N-alkylation of benzamide (1a) with sec-
ondary alcohols. A variety of acyclic and cyclic secondary
alcohols 4 were investigated as substrates for the N-alkyl-
ation reaction (Table 3).
N-alkyl arylamides and N-alkyl alkylamides from both
primary and secondary alcohols. The reaction conditions
were tolerant of a variety of functional groups, employed
short reaction times and provided good to high yields of
the corresponding highly functionalized N-alkylated am-
ides.
It was satisfying to observe that the solvent free, base-free
microwave-mediated reaction conditions developed for
the primary alcohols were applicable to secondary alco-
hols as well. The acyclic alcohols (Table 3, entries 1–3)
and cyclic alcohols (entries 4, 5) coupled with benzamide
to furnish the N-alkylated products in 65–78% yields.
Even the sterically hindered benzhydrol derivatives (entry
6 and 7) afforded the N-benzhydryl amides 5f and 5g in
good yields.
All chemicals were purchased from Aldrich Chemical Company
and used as received, unless otherwise noted. TLC: silica gel (250
μm); visualization with UV light, I2 or phosphomolybdic acid.
1
Chromatography: silica gel 60 Å (230–400 mesh). H NMR (400
MHz) and 13C NMR (100 MHz) were recorded on a Varian 400
MHz NMR spectrometer at ambient temperature in CDCl3. 1H
NMR chemical shifts are reported as δ values (ppm) relative to
TMS. 13C NMR chemical shifts are reported as δ values (ppm) rel-
ative to CDCl3 (77.0 ppm). Atlantic Microlab, Inc., Norcross, GA
performed all CHN microanalyses.
In summary, we have devised a solvent-free, base-free,
microwave-mediated process for the iridium-catalyzed al-
kylation of amides with alcohols. This environmentally
benign method furnished a variety of structurally diverse
N-Alkylation of Amides with Alcohols; General Procedure
The amide (100 mg, 1 equiv), alcohol (3 equiv) and (Cp*IrCl2)2 (2.5
mol%) were added to a microwave reactor tube. The reaction mix-
ture was subjected to microwave irradiation at 160 °C for 3 h. The
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 230–234

232
T. D. Apsunde, M. L. Trudell
PAPER
N-Benzylbenzamide (3a)16
Table 3 N-Alkylation of Benzamide (1a) with Secondary Alcoholsa
Prepared according to the general procedure using 1a (100 mg, 0.83
mmol), (Cp*IrCl2)2 (16 mg, 0.021 mmol), and benzyl alcohol (2a;
270 mg, 2.5 mmol). Purification by flash chromatography afforded
a white solid; yield: 149 mg (85%); mp 105–106 °C (Lit.16 mp 103–
104 °C).
1H NMR (CDCl3): δ = 7.79 (d, J = 7.2 Hz, 2 H), 7.52–7.30 (m, 8 H),
6.39 (br s, 1 H), 4.65 (d, J = 5.6 Hz, 2 H).
O
O
ROH 4
R
N
NH2
H
(Cp*IrCl2)2
MW, 160 °C
3 h
1a
5
Entry Alcohol 4
Amide 5 (Yield %)b
13C NMR (CDCl3): δ = 44.3, 127.2, 127.8, 128.1, 128.8, 129.0,
131.7, 134.6, 138.4, 167.6.
O
N-(4-Methylbenzyl)benzamide (3b)17
N
H
1
Prepared according to the general procedure using 1a (100 mg, 0.83
mmol), (Cp*IrCl2)2 (16 mg, 0.021 mmol), and 2b (305 mg, 2.5
mmol). Purification by flash chromatography afforded a white sol-
id; yield: 159 mg (85%); mp 138–140 °C (Lit.17 mp 137 °C).
HO
4a
5a (68)
1H NMR (CDCl3): δ = 7.80 (d, J = 7.6 Hz, 2 H), 7.49 (t, J = 7.2 Hz,
1 H), 7.41 (t, J = 7.6 Hz, 2 H), 7.24 (d, J = 8.0 Hz, 2 H), 7.16 (d,
J = 7.6 Hz, 2 H), 6.41 (br s, 1 H), 4.59 (d, J = 5.6 Hz, 2 H), 2.34 (s,
3 H).
O
N
H
2
HO
4b
13C NMR (CDCl3): δ = 21.3, 44.1, 127.3, 128.2, 128.8, 129.7, 131.7,
134.6, 135.3, 137.6, 167.5.
5b (72)
O
N-(4-Methoxybenzyl)benzamide (3c)16
HO
N
H
Prepared according to the general procedure using 1a (100 mg, 0.83
mmol), (Cp*IrCl2)2 (16 mg, 0.021 mmol), and 2c (350 mg, 2.5
mmol). Purification by flash chromatography afforded a white sol-
id; yield: 144 mg (72%); mp 94–96 °C (Lit.16 mp 97–98 °C).
3
4
4c
5c (65)
O
1H NMR (CDCl3): δ = 7.76 (d, J = 8.4 Hz, 2 H), 7.48 (t, J = 7.2 Hz,
1 H), 7.41 (t, J = 7.6 Hz, 2 H), 7.27 (d, J = 8.4 Hz, 2 H), 6.87 (d,
J = 8.4 Hz, 2 H), 6.40 (br s, 1 H), 4.57 (d, J = 5.2 Hz, 2 H), 3.79 (s,
3 H).
N
H
HO
4d
13C NMR (CDCl3): δ = 43.8, 55.5, 114.3, 127.1, 128.8, 129.5, 130.4,
5d (78)
131.7, 134.6, 159.3, 167.4.
O
N-4-Methylthiobenzylbenzamide (3d)
N
H
Prepared according to the general procedure using 1a (100 mg, 0.83
mmol), (Cp*IrCl2)2 (16 mg, 0.021 mmol), and 2d (390 mg, 2.5
mmol). Purification by flash chromatography afforded a white sol-
id; yield: 160 mg (75%); mp 109–110 °C.
5
HO
4e
5e (76)
X
X
1H NMR (CDCl3): δ = 7.77 (d, J = 7.6 Hz, 2 H), 7.49 (t, J = 7.2 Hz,
1 H), 7.40 (t, J = 7.2 Hz, 2 H), 7.21–7.28 (m, J = 7.2 Hz, 2 H), 6.47
(br s, 1 H), 4.58 (d, J = 5.6 Hz, 2 H), 2.46 (s, 3 H).
O
13C NMR (CDCl3): δ = 16.1, 43.8, 127.1, 127.2, 128.7, 128.8, 131.8,
134.5, 135.2, 128.0, 167.6.
N
H
HO
Anal. Calcd for C15H15NOS: C, 70.01; H, 5.87; N, 5.44. Found:
69.88; H, 5.71; 5.20.
Y
Y
N-4-Trifluoromethylbenzylbenzamide (3e)18
6
7
4f (X = H, Y = Cl)
4g (X = Y = F)
5f (65)
5g (65)
Prepared according to the general procedure using 1a (100 mg, 0.83
mmol), (Cp*IrCl2)2 (16 mg, 0.021 mmol), and 2e (440 mg, 2.5
mmol). Purification by flash chromatography afforded a white sol-
id; yield: 179 mg (77%); mp 134–135 °C (Lit.18 mp 131–134 °C).
a All reactions were carried out with amide (1 equiv), alcohol (3
equiv), and (Cp*IrCl2)2 (5 mol%) under microwave at 160 °C for 3 h.
b Isolated yield after flash chromatography.
1H NMR (CDCl3): δ = 7.79 (d, J = 7.2 Hz, 2 H), 7.55 (d, J = 8.4 Hz,
2 H), 7.48–7.52 (m, 1 H), 7.41 (d, J = 6.4 Hz, 2 H), 7.37–7.38 (m, 2
H), 6.91 (br s, 1 H), 4.64 (d, J = 5.6 Hz, 2 H).
13C NMR (CDCl3): δ = 43.6, 125.8, 125.9, 127.2, 128.1, 128.8,
132.0, 134.2, 142.6, 167.9.
mixture was allowed to cool to r.t. and H2O (10 mL) was added. The
mixture was extracted with EtOAc (3 × 10 mL). The combined or-
ganic layers were dried (Na2SO4) and filtered. The solvent was re-
moved under reduced pressure and the residue was purified using
flash silica gel chromatography with CH2Cl2–MeOH (95:5) to fur-
nish the N-alkylamide (Tables 2 and 3).
N-4-Chlorobenzylbenzamide (3g)11
Prepared according to the general procedure using 1a (100 mg, 0.83
mmol), (Cp*IrCl2)2 (16 mg, 0.021 mmol), and 2g (350 mg, 2.5
mmol). Purification by flash chromatography afforded a white sol-
id; yield: 132 mg (65%); mp 140–142 °C (Lit.11 mp 140–143 °C].
Synthesis 2014, 46, 230–234
© Georg Thieme Verlag Stuttgart · New York

PAPER
Iridium-Catalyzed N-Alkylation of Amides with Alcohols
233
1H NMR (CDCl3): δ = 7.77 (d, J = 7.6 Hz, 2 H), 7.49 (t, J = 7.2 Hz,
1 H), 7.39 (t, J = 7.6 Hz, 2 H), 7.22–7.28 (m, 4 H), 6.78 (br s, 1 H),
4.55 (d, J = 6.0 Hz, 2 H).
1H NMR (CDCl3): δ = 7.68 (d, J = 8.0 Hz, 2 H), 7.25–7.35 (m, 5 H),
7.18 (d, J = 7.6 Hz, 2 H), 6.71 (br s, 1 H), 4.58 (d, J = 5.6 Hz, 2 H),
2.37 (s, 3 H).
13C NMR (CDCl3): δ = 43.5, 127.2, 128.8, 129.0, 129.3, 131.9,
13C NMR (CDCl3): δ = 21.6, 44.21, 127.2, 127.7, 128.0, 128.9,
133.5, 134.3, 137.0, 167.7.
129.4, 131.7, 138.6, 142.1, 167.6.
N-(4-Bromobenzyl)benzamide (3h)19
N-Benzyl-4-methoxybenzamide (3n)24
Prepared according to the general procedure using 1a (100 mg, 0.83
mmol), (Cp*IrCl2)2 (16 mg, 0.021 mmol), and 2h (470 mg, 2.5
mmol). Purification by flash chromatography afforded a white sol-
id; yield: 163 mg (68%); mp 140–142 °C (Lit.19 mp 144–145 °C).
Prepared according to the general procedure using 1d (100 mg, 0.66
mmol), (Cp*IrCl2)2 (13 mg, 0.017 mmol), and 2a (216 mg, 2.0
mmol). Purification by flash chromatography afforded a white sol-
id; yield: 119 mg (75%); mp 126–128 °C (Lit.24 mp 126–128 °C).
1H NMR (CDCl3): δ = 7.76 (d, J = 7.2 Hz, 2 H), 7.49 (t, J = 6.8 Hz,
1 H), 7.36–7.42 (m, 4 H), 7.16 (d, J = 8.0 Hz, 2 H), 6.88 (br s, 1 H),
4.51 (d, J = 6.0 Hz, 2 H).
1H NMR (CDCl3): δ = 7.75 (d, J = 8.8 Hz, 2 H), 7.25–7.33 (m, 5 H),
7.88 (d, J = 8.8 Hz, 2 H), 6.52 (br s, 1 H), 4.59 (d, J = 5.6 Hz, 2 H),
3.82 (s, 3 H).
13C NMR (CDCl3): δ = 43.5, 115.5, 121.5, 127.2, 128.8, 129.6,
13C NMR (CDCl3): δ = 44.2, 55.6, 113.9, 126.8, 127.7, 128.1, 128.9,
131.9, 134.3, 137.6, 167.8.
129.0, 138.6, 162.4, 167.1.
N-(4-Phenylbenzyl)benzamide (3i)20
N-Benzyl-4-chlorobenzamide (3o)25
Prepared according to the general procedure using 1a (100 mg, 0.83
mmol), (Cp*IrCl2)2 (16 mg, 0.021 mmol), and 2i (220 mg, 2.5
mmol). Purification by flash chromatography afforded a white sol-
id; yield: 143 mg (60%); mp 166–167 °C (Lit.20 mp 166.9–
168.3 °C).
Prepared according to the general procedure using 1e (100 mg, 0.65
mmol), (Cp*IrCl2)2 (12 mg, 0.016 mmol), and 2a (216 mg, 2.0
mmol). Purification by flash chromatography afforded a white sol-
id; yield: 121 mg (76%); mp 162–164 °C (Lit.25 mp 162 °C).
1H NMR (CDCl3): δ = 7.72 (dd, J = 6.4, 2.0 Hz, 2 H), 7.27–7.40 (m,
7 H), 6.47 (br s, 1 H), 4.62 (d, J = 5.6 Hz, 2 H).
13C NMR (CDCl3): δ = 44.5, 127.9, 128.6, 129.0, 132.9, 138.0,
1H NMR (CDCl3): δ = 7.82 (d, J = 6.8 Hz, 2 H), 7.59–7.52 (m, 4 H),
7.49–7.35 (m, 6 H), 7.33 (d, J = 7.2 Hz, 2 H), 6.57 (s, 1 H), 4.68 (d,
J = 5.6 Hz, 2 H).
13C NMR (CDCl3): δ = 44.1, 127.2, 127.3, 127.6, 127.8, 128.6,
128.8, 129.1, 131.8, 134.6, 137.5, 140.9, 141.0, 167.7.
138.1, 166.5.
N-Benzyl-3,5-dimethoxybenzamide (3p)26
Prepared according to the general procedure using 1f (100 mg, 0.55
mmol), (Cp*IrCl2)2 (11 mg, 0.014 mmol), and 2a (180 mg, 2.5
mmol). Purification by flash chromatography afforded a white sol-
id; yield: 117 mg (78%); mp 125–126 °C.
N-Pentylbenzamide (3j)19
Prepared according to the general procedure using 1a (100 mg, 0.83
mmol), (Cp*IrCl2)2 (16 mg, 0.021 mmol), and 2j (220 mg, 2.5
mmol). Purification by flash chromatography afforded a colorless
liquid; yield: 114 mg (72%).
1H NMR (CDCl3): δ = 7.25–7.33 (m, 5 H), 6.91 (d, J = 2.0 Hz, 2 H)
6.59 (br s, 1 H), 6.55 (t, J = 2.0 Hz, 1 H), 4.59 (d, J = 6.0 Hz, 2 H),
3.78 (s, 6 H).
13C NMR (CDCl3): δ = 44.3, 55.7, 103.8, 105.1, 127.8, 128.1, 132.8,
136.8, 138.3, 161.1, 167.4.
1H NMR (CDCl3): δ = 7.74 (d, J = 7.6 Hz, 2 H), 7.44 (t, J = 7.2 Hz,
1 H), 7.35 (t, J = 7.6 Hz, 2 H), 6.64 (br s, 1 H), 3.35–3.40 (m, 2 H),
1.53–1.60 (m, 2 H), 1.26–1.31 (m, 4 H), 0.86 (t, J = 6.8 Hz, 3 H).
13C NMR (CDCl3): δ = 14.2, 22.6, 29.3, 29.5, 40.3, 127.1, 128.6,
131.4, 135.0, 167.8.
N-(Pentan-2-yl)benzamide (5a)27
Prepared according to the general procedure using 1a (100 mg, 0.83
mmol), (Cp*IrCl2)2 (16 mg, 0.021 mmol), and 4a (220 mg, 2.5
mmol). Purification by flash chromatography afforded a colorless
liquid; yield: 108 mg (68%).
N-Hexylbenzamide (3k)21
Prepared according to the general procedure using 1a (100 mg, 0.83
mmol), (Cp*IrCl2)2 (16 mg, 0.021 mmol), and 2k (260 mg, 2.5
mmol). Purification by flash chromatography afforded a white sol-
id; yield: 119 mg (70%); mp 44–45 °C (Lit.21b mp 46–47 °C).
1H NMR (CDCl3): δ = 7.74 (d, J = 7.2 Hz, 2 H), 7.42 (t, J = 7.2 Hz,
1 H), 7.35 (t, J = 7.2 Hz, 2 H), 6.58 (br s, 1 H), 3.42 (q, J = 6.0 Hz,
2 H), 1.59–1.64 (m, 1 H), 1.45 (q, J = 6.4 Hz, 2 H), 0.88–0.90 (m, 6
H).
13C NMR (CDCl3): δ = 22.7, 26.1, 38.6, 38.6, 127.1, 128.6, 131.4,
135.0, 167.8.
1H NMR (CDCl3): δ = 7.74 (d, J = 8.0 Hz, 2 H), 7.43 (t, J = 6.0 Hz,
1 H), 7.33–7.41 (m, 2 H), 6.64 (br s, 1 H), 3.35–3.40 (m, 2 H), 1.52–
1.59 (m, 2 H), 1.26–1.33 (m, 6 H), 0.83 (t, J = 6.8 Hz, 3 H).
13C NMR (CDCl3): δ = 14.2, 22.7, 26.9, 29.8, 31.7, 40.3, 127.1,
128.6, 131.4, 135.0, 167.8.
N-(Cyclopentyl)benzamide (5b)28
N-Benzylacetamide (3l)22
Prepared according to the general procedure using 1a (100 mg, 0.83
mmol), (Cp*IrCl2)2 (16 mg, 0.021 mmol), and 4b (215 mg, 2.5
mmol). Purification by flash chromatography afforded a white sol-
id; yield: 122 mg (78%); mp 158–160 °C (Lit.28 mp 160–162 °C).
Prepared according to the general procedure using 1b (100 mg, 1.7
mmol), (Cp*IrCl2)2 (32 mg, 0.041 mmol), and 2a (550 mg, 5.1
mmol). Purification by flash chromatography afforded a white sol-
id; yield: 172 mg (68%); mp 58–60 °C (Lit.22 mp 61 °C).
1H NMR (CDCl3): δ = 7.73 (d, J = 7.2 Hz, 2 H), 7.46 (t, J = 8.0 Hz,
1 H), 7.40 (d, J = 8.0 Hz, 2 H), 6.53 (br s, 1 H), 4.37–4.41 (m, 1 H),
2.06–2.10 (m, 2 H), 1.63–1.77 (m, 4 H), 1.47–1.64 (m, 2 H).
1H NMR (CDCl3): δ = 7.23–7.32 (m, 5 H), 6.27 (br s, 1 H), 4.35 (d,
J = 5.6 Hz, 2 H), 1.95 (s, 3 H).
13C NMR (CDCl3): δ = 23.3, 43.8, 127.6, 128.0, 128.8, 138.5, 170.4.
13C NMR (CDCl3): δ = 24.0, 33.4, 51.9, 127.0, 128.7, 131.4, 135.1,
167.4.
N-Benzyl-4-methylbenzamide (3m)23
N-Cyclohexylbenzamide (5c)29
Prepared according to the general procedure using 1c (100 mg, 0.74
mmol), (Cp*IrCl2)2 (14 mg, 0.019 mmol), and 2a (240 mg, 2.2
mmol). Purification by flash chromatography afforded a white sol-
id; yield: 133 mg (80%); mp 133–135 °C (Lit.23 mp 133–135 °C).
Prepared according to the general procedure using 1a (100 mg, 0.83
mmol), (Cp*IrCl2)2 (16 mg, 0.021 mmol), and 4c (250 mg, 2.5
mmol). Purification by flash chromatography afforded a white sol-
id; yield: 128 mg (76%); mp 152–154 °C (Lit.29 mp 152–154 °C).
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 230–234

234
T. D. Apsunde, M. L. Trudell
PAPER
1H NMR (CDCl3): δ = 7.74 (d, J = 7.2 Hz, 2 H), 7.47 (t, J = 7.2 Hz,
1 H), 7.40 (t, J = 7.2 Hz, 2 H), 5.98 (br s, 1 H), 3.95–3.99 (m, 1 H),
2.05–2.04 (m, 2 H), 1.63–1.77 (m, 4 H), 1.18–1.47 (m, 5 H).
13C NMR (CDCl3): δ = 25.1, 25.7, 33.4, 48.9, 127.0, 128.7, 131.4,
135.3, 166.8.
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N-(1-Phenylpropan-2-yl)benzamide (5d)30
Prepared according to the general procedure using 1a (100 mg, 0.83
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mmol). Purification by flash chromatography afforded a white sol-
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1H NMR (CDCl3): δ = 7.68 (d, J = 8.0 Hz, 2 H), 7.48 (d, J = 7.2 Hz,
1 H), 7.40 (d, J = 7.6 Hz, 2 H), 7.31 (t, J = 7.2 Hz, 2 H), 7.24 (t,
J = 7.6 Hz, 3 H), 5.91 (br s, 1 H), 4.46–4.49 (m, 1 H), 2.83–2.97 (m,
2 H), 1.21 (d, J = 6.8 Hz, 3 H).
13C NMR (400 MHz, CDCl3): δ = 20.2, 42.5, 46.6, 126.7, 126.9,
128.6, 128.7, 129.7, 131.5, 135.0, 138.0, 166.9.
N-(1-Phenylbutan-3-yl)benzamide (5e)31
Prepared according to the general procedure using 1a (100 mg, 0.83
mmol), (Cp*IrCl2)2 (16 mg, 0.021 mmol), and 4e (375 mg, 2.5
mmol). Purification by flash chromatography afforded a white sol-
id; yield: 136 mg (65%); mp 117–119 °C.
1H NMR (CDCl3): δ = 7.68 (d, J = 7.6 Hz, 2 H), 7.46–7.49 (t,
J = 8.0 Hz, 1 H), 7.40 (t, J = 7.6 Hz, 2 H), 7.27 (t, J = 7.6 Hz, 2 H),
7.18 (t, J = 6.8 Hz, 3 H), 5.93 (br s, 1 H), 4.26–4.30 (m, 1 H), 2.70–
2.74 (m, 2 H), 1.86–1.92 (m, 2 H), 1.28 (d, J = 6.8 Hz, 3 H).
13C NMR (CDCl3): δ = 21.3, 32.7, 38.8, 45.9, 126.2, 127.0, 128.6,
128.7, 131.5, 135.1, 141.9, 167.0.
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N-[(4-Chlorophenyl)(phenyl)methyl]benzamide (5f)32
Prepared according to the general procedure using 1a (100 mg, 0.83
mmol), (Cp*IrCl2)2 (16 mg, 0.021 mmol), and 4f (545 mg, 2.5
mmol). Purification by flash chromatography afforded a white sol-
id; yield: 173 mg (65%); mp 163–164 °C.
1H NMR (CDCl3): δ = 7.78 (d, J = 7.6 Hz, 2 H), 7.50 (t, J = 7.6 Hz,
1 H), 7.41 (t, J = 8.0 Hz, 2 H), 7.21–7.35 (m, 8 H), 6.80 (d, J = 7.6
Hz, 1 H), 6.38 (d, J = 7.6 Hz, 1 H).
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13C NMR (CDCl3): δ = 57.1, 115.5, 127.3, 127.8, 128.0, 128.8,
129.0, 129.0, 129.1, 132.0, 134.2, 140.2, 141.1, 166.8.
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N-Bis(4-fluorophenyl)methylbenzamide (5g)23
Prepared according to the general procedure using 1a (100 mg, 0.83
mmol), (Cp*IrCl2)2 (16 mg, 0.021 mmol), and 4g (550 mg, 2.5
mmol). Purification by flash chromatography afforded a white sol-
id; yield: 174 mg (65%); mp 177–179 °C.
1H NMR (CDCl3): δ = 7.79 (d, J = 8.0 Hz, 2 H), 7.52 (t, J = 8.0 Hz,
1 H), 7.42 (t, J = 7.6 Hz, 2 H), 7.22–7.05 (m, 4 H), 7.02 (t, J = 8.4
Hz, 4 H), 6.65 (br s, 1 H), 6.39 (d, J = 7.6 Hz, 2 H).
13C NMR (CDCl3): δ = 56.4, 115.8, 116.0, 127.2, 128.9, 129.3,
129.3, 132.1, 134.1, 137.2, 137.2, 163.6.
Acknowledgment
This research was funded by the Louisiana Board of Regents
through the Board of Regents Support Fund [contract LEQSF
(2009-12)-RD-A-26] and the University of New Orleans.
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