Iron-catalysed oxidative amidation of alcohols with amines

Article abstract of DOI:10.1039/c3ob40170g

A new iron-catalysed oxidative amidation of differently substituted benzylic alcohols with mono- and di-substituted amines was developed. The Royal Society of Chemistry 2013.

Full text of DOI:10.1039/c3ob40170g

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BiomolecularChemistry
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Volume 11 | Number 23 | 21 June 2013 | Pages 3763–3926
ISSN 1477-0520
PAPER
Lidia De Luca et al.
Iron-catalysed oxidative amidation of alcohols with amines
1477-0520(2013)11:23;1-A

Organic &
Biomolecular Chemistry
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Iron-catalysed oxidative amidation of alcohols with
amines†
Cite this: Org. Biomol. Chem., 2013, 11,
3803
Silvia Gaspa, Andrea Porcheddu and Lidia De Luca*
Received 25th January 2013,
Accepted 18th March 2013
A new iron-catalysed oxidative amidation of differently substituted benzylic alcohols with mono- and
DOI: 10.1039/c3ob40170g
di-substituted amines was developed.
www.rsc.org/obc
Nevertheless, most of the developed methodologies showed
excellent activity only with sterically unhindered alcohols and
Introduction
The amide bond is one of the most significant functional unhindered amines. Furthermore they suffer from drawbacks
groups contained in many natural products, polymers, phar- derived from the formation and stability of the hemiaminal
maceuticals and synthetic intermediates.1 The classical intermediate and the use of expensive and toxic transition
method for amide synthesis is the acylation of amines with metal catalysts. Therefore, the development of alternative
carboxylic acid derivatives (acid chlorides, anhydrides, active routes to amide bond formation from alcohols remains an
esters, etc.).2 Several alternative strategies such as the Staudin- area of active research. Recently, Wang et al.11 reported a pio-
ger reaction,3 the Schmidt reaction,4 the Beckmann rearrange- neering I2-mediated synthesis of N,N-dimethyl aryl amides
ment,5 the direct amide formation from unactivated carboxylic starting from benzylic alcohols and dimethylformamide, via a
acids with amines6 and the oxidative amidation of aldehydes7 radical pathway.
have been developed. However, many of these methods have
Indubitably it is a fundamentally different approach to
the innate drawbacks of producing a stoichiometric amount of amide synthesis, which deserves to be further developed. In
waste product and of using highly hazardous reagents. The this context, we wish to report a new and efficient procedure
direct amidation of alcohols with amines can be a potentially for the oxidative amidation of alcohols with N-chloroamines,
elegant alternative pathway since it uses cheap, abundant and prepared in situ from the corresponding amines, by the use of
stable starting materials.8 To date, the oxidative amidation of TBHP as an oxidant and iron(III) chloride as a catalyst and
alcohols is essentially promoted by homogeneous Ru- and Rh- under base-free conditions. The use of iron salts as catalysts
based catalysts. Heterogeneous Ag-9 and Au-based10 catalysts seems very attractive with respect to catalysis based on pre-
were recently reported too. Usually, these strategies consist of cious metals, because of their relative non-toxicity, easy avail-
the oxidation of an alcohol to the corresponding aldehyde that ability and low price. Recently, our group has developed new
reacts with an amine. The hemiaminal intermediate is sub- protocols for the iron12 and copper13 catalysed amidation of
sequently oxidized to give the corresponding amide aldehydes. Encouraged by our previous results, we have tested
(Scheme 1).
the possibility to perform an oxidative amidation of alcohols
in view of their stability, availability and inexpensiveness com-
pared to aldehydes.
Results and discussion
We began our investigation by treating dibenzylamine 1a
(1 equiv.) with N-chlorosuccinimide (NCS) (1.1 equiv.) in aceto-
nitrile at room temperature. After 3 h, the corresponding
N-benzyl-N-chloro-1-phenylmethanamine 2a was quantitatively
formed. This reaction mixture, containing the N-chloroamine
generated in situ, was consecutively treated, without any purifi-
cation, with benzyl alcohol 3a (5 equiv.), Cu(OAc)2·H2O
(14 mol%) and tert-butyl hydroperoxide (TBHP 70% aqueous
solution, 5 equiv.) under reflux, for 2 h, generating the amide
Scheme 1 Oxidative amidation of alcohols via hemiaminal intermediate
formation.
Dipartimento di Chimica e Farmacia, Università degli Studi di Sassari, Via Vienna 2,
Sassari, Italy. E-mail: ldeluca@uniss.it; Fax: +39-079-212069; Tel: +39-079-213529
†Electronic supplementary information (ESI) available: Experimental pro-
cedures, characterization of products, and copies of 1H NMR and 13C NMR
spectra are provided. See DOI: 10.1039/c3ob40170g
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Table 1 Oxidative amidation of alcohols: optimization of the reaction
conditionsa
Entry
Oxidant
Catalyst
Yieldb (%)
1
2
3
4
5
6
7
TBHP
TBHP
TBHP
TBPB
Benzoyl peroxide
H2O2
Oxone
TBHP
TBHP
TBHP
Cu(OAc)2·H2O
FeCl3·6H2O
FeCl2·4H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
20
96
98
35
32
—
—
27
30
58
8c
9d
10e
a Reaction conditions: dibenzylamine 1a (1 equiv.), N-chlorosuccinimide
(NCS) (1.1 equiv.), in acetonitrile at room temperature for 3 h. To this
reaction mixture were added benzyl alcohol 3a (5 equiv.), catalyst
(14 mol%) and oxidant (5 equiv.) under reflux, until the disappearance
of N-chloro amine monitored by TLC. b Yield refers to the isolated
product after column chromatography. c Reaction performed using 2.5
equiv. of 3a. d Reaction performed using 2.5 equiv. of TBHP. e Reaction
performed at room temperature for 74 h.
4a in only 20% yield (Table 1, entry 1). In order to find the
optimum reaction conditions, different parameters of the
second step such as catalyst, oxidant, stoichiometric mole
ratio of reactants and temperature were examined.
Scheme 2 Oxidative amidation of alcohols: investigation of the substrate
We performed the same reaction by the use of FeCl3·6H2O
instead of Cu(OAc)2·H2O, obtaining the product 4a with a sig-
nificant improvement of yield (96%) (Table 1, entry 2). Excel-
scope of the reaction.
lent results in terms of yields (98%) were obtained using corresponding amides were obtained, since aliphatic alcohols
FeCl2·4H2O (Table 1, entry 3), but, on the whole, FeCl3 was were not oxidized to the corresponding aldehydes under the
chosen to catalyse the reaction due to its own stability. Next optimized reaction conditions.
the role of the oxidant has been evaluated. Very poor results in
Neither the electronic properties nor the steric effects of
terms of yield were observed employing different peroxides: substituents on the aromatic ring of benzylic alcohols were
tert-butyl peroxybenzoate and benzoyl peroxide were used, found to have any influence on the reaction. Both electro-
giving respectively 35% and 32% yields (Table 1, entries 4–5). donating groups, such as benzylic C–H (Scheme 2, entries 4c
No product formation was observed using classical oxidizing and 4d and 4l) and OMe (Scheme 2, entry 4b), and withdraw-
reagents such as H2O2 and oxone (Table 1, entries 6–7).
ing groups, such as NO2 (Scheme 2, entry 4e), were well toler-
With respect to the amount of benzyl alcohol 3a in the pro- ated providing the desired amides in good yields. Benzylic
cedure, it was found that 5 equiv. were optimal. The decrease alcohol with carbonyl substituents like ester gave good results
in the amount to 2.5 equiv. was detrimental (Table 1, entry 8). too (Scheme 2, 4q). The reaction carried out on alcohols with
Likewise, the decrease in the amount of tert-butyl hydroper- halide substituents on the aromatic ring gave the correspond-
oxide (TBHP) from 5 equiv. to 2.5 equiv. led to a collapse of ing amides, which could be further transformed by traditional
the yield (30%) (Table 1, entry 9). It was possible to perform cross-coupling reactions (Scheme 2, entries 4f–i).
the reaction at room temperature (Table 1, entry 10), but this
To prove the synthetic utility of the methodology, thio-
involved a considerable lengthening of the reaction time (74 h) phene-2-carbaldehyde was subjected to optimized reaction
and a substantial yield reduction (58%). After finding the best conditions, giving the desired heteroaryl amides (Scheme 2,
performing reaction conditions, the methodology was tested entries 4k and 4m) in good yield.
with an array of commercially available alcohols and amines.
When the aromatic ring was replaced by hindered biphenyl
As illustrated in Scheme 2, the methodology was applied to or naphthyl groups, the corresponding amides were obtained
different substrates to afford a wide range of variously substi- in 72% and 81% yields respectively (Scheme 2, entries 4o
tuted amides in moderate to excellent yields.
and 4p).
The reaction was tested with a series of N,N-dialkyl-amines
When aliphatic alcohols, such as 1-octanol and 2,2-
dimethyl-1-propanol, were employed as the substrates, no showing excellent tolerance. Acyclic (Scheme 2, entries 4a–c, 4j
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layer chromatography (TLC). Analysis was performed with
Merck Kieselgel 60 F254 plates and visualized using UV light
at 254 nm and KMnO4 staining. 1H NMR and 13C NMR spectra
were measured on a Bruker Avance III 400 spectrometer
(400 MHz or 100 MHz, respectively) with CDCl3 as a solvent
and recorded in ppm relative to the internal tetramethylsilane
standard. The peak patterns are indicated as follows: s, singlet;
d, doublet; t, triplet; m, multiplet; q, quartet; br, broad. The
coupling constants, J, are reported in hertz (Hz). The IR
spectra were recorded on a Jasco FTIR-480 Plus Fourier Trans-
form spectrometer. Melting points were determined in open
capillary tubes and are uncorrected. High resolution mass
spectroscopy data of the product were collected on a Waters
Micromass GCT instrument.
General procedure for the synthesis of amides 4a–q
An amine (0.32 mmol) was added to a solution of N-chlorosuc-
cinimide (0.352 mmol) in 10 mL of acetonitrile under an N2
atmosphere and at room temperature. The reaction was moni-
tored by TLC until the disappearance of the amine
(1–2 hours), and then an alcohol (1.6 mmol), TBHP (1.6 mmol,
0.22 mL of a 70 wt% in water) and FeCl3·6H2O (0.045 mmol)
were added under an N2 atmosphere.
The resulting reaction mixture was heated in an oil bath at
85 °C (the reaction was monitored by TLC until the disappear-
ance of N-chloroamine). Then the reaction mixture was
quenched with 20 mL of a saturated solution of Na2SO3 (for
the removal of excess TBHP) and extracted three times with
40 mL of diethyl ether. The combined organic phases were
dried over anhydrous Na2SO4 and the solvent was evaporated
under reduced pressure. The crude product was purified by
silica gel column chromatography to provide the desired
amides 4a–q.
Scheme 3 Proposed mechanism and global reaction.
and 4k) as well as cyclic amines (Scheme 2, entries 4d–i and
4l) showed to be effective in this reaction. Furthermore mono-
substituted amines gave the corresponding N-mono-substi-
tuted amides in good yields (Scheme 2, entries 4m–q).
On the basis of previous studies12,13 a possible reaction
mechanism is shown in Scheme 3.
Firstly, benzyl alcohol is oxidized, by TBHP, to benz-
aldehyde.14 The Fe(III) reacts with TBHP forming the tert-butyl-
peroxy radical, Fe(II) and H+ following the mechanism
demonstrated by Barton and co-workers.15 The tert-butylperoxy
radical abstracts hydrogen from aldehyde to generate an acyl
radical, as reported by Wan,16 and the N-chloroamine, after
protonation, is converted to an amino radical by a redox reac-
tion as well documented by Minisci.17 Finally, the acyl radical
and the amino radical couple to form the desired amide.12,13
N,N-Dibenzylbenzamide (4a).13 Prepared according to the
general procedure. The product was purified by flash chrom-
atography on silica gel (v/v petroleum ether–AcOEt = 4.2/0.8),
Rf = 0.44, to afford a white solid in 96% yield (m.p.
1
113–115 °C); H NMR (400 MHz, CDCl3) δ 4.39 (s, 2H), 4.70 (s,
Conclusions
2H), 7.13–7.15 (m, 2H), 7.24–7.39 (m, 11H), 7.48–7.51 (m, 2H);
13C NMR (100 MHz, CDCl3) δ 46.8, 51.4, 126.7, 127.0, 127.5,
128.4, 128.5, 128.7, 129.6, 136.2, 172.2; IR (neat) ν = 3058,
3028, 2924, 1633, 1494, 1452, 1423, 1362, 1265, 1143, 1076,
1027, 991, 736, 700.
In conclusion we have reported a novel example of C–N bond
formation via a new iron catalysed direct oxidative amidation
of alcohols with N-chloroamines, prepared in situ from
amines. The methodology was employed to prepare amides
directly from substituted benzylic alcohols and primary and
secondary amines. The procedure appears to be simple and
convenient and uses cheap, stable and easily available
reagents.
N,N-Dibenzyl-4-methoxybenzamide (4b).13 Prepared accord-
ing to the general procedure. The product was purified by
flash chromatography on silica gel (v/v petroleum ether–
AcOEt = 3.8/1.2), Rf = 0.38, to afford a white solid in 74% yield
1
(m.p. 119–121 °C); H NMR (400 MHz, CDCl3) δ 3.80 (s, 3H),
4.48 (br s, 2H), 4.67 br (s, 2H), 6.88 (d, J = 8.8 Hz, 2H), 7.2–7.38
(m, 10H), 7.48 (d, J = 8.5 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ
44.1, 55.2, 60.3, 113.8, 126.9, 127.5, 128.2, 128.5, 128.7, 136.9,
Experimental section
All reagents and solvents were as obtained from commercial 160.2, 172.2; IR (neat) ν = 3062, 2924, 2853, 1629, 1513, 1494,
sources. All the reactions were carried out under an N2 atmos- 1421, 1363, 1265, 1176, 1030, 993, 738, 701.
phere using standard techniques. Column chromatography
N,N-Dibutyl-2-methylbenzamide (4c). Prepared according to
was generally performed on silica gel (pore size 60 Å, the general procedure. The product was purified by flash
40–63 μm particle size) and reactions were monitored by thin- chromatography on silica gel (v/v petroleum ether–AcOEt =
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4/1), Rf = 0.51, to afford a pale yellow oil in 76% yield; 1H NMR
(3-Chlorophenyl)(piperidin-1-yl)methanone (4i).20 Prepared
(400 MHz, CDCl3) δ 0.74 (t, J = 7.2 Hz, 2H), 0.98 (t, J = 7.4 Hz, according to the general procedure. The product was purified
2H), 1.1 (q, J = 7.4 Hz, 2H), 1.37–1.47 (m, 4H), 1.6–1.7 (m, 2H), by flash chromatography on silica gel (v/v petroleum ether–
2.28 (s, 3H), 3.04 (t, J = 7.4 Hz, 2H), 3.3 (br s, 2H), 3.65 (br s, AcOEt = 3.8/1.2), Rf = 0.45, to afford a yellow oil in 58% yield;
2H), 7.12–7.25 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 13.7, 1H NMR (400 MHz, CDCl3) δ 1.55 (br s, 4H), 1.71 (br s, 4H),
14.1, 19.1, 19.9, 20.6, 29.8, 30.8, 44.2, 48.2, 125.8, 125.9, 128.6, 3.35 (br s, 2H), 3.72 (br s, 2H), 7.27–7.40 (m, 4H); 13C NMR
130.4, 134.1, 137.4, 171.4; IR (neat) ν = 2958, 2931, 2869, 1633, (100 MHz, CDCl3) δ 24.5, 25.6, 26.6, 43.2, 48.8, 124.9, 127.0,
1463, 1423, 1376, 1301, 1261, 746. HRMS (EI) ([M+]) Calcd for 129.5, 129.8, 134.5, 138.2, 168.7; IR (neat) ν = 2931, 2856, 1631,
C16H25NO: 247.1936, Found: 247.1933.
1566, 1439, 1280, 800, 739.
Morpholino(o-tolyl)methanone (4d).18 Prepared according
N-Benzyl-N-methylbenzamide (4j).7h Prepared according to
to the general procedure. The product was purified by flash the general procedure. The product was purified by flash
chromatography on silica gel (v/v petroleum ether–AcOEt = chromatography on silica gel (v/v petroleum ether–Et2O = 3.5/
1
2.5/2.5), Rf = 0.31, to afford a yellow oil in 86% yield; H NMR 1.5), Rf = 0.26, to afford a pale yellow oil in 79% yield; 1H NMR
(400 MHz, CDCl3) δ 2.32 (s, 3H), 3.24 (br d, J = 4.5 Hz, 2H), (400 MHz, CDCl3) δ 2.89 (br s, 1.5H), 3.06 (br s, 1.5H), 4.54 (br
3.57 (br t, J = 4.5 Hz, 2H), 3.76–3.84 (br m, 4H), 7.14–7.3 (m, s, 1H), 4.79 (br s, 1H), 7.20–7.47 (m, 10H); 13C NMR (100 MHz,
4H); 13C NMR (100 MHz, CDCl3) δ 19.1, 41.9, 47.3, 66.9, 67.0, CDCl3) δ 33.2, 37.1, 50.8, 55.2, 126.8, 127.0, 127.6, 127.9, 128.2,
125.8, 126.0, 129.1, 130.5, 134.2, 135.6, 170.1; IR (neat) ν = 128.4, 128.8, 129.6, 136.3, 136.6, 137.1, 170.8, 171.6; IR (neat)
3054, 2983, 2923, 2859, 1633, 1431, 1265, 1157, 704.
Morpholino(4-nitrophenyl)methanone
(4e).18 Prepared
ν = 2921, 1631, 1450, 1400, 1265, 1070, 1026, 698.
N,N-Dibenzylthiophene-2-carboxamide
(4k).13 Prepared
according to the general procedure. The product was purified according to the general procedure. The product was purified
by flash chromatography on silica gel (v/v petroleum ether– by flash chromatography on silica gel (v/v petroleum ether–
AcOEt = 2.5/2.5), Rf = 0.23, to afford a white solid in 77% yield Et2O = 3/2), Rf = 0.58, to afford a white solid in 98% yield (m.p.
1
(m.p. 98–101 °C); 1H NMR (400 MHz, CDCl3) δ 3.41–3.82 (br 47–50 °C); H NMR (400 MHz, CDCl3) δ 4.75 (s, 4H), 6.98 (dd,
m, 8H), 7.61 (d, J = 8.8 Hz, 2H), 8.31 (d, J = 8.8 Hz, 2H); 13C J = 3.7 Hz, J = 5.1 Hz, 1H), 7.30–7.42 (m, 11H), 7.47 (dd, J = 1.2
NMR (100 MHz, CDCl3) δ 42.6, 48.0, 66.8, 124.0, 128.2, 141.4, Hz, J = 5.1 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 50.1, 126.9,
148.5, 168.1; IR (neat) ν = 2922, 2856, 1637, 1523, 1435, 1352, 127.6, 128.6, 128.8, 129.3, 136.6, 137.7, 165.1. IR (neat) ν =
1279, 1113, 1012, 895, 839, 735.
3062, 3004, 2978, 2954, 2914, 1611, 1583, 1519, 1494, 1453,
(4-Fluorophenyl)(piperidin-1-yl)methanone (4f).19 Prepared 1422, 1364, 1347, 1306, 1250, 1078, 889.
according to the general procedure. The product was purified
Piperidin-1-yl(o-tolyl)methanone (4l).12 Prepared according
by flash chromatography on silica gel (v/v petroleum ether– to the general procedure. The product was purified by flash
AcOEt = 3/2), Rf = 0.2, to afford a pale yellow oil in 70% yield; chromatography on silica gel (v/v petroleum ether–AcOEt =
1
1H NMR (400 MHz, CDCl3) δ 1.57 (br s, 2H), 1.71 (br s, 4H), 3.5/1.5), Rf = 0.38, to afford a pale yellow oil in 85% yield; H
3.37 (br s, 2H), 3.71 (br s, 2H), 7.08–7.12 (m, 2H), 7.39–7.43 NMR (400 MHz, CDCl3) δ 1.46 (s, 2H), 1.66 (s, 4H), 2.31 (s,
(m, 2H), 13C NMR (100 MHz, CDCl3) δ 24.6, 25.7, 26.6, 43.2, 3H), 3.17 (d, J = 4.1 Hz, 2H), 3.71 (br s, 1H), 3.79 (br s, 1H),
48.9, 115.3, 115.6, 129.0, 129.1, 132.4, 132.5, 161.9, 164.4, 7.21 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 18.9, 24.5, 25.7,
169.4; IR (neat) ν = 2942, 1628, 1442, 1265, 1157, 1004, 26.5, 42.3, 47.8, 125.6, 125.8, 128.5, 130.2, 134.0, 136.7, 169.8;
847, 739.
IR (neat) ν = 3049, 2938, 2857, 1627, 1444, 1350, 1288, 1271,
(4-Chlorophenyl)(piperidin-1-yl)methanone (4g).19 Prepared 1240, 1129, 1097, 1027, 1000, 733, 700, 665.
according to the general procedure. The product was purified
N-Benzylthiophene-2-carboxamide (4m).21 Prepared accord-
by flash chromatography on silica gel (v/v petroleum ether– ing to the general procedure. The product was purified by
Et2O = 3/2), Rf = 0.2, to afford a white solid in 69% yield flash chromatography on silica gel (v/v petroleum ether–Et2O =
1
1
(m.p. 59–61 °C); H NMR (400 MHz, CDCl3) δ 1.54 (br, s, 2H), 2.5/2.5), Rf = 0.35, to afford a pale yellow oil in 63% yield; H
1.70 (br s, 4H), 3.35 (br s, 2H), 3.71 (br s, 2H), 7.34–7.41 (m, NMR (400 MHz, CDCl3) δ 4.64 (d, J = 5.7 Hz, 2H), 6.35 (br s,
4H); 13C NMR (100 MHz, CDCl3) δ 24.5, 25.6, 26.6, 43.2, 48.9, 1H), 7.09 (dd, J = 3.7 Hz, J = 5.1 Hz, 1H), 7.31–7.35 (m, 1H),
128.4, 128.7, 134.8, 135.4, 169.2; IR (neat) ν = 2937, 1629, 1440, 7.37–7.38 (m, 4H), 7.50 (dd, J = 1.2 Hz, J = 5.1 Hz, 1H), 7.53
1277, 1090, 1003, 737.
(dd, J = 1.1 Hz, J = 2.5 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ
(4-Bromophenyl)(piperidin-1-yl)methanone (4h).7g Prepared 44.0, 127.6, 127.7, 127.9, 128.1, 128.8, 130.0, 138.0, 138.7,
according to the general procedure. The product was purified 161.8; IR (neat) ν = 2922, 1629, 1545, 1421, 1265, 737.
by flash chromatography on silica gel (v/v petroleum ether–
N-Pentylbenzamide (4n).22 Prepared according to the
Et2O = 3/2), Rf = 0.23, to afford a white solid in 80% yield (m.p. general procedure. The product was purified by flash chro-
75–78 °C); 1H NMR (400 MHz, CDCl3) δ 1.54 (br s, 2H), 1.70 matography on silica gel (v/v petroleum ether–Et2O = 2.5/2.5),
(br s, 4H), 3.26 (br s, 2H), 3.71 (br s, 2H), 7.29 (d, J = 8.5 Hz, Rf = 0.51, to afford a pale yellow oil in 92% yield; 1H NMR
2H), 7.55 (d, J = 8.5 Hz, 2H); 13C NMR (100 MHz, CDCl3) (400 MHz, CDCl3) δ 0.94 (t, J = 7.1 Hz, 3H), 1.38 (m, 4H), 1.64
δ 24.5, 25.6, 26.5, 43.3, 48.8, 123.6, 128.6, 131.6, 135.3, 169.3; (t, J = 7.3 Hz, 2H), 3.47 (q, J = 7.2 Hz, 2H), 6.19 (br s, 1H),
IR (neat) ν = 2933, 2854, 1631, 1441, 1277, 1111, 1068, 1001, 7.42–7.53 (m, 3H), 7.78 (m, 2H); 13C NMR (100 MHz, CDCl3)
833, 733.
δ 14.0, 22.4, 29.1, 29.4, 40.1, 126.8, 128.5, 131.3, 134.9, 167.5;
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IR (neat) ν = 3064, 2956, 2929, 2860, 1639, 1576, 1545, 1491,
1464, 1375, 1309, 1209, 1153, 1074, 1028, 928, 877, 804, 698.
N-Heptylbiphenyl-4-carboxamide (4o). Prepared according
to the general procedure. The product was purified by flash
chromatography on silica gel (v/v petroleum ether–AcOEt =
4/1), Rf = 0.39, to afford a pale yellow oil in 72% yield; 1H NMR
(400 MHz, CDCl3) δ 0.91 (t, J = 6.9 Hz, 3H), 1.28–1.42 (m, 8H),
1.63–1.70 (m, 2H), 3.50 (q, J = 6.9 Hz, 2H), 6.18 (br s, 1H), 7.41
(t, J = 7.3 Hz, 1H), 7.49 (t, J = 7.7 Hz, 2H), 7.62–7.69 (m, 4H),
7.85 (d, J = 8.5 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 14.1,
22.6, 27.0, 29.0, 29.7, 31.8, 40.1, 127.1, 127.2, 127.3, 127.9,
128.9, 133.5, 140.1, 144.1, 167.2; IR (neat) ν = 3041, 2922, 2852,
1630, 1537, 1469, 1265, 850, 740; HRMS (EI) ([M+]) Calcd for
C20H25NO: 295.1936, Found: 295.1938.
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N-Butylnaphthalene-2-carboxamide (4p).23 Prepared accord-
ing to the general procedure. The product was purified by
flash chromatography on silica gel (v/v petroleum ether–Et2O =
3/2), Rf = 0.25, to afford a white solid in 81% yield (m.p.
98–101 °C);1H NMR (400 MHz, CDCl3) δ 1.01 (t, J = 7.3 Hz,
3H), 1.44–1.53 (m, 2H), 1.64–1.71 (m, 2H), 3.57 (q, J = 8.4 Hz,
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130.1, 133.7, 134.9, 169.5. IR (neat) ν = 3051, 2927, 1637, 1539,
1460, 1304, 1257, 1151, 1020, 779, 734.
Methyl 4-(phenethylcarbamoyl)benzoate (4q). Prepared
according to the general procedure. The product was purified
by flash chromatography on silica gel (v/v petroleum ether–
Et2O = 2/3), Rf = 0.34, to afford a white solid in 98% yield (m.p.
9 K. Shimizu, K. Ohshima and A. Satsuma, Chem.–Eur. J.,
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1
141–145 °C); H NMR (400 MHz, CDCl3) δ 2.97 (t, J = 6.8 Hz,
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C17H17NO3: 283.1208, Found: 283.1211.
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Acknowledgements
This work was financially supported by MIUR (Ministero del-
l’Istruzione, dell’Università e della Ricerca) within the project 16 Z. Liu, J. Zhang, S. Chen, E. Shi, Y. Xu and X. Wan, Angew.
PRIN titled “DNA a quadruple elica: sintesi, studi strutturali, Chem., 2012, 51, 3231.
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