AIBN-promoted amidation of anilines with 1, 3-diketones via oxidative cleavage of C–C bond under aerobic conditions

Article abstract of DOI:10.1016/j.tet.2016.06.060

N-Acylation of anilines with 1, 3-diketones promoted by AIBN (2-2′-azoisobutyronitrile) under metal-free and peroxide-free conditions in the presence of molecular oxygen as oxidant has been described. This protocol proceeds by the oxidative cleavage of C–C bond with simultaneous intermolecular C–N bond formation under mild conditions.

Full text of DOI:10.1016/j.tet.2016.06.060

Accepted Manuscript
AIBN−Promoted amidation of anilines with 1, 3-diketones via oxidative cleavage of C–
C bond under aerobic conditions
Sadu Nageswara Rao, Darapaneni Chandra Mohan, Subbarayappa Adimurthy
PII:
S0040-4020(16)30582-8
10.1016/j.tet.2016.06.060
TET 27874
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 26 May 2016
Revised Date: 22 June 2016
Accepted Date: 23 June 2016
Please cite this article as: Rao SN, Mohan DC, Adimurthy S, AIBN−Promoted amidation of anilines with
1, 3-diketones via oxidative cleavage of C–C bond under aerobic conditions, Tetrahedron (2016), doi:
10.1016/j.tet.2016.06.060.
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ACCEPTED MANUSCRIPT
AIBN
−
Promoted Amidation of Anilines with 1, 3-diketones via Oxidative
Cleavage of C−C Bond under Aerobic Conditions
Sadu Nageswara Rao, Darapaneni Chandra Mohan and Subbarayappa Adimurthy*
Academy of Scientific & Innovative Research, CSIR–Central Salt & Marine Chemicals Research
Institute, G. B. Marg, Bhavnagar
–364 002. Gujarat (INDIA).
*E-mail: adimurthy@csmcri.org
Abstract:
N−Acylation of anilines with 1, 3−diketones promoted by AIBN (2-2'-azoisobutyronitrile) under
metal-free and peroxide-free conditions in the presence of molecular oxygen as oxidant has been
described. This protocol proceeds by the oxidative cleavage of C−C bond with simultaneous
intermolecular C−N bond formation under mild conditions.
Keywords: Acylation, Anilines, 1,3-diketones, amide synthesis, selective cleavage
--------------------------------------------------------------------------------------------------------------------
1. Introduction
Functional group interconversion is one of the most important processes in organic synthesis.
The selective transformation of amines into their corresponding amides is a crucial example
among such interconversions due to the widespread use of amides in biology and in chemical
synthesis. In addition, amides serve as versatile intermediates in the preparation of
pharmaceuticals, agrochemicals, polymers.1 Based on growing and important concept of amide
synthesis in organic chemistry, many methods have been developed for their synthesis.
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Conventional amides are being synthesized by the reaction of amines with carboxylic acid
derivatives with coupling reagents.2 In the absence of a coupling reagent, the carboxylic acid
derivatives and the amine simply form a carboxylate-ammonium salt, rather than an amide bond.
According to a recently analyzed data set by medicinal chemistry campaigns, N-acylation of
amines with activated carboxylic acids is the most common reaction performed in the synthesis
of modern pharmaceuticals to construct the amide bond.3 Several metal catalysts and oxidants
have been identified for this process,4,5 with the most promising catalysts being palladium6 and
copper/silver.7
In spite of these significant improvements, the development of novel and newer methods to
construct amide bonds avoiding the need for multiple reaction steps, activating reagents, acidic
or basic media and metal catalysts is an important goal in modern organic synthesis and deserves
investigation. Nevertheless, the direct N-acylation through the C−C bond cleavage of ketones is
still limited and attracts the continuous attention of chemists. In particular N-acylation by C−C
bond cleavage of methyl ketones without metal is of prime importance, due to the fact that, the
separation of metal catalyst from products for the synthesis of pharmaceuticals because their
residual toxicity in the target compound is a central issue to consider. Wang and Chu developed
N-acylation of aromatic amines through C−C bond cleavage to realize the transformations of
ketones to amides under metal-free conditions (Scheme 1). Despite the significance of these
Scheme 1.
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novel reactions, the direct transformation of methyl ketones through C−C bond cleavage is still a
fascinating theme.
2. Results and Discussion
In the course of our research on N−alkylation and transamidation processes under metal-free
conditions, we initially aimed to realize the N−acylation of amines with 1,3−dicarbonyl
compounds. With the hypothesis that, this transformation may occur by the radical initiator with
molecular oxygen to cleave C–C bonds without peroxides we initiated the reaction. To our
surprise, we observed the N-acylation of aniline with 1,3-dicarbonyl compound when 2-2'-
azoisobutyronitrile (AIBN) was used as radical initiator (Scheme 1). In considering possible
Table1. Optimization of reaction conditions for 3aa
aReaction conditions: 1a (0.75 mmol), 2a (0.25 mmol), AIBN (0.4 equiv), isolated yields. bReaction performed
under argon atmosphere. cReaction carried out for 12 h.
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N−acylation partners by C–C bond cleavage with radical initiator, we elected to pursue the use of
other radical initiators. To the best of knowledge, N−acylation of aniline by oxidative cleavage of
the C−C bond without metal and oxidant have been scarcely investigated. Thus, we examined the
N−acylation of aniline 2a with 2, 4−pentanedione 1a using 5 mol% of AIBN as radical initiator
at 80° C in acetonitrile under oxygen atmosphere, the desired product 3a was isolated in 15%
yield (Table 1, entry 1). The yield was improved by increasing the catalyst loading from 5 to 40
mol% (Table 1, entries 2−5). The reaction with 0.5 equiv. of AIBN, yield of the desired product
was suddenly dropped to 74% (Table 1, entry 6). It is notable that, O2 is crucial for this
N−acylation. Conducting the reaction in argon atmosphere shut down the reaction (Table 1, entry
7). The yield was dropped by lowering the reaction temperature (60° C) and time (Table 1,
entries 8 and 9). The reaction in other solvent systems like toluene, nitromethane and
dichloroethane moderate yield (48−68%) of the N−acylated product was isolated (Table 1,
entries 10−12). Moreover, other solvents were also examined (benzene, DMSO, DMF and
DMA) failed to produce the desired product (Table 1, entries 13−16). Therefore, the optimization
studies showed that 0.4 equivalent of AIBN, at 80°C in acetonitrile was found to be the best
choice of conditions for this transformation.
Under these optimized conditions, the scope for N-acylation of various anilines were investigated
using 1a as N-acylating agent (Table 2). The presence of electron donating substituents (Me,
i
OMe and Pr) on anilines at ortho/meta/para positions reacted very smoothly and gave the
desired N-acylated products 3b−3h in good to excellent yields (50-93%). Furthermore, various
anilines bearing electron withdrawing substituents on the benzene ring (F, Cl, Br, I) also gave the
corresponding N-acylated products 3i−3m in moderate to good yields. Under the optimized
conditions, no desired product formation was observed with 2-aminopyridine and pentafluoro
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aniline. However, no reaction was observed with strong electron withdrawing groups present at
the meta position of anilines. To expand the scope of the methodology, a variety of 1,3-diketones
as source of acylating agents with various anilines were subjected to synthesize the
functionalized amides (Table 3).
Table 2. Substrate scope for N-acylation of anilines with 1aa
aReaction conditions: 1a (0.75 mmol), 2a (0.25 mmol), AIBN (0.4 equiv), CH3CN (1mL), 80°C, for 24 h, Under
Oxygen atmosphere. b Isolated yields.
The reaction of 1-phenylbutane 1, 3-dione (1b) with 3-chloroaniline, 4-aminoacetophenone and
3,4-dimethoxy aniline under the optimized conditions gave the corresponding N-acylated
products 4a−4c in moderate to good yields. Similarly, the reaction of different 1, 3-diketones 1c-
1f were reacted with variety of substituted anilines and produced the desired amides 4d−4j in
good yields (56-76%). It may be noted that, in the case of unsymmetrical 1,3-diketones 1b, and
1f, the selective N-acylated products were observed rather than N-benzoylated and N-trifluoro
acetylated products. These reactions clearly indicate that, this catalytic system is selective for the
cleavage of aliphatic 1,3-diketones than aromatic ketones. However, the present methodology is
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not suitable for N-acylation of secondary amines and benzylic amines, which are not included in
the table.
Table3. Scope of different β-diketones and anilinesa
aReaction conditions: 1a (0.75 mmol), 2a (0.25 mmol), 80°C, for 24 h, isolated yields. bYield obtained with 1,3-
diketone 1f.
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To assess the scope of the present methodology, we explored the N-acylation of variety of
anilines with β-ketoesters instead of 1,3-diketones (Table 4). The reaction of β-ketoester 6a with
4-(sec-butyl)aniline and 4-(tert-butyl)aniline gave the corresponding N-acylated products 4i and
7a in good yields (81% and 76%). Other β-ketoesters 6b and 6c with representative anilines gave
corresponding N-acylated products in moderate to good yields. With β-ketoesters 6d and 6e no
reaction was observed. Products from Tables 2-4 indicates the generality of the method with
broad substrate scope.
Table4. Scope of different β-ketoesters with anilinesa
aReaction conditions: 1a (0.75 mmol), 2a (0.25 mmol), isolated yields. nr = no
reaction.
To gain insight into the reaction mechanism, some controlled experiments were carried out
(Scheme 2). Initially, the reaction of 1,3-diketone 1a was subjected with aniline at room
temperature in open air under neat conditions, the enamine product 8 was isolated in 90% yield
(Scheme 2, eq.1). When the enamine 8 was subjected to the optimized conditions, it afforded the
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N-acylated product 3a in 80% yield Scheme 2, eq.2). This reaction indicates that, the present
system proceed through the enamine intermediate formation by reaction of 1,3-diketones and
anilines which further undergoes hydrolysis to yield the desired product. Further we examined
the reaction of enamine 8 with aniline under argon atmosphere instead of oxygen, only traces of
desired product was observed (Scheme 1, eq.3). This reaction indicate the role of oxygen for the
present transformation. To check the reaction pathway, 1a and aniline was performed under
NH2
O
O
O
r.t.
(eq. 1)
N
6h
H
1b
8 :
90%
AIBN (0.4 equiv)
3a :
80%
8
(eq. 2)
(eq. 3)
CH3CN (1 mL), 80 C
12 h, O2 (balloon)
AIBN (0.4 equiv)
3a : trace
8
CH3CN (1 mL), 80 C
12 h, Ar (balloon)
NH2
O
O
Optimised
No product
(eq. 4)
(eq. 5)
conditions
TEMPO(1.0 equiv.) or BHT
1a
NH2
O
O
Optimised
No reaction
O
conditions
O
O
NH2
Optimised
conditions
(eq. 6)
N
H
O
7h;
not observed
Scheme 2. Control experiments
optimized conditions with radical scavengers TEMPO and also with BHT, in both these cases no
desired product formation was observed (Scheme 1, eq.4). Hence the present transformation
proceed through radical mechanism. Under the optimized conditions, we subjected the reaction
of aniline with acetic anhydride and 1,2-di-p-tolylethane-1,2-dione in place of 1,3-diketone to
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check the acyl or benzoyl cleavage, however, the desired product was not observed (Scheme 1,
eqs. 5 and 6). These reactions indicate the presence of methylene centre is essential between two
keto groups. Also selective cleavage occurs at acyl position rather than benzoyl positions as
indicated even in the discussion of Table 3 above.
Scheme 3. Plausible reaction mechanism.
Based on these above observations and literature reports, 8 the plausible reaction mechanism has
been proposed (Scheme 3). Initially, AIBN under thermal conditions generate the radical species
A, through the loss of nitrogen. Subsequently A in the presence of oxygen forms CPOO• active
radical species B. The condensation of 1,3-diketone 1a and aniline generates stable enamine
intermediate C and its further reaction with B, generates peroxyradical intermediate D. Further
cyclization of peroxyradical D form oxetane intermediate E. Finally thermal cleavage of E give
the desired product 3a.
3. Conclusions
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In summary, we have developed a facile and operationally convenient method for the synthesis
of amides via the oxidative cleavage of 1, 3-diketones with anilines promoted by AIBN, with
molecular oxygen as terminal oxidant. The selective cleavage of acyl group was observed in the
cases of unsymmetrical 1,3-diketones rather than benzoyl and trifluoro acyl groups. The present
method not only eliminates the use of metals but also reduces the use of stoichiometric oxidants
like peroxides for the synthesis of variety of amides with wide range of anilines and 1, 3-
diketones in good to excellent yields.
4. Experimental Section:
4.1. General: All commercially available chemicals and reagents were used without any further
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13
purification unless otherwise indicated. H and C NMR spectra were recorded at 500, and 125
MHz, respectively. The spectra were recorded in CDCl3 as solvent. Multiplicity was indicated as
follows: s (singlet); d (doublet); t (triplet); m (multiplet); dd (doublet of doublets), etc. and
coupling constants (J) were given in Hz. Chemical shifts are reported in ppm relative to TMS as
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13
an internal standard. The peaks around delta values of H NMR (7.2), and C NMR (77.0) are
correspond to deuterated solvent chloroform respectively. Mass spectra were obtained using
electron impact (EI) ionization method. Progress of the reactions was monitored by thin layer
chromatography (TLC). All products were purified through column chromatography using silica
gel 100-200 mesh size using hexane/ethyl acetate as eluent unless otherwise indicated.
4.2. General procedure for AIBN-Promoted Oxidative formation of Amides from Amines
and 1, 3-Diketones (3a): A sealed tube was equipped with a magnetic stir bar was charged
with 1, 3-di-ketone 1a (0.075 g, 0.75 mmol), aniline 2a (0.0232 g, 0.25 mmol), AIBN (0.0164 g,
0.0001 mmol), and acetonitrile (1.0 mL). The above reaction mixture was stirred at 80 ºC under
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O2 atmosphere for 24 h. After completion of the reaction, the reaction was then cooled to room
temperature, mixture was diluted with ethyl acetate. After removal of the solvent under reduced
pressure the left out residue was purified by column chromatography using silica gel with hexane
and ethyl acetate as eluent to get 3a in 82 % yield (0.0278g). The spectral data was well matched
with reported values. The above procedure is followed for the synthesis of all products reported
in this manuscript.
N-phenylacetamide (3a) 5b
(Eluent: 30% EtOAc in Hexane); white solid; 82% yield (0.0278g); 1H NMR (500 MHz, CDCl3)
δ 7.50(d, J = 8.0 Hz, 2H), 7.32-7.26 (m, 3H), 7.11 (t, J = 7.0 Hz, 1H), 2.17 (s, 3H) .13C NMR
(125 MHz, CDCl3) δ 168.4, 137.8, 128.9, 124.3, 119.9, 24.5.
N-(o-tolyl)acetamide (3b) 5b
1
(Eluent: 25% EtOAc in Hexane); white solid; 92% yield (0.0343g); H NMR (500 MHz,
CDCl3) δ 7.70 (d, J = 8.5 Hz, 2H), 7.20-7.06 (m, 4H), 2.24(s, 2H), 2.17 (s, 3H).13C NMR (125
MHz, CDCl3) δ 168.5, 135.6, 130.4, 129.6, 126.6, 125.4, 123.6, 29.7, 24.2, 17.7.
N-(m-tolyl)acetamide (3c)5b
(Eluent: 25% EtOAc in Hexane); white solid; 86% yield (0.0321g); 1H NMR (500 MHz, CDCl3)
δ 7.34 (s, 1H), 7.26-7.17(m, 3H), 6.92(d, J = 7.5 Hz, 1H), 2.33 (s, 3H), 2.16 (s, 3H) .13C NMR
(125 MHz, CDCl3) δ 168.3, 138.9, 137.7, 128.7, 125.1, 120.5, 116.9, 24.6, 21.4.
N-(p-tolyl)acetamide(3d) 5b
(Eluent: 25% EtOAc in Hexane); white solid; 93% yield (0.0345g); 1H NMR (500 MHz, CDCl3)
δ 7.46 (br s, 1H, NH), 7.37 (d, J = 8.5 Hz, 2H), 7.10 (d , J = 8.0 Hz, 2H), 2.30 (s, 3H), 2.13(s,
3H).13C NMR (125 MHz, CDCl3) δ 168.5, 135.3, 133.9, 129.4, 120.1, 24.4, 20.8.
N-(4-methoxyphenyl) acetamide (3e) 5b
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(Eluent: 25% EtOAc in Hexane); white solid; 59% yield (0.0243g); 1H NMR (500 MHz, CDCl3)
7.61 (br s, 1H, NH ), δ 7.40 (d, J = 9.0 Hz, 2H), 6.84 (d, J = 9.0 Hz, 2H ), 3.77(s, 3H), 2.04(s,
3H).13C NMR (125 MHz, CDCl3) δ 168.2, 156.2, 130.9, 121.7, 113.9, 55.2, 24.0.
N-(2-methoxyphenyl)acetamide (3f) 5c
(Eluent: 25% EtOAc in Hexane); white solid; 50% yield (0.0208g); 1H NMR (500 MHz, CDCl3)
δ 8.36 (d, J = 8.0 Hz, 1H), 7.76 (br s, 1H, NH ), 7.04 (t, J = 7.5 Hz, 1H), 6.97 (t, J = 7.5 Hz, 1H),
6.88 (d, J = 8.5 Hz, 1H), 3.88 (s, 3H), 2.20 (s, 3H).13C NMR (125 MHz, CDCl3) δ 168.1, 147.6,
127.7, 123.6, 121.1, 119.7, 109.8, 55.6, 24.9.
N-(4-isopropylphenyl)acetamide (3g) 5b
(Eluent: 30% EtOAc in Hexane); white solid; 71% yield (0.0337g); 1H NMR (500 MHz, CDCl3)
δ 7.68(br s, 1H, NH), 7.41(d, J = 8.0 Hz, 2H), 7.15 (d, J = 8.0 Hz, 2H), 2.88 (quin, J =7.0 Hz
1H), 2.13(s, 3H), 1.22(d, J = 7.0 Hz, 6H).13C NMR (125 MHz, CDCl3) δ 168.5, 144.9, 135.6,
126.8, 120.2, 33.5, 24.3., 24.0.
N-(3-isopropylphenyl)acetamide (3h) 5b
(Eluent: 30% EtOAc in Hexane); white solid; 93% yield (0.0422g); 1H NMR (500 MHz, CDCl3)
δ 7.48(t, J = 7.5 Hz, 1H),7.41(br s, 1H, NH), 7.34 (s, 1H), 7.26-7.21(m, 1H), 6.98 (d, J =7.5 Hz
1H), 2.90-2.86(m, 1H), 2.16(s, 3H), 1.23 (d, J = 7.0 Hz, 6H).13C NMR (125 MHz, CDCl3) δ
168.3, 149.7, 137.7, 133.3, 129.9, 128.7, 128.2, 122.3, 117.9, 117.3, 33.9, 24.4, 23.7.
N-(4-fluorophenyl)acetamide (3i) 5b
(Eluent: 30% EtOAc in Hexane); white solid; 58% yield (0.0220g); 1H NMR (500 MHz, CDCl3)
δ 7.60 (br s, 1H, NH), 7.46-7.43 (m, 2H), 7.00 (t, J = 8.5 Hz, 2H), 2.15 (s, 3H) .13C NMR (125
MHz, CDCl3) δ 168.5, 160.3, 158.4, 133.8, 121.89, 121.83, 115.6, 115.4, 24.3.
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N-(4-chlorophenyl)acetamide (3j) 5b
(Eluent: 30% EtOAc in Hexane); white solid; 62% yield (0.0261g); 1H NMR (500 MHz, CDCl3)
δ 7.45 (d, J = 8.5 Hz, 2H), 7.32 (br s, 1H, NH), 7.28 (d, J = 8.0 Hz, 2H), 2.17 (s, 3H) .13C NMR
(125 MHz, CDCl3) δ 168.3, 136.4, 128.9, 121.0, 24.5.
N-(4-bromophenyl)acetamide (3k) 5b
(Eluent: 30% EtOAc in Hexane); white solid; 60% yield (0.0323g); 1H NMR (500 MHz, CDCl3)
δ 7.44-7.36 (m, 5H), 2.16 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 168.4, 136.9, 131.9, 121.3,
116.8, 24.5.
N-(4-iodophenyl)acetamide (3l) 5b
(Eluent: 30% EtOAc in Hexane); white solid; 56% yield (0.0364g); 1H NMR (500 MHz, CDCl3)
δ 7.59 (d, J = 8.5 Hz, 2H), 7.35(br s, 1H, NH), 7.27(t, J = 8.5 Hz, 2H), 2.14 (s, 3H).13C NMR
(125 MHz, CDCl3) δ 168.4, 137.9, 121.6, 87.4, 29.6, 24.6.
N-(2-fluorophenyl)acetamide (3m) 3l
(Eluent: 30% EtOAc in Hexane); white solid; 74% yield (0.0283g); 1H NMR (500 MHz, CDCl3)
δ 8.30 (t, J = 8.0 Hz, 1H), 7.42 (br s, 1H, NH ), 7.13-7.03 (m, 3H), 2.22 (s, 3H).13C NMR (125
MHz, CDCl3) δ 168.4, 153.2, 151.3, 126.3, 126.2, 124.6, 124.38, 124.32, 121.8, 114.8, 114.6,
24.6.
N-(3-chlorophenyl)acetamide (4a) 5b
(Eluent: 30% EtOAc in Hexane); white solid; 65% yield (0.0276g); 1H NMR (500 MHz, CDCl3)
δ 7.81 (br s, 1H, NH ), 7.63 (s, 1H ), 7.35 (d, J = 8.0 Hz, 1H), 7.22 (t, J = 8.0 Hz, 1H), 7.07 (d, J
= 8.0 Hz, 1H), 2.17 (s, 3H), 1.29 (s, 9H).13C NMR (125 MHz, CDCl3) δ 168.7, 139.0, 134.5,
129.9, 124.3, 120.0, 117.8, 24.5.
N-(4-acetylphenyl)acetamide (4b) 5b
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(Eluent: 30% EtOAc in Hexane); white solid; 61% yield (0.0271g); 1H NMR (500 MHz, CDCl3)
δ 7.96(br s, 1H, NH), 7.93 (d, J = 8.5 Hz, 2H), 7.64 (d, J = 8.5 Hz, 2H), 2.57 (s, 3H), 2.21(s, 3H),
1.22(d, J = 7.0 Hz, 6H).13C NMR (125 MHz, CDCl3) δ 197.2, 168.8, 142.4, 129.7, 118.9, 26.4,
24.7.
N-(3,4-dimethoxyphenyl)acetamide (4c) 3n
(Eluent: 30% EtOAc in Hexane); white solid; 48% yield (0.0254g); 1H NMR (500 MHz, CDCl3)
δ 7.36 (br s, 1H, NH), 7.30 (s, 1H), 6.87-6.85 (m, 1H), 6.79-6.78 (m, 1H), 3.85(d, J = 3.5 Hz,
6H), 2.15(s, 3H).13C NMR (125 MHz, CDCl3) δ 163.2, 143.9, 140.7, 126.4, 106.9, 106.1, 100.0,
50.9, 50.7, 24.5, 19.3.
N-phenylpropionamide (4d) 5c
(Eluent: 30% EtOAc in Hexane); white solid; 56% yield (0.0208g); 1H NMR (500 MHz, CDCl3)
δ 7.52 (d, J = 7.0 Hz, 2H), 7.35-7.29 (m, 3H`), 7.09 (br s, 1H, NH ),2.39 (d, J = 7.5 Hz, 2H), 1.25
(d, J = 7.0 Hz, 3H) .13C NMR (125 MHz, CDCl3) δ 172.0, 137.9, 128.9, 124.1, 119.7, 30.7, 9.6.
N-(p-tolyl)propionamide (4e) 5b
(Eluent: 30% EtOAc in Hexane); white solid; 69% yield (0.0282g); 1H NMR (500 MHz, CDCl3)
δ 7.39 (d, J = 8.0 Hz, 2H), 7.33 (br s, 1H, NH ), 7.10 (d, J = 7.5 Hz, 2H), 2.38 (quar, J = 7.0 Hz,
2H) 2.30 (s, 3H), 1.24 (t, J = 7.5 Hz, 3H) .13C NMR (125 MHz, CDCl3) δ 172.0, 135.4, 133.7,
129.4, 119.9, 30.6, 20.8, 9.7.
N-(4-methoxyphenyl)propionamide (4f) 5b
(Eluent: 30% EtOAc in Hexane); white solid; 47% yield (0.0212g); 1H NMR (500 MHz, CDCl3)
δ 7.41 (d, J = 9.0 Hz, 2H), 7.21 (br s, 1H, NH ), 6.85 (d, J = 8.5 Hz, 2H ), 3.78 (s, 3H),
2.38(quar, J = 7.5 Hz, 2H), 1.25 (d, J = 7.5 Hz, 3H) .13C NMR (125 MHz, CDCl3) δ 171.7,
156.2, 130.9, 121.6, 113.9, 55.3, 30.4, 9.6.
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N-(3,4-dimethoxyphenyl)isobutyramide (4g) 3o
(Eluent: 30% EtOAc in Hexane); white solid; 56% yield (0.0314g); 1H NMR (500 MHz, CDCl3)
δ 7.26 (s, 1H), 7.11 (br s, 1H, NH ), 6.83-6.78 (m, 2H), 3.88 (s, 3H), 3.85 (s,3H), 2.52 (quin, J =
6.5 Hz, 1H), 1.26 (d, J = 6.5 Hz, 6H).13C NMR (125 MHz, CDCl3) δ 175.0, 149.0, 145.6, 131.7,
111.37, 111.31, 104.8, 56.1, 55.8, 36.6, 19.6.
N-(4-(trifluoromethyl)phenyl)acetamide (4h) 5d
(Eluent: 30% EtOAc in Hexane); white solid; 67% yield (0.0341g); 1H NMR (500 MHz, CDCl3)
δ 7.64 (d, J = 7.5 Hz, 2H), 7.57 (d, J = 9.0 Hz, 2H ), 7.46 (br s, 1H, NH ), 2.21 (s, 3H), 1.25-1.20
(m, 3H).13C NMR (125 MHz, CDCl3) δ 168.7, 140.9, 126.2, 122.9, 119.5, 119.3, 24.6.
N-(4-(sec-butyl)phenyl)acetamide (4i)
(Eluent: 30% EtOAc in Hexane); white solid; 58% yield (0.0275g); 1H NMR (500 MHz, CDCl3)
δ 7.40 (d, J = 8.0 Hz, 2H ), 7.24 (br s, 1H, NH), 7.13 (d, J = 8.0 Hz, 2H), 2.58 (q, J = 7.0 Hz,
1H), 2.15(s, 3H), 1.59 (quin, J = 7.5 Hz, 2H), 1.21 (d, J = 7.0 Hz, 2H), 0.81 (t, J = 7.5 Hz,
3H).13C NMR (125 MHz, CDCl3) δ 168.2, 143.8, 135.5, 127.5, 120.0, 41.1, 31.1, 24.5, 21.8,
12.1. HRMS calcd for C12H18NO: 192.1388. Found: 192.1392.
N-(4-(tert-butyl)phenyl)acetamide (7a) 3n
(Eluent: 30% EtOAc in Hexane); white solid; 76% yield (0.0362g); 1H NMR (500 MHz, CDCl3)
δ 7.41 (d, J = 7.5 Hz, 3H), 7.33 (d, J = 8.5 Hz, 2H ), 2.14 (s, 3H), 1.29 (s, 9H).13C NMR (125
MHz, CDCl3) δ 168.3, 147.2, 135.2, 125.7, 119.8, 34.3, 31.3, 24.4.
N-(3-ethylphenyl)acetamide (7b) 3m
(Eluent: 30% EtOAc in Hexane); white solid; 60% yield (0.0244g); 1H NMR (500 MHz, CDCl3)
δ 7.41(br s, 1H, NH), 7.35-7.29 (m, 2H), 7.26-7.19 (m, 1H), 6.95 (d, J = 7.5 Hz, 1H), 2.64 (quar,
J = 7.5 Hz, 2H), 2.15(s, 3H), 1.25-1.20 (m, 3H).13C NMR (125 MHz, CDCl3) δ 168.4, 145.2,
137.8, 128.8, 123.9, 119.4, 117.2, 28.8, 24.5, 15.4.
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N-(4-methoxyphenyl)propionamide (7c) 5b
(Eluent: 30% EtOAc in Hexane); white solid; 71% yield (0.0288g); 1H NMR (500 MHz, CDCl3)
δ 7.40 (d, J = 8.0 Hz, 1H), 7.36 (br s, 1H, NH ), 7.14 (d, J = 8.0 Hz, 2H ), 4.14(quar, J = 7.5 Hz,
13
1H), 2.62(quar, J = 7.5 Hz, 2H), 2.15 (s, 2H), 2.04 (s, 1H), 1.27 (t, J = 7.5 Hz, 3H). C NMR
(125 MHz, CDCl3) δ 168.1, 140.2, 135.3, 128.6, 128.5, 128.1, 120.2, 119.9, 28.1, 24.3, 15.4.
(E)-4-(phenylamino)pent-3-en-2-one (8) 5b
1
(Eluent: 30% EtOAc in Hexane); yellow solid; 90% yield: H NMR (500 MHz, CDCl3) δ 12.4
(br s, 1H, NH ), 7.35 (t, J = 7.5 Hz, 2H), 7.20 (t, J = 7.5 Hz, 1H ), 7.11 (d, J = 8.0 Hz, 2H),
5.18(s, 1H), 2.09 (s, 3H), 1.99 (s, 3H).13C NMR (125 MHz, CDCl3) δ 196.0, 160.0, 138.6,
128.9, 125.4, 124.6, 97.4, 29.0, 19.6.
ACKNOWLEDGMENT
CSIR-CSMCRI Communication No.66/2016. S.N.R is thankful to AcSIR for his Ph.D.
enrollment and the “Analytical Discipline and Centralized Instrumental Facilities” for providing
instrumentation facilities. S.N.R. is also thankful to CSIR, New Delhi for his fellowship. We
thank DST, Government of India (SR/S1/OC-13/2011), and CSIR-CSMCRI (OLP-087) for
financial support.
Supplementary Data: Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2016.
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