Alternative formation of amides and β-enaminones from aroyl chlorides using the TiCl4-trialkylamine reagent system

Article abstract of DOI:10.1039/c8ob01536h

The TiCl₄/NR₃ reagent system has been successfully employed for the synthesis of amides and β-enaminones. The reaction of variously substituted benzoyl chlorides with the TiCl₄/NR₃ reagent system, by using two different experimental procedures (Method A and Method B), afforded alternatively the corresponding amides and β-enaminones as unique or major products. The two developed protocols were investigated with a series of tertiary amines. The reactions, modulated by the presence of TiCl₄, provided the corresponding amides or β-enaminones with satisfactory yields. This paper reports a new method for carbon-carbon bond formation via the reaction of aroyl chlorides with the TiCl₄/NR₃ reagent system.

Full text of DOI:10.1039/c8ob01536h

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ARTICLE
Alternative formation of amides and β-enaminones from aroyl
chlorides using the TiCl4-trialkylamine reagent system
Received 00th January 20xx,
Accepted 00th January 20xx
Antonella Leggio,* Alessandra Comandè, Emilia Lucia Belsito, Marianna Greco, Lucia Lo Feudo,
and Angelo Liguori
DOI: 10.1039/x0xx00000x
The TiCl4/NR3 reagent system has been successfully employed for the synthesis of amides and β-enaminones. The reaction
of variously substituted benzoyl chlorides with TiCl4/NR3 reagent system, by using two different experimental procedures
(Method A and Method B), afforded alternatively the corresponding amides and β-enaminones as unique or major
products. The two developed protocols were investigated with a series of tertiary amines. The reactions, modulated by the
presence of TiCl4, provided the corresponding amides or β-enaminones with satisfactory yields. This paper reports a new
method for carbon-carbon bond formation via the reaction of aroyl chlorides with TiCl4/NR3 reagent system.
www.rsc.org/
systems.7
Introduction
Various kinds of Lewis acid are employed in organic synthesis
to promote reactions.1 In particular titanium tetrachloride is a
reagent widely used in organic synthesis for accelerating many
reactions and transforming different functional groups.2
Organotitanium compounds are also obtained by the reaction
of 1-alkynes with TiCl4-NR3 system. These reagents react with
carbonyl compounds to give the corresponding enynones.8
In all cases, the reaction is driven by the amine that generates
a carbanion by deprotonation. This carbanion by interaction
with TiCl4 originates species such as titanium enolates or
simple organotitanium compounds.
Titanium tetrachloride (TiCl4) used in combination with a
tertiary amine (NR3) represents a useful reagent system (TiCl4-
NR3) for the formation of carbon-carbon bonds, also with high
stereoselectivity, such as in aldol and other condensation
reactions.3
In the absence of organic substrates containing acidic
hydrogens, the tertiary amine reacts with titanium
tetrachloride to give an ammonium ion adduct which evolves
producing an oxidation product with iminium ion structure and
a titanium (III) specie.
Titanium enolates can be generated by the action of
triethylamine (Et3N) and TiCl4 with aldehydes or ketones
through the removal of an acid hydrogen atom and used in
conjugate addition reactions to α,β-unsaturated carbonyl
compounds.4
The iminium ion intermediate containing acidic hydrogen
atoms is converted into an organotitanium compound by the
consecutive action of the amine and titanium tetrachloride.
Such organotitanium intermediates are not isolated but react
in situ with aromatic ketones by giving the corresponding
unsaturated aldehydes (Scheme 1).9
TiCl4/Et3N reagent system is used also to promote the Baiylis-
Hilman type reaction in which arylaldehydes react with α,β-
unsaturated carbonyl compounds to provide the
corresponding chlorinated condensation product.5
Complex processes occur when TiCl4 and Et3N react with esters
generating titanium enolates. In these cases, oxidation-
reduction reactions involve dimerization of the enolates.6
Furthermore, the reaction of TiCl4/Et3N reagent system with
ketimines and ketoximes allows the formation of heterocycle
Scheme 1 Conversion of diaryl ketones into α,β-unsaturated aldehydes.
Herein we report an interesting study on the reactivity of acyl
chlorides, lacking of hydrogen atoms at the carbon atom alpha to
the carbonyl group, with organotitanium compounds obtained from
the reaction of trialkylamines with TiCl4.
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On this base we developed two different experimental procedures
that lead to the exclusive or prevalent formation of amides and β-
enaminones that are of great importance in organic synthesis.
Results and discussion
We began the investigation by testing the model reaction between
benzoyl chloride and the reagent system consisting of triethylamine
(Et3N) and titanium tetrachloride (Scheme 2).
The amount of amine used proved to be critical to the outcomes of
the reaction. Two different ways of performing the reaction were
established leading to the formation of completely different main
products as the result of two diverse reaction pathways (Method A
and Method B) (Scheme 2).
Scheme
3
Synthesis of N,N-diethylamides (Method A) or N,N-diethyl-β-
enaminones (Method B).
N,N-diethylamides (2) are the predominant reaction products by
the reaction pathway A while β-enaminones (3) are the main ones
by the reaction pathway B.
The reaction via Method A is characterized by the presence of an
excess of amine and the rapid consecutive addition of the reagents.
Benzoyl chloride (1 mmol) and TiCl4 (4 mmol) are added to a
solution of Et3N (6mmol) in methylene chloride (15 mL). The
reaction mixture is kept under magnetic stirring at room
temperature for about 12 h until complete conversion of the
benzoyl chloride. N,N-diethylbenzamide (2a) is recovered in 65 %
yield after purification of the crude reaction mixture by column
chromatography (Scheme 2).
However, with both protocols (Method A and Method B), no
particular electronic effects of the substituents on the aromatic ring
of the starting substrates are observed.
Table 1. Results of the reactions reported in Scheme 3.
R
Method
Amidea
2
β-Enaminonea
3
b
b
c
p-H3COC6H4
p-H3COC6H4
m-ClC6H4
m-ClC6H4
p-ClC6H4
A
B
A
B
A
B
A
B
62 %
8 %
8 %
65 %
70 %
7 %
c
69 %
4 %
d
d
e
e
67 %
6 %
p-ClC6H4
60 %
5 %
Scheme
2 Conversion of benzoyl chloride into the corresponding N,N-
diethylamide (Method A) or N,N-diethyl-β-enaminone (Method B).
p-O2NC6H4
p-O2NC6H4
62 %
7 %
In the Method B a solution of Et3N (4 mmol) in methylene chloride
(15 mL) is added dropwise, by means of a pressure equalized
dropping funnel, over a period of 1 hour to a solution of benzoyl
chloride (1 mmol) and TiCl4 (4 mmol) in methylene chloride (20 mL).
The reaction is complete within about 12 h. The purification of
crude reaction product by column chromatography afforded as
main reaction product the corresponding β-enaminone, (E)-3-
(diethylamino)-1-phenylprop-2-en-1-one (3a), in 63 % yield and
N,N-diethylbenzamide (2a) in 7 % yield (Scheme 2).
61 %
a Isolated yield
The reaction of benzoyl chloride with the reagent system consisting
of tripropylamine (Pr3N) and TiCl4 (Scheme 4) leads to results
consistent with those obtained with triethylamine and TiCl4. In fact,
with the method A, N,N-dipropylbenzamide (4a) is obtained in 68%
yield as unique reaction product, whereas with method B the amide
(4a) is recovered only in 4% yield and the β-enaminone (5a) is the
prevalent product (71% yield) (Scheme 4).
Under the Method B experimental conditions, the reaction occurs
in the presence of a low concentration of base.
In the light of these results, in order to confirm the outcome of the
reaction via the two methods we decided to apply the adopted
procedures (Method A and Method B) to a series of differently
substituted benzoyl chlorides (Scheme 3, Table 1).
2 | J. Name., 2012, 00, 1-3
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Scheme
4 Synthesis of N,N-dipropylamides (Method A) or N,N-dipropyl-β-
enaminones (Method B).
Scheme 6 Synthesis of N,N-dimethylamides (Method A, Method B).
Additional experiments were performed by using tertiary amines
with different alkyl substituents. To this aim, N,N-
diisopropylethylamine (DIPEA) and N,N-dimethylisopropylamine
(DMIPA), chosen as model systems, were treated with p-
chlorobenzoyl chloride (1d) and TiCl4 under the reaction conditions
of both Method A and Method B.
The outcome of the reaction of p-chlorobenzoyl chloride (1d) with
the reagent system DMIPA/TiCl4 shows that the formation of the β-
enaminone requires that at least one of the alkyl groups of the
amine has, in alpha position with respect to nitrogen atom, a
primary carbon atom with not sterically hindered hydrogens and
also a chain of at least two carbon atoms.
It is interesting to note that by using the reagent system consisting
of DIPEA and TiCl4 the two isopropyl groups of the amine are kept in
the reaction products obtained through both reaction pathways
(Scheme 5).
This finding is confirmed by the reaction of the same reagent
system DMIPA/TiCl4 with benzoyl chloride (1a) (Scheme 6, Table 2).
Also in this case, in fact, both method A and B provide exclusively
N,N-dimethylbenzamide (8a) with yields close to 65%.
Method A leads to the exclusive formation of N,N-diisopropyl-p-
chlorobenzamide (6d) (66% yield ) while method B provides the
Table 2. Results of the reactions reported in Scheme 6.
R
Method
Amidea
8
β-Enaminonea
corresponding
β-enaminone
(E)-1-(4-chlorophenyl)-3-
(diisopropylamino)prop-2-en-1-one (7d) in 75% yield and traces of
amide (6d) (4% yield) (Scheme 5).
C6H5
A
B
A
B
65 %
63 %
63 %
70 %
_
_
_
_
a
a
d
d
C6H5
p-ClC6H5
p-ClC6H5
a Isolated yield
On the basis of the collected experimental data using differently
substituted tertiary amines under the reaction conditions of the
two diverse reaction pathways, and of the available literature data9
on the reactivity of the TiCl4/Et3N reagent system, adequate
reaction mechanisms for the formation of the amides and β-
enaminones were hypothesized.
Scheme 5 Synthesis of N,N-diisopropylamides (Method A) or N,N-diisopropyl-β-
enaminones (Method B).
These results offer evidence that the ethyl group of DIPEA is
involved in the formation of the reactive intermediates and is lost
during the reaction. On the other hand, the isopropyl groups of
DIPEA do not participate in the reaction and are preserved in the
reaction products of both reaction pathways.
The key intermediate could be the ammonium ion (Adduct I)
(Scheme 7, Scheme 8) that is generated from the reaction between
the tertiary amine and titanium tetrachloride.
Instead, the reaction driven by the reagent system DMIPA/TiCl4
under both methods A and B provides a single reaction product
consisting of N,N-dimethyl-p-chlorobenzamide (8d) in 63% and 70 %
yield respectively (Scheme 6, Table 2).
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Conclusions
In this work, we have devised two methodologies that can
constitute alternative procedures for the synthesis of amides
and β-enaminones. The reported study represents a new
example of reactivity of TiCl4-NR3 reagent system with aroyl
chlorides involving carbon-carbon bond formation.
The reactions according to method A and method B, both
modulated by the presence of TiCl4, lead to the formation,
with satisfactory yields, of amides or β-enaminones that are of
great importance in organic synthesis.
Amides in fact are very important functional groups in organic
chemistry and the formation of amide bond is one of the most
used transformations in organic synthesis.10 Amides are also
biologically interesting compounds because of their presence
in molecules such as peptides, pharmaceutical agents,
naturally occurring molecules, proteins.11
Scheme 7 Proposed mechanism for amide formation (Method A)
β-enaminones represent useful synthons for the synthesis of
various heterocyclic compounds and biologically active
molecules.12
β-enaminones possess the nucleophilicity of an
The reaction path, which provides the amide as the predominant
product, is favoured when an excess of amine is present in the
reaction medium (Method A). Under these conditions, the
ammonium ion (Adduct I) reacts with the amine in excess through
an elimination process with the loss of an alkene (Hoffmann
elimination) and the formation of a nucleophile intermediate (IIA)
that reacts with the acyl chloride thus generating the amide
(Scheme 7).
enamine and the electrophilicity of an enone, therefore they
are important intermediates in organic synthesis.
Titanium tetrachloride forms with the alkyl tertiary amine an
ammonium ion adduct. In the presence of an excess of amine
this adduct generates, through an elimination process, the
amide (Method A). The formation of the amide with the
proposed method A is quite general.
When the amine is added slowly (Method B) to the reaction mixture
containing TiCl4 and the acyl chloride, the produced ammonium ion
(adduct I), in the presence of limited amount of amine, is oxidized
generating the iminium ion (IIB) which then reacts with the amine
and TiCl4 to give the imminioalkyl titanium ion (IIIB) (Scheme 8). The
reaction of acyl chloride with the organotitanium compound (IIIB)
generates the adduct IVB, that evolves to β-enaminone, and TiCl4
that is converted in titanium dioxide (TiO2) during the final
hydrolytic workup (Scheme 8).
In the absence of further amine the adduct leads to the
formation of β-enaminone (Method B). This mechanism
operates when the amine is added slowly.
The formation of the β-enaminone with the method B,
however, does not occur when the amine has a secondary
carbon directly linked to the nitrogen atom. This situation
evidently prevents the oxidation process of the amine to the
iminium ion by TiCl4. Iminium ion, in fact, constitutes the key
intermediate for the formation of the β-enaminone.
The formation of alkyltitanium species seems to be favoured at
primary carbon atoms rather than secondary ones. When β-
enaminone, for the reasons mentioned above, does not form,
the channel leading to the formation of the amide is activated.
Experimental
General experimental details
All reagents were purchased commercially without further
purification. Solvents were purified according to well-known
laboratory methods and freshly distilled prior to use. Reaction were
carried out in a tightly sealed screw-capped vial. Reactions were
magnetically stirred and monitored by thin layer chromatography
using Merck-Kieselgel 60 F254 plates. 1H and 13C NMR spectra were
recorded on a Bruker Avance 300 instrument at 300 MHz and 75
MHz, respectively. Spectroscopic analysis was performed at 293 K
on diluted solutions of each compound by using CDCl3 as the
solvent. Chemical shifts (δ) are reported in ppm. Coupling constants
(J) are reported in Hertz (Hz). GC–MS analyses were performed with
Scheme 8 Proposed mechanism for β-enaminone formation (Method B)
4 | J. Name., 2012, 00, 1-3
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DB-35MS (20
ARTICLE
a
m
×
0.18 mm, 35% Phenyl 65% 7.56-7.30 (m, 3H, ArH), 5.75 (d, J = 12.5 Hz, 1H, COCH), 3.42-3.13
dimethylpolysiloxane) capillary column. The mass detector was (m, 4H, CH2), 1.43-1.02 (m, 6H, CH3); 13C NMR (75 MHz, CDCl3) δ:
operated in the electron impact ionization mode (EI/MS) with an 188.80, 152.46, 140.78, 130.73, 128.07, 127.44, 91.77, 50.52, 42.91,
electron energy of 70 eV. The injection port was heated to 250 °C. 14.59, 11.39 (prof); GC/MS (EI, 70 eV) m/z (% rel.): 203 [M+.] (97),
The oven temperature program was initially set at 70 °C with a hold
186 (100), 174 (40), 146 (17), 126 (18), 105 (95), 98 (32), 77 (45)
.
of 2 min and ramped to 280 °C at 20 °C/min with a hold of 10 min.
Found: C, 76.56; H, 8.48; N, 6.81. C13H17NO requires C, 76.81; H,
8.43; N, 6.89%.
N,N-diethyl-4-methoxybenzamide (2b) Oil (62%); Rf = 0.71; 1H NMR
(300 MHz, CDCl3) δ: 7.22 (d, J = 8.7 Hz, 2H, ArH), 6.77 (d, J = 8.7 Hz,
2H, ArH), 3.68 (s, 3H, OCH3), 3.49-3.06 (m, 4H, CH2), 0.90-1.26 (m,
6H, CH3); 13C NMR (75 MHz, CDCl3) δ: 171.06, 160.15, 129.30,
127.99, 113.48, 55.08, 42.40, 39.81, 13.30; GC/MS (EI, 70 eV) m/z
(% rel.): 207 [M+.] (12), 206 (28), 135 (100), 107 (5), 92 (10), 77 (11).
Found: C, 69.61; H, 8.21; N, 6.65. C12H17NO2 requires C, 69.54; H,
8.27; N, 6.76%.
General procedures for the synthesis of amides and β-enaminones.
General procedure Method A
Benzoyl chloride or substituted benzoyl chloride (1 mmol) and TiCl4
(4 mmol) were added in rapid succession to a solution of
trialkylamine (6 mmol) in anhydrous dichloromethane (15 mL). The
resulting mixture was maintained under an inert atmosphere (N2)
and stirred at room temperature for about 12 hours monitoring the
reaction progress by TLC (chloroform/methanol 90:10 v/v). After
adding dichloromethane (20 mL) the mixture was washed first with
aqueous HCl 1N (3×10 mL) and then with a saturated aqueous
(E)-3-(diethylamino)-1-(4-methoxyphenyl)prop-2-en-1-one (3b) Oil
(65%); Rf = 0.64; 1H NMR (300 MHz, CDCl3) δ: 7.87 (d, J = 8.9 Hz, 2H,
solution of NaHCO3 (3 × 10 mL) and dried over anhydrous Na2SO4. ArH), 7.79 (d, J = 12.5 Hz, 1H, CHN), 6.89 (d, J = 8.9 Hz, 2H, ArH),
The evaporation of the organic solvent under reduced pressure
afforded a crude reaction product that was purified by flash column
5.74 (d, J =12.5 Hz, 1H, COCH), 3.82 (s, 3H, OCH3), 3.30 (q, J = 7.2 Hz,
4H, CH2), 1.20 (t, J = 7.2 Hz, 6H, CH3); 13C NMR (75 MHz, CDCl3) δ:
chromatography (chloroform/methanol 95:5 v/v) to provide the 187.57, 161.84, 152.02, 133.30, 129.39, 113.26, 91.15, 55.33, 45.51,
14.67; MS (EI, 70 eV) m/z (% rel.): 233 [M+.] (54), 216 (46), 204 (10),
corresponding N,N-dialkylamide (62-70 % yield) and N,N-dialkyl-β-
190 (5), 176 (7), 161 (3), 135 (100), 107 (5), 98 (26), 77 (15). Found:
C, 72.33; H, 8.29; N, 5.93. C14H19NO2 requires C, 72.07; H, 8.21; N,
6.00%.
enaminone (0-8 % yield).
General procedure Method B
To a solution of benzoyl chloride or substituted benzoyl chloride (1
mmol) in anhydrous dichloromethane (20 mL), under an inert
atmosphere (N2), TiCl4 (4 mmol) was added. To the resulting
1
3-chloro-N,N-diethylbenzamide (2c) Oil (70%); Rf = 0.50; H NMR
(300 MHz, CDCl3) δ: 8.01-7.89 (m, 1H, ArH), 7.55-7.50 (m, 1H, ArH),
7.59-7.47 (m, 1H, ArH), 7.41-7.31 (m, 1H, ArH), 7.28-7.20 (m, 1H,
ArH), 3.66-3.45 (m, 2H, CH2), 3.35-3.18 (m, 2H, CH2), 1.33-1.18 (m,
3H, CH3), 1.21-0.99 (m, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ:
169.88, 138.71, 134.49, 129.85, 129.37, 126.55, 124.41, 45.85,
33.44, 14.12, 12.70; GC/MS (EI, 70 eV) m/z (% rel.): 211 [M+.] (13),
210 (38), 182 (5), 139 (100), 111 (25), 75 (11). Found: C, 62.47; H,
6.65; N, 6.54. C11H14ClNO requires C, 62.41; H, 6.67; N, 6.62%.
solution trialkylamine
(4 mmol), dissolved in anhydrous
dichloromethane (15 mL), was added dropwise over a period of an
hour. The mixture was stirred at room temperature for about 12
hours
monitoring
the
reaction
progress
by
TLC
(chloroform/methanol 90:10 v/v). Then the mixture was washed
with aqueous HCl 1N (3×10 mL) and with a saturated aqueous
solution of NaHCO3 (3 × 10 mL) and dried (Na2SO4). The organic
solution was concentrated in vacuo and the crude residue was
purified by flash column chromatography (chloroform/methanol
95:5 v/v) to provide the corresponding N,N-dialkyl-β-enaminone
(61-75 % yield) and N,N-dialkylamide (0-7 % yield).
(E)-1-(3-chlorophenyl)-3-(diethylamino)prop-2-en-1-one (3c) Oil
(69%); Rf = 0.34; 1H NMR (300 MHz, CDCl3) δ: 7.99-7.53 (m, 3H, ArH,
CHN), 7.46-7.07 (m, 2H, ArH), 5.67 (d, J = 12.5 Hz, 1H, COCH), 3.51-
2.99 (m, 4H, CH2), 1.36-0.89 (m, 6H, CH3); 13C NMR (75 MHz, CDCl3)
δ: 186.88, 152.78, 142.49, 134.12, 130.53, 129.35, 127.50, 125.48,
91.16, 50.58, 42.82, 14.64, 11.48; GC/MS (EI, 70 eV) m/z (% rel.):
237 [M+.] (87), 222 (39), 220 (92), 208 (41), 190 (15), 180 (16), 165
(8), 154 (6), 139 (100), 126 (36), 111 (52), 98 (56), 75 (23), 56 (38).
Found: C, 65.55; H, 6.85; N, 5.84. C13H16ClNO requires C, 65.68; H,
6.78; Cl, 14.91; N, 5.89%.
N,N-diethylbenzamide (2a) Oil (65%); Rf = 0.70; 1H NMR (300 MHz,
CDCl3) δ: 7.45-7.30 (m, 5H, ArH), 3.67-3.43 (m, 2H, CH2), 3.40-3.15
(m, 2H, CH2), 1.25 (t, J = 6.0 Hz, 3H, CH3), 1.11 (t, J = 6.0 Hz, 3H,
CH3); 13C NMR (75 MHz, CDCl3) δ: 171.14, 137.12, 128.94, 128.23,
126.09, 43.13, 39.12, 14.02, 12.74; GC/MS (EI, 70 eV) m/z (% rel.):
177 [M+.] (15), 176 (42), 162 (1), 148 (3), 105 (100), 77 (32), 51 (6).
Found: C, 74.62; H, 8.56; N, 7.86. C11H15NO requires C, 74.54.13; H,
8.53; N, 7.90%
4-chloro-N,N-diethylbenzamide (2d) Oil (67%); Rf = 0.63; 1H NMR
(300 MHz, CDCl3) δ: 7.41-7.24 (m, 4H, ArH), 3.63-3.37 (m, 2H, CH2),
3.34-3.11 (m, 2H, CH2), 1.35-0.97 (m, 6H, CH3); 13C NMR (75 MHz,
CDCl3) δ: 170.21, 135.58, 135.11, 128.67, 127.82, 43.22, 39.11,
14.29, 12.82; GC/MS (EI, 70 eV) m/z (% rel.): 211 [M+.] (13), 210
(E)-3-(diethylamino)-1-phenylprop-2-en-1-one (3a) Oil (63%); Rf =
0.62; 1H-NMR (300 MHz, CDCl3) δ: 7.93-7.77 (m, 3H, ArH, CHN),
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(35), 139 (100), 111 (24), 75 (10). Found: C, 62.46; H, 6.64; N, 6.54. 1.02 (m, 12H, NCH(CH3)2); 13C NMR (75 MHz, CDCl3) δ: 169.88,
C11H14ClNO requires C, 62.41; H, 6.67; Cl, 16.75; N, 6.62%.
137.30, 134.61, 128.70, 127.13, 51.99, 20.69; GC/MS (EI, 70 eV) m/z
(% rel.): 239 [M+.] (6), 224 (5), 196 (18), 139 (100), 111 (19). Found:
C, 65.22; H, 7.64; N, 5.79. C13H18ClNO requires C, 65.13; H, 7.57; Cl,
14.79; N, 5.84%.
(E)-1-(4-chlorophenyl)-3-(diethylamino)prop-2-en-1-one (3d) Oil
(60%); Rf = 0.47; 1H NMR (300 MHz, CDCl3) δ: 7.92-7.77 (m, 3H, ArH,
CH-N), 7.45-7.32 (m, 2H, ArH), 5.71 (d, J = 12.4 Hz, 1H, COCH), 3.51-
3.18 (m, 4H, CH2), 1.38-1.13 (m, 6H, CH3); 13C NMR (300 MHz, (E)-1-(4-chlorophenyl)-3-(diisopropylamino)prop-2-en-1-one (7d)
1
CDCl3) δ: 187.17, 152.62, 139.12, 136.79, 128.88, 128.26, 91.28, Oil (75%); Rf = 0.63; H NMR (300 MHz, CDCl3) δ: 7.97 (d, J = 12.5
50.70, 42.95, 14.62, 11.60; GC/MS (EI, 70 eV) m/z (% rel.): 237 [M+.] Hz, 1H, CHN), 7.82 (d, 2H, J = 8.7 Hz, ArH), 7.35 (d, 2H, J = 8.7 Hz,
(73), 220 (78), 208 (29), 180 (13), 139 (100), 111 (35), 98 (40), 75 ArH), 5.83 (d, J = 12.5 Hz, 1H, -CO-CH=CH), 4.08-3.90 (m, 1H,
(14), 56 (19). Found: C, 65.81; H, 6.71; N, 5.96. C13H16ClNO requires NCHCH3)2), 3.73-3.51 (m, 1H, -NCH(CH3)2), 1.30-1.20 (m, 12H, -
C, 65.68; H, 6.78; Cl, 14.91; N, 5.89%.
NCH(CH3)2); 13C NMR (75 MHz, CDCl3) δ: 186.49, 149.31, 139.19,
136.65, 128.87, 128.23, 91.29, 49.51, 48.19, 23.68, 19.68; GC/MS
(EI, 70 eV) m/z (% rel.): 265 [M+.] (33), 250 (8), 222 (56), 139 (100),
126 (20), 111 (21), 43 (18). Found: C, 68.04; H, 7.67; N, 5.16.
C15H20ClNO requires C, 67.79; H, 7.58; Cl, 13.34; N, 5.27%.
1
N,N-diethyl-4-nitrobenzamide (2e) Oil (62%); Rf = 0.43; H NMR
(300 MHz, CDCl3) δ: 8.35-8.12 (m, 2H, ArH), 7.58-7.38 (m, 2H, ArH),
3.64-3.38 (m, 2H, CH2), 3.29-3.05 (m, 2H, CH2), 1.25 (t, J = 7.0 Hz,
3H, CH3), 1.11 (t, J = 7.0 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ:
168.94, 148.02, 143.38, 127.35, 123.87, 43.28, 39.48, 14.19,12.85; N,N-dimethylbenzamide (8a) Oil (65% yield method A, 63% yield
GC/MS (EI, 70 eV) m/z (% rel.): 222 [M+.] (14), 221 (34), 193 (3), 150 method B); Rf = 0.64; 1H-NMR (300 MHz, CDCl3) δ: 7.51-7.30 (m, 5H,
(100), 120 (27), 104 (31), 92 (14), 76 (19). Found: C, 59.38; H, 6.44; ArH), 3.11 (s, 3H, CH3), 2.97 (s, 3H, CH3); 13C- NMR ( 75 MHz, CDCl3)
N, 12.70. C11H14N2O3 requires C, 59.45; H, 6.35; N, 12.60%.
δ: 171.62, 136.37, 129.45, 128.29, 127.01, 39.23, 35.11; GC/MS (EI,
70 eV) m/z (% rel.): 149 [M+.] (21), 148 (64), 105 (100), 77 (53), 51
(12). Found: C, 72.50; H, 7.40; N, 9.34. C9H11NO requires C, 72.46; H,
7.43; N, 9.39%.
(E)-3-(diethylamino)-1-(4-nitrophenyl)prop-2-en-1-one (3e) Solid
1
(61%); mp = 85.0-86.6 °C; Rf = 0.30; H NMR (300 MHz, CDCl3) δ:
8.23 (d, J = 8.8 Hz, 2H, ArH), 7.99 (d, J = 8.8 Hz, 2H, ArH), 7.86 (d, J =
12.4 Hz, 1H, CHN), 5.72 (d, J = 12.4 Hz, 1H, COCH), 3.51-3.21 (m, 4H, 4-chloro-N,N-dimethylbenzamide (8d) Oil (63% yield method A,
1
CH2), 1.34-1.17 (m, 6H, -CH3); 13C NMR (75 MHz, CDCl3) δ: 185.82, 70% yield method B); Rf = 0.53; H NMR (300 MHz, CDCl3) δ: 7.42-
153.32, 148.92, 146.23, 128.23, 123.32, 91.44, 50.80, 43.02, 14.64, 7.24 (m, 4H, ArH), 3.08 (s, 3H, CH3), 2.96 (s, 3H, CH3); 13C NMR (75
11.52; GC/MS (EI, 70 eV) m/z (% rel.): 248 [M+.] (75), 231 (100), 219 MHz, CDCl3) δ: 170.51, 135.57, 134.68, 128.62, 128.59, 39.50,
(43), 173 (16), 150 (49), 98 (49), 76 (21), 56 (34). Found: C, 63.04; H, 35.55; GC/MS (EI, 70 eV) m/z (% rel.): 183 [M+.] (18), 182 (51), 139
6.45; N, 11.19. C13H16N2O3 requires C, 62.89; H, 6.50; N, 11.28%.
(100), 111 (38), 75 (16). Found: C, 58.97; H, 5.53; N, 7.58. C9H10ClNO
requires C, 58.86; H, 5.49; Cl, 19.31; N, 7.63%.
1
N,N-dipropylbenzamide (4a) Oil (68%); Rf = 0.77; H NMR (300
MHz, CDCl3) δ: 7.48-7.29 (m, 5H, ArH), 3.57-3.35 (m, 2H, NCH2),
3.25-3.07 (m, 2H, NCH2), 1.80-1.61 (m, 2H, CH2), 1.61-1.42 (m, 2H, -
CH2), 1.08-0.91 (m, 3H, CH3), 0.83-0.65 (m, 3H, CH3); 13C NMR (75
MHz, CDCl3) δ: 170.90, 136.42, 128.36, 127.52, 125.61, 49.89,
45.48, 21.05, 19.85, 10.65, 10.18; GC/MS (EI, 70 eV) m/z (% rel.):
205 [M+.] (15), 204 (20), 176 (8), 162 (2), 134 (7), 105 (100), 77 (23).
Found: C, 75.98; H, 9.35; N, 6.75. C13H19NO requires C, 76.06; H,
9.33; N, 6.82%.
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
(E)-3-(dipropylamino)-1-phenylbut-2-en-1-one (5a) Oil (71%); Rf =
1
0.66; H NMR (300 MHz, CDCl3) δ: 7.62-7.20 (m, 6H, ArH, CHN),
This work was supported by grants from MIUR (Ministero
3.28-3.02 (m 4H, NCH2), 2.08 (s, 3H, CH3), 1.69-1.46 (m, 4H,
CH2CH3), 1.09-0.70 (m, 6H, CH2CH3); 13C NMR (75 MHz, CDCl3) δ:
197.00, 155.43, 142.35, 128.83, 128.25, 127.71, 105.12, 55.05,
22.59, 10.87, 10.83; GC/MS (EI, 70 eV) m/z (% rel.): 245 [M+.] (37%),
228 (100), 216 (45), 202 (17), 168 (11), 160 (12), 145 (8), 140 (30),
105 (84), 91 (50), 77 (56). Found: C, 78.18; H, 9.38; N, 5.65.
C16H23NO requires C, 78.32; H, 9.45; N, 5.71%.
Italiano dell’Università e della Ricerca, ex-60% funds).
.
Notes and references
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4-chloro-N,N-diisopropylbenzamide (6d) Solid (66%); mp= 81.6-
1
83.7 °C; Rf = 0.70; H NMR (300 MHz, CDCl3) δ: 7.42-7.32 (m, 2H,
ArH), 7.30-7.21 (m, 2H, ArH), 3.98-3.34 (m, 2H, NCH(CH3)2), 1.61-
6 | J. Name., 2012, 00, 1-3
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