Oxidative heck reaction as a tool for para-selective olefination of aniline: A DFT supported mechanism

Article abstract of DOI:10.1021/acs.joc.7b01570

This study describes the first para-selective palladium-catalyzed alkenylation of tertiary amines. This regioselective C-H activation was conducted without any chelation moieties. A series of olefins were reacted under mild reaction conditions at 60 °C, and the corresponding products were obtained in good yields with high selectivity.

Full text of DOI:10.1021/acs.joc.7b01570

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Note
Oxidative-Heck reaction as a tool for para-selective
olefination of aniline: A DFT supported mechanism
Firouz Matloubi Moghaddam, Raheleh Pourkaveh, and Ashkan Karimi
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b01570 • Publication Date (Web): 06 Sep 2017
Downloaded from http://pubs.acs.org on September 7, 2017
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Oxidative-Heck reaction as a tool for para-selective olefination of
aniline: A DFT supported mechanism
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Firouz Matloubi Moghaddam,* Raheleh Pourkaveh, Ashkan Karimi
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Laboratory of Organic Synthesis and Natural Products, Department of Chemistry,
Sharif University of Technology, Azadi Street, PO Box 111559516 Tehran, Iran
*E-mail Address: matloubi@sharif.edu
Abstract: This study describes the first paraꢀselective palladiumꢀcatalyzed alkenylation of
tertiary amines. This regioselective CꢀH activation was conducted without any chelation
moieties. A series of olefins were reacted under mild reaction conditions at 600C and the
corresponding products were obtained in good yields with high selectivity.
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Carbonꢀcarbon bond formation is a fundamental transformation in organic chemistry.
There are two ways to approach this goal: CꢀX activation and CꢀH activation. There are many
synthetic methods for CꢀC bond construction by means of CꢀX activation such as Stille,1
Kumada2 and Hiyama3, and Negishi4 reactions which suffer from the toxicity of starting
material, limited functional group tolerance, and harsh reaction conditions. There are also,
some major economic disadvantages associated with the use of organoboron compounds as
those used in the Suzuki reaction.5 Among those methods, the MizorokiꢀHeck reaction is a
versatile tool and has received considerable attention.6 So far, a number of efficient catalytic
systems have been reported to improve origin conditions,7ꢀ8 however, all these crossꢀcoupling
reactions require a good leaving group. Furthermore, using a halide promoter results in the
formation of halide salts as a byproduct.9 In order to overcome this disadvantage, an atomꢀ
economic strategy is in high demand and this is possible via direct olefination of C (Sp2)ꢀH.8ꢀ
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Therefore, CꢀH activation is a suitable candidate to control the regioselectivity.
Hydroarylation of alkynes via transition metal catalysis is another way to introduce olefin
into arenes.14ꢀ15 Recently, using different directing groups such as carbamate,16ꢀ17
pyrimidine,18 pyridine19ꢀ20 and carbonyl21ꢀ22 have attracted a great attention to put a functional
group in a special region. By this strategy, one CꢀH bond in a molecule can be preferentially
activated over other present CꢀH bonds by forming cyclometallates. However, removing and
assembling a directing group on a molecule requires extra synthetic procedures which can be
considered a drawback for that method. Beyond directing groups, there is an emerging field
in which simple arenes without chelation moieties can induce regioselectivity.23ꢀ25 Although
arenes are quite unwilling coupling partners due to CꢀH bond strengths, great efforts have
been devoted to this field and considerable advancement has been achieved from following
the pioneering work by FujiwaraꢀMoritanin.26 Up to now, only a few reports have been
published on selective oxidative functionalization of arenes.27ꢀ30 In 2007, Shi’s group
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reported Pdꢀcatalyzed ortho functionalization of substituted toluenes via ortho olefination of
N,Nꢀdimethylbenzylamines (Scheme 1a).31 In 2009, Yu and his coꢀworkers published Pdꢀ
catalyzed metaꢀselective olefination of electronꢀdeficient arenes by applying bulky 2,6ꢀ
dialkylpyridine as a ligand at 900C (Scheme 1b).32 The role of the pyridine ligand on the
selectivity of oxidative Heck reaction was also investigated by Sanford and coꢀworkers.33 In
2011, Glorius et al. reported Rhꢀcatalyzed olefination of bromobenzene at 1400C (Scheme
1c).34
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Scheme 1: different strategies for regioselective oxidative olefination
To the best of our knowledge, this is the first report of highly paraꢀselective olefination
of tertiary anilines via noꢀchelate assisted CꢀH activation catalyzed by palladium under mild
reaction conditions. In addition, density functional theory (DFT) calculations were used to
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assess a plausible mechanism and the biological activity of the reaction products was
evaluated by QSAR methods.
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In an initial attempt N,N diethylamine was reacted with methyl acrylate in the presence of
Cu(OAc)2 as oxidant, Pd(OAc)2 as catalyst, and DCE:HOAc as solvent. After being heated in
an 800C oil bath for 5 hours the paraꢀselective oxidative Heck coupling product was formed
in 81% yield (Table S1, entry 1). It is important to note that the nitrogen of the tertiary amine
did not play a chelation role in this case to activate the ortho position of the aryl ring. Being
delighted by this result, several factors such as solvent, oxidant, reaction temperature and the
amount of catalyst were optimized via reaction between N,N diethylaniline and methyl
acrylate as a model reaction.
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In order to find the best oxidant, different organic and inorganic oxidants such as BQ,
MnO2, Ag2O, Ag2CO3, oxone, K2S2O8, and Cu(OAc)2 were tested. Among them, Cu(OAc)2
was chosen as the best oxidant. We investigated the efficiency of different solvents (Table
S1, entries 8ꢀ14). According to entries 1 and 14 controlling experiment were conducted.
Results showed that HOAc is essential in achieving higher yields because in its absence, a
significantly lower yield was obtained. In the presence of HOAc, the concentration of tertiary
aniline is tuning. Without this acidic condition, tertiary amine nitrogen atom binds strongly to
Pd (II) ion due to its strong σꢀdonor property. In the next step, the amount of catalyst required
for such a transformation was optimized. Increasing the amount of catalyst up to 5 mol%
reduced the reaction time (entry 17). Exploring the effect of reaction temperature showed that
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lowering to 60 C was also efficient and there was no sensible change in reaction yield
observed. Finally, it was found that the presence of a transition metal is necessary for
progressing the reaction (entry 18). Notably, palladium as a transition metal catalyst proved
to be crucial and the model reaction did not proceed when conducted in the presence of nickel
(entry 19). With optimum conditions in hand, the scope of the reaction with different olefins
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was investigated. As shown in table 1, both terminal and internal alkenes were suitable
substrates. Different acrylic esters such as methyl and butyl were reacted in high yields
(entries 1, 2, 16). However, acrylic acid could not act as an efficient substrate under
optimized reaction conditions. This observation may arise from strong binding of carboxylic
acid oxygen to the Pd (II) ion. Apart from acyclic alkenes, cyclic ones were also investigated.
In this case, cyclohexenone proceeds the reaction in high yield and the aryl ring of diethyl
aniline attached at the β position of the carbonyl group (entry 3). Acrylo nitrile, styrene, vinyl
acetate, and ethyl cinnamate are other examples of terminal alkenes which conducted this
transformation in good yields (entries 4, 5, 6, 7). Finally, N,N diisopropylaniline as a
sterically hindered substrate was employed and desired product in excellent yield was
obtained. In all cases, para and trans isomers were observed.
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Table 1. para-olefination of tertiary anlinesa
NR2
NR2
R4
R2
R2
R3
Pd(OAc)2 (5 mol%), Cu(OAc)2
DCE:HOAc, 600C
R3
R4
R= CH3: 1a
R=CH2CH3: 1b
Product name/ Yield %b
2
O
O
N
3ba/ 89
3bb/ 87
3bc/ 89
3bf/ 76
3bd/ 85
3be/ 80
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3bg/ 82
3bh/ 83
3bi/ 78
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3bk/ 84
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3bj/ 77
3bl/ 77
3ac/ 86
3ab/ 84
3aa/ 86
O
N
O
N
3ad/ 84
3ae/ 70
3ca/ 90
aReaction conditions: amine (0.5 mmol), alkene (0.8 mmol), Cu(OAc)2 (0.5 mmol), DCE:HOAc (1.5:1, 1mL),
Pd(OAc)2 ( 5mol%) at 600C for 5 hours.
bisolated yield.
Although there are some mechanistic studies on ortho CꢀH activation, to the best of our
knowledge there is no study on para CꢀH activation. Since this is the first report on para
olefination of tertiary aniline, a more logic mechanism was proposed by employing DFT
calculations at M06 functional to report a mechanism with an optimized geometry of the
structures and their energy profile as shown in Figure 1 (for more detailed mechanism see
Figure S1). Briefly, the mechanism contains an electrophilic metalation in the para site of the
aromatic ring. We compared the insertion of Pd in different sites and found that para insertion
is the most favorable since the concentration of free amine is tuned by ACOH. In the next
steps, a nucleophilic attack followed by a CꢀC cross coupling occurred. The rate determining
step is the conversion of INT5 to INT6 through TS3. The energy barrier of this step is 74.3
kcal/mol which is accessible in our reaction temperature (353K). ∆H and ∆G of the reaction
of dimethyl aniline and styrene (as a sample for our theoretical investigation) are 106 and 101
kcal/mol, respectively (for more details see supporting information).
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Fig 1. Plausible reaction mechanism for para-olefination of tertiary aniline
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It is important to note that trans stiblene derivatives are known to be inhibitors of TNFαꢀ
induced activation of NFꢀƙB. NFꢀƙB is a family of transcription factors which has an
influence on the expression of numerous genes involved in immunity and inflammation.35
Based on the experimental results,36 we evaluated the activity of our reaction products by
using a QSAR model. Different molecular descriptors were produced by PaDEL software37
and the model was performed using chemoface program.38 The best QSAR model was
obtained with R2= 0.942, RMSE= 0.135 and F= 114.3. According to our investigations, the
products exhibit high activity against activation of NFꢀƙB. Table S2 Shows the predicted
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IC50 values obtained from the GAꢀMLR method. IC50 for the products is in the range of nM
and the most reactive compound is (E)ꢀethyl 3ꢀ(4ꢀ(diethylamino) phenyl)ꢀ2ꢀphenylacrylate
(Table S2, entry 7) with predicted IC50 of 0.13 nM. According to our QSAR studies, all of
the products have biological activity against activation of NKꢀkB and some of them show
very high activity (IC50<10nM). In vivo experimental evaluation of biological activity of our
products to confirm our prediction is an ongoing project in our laboratory and the results will
be reported in future publications.
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Conclusion
To date, various methods have been developed to introduce olefins into arenes. This
study showed the art of governing regioselectivity via palladiumꢀcatalyzed Heckꢀtype
strategy without using a coordinating element. Under optimized reaction conditions, a wide
range of alkenes were reacted efficiently with tertiary aromatic amine and corresponding
paraꢀselective products formed in high yields. It is important to note that electronic and steric
factors of simple arenes like N,N dimethylaniline, N,N diethylaniline, and N,N
diisopropylaniline are responsible for such regioselective CꢀH bond functionalization. In the
light of DFT studies, a rational mechanism was reported and the bioactivity of the reaction products
against TNFα was also evaluated by QSAR method.
Experimental section
General information
All materials used are commercially available and were purchased from Merck and used
without any additional purification. Palladium acetate was purchased from SigmaꢀAldrich
1
with 98% purity. H NMR and 13C NMR spectra were recorded on a Bruker (Avance DRXꢀ
500) spectrometer using CDCl3 as solvent at room temperature. Chemical shifts δ were
reported in ppm relative to tetramethylsilane as an internal standard. FTIR spectra of samples
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were taken using an ABB Bomem MBꢀ100 FTIR spectrophotometer. Gas chromatography
(GC) analyses were performed on an Agilent Technologies 6890 N, equipped with a 19019 Jꢀ
413 HPꢀ5, 5% phenyl methyl siloxane, capillary column (60.0 m×250 ꢁm×1.00 ꢁm). Highꢀ
resolution mass spectroscopy was performed on a JEOL GCꢀmate II spectrometer.
Computational information
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The molecular geometries and structures were optimized at the M06 functional of theory .39
In all mechanistic calculations, LANL2DZ basis set40 was set for the Palladium atoms and 6ꢀ
31G*41 for the others. Calculations were performed at gas phase and 298.15 K. Conformer
distribution was studied by Spartan42 and Gaussian09 package43 was used for other
mechanistic calculations. First Frequency was utilized to assess whether intermediates and
transition states were in the true optimized structure. To make sure that all stationary points
are smoothly connected to each other, an IRC calculation was performed.44
General procedure for para Olefination of Tertiaryamines
In a typical experiment, N,N diethylaniline (0.5 mmol, 80 µL), alkene (0.8 mmol), Cu(OAc)2
(0.5 mmol, 100 mg), and Pd(OAc)2 (5 mol%, 5 mg) were added to a sealed tube equipped
with a magnetic stirring bar followed by the addition of DCE: HOAc (1.5:1, 1 mL). The
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reaction mixture was stirred at 60 C in an oil bath and the completion of the reaction was
monitored using TLC (nꢀHexane: Ethyl Acetate: Methanol; 25:5:2). After being completed,
the reaction mixture was cooled to room temperature and diluted with water and ethyl acetate
(4*10 mL). The organic layer was dried over anhydrous MgSO4. The solution was then
filtered and the solvent was evaporated using rotary evaporator. The residue was purified by
thin layer chromatography on 20 cm*20 cm silica gel plates (nꢀHexane: Ethyl Acetate:
Methanol; 25:5:2). Some products such as 3ba, 3bb, 3bd, 3be, 3bk, 3aa, 3ab, 3ac, 3ad, and
3ae are known compounds and have been synthesized by other methods.45ꢀ54
(E)-methyl 3-(4-(diethylamino) phenyl)acrylate (3ba)
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Yield: 103.8 mg (89%), Yellow solid; Mp. 41ꢀ42 C; H NMR (500 MHz, CDCl3, ppm): δ
1.21 (t, 6H, J= 7.0 Hz), 3.39ꢀ3.44 (q, 4H, J= 7.0 Hz), 3.79 (s, 3H), 6.20 (d, 1H, J= 15.5), 6.64
(d, 2H, J= 9.0), 7.40 (d, 2H, J= 9.0), 7.62 (d, 1H, J= 15.5); 13CꢀNMR (125 MHz, CDCl3,
ppm): δ 13.139, 46.228, 51.828, 110.572, 115.678, 123.033, 131.906, 144.632, 148.922,
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+•
168.062; HRMS (EI): m/z 233.1413 (M+• C14H19NO2 requires 233.1410).
(E)-butyl 3-(4-(diethylamino) phenyl)acrylate (3bb)
Yield: 119.8 mg (87%), Yellow oil;1H NMR (500 MHz, CDCl3, ppm): δ 0.90 (t, 3H, J= 7.0
Hz), 1.21 (t, 3H, J= 7.0 Hz), 1.49ꢀ1.60 (m, 2H), 1.69ꢀ1.83 (m, 2H), 3.39ꢀ3.43 (q, 4H, J= 7.0
Hz), 4.23 (t, 2H, J= 7Hz), 6.20 (d, 1H, J= 15.5 Hz), 6.68 (d, 2H, J= 9 Hz), 7.51 (d, 2H, J= 9
Hz), 7.62 (d, 1H, J= 15.5 Hz); 13CꢀNMR (125 MHz, CDCl3, ppm): δ 12.767, 13.862, 20.127,
32.624, 45.733, 66.267, 112.824, 117.589, 128.921, 134.128, 145.083, 150.251, 169.160;
HRMS (EI): m/z 275.1883 (M+• C17H25NO2 requires 275.1880).
+•
4'-(diethylamino)-5,6-dihydro-[1,1'-biphenyl]-3(4H)-one (3bc)
Yield: 119.2 mg (89%), Yellow oil;1H NMR (500 MHz, CDCl3, ppm): δ 1.21 (t, 6H, J= 7.0
Hz), 2.12ꢀ2.19 (m, 2H), 2.47 (t, 2H, J= 6.5 Hz), 2.77 (t, 2H, J= 6.0 Hz), 3.39ꢀ3.44 (q, 6H),
6.43 (s, 1H), 6.71 (d, 2H, J= 9.0 Hz), 7.51 (d, 2H, J= 9.0 Hz);13CꢀNMR (125 MHz, CDCl3,
ppm): δ 12.501, 22.287, 27.857, 37.400, 44.671, 11.165, 127.904, 132.527, 140.199,
146.142, 150.139, 199.328; HRMS (EI): m/z 243.1616 (M+• C16H21NO+• requires 243.1618).
(E)-3-(4-(diethylamino) phenyl)acrylonitrile (3bd)
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Yield: 85.1 mg (85%), Yellow solid; Mp. 97ꢀ98 C; H NMR (500 MHz, CDCl3, ppm): δ
1.13 (t, 6H, J= 7.0 Hz), 3.75ꢀ3.80 (q, 4H, J= 7.0 Hz), 5.95 (d, 1H, J= 12.5 Hz), 7.18 (d, 2H,
J= 7.5), 7.36 (d, 1H, J= 12.5 Hz), 7.43 (d, 2H, J= 7.5 Hz); 13CꢀNMR (125 MHz, CDCl3,
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ppm): δ 12.488, 45.044, 93.140, 112.165, 119.859, 122.198, 128.314, 150.657, 151.176;
+•
HRMS (EI): m/z 200.1307 (M+• C13H16N2 requires 200.1308).
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(E)-N,N-diethyl-4-styrylaniline (3be)
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Yield: 100.5 mg (80%), Yellow solid; Mp. 85ꢀ86 C; H NMR (500 MHz, CDCl3, ppm): δ
0.90 (t, 6H, J= 7.0 Hz), 3.44ꢀ3.48 (q, 4H, J= 7.0 Hz), 6.65 (d, 2H, J= 9.5 Hz), 7.46 (d, 1H, J=
18.0 Hz), 7.52 (d, 1H, J= 18.0 Hz), 7.56 (d, 2H, J= 9.5 Hz), 7.59ꢀ7.66 (m, 5H); 13CꢀNMR
(125 MHz, CDCl3, ppm): δ 12.504, 45.656, 112.165, 123.767, 127.444, 128.314, 128.622,
128.707, 128.891, 137.300, 148.661; HRMS (EI): m/z 251.1670 (M+• C18H21N+• requires
251.1669).
(E)-4-(diethylamino)styryl acetate (3bf)
Yield: 88.6 mg (76%), Yellow oil;1H NMR (500 MHz, CDCl3, ppm): δ 1.18 (t, 6H, J= 7.0
Hz), 2.36 (s, 3H), 3.39ꢀ3.44 (q, 4H, J= 7.0 Hz), 6.30 (d, 1H, J= 16.0 Hz), 6.64 (d, 2H, J= 9.0
Hz), 7.40 (d, 2H, J= 9.0 Hz), 7.62 (d, 1H, J= 16.0 Hz); 13CꢀNMR (125 MHz, CDCl3, ppm): δ
12.488, 20.023, 45.044, 110.111, 11.703, 130.039, 136.344, 150.657, 151.176, 169.009;
HRMS (EI): m/z 233.1409 (M+• C14H19NO2 requires 233.1410).
+•
(E)-ethyl 3-(4-(diethylamino) phenyl)-2-phenylacrylate (3bg)
Yield: 132.6 mg (82%), Yellow oil;1H NMR (500 MHz, CDCl3, ppm): δ 0.98 (t, 6H, J= 7.0
Hz), 1.23 (t, 3H, J= 7.0 Hz), 3.39ꢀ3.43 (q, 4H, J= 7Hz), 4.31ꢀ4.35 (q , 2H, J= 7.0 Hz), 6.45 (s,
13
1H), 6.66 (d, 2H, J= 9.0 Hz), 7.55 (d, 2H, J= 9.0 Hz), 7.79ꢀ7.99 (m, 5H); CꢀNMR (125
MHz, CDCl3, ppm): δ 13.190, 14.765, 46.638, 61.679, 110.572, 117.254, 125.154, 128.229,
128.689, 131.447, 140.356, 148.303, 152.388, 166.518; HRMS (EI): m/z 323.1880 (M+•
+•
C21H25NO2 requires 323.1880).
(E)-methyl 3-(4-(diethylamino) phenyl)-2-methylacrylate (3bh)
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Yield: 102.6 mg (83%), Yellow oil;1H NMR (500 MHz, CDCl3, ppm): δ 1.21 (t, 6H, J= 7
Hz), 2.19 (s, 3H), 3.39ꢀ3.43 (q, 4H, J= 7.0 Hz), 3.81 (s, 3H), 6.68 (d, 2H, J= 9.0 Hz), 7.38 (d,
2H, J= 9.0 Hz), 7.51 (s, 1H); 13CꢀNMR (125 MHz, CDCl3, ppm): δ 13.139, 14.765, 46.085,
52.227, 110.572,120.589, 123.767, 132.169, 138.910, 147.404, 170.414; HRMS (EI): m/z
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+•
247.1567 (M+• C15H21NO2 requires 247.1567).
(E)-3-(4-(diethylamino) phenyl)-2-methylacrylonitrile (3bi)
Yield: 83.6 mg (78%), Yellow oil;1H NMR (500 MHz, CDCl3, ppm): δ 1.21 (t, 6H, J= Hz),
2.92 (s, 3H), 3.39ꢀ3.44 (q, 4H, J= 7.0 Hz), 3.79 (s, 3H), 6.64 (d, 2H, J= 9.0 Hz), 7.40 (d, 2H,
J= 9.0 Hz), 7.62 (s, 1H); 13CꢀNMR (125 MHz, CDCl3, ppm): δ 13.139, 13.801, 46.442,
110.352, 115.394, 117.109, 122.049, 132.062, 139.568, 146.962; HRMS (EI): m/z 214.1463
(M+• C14H18N2 requires 214.1465).
+•
(E)-N,N-diethyl-4-(2-phenylprop-1-en-1-yl)aniline (3bj)
Yield: 102.2 mg (77%), Yellow oil;1H NMR (500 MHz, CDCl3, ppm): δ 1.21 (t, 6H, J= 7.0
Hz), 1.58 (s, 2H), 3.39ꢀ3.44 (q, 4H, J= 7.0 Hz), 6.65 (d, 2H, J= 9.5 Hz), 7.07 (s, 1H), 7.50 (t,
2H, J= 7.5 Hz), 7.63 (t, 2H, J= 7.5 Hz), 7.83 (d, 1H, J= 9.5 Hz), 8.00 (d, 2H, J= 7.5 Hz); 13Cꢀ
NMR (125 MHz, CDCl3, ppm): δ 13.139, 18.336, 46.228, 110.514, 121.926, 122.230,
126.510, 127.835, 127.978, 132.113, 132.958, 141.338, 146.962; HRMS (EI): m/z 265.1825
(M+• C19H23N+• requires 265.1825).
(E)-4-(4-(diethylamino) phenyl) but-3-en-2-one (3bk)
Yield: 91.3 mg (84%), Yellow oil;1H NMR (500 MHz, CDCl3, ppm): δ 1.22 (t, 6H, J= 7.0
Hz), 2.35 (s, 3H), 3.40ꢀ3.45 (q, 4H, J= 7.0 Hz), 6.53 (d, 1H, J= 16 Hz), 6.65 (d, 2H, J= 9.0
Hz), 7.43 (d, 2H, J= 9.0 Hz), 7.45 (d, 1H, J= 16 Hz); 13CꢀNMR (125 MHz, CDCl3, ppm): δ
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12.581, 29.112, 45.312, 112.124, 128.212, 129.512, 145.450, 150.117, 198.833; HRMS (EI):
m/z 217.1461 (M+• C14H19NO+• requires 217.1461).
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Yield: 100.6 mg (77%), Yellow oil;1H NMR (500 MHz, CDCl3, ppm): δ 1.24 (t, 6H, J= 7.0
Hz), 1.42 (t, 3H, J= 7.5 Hz), 2.51 (3H, s), 3.45ꢀ3.49 (q, 4H, J= 7.0 Hz), 4.31ꢀ4.36 (q, 2H, J=
7.5 Hz), 5.41 (s, 1H), 7.72 (d, 2H, J= 9.0 Hz), 7.89 (d, 2H, J= 9.0 Hz); 13CꢀNMR (125 MHz,
CDCl3, ppm): δ 13.322, 14.884, 18.116, 46.228, 61.316, 112.406, 117.787, 126.189, 129.996,
+•
148.070, 153.857, 168.565; HRMS (EI): m/z 261.1726 (M+• C16H23NO2
261.1723).
requires
4'-(dimethylamino)-5,6-dihydro-[1,1'-biphenyl]-3(4H)-one (3aa)
0
Yield: 92.5 mg (86%), Yellow solid; Mp. 136ꢀ137 C; 1H NMR (500 MHz, CDCl3, ppm): δ
2.12ꢀ2.19 (m, 2H), 2.47 (t, 2H, J= 6.5 Hz), 2.77 (t, 2H, J= 6.0 Hz), 6.43 (s, 1H), 6.71 (d, 2H,
J= 9.0 Hz), 7.51 (d, 2H, J= 9.0 Hz); 13CꢀNMR (125 MHz, CDCl3, ppm): δ 22.165, 27.767,
37.565, 40.322, 112.580, 127.856, 132.661, 140.219, 146.322, 151.301, 200.029; HRMS
(EI): m/z 215.1302 (M+• C14H17NO+• requires 215.1305).
(E)-N,N-dimethyl-4-(2-phenylprop-1-en-1-yl)aniline (3ab)
Yield: 99.7 mg (84%), Yellow oil;1H NMR (500 MHz, CDCl3, ppm): δ 1.58 (s, 3H), 2.92 (s,
6H), 6.65 (d, 2H, J= 9.5 Hz), 7.07 (s, 1H), 7.50 (t, 2H, J= 7.5 Hz), 7.63 (t, 2H, J= 7.5 Hz),
7.83 (d, 1H, J= 9.5 Hz), 8.00 (d, 2H, J= 7.5 Hz); 13CꢀNMR (125 MHz, CDCl3, ppm): δ
18.547, 42.192, 112.406, 122.859, 126.510, 126.546, 127.799, 127.978, 130.392, 132.958,
141.691, 149.989; HRMS (EI): m/z 237.1512 (M+• C17H19N+• requires 237.1512).
(E)-methyl 3-(4-(dimethylamino) phenyl)acrylate (3ac)
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Yield: 88.2 mg (86%), Yellow solid; Mp. 134ꢀ136 C; 1H NMR (500 MHz, CDCl3, ppm): δ
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3.42 (s, 6H), 3.79 (s, 3H), 6.20 (d, 1H, J= 15.5), 6.64 (d, 2H, J= 9.0), 7.40 (d, 2H, J= 9.0),
7.62 (d, 1H, J= 15.5);13CꢀNMR (125 MHz, CDCl3, ppm): δ 13.322, 14.884, 18.116, 46.228,
61.316, 112.406, 117.787, 126.189, 129.996, 148.070, 153.857, 168.565; HRMS (EI): m/z
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+•
205.1094 (M+• C12H15NO2 requires 205.1097).
(E)-butyl 3-(4-(dimethylamino) phenyl)acrylate (3ad)
Yield: 103.9 mg (84%), Yellow oil;1H NMR (500 MHz, CDCl3, ppm): δ 0.90 (t, 3H, J= 6.5
Hz), 1.15ꢀ122 (m, 2H), 1.28ꢀ1.40 (m, 2H), 3.40 (s, 6H), 3.79ꢀ3.84 (q, 2H), 6.20 (d, 1H, J=
15.5 Hz), 6.64 (d, 2H, J= 9.0 Hz), 7.40 (d, 2H, J= 9.0 Hz), 7.62 (d, 1H, J= 15.5 Hz); 13Cꢀ
NMR (125 MHz, CDCl3, ppm): δ 14.051, 19.828, 31.155, 40.065, 66.267, 112.625, 117.479,
129.001, 134.071, 145.155, 150.316, 170.071; HRMS (EI): m/z 247.1567 (M+• C C15H21NO2
+•
requires 247.1567).
(E)-N,N-dimethyl-4-styrylaniline (3ae)
Yield: 78.1 mg (70%), Yellow solid; Mp. 147ꢀ148 C; 1H NMR (500 MHz, CDCl3, ppm): δ
0
2.97 (s, 6H), 6.64 (d, 2H, J= 9.5 Hz), 7.45 (d, 1H, J= 18.0 Hz), 7.51 (d, 1H, J= 18.0 Hz), 7.55
(d, 2H, J= 9.5 Hz), 7.60ꢀ7.67 (m, 5H); 13CꢀNMR (125 MHz, CDCl3, ppm): δ 40.065, 11.913,
122.704, 127.768, 128.390, 128.804, 128.891, 130.039, 138.031, 151.301; HRMS (EI): m/z
223.1353 (M+• C16H17N+• requires 223.1356).
(E)-methyl 3-(4-(diisopropylamino) phenyl)acrylate (3ca)
1
Yield: 115.8 mg (90%), Yellow oil; H NMR (500 MHz, CDCl3, ppm): δ 1.76 (d, 12H, J=
6.5 Hz), 2.77ꢀ2.85 (m, 2H), 3.67 (s, 3H), 6.37 (d, 1H, J= 16 Hz), 6.67 (d, 2H, J= 9 Hz), 7.26
(d, 2H, J= 9 Hz), 7.72 (d, 1H, J= 16 Hz); 13CꢀNMR (125 MHz, CDCl3, ppm): δ 23.3, 52.5,
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55.3, 114.4, 116.0, 122.7, 132.2, 144.6, 146.1, 169.4; HRMS (EI): m/z 261.1729 (M+•
+•
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Acknowledgement
We are grateful to Xiuling Cui for the HRMS analyses and the Sharif University of
Technology (SUT) for the research grant attributed to this project.
Supporting Information
1H and 13C NMR spectra of the synthesized starting materials and products.
Reference
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