masters in advance seminar

Follow the instructions and prepare a power point presentation of 35 slides and written report of 9 pages for the following pdf which is uploaded.

Oral Presentation:

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Written Report:

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ARTICLE
pubs.acs.org/JACS
Metal-Free Intermolecular Oxidative C N Bond Formation via
Tandem C H and N H Bond Functionalization
Abhishek A. Kantak, Shathaverdhan Potavathri, Rose A. Barham, Kaitlyn M. Romano, and Brenton DeBoef*
Department of Chemistry, University of Rhode Island, 51 Lower College Road, Kingston, Rhode Island 02881, United States
bS Supporting Information
ABSTRACT: The development of a novel intermolecular oxidative
amination reaction, a synthetic transformation that involves the
simultaneous functionalization of both a N H and C H bond, is
described. The process, which is mediated by an I(III) oxidant and
contains no metal catalysts, provides a rapid and green method for
synthesizing protected anilines from simple arenes and phthalimide.
Mechanistic investigations indicate that the reaction proceeds via
nucleophilic attack of the phthalimide on an aromatic radical cation, as
opposed to the electrophilic aromatic amination that has been
reported for other I(III) amination reactions. The application of this new reaction to the synthesis of a variety of substituted
aniline derivatives is demonstrated.
’ INTRODUCTION
The formation of carbon carbon (C C) bonds via the oxidative
cross-coupling of two carbon hydrogen (C H) bonds has
recently become a field of intense interest and has resulted
in the discovery of numerous novel synthetic methods.1
The analogous technology for the oxidative cross-coupling of
C H and nitrogen hydrogen (N H) bonds to form carbon
nitrogen (C N) bonds would also be an important synthetic
advance, as amine and amide functional groups are ubiquitous in
biologically active molecules (Figure 1). However, a relatively
small amount of work has focused on the development of
oxidative methods for constructing N-arylamines and amides
via tandem C H/N H activation. The majority of literature in
this field describes the insertion of nitrenoid intermediates into
C H bonds, mediated by transition-metal catalysts.2 Cu and Pdcatalyzed reactions, as well as metal-free conditions, have also
been recently explored, but these methods are limited to the intramolecular synthesis of carbazoles, oxindoles, and diazapenones.3 5
The only reported examples of intermolecular oxidative amination involve azole-type heterocycles and proceed by attack of an
amine nucleophile on the substrate’s imine moiety.6,7 Herein, we
disclose a novel intermolecular reaction that oxidatively constructs the C N bond of phthalimide-protected anilines via the
tandem activation of N H and C H bonds.
’ DISCUSSION
Reaction Discovery. We recently discovered that heating a
solution of phthalimide (1) and PhI(OAc)2 in benzene provides
the phthalimide-protected aniline (2) in an 88% yield (Table 1,
entry 4). We initially explored the potential of Cu(I)/(III)
catalysts to perform this oxidative amination but quickly realized
that a metal catalyst was not necessary.5 We are confident that
r 2011 American Chemical Society
Figure 1. Examples of high-value molecules containing anilines.
trace metals are not the cause of the transformation, as reactions
performed in new, acid-washed flasks were similar in both yield
and rate to those performed in old flasks. Furthermore, reagents
from different commercial sources perform similarly.
While optimizing the process, we quickly discovered that the
best conditions employed microwave heating and 2.5 equiv of the
I(III) oxidant, phenyliodine(III) diacetate (PIDA). Less than
2.5 equiv of PIDA did not allow the reactions to proceed to
completion (compare entries 2, 3, and 4 in Table 1).
Importantly, we found that the arene substrate does not need
to be in large excess (i.e., solvent) for the intermolecular oxidative
amination reaction to occur. This is in stark contrast to many of
the oxidative arylation reactions that have been previously
Received: September 15, 2011
Published: October 19, 2011
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ARTICLE
Table 1. Discovery of the Intermolecular Oxidative
Aminationa
1
2
Scheme 1. Oxidative Amination of Substituted Arenes
oxidant (equiv)
solvent
temp. (°C)
time (h)
yield (%)c
PIDA (1.5)
PIDA (1.5)
PhH
PhH
145b
145
12
3
26
28
3
PIDA (2.0)
PhH
145
3
45
4
PIDA (2.5)
PhH
145
3
88
5
PIDA (2.5)
PhH
120
3
no reaction
6
PIDA (2.5)
TFE
145
3
13
7
PIDA (2.5)
DMF
145
3
4d
8
PIDA (2.5)
DMSO
145
3
no reaction
9
10
PIDA (2.5)
NCS (2.5)
MeCN
MeCN
145
145
3
3
51
3d
11
oxone (2.5)
MeCN
145
3
no reaction
12
IBX (2.5)
MeCN
145
3
no reaction
13
PIFA (1.0)
PhH
145
3
5d
14
PIFA (1.25)
PhH
145
3
decomposition
15
PIFA (1.0)
PhH
100
3
trace
16
PIFA (1.0)
PhH
25b
3
0
17
18
PIFA (1.0)
PIFA (1.0)
TFE
MeCN
145
145
3
3
3.5d
3.5d
a
General reaction conditions: 1 (0.68 mmol), oxidant (1.5 2.5 equiv),
benzene (1.5 equiv or solvent), solvent (4 mL), microwave heating.
PIDA = phenyliodine(III) diacetate, PIFA = phenyliodine(III) bis(trifluoroacetate), NCS = N-chloro-succinimide, IBX = 2-iodoxybenzoic
acid, oxone = potassium peroxymonosulfate, TFE = 2,2,2-trifluoroethanol. b Oil bath. c Yield of isolated product after column chromatography. d GC yield calculated using dodecane as internal standard.
studied.8 As shown in Table 1, entry 9, acetonitrile was used as
the solvent, and the concentration of the arene substrate was
lowered to a near-stoichiometric level (1.5 equiv). Under these
conditions, the yield for the amination of benzene dropped
from 88% to 51%, but we hypothesized that this was due to the
volatility of the arene. This was verified by the reaction of the
less volatile substrate, p-xylene, which provided an 80% yield
(Scheme 1A).
Other solvent and oxidant combinations proved to be less
effective. In particular, 2,2,2-trifluoroethanol (TFE), a solvent
that has been shown to be particularly compatible with I(III)mediated arene substitutions provided a minimal yield (Table 1,
entry 6). The fluorinated derivative of PIDA, phenlyiodine(III)
bis(trifluoroacetate) (PIFA), proved to be too harsh of an oxidant
for these reactions. Any loading of the oxidant in excess of 1 equiv
resulted in a complex mixture of products. Lowering the reaction
temperature and altering the cosolvent also failed to provide the
desired aniline 2 (Table 1, entries 13 18).
To determine whether the arene that participated in the oxidative
amination originated from the benzene solvent or the oxidant, a
crossover experiment was performed (Scheme 1B). When toluene
was used as the solvent and PhI(OAc)2 was the oxidant, the reaction
did not produce any N-phenylphthalimide (2). Rather, an inseparable mixture of regiomers arising from the oxidative amination
of the sp2-hybridized C H bonds of toluene was observed (3).
This confirmed our hypothesis that the source of the aryl group
that forms the new C N bond was the solvent, not the phenyl
group that resides on the oxidant.
Cleavage of the phthalimide protecting group allowed for the
determination of the regiomeric ratios by comparison to the
commercially available toluidine isomers. Interestingly, the major
product of the reaction was o-toluidine (4). Amination of the sp3hybridized C H bonds was not observed.
Substrate Scope. In addition to benzene, toluene, and
p-xylene, a variety of other simple arenes could be oxidatively
coupled to phthalimide (Table 2). Sterically encumbered arenes
(6) and those that contain electron-withdrawing groups (7 11)
were oxidatively aminated, albeit at reduced yields. Like toluene,
monosubstituted and asymmetrically disubstituted benzenes
produced mixtures of protected aniline products (10 19).
Electron-rich heterocycles, such as furan, decomposed under
the reaction conditions, and electron-poor heterocycles, such as
benzoxazole, failed to produce any aminated products.
The regioselectivity of these amination reactions appears to be
slightly directed by electronic factors. For example, p-methylanisole was 50% more likely to be aminated at the position ortho to
the larger, but more electron-donating methoxy group (15).
Likewise, both the ortho and para positions of toluene were
67% more likely to be aminated than the meta position. The only
exception to this rule was the amination of p-tert-butylanisole (16),
where the size of the tert-butyl group prevented ortho-amination.
Other amine sources, in addition to phthalimide, were also
investigated. Succinimide also provided very good yields of
oxidative amination products (20), while pyrrolidin-2-one performed the oxidative amination reaction but resulted in a poor
yield (16%, 21). N-tosylamide and pyrrolidine failed to oxidatively aminate benzene. These data led us to conclude that the
requirements for the amine coupling partner were two-fold: (1)
The N H bond must be relatively acidic (phthalimide pKa =
8.3), and (2) the amine coupling partner must be secondary,
preferably a cyclic imide. In keeping with these requirements,
other imides with acidic N H bonds performed the oxidative
amination reaction, albeit in lower yields (22 24). Surprisingly,
acyclic imides, such as diacetamide, N-acetylanilines, and hetercycles,
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Table 2. Substrate Scope of the Intermolecular Oxidative
Amination
ARTICLE
Table 3. Competition Reactions
a
a
1 (0.68 mmol), PhI(OAc)2 (2.5 equiv), 4 mL of arene substrate,
145 °C (microwave), 3 h. b 1 (0.68 mmol), PhI(OAc)2 (2.5 equiv),
Arene substrate (1.5 equiv.), 4 mL of acetonitrile, 145 °C (microwave),
3 h. c Amide substrate (0.68 mmol), PhI(OAc)2 (2.5 equiv), 4 mL of
benzene, 145 °C (microwave), 3 h.
such as indole and benzimidazole, produced only trace amounts
of products.
Mole fractions determined by GC/MS.
Competition and Kinetic Studies. Competition studies were
performed to explore the mechanism of the novel process
(Table 3). In all cases, the amination of electron-rich arenes
was favored. In particular, the competition between p-xylene and
p-difluorobenzene shows a dramatic preference for the amination
of the electron-rich p-xylene substrate (Table 3, entry 2).
The kinetic isotope effect (KIE) of the reaction was assessed
using a competition experiment between equimolar amounts of
benzene and benzene-d6. The near-unity KIE of 1.03 implies that
C H bond breaking is not involved in the rate-determining step
of the reaction. This is also a stark contrast with the literature
describing oxidative arylation processes for forming C C bonds,
where C H bond breaking is often rate limiting, as indicated by
large KIEs.9 The KIE of the reaction involving equimolar
amounts of phthalimide and phthalimide-d was observed to be
0.98, which indicates that the cleavage of the N H bond is also
not rate limiting.
Kinetic analysis of the oxidative amination provided more
mechanistic clues. The reaction rate was unaffected by changing
the concentration of the arene but was dependent on the concentration of the both oxidant and phthalimide. Both reagents
demonstrated first-order dependencies (Figure 2).
The preference for imides and electron-rich arenes is consistent with two possible mechanisms (Scheme 2). The first involves the in situ formation of a PhI(OAc)(NR2) species (25
and 26), which is highly electrophilic, functioning essentially as
an R2N+ equivalent.10 Electrophilic aromatic substitution then
forms the desired C N bond (2) (Scheme 2A).11 Alternatively,
a single electron transfer may occur, forming an ion pair with the
arene substrate and the I(III) reagent. The radical cation 27
could then undergo a nucleophilic attack by phthalimide (or its
anion), giving rise to the desired product (3, Scheme 2B). Kita
has previously described such a mechanism for oxidative reactions between arenes and soft nucleophiles, such as β-diketones
and TMS-N3.12
N-centered radicals have also been proposed in I(III)
mediated C N forming reactions,13 but they are not likely to
be involved in the reactions shown in Table 1. The weaker C H
bonds of the methyl group of toluene were not aminated, as one
would expect for reactions involving N-centered radicals.
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ARTICLE
Scheme 3. Resonance Structures of the Aryl Radical Cation
Explain the Observed Regioselectivities
Scheme 4. Formation of Substitution Products Corroborates
the Intermediacy of Arene Radical Cations
Figure 2. Kinetic analysis of oxidative amination reaction with various
amounts of PhI(OAc)2 (oxidant) and phthalimide.
Scheme 2. Two Possible Mechanisms for the Oxidative
Amination
Proposed Mechanism. Based these data, a mechanism involving electrophilic aromatic substitution (EAS) seems unlikely, as
the ratio of products obtained from the oxidative amination of
toluene (3) are not indicative of the expected EAS regioselectivity (Scheme 2A). While the ortho- and para-aminated products were somewhat favored in the reaction of arenes containing
electron-donating groups, reactions operating via SEAr mechanisms tend to form little, if any, meta-substituted products.
Alternatively, PhI(OAc)2 could oxidize the electron-rich arene
substrate to a radical cation (27), and nucleophilic attack on such a
radical cation should be relatively nonregioselective (Scheme 2B).
The consequent radical intermediate (28) could then be oxidized to
form a Wheland-type arenium ion. These two individual oxidation
steps may indicate why two equivalents of PhI(OAc)2 are required to
achieve complete conversion. The fates of the reduced iodine
intermediates are less clear, but the two other byproducts that are
observed in all of these reactions are iodobenzene and phenyl acetate.
Consequently, we hypothesize that a single electron-transfer
mechanism is operating in these oxidative amination reactions. This
hypothesis is supported by the observation that the reaction was
partially inhibited by BHT and completely inhibited by TEMPO,
common radical inhibitors. Our hypothesis is supported by the
prior work of Kita, who has extensively shown that arene radical
cation intermediates, such as 27, are formed by the action of I(III)
oxidants and can be directly observed by EPR spectroscopy.12
It should be noted that Cho and Chang have recently proposed
an electrophilic mechanism for the same reaction described
herein.7b This hypothesis was supported by the observation of
25 by mass spectrometry. In comparing our data with those of Kita
and both Cho and Chang, it seems likely that several I(III) species
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are simultaneously present in solution. However, we reason that the
observed regioselectivities for aminations of monosubstituted arenes
that were observed by both us and Cho and Chang are best
explained by the intermediacy of a radical cation intermediate (27).
Furthermore, the unique regioselectivities that were observed
in the oxidative amination of toluene (o:m:p = 10:6:5) corroborate the intermediacy of an aromatic radical cation (Scheme 3).
The yields of ortho- and para-aminated products, which arise
from the nucleophilic attack on resonance forms 27b and 27c, are
statistically equivalent. This seems plausible as both contain a
tertiary radical and a secondary carbocation. Additionally, reactions with p-methylanisole and p-tert-butylanisole (28) not only
produced the aforementioned aminated products (14 16), but
substitution products, arising from SNAr-type attack on the
tertiary cation intermediate (29b) followed by ejection of the
methoxide leaving group (30), were also observed (Scheme 4).
’ CONCLUSION
In conclusion, the ability to oxidatively couple phthalimide
to unfunctionalized arenes is a useful method for synthesizing
anilines that is orthogonal to conventional amination techniques,
which rely on electrophilic nitration/reduction strategies or metalcatalyzed coupling of prefunctionalized arenes. Phthalimide, in
particular, is an ideal starting point for the development of the
aforementioned oxidative amination technology. It is commercially available, inexpensive, and easy to handle, and once coupled,
it can be readily converted to a primary amine, which can be further
derivatized. Additionally, N-arylphthalimides like those shown in
Table 1 have recently been shown to have anticancer activity.14
Future work in our laboratory will be dedicated to the mechanistic
study and application of this unique method for constructing
C N bonds.
’ EXPERIMENTAL SECTION
Representative Procedure with Arene Solvent. A magnetically stirred solution of the imide substrate (0.68 mmol) and iodobenzene diacetate (1.7 mmol) in 4 mL of the simple arene substrate was
microwave heated at 145 °C for 3 h. The excess solvent from the mixture
was removed at reduced pressure by rotary evaporation, and the crude
product was purified by column chromatography (see Supporting
Information for more details).
N-phenylphthalimide 2. Yield = 0.133 g (88%). The NMR spectra
matched the previously published data.15 Rf = 0.31, hexane/ethyl acetate
(8:2 v/v). 1H NMR (400 MHz, CDCl3): δ = 7.39 7.53 (m, 5H), 7.80
(dd, J = 5.4 Hz, 2.8 Hz, 2H), 7.96 (dd, J = 5.6 Hz, 3.2 Hz, 2H). 13C NMR
(100 MHz, CDCl3): δ = 123.7, 126.5, 128.1, 129.1, 131.7, 134.4, 167.30.
LRMS EI (m/z): [M+] calcd for C14H9NO2 223.06, observed 223.10 m/z.
3 (o:m:p = 10:6:5) 0.1071 g (70%). The isomers were identified by
comparing with known NMR spectra.14 Rf = 0.2, hexane/ethyl acetate
(9:1 v/v) . 1H NMR (300 MHz, CDCl3): δ = 2.21 (s, 3H), 2.41 (s, 1H),
2.42 (s, 2H), 7.18 7.43 (m, 10H), 7.80 (dd, J = 5.4, 3.1 Hz, 5H),
7.92 7.99 (m, 4H). 13C NMR (75 MHz, CDCl3): δ = 18.06, 21.23,
21.42, 123.70, 123.72, 123.78, 126.47, 126.89, 127.29, 128.73, 128.95,
129.07, 129.47, 129.80, 130.57, 131.17, 131.48, 131.80, 132.02, 134.33,
134.35, 136.55, 138.20, 139.15, 167.37. LRMS EI (m/z): [M+] calcd for
C14H9NO2 237.08, observed 237.10 m/z.
2-(2,5-Dimethylphenyl)isoindoline-1,3-dione 5. Yield = 0.1535 g
(90%). Rf =0.19, hexane/ethyl acetate (9:1 v/v).1H NMR (300 MHz,
CDCl3): δ = 2.16(s, 3H), 2.36 (s, 3H), 7.17 7.28 (m, 3H), 7.80 (dd, J =
6 Hz, J = 3 Hz, 2H), 7.97 (dd, J = 3 Hz, J = 3 Hz, 2H). 13C NMR (75
MHz, CDCl3): δ = 17.56, 20.83, 123.74, 129.15, 130.29, 130.37, 130.95,
ARTICLE
132.05, 133.27, 134.29, 136.72, 167.47. LRMS EI (m/z): [M+] calcd for
C16H13NO2 251.09, observed 251.10 m/z.
2-(Perfluorophenyl)isoindoline-1,3-dione 7. Yield = 7 0.04 g (20%).
Rf = 0.18, hexane/ethyl acetate (9:1 v/v). 1H NMR (300 MHz, CDCl3):
δ = 7.87 (dd, J = 3 Hz, J = 3 Hz, 2H), 8.01 (dd, J = 3 Hz, J = 3 Hz, 2H).
13
C NMR (75 MHz, CDCl3): δ = 123.89, 123.91, 124.35, 124.5, 125.82,
128.13, 131.69, 134.62, 134.88, 134.95, 135.05, 138.27. LRMS EI (m/z):
[M+] calcd for C14H4 F5NO2 313.02, observed 313.0 m/z
2-(2, 5-Difluorophenyl)isoindoline-1,3-dione 8. Yield = 0.0917 g
(53%). Rf = 0.19, hexane/ethyl acetate (9:1 v/v). 1H NMR (300 MHz,
CDCl3): δ = 7.12 7.26 (m, 3H), 7.82 (dd, J = 3 Hz, J = 3 Hz, 2H), 7.98
(dd, J = 3 Hz, J = 3 Hz, 2H). 13C NMR (75 MHz, CDCl3): δ = 116.00,
116.30, 116.64, 124.10, 128.44, 131.77, 134.67, 166.06, 167.22. LRMS
EI (m/z): [M+] calcd for C14H7F2NO2 259.04, observed 259.1 m/z.
2-(2, 5-bis(Trifluoromethyl)phenyl)isoindoline-1, 3-dione 9. Yield =
0.2441 g (24%). Rf = 0.2187, hexane/ethyl acetate (9:1 v/v) . 1H NMR
(300 MHz, CDCl3): δ = 7.22 7.26 (m, 1H), 7.67 (s, 1H), 7.82 8.02
(m, 5H). 13C NMR (75 MHz, CDCl3): δ = 123.89, 124.25, 127.18,
128.13, 129.00, 130.48, 131.72, 134.63, 134.82, 138.27, 166.66. LRMS
EI (m/z): [M+] calcd for C16H7 F6NO2 359.0, observed 359.0 m/z.
2-(3,4-Dichlorophenyl)isoindoline-1,3-dione 10. Yield = 0.1118 g
(56%). Rf = 0.19, hexane/ethyl acetate (9:1 v/v). 1H NMR (300 MHz,
CDCl3): δ = 7.37 (dd, J = 8.6, 2.4 Hz, 1H), 7.58 (d, J = 8.6 Hz, 1H), 7.64
(d, J = 2.4 Hz, 1H), 7.86 7.79 (m, 2H), 7.98 7.94 (m, 2H). 13C
NMR (75 MHz, CDCl3): δ = 124.01, 125.53, 128.16, 130.70, 131.05,
131.43, 132.12, 133.02, 134.77, 166.63. LRMS EI (m/z): [M+] calcd for
C14H7F2NO2 291.0, observed 291.0 m/z.
2-(2,3-Dichlorophenyl)isoindoline-1,3-dione 11. Yield = 0.034 g
(17%). Rf = 0.09, hexane/ethyl acetate (9:1 v/v). 1H NMR (300
MHz, CDCl3): δ = 7.27 7.4 (m, 2H), 7.59 7.62 (m, 1H), 7.83 (dd,
J = 3, 3 Hz, 2H), 7.99 (dd, J = 3 Hz, 3 Hz, 2H). 13C NMR (75 MHz,
CDCl3): δ = 124.11, 127.71, 128.97, 131.32, 131.49, 131.75, 132.32,
134.35, 134.66, 166.37. LRMS EI (m/z): [M+] calcd for C14H7F2NO2
291.0, observed 291.0 m/z.
14 and 15: Yield = 0.1287 g (70%, 14:15 = 2:3). Rf = 0.1714, hexane/
ethyl acetate (9:1 v/v) . 1H NMR (300 MHz, CDCl3): δ = 2.13 (s, 2H),
2.34 (s, 3H), 3.78 (dd, J = 9.6, 2.1 Hz, 6H), 6.75 (d, J = 2.5 Hz, 1H), 6.95
(d, J = 8.4 Hz, 2H), 7.07 (s, 1H), 7.20 7.30 (m, 3H), 7.76 7.82 (m,
4H), 7.91 7.99 (m, 4H). 13C NMR (75 MHz, CDCl3): δ = 17.15,
20.40, 55.45, 55.91, 112.02, 113.85, 115.65, 119.75, 123.66, 123.80,
128.29, 130.38, 131.16, 131.70, 131.96, 132.24, 134.10, 134.36, 153.22,
158.27, 167.30, 167.53. LRMS EI (m/z): [M+] calcd for C14H9NO2
267.09, observed 267.10 m/z.
12 and 13: Yield = 0.1333 g (80%, 12:13 = 3:4). Rf = 0.22, hexane/
ethyl acetate (9:1 v/v) . 1H NMR (300 MHz, CDCl3): δ = 2.08 (s, 3H),
2.31 (s, 5H), 2.35 (s, 3H), 7.23 7.28 (m, 7H), 7.76 7.81 (m, 4H),
7.93 7.98 (m, 4H). 13C NMR (75 MHz, CDCl3): δ = 14.67, 19.55,
19.91, 20.45, 123.67, 123.77, 124.16, 126.28, 127.76, 129.12, 130.29,
130.48, 131.00, 131.88, 132.06, 134.29, 135.13, 137.07, 137.66, 138.43,
167.57. LRMS EI (m/z): [M+] calcd for C14H9NO2 251.09, observed
251.10 m/z.
17, 18, and 19: Yield = 0.128 g (75%, 17:18:19 = 4:3:4). Rf = 0.1666,
hexane/ethyl acetate (9:1 v/v). 1H NMR (300 MHz, CDCl3): δ = 2.17
(s, 9H), 2.38 (s, 7H), 7.32 6.99 (m, 11H), 7.76 7.84 (m, 6H),
7.92 8.00 (m, 6H). 13C NMR (75 MHz, CDCl3): δ = 17.94, 18.09,
21.21, 21.31, 123.73, 123.79, 124.52, 127.65, 127.85, 128.45, 128.49,
129.48, 130.16, 131.91, 132.07, 134.26, 134.33, 136.16, 136.86, 138.93,
139.50, 167.55. LRMS EI (m/z): [M+] calcd for C14H9NO2 251.09,
observed 251.10 m/z.
1-Phenylpyrrolidine-2,5-dione 20. Yield = 0.0982 g (83%). The
NMR spectra matched with that of previously published.15 Rf = 0.44
hexane/ethyl acetate (1:1 v/v) . 1H NMR (400 MHz, CDCl3): δ = 2.9(s,
4H), 7.28 (d, J = 7.2 Hz, 2H),7.39 7.4 (m,1H), 7.49 7.5(m, 2H).
13
C NMR (100 MHz, CDCl3): δ = 28.4, 126.4, 128.6, 129.2, 131.8,
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176.2. LRMS EI (m/z): [M+] calcd for C10H9 NO2 175.06, observed
175.10 m/z.
5-Nitro-2-phenylisoindoline-1,3-dione 22. Yield = 0.0557 g (40%).
Rf = 0.33, hexane/ethyl acetate (8:2 v/v). 1H NMR (300 MHz, CDCl3):
δ = 7.26 7.55 (m, 5H), 8.17 (d, J = 9 Hz, 1H), 8.68 (d, J = 6 Hz, 1H),
8.78 (s, 1H). 13C NMR (75 MHz, CDCl3): δ= 119.21, 125.04, 126.36,
128.75, 129.35, 129.62, 133.13, 151.82, 164.93. LRMS EI (m/z): [M+]
calcd for C14H8 N2O4 268.05, observed 268.0 m/z.
N-Phenyl-1,8-naphthalimide 23. Yield = 0.0356 g (27%). Rf = 0.34,
hexane/ethyl acetate (7:3 v/v). 1H NMR (300 MHz, CDCl3): δ =
7.32 7.59 (m, 5H), 7.78 7.83(m, 2H), 8.28 (d, J = 9 Hz, 2H), 8.66 (d,
J = 6 Hz, 2H). 13C NMR (75 MHz, CDCl3): δ = 122.81, 127.05, 128.61,
128.73, 129.42, 131.64, 134.30, 135.41, 164.39. LRMS EI (m/z): [M+]
calcd for C18H11NO2, 273.08, observed 273.10 m/z.
N-Phenyl-1,1-dioxo-1,2-benzothiazol-3-one 24. Yield = 0.037 g
(26%). Rf = 0.26, hexane/ethyl acetate (7:3 v/v) 1H NMR (300 MHz,
CDCl3): δ = 7.55 (s, 5H), 7.87 8.01(m, 3H), 8.15 (d, J = 9 Hz, 1H).
13
C NMR (75 MHz, CDCl3): δ = 120.75, 121.25, 125.65, 127.16,
128.69, 128.75, 129.94, 130.13, 134.49, 135.12, 137.56, 158.40. LRMS
EI (m/z): [M+] calcd for C13H9 NO3S, 259.03, observed 259.0 m/z.
Representative Procedure with Stoichiometric Arene. A
magnetically stirred solution of phthalimide (0.68 mmol), iodobenzene
diacetate (1.7 mmol), and the simple arene substrate (2.0 mmol) in 4 mL
of acetonitrile was microwave heated at 145 °C for 3 h. The excess solvent
from the mixture was removed at reduced pressure by rotary evaporation,
and the crude product was purified by column chromatography.
2-(2,3,4,5,6-Pentamethylphenyl)isoindoline-1,3-dione 6. Yield =
0.085 g (43%). Rf = 0.23, hexane/ethyl acetate (9:1 v/v). 1H NMR
(300 MHz, CDCl3): δ = 2.06 2.26 (m, 15H), 7.79 (dd, J = 3 Hz, 3 Hz,
2H), 7.97 (dd, J = 3 Hz, 3 Hz, 2H). 13C NMR (75 MHz, CDCl3): δ =
15.51, 16.81, 17.04, 123.76, 126.99, 131.77, 131.97, 133.57, 134.26,
136.9, 167.81. LRMS EI (m/z): [M+] calcd for C19H19NO2 293.14,
observed 293.15 m/z.
2-(5-tert-Butyl-2-methoxyphenyl)isoindoline-1,3-dione 16. Yield =
0.117 g (56%), Rf = 0.11, hexane/ethyl acetate (9:1 v/v) 1H NMR (300 MHz,
CDCl3): δ = 1.29 1.32 (m, 9H), 3.77 (s, 3H), 6.98 (d, J = 9 Hz, 1H),
7.25 (m, 1H) 7.44 (dd, J = 3 Hz, 3 Hz, 1 H) 7.77 (dd, J = 3 Hz, 3 Hz, 2H),
7.94 (dd, J = 3 Hz, 3 Hz, 2H). 13C NMR (75 MHz, CDCl3): δ = 31.42,
34.17, 55.87, 111.64, 119.51, 123.61, 126.98, 132.29, 134.06, 143.74,
153.05, 167.55. LRMS EI (m/z): [M+] calcd for C19H19NO3 309.14,
observed 309.12 m/z.
’ ASSOCIATED CONTENT
bS Supporting Information. Complete experimental de-
tails, compound characterization, analysis of product purity and
both 1H and 13C NMR data for novel compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
ARTICLE
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’ ACKNOWLEDGMENT
This work was supported by the National Science Foundation
(CAREER 0847222) and the National Institutes of Health
(NIGMS, 1R15GM097708-01).
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