Decarboxylative Halogenation and Cyanation of Electron-Deficient Aryl Carboxylic Acids via Cu Mediator as Well as Electron-Rich Ones through Pd Catalyst under Aerobic Conditions

Article abstract of DOI:10.1021/acs.joc.5b02873

Simple strategies for decarboxylative functionalizations of electron-deficient benzoic acids via using Cu(I) as promoter and electron-rich ones by employing Pd(II) as catalyst under aerobic conditions have been established, which lead to smooth synthesis of aryl halides (-I, Br, and Cl) through the decarboxylative functionalization of benzoic acids with readily available halogen sources CuX (X = I, Br, Cl), and easy preparation of benzonitriles from decarboxylative cyanation of aryl carboxylic acids with nontoxic and low-cost K₄Fe(CN)₆ under an oxygen atmosphere for the first time.

Full text of DOI:10.1021/acs.joc.5b02873

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Article
Decarboxylative Halogenation and Cyanation of Electron-
deficient Aryl Carboxylic Acids via Cu Mediator as well as
Electron-rich Ones through Pd Catalyst under Aerobic Conditions
Zhengjiang Fu, Zhaojie Li, Yuanyuan Song, Ruchun Yang, Yanzhu Liu, and Hu Cai
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.5b02873 • Publication Date (Web): 03 Mar 2016
Downloaded from http://pubs.acs.org on March 4, 2016
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Decarboxylative Halogenation and Cyanation of Electron-deficient
Aryl Carboxylic Acids via Cu Mediator as well as Electron-rich Ones
through Pd Catalyst under Aerobic Conditions
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Zhengjiang Fu, Zhaojie Li, Yuanyuan Song, Ruchun Yang, Yanzhu Liu
and Hu Cai*
College of Chemistry, Nanchang University, Nanchang 330031 (China).
ABSTRACT: Simple strategies for decarboxylative functionalizations of
electron-deficient benzoic acids via using Cu(I) as promoter and
electron-rich ones by employing Pd(II) as catalyst under aerobic
conditions have been established, which lead to smooth synthesis of aryl
halides (-I, Br and Cl) through the decarboxylative functionalization of
benzoic acids with readily available halogen sources CuX (X = I, Br, Cl),
and easy preparation of benzonitriles from decarboxylative cyanation of
aryl carboxylic acids with nontoxic and low-cost K Fe(CN) under an
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oxygen atmosphere for the first time.
1
. INTRODUCTION
Transition-metal mediated transformations of functional groups are
hot research topics to generate C-X (X = heteroatom) and C-C
bonds in organic community, as a result, many methods have been
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made to create new C-X and C-C bonds. Owing to the attractive
features of low toxicity, low cost, high stability and easy availability,
carboxylic acids represent as valuable starting materials in synthetic
organic chemistry. Under transition-metal catalysis, the
decarboxylative reaction only takes place at neighboring position to
carboxyl group with high regioselectivity and releases innocuous
carbon dioxide as sole by-product. Hence, carboxylic acids and
transition metal-catalyzed decarboxylative reactions have displayed
promising strategies to create C-X and C-C bonds during the last
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decade. In this field, Myers, Goossen and Forgione have done
some seminal studies to generate new C-C bond through
transition-metal
catalyzed
decarboxylative
coupling
of
(hetero)aromatic carboxylic acids with alkenes and aryl halides
respectively. These pioneering works have showed that traditional
electrophilic aryl halides and nucleophilic organometallic reagents
can be replaced by distinctly attractive carboxylic acid substrates.
Basing on the fundamental importance of transition-metal
catalyzed decarboxylative coupling in synthetic organic chemistry,
great progress has been made to create C-C, C-O, C-P and C-S
bonds via decarboxylation of carboxylic acids with various coupling
3,6
4,5,7
8
9
partners including olefins
aryl halides,
alkynes, arenes,
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organoboron compounds, trifluoromethylating agents, silicate
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esters,
H
-phosphine oxides, trifluoromethylthiolating reagents,
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thiols and disulfides. Although carbon-halogen bond could be used
1
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for later stage installing other functional groups, however, the
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old-established or improved Hunsdiecker reaction through direct
halodecarboxylation of carboxylic acids suffered from limitations
with regard to mere aliphatic carboxylic acids substrates and harsh
reaction conditions.
Aryl halides are more widely employed as versatile coupling
partners in transition-metal catalyzed coupling reactions to construct
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complex molecules.
In this context, Gandelman reported
conversion of aromatic carboxylic acids into aryl iodides by using
,3-diiodo-5,5-dimethylhydantoin (DIH) as halogen source in
1
2
0
1,2-dichloroethane, since high cost and moisture sensitivity of
DIH, high toxicity of the solvent, moreover, aryl bromides and
chlorides couldn’t be achieved from this method, thus, it’s neither a
practical nor economical procedure to prepare aryl halides. Wu
disclosed Ag-catalyzed decarboxylative halogenations (-Br and Cl)
of electron-deficient arene carboxylic acids with the use of
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stoichiometric strong base KOH, however, aryl iodides couldn’t be
prepared through this method, and the method suffered from
limitations with regard to the exclusion of electron-rich aryl and
heteroaryl carboxylic acids from the reaction. Larrosa also
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developed noble stoichiometric Au/Ag bimetallic mediated
decarboxylation of limited substrate scope of electron-deficient aryl
carboxylic acids followed by addition of NBS or NIS to afford
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corresponding haloarenes, unfortunately, there were only three
electron-deficient aryl carboxylic acids substrates furnished
decarboxylative bromination and iodination rather than
chlorodecarboxylation products. Liu revealed a method for
Pd/Ag-catalyzed bromo- and chlorodecarboxylation of electron-rich
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arene carboxylic acids, nevertheless, it’s neither an economical nor
practical procedure for high loadings of Ag CO and limited
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electron-rich aryl carboxylic acids substrates as well as low yields in
the transformations.
In contrast to well-documented formation of C-C bond via
decarboxylative coupling of carboxylic acids with various
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C
-containing reagents, transition-metal catalyzed decarboxylative
functionalization of carboxylic acids into nitriles has been almost
untouched. The only one example of conversion of arene carboxylic
acids into aryl nitriles was made by Taran by using cyanohydrin as
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cyanide source with Pd/Ag as promoter, in view of the
requirement for high loadings of silver salt and cost of cyanohydrin,
there is still significant room for improvement of the
decarboxylative cyanation reaction. Although Song observed a
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Cu-catalyzed decarboxylation at sp -hybridized carbon atoms of
phenylacetic acids to form benzonitriles via employing urea as
cyanide source, however, no benzonitriles generated in the case of
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sp -hybridized benzoic acids. K Fe(CN) is a nontoxic food
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additive, which could serve as a green cyanide source for transition
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metal-catalyzed cyanation of aryl halides. Nevertheless, to date, no
practical method for decarboxylative cyanation has been explored
between benzoic acids and that green cyanide source.
Basing on above reports, it is highly desirable to develop simple,
green and practical method to synthesize aryl halides (-I, Br and Cl)
and nitriles via decarboxylative functionalization of readily
accessible aromatic carboxylic acids. For the standpoint of
sustainable chemistry, there is an increasing demand for the use of
molecular oxygen as the terminal oxidant in oxidative
transformation. In this regard, despite remarkable advance has been
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made in transition-metal catalyzed oxidative C-H halogenation
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and cyanation, to the best of our knowledge, only few reports on
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the use of dioxygen in the halodecarboxylation transformation and
2
5
decarboxylative cyanation have been reported. In view of the
significance of aryl halides and nitriles, and our continuing research
pursuit in the functionalization of aromatic carboxylic acids, very
recently, we have established the synthesis of aryl methyl thioethers
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and biaryls through Pd/Cu-catalyzed decarboxylation of benzoic
acids with DMSO and Cu-catalyzed decarboxylative homocoupling
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of benzoic acids respectively. Herein, we firstly reveal a range of
benzoic acids including electron-sufficient and -deficient aromatic
as well as heteroaromatic carboxylic acids directly underwent
decarboxylative halogenation and cyanation with good functional
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group
tolerance
under
aerobic
conditions,
namely,
iododecarboxylation of electron-deficient ortho-nitrobenzoic acids
and heteroaromatic carboxylic acids in the presence of 1.2
equivalents of CuI as both mediator and iodine source,
decarboxylative bromination and chlorination of electron-deficient
ortho-nitrobenzoic acids and heteroaromatic carboxylic acids with
the employment of CuI (0.3 equiv) as promoter and CuX (X = Br,
Cl) (1.2 equiv) as halogen source, decarboxylative cyanation of
electron-deficient ortho-nitrobenzoic acids and heteroaromatic
carboxylic acids with the employment of CuI (1 equiv) as promoter
and nontoxic K Fe(CN) (0.2 equiv) as cyanide source, while
4
6
decarboxylative functionalization of electron-sufficient benzoic
acids to synthesize aryl halides and nitriles were observed with the
assistance of 10 mol% Pd(OAc) as catalyst under otherwise equal
2
conditions.
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2
. RESULTS AND DISCUSSION
We initially tested iododecarboxylation toward different aryl
carboxylic acids substrates, as shown in Table 1. In the beginning,
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the reaction of electron-deficient 4-chloro-2-nitrobenzoic acid
1 in
the presence of CuI (2 equiv) in DMSO at 160 °C under air
atmosphere furnished desired 4-chloro-1-iodo-2-nitrobenzene 1a in
40% yield (entry 1, Table 1). Gratifyingly, the reaction conducted
under 1 atm of dioxygen proceeded more efficiently than under air
atmosphere (entry 2). However, studies showed that lowering
temperature to 140 °C dramatically reduced the reaction conversion
(entry 3). A brief survey of the solvents including single and mixed
solvents under aerobic conditions illustrated inferior yields were
detected than that in DMSO (entries 4-5). Subsequently, it’s found
that the base has no beneficial effect on the transformation (entries
6-7). Notably, decreasing the loading of CuI to 1.2 equivalents did
not affect the efficiency (72%) (entry 8). The reaction time extended
to 30 h readily gave final product 1a in synthetically useful levels
(87% yield), and comparable yield was obtained when reaction run
for prolonged 40 h (entries 9-10). Unfortunately, useless yields were
obtained when other iodide compounds as iodine source were
employed with catalytic Cu(I), regardless of the presence or absence
of a nitrogen ligand in the reaction system (entries 11-14).
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Table 1. Selected Screening Results for Iododecarboxylation of
a
Arene Carboxylic Acid 1 and 17 under Aerobic Conditions
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a
Conditions: acid (0.2 mmol), solvent (2 mL), O (1 atm), 20 h.
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b
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Average of two runs. Reaction performed under air atmosphere.
e
f
Reaction conducted at 140 °C. Reaction run for 30 h. Reaction run
for 40 h.
Applying the optimized conditions of decarboxylative iodination of
electron-deficient carboxylic acid 1a to an electron-rich aryl
carboxylic acid, unfortunately, no desired product 17a was detected
for the iododecarboxylation of 2,6-dimethoxybenzoic acid 17 (entry
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5). Under otherwise identical conditions, much to our surprise, the
yield of 17a was remarkably improved in the presence of 0.1
equivalent of Pd catalyst, especially in the case of the introduction
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of Pd(OAc) (entries 16-17). Study also showed that a lower loading
2
of palladium led to slightly lower conversion (entry 18). Finally, the
synthesis of aryl iodide in DMSO in the presence of CuI (1.2 equiv)
for 30 hours under aerobic conditions was chose as the optimal
reaction conditions (entry 9) for the iododecarboxylation of
electron-deficient aryl carboxylic acid, while the reaction in the
presence of the combination of Pd(OAc) (0.1 equiv) and CuI (1.2
2
equiv) in DMSO for 20 hours under aerobic conditions was defined
as the optimized reaction conditions (entry 17) for the
decarboxylative iodination of electron-rich aryl carboxylic acid.
With the optimized reaction conditions in hand, we next
examined the scope of substituted benzoic acids in this
iododecarboxylation process (Scheme 1). Under aerobic conditions,
2
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similarly to our recent observation,
this Cu-mediated
decarboxylative iodination of electron-deficient aryl carboxylic
acids was shown to be effective for a range of ortho-nitrobenzoic
acids (
carboxylic acids (14
of ortho-methoxylbenzoic acids (17
1
-
13) as well as
16), whereas iododecaboxylation of a variety
20) and -methylindole-3-
S- and O-containing heteroaromatic
-
-
N
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Scheme 1. Decarboxylative Iodination of Electron-deficient Aryl
and Heteroaromatic Carboxylic Acids via CuI as well as
Electron-rich Benzoic Acids through Pd(OAc) under Aerobic
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Conditions
a
Acid (0.2 mmol), CuI (1.2 equiv), DMSO (2 mL), O (1 atm), 160
2
b
°C, 30 h. Acid (0.2 mmol), Pd(OAc) (0.1 equiv), CuI (1.2 equiv),
2
DMSO (2 mL), O (1 atm), 160 °C, 20 h.
2
carboxylic acid (21) resulted from the contribution of Pd(OAc) /CuI
2
bimetallic system. Ortho-nitrobenzoic acid
6 was an effective
substrate to afford 61% yield in the presence of 1.2 equivalents of
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CuI, which was also the divide between electron-withdrawing
(
chloro, fluoro and trifluoromethyl) and -donating groups (methoxy
and methyl) on the aromatic ring of 2-nitrobenzoic acid substrate.
Furthermore, it’s found electronic nature of substituent on
ortho-nitrobenzoic acid substrate had an influence on the
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transformation,
electron-withdrawing groups (
products in satisfied to excellent yields, except the case of 2-nitro-4-
(trifluoromethyl)benzoic acid , whereas 2-nitrobenzoic acids
tolerated electron-donating groups ( 13) provided desired products
in moderate to good yields. Compared with its isomer
-fluoro-2-nitrobenzoic acid , 4-fluoro-2-nitrobenzoic acid was a
less effective substrate, likewise, a similar observation was
consistent with good conversion for substrates of
2,6-dimethoxylbenzoic acid 17 and 2,4,6-trimethoxylbenzoic acid
, but modest yields were observed for the substrates of their
namely,
2-nitrobenzoic
acids
bearing
1-4
) furnished corresponding
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7
-
5
4
3
20
isomer 2,4-dimethoxylbenzoic acid 18 and 2,4,5-trimethoxylbenzoic
acid 19. Pleasingly, an amount of 1.2 equivalents of CuI with 1 atm
of O gave good yields for
S
- and
O-containing heterocyclic
2
carboxylic acids (14
-16), regardless of the presence an
electron-donating or -withdrawing substituent on the position ortho
to the carboxyl group. Besides desired C3-decarboxylative
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Scheme 2. Decarboxylative Bromination, Chlorination and
Cyanation of 4-Chloro-2-nitrobenzoic Acid
1
with
a
Corresponding Functional Group under Aerobic Conditions
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a
Conditions:
1
(0.2 mmol), CuX (1.2 equiv), DMSO (2 mL), O (1
2
b
atm), 160 °C, 30 h.
1
(0.2 mmol), CuI (0.3 equiv), CuX (1.2 equiv),
c
DMSO (2 mL), O (1 atm), 160 °C, 30 h.
1 (0.2 mmol), CuI (1
2
equiv), K Fe(CN) (0.2 equiv), DMSO (2 mL), O (1 atm), 160 °C,
4
6
2
1
0 h.
iodination product,
N
-methylindole-3-carboxylic acid (21) also
afforded another 2,3-diiodinated
N-methylindole product, namely,
the iododecaboxylation along with heterocyclic ring C2-iodination.
The preliminarily successful iododecarboxylation reactions
evoked us to test whether the use of other analogous copper salt
CuX (X = Br, Cl, CN) could be equally effective under aerobic
conditions, thereby introducing similar functional group onto the
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aryl ring followed by decarboxylation. As represented in Scheme 2,
the bromo- and chlorodecarboxylation of 4-chloro-2-nitrobenzoic
acid
1 were achieved in moderate yields (64% and 57%) at the
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outset via utilizing corresponding stoichiometric amounts of
copper(I) halide without any Pd or Ag additive. In contrast,
attractive decarboxylative cyanation was observed in a troublesome
yield (18%) by employing stoichiometric amounts of CuCN under
aerobic conditions. Consequently, there was still a need for
improvement of the original decarboxylative functionalization
results. Further investigations revealed that by employing CuI (0.3
equiv) as additional catalyst on the basis of original conditions,
good yields (81% and 78%) of bromo- and chlorodecarboxylation
were obtained with corresponding copper(I) halide (1.2 equiv) as
halogen source, and drastically increased yield (73%) of
decarboxylative cyanation was observed with K Fe(CN) (0.2
4
6
equiv) as cyanide source. However, increasing the loadings of
K Fe(CN) had a detrimental effect on the efficiency of
4
6
decarboxylative cyanation reaction, which could be the result of
transition-metal copper poisoned by excess of cyanide ions from the
Fe(II) center.
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Thereafter, these impressive results inspired us to evaluate the
possible substrate scope of this decarboxylative halogenation
(halogen = Br, Cl) and cyanation protocol with respect to aromatic
0
1
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Scheme 3. Decarboxylative Bromination, Chlorination and
Cyanation of Electron-deficient Aryl and Heteroaromatic
Carboxylic Acids via Cu Mediator as well as Electron-rich
Benzoic Acids through Pd Catalyst with Corresponding
Functional Group under Aerobic Conditions
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a
Acid (0.2 mmol), CuI (0.3 equiv), CuBr (1.2 equiv), DMSO (2
b
mL), O (1 atm), 160 °C, 30 h. Acid (0.2 mmol), CuI (0.3 equiv),
2
c
CuCl (1.2 equiv), DMSO (2 mL), O (1 atm), 160 °C, 30 h. Acid
2
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d
(
0.2 mmol), CuI (1 equiv), K Fe(CN) (0.2 equiv) ,10 h. Acid (0.2
4
6
mmol), Pd(OAc) (0.1 equiv), CuI (0.3 equiv), CuBr (1.2 equiv),
2
e
DMSO (2 mL), O (1 atm), 160 °C, 20 h. Acid (0.2 mmol),
2
Pd(OAc) (0.1 equiv), CuI (0.3 equiv), CuCl (1.2 equiv), DMSO (2
2
f
mL), O (1 atm), 160 °C, 20 h. Acid (0.2 mmol), Pd(OAc) (0.1
2
2
equiv), CuI (1 equiv), K Fe(CN) (0.2 equiv), DMSO (2 mL), O (1
4
6
2
g
atm), 160 °C, 20 h. Acid (0.2 mmol), Pd(OAc) (0.1 equiv), CuI
2
(0.3 equiv), CuCl (1.2 equiv), DMF (2 mL), O (1 atm), 160 °C, 20
2
h.
carboxylic acids. As clearly shown in Scheme 3, it’s also found that
the combination of CuI/CuX (X = Br, Cl) and CuI/K Fe(CN)
4
6
worked well for various ortho-nitrobenzoic acids (2-13) bearing
different substituents including electron-withdrawing (chloro, fluoro
and trifluoromethyl) and -donating groups (methoxy and methyl) as
well as other classes of
S- and O-containing heteroaromatic
carboxylic acids (14 16), while smooth decarboxylative
-
functionalization of ortho-methoxylbenzoic acids (17
-20) were
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conveniently realized with the assistance of Pd(OAc) catalyst under
2
otherwise equal conditions as well.
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3. CONCLUSIONS
In summary, we have established simple, general and flexible
methods for synthesis of valuable aryl iodides, bromides, chlorides
and nitriles from easily available aryl carboxylic acids. In the case
of electron-deficient ortho-nitrobenzoic acids and heteroaromatic
carboxylic acids, the protocols employed CuI and CuI/CuX (X = Br,
Cl) as well as CuI/K Fe(CN) respectively provided target products
4
6
under aerobic conditions, whereas decarboxylative functionalization
of electron-rich ortho-methoxylbenzoic acids were observed with
the assistance of Pd(OAc) as catalyst under otherwise equal
2
2
0-24
conditions. Compared to previously reported methods,
there are
several distinguishing features in our protocols: extensive substrate
scope including electron-sufficient and -deficient benzoic acids as
well as heteroaromatic carboxylic acids with good functional group
tolerance, simple reaction system to afford aryl halides and nitriles
products in good yields with readily available halogen and cyanide
sources, green and cheap dioxygen as sole terminal oxidant in the
reaction. To the best of our knowledge, no general method for the
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assembly of functional groups (-I, Br, Cl, CN) on aromatic rings has
been reported before now, so our simple and general methods will
attract much attention in academic and industrial fields.
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4. EXPERIMENTAL SECTION
4
.1 General Information. The Reagents used for experiments
were commercially available and used as received unless otherwise
noted. DMSO was distilled from CaH under reduced pressure and
2
stored under nitrogen. All reactions were performed under dioxygen
with the strict exclusion of moisture via using Schlenk techniques.
Column chromatography was performed on silica gel 300-400 mesh.
The yields reported are the isolated yields and the average of two
1
13
19
runs. H, C and F NMR spectra were recorded at 400, 100 and
3
77 MHz with CDCl as solvent respectively. All coupling
3
constants (
J values) were reported in Hertz (Hz). HRMS was
performed in electron impact (EI) mode and TOF was used for
HRMS measurements. Melting points (mp) were uncorrected and
measured on micro melting point apparatus with samples in open
capillary tubes.
4
.2 Synthesis of
o-Nitroiodobenzenes. Synthesis of
3
0
4ꢀchloroꢀ1ꢀiodoꢀ2ꢀnitrobenzene (1a, Scheme 1). An oven-dried
Schlenk tube equipped with a stir bar was charged with
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6
4
0
-chloro-2-nitrobenzoic acid (40.3 mg, 0.2 mmol) and CuI (45.7 mg,
.24 mmol, 1.2 equiv). The tube was fitted with a rubber septum,
and then it was evacuated and refilled with dioxygen three times.
Under dioxygen, DMSO (2 mL) was added via syringe. The rubber
septum was replaced with a Teflon screwcap under dioxygen flow,
and the Schlenk tube was pressurized to 1 atm. With stirring, the
reaction mixtures were heated at 160 °C for the indicated amount of
time (unless otherwise specified), and then cooled down to room
temperature. The resultant mixture was filtered through a short plug
of silica gel and then concentrated in vacuo. The residue was then
purified by flash chromatography on silica gel (1% ether in hexane)
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1
2
3
4
5
6
7
8
9
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2
3
4
5
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7
8
9
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2
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5
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8
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7
8
9
0
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2
3
4
5
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7
8
9
0
1
to afford 49.4 mg (87%) of the product as a yellow solid. H NMR
(400 MHz, CDCl ):
δ
7.95 (d,
J
= 8.5 Hz, 1 H), 7.84 (d,
J
= 2.0 Hz,
3
13
1
H), 7.28 - 7.25 (m, 1 H). C NMR (100 MHz, CDCl ): δ 142.7,
3
135.3, 133.6, 125.7, 83.6.
The same procedure as for 4-chloro-1-iodo-2-nitrobenzene 1a
was used to synthesize the other -nitroiodobenzenes.
Basing on this procedure, Pd(OAc) (0.01equiv) was added as
o
2
additional catalyst to prepare
o
-methoxyiodobenzenes.
31
4
ꢀchloroꢀ2ꢀiodoꢀ1ꢀnitrobenzene (2a). Eluent: 1% ether in hexane.
1
Yellow solid, yield 52.2 mg (92%). H NMR (400 MHz, CDCl ): δ 8.05
3
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(
d, J = 2.1 Hz, 1 H), 7.84 (d, J = 8.7 Hz, 1 H), 7.47 (dd, J = 2.1, 8.7 Hz, 1
13
H). C NMR (100 MHz, CDCl ): δ 141.4, 139.3, 129.2, 126.3, 87.0.
3
32
4
ꢀfluoroꢀ1ꢀiodoꢀ2ꢀnitrobenzene (3a). Eluent: 1% ether in hexane.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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1
Yellow liquid, yield 36.3 mg (68%). H NMR (400 MHz, CDCl ): δ 8.02
3
(
q, J =4.0 Hz, 1 H), 7.64 (dd, J = 2.8, 8.0 Hz, 1 H), 7.07 (ddd, J = 2.8, 7.5,
13
8
.6 Hz, 1 H). C NMR (100 MHz, CDCl ): δ 163.5, 161.0, 143.1 (d, J =
3
19
7.4 Hz), 121.2 (d, J = 21.2 Hz), 113.7 (d, J = 26.3 Hz), 79.7 (m). F
NMR (377 MHz, CDCl ): δ -109.6 - -109.7 (m, 1 F).
3
33
4ꢀfluoroꢀ2ꢀiodoꢀ1ꢀnitrobenzene (4a). Eluent: 1% ether in hexane.
1
Yellow liquid, yield 47.5 mg (89%). H NMR (400 MHz, CDCl ): δ 7.96
3
(q, J = 8.0Hz, 1 H), 7.77 (dd, J = 2.4, 7.6 Hz, 1 H), 7.20 (ddd, J = 2.3, 7.3
13
9
.4 Hz, 1 H). C NMR (100 MHz, CDCl ): δ 164.7, 162.1, 129.1 (d, J =
3
19
26.3 Hz), 127.4 (d, J = 9.7 Hz), 116.3, 116.0. F NMR (377 MHz,
CDCl ): δ -103.8 (dd, J = 7.2, 12.6 Hz, 1 F).
3
30
1ꢀiodoꢀ2ꢀnitroꢀ4ꢀ(trifluoromethyl)benzene (5a). Eluent: 1% ether in
1
hexane. Yellow solid, yield 29.8 mg (47%). H NMR (400 MHz, CDCl ):
3
δ 8.22 (d, J = 8.3 Hz, 1 H), 8.11 (d, J = 1.2 Hz, 1 H), 7.51 (dd, J =1.5, 8.3
13
Hz, 1 H). C NMR (100 MHz, CDCl ): δ 143.0, 129.6 (q, J = 3.4 Hz),
3
19
122.4 (q, J = 3.9 Hz), 90.9 (d, J = 0.8 Hz). F NMR (377 MHz, CDCl ):
3
δ -63.3 (s, 3 F).
3
4
1ꢀiodoꢀ2ꢀnitrobenzene (6a). Eluent: 1% ether in hexane. Yellow
1
liquid, yield 30.4 mg (61%). H NMR (400 MHz, CDCl ): δ 8.04 (dd, J =
3
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2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
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3
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4
4
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1
7
1
.0, 7.9 Hz, 1 H), 7.85 (dd, J = 1.3, 8.1 Hz, 1 H), 7.51 - 7.47 (m, 1 H),
1
3
.28 - 7.24 (m, 1 H). C NMR (100 MHz, CDCl ): δ 141.9, 133.4, 129.0,
3
25.4, 110.0.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
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8
9
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7
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0
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1
ꢀiodoꢀ4ꢀmethylꢀ2ꢀnitrobenzene (7a). Eluent: 1% ether in hexane.
1
Yellow solid, yield 27.9 mg (53%). H NMR (400 MHz, CDCl ): δ 7.88
3
(
d, J = 8.1 Hz, 1 H), 7.67 (s, 1 H), 7.08 (d, J = 8.0 Hz, 1 H), 2.39 (s, 3 H).
1
3
C NMR (100 MHz, CDCl ): δ 141.5, 139.9, 134.4, 126.0, 82.0, 20.8.
3
2
ꢀiodoꢀ4ꢀmethylꢀ1ꢀnitrobenzene (8a). Eluent: 1% ether in hexane.
1
Yellow oil, yield 28.4 mg (54%). H NMR (400 MHz, CDCl ): δ 7.86 (s,
3
13
1
H), 7.80 (d, J = 8.3 Hz, 1 H), 7.25 (s, 1 H), 2.37 (s, 3 H). C NMR (100
MHz, CDCl ): δ 144.9, 142.4, 129.6, 1255, 86.5, 20.9. HRMS: m/z
3
(
EI-TOF) calculated [M]: 262.9443, found: 262.9447.
1ꢀiodoꢀ3ꢀmethylꢀ2ꢀnitrobenzene (9a). Eluent: 1% ether in hexane.
1
Yellow solid, mp 120 - 121 °C, yield 23.7 mg (45%). H NMR (400 MHz,
CDCl ): δ 8.28 (d, J = 1.5 Hz, 1 H), 7.80 (dd, J = 1.5, 8.1 Hz, 1 H), 7.08
3
13
(
d, J = 8.1 Hz, 1 H), 2.54 (s, 3 H). C NMR (100 MHz, CDCl ): δ 141.8,
3
134.2, 133.2, 89.7, 20.1. HRMS: m/z (EI-TOF) calculated [M]: 262.9443,
found: 262.9444.
2ꢀiodoꢀ1ꢀmethylꢀ3ꢀnitrobenzene (10a). Eluent: 1% ether in hexane.
1
Yellow solid, mp 56 - 58 °C, yield 32.1 mg (61%). H NMR (400 MHz,
1
3
CDCl ): δ 7.42 (d, J = 7.7 Hz, 1 H), 7.36 -7.31 (m, 1 H), 2.58 (s, 3 H). C
3
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NMR (100 MHz, CDCl ): δ 145.2, 132.3, 128.6, 121.8, 110.0, 92.4, 29.7.
3
HRMS: m/z (EI-TOF) calculated [M]: 262.9443, found: 262.9441.
1
ꢀiodoꢀ4ꢀmethoxyꢀ2ꢀnitrobenzene (11a). Eluent: 3% ether in hexane.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
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59
60
1
Yellow solid, mp 61 - 62 °C, yield 33.5 mg (60%). H NMR (400 MHz,
CDCl ): δ 7.87 (d, J = 8.8 Hz, 1H), 7.41 (d, J = 2.9 Hz, 1H), 6.86 (dd, J =
3
1
3
2
.9, 8.7 Hz, 1H), 3.86 (s, 3H). C NMR (100 MHz, CDCl ): δ 160.1,
3
142.1, 120.5, 110.9, 74.5, 56.0. HRMS: m/z (EI-TOF) calculated [M]:
2
78.9392, found: 278.9394.
2ꢀiodoꢀ4ꢀmethoxyꢀ1ꢀnitrobenzene (12a). Eluent: 3% ether in hexane.
1
Yellow solid, mp 65 - 67 °C, yield 27.3 mg (49%). H NMR (400 MHz,
CDCl ): δ 7.99 (d, J = 9.1 Hz, 1 H), 7.53 (d, J = 2.6 Hz, 1 H), 6.94 (dd, J
3
13
=
2.5, 9.1 Hz, 1 H), 3.88 (s, 3 H). C NMR (100 MHz, CDCl ): δ 162.5,
3
127.5, 127.1, 114.2, 88.2, 56.1. HRMS: m/z (EI-TOF) calculated [M]:
2
78.9392, found: 278.9391.
1ꢀiodoꢀ4,5ꢀdimethoxyꢀ2ꢀnitrobenzene (13a). Eluent: 10% ether in
1
hexane. Yellow solid, mp 86 - 88 °C, yield 36.5 mg (59%). H NMR (400
MHz, CDCl ): δ 7.61 (s, 1 H), 7.39 (s, 1 H), 3.96 (s, 3 H), 3.93 (s, 3 H).
3
13
C NMR (100 MHz, CDCl ): δ 152.7, 149.0, 123.1, 109.0, 56.7, 56.4.
3
HRMS: m/z (EI-TOF) calculated [M]: 308.9498, found: 308.9496.
3
ꢀchloroꢀ2ꢀiodobenzo[b]thiophene (14a). Eluent: 1% ether in hexane.
1
Yellow solid, mp 95 - 97 °C, yield 57.1 mg (97%). H NMR (400 MHz,
13
CDCl ): δ 7.76 (dd, J = 8.0, 20.0 Hz, 2 H), 7.44 - 7.32 (m, 2 H). C NMR
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2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
(
100 MHz, CDCl ): δ 142.1, 135.8, 128.6, 125.4, 125.2, 122.0, 121.8,
3
7
8.7. HRMS: m/z (EI-TOF) calculated [M]: 293.8767, found: 293.8771.
2
ꢀiodoꢀ3ꢀmethylbenzo[b]thiophene (15a). Eluent: 1% ether in hexane.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
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3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
Yellow solid, mp 62 - 64 °C, yield 31.8 mg (58%). H NMR (400 MHz,
CDCl ): δ 7.70 (dd, J = 7.2, 32.5 Hz, 2 H), 7.36 - 7.27 (m, 2 H), 2.41 (s, 3
3
1
3
H). C NMR (100 MHz, CDCl ): δ 143.5, 138.5, 137.2, 124.3, 124.2,
3
121.6, 121.5, 79.9, 16.1. HRMS: m/z (EI-TOF) calculated [M]: 273.9313,
found: 273.9316.
2ꢀiodoꢀ3ꢀmethylbenzofuran (16a). Eluent: 1% ether in hexane.
1
Colorless oil, yield 50.6 mg (98%). H NMR (400 MHz, CDCl ):
δ
3
1
3
7.48 - 7.41 (m, 2 H), 7.24 - 7.20 (m, 2 H), 2.22 (s, 3 H). C NMR
(
100 MHz, CDCl ): 157.9, 128.9, 124.1, 123.0, 122.6, 118.5,
δ
3
110.8, 97.4, 10.4. HRMS: m/z (EI-TOF) calculated [M]: 257.9542,
found: 257.9539.
3
5
2ꢀiodoꢀ1,3ꢀdimethoxybenzene (17a).
Eluent: 1% ether in
1
hexane. White solid, yield 50.2 mg (95%). H NMR (400 MHz,
CDCl ):
δ
7.24 (t,
J
= 8.3 Hz, 1 H), 6.49 (d,
J = 8.3 Hz, 2 H), 3.87
3
13
(
s, 6 H). C NMR (100 MHz, CDCl ):
δ
159.5, 129.9, 104.1, 56.6.
3
3
6
1ꢀiodoꢀ2,4ꢀdimethoxybenzene (18a). Eluent: 1% ether in hexane.
1
White solid, yield 29.0 mg (55%). H NMR (400 MHz, CDCl ): δ 7.61 (d,
3
J = 8.6 Hz, 1 H), 6.43 (d, J = 2.4 Hz, 1 H), 6.32 (dd, J = 2.3, 8.6 Hz, 1 H),
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3
3
1
.85 (s, 3 H), 3.79 (s, 3 H). C NMR (100 MHz, CDCl ): δ 161.4, 158.8,
3
39.2, 116.2, 107.0, 99.2, 74.8, 56.2, 55.5.
1
ꢀiodoꢀ2,4,5ꢀtrimethoxybenzene (19a). Eluent: 10% ether in hexane.
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11
12
13
14
15
16
17
18
19
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59
60
1
White solid, mp 75 - 76 °C, yield 30.0 mg (51%). H NMR (400 MHz,
CDCl ): δ 7.20 (s, 1 H), 6.51 (s, 1 H), 3.89 (s, 3 H), 3.85 (s, 3 H), 3.83 (s,
3
13
3
H). C NMR (100 MHz, CDCl ): δ 153.0, 150.2, 144.2, 121.8, 97.7,
3
72.9, 57.3, 56.7, 56.1. HRMS: m/z (EI-TOF) calculated [M]: 293.9753,
found: 293.9751.
3
7
2ꢀiodoꢀ1,3,5ꢀtrimethoxybenzene (20a). Eluent: 10% ether in hexane.
1
White solid, yield 41.2 mg (70%). H NMR (400 MHz, CDCl ): δ 6.14 (s,
3
2 H), 3.86 (s, 6 H), 3.83 (s, 3 H). 13C NMR (100 MHz, CDCl ): δ 162.1,
3
1
59.8, 91.2, 66.7, 56.5, 55.5.
3ꢀiodoꢀ1ꢀmethylꢀ1Hꢀindole (21a). Eluent: 1% ether in hexane. Yellow
1
solid, yield 24.7 mg (48%). H NMR (400 MHz, CDCl ): δ 7.43 (d, J =
3
7.7 Hz, 1 H), 7.30 - 7.24 (m, 2 H), 7.21 - 7.17 (m, 1 H), 7.12 (s, 1 H),
13
3
.78 (s, 3 H). C NMR (100 MHz, CDCl ): δ 136.8, 132.7, 130.4, 122.6,
3
121.1, 120.2, 109.4, 54.7, 33.1. HRMS: m/z (EI-TOF) calculated [M]:
2
56.9702, found: 256.9703.
2,3ꢀdiiodoꢀ1ꢀmethylꢀ1Hꢀindole (21a′). Eluent: 30% ether in hexane.
1
Yellow solid, mp 135 - 137 °C, yield 9.7 mg (21%). H NMR (400 MHz,
CDCl ): δ 7.62 - 7.58 (m, J = 8.2 Hz, 2 H), 7.12 (t, J = 7.5 Hz, 1 H), 6.89
3
13
(
d, J = 7.7 Hz, 1 H), 3.25 (s, 3 H). C NMR (100 MHz, CDCl ): δ 183.3,
3
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6
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58.2, 151.4, 138.4, 125.3, 123.8, 117.4, 109.9, 26.2. HRMS: m/z
(
EI-TOF) calculated [M]: 382.8668, found: 382.8673.
4
.3 Synthesis of o-Nitrohalobenzenes (halo = bromo, chloro).
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8
9
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Synthesis of 1ꢀbromoꢀ4ꢀchloroꢀ2ꢀnitrobenzene (1b, Scheme 2). An
oven-dried Schlenk tube equipped with a stir bar was charged with
4
-chloro-2-nitrobenzoic acid (40.3 mg, 0.2 mmol), CuI (11.4 mg,
0.06 mmol, 0.3 equiv) and CuBr (34.4 mg, 0.24 mmol, 1.2 equiv).
The tube was fitted with a rubber septum, and then it was evacuated
and refilled with dioxygen three times. Under dioxygen, DMSO (2
mL) was added via syringe. The rubber septum was replaced with a
Teflon screwcap under dioxygen flow, and the Schlenk tube was
pressurized to 1 atm. With stirring, the reaction mixtures were
heated at 160 °C for the indicated amount of time (unless otherwise
specified), and then cooled down to room temperature. The resultant
mixture was filtered through a short plug of silica gel and then
concentrated in vacuo. The residue was then purified by flash
chromatography on silica gel (1% ether in hexane) to afford 38.2 mg
1
(81%) of the product as a yellow solid. H NMR (400 MHz,
CDCl ):
δ
7.85 (d,
J
= 2.1 Hz, 1 H), 7.69 (d, J = 8.6 Hz, 1 H), 7.42
3
13
(dd,
J
= 2.2, 8.5 Hz, 1 H). C NMR (100 MHz, CDCl ):
δ
135.9,
3
133.3, 125.8, 112.6.
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The same procedure as for 1-bromo-4-chloro-2-nitrobenzene 1b
was used to synthesize the other
chloro).
o-nitrohalobenzenes (halo = bromo,
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11
12
13
14
15
16
17
18
19
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Basing on this procedure, Pd(OAc) (0.01equiv) was added as
2
additional catalyst to prepare o-methoxyhalobenzenes (halo = bromo,
chloro); The solvent of DMSO was replace with DMF as solvent to
synthesize 1-chloro-2,4-dimethoxybenzene (18c).
1
,4ꢀdichloroꢀ2ꢀnitrobenzene (1c). Eluent: 1% ether in hexane.
1
Yellow liquid, yield 29.9 mg (78%). H NMR (400 MHz, CDCl ):
δ
3
13
7
.88 (s, 1 H), 7.50 (d, J = 0.8 Hz, 2 H). C NMR (100 MHz,
CDCl ):
δ 133.3, 132.8, 125.7. HRMS: m/z (EI-TOF) calculated
3
[
M]: 190.9541, found: 190.9543.
2
1
2,4ꢀdichloroꢀ1ꢀnitrobenzene (2c, Scheme 3). Eluent: 1% ether in
1
hexane. Yellow liquid, yield 35.8 mg (93%). H NMR (400 MHz,
CDCl ):
δ
7.88 (d,
J
= 8.7 Hz, 1 H), 7.58 (d,
J
= 1.8 Hz, 1 H), 7.40
3
13
(
dd,
J = 1.7, 8.7 Hz, 1 H). C NMR (100 MHz, CDCl ): δ 131.8,
3
127.9, 126.7.
39
1
ꢀbromoꢀ4ꢀfluoroꢀ2ꢀnitrobenzene (3b). Eluent: 1% ether in hexane.
1
Yellow liquid, yield 25.1 mg (57%). H NMR (400 MHz, CDCl ): δ 7.73
3
(
q, J = 4.0 Hz, 1 H), 7.62 (dd, J = 2.6, 7.7 Hz, 1 H), 7.21 (td , J = 4.0, 8.0
13
Hz, 1 H). C NMR (100 MHz, CDCl ): δ 136.3 (d, J = 8.1 Hz), 120.9 (d,
3
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6
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9
J = 22.2 Hz), 113.6 (d, J = 27.3 Hz), 109.2 (d, J = 3.0 Hz). F NMR (377
MHz, CDCl ): δ -110.2 (dd, J = 7.4, 12.7 Hz, 1 F).
3
1
ꢀchloroꢀ4ꢀfluoroꢀ2ꢀnitrobenzene (3c). Eluent: 1% ether in
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
hexane. Yellow liquid, yield 17.2 mg (49%). H NMR (400 MHz,
CDCl ):
δ
7.64 (dd,
J = 2.2, 7.5 Hz, 1 H), 7.55 (q, J = 4.0 Hz, 1 H),
3
1
3
7
.29 (dd,
J
= 2.3, 7.6 Hz, 1 H). C NMR (100 MHz, CDCl ): δ
3
133.2 (d,
J
= 7.7 Hz), 120.8 (d,
J
=22.2 Hz), 113.5 (d,
J = 27.3 Hz).
19
F NMR (377 MHz, CDCl ):
δ -110.7 - -110.6 (m, 1 F). HRMS:
3
m/z (EI-TOF) calculated [M]: 174.9836, found: 174.9830.
39
2
ꢀbromoꢀ4ꢀfluoroꢀ1ꢀnitrobenzene (4b). Eluent: 1% ether in hexane.
1
Yellow liquid, yield 34.3 mg (78%). H NMR (400 MHz, CDCl ): δ 8.50
3
13
(
q, J = 4.0 Hz, 1 H), 8.24 - 8.20 (m, 1 H), 7.36 - 7.21 (m, 1H). C NMR
(100 MHz, CDCl ): δ 164.2, 161.6, 129.6 (d, J = 2.2 Hz), 124.8 (d, J =
3
19
9
.1 Hz), 117.0 (d, J = 25.3 Hz), 110.1 (d, J = 23.2 Hz). F NMR (377
MHz, CDCl ): δ -96.0 - -96.1 (m, 1 F).
3
2
ꢀchloroꢀ4ꢀfluoroꢀ1ꢀnitrobenzene (4c). Eluent: 1% ether in
1
hexane. Yellow liquid, yield 17.9 mg (51%). H NMR (400 MHz,
CDCl ):
δ 8.36 (dd, J = 6.1, 2.5 Hz, 1 H), 8.20 - 8.16 (m, 1 H), 7.32
3
1
3
(t,
.5 Hz), 124.0 (d,
MHz, CDCl ):
J = 8.5 Hz, 1 H). C NMR (100 MHz, CDCl ): δ 126.7 (d, J =
3
19
1
J
= 8.9 Hz), 117.2 (d,
J = 23.2 Hz). F NMR (377
δ
-103.9 - -104.0 (m, 1 F). HRMS: m/z (EI-TOF)
3
calculated [M]: 174.9836, found: 174.9833.
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ꢀbromoꢀ2ꢀnitroꢀ4ꢀ(trifluoromethyl)benzene (5b). Eluent: 1% ether in
1
hexane. Yellow liquid, yield 22.7 mg (42%). H NMR (400 MHz, CDCl ):
3
13
δ 8.11 (s, 1 H), 7.92 (d, J = 8.4 Hz, 1 H), 7.69 (d, J = 8.3 Hz, 1 H). C
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57
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59
60
NMR (100 MHz, CDCl ): δ 136.1, 129.6 - 129.5 (m), 123.8, 122.9 -
3
19
1
22.8 (m), 118.7, 110.0. F NMR (377 MHz, CDCl ): δ -63.1 (s, 1 F).
3
HRMS: m/z (EI-TOF) calculated [M]: 268.9301, found: 268.9299.
4
0
1ꢀchloroꢀ2ꢀnitroꢀ4ꢀ(trifluoromethyl)benzene (5c). Eluent: 1%
1
ether in hexane. Yellow liquid, yield 19.8 mg (44%). H NMR (400
1
3
MHz, CDCl ):
δ
δ
δ
8.16 (s, 1 H), 7.80 - 7.72 (m, 2 H). C NMR (100
3
19
MHz, CDCl ):
132.9, 129.7 (m), 123.0 (m), 110.0. F NMR (377
3
MHz, CDCl ):
-63.0 (s, 3 F).
3
21
1
ꢀbromoꢀ2ꢀnitrobenzene (6b). Eluent: 1% ether in hexane. Yellow
1
liquid, yield 17.8 mg (44%). H NMR (400 MHz, CDCl ): δ 7.84 (dd, J =
3
13
1
.8, 7.4 Hz, 1 H), 7.75 (dd, J = 1.5, 7.2 Hz, 1 H), 7.52 - 7.37 (m, 2 H). C
NMR (100 MHz, CDCl ): δ 135.1, 133.2, 128.2, 125.6, 114.4.
3
21
1
ꢀchloroꢀ2ꢀnitrobenzene (6c). Eluent: 1% ether in hexane.
1
Yellow liquid, yield 11.0 mg (35%). H NMR (400 MHz, CDCl ):
δ
3
7
.86 (d,
J
= 8.0 Hz, 1 H), 7.56 - 7.50 (m, 2 H), 7.44 - 7.39 (m, 1H).
1
3
C NMR (100 MHz, CDCl ): 133.1, 131.8, 127.5, 127.0, 125.5.
δ
3
1
ꢀbromoꢀ4ꢀmethylꢀ2ꢀnitrobenzene (7b). Eluent: 1% ether in hexane.
1
Yellow liquid, yield 16.4 mg (38%). H NMR (400 MHz, CDCl ): δ 7.64
3
(
s, 1 H), 7.59 (d, J = 8.2 Hz, 1 H), 7.23 (d, J = 8.2 Hz, 1 H), 2.39 (s, 3 H).
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4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
3
C NMR (100 MHz, CDCl ): δ 139.0, 134.6, 134.1, 126.0, 110.9, 20.7.
3
HRMS: m/z (EI-TOF) calculated [M]: 214.9580, found: 214.9582.
1
ꢀchloroꢀ4ꢀmethylꢀ2ꢀnitrobenzene (7c). Eluent: 1% ether in
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
hexane. Yellow liquid, yield 6.5 mg (19%). H NMR (400 MHz,
CDCl ):
δ
8.03 (s, 1 H), 7.94 (s, 1 H), 7.50 (s, 1 H), 2.46 (s, 3 H).
C NMR (100 MHz, CDCl ): 135.2, 122.2, 121.0, 21.2. HRMS:
m/z (EI-TOF) calculated [M]: 171.0089, found: 171.0087.
3
1
3
δ
3
2
ꢀchloroꢀ4ꢀmethylꢀ1ꢀnitrobenzene (8c). Eluent: 1% ether in hexane.
1
Yellow liquid, yield 10.6 mg (31%). H NMR (400 MHz, CDCl ): δ 7.81
3
(
d, J = 8.3 Hz, 1 H), 7.35 (s, 1 H), 7.19 (d, J = 8.2 Hz, 1 H), 2.42 (s, 3 H).
1
3
C NMR (100 MHz, CDCl ): δ 144.7, 132.2, 128.1, 127.1, 125.7, 21.1.
3
HRMS: m/z (EI-TOF) calculated [M]: 171.0092, found: 171.0087.
1ꢀbromoꢀ3ꢀmethylꢀ2ꢀnitrobenzene (9b). Eluent: 1% ether in hexane.
1
Yellow liquid, yield 17.3 mg (40%). H NMR (400 MHz, CDCl ): δ 8.12
3
(s, 1 H), 7.62 (d, J = 8.2 Hz, 1 H), 7.23 (d, J = 8.2 Hz, 1 H), 2.55 (s, 3 H).
13
C NMR (100 MHz, CDCl ): δ 135.9, 134.1, 132.5, 127.5, 119.6, 20.1.
3
HRMS: m/z (EI-TOF) calculated [M]: 214.9582, found: 214.9579.
41
2
ꢀbromoꢀ1ꢀmethylꢀ3ꢀnitrobenzene (10b). Eluent: 1% ether in
1
hexane. Yellow liquid, yield 8.6 mg (20%). H NMR (400 MHz,
CDCl ):
δ
7.52 (d,
J = 7.9 Hz, 1 H), 7.43 (d, J = 7.4 Hz, 1 H), 7.33
3
1
3
(t,
J
= 7.8 Hz, 1 H), 2.52 (s, 3 H). C NMR (100 MHz, CDCl ):
δ
3
1
41.3, 133.4, 127.5, 122.3, 115.8, 23.6.
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ꢀbromoꢀ4ꢀmethoxyꢀ2ꢀnitrobenzene (11b).
Eluent: 1% ether in
1
hexane. Yellow solid, yield 21.3 mg (46%). H NMR (400 MHz, CDCl ):
3
δ 7.58 (d, J = 8.9 Hz, 1 H), 7.35 (d, J = 2.8 Hz, 1 H), 6.98 (dd, J = 8.9,
10
11
12
13
14
15
16
17
18
19
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22
23
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50
51
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56
57
58
59
60
1
3
2
1
.9 Hz, 1 H), 3.85 (s, 3 H). C NMR (100 MHz, CDCl ): δ 160.6, 123.9,
3
23.0, 119.0, 107.7, 56.2.
4
2
1
ꢀchloroꢀ4ꢀmethoxyꢀ2ꢀnitrobenzene (11c). Eluent: 1% ether in
1
hexane. Yellow solid, yield 17.3 mg (46%). H NMR (400 MHz,
CDCl ):
δ
7.43 (d,
= 2.9, 8.9 Hz, 1 H), 3.86 (s, 3 H). C NMR (100 MHz,
CDCl ): 158.4, 132.4, 119.9, 118.2, 110.4, 56.1.
J = 8.9 Hz, 1 H), 7.39 (d, J = 2.8 Hz, 1 H), 7.06
3
13
(dd,
J
δ
3
21
2ꢀbromoꢀ4ꢀmethoxyꢀ1ꢀnitrobenzene (12b).
Eluent: 3% ether in
1
hexane. Yellow solid, yield 26.9 mg (58%). H NMR (400 MHz, CDCl ):
3
δ 7.97 (d, J = 9.1 Hz, 1 H), 7.21 (d, J = 2.3 Hz, 1 H), 6.91 (dd, J = 2.2,
13
9
.1 Hz, 1 H), 3.89 (s, 3 H). C NMR (100 MHz, CDCl ): δ 162.7, 128.0,
3
120.1, 116.8, 113.5, 56.2.
ꢀchloroꢀ4ꢀmethoxyꢀ1ꢀnitrobenzene (12c). Eluent: 3% ether in
21
2
1
hexane. Yellow solid, yield 21.0 mg (56%). H NMR (400 MHz,
CDCl ): 7.98 (d, = 9.4 Hz, 1 H), 7.00 (d, = 2.2 Hz, 1 H), 6.86
= 2.1, 9.1 Hz, 1 H), 3.88 (s, 3 H). C NMR (100 MHz,
δ
J
J
3
13
(dd,
J
CDCl3):
δ
162.9, 129.6, 128.0, 116.8, 113.0, 56.2.
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