Seven FDA-certified food dyes have been investigated as organocatalysts. As a result, Fast Green FCF and Brilliant Blue FCF have been discovered as catalysts for the chlorination of a wide range of arenes and heteroarenes in moderate to excellent yields and high regioselectivity. Mechanistic investigations of the separate systems indicate that different modes of activation are in operation, with Fast Green FCF being a light-promoted photoredox catalyst that is facilitating a one-electron oxidation of N-chlorosuccinimide (NCS) and Brilliant Blue FCF serving as a chlorine-transfer catalyst in its sulfonphthalein form with 1,3-dichloro-5,5-dimethylhydantoin (DCDMH) as stoichiometric chlorine source. Dearomatization of naphthol and indole substrates was observed in some examples using the Brilliant Blue/DCDMH system.
Seven FDA-certified food dyes have been investigated as organocatalysts. As a result, Fast Green FCF and Brilliant Blue FCF have been discovered as catalysts for the chlorination of a wide range of arenes and heteroarenes in moderate to excellent yields and high regioselectivity. Mechanistic investigations of the separate systems indicate that different modes of activation are in operation, with Fast Green FCF being a light-promoted photoredox catalyst that is facilitating a one-electron oxidation of N-chlorosuccinimide (NCS) and Brilliant Blue FCF serving as a chlorine-transfer catalyst in its sulfonphthalein form with 1,3-dichloro-5,5-dimethylhydantoin (DCDMH) as stoichiometric chlorine source. Dearomatization of naphthol and indole substrates was observed in some examples using the Brilliant Blue/DCDMH system.
In the realm of drug
discovery and medicinal chemistry, organocatalysis
offers distinct advantages to organometallic and enzymatic catalysis.
For example, organocatalysts are usually robust, inexpensive, non-toxic,
and more inert toward conditions containing moisture and oxygen.[1] The avoidance of hazardous metallic traces in
final products make organocatalytic methods especially attractive
for the synthesis of materials that interact in biological systems
such as pharmaceuticals, agrochemicals, food preservatives/additives,
biocompatible materials, and drug delivery agents.[2] The use of organocatalysts for important reactions in medicinal
chemistry has received attention in the past 20 years, largely in
the realm of asymmetric catalysis,[1c,3] but many of
the most frequently performed reactions in the construction of bioactive
molecules are still heavily mediated by metals.[4]The halogenation of an arene or heteroarene scaffold
is one of
the top 20 most frequently employed reactions in medicinal chemistry.[4] The installation of a halogen, such as chlorine,
can provide products (i.e., Zoloft, Plavix, Lorazepam, etc.) with
altered electronic and physical properties or intermediates for further
functionalization via nucleophilic aromatic substitution (SNAr) reactions and other various methods of derivatization.[5] Halogenation approaches that employ transition
metals (i.e., Ni, Rh, Pd, Au, Ag, etc.) for aromatic chlorination
can be highly predictable regarding regioselectivity; however, the
catalysts are relatively expensive.[5] Direct
C(sp2)–H electrophilic aromatic substitution (SEAr) mechanistic pathways are attractive with regard to selectivity
and economy, and many chlorinating agents operate through the presence
of an electrophilic chlorine.[6] Recent development
of chlorinating agents such as Palau’chlor,[7]N-chloro-N-fluorobenzenesulfonylamine
(CFBSA),[8] 1-chloro-1,2-benzodioxol-3-one,[9] and others[10] have
expanded the toolkit for chlorination of arenes and heteroarenes;
however, there is still a strong reliance on using commercially available,
stable chlorinating agents such as N-chlorosuccinimide
(NCS), 1,3-dichloro-5,5-dimethylhydantoin (DCDMH), and trichloroisocyanuric
acid (TCCA). These air- and temperature-stable chlorinating agents
require activation, frequently by a harsh acid or metal.[11] The necessity for acidic activation is not conducive
for chlorination of many of the heteroarenes and other privileged
scaffolds found in medicinal chemistry that contain basic sites or
acid-sensitive features. Thus, further exploration toward the discovery
of environmentally and biologically benign, inexpensive, mild, and
selective organocatalysts that operate under non-acidic conditions
for the chlorination of arenes and heteroarenes remains a valuable
pursuit.As shown in Scheme , reports of organocatalytic methods for chlorination
of arenes and/or
heteroarenes with an N-chloro reagent can be broadly
categorized into systems that operate through either transfer of the
chlorine atom to a catalyst (Method A) or amplification of the electrophilicity
of the N-chloro reagent (Methods B and C). Organocatalysts
reported as chlorine transfer agents include Ph3P=S,[12] trimethylsilyl chloride (TMSCl),[13] 2,4,6-trimethylaniline,[14] secondary ammonium salts,[15] and imidazoliumsalts.[16] Electrophilic amplification is
the most common approach and is dominated by traditional acidic activation
(Scheme , Path B).
As an alternative approach, an organic dye visible-light photoredox
catalyst (VLPC) is used to initiate a single electron oxidation of
the chlorinating agent, effectively amplifying the electrophilicity
of the chlorine atom by increasing the polarization of the N–Cl
bond (Scheme , Path
C).[17] Due to our previous success employing
the food dye erythrosine B as a VLPC for activation of N-bromosuccinimide (NBS) in the bromination of arenes and heteroarenes,[18] we turned our attention toward exploring additional
food dyes in light-promoted activation of chlorinating agents.
Scheme 1
Organocatalytic Methods for Arene Chlorination Using N-Chloro Reagents (NCS Is Shown As a Representative Reagent)
In the United States, there are seven water-soluble
synthetic food
colorants (Figure ) approved for general use. In contrast to colors extracted from
natural sources, these synthetic dyes are subject to batch certification
by the U. S. Food and Drug Administration (FDA) and are widely used
due to their high stability, consistency, safety, and strict regulation.
To date, investigations regarding these compounds have focused upon
the development of analytical methods for their detection,[19] their biological or environmental evaluation,[20] or the development of methods for their degradation.[21] Despite the widespread availability, low cost,
and benign environmental impact of the dyes, reports of their use
as organocatalysts in the development of new synthetic methodology
are extremely limited. Herein, we report the use of FDA-certified
food dyes as light-promoted organocatalysts in the chlorination of
aromatic and heteroaromatic substrates using N-chloro
reagents.
Figure 1
FDA-approved food dyes.
FDA-approved food dyes.
Results
and Discussion
Initial Screening
To begin our investigation,
seven
FDA-certified food dyes (Figure ) were screened for activity as catalysts in the chlorination
of a representative aromatic, naphthalene, using NCS and DCDMH as
stoichiometric chlorinating agents (Table ). Initial conditions were chosen to screen
for a highly practical reaction (i.e., open to air, room temperature,
and white LED). Anticipating a potential role of the dyes as photoredox
catalysts, the excited-state reduction (E*red) potential of each dye was determined (see the Supporting Information) and is reported in Table . As a result of screening with
NCS, Fast Green FCF produced a 59% yield of 1-chloronaphthalene 1 and was selected as the best performing catalyst. Screening
the catalysts with DCDMH as a chlorinating agent, however, resulted
in Brilliant Blue FCF emerging as the most efficient catalyst as 1 was produced in 84% yield. Interestingly, a 77% yield was
obtained in the absence of light, indicating that the catalyst is
operating through a different reactive mechanism than the light-activated
VLPC mode shown in Scheme , Path C.
Table 1
Screening of Food Dyes for Chlorination
of Naphthalene
% yield 1a
entry
food dye
excited-state
energy (eV)
E*redb (V)
NCS
DCDMH
1
none
3 (2)c
2 (0)c
2
Allura Red AC
2.24
+1.81
5 (0)c
4 (2)c
3
Brilliant Blue FCF
1.94
+1.35
11 (0)c
84 (77)c
4
Erythrosine B
2.28
+1.57
23 (0)c
3 (6)c
5
Fast Green FCF
1.98
+1.31
59 (10)c
47 (21)c
6
Indigo Carmine
1.98
+1.46
6 (12)c
59 (21)c
7
Sunset Yellow FCF
2.39
+2.02
0 (0)c
12 (0)c
8
Tartrazine
2.62
+2.14
0 (0)c
0 (0)c
Gas chromatography (GC) yields calculated
using adamantane as internal standard. Reactions were run in duplicate,
and the product yields were averaged.
All values vs SCE.
Yields in parentheses correspond
to reactions performed in the dark.
Gas chromatography (GC) yields calculated
using adamantane as internal standard. Reactions were run in duplicate,
and the product yields were averaged.All values vs SCE.Yields in parentheses correspond
to reactions performed in the dark.Fast Green FCF and Brilliant Blue FCF both belong
to the triphenylmethane
dye structural classification, which is conspicuously underutilized
in the realm of VLPCs. Fast Green FCF has been reported as a photosensitizer,[22] and Brilliant Blue FCF has been used to modify
electrodes[23] in materials as a humidity
indicator[24] and in photogalvanic cells,[25] but to our knowledge, this is the first report
to utilize either Fast Green FCF or Brilliant Blue FCF in an organocatalytic
role. Due to the initial indication of different modes of chlorinating
agent activation from the comparison of yields in the presence and
absence of light, the Fast Green FCF and Brilliant Blue FCF catalytic
systems were investigated separately.
Investigation of Fast Green
FCF and NCS
Using naphthalene
with NCS and catalytic Fast Green FCF, an optimization of stoichiometry
and reaction conditions was performed (Table ), which resulted in the following conditions:
1 equiv of naphthalene, 1.1 equiv of NCS, 0.02 equiv of Fast Green
FCF in acetonitrile (0.1 M relative to naphthalene) open to air in
a white LED photochamber for 24 h at ambient temperature. Though slightly
higher yields were obtained using either 3 equiv of NCS (Table , entry 3) or from
a longer reaction time (entry 4), the conditions shown in entry 2
were chosen for economy and convenience. Increased catalyst loading,
adjustments to solvent and concentration, and addition of external
oxidants all resulted in decreased yield of 1.
Table 2
Optimization of Stoichiometry and
Reaction Conditions for Chlorination of Naphthalene Using NCS and
Fast Green FCF
entry
NCS (equiv)
solvent (0.1
M)
catalyst (mol %)
time (h)
additive
(equiv)
yield 1 (%)a
1
1
MeCN
2
24
59
2
1.1
MeCN
2
24
68
3
3
MeCN
2
24
72
4
1.1
MeCN
2
48
74
5
1.1
MeCN
1
24
34
6
1.1
MeCN
5
24
59
7
1.1
MeCN
10
24
56
8
1.1
MeCN
2
24
42
9
1.1
DCM
2
24
0
10
1.1
4:1 MeCN/H2O
2
24
3
11
1.1
MeCN (0.2 M)
2
24
64
12
1.1
MeCN (0.05 M)
2
24
52
13
1.1
MeCN
2
24
(NH4)2S2O8 (1)
41
14
1.1
MeCN
2
24
(NH4)2S2O8 (0.1)
45
15
1.1
MeCN
2
24
oxone (1)
20
Gas chromatography
(GC) yields calculated
using adamantane as internal standard.
Gas chromatography
(GC) yields calculated
using adamantane as internal standard.With optimized reaction conditions, the scope of arene
and heteroarene
substrates was explored using the NCS/Fast Green chlorinating system
(Figure ). The use
of monosubstituted benzene derivatives such as anisole and acetanilide
resulted in chlorination at the para position in yields substantially
above non-catalyzed NCS chlorination (products 2 and 3). Disubstituted benzene derivatives were also tested, and
examples that contain at least one deactivating (electron-withdrawing)
group resulted in moderate to good yields of chlorinated products
(4–7). In examples where a mixture of mono- and
dichlorinated products was observed, 2.2 equiv of NCS was used to
exclusively form dichlorinated product (6 and 17). Electron-rich aromatics and naphthalene derivatives resulted in
good to excellent yields of monochlorinated products (8–12). Lidocaine, a local anesthetic, was chlorinated in modest yield
to produce 13. Nitrogen-containing heteroarenes are of
particular significance to drug discovery and medicinal chemistry
as privileged scaffolds;[26] therefore, we
tested a range of representative heteroarene substrates using the
optimized conditions (Figure , 14–19). Pyrrole, indole, indazole, and
pyridine heteroaromatics all performed well with significant improvement
over uncatalyzed reactions. Finally, known pharmaceuticals antipyrine
(phenazone) and caffeine were chlorinated cleanly without evidence
of byproduct formation (products 20 and 21). Throughout the substrate scope investigation, regioselectivity
of chlorination was consistent with a SEAr mechanism. The
substrate scope of the mild, non-acidic reaction demonstrates the
tolerance of a wide range of functionalities including aryl halide,
ether, phenol, aniline and 3° amine, nitrile, ketone, amide,
aldehyde, ester, and benzylic and α to carbonyl C(sp3)–H’s.
Figure 2
Substrate scope of Fast Green FCF-catalyzed arene and
heteroarene
chlorination.
Substrate scope of Fast Green FCF-catalyzed arene and
heteroarene
chlorination.Initial indications from the screening
(Table ) led us to
believe that light plays a crucial
role as observed by the enhancement under visible-light conditions,
suggesting that Fast Green FCF may be serving as a light-promoted
photoredox catalyst. In order to ascertain the mode of action of the
Fast Green FCF catalyst, an additional series of control experiments
were performed (Table ). Known radical inhibitor 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO)
(Table , entries 3
and 4) suppressed formation of 1, potentially implicating
the role of a radical species in the reaction mechanism. Suspecting
that light may initiate a chain propagation cycle, an experiment was
performed in which the reaction was conducted under white LED light
for 5 h and then stirred in the absence of light for an additional
19 h (Table , entry
5). A drastically reduced yield (27%) was obtained, similar to a yield
from a reaction quenched by TEMPO at 5 h (entry 4), indicating that
the reaction most likely does not undergo chain propagation. The source
of LED light was varied (white, blue, green, and red), and a trend
was observed that correlates higher energy wavelength (blue, green,
then red) to yield of 1. The λmax of
Fast Green FCF in acetonitrile is observed at 619 nm; however, production
of 1 using red LED was least efficient (48%). Lastly,
the iodide test (NaI in glacial acetic acid) was performed (see the Supporting Information) to detect the presence
of H2O2 formed by superoxide produced from air
during the reaction. Results of the test indicate that hydrogen peroxide
is formed in very small amount, indicating that air (O2) is most likely not a necessary component in the reaction mechanism.
Table 3
Control and Mechanistic Experiments
entry
deviation
from standard conditions
% yield 1a
1
none
68
2
no Fast Green FCF
4
3
1 equiv TEMPO added
4
4
1 equiv TEMPO added after
5 h
20
5
white LED for 5 h, then
dark for 19 h
27
6
blue LED
67
7
green LED
58
8
red LED
48
9
darkb
11
GC yields calculated
using adamantane
as an internal standard. Reactions were performed in triplicate, and
the three trials were averaged.
Reaction vessel was covered in aluminum
foil, and the reaction was carried out in a laboratory with the lights
turned off.
GC yields calculated
using adamantane
as an internal standard. Reactions were performed in triplicate, and
the three trials were averaged.Reaction vessel was covered in aluminum
foil, and the reaction was carried out in a laboratory with the lights
turned off.A plausible
mechanism is shown in Scheme , which is based upon literature reports
of previous systems[17a,18] and observed experimental results
that include the following observations: (i) increasing catalyst loading
did not increase the product yield (Table ), (ii) small background reaction obtained
in dark (Table ),
(iii) inhibition by radical inhibitor (Table ); (iv) faint positive result from iodide
test, (v) regioselectivity consistent with SEAr (Figure ), and (vi) indication
of a lack of significant light-initiated radical chain propagation[27] (Table , entry 5). The conclusion drawn from these results is that
Fast Green FCF most likely serves as a light-promoted, photoredox
initiator for the oxidation of NCS to promote SEAr chlorination
of arenes. In the proposed mechanism shown in Scheme , excited-state Fast Green FCF activates
NCS to produce oxidized species B, which can then undergo
aromatic chlorination. Species C, which results from
the loss of chlorine, most likely serves to return the reduced Fast
Green to its ground state in a closed catalytic cycle, as opposed
to a chain propagation step. Fast Green FCF may also serve in a minor
capacity as a chlorine transfer agent as evidenced by the formation
of a chlorinated product in the absence of light.
Scheme 2
Plausible Mechanism
for Fast Green/NCS Chlorination
Investigation of Brilliant Blue FCF and DCDMH
A separate
optimization of stoichiometry and reaction conditions using naphthalene,
DCDMH, and Brilliant Blue FCF (Supporting Information, Table S1) resulted in the following set of optimized
conditions: 1 equiv of naphthalene, 1.1 equiv of NCS, 0.04 equiv of
Brilliant Blue FCF in acetonitrile (0.1 M relative to naphthalene)
open to air for 24 h at ambient temperature.With optimized
reaction conditions, we turned our attention toward exploring the
substrate scope. In a number of examples, the DCDMH/Brilliant Blue
FCF system behaved similarly to the NCS/Fast Green FCF system, resulting
in comparable yields of chlorinated products (Figure ; compounds 2, 8, 12, 19, and 20). In several
examples, however, dichlorinated products were isolated as minor products
(22, 23, and 28) and as major
product (26), indicating that the method of chlorination
is more active than the NCS/Fast Green FCF system. Improved yields
of products 13 (lidocaine) and 24 were obtained
using the DCDMH/Brilliant Blue FCF system. Of particular interest,
the chlorination of acetanilide using the light-activated NCS/Fast
Green system resulted in the exclusive production of the para-chlorinated
isomer in 47% yield (Figure , product 3), whereas chlorination using the
DCDMH/Brilliant Blue system (Figure , product 24) resulted in the ortho-chlorinated
isomer being the major product formed (90% yield total, 2:7 p/o).
A handful of additional substrates that contain at least one electron-withdrawing
substituent (25–27) or a heteroaromatic core (29) were chlorinated in moderate to good yield. Similar to
the NCS/Fast Green system, the regioselectivity of chlorination using
the DCDMH/Brilliant Blue method was consistent with a SEAr mechanism. A wide range of functionalities are tolerated by the
chlorination reaction, including aryl ether, phenol, 3° amine,
nitrile, nitro, ketone, amide, aldehyde, ester, and benzylic and α
to carbonyl C(sp3)–H’s.
Figure 3
Substrate scope of DCDMH/Brilliant
Blue FCF chlorination of arenes
and heteroarenes.
Substrate scope of DCDMH/Brilliant
Blue FCF chlorination of arenes
and heteroarenes.During the substrate
scope investigation using DCDMH/Brilliant
Blue, we observed the dearomatization of 2-naphthol and indole (Scheme ), which was not
detected using the milder NCS/Fast Green system. A great deal of attention
has been recently devoted to dearomatization of polycyclic aromatic
cores as a valuable synthetic approach to produce stereogenic centers.[28] Dearomatization of naphthol derivatives to produce
monochlorinated products has previously been reported using DCDMH.[28a] However, using catalytic Brilliant Blue, an
88% of dichlorinated product 30 was isolated. A plausible
mechanism for the production of 30 is provided in the
Supporting Information (Scheme S1). Additionally,
difunctionalization across the 2,3-positions of indole derivatives
has garnered attention recently from the synthetic community.[28d,29] The attempted chlorination of indole using Brilliant Blue/DCDMH
resulted in a 38% yield of dichlorinated product 31 (Scheme ), with di- and monochlorinated
indanone derivatives resulting as minor components (32 and 33).
Scheme 3
Dearomatization of Arenes and Heteroarenes
Using the DCDMH/Brilliant
Blue FCF Chlorination System
With clear differences in the reactivity of the DCDMH/Brilliant
Blue system compared to the NCS/Fast Green method, we set out to determine
the mechanism of the Brilliant Blue organocatalyzed chlorination of
aromatics. During the screening of catalysts, a gradual color change
of the reaction mixture over a 24 h period was observed. The UV–Vis
spectra of Brilliant Blue FCF in MeCN and Brilliant Blue with DCDMH
over a 24 h mixing time are shown in Figure . The bathochromic shift observed (dark blue
to a pale yellow) upon mixing with DCDMH indicates that Brilliant
Blue is likely adopting the sulfonphthalein form,[30] which would result in disruption of the π-conjugation
of the dye and lead to a yellow appearance.[31]
Figure 4
UV–Vis
absorbance of Brilliant Blue FCF (shown in blue),
Brilliant Blue stirred with 1 equiv of DCDMH for 24 h (shown in red),
and DCDMH (shown in green).
UV–Vis
absorbance of Brilliant Blue FCF (shown in blue),
Brilliant Blue stirred with 1 equiv of DCDMH for 24 h (shown in red),
and DCDMH (shown in green).To compare the reactivity of the dark blue mixture of Brilliant
Blue/DCDMH at time zero (BB, DCDMH, and substrate are all added at
the same time to begin the reaction) with the pre-formed yellow mixture
of Brilliant Blue/DCDMH (BB and DCDMH are stirred for 18 h, then the
aromatic substrate is added to begin the reaction), an experiment
was conducted to monitor the rate of chlorination of 2-methylnaphthalene
using each of the versions of Brilliant Blue (Figure ). It was observed that the yellow mixture
produces 12 significantly faster, indicating that this
species that forms over a 24 h period in a standard reaction is most
likely the actual chlorinating species in the reaction.
Figure 5
Monitoring
of the chlorination of 2-methylnaphthalene by DCDMH
with pre-formed (18 h) Brilliant Blue/DCDMH mixture (red curve) versus
Brilliant Blue/DCDMH performed under standard conditions (no pre-mixing;
blue curve).
Monitoring
of the chlorination of 2-methylnaphthalene by DCDMH
with pre-formed (18 h) Brilliant Blue/DCDMH mixture (red curve) versus
Brilliant Blue/DCDMH performed under standard conditions (no pre-mixing;
blue curve).A plausible mechanism for DCDMH/Brilliant
Blue chlorination is
shown in Scheme ,
which is based upon experimental results that include the following
observations: (i) increasing catalyst loading did not decrease product
yield (Supporting Information, Table S1); (ii) comparable yield obtained in the absence of light (Table ); (iii) evidence
of a chlorinated dye species, which, when pre-formed, reacts more
efficiently than Brilliant Blue (Figures and 5); and (iv)
regioselectivity consistent with SEAr (Figure ). The conclusion drawn from
these results is that Brilliant Blue FCF most likely serves as an
organocatalytic chlorine-transfer agent (such as Scheme , A) in the presence of stoichiometric
DCDMH to promote SEAr chlorination of arenes. In the proposed
mechanism shown in Scheme , Brilliant Blue is initially chlorinated by DCDMH to produce
species A. Formation of the dichlorinated, neutral sulfonphthalein
species B results in a loss of π-conjugation and
the observed yellow color.[30,31] Dichlorinated species B then serves as the source of electrophilic chlorine for
(hetero)arene chlorination reactions. Upon electrophilic aromatic
chlorination, monochlorinated sulfonphthalein species C is produced, which can convert back to the active catalytic chlorinating
species B by obtaining another chlorine atom from stoichiometric
DCDMH.
Scheme 4
Plausible Mechanism of Brilliant Blue/DCDMH Chlorination of
Arenes
Conclusions
In
conclusion, we have described two new systems that employ FDA-certified
food dyes for mild, organocatalyzed chlorination of arenes and heteroarenes.
Mechanistic investigations of the separate systems indicate that different
modes of activation are in operation, with Fast Green FCF being a
light-promoted photoredox catalyst that is facilitating a one-electron
oxidation of NCS and Brilliant Blue FCF serving as a chlorine-transfer
catalyst with DCDMH in its sulfonphthalein form. The organocatalytic
systems are highlighted by their inexpensive and readily available
materials, operational simplicity, generation of chlorinated arenes
and heteroarenes in moderate to excellent yields, and tolerance of
a wide variety of functionalities that might be present during the
synthesis of complex molecules. Differences in reactivity of the two
systems toward (hetero)aromatic substrates were also observed. For
example, the NCS/Fast Green FCF proved to be a milder method with
monochlorination occurring primarily, and the Brilliant Blue FCF system
is capable of forming dichlorinated products from substrates containing
deactivating (electron-withdrawing) groups and generating dearomatized
naphthol and indole products. In addition to providing new catalysts
for chlorination and insight into the photoelectronic properties of
FDA-certified food dyes, this work may also lead to new investigations
regarding the degradation of food dyes and/or organic pollutants under
visible-light (solar) conditions.
Experimental Section
Materials
and Instrumentation
All reagents and solvents
were purchased from commercial sources and used without further purification.
Fast Green FCF (CAS #2353-45-9; FW = 808.86), Brilliant Blue FCF (CAS
#3844-45-9; FW = 792.84), and Indigo Carmine (CAS #860-22-0; FW =
466.36) were purchased from Alfa Aesar. Erythrosine B (CAS #16423-68-0;
FW = 879.86) and Tartrazine (CAS #1934-21-0; FW = 534.36) were purchased
from Spectrum. Allura Red AC (CAS #25956-17-6; FW = 496.42) and Sunset
Yellow FCF (CAS #2783-94-0; FW = 452.36) were purchased from TCI America. 1H and 13CNMR spectra were recorded on a Varian
400/100 (400 MHz) spectrometer in deuterated chloroform (CDCl3), dimethyl sulfoxide (DMSO), or methanol (CD3OD)
with the solvent residual peak as internal reference unless otherwise
stated (CDCl3: 1H = 7.26 ppm, 13C
= 77.02 ppm; DMSO: 1H = 2.50 ppm, 13C = 39.52
ppm; CD3OD: 1H = 3.31 ppm, 13C =
49.00 ppm). Data are reported in the following order: Chemical shifts
(δ) are reported in ppm, and spin–spin coupling constants
(J) are reported in Hz, while multiplicities are
abbreviated by s (singlet), bs (broad singlet), d (doublet), dd (doublet
of doublets), t (triplet), dt (double of triplets), td (triplet of
doublets), m (multiplet), and q (quartet). Infrared spectra were recorded
on a Nicolet iS50 FT-IR spectrometer, and peaks are reported in reciprocal
centimeters (cm–1). Melting points (m.p.) were recorded
on a Mel-Temp II (Laboratory Devices, USA) and were uncorrected. Nominal
MS (EI) were obtained using a Shimadzu GC-2010 Plus with GCMS-QP2010.
Relative intensity (in percentage) is shown in parentheses following
the fragment peak where appropriate.
Determination of Photoexcited
Energy via Fluorescence Emission
Excitation energy (E0,0) was determined
by calculating the energy of the wavelength (in nm) where the substrate’s
UV–Vis absorption and fluorescence emission spectra overlap.
The wavelength (nM) was converted to eV using an energy converter
described in the Supporting Information.
Procedure
UV–Vis spectroscopy was performed
using a Shimadzu UV-1800 spectrometer using a 3D-printed vial adaptor[32] for convenience, while fluorescence measurements
were performed using a Tecan Safire spectrometer with a clear-bottom
96-well plate. Solutions were prepared by saturating a pure ACN solution
or a 7:1 ACN:water solution with the dye of interest, centrifuging
the sample at 1500 rpm for 2 min, then analyzing the supernatant.
In most cases, the solution was diluted for UV–Vis measurements
to keep the absorbance value below 1.5. For fluorescence measurements,
excitation was performed at 15 nm below the peak absorption value
to determine overlap with the absorbance spectra. The wavelength of
this emission and absorbance spectra was used in combination with
the reduction potential determined in the electrochemical analysis
to determine the excited-state reduction potential as has been previously
reported in the literature.[33]
Determination
of Ground-State Dye Reduction Potential
Electrochemical experiments
were performed using a Biologic SP300
Potentiostat with a glassy carbon working electrode (3 mm diameter),
a platinum counter electrode (2 mm diameter), and a Ag/AgCl reference
electrode. All voltage data was adjusted to SCE by adding 0.045 V
to the experimental data. The electrolyte consisted of a 7:1 ACN:water
solution, 1 mM tetrabutylammonium hexafluorophosphate, and saturated
with the dye of interest. Cyclic voltammetry was performed at a scan
rate of 100 mV/s, starting at the open-circuit potential and scanning
across the voltage range displayed (see the Supporting Information for individual cyclic voltammograms).
General Procedure
A for Light-Promoted (Fast Green/NCS) Chlorination
of Aromatics/Heteroaromatics
To an oven-dried flask was added
a magnetic stir bar, Fast Green FCF (8.1 mg, 0.02 equiv, 0.01 mmol),
arene/heteroarene (1 equiv, 0.5 mmol), acetonitrile (2.5 mL), and
then N-chlorosuccinimide (73.4 mg, 1.1 equiv, 0.55
mmol). The reaction mixture was stirred open to air at room temperature
(20 °C) in a white LED chamber (see the Supporting Information for description of construction) for 24 h. For
substrates that produced a mixture of mono- and dibrominated products
upon full conversion, 2.2 equiv (1.1 mmol) of N-chlorosuccinimide
was employed. Upon completion of the reaction, the crude mixture was
evaporated under pressure, and the chlorinated product was isolated
via column chromatography on silica gel.
General Procedure B for
Brilliant Blue/DCDMH Chlorination of
Aromatics/Heteroaromatics
To an oven-dried flask was added
a magnetic stir bar, Brilliant Blue FCF (15.9 mg, 0.04 equiv, 0.02
mmol), arene/heteroarene (1 equiv, 0.5 mmol), acetonitrile (2.5 mL),
and then DCDMH (108.4 mg, 1.1 equiv, 0.55 mmol). The reaction mixture
was stirred open to air at room temperature (20 °C) for 24 h.
Upon completion of the reaction, the crude mixture was evaporated
under pressure, and the chlorinated product was isolated via column
chromatography on silica gel.
Product Characterization
All chloroarenes were isolated
according to general procedure unless otherwise noted and display
the characterizational data shown below (spectra available in the Supporting Information).
1-Chloronaphthalene (1)[17c]
The title compound
was prepared according to general procedure
A or B and quantified using gas chromatography with adamantane as
an internal standard. A standard curve of 1-chloronaphthalene was
prepared in six separate reaction vessels by adding varying amounts
of 1-chloronaphthalene (between 0 and 0.25 mmol) to 3 mL of acetonitrile.[17c] To each of the 3 mL acetonitrile solutions
was added 8 mL of hexanes and 0.156 mmol (20 mg) of adamantane. The
acetonitrile solution was extracted with the hexanes, and 1 mL of
the hexanes portion was removed for gas chromatography injection.
Gas chromatography was performed using a Shimadzu GC-2010 Plus with
GCMS-QP2010 with a Restek Rtx-5MS capillary column (30 m; 0.25 mm
ID; 0.25 μm df; Crossbond – 5% diphenyl/95% dimethylpilosiloxane). The GC method was as follows: 40 °C for 5 min,
then increase at 10 °C/min for 16 min (up to 200 °C). A
200 °C temperature is maintained for 10 additional min. The title
compound 1-chloronaphthalene is observed at 16.8 min[17c] and confirmed by MS (EI) m/z 164 (M+2, 30), 162 (M+, 100), 127(48), 74(36), 63(56).
4-Chloroanisole
and 2-Chloroanisole (2)[34,35]
The
title compounds were prepared according to general
procedure A or B, and characterizational spectra were consistent with
literature values. A mixture (according to 1HNMR integration)
of para/ortho isomers was isolated, and data regarding the para (major)
isomer is reported below. Clear oil (Procedure A: 44.9 mg, 63% yield
total, 8:1 para/ortho; Procedure B: 46.3 mg, 65% yield total, 20:1
para/ortho). Purification (6 mL of 4 M NaOH was added to the crude
reaction mixture and extraction using EtOAc (3 × 10 mL) was performed
followed by drying with sodium sulfate). 1HNMR (400 MHz,
CDCl3) from product of Procedure A – peaks reported
correspond to major (para) isomer: δ = 7.23 (d, J = 6.9 Hz, 2H), 6.83 (d, J = 6.9 Hz, 2H), 3.78 (s,
3H) ppm. 13CNMR (100 MHz, CDCl3) from product
of Procedure A – peaks reported correspond to major (para)
isomer: δ = 158.2, 129.3, 125.5, 115.2, 55.5. MS (EI): m/z 144 (M+2, 30), 142 (M+, 84), 127(60),
99(100), 75(40), 73(40), 63(52).
4-Chloroacetanilide (3)[17c]
The title compound
was prepared according to general procedure
A, and characterizational spectra were consistent with literature
values. White solid (39.8 mg, 47% yield). m.p. 178–181 °C.
Purification (6 mL of 4 M NaOH was added to the crude reaction mixture
and extraction using EtOAc (3 × 10 mL) was performed followed
by drying with sodium sulfate. Column chromatography using a 4:1 hexanes:EtOAc
eluent resulted in pure compound). R =
0.13. 1HNMR (400 MHz, CDCl3): δ = 7.45
(d, J = 8.6 Hz, 2H), 7.27 (d, J =
8.6 Hz, 2H), 7.21 (bs, 1H), 2.17 (s, 3H) ppm. 13CNMR (100
MHz, CDCl3): δ = 168.3, 136.4, 129.3, 129.0, 121.0,
24.6. MS (EI): m/z 171 (M+2, 3),
169 (M+, 11), 129(23), 127(75), 65(10), 63(11), 43(100), 39(12).
4-Bromo-3-chloroanisole (4)[17b]
The title compound was prepared according to general
procedure A, and characterizational spectra were consistent with literature
values. Clear oil (60.0 mg, 54% yield). Purification (6 mL of 4 M
NaOH was added to the crude reaction mixture and extraction using
EtOAc (3 × 10 mL) was performed followed by drying with sodium
sulfate. Column chromatography using a 95:5 hexanes:EtOAc eluent resulted
in pure compound). R = 0.44. 1HNMR (400 MHz, CDCl3): δ = 7.50 (d, J = 2.4 Hz, 1H), 7.33 (dd, J1 = 8.8 Hz, J2 = 2.4 Hz, 1H), 6.80 (d, J = 8.8 Hz, 1H), 3.88 (s, 3H) ppm. 13CNMR (100 MHz, CDCl3): δ = 154.3, 132.7, 130.5, 123.6, 113.3, 112.5, 56.3.
MS (EI): m/z 224 (M+4, 16), 222
(M+2, 56), 220 (M+, 53), 207(51), 205(42), 179(45), 177(37), 75(36),
63(100), 62(40), 50(36).
3-Chloro-4-methoxyacetophenone (5)[10e]
The title compound was prepared
according
to general procedure A, and characterizational spectra were consistent
with literature values. White solid (32.2 mg, 34% yield). m.p. 73–76
°C. Purification (Hexanes:DCM = 30:70). R = 0.40. 1HNMR (400 MHz, CDCl3):
δ = 7.98 (d, J = 2.0 Hz, 1H), 7.86 (dd, J1 = 8.6 Hz, J2 =
2.0 Hz, 1H), 6.96 (d, J = 8.6 Hz, 1H), 3.96 (s, 3H),
2.55 (s, 3H) ppm. 13CNMR (100 MHz, CDCl3):
δ = 195.7, 158.7, 130.7, 130.6, 128.8, 122.8, 111.2, 56.4, 26.3.
MS (EI): m/z 186 (M+2, 11), 184
(M+, 31), 171(20), 169(100), 141(15), 77(40), 75(15), 63(42), 62(12),
43(76).
4-Bromo-2,6-dichloroaniline (6)[17b]
The title compound was prepared according to general
procedure A with 2.2 equiv of NCS, and characterizational spectra
were consistent with literature values. Red solid (85.3 mg, 70% yield).
m.p. 77–80 °C. Purification (Hexanes:EtOAc = 95:5). R = 0.31. 1HNMR (400 MHz, CDCl3): δ = 7.31 (s, 2H), 4.45 (bs, 2H) ppm. 13CNMR (100 MHz, CDCl3): δ = 139.4, 130.2, 120.0,
107.9. MS (EI): m/z 243(M+4, 41),
242(M+3, 40), 241(M+2, 100), 239(M+, 55), 162(17), 160(27), 124(37),
63(50), 62(62), 61(35), 52(32).
3-Chloro-4-hydroxyphenol
(7)[17c]
The title
compound was prepared according to general
procedure A, and characterizational spectra were consistent with literature
values. White solid (16.2 mg, 21% yield). m.p. 158–160 °C.
Purification (Hexanes:DCM = 1:3). R =
0.10. 1HNMR (400 MHz, CDCl3): δ = 7.66
(d, J = 2.0 Hz, 1H), 7.50 (dd, J1 = 8.2 Hz, J2 = 2.0 Hz, 1H),
7.10 (d, J = 8.2 Hz, 1H), 6.23 (bs, 1H) ppm. 13CNMR (100 MHz, CDCl3): δ = 155.4, 133.1,
132.8, 120.8, 117.7, 117.2, 104.9. MS (EI): m/z 155 (M+2, 32), 153 (M+, 100), 89(53), 63(52), 62(68),
38(73), 37(54).
2-Chloromesitylene (8)[36]
The title compound was prepared according
to general procedure
A or B, and characterizational spectra were consistent with literature
values. Clear oil (Procedure A: 48.0 mg, 62% yield; Procedure B: 51.8
mg, 67% yield). Purification (6 mL of 4 M NaOH was added to the crude
reaction mixture and extraction using EtOAc (3 × 10 mL) was performed
followed by drying with sodium sulfate). 1HNMR (400 MHz,
CDCl3): δ = 6.89 (s, 2H), 2.34 (s, 6H), 2.25 (s,
3H) ppm. 13CNMR (100 MHz, CDCl3): δ =
135.8, 135.5, 131.5, 129.1, 20.7, 20.6. MS (EI): m/z 190 (M+2, 25), 188 (M+, 31), 155(40), 153(100),
117(30), 115(60), 91(30).
2-Chloro-1,3,5-trimethoxybenzene (9)[37]
The title compound was prepared
according
to general procedure A, and characterizational spectra were consistent
with literature values. White solid (73.3 mg, 73% yield). m.p. 91–94
°C. Purification (Hexanes:EtOAc = 80:20). R = 0.52. 1HNMR (400 MHz, CDCl3):
δ = 6.18 (s, 2H), 3.87 (s, 6H), 3.81 (s, 3H) ppm. 13CNMR (100 MHz, CDCl3): δ = 159.4, 156.5, 102.6,
91.5, 56.3, 55.5. MS (EI): m/z 204
(M+2, 32), 202 (M+, 100), 173(32), 159(32), 144(15), 139(17), 138(33),
137(16), 69(29), 59(30).
3,4-Methylenedioxychlorobenzene (10)[17c]
The title compound was prepared
according
to general procedure A, and characterizational spectra were consistent
with literature values. Clear oil (70.7 mg, 90% yield). Purification
(Hexanes:EtOAc = 90:10). R = 0.60. 1HNMR (400 MHz, CDCl3): δ = 6.84–6.77
(m, 2H), 6.72 (dd, J1 = 8.0 Hz, J2 = 0.4 Hz, 1H), 5.97 (s, 2H) ppm. 13CNMR (100 MHz, CDCl3): δ = 148.3, 146.4, 126.2,
121.3, 109.6, 108.9, 101.7. MS (EI): m/z 157 (M+2, 34), 155 (M+, 87), 65(23), 63(100), 62(36).
1-Chloro-2-naphthol
(11)[17b]
The title
compound was prepared according to general procedure
A, and characterizational spectra were consistent with literature
values. Yellow solid (85.9 mg, 94% yield). m.p. 65–68 °C.
Purification (Hexanes:EtOAc = 80:20). R = 0.24. 1HNMR (400 MHz, CDCl3): δ =
8.08 (d, J1 = 8.6 Hz, 1H), 7.80 (d, J1 = 8.2 Hz, 1H), 7.71 (d, J = 9.0 Hz, d, 1H), 7.59 (ddd, J1 = 8.6
Hz, J2 = 7.0 Hz, J3 = 1.2 Hz, 1H), 7.41 (ddd, J1 =
8.2 Hz, J2 = 7.0 Hz, J3 = 1.2 Hz, 1H), 7.28 (d, J = 9.0 Hz,
1H), 5.93 (s, 1H) ppm. 13CNMR (100 MHz, CDCl3): δ = 149.3, 131.0, 129.4, 128.4, 128.2, 127.6, 124.1, 122.7,
117.2, 113.3. MS (EI): m/z 180 (M+2, 33), 178 (M+,
100), 115(33), 114(80), 113(22), 89(25), 63(28), 57(49).
1-Chloro-2-methylnaphthalene
(12)[17b]
The title
compound was prepared according to general
procedure A or B, and characterizational spectra were consistent with
literature values. Clear oil (Procedure A: 79.4 mg, 90% yield; Procedure
B: 73.2 mg, 84%). Purification (Hexanes). R = 0.55. 1HNMR (400 MHz, CDCl3): δ =
8.33 (d, J = 8.2 Hz, 1H), 7.83 (d, J = 8.2 Hz, 1H), 7.69 (d, J = 8.2 Hz, 1H), 7.60 (ddd, J1 = 8.2 Hz, J2 =
7.0 Hz, J3 = 1.2 Hz, 1H), 7.50 (ddd, J1 = 8.2 Hz, J2 =
7.0 Hz, J3 = 1.2 Hz, 1H), 7.36 (d, J = 8.2 Hz, 1H), 2.62 (s, 3H) ppm. 13CNMR (100
MHz, CDCl3): δ = 133.4, 133.0, 131.1, 130.6, 128.7,
128.0, 127.0, 126.4, 125.6, 124.1, 20.8. MS (EI): m/z 178 (M+2, 17), 176 (M+, 52), 141(100), 139(28),
115(24), 70(72).
The title compound was prepared according to general procedure
A or B, and characterizational spectra were consistent with literature
values. Light green solid (Procedure A: 102.3 mg, 92% yield; Procedure
B: 87.8 mg, 79% yield). m.p. 117–121 °C. Purification
(Hexanes:EtOAc 80:20). R = 0.20. 1HNMR (400 MHz, CDCl3): δ = 7.69 (m, 2H),
7.42 (m, 2H), 7.24 (m, 1H), 2.86 (s, 3H), 1.81 (s, 3H) ppm. 13CNMR (100 MHz, CDCl3): δ = 161.7, 136.1, 129.2,
126.3, 120.7, 91.7, 86.0, 37.6, 20.2. MS (EI): m/z 191(61), 190(49), 189(95), 77(84), 43(82), 36(77), 51(56),
42(40), 38(39), 39(36).
8-Chlorocaffeine (21)[17b]
The title compound was prepared according
to general procedure
A, and characterizational spectra were consistent with literature
values. White solid (103.1 mg, 90% yield). m.p. 102–105 °C.
Purification (Hexanes:EtOAc 1:1). R =
0.30. 1HNMR (400 MHz, CDCl3): δ = 3.92
(s, 3H), 3.50 (s, 3H), 3.35 (s, 3H) ppm. 13CNMR (100 MHz,
CDCl3): δ = 154.5, 151.2, 147.0, 138.9, 108.1, 32.6,
29.7, 27.9. MS (EI): m/z 230 (M+2,
21), 228 (M+, 63), 143(50), 82(33), 67(94), 55(100).
2,4-Dichloroanisole
(22)[38]
The title
compound was prepared according to general procedure
B, and characterizational spectra were consistent with literature
values. Clear oil (40.0 mg, 35% yield). Purification: 3 mL of 4 M
NaOH was added to the crude reaction mixture, and extraction using
EtOAc (3 × 10 mL) was performed followed by drying with sodium
sulfate and chromatography (100% benzene). R = 0.90. 1HNMR (400 MHz, CDCl3): δ =
7.36 (d, J = 2.4 Hz, 1H), 7.19 (dd, J1 = 8.8 Hz, J2 = 2.4 Hz, 1H),
6.84 (d, J = 8.8 Hz, 1H), 3.88 (s, 3H) ppm. 13CNMR (100 MHz, CDCl3): δ = 153.9, 130.0,
127.6, 125.6, 123.3, 112.8, 56.4. MS (EI): m/z 178 (M+2, 50), 176 (M+, 78), 163(62), 161(100), 135(40),
133(65), 75(26), 73(26).
2,4-Dichloro-1,3,5-trimethylbenzene (23)[39,40]
The title compound was
prepared according to general procedure
B. White solid (27.4 mg, 29% yield). m.p. 56–59 °C. Purification
(Hexanes:EtOAc 9:1). R = 0.90. 1HNMR (400 MHz, CDCl3): δ = 6.97 (s, 1H), 2.49 (s,
3H), 2.32 (s, 6H) ppm. 13CNMR (100 MHz, CDCl3): δ = 134.2, 134.0, 132.7, 129.8, 20.6, 18.4. MS (EI): m/z 190 (M+2, 25), 188 (M+, 32), 155(30),
153(100), 115(32), 57(43), 51(28).
2-Chloroacetanilide and
4-Chloroacetanilide (24)[17c]
The title compounds were
prepared according to general procedure B, and characterizational
spectra were consistent with literature values.2-chloroacetanilide:
White solid (59.4 mg, 70% yield). m.p. 86–89 °C. Purification
(Hexanes:EtOAc 80:20). R = 0.40. 1HNMR (400 MHz, CDCl3): δ = 8.31 (d, J = 9.0 Hz, 1H), 7.59 (bs, 1H), 7.36 (d, J = 2.3 Hz, 1H), 7.23 (dd, J1 = 9.0 Hz, J2 = 2.3 Hz, 1H), 2.23 (s, 3H) ppm. 13CNMR (100 MHz, CDCl3): δ = 168.2, 133.4, 129.0,
128.7, 127.9, 122.9, 122.3, 24.9. MS (EI): m/z 171 (M+2, 2), 169 (M+, 7), 134(25), 129(25), 127(79),
43(100).4-chloroacetanilide (3): White solid (16.3
mg, 20%
yield). m.p. 174–177 °C. Purification (Hexanes:EtOAc 80:20). R = 0.10. 1HNMR (400 MHz, CDCl3) δ = 7.45 (d, J = 8.6 Hz, 2H), 7.27
(d, J = 8.6 Hz, 2H), 7.21 (bs, 1H), 2.17 (s, 3H)
ppm. 13CNMR (100 MHz, CDCl3): δ = 168.2,
136.4, 129.3, 129.0, 121.0, 24.6.
2-Chloro-4-nitrophenol
(25)[11b]
The title
compound was prepared according to general
procedure B, and characterizational spectra were consistent with literature
values. Yellow solid (50.3 mg, 58% yield). m.p. 103–105 °C.
Purification: chromatography (100% DCM) followed by recrystallization
with hexanes:EtOAc. R = 0.10. 1HNMR (400 MHz, CDCl3): δ = 8.30 (d, J = 2.7 Hz, 1H), 8.13 (dd, J1 = 9.0 Hz, J2 = 2.7 Hz, 1H), 7.14 (d, J = 9.0 Hz, 1H), 6.20 (bs, 1H) ppm. 13CNMR (100 MHz, CDCl3): δ = 156.8, 125.3, 124.6, 124.3, 120.3, 116.3 ppm.
MS (EI): m/z 175 (M+2, 22), 173
(M+, 68), 143(49), 99(56), 63(100), 53(67).
3,5-Dichloro-4-hydroxybenzonitrile
(26)[17b]
The title
compound was prepared according
to general procedure B, and characterizational spectra were consistent
with literature values. White solid (16.9 mg, 18% yield). m.p. 137–140
°C. Purification (Hexanes:EtOAc 80:20). R = 0.50. 1HNMR (400 MHz, DMSO): δ = 11.57
(bs, 1H), 7.98 (s, 2H) ppm. 13CNMR (100 MHz, DMSO): δ
= 153.8, 132.7, 122.7, 117.1, 103.1.
3-Chloro-4-methoxybenzaldehyde
(27)[17b]
The title
compound was prepared according
to general procedure B, and characterizational spectra were consistent
with literature values. Red solid (58.8 mg, 69% yield). m.p. 51–56
°C. Purification (Hexanes:DCM 1:1). R = 0.50. 1HNMR (400 MHz, CDCl3): δ =
9.85 (s, 1H), 7.90 (d, J = 2.0 Hz, 1H), 7.77 (d, J1 = 8.6 Hz, J2 =
2.0 Hz, 1H), 7.04 (d, J = 8.6, 1H), 3.99 (s, 3H)
ppm. 13CNMR (100 MHz, CDCl3) δ 189.7,
159.8, 131.2, 130.6, 130.3, 123.7, 111.7, 56.5.
3,5-Dichloro-4-methoxybenzaldehyde
(28)[17b]
The title
compound was prepared according
to general procedure B, and characterizational spectra were consistent
with literature values. Red solid (18.5 mg, 18% yield). m.p. 58–63
°C. Purification (Hexanes:DCM 1:1). R = 0.30. 1HNMR (400 MHz, CDCl3): δ =
9.87 (s, 1H), 7.82 (s, 2H), 3.99 (s, 3H) ppm. 13CNMR (100
MHz, CDCl3) δ 188.7, 157.3, 133.1, 130.7, 130.1,
61.0.
8-Chloro-7-methylquinoline (29)[17b]
The title compound was prepared according to general
procedure B, and characterizational spectra were consistent with literature
values. Yellow oily solid (27.5 mg, 31% yield). Purification (Hexanes:EtOAc
80:20). R = 0.40. 1HNMR (400
MHz, CDCl3): δ = 9.01 (dd, J1 = 4.3 Hz, J2 = 1.6 Hz, 1H), 8.10
(dd, J1 = 8.2 Hz, J2 = 1.6 Hz, 1H), 7.61 (d, J = 8.2 Hz, 1H),
7.39 (m, 2H), 2.61 (s, 3H) ppm. 13CNMR (100 MHz, CDCl3) δ 150.8, 144.6, 137.7, 136.2, 132.1, 129.4, 127.7,
125.7, 120.9, 21.0. MS (EI) m/z 179(15),
177(54), 142(100), 141(25), 89(29), 75(23), 71(25), 57(26), 39(24).
1,1-Dichloronaphtalene-2(1H)-one (30)[28a]
The title compound was prepared
according to general procedure B, and characterizational spectra were
consistent with literature values. Red oil (92.4 mg, 88% yield). Purification
(Hexanes:EtOAc 80:20). R = 0.58. 1HNMR (400 MHz, CDCl3): δ = 8.07 (dd, J1 = 7.8 Hz, J2 =
1.0 Hz, 1H), 7.53 (td, J1,2 = 7.8 Hz, J3 = 1.0 Hz, 1H), 7.47 (td, J1,2 = 7.6 Hz, J3 = 1.2 Hz,
1H), 7.45 (d, J = 10.0 Hz, 1H), 7.33 (dd, J1 = 7.6 Hz, J2 =
1.2 Hz, 1H), 6.34 (d, J = 10.0 Hz, 1H); 13CNMR (100 MHz, CDCl3) δ 185.9, 144.9, 140.7, 131.2,
130.6, 129.54, 129.52, 126.9, 122.6, 80.4.
3,5-Dichloro-1H-Indole (31)[41]
The
title compound was prepared according
to general procedure B, and characterizational spectra were consistent
with literature values. Red-brown solid (35.2 mg, 38% yield). m.p.
102–104 °C. Purification (Hexanes:EtOAc 80:20). R = 0.80. 1HNMR (400 MHz, CDCl3) δ = 8.03 (bs, 1H), 7.54 (d, J = 7.8
Hz, 1H), 7.26–7.16 (m, 3H) ppm. 13CNMR (100 MHz,
CDCl3): δ = 133.2, 125.5, 123.4, 121.1, 120.0, 117.8,
110.8, 103.8. MS (EI): m/z 187 (M+2,
64), 185 (M+, 100), 152(28), 150(81), 123(32), 114(29), 92(28), 74(27),
61(25).
3,3-Dichloro-2-oxindole (32)[42]
The title compound was prepared according
to general
procedure B, and characterizational spectra were consistent with literature
values. Brown solid (9.8 mg, 10% yield). m.p. 163–166 °C.
Purification (Hexanes:EtOAc 80:20). R = 0.47. 1HNMR (400 MHz, CDCl3): δ =
9.15 (bs, 1H), 7.62 (d, J = 7.6 Hz, 1H), 7.37 (t, J = 7.6 Hz, 1H), 7.18 (t, J1 = 7.6 Hz, 1H), 7.00 (d, J = 7.6 Hz, 1H) ppm. 13CNMR (100 MHz, CDCl3): δ = 171.1, 137.8,
132.0, 129.7, 125.1, 124.4, 111.3, 74.6 ppm. FT-IR (neat, cm–1): ν = 3146, 2940, 1730, 1681, 1621, 1486, 1469, 1396, 1206,
1188. MS (EI): m/z 169 (M+2, 7), 167 (M+, 26), 133(23),
132(100), 104(45), 77(39), 52(50), 51(81), 50(41), 38(24).
3-Chloro-2-oxindole
(33)[43]
The title
compound was prepared according to general procedure
B, and characterizational spectra were consistent with literature
values. Brown solid (15.1 mg, 18% yield). m.p. 156–158 °C.
Purification (Hexanes:EtOAc 80:20). R = 0.31. 1HNMR (400 MHz, CDCl3): δ =
8.54 (bs, 1H), 7.41 (d, J = 7.6 Hz, 1H), 7.31 (t, J = 7.6 Hz, 1H), 7.11 (t, J = 7.6 Hz, 1H),
6.94 (d, J = 7.6 Hz, 1H), 5.16 (s, 1H) ppm. 13CNMR (100 MHz, CDCl3): δ = 174.2, 140.9,
130.6, 126.2, 126.0, 123.5, 110.5, 51.8.
Scheme 1
Figure 1
Figure 2
Scheme 2
Figure 3
Scheme 3
Figure 4
Figure 5
Scheme 4