O-Iodoxybenzoic Acid-Initiated One-Pot Synthesis of 4-Arylthio-1,2-naphthoquinones, 4-Arylthio-1,2-diacetoxynaphthalenes, and 5-Arylthio-/5-Aminobenzo[a]phenazines

Article abstract of DOI:10.1021/acs.joc.6b01105

1,2-Naphthoquiones and their derivatives constitute an important category of compounds of relevance in pharmaceutical and material chemistry. It is shown that 1,2-naphthoquinones generated by o-iodoxybenzoic acid-mediated oxidation of 2-naphthols can be subjected to a cascade of reactions, namely oxidation, Michael addition, reduction, acetylation, and cyclocondensation, in the same pot to afford diverse 4-arylthio-1,2-naphthoquinones 2, 4-arylthio-1,2-diacetoxynaphthalenes 3, and 5-arylthio-/5-aminobenzo[a]phenazines 4 in very good isolated yields. The multistep single-pot synthesis occurs smoothly in DMF at rt.

Full text of DOI:10.1021/acs.joc.6b01105

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Article
IBX (o-Iodoxybenzoic Acid)-Initiated One-Pot Synthesis
of 4-Arylthio-1,2-naphthoquinones, 4-Arylthio-1,2-
diacetoxynaphthalenes and 5-Arylthio-/5-aminobenzo[a]phenazines
Abhaya Kumar Mishra, and Jarugu Narasimha Moorthy
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b01105 • Publication Date (Web): 13 Jul 2016
Downloaded from http://pubs.acs.org on July 22, 2016
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IBX (o-Iodoxybenzoic Acid)-Initiated One-Pot Synthesis of 4-Arylthio-1,2-naphthoquinones,
4-Arylthio-1,2-diacetoxynaphthalenes and 5-Arylthio-/5-aminobenzo[a]phenazines†
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Abhaya Kumar Mishra and Jarugu Narasimha Moorthy*
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Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur 208016, INDIA
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E-mail: moorthy@iitk.ac.in
ABSTRACT
1,2-Naphthoquiones and their derivatives constitute an important category of compounds of relevance in
pharmaceutical and material chemistry. It is shown that 1,2-naphthoquinones−generated by IBX-mediated
oxidation of 2-naphthols−can be subjected to a cascade of reactions, namely, oxidation, Michael addition,
reduction, acetylation and cyclocondensation−in the same pot to afford diverse 4-arylthio-1,2-
naphthoquinones 2, 4-arylthio-1,2-diacetoxynaphthalenes 3 and 5-arylthio-/5-aminobenzo[a]phenazines 4
in very good isolated yields. The multistep single-pot synthesis occurs smoothly in DMF at rt.
Graphic for TOC
Ø One-pot (3-4 steps)
Ø Mild Conditions
Ø Broad Substrate Scope (35 compounds)
R: H, Br, CN, OCH3
Nu: S/N
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INTRODUCTION
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The derivatives of 1,2-naphthoquinones, 1,2-naphthalenediols and phenazines are widely distributed in a
variety of natural products1 and organic functional materials.1-6 Furthermore,1,2-naphthoquinone
derivatives have been enormously explored for a range of biological activities2,3 such as antidiabetic,2b
anti-inflammatory,2d,e neuroprotection,2d,e anticancer,2d,e phosphatase inhibition,2c etc., cf. Figure 1.4 The
applications of 1,2-naphthoquinones, 1,2-diacetoxynaphthalenes5 and benzo[a]phenazine derivatives
derived thereof have led to simplification of synthetic procedures to access them.2-6
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Figure 1. Selective examples of biologically active 1,2-naphthoquinones, diacetoxynaphthalenes and phenazine
derivatives: a–c (anticancer),1d d–f (antidiabetic),2a g (anti-inflammatory),2d h (Cdc25 phosphatase inhibitor),2c
(anticholinesterase)5a and j (antimicrobial)2h.
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At present, there is a growing interest in the development of sustainable synthetic procedures that permit
high efficiency, environmentally-benign attributes, minimum reaction steps, good overall yield, short
reaction times, low cost, etc. One-pot multistep synthesis has emerged as an important dimension in the
modern organic synthesis.7 The one-pot multistep synthesis obviates isolation of products at the end of
each step, and allows 'step economy'8 as well as 'pot economy'.9 This concept has been applied as a
straight forward route that minimizes synthetic steps to access diverse molecular entities endowed with
structural complexity in an atom economic manner.10 We surmised that the electrophilic 1,2-
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naphthoquionones can be exploited to synthesize several derivatives that include 4-arylthio-1,2-
naphthoquionones, 4-arylthio-1,2-diacetoxynaphthalenes and 5-arylthio/5-aminobenzo[a]phenazines. 1,2-
Naphthoquinones are generally accessed from commercially-available 1- and 2-naphthols using several
oxidation reagents11 with o-iodoxybenzoic acid (IBX) being one of the best reagents for oxidation under
mild reaction conditions. The latter was indeed the motivation for our efforts to develop IBX-initiated
one-pot multistep synthesis of napthoquinone-derived molecular entities mentioned at the outset. Of
course, our own research interests for some time now have been concerned with development of IBX-
mediated reactions, modified analogs of IBX and catalytic oxidations with in situ-generated IBX.12 Thus,
our objective was to employ IBX as an oxidation reagent for in situ generation of 1,2-naphthoquionones
and perform multistep reactions in a cascade manner in one pot leading to several end products by
judicious manipulation of the reagents, cf. Scheme 1.13 Herein we report one-pot synthesis of libraries of
4-arylthio-1,2-naphthoquinones, 1,2-diacetoxynaphthalenes and benzo[a]phenazines under mild reaction
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Scheme 1. The Envisaged One-pot Cascade Leading to Phenylthionaphthalene-1,2-dione/diacetate and
Phenylthiophenazine.
conditions. Notably, all the steps involved in this methodology are known individually, but each step
requires different reaction conditions in terms of solvent, reagent, temperature and work-up procedure.
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We have thus integrated operation of 3-4 reactions, namely, oxidation, nucleophilic addition, reduction,
acetylation and condensation of 1,2-naphthoquionone with o-phenylenediamine, in one-pot, leading to
different end products in respectable isolated yields, Scheme 1. To the best of our knowledge, one-pot
syntheses of substituted 1,2-naphthoquinones, 1,2-diacetoxynaphthalenes and benzo[a]phenazine
derivatives are heretofore unknown.
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RESULTS AND DISCUSSION
To begin with, we shall consider one-pot reaction cascade that leads to 4-arylthio-1,2-naphthoquinones.
As a representative case, oxidation of 2-naphthol to 1,2-naphthoquinone by IBX was examined in
different solvents such as acetonitrile, DMF, DCM, DCE, THF and toluene at rt. While the reaction was
found to be quite messy in acetonitrile, that in THF was found to occur in 3 h. In all other solvents, except
for DMF, the reaction was found to go to completion in 10-12 h, as monitored by TLC analysis. In DMF
the oxidation was found to occur in 30 min, which is remarkably faster than in the other solvents tested.
Therefore, DMF was chosen as the solvent to generate 1,2-naphthoquinone by IBX-mediated oxidation of
2-naphthol. After complete disappearance of the naphthol as monitored by TLC, thiophenol was
introduced into the same pot as a nucleophile to perform Michael addition. The reaction was monitored
by TLC until the disappearance of the colored naphthoquinone. As the oxidation is carried out in open air
conditions, the formation of a mixture of 1,2-dione and 1,2-diol was obtained as the products of Michael
addition. This is because naphthalene-1,2-diol is highly reactive to undergo partial oxidation aerially.
Introduction of 0.5 equiv of IBX was found to ensure complete oxidation within ca. 30 min to afford
stable 4-phenylthionaphthalene-1,2-dione (2a, Scheme 2). The fact that the diol undergoes aerial
oxidation was established in an independent reaction, wherein the dione was produced aerially in an
isolated yield of 72 % over a period of 9 h.
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Scheme 2. IBX-Initiated One-Pot Synthesis of 4-Arylthio-1,2-naphthoquinones.a
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aAll the reactions were performed in DMF at rt without any precaution. Products were isolated by silica-gel column
b
chromatography. Michael addition of thiol was found to be the slowest of all reactions. The reaction time given
under each of the products in parentheses refers to this step.
The initial as well as the final oxidations were found to occur within 20-30 min, while Michael addition
reaction occurred over a period of 5 h; the latter is, therefore, the rate-determining step in the reaction
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cascade. Gratifyingly, the end product, i.e., 4-phenylthionaphthalene-1,2-dione 2a, was isolated in 82%
yield after silica-gel column chromatography of the crude reaction mixture isolated after regular work-up.
Encouraged by this result, 2-naphthols substituted with electron rich as well as poor substitutents such as
Br, OMe and CN were subjected to one-pot cascade with differently substituted thiophenols as
nucleophiles, leading to a library of 4-arylthionaphthalene-1,2-diones 2a-m in 60-82% isolated yields, cf.
Scheme 2. Lower yields were noted when the naphthol is substituted with a cyano group and also when
the nucleophilic thiophenol is either sterically hindered or substituted with an electron-withdrawing
group. In these instances, monitoring of the reactions by TLC analyses showed that the Michael addition
occurs over longer periods, ca. 5-10 h. Otherwise, three reactions, i.e., oxidation of 2-naphthol, Michael
addition with arylthiols and oxidation, occur at rt in DMF as the solvent leading to the end-products in
respectable isolated yields.
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In the same manner, we wondered if 4-phenylthionaphthalene-1,2-diol could be acetylated, cf. Scheme 1.
Because the addition of arylthiol in a Michael fashion occurred over a period of 5-12 h, the initially
produced diol was able to undergo oxidation partially to the dione. Therefore, before acylation with 2.5
equiv of Ac2O, the mixture was reduced to the corresponding hydroquinone with 2 equiv of Na2S2O4.
The addition of Na2S2O4 also facilitated the acetylation. We have found in an independent experiment that
addition of 1 equivalent of Na2S2O4 to catechol in DMF in the presence of 2.5 equivalents Ac2O leads to
catechol diacetate almost quantitatively, while the acetylation was found to virtually not occur without the
added Na2S2O4. Presumably, the latter functions as a mild base to deprotonate the catechol, whereby
acetylation with Ac2O is promoted. Regular work-up followed by silica-gel chromatography of the
reaction mixture led to 4-phenylthio-1,2-diacetoxynaphthalene (3a, Scheme 3) in a remarkable isolated
yield of 82%. A variety of substituted 2-naphthols were thus subjected to oxidation-Michael addition-
reduction-acetylation cascade in one pot to access diverse 4-arylthio-1,2-diacetoxynapthalene in 60-85%
isolated yields, cf. Scheme 3; as in the previous case, rather lower yields of products were observed for
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cyano-substituted 2-naphthols and thiols that are sterically hindered and substituted with electron-
withdrawing groups.
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Scheme 3. IBX-Initiated One-Pot Synthesis of 4-Arylthio-1,2-diacetoxynaphthalenes.a
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OAc
S
OAc
S
OAc
S
OAc
S
OAc
S
OAc
S
OAc
OAc
Br
OAc
CH3
OAc
OAc
Br
OAc
Br
H3C
tBu
Br
CH3
Br
3b
(5h, 68%)
3e
3a
(5h, 82%)
3d
(5h, 79%)
3f
3c
(5h, 85%)
(8h, 69%)
(5h, 75%)
OAc
OAc
OAc
OAc
OAc
OAc
S
OAc
H3CO
OAc
OAc
OAc
NC
Br
Br
NC
S
S
S
S
CH3
tBu
NO2
NO2
Br
3k
(5h, 63%)
3j
3g
(5h, 80%)
3h
3i
(6h, 68%)
(9h, 60%)
(12h, 63%)
aAll the reactions were performed in DMF at rt without any precaution. Products were isolated by silica-gel column
chromatography. b The addition of thiol was found to be the slowest of all reactions, and the time given under each
of the products in parentheses refers to this step.
The diketo compounds can be converted into phenazines by treatment with o-phenylenediamine.4a
Therefore, the diketones 2 generated by a 3-step cascade in DMF were treated in the same pot with o-
phenylenediamine at rt. The TLC monitoring revealed gradual appearance of the product with reactions
going to completion over a period of 6-24 h. At the end, the reaction mixtures were worked up in a
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regular manner and subjected to chromatographic purifications. Arylthiophenazines 4 were isolated in 73-
88% yields for a variety of 2-naphthols and nucleophilic thiophenols, cf. Scheme 4. What is noteworthy is
the fact that the yields of phenazines after a 4-step cascade are higher than diketones 2 isolated after a
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Scheme 4. One-Pot Synthesis of 5-Arylthio/5-aminobenzo[a]phenazines using IBX.a
aAll the reactions were performed in DMF at rt without any precaution. Products were isolated by silica gel column
b
chromatography. The Michael addition of thiol was found to be the slowest of all reactions. The reaction time
given under each of the products in parentheses refers to the Michael addition reaction.
3-step cascade. For example, the yield of methoxy-diketone 2j (Scheme 2) is only 60%, while an
additional step leads to 73% yield of the phenazine 4g (Scheme 4). Evidently, the diketones appear to
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decompose during the course of their isolation, while their in-situ trapping by condensation leading to
phenazines precludes such losses. Notably, amines could also be employed as nucleophiles, whereby 5-
aminosubstituted phenazines could be accessed in 40-78% isolated yields, cf. Scheme 4. Thus, with
primary aniline, the product 4h was isolated in 56% yield, while secondary N-methylaniline and
diphenylamine led to the products 4i and 4j in 78 and 40% yields, respectively. With tertiary N,N-
diethylaniline, C-C bond formation occurred at the para position leading to 5-(4-(N,N-
diethylamino)phenyl)benzo[a]phenazine 4k in 72% isolated yield.
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Mechanisms of Cascade Reactions. Overall, 3 to 4 reactions are sequentially involved in the one-pot
syntheses. These are shown in Schemes 2, 3 and 4. Scheme 5 shows the pertinent mechanisms involved.
It has long been established that the reaction of either 1- or 2-naphthol with one equivalent of IBX yields
1,2-naphthoquinone quantitatively along with o-iodobenzoic acid.14 Therefore, because 2-naphthols are
inexpensive and readily available, they were employed for all cascade reactions initiated by IBX. It has
also been well established that 1,2-naphthoquinones are excellent Michael acceptors,4a,15 so the conjugate
addition of thiols was expected to occur smoothly. It has been reported that the 1,2-diols of the type
formed are very sensitive to undergo aerial oxidation to the corresponding naphthoquinones.2c,4a,15
Because of this reason, it was necessary to use sodium dithionite16,17 to reduce any quinone that was
present before the acylation to form the diacetates 3, cf. Scheme 3. On the other hand, complete oxidation
to the corresponding naphthoquinones was accomplished by the addition of 0.5 equiv of IBX before
reaction with o-phenylenediamine to produce phenazines 4. Presumably, the acidic conditions
contributed by o-iodobenzoic acid facilitate the condensation.
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Scheme 5. Mechanisms of One-pot Syntheses of Arylthio-1,2-naphthoquinones 2, Arylthio-1,2-
diacetoxynaphthalenes 3 and Arylthiophenazines 4 Starting from 2-Naphthol.
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As mentioned at the outset, each of the reactions is independently known. Integration of 3-4 reactions into
one-pot operation leading to respectable yields of the end-products with step-economy is a noteworthy
development. The cascade reactions occur cleanly in DMF as the solvent at room temperature.
CONCLUSIONS
A convenient one-pot synthesis of a variety of naphthalene derivatives, namely, arylthionaphthoquinones,
arylthio-1,2-diacetoxynaphthalenes and arylthiophenazines, which are relevant in pharmaceutical and
materials chemistry, is demonstrated under mild conditions in DMF at room temperature. Although each
of the reactions is independently known, a cascade of 3-4 reactions, i.e., oxidation of 2-naphthols to 1,2-
napthoquinones, Michael addition, reduction, acetylation and cyclocondensation, have been integrated
into one-pot operation. The reactions occur smoothly leading to respectable yields of the end-products
with pot-economy.
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EXPERIMENTAL SECTION
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Solvents were distilled prior to use. All the reactions were carried out in an open atmosphere without any
precaution. The products were isolated by column chromatography with a silica gel of 100−200 µm
particle size. NMR spectra were recorded with 400 and 500 MHz spectrometers. IR spectra were
recorded on an FT-IR spectrophotometer. Mass spectral analyses were carried out with ESI-QTOF
instrument.
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General Procedure for One-Pot Synthesis of 4-Arylthionaphthalene-1,2-diones (2a–m). A
representative procedure is described below for 4-phenylthionaphthalene-1,2-dione 2a. A similar
procedure was employed for all other compounds, i.e., 2b-2m.
To a solution of 2-naphthol (0.1 g, 0.69 mmol) in 3 mL of DMF, IBX (0.214 g, 0.76 mmol) was added
and the resultant mixture was stirred in open atmosphere at rt for 0.5 h; the disappearance of 2-naphthol
was monitored by thin layer chromatography (TLC). Subsequently, thiophenol (0.091 g, 0.82 mmol) was
introduced into the reaction mixture and the contents were stirred at rt until naphthalene-1,2-dione was
consumed. IBX (0.34 mmol) was introduced into the same reaction mixture and stirred for additional 0.5
h. The contents were extracted with 50 mL of ethyl acetate 2-3 times, and the organic extract was washed
with saturated NaHCO3 followed by brine. It was dried over anhyd Na2SO4 and the solvent removed in a
rotary evaporator under reduced pressure. The residue was subjected to silica-gel column chromatography
to isolate 4-phenylthionaphthalene-1,2-dione (2a) as a reddish crystalline product using 20% ethyl acetate
in pet. ether. Yield 82% (0.151 g); mp 168–170 °C; IR (KBr) cm-1 1697 (m), 1641 (s), 1578 (m), 1544 (s);
1H NMR (400 MHz, CDCl3) δ 5.88 (s, 1H), 7.49–7.75 (m, 6H), 7.73 (dt, J = 7.2, 1.4 Hz, 1H), 7.95 (d, J =
7.6 Hz, 1H), 8.18 (d, J = 7.6 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 121.3, 125.0, 126.3, 129.5, 130.3,
130.4, 131.1, 131.3, 133.4, 135.1, 136.0, 161.5, 176.6, 179.5; ESI-MS+ m/z: Exact mass calculated for
C16H10O2SNa [M+Na]+: 289.0299, found: 289.0291.
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4-(2-Bromophenylthio)naphthalene-1,2-dione (2b). Reddish solid; 0.185 g, yield 78%; mp 194–196 °C;
IR (KBr) cm-1 1690 (m), 1645 (s), 1579 (m), 1543 (s); 1H NMR (400 MHz, CDCl3) δ 5.77 (s, 1H), 7.40–
7.49 (m, 2H), 7.62 (t, J = 7.8 Hz, 1H), 7.70–7.77 (m, 2H), 7.81 (dd, J = 1.8, 1.3 Hz, 1H), 7.95 (d, J = 8.2
Hz, 1H), 8.20 (d, J = 7.7 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 121.2, 125.2, 127.9, 129.1, 129.6,
130.6, 130.8, 131.4, 132.8, 133.2, 134.7, 135.2, 138.2, 158.7, 176.6, 179.5; ESI-MS+ m/z: Exact mass
calculated for C16H10BrO2S [M+H]+: 344.9584, found: 344.9582.
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4-(4-Bromophenylthio)naphthalene-1,2-dione (2c). Reddish solid; 0.197 g, yield 80%; mp 204–206 °C;
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IR (KBr) cm-1 1691 (m), 1639 (s) 1578 (m), 1544 (s); H NMR (400 MHz, CDCl3) δ 5.86 (s, 1H), 7.45
(d, J = 8.2 Hz, 2H), 7.61 (t, J = 7.8 Hz, 1H), 7.66 (d, J = 8.2 Hz, 2H), 7.74 (t, J = 7.8 Hz, 1H), 7.92 (d, J =
7.7 Hz, 1H), 8.18 (d, J = 7.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 121.4, 125.0, 125.4, 126.2, 129.6,
130.4, 131.5, 133.2, 133.7, 135.1, 137.4, 160.6, 176.6, 179.3; ESI-MS+ m/z: Exact mass calculated for
C16H10BrO2S [M+H]+: 344.9584, found: 344.9590.
4-(4-tert-Butylphenylthio)naphthalene-1,2-dione (2d). Reddish solid; 0.167 g, yield 75%; mp 196–198
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°C; IR (KBr) cm-1 3069 (m), 2964 (s), 1695 (m), 1641 (s), 1578 (m), 1536 (s); H NMR (400 MHz,
CDCl3) δ 1.36 (s, 9H), 5.95 (s, 1H), 7.45–7.54 (AA'BB', 4H), 7.60 (dt, J = 7.8 Hz, 0.9 Hz, 1H), 7.73 (dt,
J = 7.6, 1.8 Hz, 1H), 7.96 (d, J = 7.8 Hz, 1H), 8.18 (dd, J = 7.8, 1.4 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 31.5, 35.0, 121.2, 122.6, 125.0, 127.5, 129.5, 130.3, 131.3, 133.5, 135.0, 135.7, 154.7, 162.0,
176.7, 179.6; ESI-MS+ m/z: Exact mass calculated for C20H19O2S [M+H]+: 323.1106, found: 323.1100.
6-Bromo-4-phenylthionaphthalene-1,2-dione (2e). Reddish solid; 0.12 g, yield 78%; mp 188–190 °C; IR
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(KBr) cm-1 1693 (m), 1643 (s), 1571 (m), 1545 (m); H NMR (400 MHz, CDCl3) δ 5.91 (s, 1H), 7.51–
7.59 (m, 5H), 7.75 (dd, J = 8.4, 1.3 Hz, 1H), 8.03 (d, J = 8.2 Hz, 1H), 8.08 (d, J = 1.4 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ 122.2, 125.8, 128.2, 129.0, 130.5, 130.7, 130.8, 131.3, 134.3, 134.9, 136.0, 159.9,
176.2, 178.6; ESI-MS+ m/z: Exact mass calculated for C16H10BrO2S [M+H]+: 344.9585, found: 344.9579.
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6-Bromo-4-(2-bromophenylthio)naphthalene-1,2-dione (2f). Reddish solid; 0.154 g, yield 81%; mp 192–
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194 °C; IR (KBr) 1694 (m), 1638 (s), 1577 (m), 1542 (m); H NMR (400 MHz, CDCl3) δ 5.78 (s, 1H),
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7.42–7.49 (m, 2H), 7.70 (d, J = 6.8 Hz, 1H), 7.76 (d, J = 7.8 Hz, 1H), 7.82 (d, J = 7.3 Hz, 1H), 8.04–8.07
(m, 2H), 13C NMR (100 MHz, CDCl3) δ 122.0, 127.4, 128.2, 128.3, 129.1, 129.2, 130.8, 130.9, 133.0,
134.4, 134.5, 134.8, 138.2, 157.1, 176.2, 178.5; ESI-MS+ m/z: Exact mass calculated for C16H9Br2O2S
[M+H]+: 422.8689, found: 422.8685.
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6-Bromo-4-(4-bromophenylthio)naphthalene-1,2-dione (2g). Reddish solid; 0.14 g, yield 74%; mp 184–
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186 °C; IR (KBr) cm-1 1699 (m), 1645 (s), 1575 (m), 1542 (m); H NMR (400 MHz, CDCl3) δ 5.88 (s,
1H), 7.44 (d, J = 8.2 Hz, 2H), 7.67 (d, J = 8.2 Hz, 2H), 7.76 (dd, J = 8.4, 1.4 Hz, 1H), 8.04 (d, J = 8.2 Hz,
2H); 13C NMR (100 MHz, CDCl3) δ 122.3, 124.9, 126.5, 128.2, 128.9, 130.8, 130.9, 133.9, 134.4, 134.6,
137.4, 159.0, 176.2, 178.4; ESI-MS+ m/z: Exact mass calculated for C16H9Br2O2S [M+H]+: 422.8689,
found: 422.8698.
6-Bromo-4-(4-tert-butylphenylthio)naphthalene-1,2-dione (2h). Reddish solid; 0.14 g, yield 78%; mp
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188–189 °C; IR (KBr) cm-1 2957 (s), 2890 (m), 1698 (m), 1659 (s), 1573 (m); H NMR (400 MHz,
CDCl3) δ 1.37(s, 9H), 5.97 (s, 1H), 7.48 d, J = 8.7 Hz, 2H), 7.54 (d, J = 8.7 Hz, 2H), 7.75 (dd, J = 8.2, 1.8
Hz, 1H), 8.03 (d, J = 8.3 Hz, 1H), 8.09 (d, J = 1.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 31.1, 35.5,
122.0, 122.1,127.7, 128.2, 128.9, 130.6, 130.7, 134.2, 134.8, 135.6, 154.9, 160.4, 176.2, 178.8; ESI-MS+
m/z: Exact mass calculated for C20H18BrO2S [M+H]+: 401.0211, found: 401.0215.
7-Methoxy-4-phenylthionaphthalene-1,2-dione (2i). Reddish solid; 0.129 g, yield 76%; mp 190–192 °C;
IR (KBr) cm-1 3027 (m), 2944 (s), 1697 (m), 1641 (s), 1594 (m), 1533 (m); 1H NMR (400 MHz, CDCl3) δ
3.93 (s, 3H), 5.76 (s, 1H), 7.19 (dd, J = 8.9, 2.7 Hz, 1H), 7.48–7.58 (m, 5H), 7.66 (d, J = 2.7 Hz, 1H),
7.86 (d, J = 9.1 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 55.9, 113.6, 119.0, 121.0, 126.4, 126.5, 126.8,
130.3, 131.0, 132.0, 136.0, 161.9, 162.1, 176.8, 179.6; ESI-MS+ m/z: Exact mass calculated for
C17H13O3S [M+H]+: 297.0585, found: 297.0580.
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7-Methoxy-4-(2,4,6-trimethylphenylthio)naphthalene-1,2-dione (2j). Reddish solid; 0.116 g, yield 60%;
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mp 196–198 °C; IR (KBr) cm-1 2922 (m), 3030 (m), 1698 (m), 1642 (s), 1597 (m), 1577 (m); H NMR
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(400 MHz, CDCl3) δ 2.33 (s, 3H), 2.37 (s, 6H), 3.93 (s, 3H), 5.60 (s, 1H), 7.04 (s, 2H), 7.21 (dd, J = 8.7,
2.7 Hz, 1H), 7.66 (d, J = 2.7 Hz, 1H), 7.95 (d, J = 8.7 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 21.2, 21.3,
55.9, 113.3, 117.3, 121.0, 121.7, 126.5, 127.2, 130.1, 132.2, 141.5, 143.5, 160.5, 162.0, 176.7, 179.9;
ESI-MS+ m/z: Exact mass calculated for C20H19O3S [M+H]+: 339.1055, found: 339.1054.
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7-Methoxy-4-(4-nitrophenylthio)naphthalene-1,2-dione (2k). Reddish solid; 0.125 g, yield 64%; mp 198–
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200 °C; FT- IR (KBr) cm-1 3029 (m), 2978 (m), 1699 (m), 1648 (s), 1596 (m), 1575 (m); H NMR (400
MHz, CDCl3) δ 3.94 (s, 3H), 5.76 (s, 1H), 7.20 (dd, J = 8.9, 2.9 Hz, 1H), 7.67 (d, J = 2.7 Hz, 1H), 7.77–
7.82 (m, 3H), 8.34 (d, J = 8.7 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 56.0, 114.2, 120.0, 121.1, 125.0,
125.7, 127.1, 132.1, 135.3, 136.4, 149.1, 159.0, 162.4, 176.9, 178.9; ESI-MS+ m/z: Exact mass calculated
for C17H12NO5S [M+H]+: 342.0436, found: 342.0430.
6-Cyano-4-phenylthionaphthalene-1,2-dione (2l). Reddish solid; 0.135 g, yield 68%; mp 199–201 °C; IR
(KBr) cm-1 2232 (m), 1700 (m), 1644 (s), 1566 (m), 1542 (s); 1H NMR (400 MHz, CDCl3) δ 6.00 (s, 1H),
7.53–7.59 (m, 5H), 7.90 (dd, J = 8.0, 1.4 Hz, 1H), 8.23 (d, J = 0.9 Hz, 1H), 8.27 (d, J = 8.2 Hz, 1H); 13C
NMR (100 MHz, CDCl3) δ 116.9, 118.5, 122.7, 125.3, 125.4, 128.5, 129.7, 130.7, 131.5, 132.5, 134.3,
135.9, 159.2, 175.4, 178.1; ESI-MS+ m/z: Exact mass calculated for C17H10NO2S [M+H]+: 292.0432,
found: 292.0435.
6-Cyano-4-(2,4,6-trimethylphenylthio)naphthalene-1,2-dione (2m). Reddish solid; 0.121 g, yield 62%;
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mp 202–204 °C; IR (KBr) cm-1 2920 (m), 2234 (m), 1720 (m), 1649 (s), 1599 (m), 1567 (m); H NMR
(400 MHz, CDCl3) δ 2.35 (s, 3H), 2.38 (s, 6H), 5.83 (s, 1H), 7.08 (s, 2H), 7.89 (dd, J = 8.2, 1.4 Hz, 1H),
8.27 (d, J = 7.8 Hz, 1H), 8.33 (d, J = 0.9 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 21.2, 21.3, 117.0,
118.5, 120.7, 121.1, 129.0, 129.6, 130.4, 132.7, 134.2, 134.4, 142.2, 143.4, 157.8, 175.2, 175.6; ESI-MS+
m/z: Exact mass calculated for C20H16NO2S [M+H]+: 334.0902, found: 334.0900.
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General Procedure for One-Pot Synthesis of 4-Arylthio-1,2-Diacetoxynaphthalenes (3a–k). A typical
procedure is describe below for 4-phenylthio-1,2-diacetoxynaphthalene 3a. A similar procedure was
adopted for the synthesis of all others, i.e., 3b-3k.
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To a solution of 2-naphthol (0.1 g, 0.69 mmol) in 4 mL DMF, IBX (0.214 g, 0.76 mmol) was added and
stirred in open atmosphere for 0.5 h at rt. The disappearance of 2-naphthol was followed by TLC analysis.
At the end of complete oxidation, thiophenol (0.091 g, 0.82 mmol) was added to the reaction mixture at
rt. After complete consumption of naphthalene-1,2-dione as monitored by TLC analysis, Na2S2O4 (0.241
g, 1.38 mmol) was introduced into the same pot followed by acetic anhydride (0.177 g, 1.72 mmol) to
afford 4-phenylthio-1,2-diacetoxynaphthalene (3a); it should be noted that the reaction flask was kept
stoppered during acetylation. At the end of the reaction, 60 mL of ethyl acetate was added to the reaction
mixture and washed thoroughly with saturated NaHCO3 followed by brine. The ethyl acetate extract was
dried over Na2SO4 and solvent removed under reduced pressure. The residue was subjected to silica-gel
column chromatography to isolate 4-phenylthio-1,2-diacetoxynaphthalene (3a) as a colorless semi-solid
material using 10% ethyl acetate in pet. ether. Yield 82% (0.2 g); IR (KBr) cm-1 3070 (m), 1774 (s), 1601
(m), 1582 (w); 1H NMR (400 MHz, CDCl3) δ 2.30 (s, 3H), 2.47 (s, 3H), 7.22–7.31 (m, 5H), 7.44 (s, 1H),
7.52–7.59 (m, 2H), 7.89 (dd, J = 7.5, 1.5 Hz, 1H), 8.38 (dd, J = 9.0, 1.8 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 20.4, 20.6, 121.7, 125.7, 126.7, 126.8, 126.9, 127.4, 128.2, 129.2, 130.0, 131.1, 131.9, 135.2,
137.2, 138.7, 167.9, 168.1; ESI-MS+ m/z: Exact mass calculated for C20H16O4SNH4 [M+NH4]+: 370.1113,
found: 370.1116.
4-(4-Bromophenylthio)-1,2-diacetoxynaphthalene (3b). White crystalline material, 0.202 g, yield 68%;
mp 88–90 °C; IR (KBr) cm-1 3074 (m), 1770 (s), 1632 (m), 1600 (m); 1H NMR (400 MHz, CDCl3) δ 2.32
(s, 3H), 2.47 (s, 3H), 7.09 (d, J = 8.7 Hz, 2H), 7.37 (d, J = 8.7 Hz, 2H), 7.48 (s, 1H), 7.56 (m, 2H), 7.88
(d, J = 7.4 Hz, 1H), 8.31 (d, J = 7.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 20.4, 20.7, 120.6, 121.8,
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125.7, 127.2, 127.5, 127.6, 128.4, 129.8, 130.9, 132.0, 132.3, 134.9, 137.7, 138.7, 167.9, 168.1; ESI-MS+
m/z: Exact mass calculated for C20H15BrO4SNH4 [M+NH4]+: 448.0218, found: 448.0214.
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4-(4-tert-Butylphenylthio)-1,2-diacetoxynaphthalene (3c). White solid, 0.212 g, yield 75%; mp 92–94 °C;
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IR (KBr) cm-1 2962 (s), 2868 (m), 1778 (s), 1600 (m), 1570 (m); H NMR (400 MHz, CDCl3) δ 1.30 (s,
9H), 2.30 (s, 3H), 2.46 (s, 3H), 7.27 (d, J = 8.7 Hz, 2H), 7.33 (d, J = 8.7 Hz, 2H), 7.38 (s, 1H), 7.54–7.58
(m, 2H), 7.88 (dd, J = 8.9, 2.3 Hz, 1H), 8.40 (dd, J = 7.1, 3.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ
20.4, 20.6, 31.2, 34.5, 121.7, 125.7, 125.9, 126.4, 126.9, 127.4, 128.2, 130.4, 131.2, 131.8, 132.0, 136.9,
138.8, 150.4, 167.9, 168.1; ESI-MS+ m/z: Exact mass calculated for C24H24O4SNH4 [M+NH4]+: 426.1739,
found: 426.1730.
6-Bromo-4-phenylthio-1,2-diacetoxynaphthalene (3d). White solid, 0.152 g, yield 79%; mp 96–98 °C; IR
(KBr) cm-1 3045 (m), 1763 (s), 1586 (m), 1479 (m); H NMR (400 MHz, CDCl3) δ 2.29 (s, 3H), 2.45 (s,
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3H), 7.23–7.31 (m, 5H), 7.39 (s, 1H), 7.63 (dd, J = 9.1, 1.8 Hz, 1H), 7.73 (d, J = 9.1 Hz, 1H), 8.56 (d, J =
1.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 20.4, 20.6, 121.7, 123.5, 126.9, 127.3, 127.6, 128.0, 129.5,
130.5, 130.7, 130.9, 132.9, 134.5, 137.2, 139.0, 167.8, 167.9; ESI-MS+ m/z: Exact mass calculated for
C20H15BrO4SNa [M+Na]+: 452.9772, found: 452.9774.
6-Bromo-4-(4-bromophenylthio)-1,2-diacetoxynaphthalene (3e). White solid, 0.195 g, yield 85%; mp
131–133 °C; IR (KBr) cm-1 3068 (m), 2937 (m), 1762 (s), 1589 (m); H NMR (400 MHz, CDCl3) δ 2.31
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(s, 3H), 2.45 (s, 3H), 7.12 (d, J = 8.4 Hz, 2H), 7.40 (d, J = 8.4 Hz, 2H), 7.44 (s, 1H), 7.64 (dd, J = 8.7, 1.8
Hz, 1H), 7.67 (d, J = 9.2 Hz, 1H), 8.51 (d, J = 1.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 20.4, 20.7,
121.2, 122.0, 123.6, 127.0, 127.9, 128.5, 129.4, 131.0, 131.4, 132.5, 133.0, 134.2, 137.7, 139.0, 167.7,
168.0; ESI-MS+ m/z: Exact mass calculated for C20H14Br2O4SNH4 [M+NH4]+: 525.9323, found: 525.9327.
6-Bromo-4-(2,4,6-trimethylphenylthio)-1,2-diacetoxynaphthalene (3f). White solid, 0.146 g, yield 69%;
mp 188–190 °C; IR (KBr) cm-1 2920 (w), 1776 (s), 1588 (m); 1H NMR (400 MHz, CDCl3) δ 2.20 (s, 3H),
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2.35 (s, 3H), 2.39 (s, 6H), 2.40 (s, 3H), 6.36 (s, 1H), 7.06 (s, 2H), 7.62–7.69 (m, 2H), 8.53 (s, 1H); 13C
NMR (100 MHz, CDCl3) δ 20.4, 20.7, 21.2, 21.5, 117.7, 120.6, 123.6, 124.8, 126.6, 126.7, 129.7 (2),
130.2, 130.6, 134.3, 139.6, 140.0, 144.1, 167.9, 168.1; ESI-MS+ m/z: Exact mass calculated for
C23H21BrO4SNH4 [M+NH4]+: 490.0687, found: 490.0683.
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6-Bromo-4-(4-tert-butylphenylthio)-1,2-diacetoxynaphthalene (3g). White solid, 0.174 g, yield 80%; mp
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190–194 °C; IR (KBr) cm-1 2965 (m), 2904 (w), 2867 (w), 1774 (s), 1589 (m); H NMR (400 MHz,
CDCl3) δ 1.30 (s, 9H), 2.28 (s, 3H), 2.44 (s, 3H), 7.27 (d, J = 7.6 Hz, 2H), 7.33 (d, J = 7.6 Hz, 2H), 7.35
(s, 1H), 7.63 (dd, J = 9.1, 1.8 Hz, 1H), 7.12 (d, J = 9.1 Hz, 1H), 8.59 (d, J = 1.8 Hz, 1H); 13C NMR (100
MHz, CDCl3) δ 20.4, 20.7, 31.2, 34.6, 121.5, 123.5, 126.6 (2), 126.9, 127.9, 130.5, 130.8 (2), 131.6,
132.8, 136.9, 139.1, 150.8, 167.8, 167.9; ESI-MS+ m/z: Exact mass calculated for C24H23BrO4SNH4
[M+NH4]+: 504.0844, found: 504.0842.
6-Bromo-4-(4-nitrophenylthio)-1,2-diacetoxynaphthalene (3h). White solid, 0.127 g, yield 60%; mp 171–
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173 °C; IR (KBr) cm-1 3102 (w), 1775 (s), 1662 (m), 1590 (s), 1336 (s); H NMR (400 MHz, CDCl3) δ
2.34 (s, 3H), 2.50 (s, 3H), 7.14 (d, J = 9.1 Hz, 2H), 7.68 (dd, J = 9.1, 1.8 Hz, 1H), 7.79 (s, 1H) 7.82 (d, J
= 9.1 Hz, 1H), 8.06 (d, J = 9.1Hz, 2H), 8.45 (d, J = 1.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 20.4,
20.7, 123.9, 124.3, 124.9, 126.6 (2), 127.4, 127.8, 128.1, 132.4, 134.1, 139.0, 139.4, 145.7, 146.5, 167.5,
167.9; ESI-MS– m/z Exact mass calculated for C16H9BrNO4S [M-(2CH3CO+H)]–: 389.94356, found:
389.9444.
7-Methoxy-4-(4-nitrophenylthio)-1,2-diacetoxynaphthalene (3i). White solid, 0.157 g, yield 63%; mp 97–
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99 °C; IR (KBr) cm-1 3070 (w), 2893 (w), 1769 (s), 1625 (m), 1595 (m), 1578 (s), 1507 (s), 1337 (s); H
NMR (400 MHz, CDCl3) δ 2.34 (s, 3H), 2.50 (s, 3H), 3.92 (s, 3H), 7.11 (d, J = 8.7 Hz, 2H), 7.17–1.20
(m, 2H), 7.62 (s, 1H), 8.02 (d, J = 8.7 Hz, 2H), 8.13 (s, J = 9.1 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ
20.5, 20.7, 55.4, 100.7, 120.3, 124.1, 125.3, 126.3, 127.7, 128.3, 128.4, 130.2, 138.4, 139.4, 145.4, 147.4,
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159.2, 167.7, 168.0; ESI-MS+ m/z: Exact mass calculated for C21H17NO7SNH4 [M+NH4]+: 445.1069,
found: 445.1070.
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6-Cyano-4-(4-bromophenylthio)-1,2-diacetoxynaphthalene (3j). White solid; 0.183 g, yield 68%; mp
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156–158 °C; FT- IR (KBr) cm-1 3074 (w), 2227 (m), 1778 (s), 1605 (m); H NMR (400 MHz, CDCl3) δ
2.32 (s, 3H), 2.47 (s, 3H), 7.16 (d, J = 8.7 Hz, 2H), 7.44 (d, J = 8.7 Hz, 2H), 7.48 (s, 1H), 7.70 (dd, J =
8.7, 1.3 Hz, 1H), 7.97 (d, J = 8.7 Hz, 1H), 8.73 (d, J = 1.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 20.4,
20.7, 110.8, 118.5, 121.9, 123.4, 128..0, 128.4, 130.1. 130.6, 131.6, 132.1, 132.2, 132.8, 133.1, 137.2,
141.3, 167.6, 167.7; ESI-MS+ m/z: Exact mass calculated for C21H14BrNO4SNH4 [M+NH4]+: 473.0171,
found: 473.0172.
6-Cyano-4-(4-methylphenylthio)-1,2-diacetoxynaphthalene (3k). White solid, 0.145 g, yield 63%; mp
140–143 °C; FT- IR (KBr) cm-1 3071 (w), 2937 (w), 2231 (m), 1774 (s), 1604 (w); H NMR (400 MHz,
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CDCl3) δ 2.29, (s, 3H), 2.35 (s, 3H), 2.46 (s, 3H) 7.17 (d, J = 8.2 Hz, 2H), 7.30 (d, J = 6.8 Hz, 3H), 7.68
(d, J = 7.8 Hz, 1H), 7.93 (d, J = 9.1 Hz, 1H), 8.76 (s, 1H), 13C NMR (100 MHz, CDCl3) δ 20.4, 20.7,
21.2, 110.3, 118.7, 123.3, 126.1, 127.9, 129.1, 129.9, 130.1, 130.5, 131.5, 132.3, 134.9, 136.2, 138.7,
141.4, 167.6, 167.7; ESI-MS+ m/z: Exact mass calculated for C22H17NO4SNH4 [M+NH4]+: 409.1222,
found: 409.1221.
General Procedure for One-Pot Synthesis of 5-Arylthio-/5-arylaminobenzo[a]phenazines (4a–k). A
representative procedure is described below for 5-phenylthiobenzo[a]phenazine 4a. A similar procedure
was followed for all other phenazines 4b-4k.
To a solution of 4-phenylthionaphthalene-1,2-dione prepared by above procedure starting from 2-
naphthol (0.1 g, 0.69 mmol), o-phenylenediamine (0.09 g, 0.82 mmol) was added at rt and allowed to stir
for 1 h in open air. The disappearance of 4-arylthionaphthalene-1,2-diones was monitored by TLC. At the
end of the reaction, the reaction mixture was diluted with DCM and the organic layer was washed with
saturated NaHCO3 followed by brine. It was later dried over Na2SO4 and the solvent removed in rotary
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evaporator under reduced pressure. Silica-gel column chromatography was performed to isolate 5-
phenylthiobenzo[a]phenazine (4a) as a yellow colored solid material using 25% DCM in pet. ether. Yield
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88% (0.206 g); mp 192–194 °C; IR (KBr) cm-1 1608 (s), 1584 (m), 1497 (m); H NMR (400 MHz,
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CDCl3) δ 7.46–7.47 (m, 3H), 7.54 (s, 1H), 7.63–7.65 (m, 2H), 7.80–7.88 (m, 4H), 8.14–8.16 (m, 1H),
8.30–8.33 (m, 1H), 8.41–8.43 (m, 1H), 9.48 (dd, 7.0, 2.5 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 124.5,
124.6, 125.6, 128.4, 128.8, 129.4, 129.4, 129.6, 130.0 (2), 130.1, 130.8, 131.5, 134.6 (2), 141.6, 141.9,
142.6, 142.9, 143.2; ESI-MS+ m/z: Exact mass calculated for C22H14N2S [M]+: 338.0878, found:
338.0877.
5-(4-Bromophenylthio)benzo[a]phenazine (4b). Yellow solid, 0.237 g, yield 82%; mp 220–220 °C; IR
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(KBr) cm-1 1616 (m), 1580 (m), 1489 (s); H NMR (400 MHz, CDCl3) δ 7.47 (d, J = 8.7 Hz, 2H), 7.57
(d, J = 7.8 Hz, 3H), 7.82–7.88 (m, 4H), 8.16–8.19 (m, 1H), 8.31–8.38 (m, 2H), 9.48 (dd, J = 7.6, 1.5 Hz,
1H); 13C NMR (100 MHz, CDCl3) δ 123.5, 124.6, 125.7, 125.8, 128.6, 128.9, 129.7 (2), 130.1, 130.3,
130.5, 131.5, 131.5, 133.2, 135.5, 141.5, 141.8, 142.0, 142.9, 143.0; ESI-MS+ m/z: Exact mass calculated
for C22H14BrN2S [M+H]+: 417.0062, found: 417.0066.
5-(4-Methylphenylthio)benzo[a]phenazine (4c). Yellow solid, 0.197 g, yield 81%; mp 196–198 °C; IR
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(KBr) cm-1 3032 (w), 2919 (w), 1616 (w), 1580 (m), 1490 (m); H NMR (500 MHz, CDCl3) δ 2.44 (s,
3H), 7.30 (d, J = 8.0 Hz, 2H), 7.39 (s, 1H), 7.56 (d, J = 8.0 Hz, 2H), 7.76–7.80 (m, 2H), 7.82–7.85 (m,
2H), 8.11–8.13 (m, 1H), 8.27–8.29 (m, 1H), 8.38–8.39 (m, 1H), 9.44 (dd, J = 7.2, 2.5 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ 21.3, 123.2, 124.3, 125.6, 126.5, 128.3, 128.7, 129.2, 129.7, 129.9, 130.0, 130.7,
130.9, 131.4, 135.2, 139.8, 141.5, 141.9, 142.9, 143.3, 143.8; ESI-MS+ m/z: Exact mass calculated for
C23H16N2S [M]+: 352.1034, found: 352.1036.
3-Bromo-5-phenylthiobenzo[a]phenazine (4d). Yellow solid, 0.157 g, yield 84%; mp 238–240; IR (KBr)
cm-1 1616 (w), 1591 (m), 1354 (m); 1H NMR (400 MHz, CDCl3) δ 7.47–7.49 (m, 3H), 7.55 (s, 1H), 7.63–
7.65 (m, 2H), 7.81–7.83 (m, 2H), 7.94 (d, J = 8.7 Hz, 1H), 8.14 (m, 1H), 8.27–8.30 (m, 1H), 8.56 (s, 1H),
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9.31 (d, J = 8.7 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 121.6, 124.9, 125.2, 125.8, 127.4, 128.9, 129.5,
129.7, 129.8, 130.1 (2), 130.4, 130.5, 131.6, 133.0, 134.7, 141.5, 141.8, 142.9, 143.1; ESI-MS+ m/z: Exact
mass calculated for C22H14BrN2S [M+H]+: 417.0062, found: 417.0065.
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3-Bromo-5-(2,4,6-trimethylphenylthio)benzo[a]phenazine (4e). Yellow solid, 0.164 g, yield 80%; mp
237–239 °C; IR (KBr) cm-1 2955 (m), 1590 (m), 1481 (m), 1354 (s); 1H NMR (400 MHz, CDCl3) δ 2.39,
(s, 3H), 2.44 (s, 6H), 7.03 (s, 1H), 7.12 (s, 2H), 7.78–78 (m, 2H), 7.95 (dd, J = 8.9, 1.8 Hz, 1H), 8.08–
8.10 (m, 1H), 8.26–8.28 (m, 1H), 8.62 (d, J = 1.4 Hz, 1H), 9.32 (d, J = 8.7 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 21.2, 21.5, 120.3, 123.7, 124.8, 127.0, 127.4, 128.7, 129.4, 129.6, 129.7, 130.1, 130.3, 131.4,
132.9, 140.6, 141.2, 141.4, 141.5, 143.0, 143.2, 144.1; ESI-MS+ m/z: Exact mass calculated for
C25H20BrN2S [M+H]+: 459.0530, found: 459.0537.
2-Methoxy-5-phenylthiobenzo[a]phenazine (4f). Yellow solid, 0.16 g, yield 76%; mp 224–226 °C; IR
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(KBr) cm-1 3053 (m), 2955 (m), 1608 (s), 1584 (m); H NMR (400 MHz, CDCl3) δ 4.13 (s, 3H), 7.40–
7.48 (m, 5H), 7.61–7.63 (m, 2H), 7.79–7.82 (m, 2H), 8.13–8.15 (m, 1H), 8.30–8.33 (m, 2H), 8.90 (d, J =
2.7 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 55.5, 106.8, 119.5, 122.5, 125.6, 126.3, 128.8, 129.1, 129.3,
129.6, 129.9, 130.2, 131.1, 132.7, 134.4, 141.3, 141.7, 142.4, 143.0, 143.7, 159.9; ESI-MS+ m/z: Exact
mass calculated for C23H17N2OS [M+H]+: 369.1062, found: 369.1061.
2-Methoxy-5-(4-methylphenylthio)benzo[a]phenazine (4g). Yellow solid, 0.16 g, yield 73%; mp 218–220;
IR (KBr) cm-1 3050 (m), 2958 (m), 1610 (m), 1583 (m); 1H NMR (400 MHz, CDCl3) δ 2.43 (s, 3H), 4.12
(s, 3H), 7.28 (d, J = 7.2 Hz, 3H), 7.41 (dd, J = 7.2, 2.7 Hz, 1H), 7.54 (d, J = 8.2 Hz, 2H), 7.77–7.80 (m,
2H), 8.11–8.13 (m, 1H), 8.29–8.31 (m, 2H), 8.78 (d, J = 2.7 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ
21.3, 55.8, 106.8, 119.4, 120.9, 125.9, 125.6, 126.6, 128.7, 129.0, 129.6, 130.1, 130.8, 132.6, 135.2,
139.7, 141.2, 141.5, 142.9, 143.6, 143.7, 159.8; ESI-MS+ m/z: Exact mass calculated for C24H19N2OS
[M+H]+: 383.1218, found: 383.1219.
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5-(N-Phenylamino)benzo[a]phenazine (4h).4a Yellow solid, 0.124 g, yield 56%; IR (KBr) cm-1 3420 (s),
1620 (m), 1590 (s); 1H NMR (500 MHz, CDCl3) δ 6.48 (s, 1H), 7.18 (t, J = 7.4 Hz, 1H), 7.38 (d, J = 7.4
Hz, 2H), 7.43 (t, J = 8.5 Hz, 2H), 7.53 (s, 1H), 7.71–7.79 (m, 2H), 7.84–7.88 (m, 2H), 8.09–8.11(m, 2H),
8.28 (dd, J = 8.3, 1.1 Hz, 1H), 9.51 (dd, J = 7.5, 2.3Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 104.5, 120.4,
122.6 (2), 124.1, 126.3, 127.8, 127.9, 128.2, 128.4, 129.6, 129.7 (2), 129.9, 131.9, 140.5, 140.7, 143.3,
143.7, 145.3.
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5-(N-Methyl-N-phenylamino)benzo[a]phenazine (4i). Yellow solid, 0.181 g, yield 78%; mp 140–142 °C;
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IR (KBr) cm-1 3056 (w), 1619 (w), 1587 (s); H NMR (400 MHz, CDCl3) δ 3.59 (s, 3H), 6.90–6.93 (m,
3H), 7.72 (t, J = 7.8 Hz, 2H), 7.62 (dt, J = 8.2, 1.4 Hz, 1H), 7.67 (dt, J = 8.0, 0.9 Hz, 1H), 7.79 (s, 1H),
7.83–7.86 (m, 2H), 7.89 (d, J = 8.2 Hz, 1H), 8.22–8.25 (m, 1H), 8.34–8.37 (m, 1H), 9.46 (dd, J = 8.2, 0.9
Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 41.8, 118.2, 120.4, 120.5, 125.4, 125.7, 127.9, 128.7, 128.7,
129.3, 129.3, 129.5, 130.1, 131.4, 132.2, 133.2, 141.5, 141.8, 144.5, 149.9, 150.3; ESI-MS+ m/z: Exact
mass calculated for C23H18N3 [M+H]+: 336.1501, found: 336.1502.
5-(N,N-Diphenylamino)benzo[a]phenazine (4j).4a Yellow solid, 0.11 g, yield 40%; IR (KBr) cm-1 1623
(w), 1590 (s), 1488 (s); 1H NMR (500 MHz, CDCl3) δ 7.06 (t, J = 7.4 Hz, 2H), 7.15 (d, J = 8.0 Hz, 4H),
7.28 (d, J = 8.0 Hz, 4H), 7.61 (dt, J = 6.8, 1.1 Hz, 1H), 7.67 (s, 1H), 7.77 (dt, J = 7.7, 1.1 Hz, 1H), 7.82–
7.85 (m, 2H), 8.01 (d, J = 8.0 Hz, 1H), 8.15–8.18 (m, 1H), 8.34–8.37 (m, 1H), 9.49 (dd, J = 8.0, 1.2 Hz,
1H); 13C NMR (125 MHz, CDCl3) δ 123.2, 123.7, 124.6, 125.7, 128.0, 128.7, 129.3, 129.4 (2), 129.6,
129.7, 130.1, 131.7, 132.4, 141.5, 141.9, 143.0, 144.3, 148.3, 140.1.
5-(4-(N,N-Diethylamino)phenyl)benzo[a]phenazine (4k). Yellow solid, 0.188 g, yield 72%; mp 143–145;
IR (KBr) cm-1 3055 (w), 2971 (m), 2933 (w), 1606 (s), 1518 (s); 1H NMR (400 MHz, CDCl3) δ 1.26 (t, J
= 6.9 Hz, 6H), 3.46 (q, J = 6.9 Hz, 4H), 6.84 (d, J = 8.7 Hz, 2H), 6.84 (d, J = 8.7 Hz, 2H), 7.52 (d, J = 8.7
Hz, 1H), 7.72 (t, J = 8.3 Hz, 1H), 7.79 (d, J = 7.8 Hz, 1H), 7.82–7.85 (m, 2H), 8.15(d, J = 7.8 Hz, 1H),
8.25–8.27 (m, 1H), 8.35–8.37 (m, 1H), 9.52 (d, J = 7.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 12.7,
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44.4, 111.2, 125.6, 125.8, 126.2, 127.3, 127.5, 128.9, 129.2, 129.4, 129.7, 129.8, 130.9, 131.5, 133.2,
141.7, 142.3, 143.1, 143.6, 145.7, 147.7; ESI-MS+ m/z: Exact mass calculated for C26H24N3 [M+H]+:
378.1970, found: 378. 1970.
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Acknowledgments. JNM is thankful to the CSIR, India for generous financial support. AKM gratefully
acknowledges the senior research fellowship from UGC, New Delhi.
†Dedication. This paper is dedicated to Prof. Hiryakkanavar Junjappa on the occasion of his 80th
birthday.
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Supporting Information. H and 13C NMR spectral reproductions for all the products of multistep
synthesis. This material is available free of charge via the internet at http://pubs.acs.org.
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