Electrophile-Induced Cyclization of 3-Alkynyl-2-arylquinoxalines: A Method for Benzo- and Naphthophenazine Synthesis

Article abstract of DOI:10.1002/ejoc.201600660

A facile synthesis of benzo[a]-, naphtho[1,2-a]- and naphtho[2,1-a]phenazines by ICl-promoted 6-endo-dig cyclization of 3-alkynyl-2-arylquinoxalines has been developed. The starting 3-alkynyl-2-arylquinoxalines were synthesized from 2,3-dichloroquinoxaline by two successive Sonogashira and Suzuki–Miyaura reactions. The method works well for 3-alkynyl-2-arylquinoxalines bearing various functional groups at the alkyne moiety. The arrangement and nature of the substituent in the 2-aryl fragment affect the regioselectivity of the cyclization. For the substrate of one particular type, namely 2-(4-methoxyphenyl)-3-(p-tolylethynyl)quinoxaline, the treatment with ICl leads to the alternative 5-endo-dig cyclization followed by demethylation of the methoxy group to give a spirocyclohexadienone derivative.

Full text of DOI:10.1002/ejoc.201600660

DOI: 10.1002/ejoc.201600660
Full Paper
Benzo[a]phenazines by Iodocyclization
Electrophile-Induced Cyclization of 3-Alkynyl-2-arylquinoxalines:
A Method for Benzo- and Naphthophenazine Synthesis
Anna V. Gulevskaya*[a]
Abstract: A facile synthesis of benzo[a]-, naphtho[1,2-a]- and moiety. The arrangement and nature of the substituent in the
naphtho[2,1-a]phenazines by ICl-promoted 6-endo-dig cycliza- 2-aryl fragment affect the regioselectivity of the cyclization. For
tion of 3-alkynyl-2-arylquinoxalines has been developed. The the substrate of one particular type, namely 2-(4-methoxy-
starting 3-alkynyl-2-arylquinoxalines were synthesized from 2,3- phenyl)-3-(p-tolylethynyl)quinoxaline, the treatment with ICl
dichloroquinoxaline by two successive Sonogashira and Suzuki– leads to the alternative 5-endo-dig cyclization followed by de-
Miyaura reactions. The method works well for 3-alkynyl-2-aryl- methylation of the methoxy group to give a spirocyclohexadi-
quinoxalines bearing various functional groups at the alkyne enone derivative.
Introduction
The phenazine core is an integral part of many biologically ac-
tive compounds, including more than 100 natural antibiotics,
produced by Pseudomonas, Streptomyces, marine and other
microorganisms.[1a] Antibiotic, antitumor, antimalarial and anti-
parasitic properties of phenazines are well documented.[1a–1i]
The biological activity of phenazines is based on their ability for
intercalation, inhibition of topoisomerases and radical oxidation
processes, transfer of electrons in the process of methanogene-
sis and so on.
The most general approaches for the synthesis of phen-
azines, including condensed ones, consist of (Scheme 1):[1a]
(i) base-catalyzed thermal condensation of anilines with nitro-
benzenes (Wohl–Aue method),[1j] (ii) fusing of two molecules of
4-substituted nitrosobenzene under acidic conditions (Bamber-
ger–Ham method),[1k] (iii) dehydrative condensation of benzo-
furoxanes with phenols (Beirut reaction),[1l] (iv) condensation of
ortho-quinones (sometimes in situ generated) with benzene-
1,2-diamines,[1m] and (v) condensation of 2-halonitrobenzenes
with 2-bromoanilines by two sequential Pd-catalyzed Buch-
wald–Hartwig arylamination reactions.[1n] The majority of the
known methods have some limitations due to the arrangement
and the electronic nature of substituents in the starting rea-
gents. The low output of products and rather harsh reaction
conditions are other drawbacks in the existing protocols. Cur-
rently, catalytic methods for phenazine synthesis, based on the
Buchwald–Hartwig reactions, seem to be the most effective.
The development of new strategies to enable the preparation
of phenazines therefore remains of major interest.
Scheme 1. Synthetic methods for the preparation of phenazines.
Some years ago, the electrophile-induced carbocyclization
of 2-(1-alkynyl)biphenyls to phenanthrene derivatives had been
reported (Scheme 2).[2] Despite tremendous synthetic potential
of this type of cyclization its other applications are still lim-
ited.[3]
From this and following our interest in quinoxalines[4a–4d]
and phenazines[4e] we reasoned that the analogous reaction of
3-alkynyl-2-arylquinoxalines 1 with electrophiles could result in
the formation of benzo[a]phenazine derivatives 2 (Scheme 3).
Herein, we wish to report on the results of this approach
allowing to synthesize benzo[a]-, naphtho[1,2-a]- and naphtho-
[2,1-a]phenazines in a simple and convenient way.
[a] Department of Chemistry, Southern Federal University,
Zorge str., 7 Rostov-on-Don 344090, Russian Federation
E-mail: agulevskaya@sfedu.ru
http://www.sfedu.ru
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/ejoc.201600660.
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phenylacetylene gave the target product in low yield.[5g] Ynedi-
ones with π-excessive hetaryl substituents were mostly used in
method (ii), though being modified the method also enables
the introduction of electroneutral aryl substituents (phenyl,
mesityl) at position 2 of 3-alkynyl-2-arylquinoxalines.[5f] The
best of these protocols, e.g. cyclization of ortho-phenylenedi-
amines with terminal alkynes, strongly depends on the catalyst.
For example, the use of the Cu(OAc)2/Cs2CO3/DMAP/toluene
system led to complicated product compositions and formation
of isomeric 3-alkynyl-2-arylquinoxalines when using substituted
ortho-phenylenediamines.[5a] CuCl[5b] and Fe3O4@Cu2O-graph-
ene oxide nanocomposite[5b] catalysts did not give isomers.
However, this method does not allow the preparation of 3-alk-
ynyl-2-arylquinoxalines with different substituents at the triple
bond and in position 2 of the quinoxaline ring.
We suggested that the desired 3-alkynyl-2-arylquinoxalines
could be obtained from available 2,3-dichloroquinoxaline[6]
through a Sonogashira reaction/Suzuki–Miyaura coupling or re-
verse synthetic sequence. We chose the Sonogashira reaction/
Suzuki–Miyaura coupling way, because it was reported that the
Suzuki coupling of 2,3-dichloroquinoxaline with phenylboronic
acid (1.2 equiv.) produced a hardly separable mixture of 2-
chloro-3-phenylquinoxaline (50 %) and 2,3-diphenylquinoxaline
(20 %).[7] Another known method for 3-aryl-2-chloroquinoxal-
ines consists of the AlCl3-induced arylation of 2,3-dichloroquin-
oxaline.[8] Unfortunately, it allows to introduce π-excessive het-
aryl or aryl substituents only.
Scheme 2. Electrophile-induced cyclization of 2-(1-alkynyl)biphenyls to phen-
anthrenes.
Scheme 3. Strategy for the synthesis of benzo[a]phenazines.
3-Alkynyl-2-chloroquinoxalines 5a–c were readily prepared
by the Sonogashira reaction of 2,3-dichloroquinoxaline 3 with
arylacetylenes 4a–c using the Pd(PPh3)2Cl2/CuI/iPr2NH/DMSO
catalytic system (Scheme 5). The yields of this process range
from 69 % to 88 % for arylacetylenes with both electron-with-
drawing and electron-releasing groups.
Results and Discussion
We began our study by preparing 3-alkynyl-2-arylquinoxalines
1. Three methods for their synthesis have been described previ-
ously (Scheme 4): (i) transition-metal-catalyzed cyclization of
ortho-phenylenediamines with terminal alkynes,[5a–5c] (ii) cycli-
zation of ynediones and ortho-phenylenediamines in the
presence of acetic acid,[5d–5f] and (iii) Sonogashira coupling of
4-(3-chloroquinoxalin-2-yl)benzene-1,3-diol with phenylacetyl-
ene.[5g]
Scheme 5. Synthesis of 3-alkynyl-2-chloroquinoxalines.
Coupling of 3-alkynyl-2-chloroquinoxalines 5a–c with aryl-
boronic acids by using the Pd(PPh3)4/K3PO4/THF catalytic sys-
tem under reflux for 9–10 h afforded the desired 3-alkynyl-2-
arylquinoxalines 1a–k in 66–88 % yields (Table 1). The reaction
was tolerant to both electron-withdrawing and electron-donat-
ing groups in the starting compounds. The nature and arrange-
ment of the substituent in the used arylboronic acid has a
greater influence on the yield. Taking into account that the bor-
onic acid is formally a nucleophilic component in the Suzuki
reaction, the highest yield of the coupled product 1d with
4-methoxyphenylboronic acid (Table 1, Entry 4) looks quite
Scheme 4. Synthetic methods for the preparation of 3-alkynyl-2-arylquinoxal-
ines.
All these approaches have some limitations. The Sonogashira logical. Apparently, some decrease in the yields with meta-
coupling of 4-(3-chloroquinoxalin-2-yl)benzene-1,3-diol with substituted arylboronic acids (Table 1, Entries 3, 5, 9, 11) and
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naphthylboronic acids (Table 1, Entries 6 and 7) is due to steric gation of the reaction time resulted in only a slight increase of
reasons.
the yield of 2a (Table 2, Entry 3). Thus, our optimized reaction
conditions employ 0.2 mmol of 1 and 1.2 equiv. of ICl in dry
CH2Cl2 at –20 °C.
Table 1. Synthesis of 3-alkynyl-2-arylquinoxalines.
With this protocol in hand, we examined the substrate scope
of this transformation. 3-[(4-Methoxyphenyl)ethynyl]-2-phenyl-
quinoxaline (1j) worked smoothly to afford benzophenazine 2c
in 66 % yields (Table 2, Entry 6). It should be noted that the
direct electrophilic substitution to the electron-rich 4-methoxy-
phenyl fragment of 1j does not appear to be competitive with
iodocyclization. At the same time, alkyne 1h with the electron-
withdrawing trifluoromethyl group gave 2d in 38 % yield, even
after 72 h of reaction time (Table 2, Entry 7).
We were pleased to find that 2-(naphthalen-2-yl)-3-(p-tolyl-
ethynyl)quinoxaline (1g) afforded the cyclization product 2e in
86 % yield (Scheme 6). Changing the naphthalen-2-yl group of
1g to the naphthalen-1-yl group of 1f dramatically decreased
the yield to 47 % (Scheme 6). This agrees with the well-known
fact that electrophilic attack on the position ꢀ of the naphthal-
ene ring proceeds more difficult than on the C(α) atom.
Entry
R1
Ar
Product
Yield [%]
1
2
3
4
5
6
7
8
9
Me
Me
Me
Me
Me
Me
Me
CF3
CF3
MeO
MeO
Ph
p-Tol
m-Tol
1a
1b
1c
1d
1e
1f
1g
1h
1i
82
85
72
88
66
71
71
80
70
75
79
4-MeOC6H4
3-OHCC6H4
naphthalen-1-yl
naphthalen-2-yl
Ph
m-Tol
Ph
m-Tol
10
11
1j
1k
To explore the feasibility of the above electrophilic cycliza-
tion strategy, the reactions of 2-phenyl-3-(p-tolylethynyl)quinox-
aline (1a) with various electrophiles (ICl, Br2, NCS) in dry CH2Cl2
at room temperature for 24 h were been studied (Table 2). The
expected 6-iodo-5-p-tolylbenzo[a]phenazine (2a) was obtained
in 62 % yield when ICl (1.2 equiv.) was used as electrophile
(Table 2, Entry 1). However, the reaction was not selective pro-
ducing small amounts of side-products (presumably 1,2-ad-
ducts formed by ICl addition to the C≡ C bond and oligomeriza-
tion products). The use of bromine as electrophile led to a com-
plicated reaction mixture. From this we were able to isolate the
desired product 2b in only 15 % yield (Table 2, Entry 4). NCS did
not react noticeably with 2-phenyl-3-(p-tolylethynyl)quinoxaline
(1a) even for 6 d (Table 2, Entry 5).
Table 2. Electrophile-induced cyclization of 3-alkynyl-2-phenylquinoxalines.
Scheme 6. Synthesis of naphtho[2,1-a]- and naphtho[1,2-a]phenazines.
The structure of 8-iodo-7-p-tolylnaphtho[1,2-a]phenazine
(2f) was proved by X-ray single crystal study (Figure 1). Com-
pound 2f has a helicene-like structure with an interplanar angle
between the rings A and D of ca. 14°. For comparison, the inter-
planar angle between the two terminal rings of [4]helicene
(benzo[c]phenanthrene) is equal to 26.7°.[9] To date, only one
structure containing the 1-aza-[4]helicene fragment was regis-
tered in the CCDC database, namely, 14-aza-9-methyldibenzo-
[f,pqr]picene. The interplanar angle between the two terminal
rings of this fragment in the last molecule is 20.4°.[10] Thus, 1-
aza-[4]helicenes are not so twisted as [4]helicene. One can sug-
gest that this originates from the existence of C–H···N hydrogen
bonding in 1-aza-[4]helicenes. The short intramolecular contact
H(1)···N(14) (2.195 Å) in the crystal of 2f strongly supports this
opinion. Apparently, such kind of interaction is also realized in
Entry
R1
E+X–
Reaction conditions
Product
Yield [%]
1
2
3
4
5
6
7
Me
Me
Me
Me
Me
ICl
ICl
ICl
Br2
NCS
ICl
r.t., 24 h
2a
2a
2a
2b
–
62
63
67
15
–
–20 to –18 °C, 24 h
–20 to –18 °C, 72 h
r.t., 24 h
r.t., 6 d
–20 to –18 °C, 48 h
–20 to –18 °C, 72 h
MeO
CF3
2c
2d
66
38
ICl
Next, we carried out the reaction of 1a with ICl in CH2Cl2 at solution since the signal of the H(1) proton of 2f in the 1H NMR
–20 °C for 24 h in order to increase the selectivity. However, spectrum appeared at an extremely low field of δ = 11.1 ppm.
benzophenazine 2a was obtained with the same yield (Table 2, This observation is consistent with the remarkable deshielding
Entry 2). Besides 2a, the reaction mixture contained the starting of the H(12) proton of a helicene-like naphtho[2,1-h]quinoline
material and again some other inseparable by-products. Prolon- (δ = 11.25 ppm).[11] For comparison, the chemical shifts of the
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Figure 1. ORTEP plot of the X-ray crystal structure of 2f.
H(1) protons of other compounds 2 range between δ = 9.5 ppm azine 2k and iodomethyl derivative 2l in 43 % total yield
and δ = 9.7 ppm.
(Scheme 8). The ratio of these products strongly depended on
the reaction temperature. When the cyclization was carried out
at –20 °C for 48 h, a ca. 4.3:1 mixture of 2k/2l was obtained
(1H NMR spectroscopic data). The room-temperature protocol
provided compounds 2k and 2l in a ca. 2:1 ratio. We were
unable to separate these compounds because of the similarity
of their retention factors. However, short-term heating of their
mixture with an excess of morpholine allowed to convert com-
pound 2l into the aminomethyl derivative 2m. Fortunately, re-
tention factors of compounds 2k and 2m were significantly dif-
ferent allowing to separate them. Evidently, the formation of
compound 2l is the result of iodination of 3-methyl-
benzo[a]phenazine (2k). The exact mechanism (radical or ionic)
of this transformation is not clear. However, there are some
published examples of iodination of alkylbenzenes in the alkyl
chain by tert-butyl hypoiodate.[14]
To the best of our knowledge, only two derivatives of
naphtho[1,2-a]phenazine have been described in literature: 8-
isopropyl-4-methylnaphtho[1,2-a]phenazine[12a] and 2-meth-
oxynaphtho[1,2-a]phenazin-7-ol[12b] prepared by condensation
of ortho-phenylenediamine with 2-isopropyl-8-methylphen-
anthrene-3,4-dione and 3,6-dimethoxyphenanthrene-1,4-dione,
respectively. Data on the synthesis of naphtho[2,1-a]phenazines
are also very limited.[13]
Encouraged by the success with the aforementioned sub-
strates we also investigated the cyclizations of acetylenes 1b–
c,i in which various substituents were placed in the 2-phenyl
fragment. Treatment of 3-(p-tolylethynyl)-2-m-tolylquinoxaline
(1c) with ICl at –20 °C for 48 h afforded a mixture of isomeric
cyclization products 2g and 2h (Scheme 7) in 80 % total yield
and in a 2:1 ratio (1H NMR spectroscopic data). The predomi-
nant isomer 2g evidendly arose from cyclization onto the less
hindered position 4 of the m-tolyl moiety. A similar result was
obtained using 1i as a substrate, though the total yield of regio-
isomers 2i and 2j was lower (58 %).
Scheme 8. ICl-induced cyclizations of 3-(p-tolylethynyl)-2-p-tolylquinoxaline
1b.
When substrate 1d containing a p-methoxyphenyl fragment
was treated with iodochloride at –20 °C for 48 h, spirocyclic
compound 8 was obtained as the only product in 88 % yield
(Scheme 9). The distinct behavior of compound 1d may be at-
tributed to the directing effect of the p-methoxy group to favor
5-endo-dig cyclization of intermediate 6 instead of the usual 6-
endo-dig process. Thus formed spirocycle 7 underwent the SN2
demethylation producing compound 8. The structure of 3′-
iodo-2′-p-tolylspiro[cyclohexa-2,5-diene-1,1′-cyclopenta[b]quin-
oxalin]-4-one (8) was proved by X-ray single crystal study (Fig-
Scheme 7. ICl-induced cyclizations of 3-alkynyl-2-m-tolylquinoxalines 1c,i.
Substrate 1b, containing the 2-p-tolyl group, underwent ure S1). Previously, ICl-induced ipso-cyclization was reported
iodocyclization to afford a mixture of the desired benzophen- for 4′-methoxy-2-alkynylbiphenyls,[3d] 4-(p-methoxyaryl)-1-alk-
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ynes,[15a] 1-[4′-methoxy-1,1′-biphenyl-2-yl]alkynones,[15b] bis(4-
methoxybenzylthio)acetylenes,[15c] N-arylpropiolamides, and
phenyl 3-phenylpropiolates.[15d]
8.0 Hz, 2 H), 7.60 (d, J = 8.0 Hz, 2 H), 7.73–7.80 (m, 2 H), 7.96–8.02
(m, 1 H), 8.05–8.12 (m, 1 H) ppm. 13C NMR (62.9 MHz, CDCl3): δ =
21.7, 85.2, 97.7, 118.2, 128.2, 128.8, 129.4, 130.6, 131.2, 132.4, 138.8,
140.2, 140.6, 140.7, 148.0 ppm. IR (KBr): ν = 2212 (C≡ C) cm–1. MS:
˜
m/z (%) = 280 (33) [M(37Cl)]+, 278 (100) [M(35Cl)]+, 243 (68).
C17H11ClN2 (278.74): calcd. C 73.25, H 3.98, N 10.05; found C 73.41,
H 4.05, N 9.83.
2-Chloro-3-[(4-methoxyphenyl)ethynyl]quinoxaline (5b): Yield
204 mg (69 %), yellow needles with m.p. 147–149 °C (iPrOH). 1H
NMR (250 MHz, CDCl3): δ = 3.84 (s, 3 H), 6.92 (d, J = 8.9 Hz, 2 H),
7.65 (d, J = 8.9 Hz, 2 H), 7.72–7.79 (m, 2 H), 7.95–8.01 (m, 1 H), 8.04–
8.11 (m, 1 H) ppm. 13C NMR (62.9 MHz, CDCl3): δ = 55.4, 84.9, 98.0,
113.2, 114.3, 128.2, 128.8, 130.6, 131.1, 134.2, 138.9, 140.1, 140.8,
147.9, 161.1 ppm. IR (KBr): ν = 2212 (C≡ C) cm–1. MS: m/z (%) = 296
˜
(23) [M(37Cl)]+, 294 (100) [M(35Cl)]+, 259 (44), 244 (12), 216 (24), 114
(11), 102 (12), 76 (15). C17H11ClN2O (294.74): calcd. C 69.28, H 3.76,
N 9.50; found C 69.06, H 3.90, N 9.33.
2-Chloro-3-{[4-(trifluoromethyl)phenyl]ethynyl}quinoxaline
(5c): Yield 292 mg (88 %), off-white needles with m.p. 138–140 °C
(iPrOH). 1H NMR (250 MHz, CDCl3): δ = 7.67 (d, J = 8.3 Hz, 2 H),
7.78–7.82 (m, 4 H), 7.98–8.05 (m, 1 H), 8.07–8.12 (m, 1 H) ppm. 13C
NMR (62.9 MHz, CDCl3): δ = 87.2, 94.8, 123.7 (q, J = 272.5 Hz), 125.0,
125.5 (q, J = 3.8 Hz), 128.3, 128.9, 130.8, 131.3, 131.8, 132.7, 137.9,
Scheme 9. Electrophile-induced cyclization of 2-(4-methoxyphenyl)-3-(p-tolyl-
ethynyl)quinoxaline (1d).
140.5, 140.7, 147.9 ppm. IR (KBr): ν = 2215 (C≡ C) cm–1. MS: m/z
˜
(%) = 334 (32) [M(37Cl)]+, 332 (98) [M(35Cl)]+, 297 (100). C17H8ClF3N2
(332.71): calcd. C 61.37, H 2.42, N 8.42; found C 61.15, H 2.49, N
8.23.
Conclusions
We have achieved a facile synthesis of benzo[a]-, naphtho[1,2-
a]- and naphtho[2,1-a]phenazines by ICl-promoted cyclization
of 3-alkynyl-2-arylquinoxalines under very mild conditions. The
starting 3-alkynyl-2-arylquinoxalines were synthesized from 2,3-
dichloroquinoxaline in two steps by the Sonogashira reaction/
General Procedure for the Synthesis of 3-Alkynyl-2-arylquinox-
alines 1: 3-Alkynyl-2-chloroquinoxaline 5 (0.5 mmol), arylboronic
acid (0.6 mmol), Pd(PPh3)4 (15 mg, 0.013 mmol), K3PO4 (212 mg,
1.0 mmol) and dry THF (5 mL) were stirred and refluxed under
argon for 9 h. The reaction mixture was then concentrated to dry-
Suzuki–Miyaura coupling. The methodology accommodates ness. The residue was treated with water (30 mL) and extracted
with CH2Cl2 (3 × 10 mL). The extract was dried with Na2SO4 and
purified by flash column chromatography on silica gel (3.5 × 40 cm)
with CH2Cl2 as the eluent. The fraction with Rf = 0.7–0.8 was recov-
ered starting compound 5. The next yellowish fraction with Rf =
0.3–0.5 gave 3-alkynyl-2-arylquinoxaline 1 (see Table 1 for yields).
The product was crystallized from iPrOH.
various functional groups and affords little-known benzo- and
naphthophenazines in good yields. For the substrate of one
particular type, namely 2-(4-methoxyphenyl)-3-(p-tolylethynyl)-
quinoxaline, it was found that the ICl treatment leads to ipso-
cyclization to give a spirocyclohexadienone derivative. It is also
obvious that the presence of the iodo and alkynyl groups in
the synthesized phenazines allows further modification of these
molecules.
2-Phenyl-3-(p-tolylethynyl)quinoxaline (1a): Colorless needles
with m.p. 139–141 °C. 1H NMR (250 MHz, CDCl3): δ = 2.33 (s, 3 H,
Me), 7.12 (d, J = 8.0 Hz, 2 H, p-Tol), 7.36 (d, J = 8.0 Hz, 2 H, p-Tol),
7.52–7.59 (m, 3 H), 7.72–7.76 (m, 2 H), 8.07–8.14 (m, 4 H) ppm. 13C
NMR (62.9 MHz, CDCl3): δ = 21.7, 88.0, 95.7, 118.7, 128.2, 128.7,
129.2(8), 129.3(2), 129.7, 129.8, 130.3, 130.6, 132.1, 137.7, 138.3,
Experimental Section
140.1, 140.7, 141.0, 155.1 ppm. IR (KBr): ν = 2212 (C≡ C) cm–1. MS:
General Procedure for the Synthesis of 3-Alkynyl-2-chloroquin-
oxalines 5: A mixture of 2,3-dichloroquinoxaline 3 (199 mg,
1.0 mmol), Pd(PPh3)2Cl2 (10 mg, 0.014 mmol), CuI (2 mg,
0.01 mmol), iPr2NH (1 mL), and DMSO (2 mL) was stirred under
argon at room temperature for 20 min. Then, a solution of the corre-
sponding alkyne (1.1 mmol) in iPr2NH (1.5 mL) was added dropwise.
The reaction mixture was stirred at room temperature for 5–6 h,
then concentrated without heating to remove iPr2NH, treated with
H2O (100 mL) and extracted with CHCl3 (2 × 20 mL). The extract
was dried with Na2SO4, and the solvents were evaporated to dry-
ness. The residue was purified by flash column chromatography on
silica gel (3.5 × 40 cm) with CH2Cl2 as the eluent. The colorless frac-
tion with Rf = 0.7–0.8 and blue violet fluorescence gave 5.
˜
m/z (%) = 320 (100) [M+], 305 (26), 178 (13), 140 (15), 76 (11).
C23H16N2 (320.39): calcd. C 86.22, H 5.03, N 8.74; found C 86.45, H
5.19, N 8.90.
2-p-Tolyl-3-(p-tolylethynyl)quinoxaline (1b): Colorless solid with
m.p. 159–161 °C (ref.[5a] light yellow solid with m.p. 112–114 °C). 1H
NMR (250 MHz, CDCl3): δ = 2.36 (s, 3 H, Me), 2.46 (s, 3 H, Me), 7.15
(dd, J = 8.5, 0.6 Hz, 2 H, p-Tol), 7.35 (dd, J = 8.5, 0.6 Hz, 2 H, p-Tol),
7.41 (m, 2 H, p-Tol), 7.70–7.77 (m, 2 H), 8.03 (m, 2 H, p-Tol), 8.07–
8.13 (m, 2 H) ppm. 13C NMR (62.9 MHz, CDCl3): δ = 21.5, 21.7, 88.2,
95.3, 118.8, 128.7, 128.9, 129.2(6), 129.2(7), 129.7, 130.0, 130.5, 132.1,
134.9, 138.2, 139.8, 140.0, 140.8, 140.9, 154.9 ppm. IR (KBr): ν = 2214
˜
(C≡ C) cm–1. MS: m/z (%) = 334 (100) [M+], 319 (71), 216 (16), 192
(40), 165 (37), 159 (40), 140 (61), 116 (29), 89 (26), 76 (43). C24H18N2
(334.42): calcd. C 86.20, H 5.43, N 8.38; found C 86.17, H 5.25, N
8.21.
2-Chloro-3-(p-tolylethynyl)quinoxaline (5a): Yield 223 mg (80 %),
colorless needles with m.p. 172–174 °C (EtOH) (ref.[16] light brown
1
semi solid). H NMR (250 MHz, CDCl3): δ = 2.39 (s, 3 H), 7.12 (d, J =
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2-m-Tolyl-3-(p-tolylethynyl)quinoxaline (1c): Colorless prisms
with m.p. 116–117 °C. 1H NMR (250 MHz, CDCl3): δ = 2.31 (s, 3 H,
Me), 2.46 (s, 3 H, Me), 7.10 (d, J = 7.9 Hz, 2 H), 7.31–7.46 (m, 4 H),
272.4 Hz), 125.4 (q, J = 3.8 Hz), 128.2, 128.9, 129.4, 129.7, 129.9,
130.5, 130.9, 131.1, 131.4, 132.3, 137.5, 137.6, 140.9, 141.0,
155.2 ppm. IR (KBr): ν = 2220 (C≡ C) cm–1. MS: m/z (%) = 374 (100)
˜
7.67–7.74 (m, 2 H), 7.91 (dm, J = 8.6 Hz, 2 H), 8.06–8.13 (m, 2 H) [M+], 305 (11), 179 (10). C23H13F3N2 (374.36): calcd. C 73.79, H 3.50,
ppm. 13C NMR (62.9 MHz, CDCl3): δ = 21.6, 21.7, 88.2, 95.6, 118.7,
N 7.48; found C 73.92, H 3.73, N 7.23.
126.9, 128.0, 128.7, 129.2, 129.3, 130.2, 130.3, 130.4, 130.5, 132.1 (2
2-m-Tolyl-3-{[4-(trifluoromethyl)phenyl]ethynyl}quinoxaline
(1i): Colorless needles with m.p. 158–159 °C. 1H NMR (250 MHz,
CDCl3): δ = 2.47 (s, 3 H, Me), 7.35 (d, J = 7.8 Hz, 1 H), 7.44 (t, J =
7.6 Hz, 1 H), 7.54–7.63 (m, 4 H), 7.75–7.82 (m, 2 H), 7.86–7.89 (m, 2
H), 8.10–8.18 (m, 2 H) ppm. 13C NMR (62.9 MHz, CDCl3): δ = 21.6,
90.3, 92.9, 123.7 (q, J = 272.4 Hz, CF3), 125.4 (q, J = 3.8 Hz, C-CF3),
126.8, 128.0, 128.8, 129.4, 130.3, 130.4, 130.6, 130.8, 131.0, 131.4,
C), 137.6, 137.8, 138.3, 140.0, 140.7, 141.0, 155.2 ppm. IR (KBr): ν =
˜
2210 (C≡ C) cm–1. MS: m/z (%) = 334 (86) [M+], 333 (100), 319 (89),
192 (10), 165 (11), 159 (12), 140 (15). C24H18N2 (334.42): calcd. C
86.20, H 5.43, N 8.38; found C 86.39, H 5.28, N 8.43.
2-(4-Methoxyphenyl)-3-(p-tolylethynyl)quinoxaline (1d): Light
yellow needles with m.p. 122–124 °C. 1H NMR (250 MHz, CDCl3):
δ = 2.36 (s, 3 H, Me), 3.89 (s, 3 H, OMe), 7.06 (dm, J = 8.9 Hz, 2 H),
7.15 (d, J = 8.0 Hz, 2 H), 7.42 (d, J = 8.0 Hz, 2 H), 7.69–7.76 (m, 2 H),
8.05–8.15 (m, 4 H) ppm. 13C NMR (62.9 MHz, CDCl3): δ = 21.7, 55.5,
88.2, 95.3, 113.6, 118.7, 128.7, 129.1, 129.3 (2 C), 129.9, 130.1, 130.5,
132.3, 137.4, 137.5, 138.0, 140.9, 141.0, 155.3 ppm. IR (KBr): ν = 2219
˜
(C≡ C) cm–1. MS: m/z (%) = 388 (89) [M+], 387 (100), 373 (37), 319
(33), 192 (40), 176 (13), 165 (41), 116 (31), 102 (19), 90 (29), 76 (83).
C24H15F3N2 (388.39): calcd. C 74.22, H 3.89, N 7.21; found C 74.02,
H 4.02, N 7.44.
131.3, 132.1, 138.1, 140.1, 140.8, 154.4, 161.0 ppm. IR (KBr): ν = 2212
˜
(C≡ C) cm–1. MS: m/z (%) = 350 (100) [M+], 335 (13), 319 (18), 307
(11), 166 (10), 140 (10). C24H18N2O (350.42): calcd. C 82.26, H 5.18,
N 7.99; found C 82.15, H 5.43, N 7.83.
2-[(4-Methoxyphenyl)ethynyl]-3-phenylquinoxaline (1j): Color-
less needles with m.p. 142–143 °C. 1H NMR (250 MHz, CDCl3): δ =
3.79 (s, 3 H, OMe), 6.84 (d, J = 8.8 Hz, 2 H), 7.40 (d, J = 8.8 Hz, 2 H),
7.53–7.59 (m, 3 H), 7.69–7.77 (m, 2 H), 8.06–8.12 (m, 4 H) ppm. 13C
NMR (62.9 MHz, CDCl3): δ = 55.3, 87.7, 95.8, 113.7, 114.2, 128.1,
128.6, 128.7, 129.3, 129.7, 130.2, 130.4, 133.8, 137.8, 138.5, 140.6,
3-[3-(p-Tolylethynyl)quinoxalin-2-yl]benzaldehyde (1e): Color-
less needles with m.p. 158–160 °C. 1H NMR (250 MHz, CDCl3): δ =
2.35 (s, 3 H, Me), 7.14 (d, J = 7.9 Hz, 2 H), 7.36 (d, J = 8.1 Hz, 2 H),
7.72 (t, J = 7.7 Hz, 1 H), 7.76–7.83 (m, 2 H), 8.06 (dm, J = 7.7 Hz, 1
H), 8.10–8.18 (m, 2 H), 8.41 (dm, J = 7.7 Hz, 1 H), 8.68 (t, J = 1.5 Hz,
1 H), 10.14 (s, 1 H, CH=O) ppm. 13C NMR (62.9 MHz, CDCl3): δ =
21.7, 87.6, 96.1, 118.3, 128.8, 128.9, 129.3, 129.4, 130.4, 130.7, 130.8,
131.3, 132.0, 135.6, 136.4, 137.8, 138.6, 140.3, 140.6, 141.2, 153.2,
141.1, 155.0, 160.7 ppm. IR (KBr): ν = 2202 (C≡ C) cm–1. MS: m/z
˜
(%) = 336 (100) [M+], 321 (26), 305 (10), 292 (28), 190 (15), 178 (24),
157 (13), 152 (12), 146 (11), 114 (23), 76 (21). C23H16N2O (336.39):
calcd. C 82.12, H 4.79, N 8.33; found C 81.95, H 4.93, N 8.45.
191.8 ppm. IR (KBr): ν = 1703 (C=O), 2208 (C≡ C) cm–1. MS: m/z (%) =
2-[(4-Methoxyphenyl)ethynyl]-3-m-tolylquinoxaline (1k): Yel-
˜
1
348 (79) [M+], 347 (100), 319 (30), 305 (11), 216 (11), 178 (16), 159
(11), 152 (14), 140 (35), 114 (12), 76 (37). C24H16N2O (348.40): calcd.
C 82.74, H 4.63, N 8.04; found C 82.55, H 4.72, N 8.19.
lowish needles with m.p. 93–95 °C. H NMR (250 MHz, CDCl3): δ =
2.54 (s, 3 H, Me), 3.88 (s, 3 H, OMe), 6.92 (d, J = 8.9 Hz, 2 H), 7.31–
7.53 (m, 4 H), 7.77–7.85 (m, 2 H), 7.94–7.98 (m, 2 H), 8.16–8.20 (m,
2 H) ppm. 13C NMR (62.9 MHz, CDCl3): δ = 21.6, 55.3, 87.8, 95.8,
113.8, 114.2, 126.9, 128.0, 128.7, 129.3, 130.2, 130.3, 130.4, 130.5,
133.8, 137.7, 137.8, 138.5, 140.6, 141.0, 155.2, 160.7 ppm. IR (KBr):
2-(Naphthalen-1-yl)-3-(p-tolylethynyl)quinoxaline (1f): Colorless
1
needles with m.p. 146–147 °C. H NMR (250 MHz, CDCl3): δ = 2.25
ν = 2206 (C≡ C) cm–1. MS: m/z (%) = 350 (32) [M+], 335 (18), 111 (14),
(s, 3 H, Me), 6.76 (dm, J = 8.1 Hz, 2 H), 6.96 (dm, J = 7.0 Hz, 2 H),
7.42 (ddd, J = 8.2, 6.8, 1.4 Hz, 1 H), 7.51 (ddd, J = 8.2, 6.8, 1.4 Hz, 1
H), 7.63 (dd, J = 8.2, 7.1 Hz, 1 H), 7.71–7.87 (m, 4 H), 7.96 (dd, J =
8.4, 1.0 Hz, 1 H), 8.03 (d, J = 8.2 Hz, 1 H), 8.13–8.24 (m, 2 H) ppm.
13C NMR (62.9 MHz, CDCl3): δ = 21.6, 87.6, 96.6, 118.3, 125.2, 125.7,
126.2, 126.7, 128.2, 128.4, 128.9, 129.0, 129.4, 129.8, 130.6, 130.7,
131.6, 132.0, 133.7, 135.7, 139.9, 140.3, 140.5, 141.4, 156.2 ppm. IR
˜
97 (24), 85 (49), 57 (100). C24H18N2O (350.42): calcd. C 82.26, H 5.18,
N 7.99; found C 82.06, H 5.31, N 8.23.
General Procedure for the Synthesis of Benzo- and Naphtho-
phenazines 2: To a cooled (–20 °C) solution of 2-alkynyl-3-arylquin-
oxaline 1 (0.2 mmol) in dry CH2Cl2 (3 mL) was added a cooled
(–20 °C) solution of ICl (39 mg, 0.24 mmol) in dry CH2Cl2 (2 mL).
The reaction mixture was kept at –20 to –18 °C for 48 h. Then the
reaction mixture was treated with saturated aqueous Na2S2O3
(5 mL) and extracted with CH2Cl2 (2 × 5 mL). The extract was dried
with Na2SO4 and purified by flash column chromatography on silica
gel (2.5 × 40 cm) with CHCl3 as the eluent. The first yellow or bright
yellow fraction with Rf = 0.9 gave compound 2 (see Table 2 for
yields). Product 2 was crystallized from iPrOH.
(KBr): ν = 2210 (C≡ C) cm–1. MS: m/z (%) = 370 (51) [M+], 369 (100),
˜
355 (34), 228 (27), 202 (10), 184 (27), 153 (38), 140 (29), 126 (22),
114 (11), 77 (11). C27H18N2 (370.45): calcd. C 87.54, H 4.90, N 7.56;
found C 87.32, H 4.67, N 7.39.
2-(Naphthalen-2-yl)-3-(p-tolylethynyl)quinoxaline (1g): Colorless
1
needles with m.p. 157–158 °C. H NMR (250 MHz, CDCl3): δ = 2.33
(s, 3 H, Me), 7.10 (d, J = 8.0 Hz, 2 H, p-Tol), 7.35 (d, J = 8.0 Hz, 2 H,
p-Tol), 7.54–7.60 (m, 2 H), 7.75–7.80 (m, 2 H), 7.91–7.98 (m, 2 H),
8.01 (d, J = 8.7 Hz, 1 H), 8.13–8.18 (m, 2 H), 8.22 (dd, J = 8.5, 1.8 Hz,
1 H), 8.69 (d, J = 1.0 Hz, 1 H) ppm. 13C NMR (62.9 MHz, CDCl3): δ =
21.7, 88.3, 95.8, 118.6, 126.5, 127.0, 127.1, 127.8, 128.7, 128.8, 129.2,
129.3, 129.4, 129.9, 130.3, 130.6, 132.1, 133.0, 133.9, 135.0, 138.4,
For the synthesis of 2b, bromine (38 mg, 0.24 mmol) was used
instead of ICl. The reaction was carried out at room temperature.
6-Iodo-5-p-tolylbenzo[a]phenazine (2a): Yellow solid with m.p.
256–258 °C. 1H NMR (250 MHz, CDCl3): δ = 2.51 (s, 3 H, Me), 7.25
(d, J = 7.8 Hz, 2 H, p-Tol), 7.47 (d, J = 7.8 Hz, 2 H, p-Tol), 7.45 (d, J =
8.4 Hz, 1 H), 7.58 (t, J = 7.5 Hz, 1 H), 7.79 (t, J = 7.5 Hz, 1 H), 7.88–
7.92 (m, 2 H), 8.38–8.43 (m, 2 H), 9.47 (d, J = 8.0 Hz, 1 H) ppm. 13C
NMR (62.9 MHz, CDCl3): δ = 21.5, 108.1, 125.6, 128.2, 128.5, 129.1,
129.3, 129.4, 129.6, 130.0, 130.3, 130.5, 131.1, 134.2, 138.0, 140.8,
141.6, 142.0, 142.4, 143.4, 151.1 ppm. UV/Vis: λmax (lg ε) = 277 sh
(4.56), 287 (4.62), 300 (4.64), 367 sh (3.98), 391 (4.10), 410 (4.08) nm
. MS: m/z (%) = 446 (100) [M+], 319 (56), 304 (19), 159 (27). C23H15IN2
140.1, 140.8, 141.0, 154.7 ppm. IR (KBr): ν = 2209 (C≡ C) cm–1. MS:
˜
m/z (%) = 370 (77) [M+], 369 (100), 355 (33), 228 (14), 177 (14), 153
(21), 140 (12). C27H18N2 (370.45): calcd. C 87.54, H 4.90, N 7.56; found
C 87.40, H 5.09, N 7.41.
2-Phenyl-3-{[4-(trifluoromethyl)phenyl]ethynyl}quinoxaline
(1h): Colorless needles with m.p. 173–175 °C. 1H NMR (250 MHz,
CDCl3): δ = 7.54–7.62 (m, 7 H), 7.74–7.82 (m, 2 H), 8.03–8.17 (m, 4
H) ppm. 13C NMR (62.9 MHz, CDCl3): δ = 90.2, 93.0, 123.7 (q, J =
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(446.29): calcd. C 61.90, H 3.39, N 6.28; found C 62.09, H 3.54, N
6.03.
(4.25), 321 (4.32), 379 sh (3.61), 404 (3.91), 425 (3.94), end absorp-
tion up to 470 nm. MS: m/z (%) = 496 (100) [M+], 369 (51), 354 (18),
184 (23). C27H17IN2 (496.35): calcd. C 65.34, H 3.45, N 5.64; found C
65.49, H 3.61, N 5.36.
6-Bromo-5-p-tolylbenzo[a]phenazine (2b): Yellow solid with m.p.
1
259–261 °C (decomp.). H NMR (250 MHz, CDCl3): δ = 2.52 (s, 3 H,
Synthesis of 6-Iodo-3-methyl-5-p-tolylbenzo[a]phenazine (2k)
and 4-[(6-Iodo-5-p-tolylbenzo[a]phenazin-3-yl)methyl]morph-
oline (2m): A solution of 2-p-tolyl-3-(p-tolylethynyl)quinoxaline (1b)
(80 mg, 0.24 mmol) and ICl (47 mg, 0.29 mmol) in dry CH2Cl2 (6 mL)
was kept at room temperature for 48 h. Then the reaction mixture
was treated with saturated aqueous Na2S2O3 (5 mL) and extracted
with CH2Cl2 (2 × 5 mL). The extract was dried with Na2SO4 and
purified by flash column chromatography on silica gel (2.5 × 40 cm)
with CHCl3 as the eluent. The first yellow fraction with Rf = 0.9 gave
50 mg of 6-iodo-3-methyl-5-p-tolylbenzo[a]phenazine (2k) and 6-
iodo-3-(iodomethyl)-5-p-tolylbenzo[a]phenazine (2l) as a 2:1 mix-
ture (1H NMR spectroscopic data). This mixture was heated with
morpholine (0.5 mL) for 2–3 min, and the solvents were evaporated
to dryness. The residue was purified by flash column chromatogra-
phy on silica gel (2.5 × 40 cm) with CHCl3 as the eluent. The first
yellow fraction with Rf = 0.9 gave 6-iodo-3-methyl-5-p-tolyl-
benzo[a]phenazine (2k) (28 mg, 25 %). The yellow fraction with Rf =
0.1 was “cut” from the column, eluted with iPrOH and additionally
purified by flash column chromatography on silica gel (2.5 × 15 cm)
with CH2Cl2/acetone (50:1) as the eluent. The yield of 4-[(6-iodo-
5-p-tolylbenzo[a]phenazin-3-yl)methyl]morpholine (2m) was 18 mg
(13 %).
Me), 7.30 (d, J = 7.9 Hz, 2 H, p-Tol), 7.40 (d, J = 7.9 Hz, 2 H, p-Tol),
7.46 (d, J = 8.1 Hz, 1 H), 7.60 (ddd, J = 8.1, 7.0, 1.3 Hz, 1 H), 7.78
(ddd, J = 8.1, 7.0, 1.2 Hz, 1 H), 7.86–7.94 (m, 2 H), 8.37–8.44 (m, 2
H), 9.46 (d, J = 8.1 Hz, 1 H) ppm. 13C NMR (62.9 MHz, CDCl3): δ =
21.5, 123.7, 125.6, 127.9, 128.0, 129.3(3), 129.3(6), 129.4, 129.8, 130.0,
130.4, 130.5, 130.6, 134.2, 136.7, 138.0, 140.8, 142.1, 142.2, 143.0,
145.6 ppm. UV/Vis: λmax (lg ε) = 285 (4.52), 297 (4.49), 368 sh (3.84),
390 (3.97), 411 (3.97) nm. MS: m/z (%) = 400 (100) [M(81Br)]+, 398
(99) [M(79Br)]+, 319 (53), 317 (35), 304 (45), 159 (39). C23H15BrN2
(399.29): calcd. C 69.19, H 3.79, N 7.02; found C 69.13, H 3.93, N
6.87.
6-Iodo-5-(4-methoxyphenyl)benzo[a]phenazine (2c): Yellow
1
solid with m.p. 230–232 °C. H NMR (250 MHz, CDCl3): δ = 3.93 (s,
3 H, OMe), 7.12 (d, J = 8.7 Hz, 2 H), 7.28 (d, J = 8.7 Hz, 2 H), 7.48 (d,
J = 8.1 Hz, 1 H), 7.58 (ddd, J = 8.0, 7.0, 1.3 Hz, 1 H), 7.79 (ddd, J =
8.0, 7.0, 1.2 Hz, 1 H), 7.86–7.93 (m, 2 H), 8.38–8.43 (m, 2 H), 9.47 (dd,
J = 8.0, 0.9 Hz, 1 H) ppm. 13C NMR (62.9 MHz, CDCl3): δ = 55.4,
108.7, 114.0, 125.6, 128.1, 128.5, 129.1, 129.6, 130.0, 130.3, 130.5,
130.7, 131.1, 134.4, 136.0, 141.6, 142.0, 142.4, 143.4, 150.9,
159.5 ppm. UV/Vis: λmax (lg ε) = 286 (4.57), 300 (4.57), 371 sh (3.96),
393 (4.05), 410 (4.03) nm. MS: m/z (%) = 462 (100) [M+], 292 (31).
C23H15IN2O (462.29): calcd. C 59.76, H 3.27, N 6.06; found C 60.02,
6-Iodo-3-methyl-5-p-tolylbenzo[a]phenazine (2k): Yellow solid
with m.p. 281–283 °C. 1H NMR (250 MHz, CDCl3): δ = 2.43 (s, 3 H,
Me), 2.52 (s, 3 H, Me), 7.22–7.25 (m, 3 H), 7.40 (d, J = 7.8 Hz, 2 H),
7.60 (dd, J = 8.2, 1.2 Hz, 1 H), 7.83–7.91 (m, 2 H), 8.36–8.41 (m, 2 H),
9.33 (d, J = 8.2 Hz, 1 H) ppm. 13C NMR (62.9 MHz, CDCl3): δ = 21.6,
21.9, 108.2, 125.5, 128.3, 128.8, 129.0, 129.2(9), 129.3(1), 129.6, 129.7,
130.0, 130.4, 134.3, 137.9, 140.4, 140.9, 141.7, 141.8, 142.4, 143.2,
151.1 ppm. UV/Vis: λmax (lg ε) = 291 (4.59), 301 (4.62), 371 sh (3.77),
391 (4.11), 411 nm (4.10). MS: m/z (%) = 460 (100) [M+], 333 (19),
318 (14), 158 (13). C24H17IN2 (460.32): calcd. C 62.62, H 3.72, N 6.09;
found C 62.51, H 3.84, N 5.83.
H 3.41, N 6.22.
6-Iodo-5-[4-(trifluoromethyl)phenyl]benzo[a]phenazine (2d):
Yellow solid with m.p. 267–269 °C. 1H NMR (250 MHz, CDCl3): δ =
7.30 (d, J = 8.1 Hz, 1 H), 7.50 (d, J = 8.1 Hz, 2 H), 7.58 (ddd, J = 8.2,
7.0, 1.2 Hz, 1 H), 7.77–7.95 (m, 5 H), 8.36–8.42 (m, 2 H), 9.48 (d, J =
8.0 Hz, 1 H) ppm. 13C NMR (62.9 MHz, CDCl3): δ = 107.9, 124.2 (q,
J = 272.2 Hz), 125.7(8) (q, J = 4.1 Hz), 125.8(2), 127.9, 128.4, 129.2,
129.6, 130.2, 130.3, 130.5, 130.8, 131.1, 133.5, 141.4, 141.6, 142.6,
143.5, 147.0(9), 147.1(1), 149.4 ppm. UV/Vis: λmax (lg ε) = 287 (4.48),
300 (4.47), 368 sh (3.85), 388 (3.97), 408 nm (3.94). MS: m/z (%) =
500 (100) [M+], 374 (11), 304 (11), 77 (10), 75 (13), 69 (16).
C23H12F3IN2 (500.26): calcd. C 55.22, H 2.42, N 5.60; found C 55.04,
H 2.65, N 5.37.
4-[(6-Iodo-5-p-tolylbenzo[a]phenazin-3-yl)methyl]morpholine
1
(2m): Yellow solid with m.p. 187–189 °C. H NMR (250 MHz, CDCl3):
δ = 2.40–2.43 (m, 4 H), 2.52 (s, 3 H, Me), 3.59 (s, 2 H, CH2), 3.64–
3.68 (m, 4 H), 7.23 (d, J = 7.8 Hz, 2 H), 7.33 (d, J = 1.0 Hz, 1 H), 7.40
(d, J = 7.8 Hz, 2 H), 7.81 (dd, J = 8.4, 1.5 Hz, 1 H), 7.85–7.92 (m, 2
H), 8.36–8.42 (m, 2 H), 9.40 (d, J = 8.4 Hz, 1 H) ppm. 13C NMR
(62.9 MHz, CDCl3): δ = 21.6, 53.5, 62.9, 67.0, 108.3, 125.7, 128.5,
128.9, 129.1, 129.2(9), 129.3(1), 129.6, 130.2, 130.5, 134.2, 138.0,
140.2, 140.7, 141.5, 141.9, 142.4, 143.4, 151.0 ppm. MS: m/z (%) =
545 (42) [M+], 460 (100), 331 (11), 56 (22). C28H24IN3O (545.42): calcd.
C 61.66, H 4.44, N 7.70; found C 61.52, H 4.40, N 7.59.
8-Iodo-7-p-tolylnaphtho[2,1-a]phenazine (2e): Bright yellow
solid with m.p. 247–249 °C. H NMR (250 MHz, CDCl3): δ = 2.57 (s,
1
3 H, Me), 7.13 (ddd, J = 8.7, 6.9, 1.6 Hz, 1 H), 7.28 (d, J = 8.0 Hz, 2
H, p-Tol), 7.40 (d, J = 8.0 Hz, 2 H, p-Tol), 7.47 (ddd, J = 8.0, 6.9, 1.0 Hz,
1 H), 7.53 (d, J = 8.7 Hz, 1 H), 7.88–7.97 (m, 3 H), 8.18 (d, J = 8.8 Hz,
1 H), 8.40–8.49 (m, 2 H), 9.66 (d, J = 8.8 Hz, 1 H) ppm. 13C NMR
(62.9 MHz, CDCl3): δ = 21.6, 112.7, 122.6, 125.5, 126.6, 128.5, 128.8,
129.3, 129.6, 129.8, 129.9, 130.0, 130.1, 130.5, 130.6, 130.8, 131.1,
135.3, 138.1, 140.6, 141.5, 142.8, 143.8, 145.3, 149.7 ppm. UV/Vis:
λmax (lg ε) = 270 (4.76), 302 (4.64), 325 (4.60), 379 sh (4.01), 402
(4.16), 443 sh (3.79), end absorption up to 492 nm. MS: m/z (%) =
496 (100) [M+], 369 (39), 354 (28), 183 (18). C27H17IN2 (496.35): calcd.
C 65.34, H 3.45, N 5.64; found C 65.25, H 3.19, N 5.80.
Synthesis of 3′-Iodo-2′-p-tolylspiro[cyclohexa-2,5-diene-1,1′-
cyclopenta[b]quinoxalin]-4-one (8): To a cooled (–20 °C) solution
of 2-(4-methoxyphenyl)-3-(p-tolylethynyl)quinoxaline (1d) (105 mg,
0.3 mmol) in dry CH2Cl2 (4 mL) was added a cooled (–20 °C) solution
of ICl (59 mg, 0.36 mmol) in dry CH2Cl2 (4 mL). The reaction mixture
was kept at –20 to –18 °C for 48 h. The reaction mixture was filtered
giving rise to orange needles of the crude product 8 (122 mg,
88 %). After recrystallization from iPrOH, compound 8 was obtained
8-Iodo-7-p-tolylnaphtho[1,2-a]phenazine (2f): Bright yellow solid
with m.p. 275–277 °C. 1H NMR (250 MHz, CDCl3): δ = 2.54 (s, 3 H,
Me), 7.27 (d, J = 8.1 Hz, 2 H, p-Tol), 7.43 (d, J = 8.1 Hz, 2 H, p-Tol),
7.55 (d, J = 8.9 Hz, 1 H), 7.70 (t, J = 7.3 Hz, 1 H), 7.85–7.99 (m, 5 H),
8.41–8.46 (m, 1 H), 8.53–8.59 (m, 1 H), 11.14 (d, J = 9.0 Hz, 1 H)
ppm. 13C NMR (62.9 MHz, CDCl3): δ = 21.6, 109.3, 125.8, 126.4, 127.0,
1
as off-white solid with m.p. 249–251 °C. H NMR (250 MHz, CDCl3):
δ = 2.37 (s, 3 H, Me), 6.60 (pseudo s, 4 H), 7.20 (d, J = 8.1 Hz, 2 H),
7.38 (d, J = 8.1 Hz, 2 H), 7.68–7.83 (m, 2 H), 8.08 (dd, J = 8.1, 1.6 Hz,
128.3, 128.7, 129.2, 129.4(1), 129.4(4), 129.4(5), 130.5(0), 130.5(3), 1 H), 8.23 (dd, J = 8.2, 1.3 Hz, 1 H) ppm. 13C NMR (62.9 MHz, CDCl3):
130.5(9), 131.2, 131.4, 133.8, 134.3, 138.0, 141.7(3), 141.7(4), 141.8, δ = 21.5, 61.7, 101.1, 128.0, 129.2, 129.3, 129.4, 129.8, 130.5, 131.2,
142.0, 143.6, 151.3 ppm. UV/Vis: λmax (lg ε) = 271 (4.45), 309 sh
133.2, 140.3, 141.7, 142.9, 144.0, 155.2, 156.2, 159.1, 185.2 ppm. UV/
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Vis: λmax (lg ε) = 363 nm (4.34). MS: m/z (%) = 462 (100) [M+], 447
(14), 335 (41), 320 (15), 307 (44), 292 (27). C23H15IN2O (462.29): calcd.
C 59.76, H 3.27, N 6.06; found C 59.91, H 3.17, N 6.13.
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Supporting Information: Copies of the 1H and 13C NMR spectra of
all compounds, ORTEP plot of X-ray crystal structure of 8.
Acknowledgments
The author gratefully acknowledges the Russian Foundation for
Basic Research (grant no. 14-03-00032-a) for financial support
of this research. The author also thanks Drs. Anna V. Tkachuk
and Oleg N. Burov (Scientific and Educational Laboratory of Res-
onance Spectroscopy, Department of Natural and High Molec-
ular Compound Chemistry, Southern Federal University) for
NMR measurements and Dr. Kyrill Y. Suponitsky (A. N. Nesmey-
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Keywords: Synthetic methods · Electrophilic addition ·
Nitrogen heterocycles · Alkynes · Spiro compounds ·
Benzo[a]phenazines · Naphthophenazines
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Received: May 28, 2016
Published Online: ■
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Benzo[a]phenazines by Iodocycli-
zation
A. V. Gulevskaya* ............................... 1–9
Electrophile-Induced Cyclization of
3-Alkynyl-2-arylquinoxalines:
A
Method for Benzo- and Naphtho-
phenazine Synthesis
A
facile synthesis of benzo[a]-, the treatment with ICl leads to the
naphtho[1,2-a]- and naphtho[2,1-a]- alternative 5-endo-dig cyclization fol-
phenazines by ICl-promoted 6-endo- lowed by demethylation of the meth-
dig cyclization of 3-alkynyl-2-arylquin- oxy group to give a spirocyclohexadi-
oxalines is reported. For 2-(4-methoxy- enone derivative.
phenyl)-3-(p-tolylethynyl)quinoxaline,
DOI: 10.1002/ejoc.201600660
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