Quinoxalines. Part 13: Synthesis and mass spectrometric study of aryloxymethylquinoxalines and benzo[b]furylquinoxalines

Article abstract of DOI:10.1016/j.tet.2004.05.064

A series of new aryloxymethylquinoxalines, benzo[b]- and naphtho[2,1-b]furylquinoxalines, possessing potential biological activity, was prepared, characterized by IR and NMR spectroscopy and their electron ionization (EI) mass spectra studied in detail. The aryloxymethylquinoxalines were obtained by reacting halogenomethylquinoxalines with bifunctional O-nucleophiles. The benzo[b]furylquinoxalines and naphtho[2,1-b] furylquinoxalines were prepared via two routes, which differed in the order of the two cyclization steps involved in the syntheses. The composition of the ions obtained by EI mass spectrometry were determined by accurate mass measurements and the fragmentation pathways clarified by B/E linked scans and collision induced dissociation. The mass spectrometric behaviour of the compounds studied as to the possible loss of OH^· radicals proved to be very characteristic.

Full text of DOI:10.1016/j.tet.2004.05.064

Tetrahedron 60 (2004) 6063–6078
Quinoxalines. Part 13: Synthesis and mass spectrometric study of
aryloxymethylquinoxalines and benzo[b]furylquinoxalinesq,qq,w
Ines Starke,a Gerhard Sarodnick,a Vladimir V. Ovcharenko,b Kalevi Pihlajab
and Erich Kleinpetera
,
*
a
¨
Chemisches Institut der Universitat Potsdam, Postfach 60 15 53, D-14415 Potsdam, Germany
bDepartment of Chemistry, University of Turku, FIN-20014 Turku, Finland
Received 5 March 2004; revised 21 May 2004; accepted 24 May 2004
Abstract—A series of new aryloxymethylquinoxalines, benzo[b]- and naphtho[2,1-b]furylquinoxalines, possessing potential biological
activity, was prepared, characterized by IR and NMR spectroscopy and their electron ionization (EI) mass spectra studied in detail. The
aryloxymethylquinoxalines were obtained by reacting halogenomethylquinoxalines with bifunctional O-nucleophiles. The benzo[b]-
furylquinoxalines and naphtho[2,1-b]furylquinoxalines were prepared via two routes, which differed in the order of the two cyclization steps
involved in the syntheses. The composition of the ions obtained by EI mass spectrometry were determined by accurate mass measurements
and the fragmentation pathways clarified by B/E linked scans and collision induced dissociation. The mass spectrometric behaviour of the
compounds studied as to the possible loss of OHz radicals proved to be very characteristic.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
established by IR and NMR. Their EI and ESI/CID
(MS/MS) mass spectra deserve a special discussion because
they proved to be sensitive to a number of structural factors
including the substitution pattern in positions 2 and 3 of the
quinoxaline ring.
In our previous report the mass spectrometric fragmentation
of differently substituted aryl- and heteroaryloxymethyl-
quinoxalines was discussed.1 In this paper, both the
syntheses and the mass spectral fragmentation of several
new
aryloxymethylquinoxalines,
benzo[b]-
and
naphtho[2,1-b]-furylquinoxalines 3a–11c and 16a–22c
will be reported (cf. Scheme 1a and b). Their mass spectra
did not exhibit the [M2RCN]þ peaks, previously reported
as typical of quinoxalines;2 in contrast, the presence of the
[M2OH]þ ions, depending on the substitution pattern of the
aryl moiety, was observed. The fragmentation pattern
involving aryl migration to the methyl group in position 3
of the quinoxaline ring system, described in our earlier
study,1 was observed in the present case as well.
2. Results and discussion
2.1. Syntheses
The chemistry of quinoxaline and its derivatives attracts
continuous attention as a consequence of the potential
biological activity of this class of compounds. Recently, we
published a new synthetic route to pyrazolo[3,4-b]quinox-
alines.3 Continuing this research, in the present study, the
syntheses of several new aryloxymethyl-, benzo[b]-, and
naphtho[2,1-b]-quinoxalines will be reported. Compound 4
(cf. Scheme 1a), for instance, was found to be a useful
intermediate for the preparation of the substituted phenoxy
acetic acid derivatives. This group of compounds has been
patented as inhibitors of the arachidonic acid metabolism.4
The ‘quizalofop-P’ (cf. Scheme 2) and related compounds
are hormone weedkillers. The ‘quizalofop-P’ is a selective
systemic herbicide, which is used for post-emergence
control of annual and perennial grass weeds in broad-leaved
crops, applied as a mixture with other herbicides in amounts
of 150 g/ha.5–8 The benzo[b]- and naphtho[2,1-b]quinox-
alinesarechemicallysimilartothearyloxymethylquinoxalines
The structures of the compounds synthesized were
q Part 12, see Ref. 3.
qq CDRI Communication No. 6414.
w Supplementary data associated with this article can be found in the online
version, at doi: 10.1016/j.tet.2004.05.064
Keywords: Aryloxymethylquinoxalines; Benzo[b]furylquinoxalines;
Halogenomethylquinoxalines; Mass spectrometric behaviour; Structure–
fragmentation relationship; OHz; Aryl migration.
*
Corresponding author. Tel.: þ49-331-977-5210; fax: þ49-331-977-5064;
e-mail address: kp@chem.uni-potsdam.de
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.05.064

6064
I. Starke et al. / Tetrahedron 60 (2004) 6063–6078
Scheme 1a.
and some of their derivatives, and have been proved to be
biologically active. The unsubstituted compound 16a (cf.
Scheme 1b) was used, for instance, in the chlorella test and
was found by a factor of 10 more active than the known
herbicide di-nitro(ortho)cresole DNOC.9
60–65% yields. Compounds 8a, 8b were further converted
to their potassium salts by heating in ethanolic KOH and
subsequently to the corresponding free carboxylic acids 9a,
9b by acidifying the solution with acetic acid.
The o- and p-hydroxy benzyl alcohols 10a–c reacted with
1a and KOH in a molar ratio of ca. 1:1:1 affording the
aryloxymethylquinoxalines 11a–c (cf. Scheme 5).
The reaction of dihydroxy benzenes (2) with halomethyl-
quinoxaline 1 (in a molar ratio 1:2) afforded the aryloxy-
methylquinoxalines 3 (cf. Scheme 3); if the molar ratio was
1:1, a mixture of 2, 3 and the monoether 4 was obtained. To
protect one of the hydroxy groups, 2a–c were reacted with
benzoyl chloride; if the reaction was carried out at room
temperature, the monobenzoyl products 5 were obtained in
90% yield.10 These monohydroxy derivatives 5a–c reacted
with halomethyl compounds 1a,b in 2-butanone solution in
the presence of anhydrous powdered potassium carbonate
when heated under reflux for several hours, giving the
corresponding aryloxymethylquinoxalines 6a–c. The latter
could be easily converted back to the corresponding phenol
derivatives 4a–c by alkaline hydrolysis.
The benzo[b]furylquinoxalines 16, 20 and 22 (cf.
Scheme 1b), which behave chemically very similar to the
aryloxymethylquinoxalines, were synthesized along two
routes which differ in the sequence of the two ring closures
involved in the procedures. In the first procedure, the initial
step was cyclization of salicylaldehydes 12a–c with bromo-
or chloroacetone to yield the corresponding 2-acetyl-
benzo[b]furanes 13a–c;11 these were oxidized with SeO2
to give the glyoxals 14a–c which, without isolation, were
cyclized with 1,2-phenylene diamines 15a–c to the
quinoxalines 16a–g (cf. Scheme 6).
The para-disubstituted derivative 4c reacted with bromo-
acetic acid ethylester (7a) or with 2-bromopropionic acid
methylester (7b) in the presence of K2CO3 and gave the
corresponding esters 8a and 8b as depicted in Scheme 4 in
In the second procedure, the ring closure to the benzofuran
ring happened after the cyclization step of the quinoxaline
ring system (cf. Scheme 7). Precursors for this second type
of syntheses are halogenomethylquinoxalines already

I. Starke et al. / Tetrahedron 60 (2004) 6063–6078
6065
Scheme 1b.
exothermically with 1,2-phenylene diamine leading to
2-(bromomethyl)-3-(4-chlorophenyl)quinoxaline 1c.
The CH2Hal group in 1a–g is highly reactive because of the
electron-withdrawing activity of both the halogen atoms and
the quinoxaline ring. Hence nucleophilic attack on this
carbon atom can easily take place by the phenolate anion,
which was obtained by addition of an equimolar amount of
KOH. This nucleophilic substitution of the halogen by the
phenolate led to the aryloxymethylquinoxalines 17, 19 and
21 (cf. Scheme 7). Since these new ether derivatives possess
an adequately active carbonyl group in the neighbourhood
of the ether bond (in ortho-position of the phenyl moiety),
addition of a second equivalent of KOH enforces the
cyclization to the benzo[b]furane system.
Scheme 2.
known: 2-(chloromethyl)quinoxaline 1g,12 2-(bromo-
methyl)-3-methylquinoxaline 1a13 and 2-(bromomethyl)-
3-phenylquinoxaline 1b, respectively.14 2-(Bromomethyl)-
3-(4-chlorophenyl)quinoxaline 1c was synthesized from
4-chloropropiophenone by converting it into the isonitroso
compound using ethyl nitrite. The isonitroso compound was
hydrolyzed into the 1,2-diketone by steam distillation from
a sulfuric acid solution; this compound was treated with
bromine in boiling chloroform to afford the 1-(4-chloro-
phenyl)-3-bromopropan-1,2-dione, which was used further
without isolation. Finally, the latter compound reacted
As phenolate precursors, salicylic aldehydes 12a–c,
2-hydroxy-naphthalen-1-carbaldehyde 18 and 2-hydroxy-
ketones 12d, 12e were used;15 yields for the final
benzo[b]furylquinoxalines were between 80–90%.

6066
I. Starke et al. / Tetrahedron 60 (2004) 6063–6078
Scheme 3.
Scheme 4.
Scheme 5.
2.2. Mass spectrometry
processes. This kind of skeletal rearrangements involving
aryl migrations have been invoked to explain the fragmen-
tation modes of different types of compounds and have been
described in detail.16–22 The corresponding aryl migration
can be revealed from the spectra of the compounds 6a, 6c,
8a and 9a which leads to weak ions at m/z 211 (C14H11O2)
and m/z 193 (C11H13O3) for 8a and 9a, respectively. The
2.2.1. Aryloxymethylquinoxalines. The main peaks of the
low resolution 70 eV EI mass spectra of the compounds
studied (cf. Scheme 1a and b) are listed in Table 1a of
Supplementary Material. The EI mass spectra of compounds
3a–c, 6a–b, 8a, and 9a are dominated by rearrangement

I. Starke et al. / Tetrahedron 60 (2004) 6063–6078
6067
Scheme 6.
Scheme 7.
presence of these fragment ions together with their accurate
masses (cf. Table 2a in Supplementary Material) reveals
that the aryl substituent migrates to the methyl group at
position 3 of the quinoxaline ring system (cf. Scheme 8).
Previously,1 the aryl migrations in aryloxymethyl quinox-
alines were found to be favoured by electron donating
substituents in the migrating aryl group; accordingly, in the
cases of compounds 4a–c, 8b, 9b, and 11a–c no aryl
migration was observed.
In 3a–c, 6a and 6c the relatively abundant ions
[M2C6H5O2]þ and [M2C7H7O2]þ (and the ions
[M2C6H5O2]þ and [M2C7H4O3]þ for 6a and 6c,
respectively) prove a skeletal rearrangement to occur. This

6068
I. Starke et al. / Tetrahedron 60 (2004) 6063–6078
Scheme 8.
is also the case for compound 3d (with Ph on position 3); the
ejection of the aroyl system was observed but only to a very
small extent (m/z 437, ,1% relative abundance—RA). The
key step of the aroyl loss from compounds 3a–c when
compared to 6a and 6c should involve the rearrangement of
the corresponding molecular ions in two different ways. The
elimination of the aroyl group from compounds 6a and 6c
can be rationalized with an aryl migration which occurs to
the methyl group at position 3 (R1¼CH3), as described in
Scheme 8. The location of the phenyl substituents is very
important for the relative abundance of the resulting ions
[M2C6H5O2]þ or [M2C7H4O3]þ. The mass spectrum of
6a exhibits the strongest loss of C6H5O2 radical
([M2C6H5O2]þ ca. 61% RA), while for 6c the RA of the
corresponding ion was only 2%. In the mass spectrum of
compound 6b the ions [M2C6H5O2]þ or [M2C7H4O3]þ
could not be observed at all, thus no aryl migration takes
place (cf. Scheme 8).
correspond exactly to the EI mass spectra and the ions m/z
314 and 299 to the loss of the aroyl group. Obviously, the
aryl migration is induced exclusively by electron ionization,
while the same rearrangement in compounds 3a–c occurs
also under the soft ESI conditions.
2.2.2. Benzo[b]- and naphtho[2,1-b]furyl quinoxalines.
The highly conjugated nature of compounds 16a–s, 20a,b
and 22a–c (depicted in Scheme 1b) is reflected in the
stability of their molecular ions (cf. Table 1b in Supple-
mentary Material; RA 100% except for compounds 16k and
16m–r). The loss of HCN and RCN from the molecular
ions and the formation of the [M2CHO]þ ions from the
benzofuran ring unit were reported in similar compounds.2
Surprisingly, the ester derivatives 16m–o, 16q and 16r did
not show the [M2RCN]þ peaks like the aryloxymethyl-
quinoxalines mentioned above. Comparison of the spectra
of compounds 16a, 16h, 16p and 22a with cases where
R1¼H, CH3, Ph or benzofuryl show that the fragmentation
patterns are quite similar for these compounds (cf. Tables 1b
and 2b in Supplementary Material). Different substituents
(CH3, Cl, and Br) at different positions R3, R4, R5, R6
(compared to compounds 16b–g, 16i–j) did not influence
the fragmentation behaviour.23
However, the observation of the relatively abundant ions
[M2C6H5O2]þ and [M2C7H7O2]þ in the EI mass spectra
of 3a-c should result from another rearrangement process. In
order to get deeper insight into the mechanism of these
fragmentations we also recorded the mass spectra of 6a,c,
8a,b and 11b (beside 3a–c), generated by positive
electrospray ionization (ESI). The corresponding [MþH]þ
ions were used as precursor ions and their CID fragmenta-
tions were studied. The main results of the MS/MS
measurements are depicted in Table 3a. In compounds 6a
and 6c, the EI fragmentations, however, differ clearly from
those of the ESI mass spectra since the [M2C6H5O2]þ or
[M2C7H4O3]þ ions (RA of the latter being 60% under EI
conditions) were not found at all.
The relative abundance of the [M2OH]þ ions in the
MS/MS spectra proved to be very characteristic for the
compounds studied: In case of the benzo[b]furylquinox-
alines, the replacement of the methyl group in position 3 of
the quinoxaline moiety by phenyl or benzofuryl modifies
significantly the loss of OHz radicals from the molecular
ions compared with the corresponding aryloxymethyl-
quinoxalines. In addition for determining the structure–
fragmentation relationship of these compounds, the main
mass spectrometric fragmentation patterns of some
Interestingly, only the CID spectra of compounds 3a–c
Table 3a. Characteristic fragment ions of compounds 3a, 6a, 8a and 8b as proved by collision induced decomposition of the selected precursor ion from ESI
positive spectra
No. of compound
Results from the CID-spectra m/z
3a
6a
8a
MS from m/z 423
MS from m/z 371
MS from m/z 353
314[M2C6H5O2]þ, 299[M2C7H7O2]þ, 265[M2C10H9N2]þ,
249[M2C10H9N2O]þ, 157[M2C16H13N2O2]þ
353[M2OH]þ, 249[M2C7H5O2]þ, 197[M2C10H9N2O]þ,
157[M2C13H8O3]þ, 105[M2C16H13N2O2]þ
337[M2CH3]þ, 335[M2OH]þ, 279[M2COOCH2CH3]þ,
266[M2CH2COOCH2CH3]þ, 249[M2OCH2COOCH2CH3]þ
157[M2C10H10O4]þ
8b
MS from m/z 325
310[M2CH3]þ, 307[M2OH]þ, 279[M2COOH]þ,
266[M2CH2COOH]þ, 249[M2OCH2COOH]þ, 157[M2C8H7O4]þ

I. Starke et al. / Tetrahedron 60 (2004) 6063–6078
6069
Table 3b. Characteristic fragment ions of compounds 16p, 16s, 20a–b, 22a as proved by linked scan measurements
No of compound
Result of the linked scans m/z
16p
16s
B/E from m/z 322
B/E from m/z 293
B/E from m/z 356
305[M2OH]þ, 293[M2CHO]þ, 245[M2Ph]þz, 219[M2PhCN]þz
266[M2HCO–HCN]þ, 190[þM2HCO–PhCN]þ
339[M2OH]þþ, 328[M2CO] , 321[M2Cl]þ, 219[M2PhCNCl]þz
213[M2143]
,
B/E from m/z 339
B/E from m/z 310
B/E from m/z 372
304[M2OH–Cl]þ
20a
20b
393[M2OH]þ, 281[M2CHO]þ, 269[M2CH3CN]þz
355[M2OH]þ, 343[Mþ2CHO]þ, 269[M2PhCN]þz
345[M2OH]þ, 334[M2CO]þ
316[F2CHO]þ
,
205[M2naphthofuryl]
22a
B/E from m/z 362
B/E from m/z 345
characteristic compounds were analyzed as a function of the
substituents at positions 2 and 3 of the quinoxaline moiety.
benzo[b]furyl substituent at position 2) play the most
important role as to the RA of the [M2OH]þ peaks (cf.
Scheme 9). The benzofuryl quinoxalines with hydrogen or
methyl at position 3 are well conjugated (f¼1808). If the
torsional angle f between the quinoxaline ring system and
the attached benzofuryl/naphthofuryl system is 1808, a
complete delocalisation of the p-electrons and a full
interannular conjugation will be possible and nearly no
loss of OHz radical occurs. Torsional twist from 1808 in case
of compounds 16p, 16s, 20b, 22a–22c (R1¼Ph, ClC6H4 or
benzofuryl), however, disturbs the interannular p-conju-
gation and the compounds lose easily the OHz radical (RA of
[M2OH]þ ions 15–28%).
2.2.3. Influence of the substituents (H, CH3, and Ar) at
position 3 on the loss of OHz radical from the
aryloxymethylquinoxalines, as compared to the benzo-
[b]- and naphtho[2,1-b]furyl quinoxalines. The aryloxy-
methyl quinoxalines with hydrogen or methyl at position 3
of the quinoxaline moiety (R1¼H or CH3) exhibit
[M2OH]þ and [M2CHO]þ ions as the main rearrangement
products. In contrast the mass spectra of the 2-benzo[b]furyl
quinoxalines having hydrogen or methyl at position 3 did
not exhibit these peaks at all or only in a very small
abundance (RA,3%). However, with Ph or benzofuryl at
position 1 the mass spectra exhibit the strongest loss of OHz
radical (RA of [M2OH]þ ions 5–30%). Metastable data
from B/E scan confirm the formation of these ions directly
from [M]þz (depicted in Table 3b).24
The aryl migration discussed for the aryloxymethyl
quinoxalines is not observed in the mass spectra of the
benzo[b]-, and naphtho[2,1-b]furyl quinoxalines.
Previous investigations based on NMR spectroscopy show
that the conformation of the02-benzo[b]furyl quinoxalines is
flexible about the C(2)–C(2 ) bond. If there are substituents
in the 3,30-positions, the free rotation was proved to be
sterically hindered and the two heteroaromatic moieties are
twisted (cf. Scheme 9).25 Obviously in the case of the
benzo[b]- and naphtho[2,1-b]furyl type quinoxalines, the
torsional angle f (interannular p-conjugation between
the p-deficient quinoxaline ring system and the p-rich
3. Conclusions
A large variety of aryloxymethylquinoxalines, benzo[b]-
and naphtho[2,1-b]furyl quinoxalines possessing potential
biological activities were prepared and studied by IR, NMR,
and MS.
The aryloxymethylquinoxalines were prepared by reacting
halomethylquinoxalines with different substituted mono-
hydroxy- or dihydroxy compounds. Several of the aryloxy-
methylquinoxalines consist of building blocks of the known
herbicide quizalofop. The benzo[b]furyl quinoxalines were
prepared with two methods, which differ in the order of
cyclization. In the first approach, acetyl-substituted ben-
zo[b]furanes 13 were used as starting material, which was
oxidized with SeO2; the resulting glyoxals were cyclized
with 1,2-phenylene diamine into the quinoxaline without
isolation of the glyoxals. In the second procedure,
halomethyl-substituted quinoxalines were reacted with
aromatic 2-hydroxy carbonyl compounds after addition of
one equivalent of base to obtain the aryloxymethylquinoxa-
lines and then adding another equivalent of base to carry out
the cyclization to the benzo[b]furyl quinoxalines. These two
step syntheses can be conveniently carried out in one pot.
Detailed analysis of the mass spectra of the quinoxaline
derivatives, thus obtained, allows the following conclusions
to be drawn. Generally, the fragmentation pathways of the
molecular ions depend on the substituents on position 2 of
the quinoxaline moiety. The mass spectra of the variously
substituted derivatives resemble very much each other. The
Scheme 9.

6070
I. Starke et al. / Tetrahedron 60 (2004) 6063–6078
aryloxymethylquinoxalines did not exhibit the loss of HCN
and RCN, although the spectra of the corresponding
benzo[b]- and naphtho[2,1-b]furyl quinoxalines exhibit the
[M2HCN]þz and [M2RCN]þz ions. The aryloxymethyl-
quinoxalines with methyl in position 3 of the quinoxaline
ring moiety exhibit [M2OH]þ ions as the main aryl
migration/rearrangement products. The corresponding
benzo[b]furyl quinoxalines with R1¼H, CH3 do not lose
the OHz radical or do so only in very low amounts (RA
1–3%). In contrast, the benzo[b]- and naphtho[2,1-b]furyl
quinoxalines with a phenyl or benzofuryl group at position 3
exhibit the strongest loss of OHz (RA 15–28%). The
p-conjugation between the quinoxaline moiety and the
benzo[b]- or naphtho[2,1-b]furyl substituents play the most
important role as to the RA of the [M2OH]þ peaks.
the collision gas (,5£1025 mbar) and the gas cell was
maintained between 15 and 20 eV.
4.2. Syntheses of the compounds
Compounds 17a–h, 19a,b and 21a–c were characterized by
1
hr-MS or H/13C NMR spectroscopy (IR data are given
generally); they were reacted into the final products 16 and
20 immediately. In cases, where hr-MS data are not given in
the procedures, they are collected in Tables 2a and b in the
Supplementary Material.
2-(Bromomethyl)-3-(4-chlorophenyl)quinoxaline (1c).
Step 1. 1-(4-Chlorophenyl)-2-hydroxyiminopropan-1-on
(CAUTION! To breath in ethylnitrite causes dizziness.
Use fumehood.) The generator for the ethylnitrite consists
of a two-necked flask and a dropping funnel. A solution of
HCl (725 mmol, ca. 60 ml), EtOH (375 mmol, 17.25 g,
22 ml) and water (140 ml) are added to a NaNO2 solution
(725 mmol, 50 g) in EtOH (350 mmol, 16.1 g, 20.5 ml) and
water (140 ml). The resulting gaseous ethylnitrite reacts
with a solution of 40-chloropropiophenone (650 mmol,
110 g) in EtOH (2 mol, 92 g, 117 ml) in a 500 ml
three-necked flask equipped with a cooler, thermometer
and a gas inlet. At the beginning of the reaction, the
propiophenone solution was acidified with 5 ml conc. HCl
and heated to 50 8C. The reaction time took place in 4 h.
After intensive cooling the product crystallized in 61%
yield and it was recrystallized from aqueous ethanol, mp
116–117 8C.
If position 30 of the benzofuryl ring contains an ester group
the main fragmentation of the molecular ion is due to an
elimination of the ester radical and no [M2RCN]þz ions are
observed. The quinoxalines with benzo[b]furyl and
naphtho[2,1-b]furyl groups undergo ring cleavage at the
carbon nitrogen bond N(1)–C(9) due to the opening of the
quinoxaline ring, but in the mass spectra of the aryloxy-
methylquinoxalines no such fragments occur.
4. Experimental
Melting points were determined on a Boetius micro hotstage
microscope. The IR spectra were recorded with a Perkin–
Elmer FTIR 1600 spectrometer (cm21). The NMR spectra
were acquired with a Bruker NMR ARX 300 spectrometer.
Step 2. 1-(4-Chlorophenyl)propan-1,2-dione. After steam
distillation of a mixture of 1-(4-chlorophenyl)-2-hydroxy-
iminopropan-1-one (400 mmol, 79 g) and 1 M sulfuric acid
(550 ml), the diketone was extracted with dichloromethane
from 4 l of the distillate. The product was dried on
sodium sulfate and filtered. After removing the solvent the
oil was isolated in 88% yield by cooling in a refrigerator; mp
22–23 8C.
1
The H and 13C chemical shifts are given in the d scale
(ppm) downfield from tetramethylsilane (TMS) as internal
standard.
4.1. Mass spectrometry
The low resolution EI mass spectra were obtained using a
Thermo Finnigan SSQ710 instrument (Finnigan, San Jose,
CA, USA) with an electron energy of 70 eV, and source
temperatures between 430 and 470 K, using a direct
insertion probe. Elemental compositions were determined
by accurate mass measurement within an average accuracy
of ca 3£1024 au, at a resolution of 10.000–12.000 (10%
valley) with a VG Zabspec instrument using the peak
matching technique and a Micromass GC-TOFmicro mass
spectrometer (Micromass, Wythenshawe, UK) with stan-
dard deviation ,5 ppm. Perfluorokerosene (PFK) was used
as reference compound in both cases. Metastable ion spectra
(B/E and B2/E linked scans; MIKES) were recorded using
the VG ZABspec.
Steps 3 and 4. 1-(4-Chlorophenyl)-3-bromo-propan-1,2-
dione and 2-(Bromomethyl)-3-(4-chlorophenyl)-quinoxa-
line (1c). (CAUTION! Halodiketones are lacrimatory!) A
solution of bromine (350 mmol, 55.93 g) in chloroform
(200 ml) was added to a boiling solution of 1-(4-chloro-
phenyl)propan-1,2-dione (350 mmol, 63.91 g) in chloro-
form (100 ml). The addition was carried out in ca 30 min.
The mixture was heated under reflux for 30 min and washed
after cooling four times with 150 ml ice water. Then a
solution of o-phenylene-diamine (350 mmol, 37.8 g) in
chloroform (500 ml, 50 8C) was added slowly to 3-bromo-
1,2-dione (exothermic reaction!). The mixture was heated
under reflux for 20 min, dried on CaCl2 and filtered. The
solvent was removed in vacuo. After washing with a little
amount of cold methanol, the product was filtered by suction
and recrystallized from 1-butanone, yield 58%, mp 175–
177 8C.
The ESI and CID spectra were recorded using a Micromass
Q-TOFmicro mass spectrometer in positive electrospray
mode. All samples were injected (10–15 ml/min) with a
Harvard syringe pump. The capillary voltage was set to
2.8 kV, with a cone voltage between 25–35 V. The source
temperature was 80 8C and the desolvation temperature
150 8C. The cone and desolvation gases (nitrogen) were
delivered at 50 and 360 l h21 respectively. For MS/MS after
selection of the appropriate precursor ion, argon was used as
4.2.1. General procedure for the synthesis of the
compounds 3a, 3c, and 3d. The diol 2 (10 mmol, 1.1 g),
dissolved in 50 ml EtOH under argon, was mixed with a
KOH solution (20 mmol, 1.12 g) in 50 ml EtOH and a
solution of the 3-substituted 2-(bromomethyl)quinoxaline

I. Starke et al. / Tetrahedron 60 (2004) 6063–6078
6071
(20 mmol) in EtOH by stirring under argon. The mixture
was refluxed for 2 h, concentrated in vacuo and kept in a
refrigerator overnight. The solid was collected by filtration,
washed with water and recrystallized.
m-Phenylene-bis[oxymethylen(3-methyl-quinoxalin-2-yl)]
(3b). This compound26,27 was obtained from resorcinol
(2b) (10 mmol, 1.10 g) and 1a in 32% yield as pale rosa,
nearly colorless needles, mp 148–151 8C (octane); IR:
3030, 2930, 2870, 1600, 1490, 1455, 1430, 1400, 1365,
1350, 1325, 1280, 1205, 1185, 1165, 1150, 1130, 1045,
985, 955, 930, 900, 825, 745, 630, 605, 595, 440; 1H NMR
(CDCl3): d 8.08–8.00, 7.74–7.65 (m, 8H, quin), 7.23–
7.18, 6.83–6.82, 6.72–6.68 (m, 4H, phen), 5.34 (s, 4H,
2CH2), 2.83 (s, 6H, 2CH3); 13C NMR (CDCl3): d 159.4,
153.7, 150.1, 141.6, 140.3 (5£2 quart. C), 130.1, 129.1,
128.9, 128.1, 107.7, 102.2 (6£2 tert. C), 70.5 (2CH2), 22.2
(2CH3). Anal. Calcd for C26H22N4O2 (422.49 g/mol): C,
73.92; H, 5.25; N, 13.26. Found: C, 73.72; H, 5.54; N,
13.51.
o-Phenylene-bis[oxymethylen(3-methyl-quinoxalin-2-yl)]
(3a). This compound26,27 was obtained from 1a (4.75 g,
dissolved in 130 ml EtOH) and 2a in 77% yield as pale
beige needles, mp 176–178 8C (1-butanol); IR: 3060, 3040,
2955, 2930, 2825, 1590, 1515, 1500, 1455, 1400, 1370,
1350, 1325, 1290, 1250, 1200, 1155, 1120, 1050, 1025,
1005, 930, 950, 900, 840, 810, 750, 730, 680, 660, 605, 590,
1
555, 520, 480, 455, 425; H NMR (CDCl3): d 8.02–7.96,
7.71–7.66 (m, 8H, quin), 7.15–7.13, 6.97–6.94 (m, 4H,
phen.), 5.38 (s, 4H, 2CH2), 2.82 (s, 6H, 2CH3); 13C NMR
(CDCl3): d 153.9, 150.3, 148.5, 141.7, 140.3 (5£2 quart. C),
130.0, 129.0, 129.0, 128.2, 122.1, 114.9 (6£2 tert. C), 71.7
(2CH2), 22.2 (2CH3). Anal. Calcd for C26H22N4O2
(422.49 g/mol): C, 73.92; H, 5.25; N, 13.26. Found: C,
73.79; H, 5.43; N, 13.07.
2-(3-Methylquinoxalin-2-ylmethoxy)phenyl benzoate (6a).
This compound was obtained from 2-hydroxyphenyl
benzoate (5a) (20 mmol, 4.28 g) and 1a (20 mmol, 4.74 g)
in 59% yield as colorless needles, mp 153–155 8C; IR:
3068, 1728, 1604, 1500, 1454, 1380, 1306, 1284, 1252,
1178, 1110, 1082, 1064, 1026, 1010, 906, 854, 832, 792,
p-Phenylene-bis[oxymethylen-(3-methyl-quinoxalin-2-yl)]
26,27
1
(3c). This compound
was obtained from 1a (4.75 g,
764, 754, 718, 676, 612, 580, 424; H NMR (CDCl3): d
dissolved in 130 ml EtOH) and 2c in 73% yield as colorless
needles, mp 214.5–215.5 8C (from DMF); IR: 3046, 2932,
2874, 1854, 1610, 1566, 1588, 1488, 1460, 1434, 1372,
1354, 1324, 1288, 1265, 1232, 1164, 1130, 1114, 1036, 958,
904, 822, 786, 758, 696, 688, 612, 554, 522, 448; 1H NMR
(CDCl3): d 8.10–8.02, 7.78–7.69 (m, 8H, quin), 7.01 (s,
4H, phen), 5.33 (s, 4H, 2CH2), 2.87 (s, 6H, 2CH3); 13C
NMR (CDCl3): d 153.9, 153.1, 150.1, 141.7, 140.3 (5£2
quart. C), 130.2, 129.2, 129.0, 128.2, 115.9 (6£2 tert. C),
71.2, (2CH2), 22.2 (2CH3). Anal. Calcd for C26H22N4O2
(422.49 g/mol): C, 73.92; H, 5.25; N, 13.26. Found: C,
73.70; H, 5.36; N, 13.47.
8.15–8.12, 7.96–7.94 (m, 4H, quin), 7.66–6.99 (m, 9H,
phen, o-phenylene), 5.39 (s, 2H, CH2), 2.74 (s, 3H, CH3);
13C NMR (CDCl3): d 164.7, 153.9, 149.9, 141.6, 140.2
(8 quart. C), 133.4, 130.1, 129.1, 129.0, 128.4, 128.1,
126.9, 123.2, 121.7, 114.3 (13 tert. C), 71.4 (CH2), 22.0
(CH3). hr-MS: Calcd for C23H18N2Oþ3 : 370.1317, found
370.1300.
3-(3-Methylquinoxalin-2-ylmethoxy)phenyl benzoate (6b).
This compound was obtained from 3-hydroxyphenyl
benzoate (5b) (20 mmol, 4.28 g) and 1a (20 mmol, 4.74 g)
in 72% yield as light brown needles, mp 85–87 8C; IR:
3082, 2874, 1732, 1598, 1488, 1452, 1372, 1356, 1314,
1272, 1246, 1168, 1138, 1078, 1064, 1046, 1024, 998, 930,
892, 868, 826, 776, 762, 734, 706, 690, 678, 614, 694, 436,
p-Phenylene-bis[oxymethylen(3-phenyl-quinoxalin-2-yl)]
(3d). This compound was obtained from 1b (6.00 g, in
500 ml EtOH) and 2c in 54% yield as beige prisms, mp
200–202 8C (pyridine); IR: 3062, 2943, 1550, 1504, 1219,
842, 820, 767, 702; 1H NMR (CDCl3): d 8.64–8.61, 8.22–
8.17 (m, 8H, 2£4H in the condensed benzo-cycle), 7.83–
7.26 (m, 10H, 2£phenyl), 6.84 (s, 4H, 1,4 subst phen 25.26
(s, 4H, 2£CH2); 13C NMR (CDCl3): d 155.0, 153.0, 149.0,
141.9, 141.3, 138.1, 135.9, 135.9, 130.6, 130.0, 129.3, 129.3
(12 quart. C), 149.8 (4), 129.2 (2), 129.0 (4), 128.6 (4),
123.7 (4), 116.0 (4), (22 tert. C), 70.6 (2CH2).
1
420; H NMR (CDCl3): d 8.19–8.16, 8.08–8. 01, 7.72–
6.86 (m, 13H, phen, 5.36 (s, 2H, CH2), 2.86 (s, 3H, CH3);
13C NMR (CDCl3): d 164.8, 159.1, 153.7, 151.8, 149.9,
141.8, 140.3, 129.3 (8 quart. C), 133.5, 130.1, 130.0, 130.0,
129.9, 129.1, 129.0, 128.4, 128.4, 128.2, 114.7, 112.3, 108.7
(13 tert. C), 70.7 (CH2), 22.1 (CH3).
hr-MS: Calcd for C23H18N2Oþ3 : 370.1317, found 370.1304.
4-(3-Methylquinoxalin-2-ylmethoxy)phenyl benzoate (6c).
This compound was obtained from 4-hydroxyphenyl
benzoate (5c) (20 mmol, 4.28 g) and 1a (20 mmol, 4.74 g)
in 51% yield as colorless needles, mp 157–158 8C; IR:
3060, 2936, 1872, 1738, 1600, 1566, 1506, 1400, 1460,
1450, 1372, 1358, 1314, 1272, 1248, 1198, 1168, 1132,
1104, 1082, 1062, 1026, 1014, 1002, 934, 904, 866, 814,
788, 764, 736, 702, 682, 672, 614, 580, 540, 526, 470, 428;
1H NMR (CDCl3): d 8.19–8.03 (m, 4H, quin), 7.73–7.45,
hr-MS: m/z Calcd for C36H26N4Oþ2 : 546.2056 found.
546.2009.
4.2.2. General procedure for the synthesis of compounds
(3b, 6a–c). In the case of monohydroxy phenols, 20 mmol,
in case of diols 10 mmol were applied. A mixture of the
hydroxy-compound, 2-(bromomethyl)-3-methyl-quinoxa-
line (20 mmol, 4.75 g) and anhydrous potassium carbonate
(30 mmol, 4.15 g) in 2-butanone (100 ml) was heated under
argon at reflux for 5 h with vigorous stirring. Inorganic salts
were separated by filtering the boiling solution. The residue
was washed two times with hot 2-butanone (30 ml). The
filtrates were combined and the solvent removed. The
resulting oil crystallized by mixing with EtOH (10 ml) and
the product was purified by recrystallization.
7.14–7.09, phen, 5.37 (s, 2H, CH2), 2.87 (s, 3H, CH3); 13
C
NMR (CDCl3): d 165.3, 156.0, 153.8, 150.2, 144.9, 141.8,
140.4, 133.5 (8 quart. C), 130.2, 130.0, 130.0, 129.4, 129.1,
129.0, 128.4, 128.4, 128.3, 122.5, 122.5, 115.5, 115.5 (13
tert. C), 71.0 (CH2), 22.2 (CH3).
hr-MS: Calcd for C23H18N2Oþ3 : 370.1304, found 370.1317.

6072
I. Starke et al. / Tetrahedron 60 (2004) 6063–6078
4.2.3. General procedure for the synthesis of phenols 4
from the benzoates 6. The solution of the appropriate
benzoate 6 (10 mmol, 3.70 g) in hot ethanol was treated
with a 2.5 N aqueous potassium hydroxide (10 ml,
25 mmol). The mixture was heated at reflux for 15 min.
After the addition of acetic acid (25 mmol, 1.5 g) the
solution was concentrated in vacuo. The resulting mixture
was kept in a refrigerator overnight and the precipitate was
collected by suction filtration, washed with aqueous solution
of sodium hydrogen carbonate and with water. The crude
product was purified by recrystallization.
hot 2-butanone. The filtrates were combined and the solvent
was removed totally. The resulting oil crystallized by
mixing with ice-cold alcohol (10 ml).
Ethyl 2-[4-(3-methyl-quinoxalin-2-ylmethoxy)phenoxy]-
acetate (8a). This compound was obtained from ethyl
bromacetate (4.01 g) in 62% yield as colorless columns, mp
91–93 8C (EtOH); IR: 3060, 2984, 2912, 1750, 1612, 1594,
1566, 1508, 1474, 1462, 1436, 1406, 1382, 1374, 1356,
1326, 1308, 1234, 1178, 1162, 1128, 1108, 1090, 1036,
1018, 962, 906, 858, 832, 816, 792, 766, 680, 612, 576, 540,
1
524, 458, 426; H NMR (CDCl3): d 8.08–8.00, 7.73–7.69
2-(3-Methyl-quinoxalin-2-ylmethoxy)phenol (4a). This
compound was obtained from 6a in 75% yield as pale
beige, nearly colorless prisms, mp 164–165 8C (EtOH); IR:
3052, 2937, 1596, 1570, 1500, 1464, 1430, 1376, 1358,
1330, 1300, 1266, 1206, 1132, 1110, 1028, 1010, 910, 852,
832, 786, 758, 736, 680, 618, 540, 450; 1H NMR (CDCl3): d
9.57 (s, 1H, OH), 7.98–7.91, 7.71–7.66 (m, 4H, quin),
7.12–6.85 (m, 4H, phen), 5.32 (s, 2H, CH2), 2.62 (s, 3H,
CH3); 13C NMR (CDCl3): d 151.7, 150.4, 148.5, 147.3,
141.4, 139.3 (6 quart. C), 130.2, 129.6, 128.2, 128.1, 124.2,
120.0, 117.4, 116.9 (8 tert. C), 72.6 (CH2), 21.5 (CH3).
(m, 4H, quin), 6.99, 6.86 (dd, 4H, p-subst.phen), 5.31 (s, 2H,
CH2O), 4.56 (s, 2H, acetate-CH2O), 4.26 (q, J¼7.1 Hz, 2H,
ethyl-CH2O), 2.85 (s, 3H, 3-CH3), 1.27 (t, J¼7.1 Hz, 3H,
ethyl-CH3); 13C NMR (CDCl3): d 168.5, 153.4, 152.7,
152.0, 150.0, 141.3, 140.0 (7 quart.C), 129.6, 128.6, 128.5,
127.8 (4 tert. C), 115.3 (4 tert. C), 71.0, 65.6, 60.7 (3 sec. C),
21.8 (3-CH3), 13.6 (ester-CH3).
hr-MS: Calcd for C20H20N2Oþ4 : 352.1423, found 352.1404.
Methyl 2-[4-(3-methyl-quinoxalin-2-ylmethoxy)phenoxy]-
propionate (8b). This compound was obtained from methyl
2-bromopropionate (4.01 g) in 63% yield as colorless
columns, mp 90–91 8C; IR: 3066, 2996, 2950, 1740,
1598, 1568, 1508, 1458, 1434, 1372, 1326, 1306, 1222,
160, 1130, 1110, 1050, 1032, 1010, 982, 946, 906, 860, 822,
hr-MS: Calcd for C16H14N2Oþ2 : 266.1055, found 266.1059.
3-(3-Methyl-quinoxalin-2-ylmethoxy)phenol (4b). This
compound was obtained from 6b in 71% yield as beige
prisms, mp 190–192 8C (1-propanol); IR: 3400–2250 (br),
3068, 2957, 2734, 2608, 1598, 1508, 1494, 1462, 1372,
1312, 1290, 1246, 1210, 1184, 1146, 1074, 1054, 1010, 944,
912, 862, 824, 774, 686, 668, 618, 532, 484, 458, 438, 422;
1H NMR (DMSO): d 9.58 (s, 1H, OH), 8.12–8.04, 7.88–
7.80 (m, 4H, quin), 7.15–7.10, 6.58–6.44 (m, 4H, phen),
5.40 (s, 2H, CH2), 2.80 (s, 3H, CH3); 13C NMR (DMSO): d
159.5, 158.7, 154.1, 151.1, 141.2, 139.8 (6 quart. C), 130.3,
130.1, 129.5, 128.8, 128.2, 108.6, 105.5, 102.3 (8 tert. C),
69.8 (CH2), 22.0 (CH3).
1
786, 762, 706, 680, 614, 522, 420; H NMR (CDCl3): d
8.08–8.00, 7.73–7.69 (2m, 4H, quin), 6.98–6.96, 6.85–
6.82 (dd, 4H, p-subst phen), 5.31 (s, 2H, CH2O), 4.67 (q,
J¼6.8 Hz, 3.74 (s, 3H, OCH3), 2.84 (s, 3H, 3-CH3), 1.57 (d,
J¼6.8 Hz, 3H, 13C NMR (CDCl3): d 172.7 (CvO), 153.8,
153.1, 152.1, 150.4, 141.7, 140.3 (6 quart. C), 130.0, 129.0,
128.9, 128.2 (4 tert. C), 116.3 (2 tert. C), 115.8 (2 tert.),
73.2, 71.1 (2 sec. C), 52.2 (OCH3), 22.2 (3-CH3), 18.5
(2-CH3).
hr-MS: Calcd for C18H16N2Oþ4 : 324.1110, found 324.1108.
hr-MS: Calcd for C16H14N2Oþ2 : 266.1055, found 266.1060.
4.2.5. A procedure for preparing compounds 9a, 9b. The
ethanolic solution of the esters 8a, 8b (10 mmol [3.52 g] in
50 ml EtOH) was mixed with the ethanolic KOH (11 mmol
[0.62 g] in 50 ml EtOH). The mixture was heated at reflux
for 15 min. The potassium salt, precipitating from the
boiling solution, was filtered by suction under cooling to
room temperature. The potassium salt—yield nearly
quantitative—was dissolved in water (50 ml). This solution
was treated with aquous acetic acid (20 mmol [1.2 g]
AcOH, 12 ml H2O). The resulting acids 9a/9b, first often
colloidally dissolved, were separated in crystallic form by
inoculation and/or stirring and keeping in the refrigerator
overnight. The product in question was separated by
filtration, washed with water (50 ml) and recrystallized.
4-(3-Methyl-quinoxalin-2-ylmethoxy)phenol (4c). This
compound was obtained from 6c in 82% yield as colorless
prisms, mp 206–209 8C (1-butanol); IR: 3500–2250 (br),
3168, 3059, 2882, 2360, 1734, 1616, 1572, 1514, 1492,
1452, 1374, 1318, 1262, 1228, 1156, 1124, 1102, 1084,
1006, 924, 878, 852, 828, 770, 736, 710, 680, 616, 762, 538,
516, 426; 1H NMR (DMSO): d 9.06 (s, 1H, OH), 8.06–8.00,
7.83–7.74 (m, 4H, quin), 6.94–6.91, 6.72–6.69 (m, 4H,
phen), 5.38 (s, 2H, CH2), 2.77 (s, 3H, CH3); 13C NMR
(DMSO): d 154.1, 151.8, 151.4, 151.1, 141.2, 139.8 (6
quart. C), 130.2, 129.4, 128.7, 128.1, 116.1, 116.1, 115.8,
115.8 (8 tert. C), 70.7 (CH2), 22.0 (CH3).
hr-MS: Calcd for C16H14N2Oþ2 : 266.1055, found 266.1055.
4-(3-Methylquinoxalin-2-ylmethoxy)phenyloxyacetic acid
(9a). This compound was obtained from 8a in 78% yield
as colorless crystals, mp 157 8C (dec.) (EtOH); IR: 3062,
2936, 2518, 1724, 1598, 1574, 1500, 1464, 1448, 1382,
1364, 1328, 1306, 1268, 1238, 1198, 1164, 1132, 1108,
1076, 1030, 1012, 968, 910, 882, 860, 840, 818, 800, 778,
4.2.4. General procedure for the synthesis of compounds
8a and 8b. A mixture of 4c (20 mmol, 5.32 g), 2-bromo-
alkanoic acid alkyl ester (24 mmol) and powdered
anhydrous potassium carbonate (29 mmol, 4.01 g) in
2-butanone (400 ml) was heated at reflux for 5 h by
vigorous stirring. Inorganic salts were separated by filtering
the boiling solution. The residue was washed two times with
1
764, 704690, 670, 636, 620, 582, 520, 482, 426; H NMR
(DMSO): d 8.07–8.03, 7.84–7.79 (m, 4H, quin), 5.39 (s,

I. Starke et al. / Tetrahedron 60 (2004) 6063–6078
6073
2H, CH2O), 4.66 (s, 2H, CH2O), 3.9 (br., s, 1H, COOH, 2.80
(s, 3H, CH3); 13C NMR (DMSO): d 170.5 (CvO), 154.1,
152.7, 152.4, 151.2, (4 tert. C), 141.2, 139.9 (2 each tert. C),
130.3, 129.4, 128.8, 128.2 (4 tert. C), 115.9, 115.5 (je 2
tert.C), 70.5, 65.1 (2 sec. C), 22.0 (CH3).
4.26 (s, 2H, CH2OH), 3.5 (br., s, 1H, OH,), 2.59 (s, 3H,
CH3); 13C NMR (DMSO): d 157.2, 154.0, 151.1, 141.2,
139.8, 135.3 (6 quart.C), 130.3, 129.4, 128.8, 128.2, 128.1,
128.1, 114.6, 114.6 (8 tert.C), 69.9, 62.6 (2CH2), 22.0
(CH3).
hr-MS: Calcd for C20H20N2Oþ4 : 352.1423, found 352.1368.
hr-MS: Calcd for C17H16N2Oþ2 : 280.1212, found 280.1218.
2-[4-(3-Methyl-quinoxalin-2-ylmethoxy)phenyloxy]pro-
pionic acid (9b). This compound was obtained from 8b in
63% yield as colorless crystals, mp 146 8C (dec.)(50%
EtOH); IR: 2926, 1732, 1568, 1508, 1462, 1376, 1330,
1288, 1228, 1166, 1134, 1102, 1040, 952, 908, 816, 784,
3-Methoxy-4-(3-methylquinoxalin-2-ylmethoxy)benzyl
alcohol (11c). This compound was obtained from
4-hydroxy-3-methoxybenzyl alcohol (3.39 g) in 72% yield
as colorless needles, mp 159–160 8C (toluene); IR: 3388,
3046, 2994, 2942, 2872, 1594, 1568, 1514, 1466, 1422,
1376, 1328, 1260, 1234, 1162, 1136, 1030, 908, 846, 826,
802, 764, 740, 680, 642, 616, 550, 442; 1H NMR (DMSO): d
8.06–8.00, 7.83–7.75 (m, 4H, quin), 7.08, (d, 1H, o-phen),
6.96 (s, 1H, phen), 6.82 (d, 1H, o-phen), 5.37 (s, 2H, CH2O),
5.15 (t, J¼5.6 Hz, 1H,OH), 4.42 (d, J¼5.6 Hz, 2H,
CH2OH), 3.73 (s, 3H, CH3O), 2.80 (s, 3H, 3-CH3); 13C
NMR (DMSO): d 154.4, 151.2, 149.3, 146.3, 141.2, 139.8,
136.5 (7 quart.C), 130.3, 129.4, 128.8, 128.1, 118.6, 114.5,
110.9 (7 tert.C), 71.2 (CH2), 62.8 (CH2), 55.5 (OCH3), 21.9
(3-CH3).
1
770, 756, 728, 684, 614, 558, 522, 460, 424; H NMR
(DMSO): d 7.88–7.82, 7.65–7.56 (m, 4H, quin), 6.86–
6.89, 6.67–6.64 (dd, 4H, phen), 5.17, (s, 2H, CH2O), 4.53
(q, J¼6.7 Hz, 1H, alpha-CH), 2.58 (s, 3H, 3-CH3), 2.30 (s,
1H, COOH), 1.29 (d, J¼6.7 Hz, 3H, a-CCH3); 13C NMR
(DMSO): d 173.5 (CvO), 154.1, 152.6, 152.1, 151.2, 141.2,
139.8 (6 quart. C), 130.3, 129.4, 128.8, 128.2 (4 tert. C),
151.9 (4 tert. C), 72.2 (O–CH), 70.5 (OC–H2), 22.0
(3-CH3), 18.5 (CH3).
hr-MS: Calcd. for C19H18N2Oþ4 : 338.1267, found 338.1263.
hr-MS: Calcd for C18H18N2Oþ3 : 310.1317, found 310.1307.
4.2.6. General procedure for the synthesis of compounds
11a–c. To the solution of a hydroxybenzyl alcohol
(22 mmol) in EtOH (50 ml) was first added ethanolic
KOH solution (21 mmol, 1.18 g in 50 ml EtOH) and
thereafter a solution of 2-(bromomethyl)-3-methylquinoxa-
line (20 mmol, 4.74 g) in warm EtOH (120 ml) under
stirring. The mixture was heated at reflux for 2 h. KBr
crystallized during this time was filtered off from the boiling
solution. After the addition of water (40 ml), the EtOH was
evaporated in vacuo. The residue was kept in the refrigerator
overnight. The solid product was collected by filtration,
washed with 50% aqueous ethanol and recrystallized.
4.2.7. General procedure for the synthesis of compounds
16a–g. The solution of SeO2 (20 mmol, 2.22 g) in aqueous
dioxane (19 ml dioxane and 1 ml water) was added to the
solution of an acetyl compound 13a-c (20 mmol) in dioxane
(30 ml). The mixture was heated at reflux for 2–3 h, while
the acetyl group was oxidized into the glyoxalyl group,
selen was precipitated and the mixture became dark.
The precipitate was filtered off from the boiling
mixture and washed with hot dioxane (25 ml). The dioxane
solutions were combined and mixed with a solution of an
appropriate 1,2-phenylenediamine 15a-c (20 mmol) in
dioxane (25 ml). The resulting mixture was heated at reflux
for 2 h again, concentrated in vacuo and kept at room
temperature overnight. The product was collected by
filtration, washed with icecold MeOH and with water and
recrystallized.
2-(3-Methylquinoxalin-2-ylmethoxy)benzyl alcohol (11a).
This compound was obtained from 2-hydroxybenzyl
alcohol (2.73 g) in 86% yield as colorless needles, mp
119–121 8C (EtOH); IR: 3286, 3182, 3062, 2920, 2882,
1602, 1588, 1568, 1490, 1454, 1434, 1402, 1370, 1326,
1282, 1240, 1162, 1132, 1112, 1038, 1008, 930, 906, 848,
2-(Benzo[b]fur-2-yl)quinoxaline (16a). This compound13,14
was obtained from 3.20 g 13a and 2.16 g 15a in 64% yield
as pale yellow prisms, mp 174–175 8C (1-butanol); IR:
3115, 3060, 1590, 1540, 1305, 1255, 920, 765, 750, 745,
1
824, 772, 758, 712, 682, 614, 598, 490, 434, H NMR
(CDCl3): d 8.05–7.95, 7.69–7.65, 7.32–7.23, 7.04–6.94
(m, 8H, quin, phen.), 5.38 (s, 2H, CH2O), 4.76 (s, 2H,
CH2OH), 2.70 (s, 3H, CH3); 13C NMR (CDCl3): d 156.4,
152.2, 150.2, 141.5, 140.1 (5 quart. C), 130.3, 130.1, 129.3,
129.1, 128.8, 128.6, 128.1, 121.5, 111.7 (9 tert. C), 68.7,
61.7 (2 sec. C), 21.8 (CH3).
1
690; H and 13C NMR-data.28
hr-MS: m/z Calcd. for C16H10N2O: 246.0799, found
246.0793.
hr-MS: Calcd for C17H16N2Oþ2 : 280.1212, found 280.1199.
2-(Benzo[b]fur-2-yl)-6,7-dichloroquinoxaline (16b). This
compound was obtained from 3.20 g 13a and 3.54 g 15b
in 58% yield as colorless needles, mp 206–208 8C
(1-pentanol); IR 3098, 1932, 1750, 1602, 1576, 1536,
1456, 1392, 1348, 1308, 1286, 1260, 1184, 1144, 1106,
1052, 962, 932, 920, 906, 882, 852, 822, 784, 750, 688, 680,
4-(3-Methylquinoxalin-2-ylmethoxy)benzyl alcohol (11b).
This compound was obtained from 4-hydroxybenzyl
alcohol (2.73 g) in 59% yield as colorless needles, mp
149–151.5 8C (EtOH); IR: 3368, 3044, 2920, 2868, 1606,
1584, 1510, 1492, 1464, 1438, 1404, 1370, 1328, 1292,
1246, 1172, 1130, 1114, 1034, 1004, 906, 874, 852, 834,
798, 782, 762, 738, 700, 680, 614, 586, 550, 512, 488, 460,
1
658, 624, 608, 558, 494, 424; H NMR (CDCl3): d 9.40,
8.27, 8.21 (s, 3H-quin.), d 7.32–7.46 and d 7.64–7.73 (m,
4H-benzf.), 13C NMR (CDCl3): d 128.6, 134.8, 135.8,
141.4, 140.8, 145.2, 152.7, 156.4 (8 quart.C), 109.3, 112.4,
122.6, 124.3, 127.2, 129.9, 130.3, 143.9 (8 tert.C).
1
434; H NMR (DMSO): d 7.89–7.82, 7.63–7.59 (m, 4H,
quin), 7.08, 6.88 (dd, 4H, subst. phen.), 5.23 (s, 2H, CH2O),

6074
I. Starke et al. / Tetrahedron 60 (2004) 6063–6078
hr-MS: m/z Calcd. for C16H8Cl2N2O: 314.0014, found
314.0010.
2-(5-Bromobenzo[b]fur-2-yl)quinoxaline (16g). This com-
pound was obtained from 4.78 g 13c and 2.16 g 15a in 34%
yield as reddish-brown crystals, mp 200–204 8C (nonane);
IR 3068, 3018, 1890, 1732, 1610, 1578, 1540, 1484, 1438,
1406, 1364, 1346, 1324, 1290, 1262, 1204, 1158, 1126,
1046, 960, 924, 868, 810, 762, 696, 670, 626, 608, 576, 558,
524, 458, 426, 412; 1H NMR(CDCl3): d 9.40 (s 1H-quin.) d
8.24–8.10 (m, 2H-quin.) d 7.83–7.76 and 7.61–7.79 (m,
6H-quin and benzf.), 13C NMR (CDCl3): d 116.8, 141.9,
142.2, 142.3, 143.5, 154.2, 154.5 (7 quart.C), 106.9, 113.4,
124.5, 129.1, 129.3, 129.5, 130.2, 130.3, 130.8 (9 tert.C).
2-(Benzo[b]fur-2-yl)-6,7-dimethylquinoxaline (16c). This
compound was obtained from 3.20 g 13a and 2.72 g 15c in
42% yield as yellow prisms, mp 184–185 8C (cyclohexane);
IR 3050, 2972, 2916, 1930, 1748, 1626, 1590, 1538, 1486,
1448, 1360, 1310, 1294, 1260, 1210, 1178, 1156, 1144, 1110,
1048, 1026, 1002, 970, 920, 910, 882, 868, 810, 792, 742,
694, 648, 628, 610, 514, 488, 426; 1H NMR(CDCl3): d 9.27,
7.89, 7.81 (s, 3H-quin.), d 7.58–7.68 and 7.27–7.41 (m, 5H-
benzf.), 13C NMR (CDCl3): d 140.6, 140.7, 141.0, 141.2,
141.5, 143.0, 153.2, 155.7 (8 quart.C), 107.0, 111.8, 121.8,
123.5, 125.9, 128.2, 128.4, 128.5 (8 tert.C), 20.3 (2CH3).
hr-MS: m/z Calcd for C16H9BrN2O: 323.9898, found
323.9885.
hr-MS: m/z Calcd for C18H14N2O: 274.1106, found
274.1101.
4.2.8. General procedure for the synthesis of compounds
16a,h–j,l,p,s, 20a,b from compounds 17a–h, 19a,b,
respectively. The respective compound (17a–h, 19a,b)
was dissolved in EtOH under heating and then mixed with
the equimolar amount of ethanolic KOH. The mixture was
heated at reflux for 2–3 h, concentrated in vacuo, water
added and the mixture was kept in the refrigerator
overnight, the product was collected by filtration, washed
with water and with icecold MeOH and purified by
recrystalization.
2-(5-Chlorobenzo[b]fur-2-yl)quinoxaline (16d). This com-
pound was obtained from 3.89 g 13b and 2.16 g 15a in 57%
yield as colorless needles, mp 200–204 8C (nonane); IR 3068,
3028, 1612, 1582, 1546, 1486, 1466, 1446, 1410, 1366, 1348,
1328, 1292, 1266, 1240, 1206, 1168, 1132, 1054, 958, 926,
908, 876, 864, 826, 812, 760, 696, 628, 612, 582, 436, 410;
1HNMR(CDCl3): d 9.31 (s 1H-quin.), d 8.08–8.15 and 7.72–
7.81 (m, 4H-quin.), d 7.31–7.58 and 7.57–7.63 (m, 4H-
benzf.), 13C NMR (CDCl3): d 129.58, 141.9, 142.1, 142.3,
143.4, 154.1, 154.3 (7 quart.C), 107.0, 112.9, 121.4, 126.4,
129.27, 129.31, 129.45, 130.1, 130.7 (9 tert.C).
2-(Benzo[b]fur-2-yl)quinoxaline (16a).28 This compound
was obtained from the compound 17a in 62% yield.
2-(Benzo[b]fur-2-yl)-3-methylquinoxaline (16h). This com-
pound was obtained from the compound 17b in 92% yield as
pale yellow needles, mp 142–143.5 8C (EtOH); IR 3055,
3200, 2992, 1570, 1535, 1480, 1430, 1390, 1375, 1330,
1315, 1240, 1195, 1150, 1130, 1010, 920, 980, 830, 815,
hr-MS: m/z Calcd for C16H9ClN2O: 280.0403, found
280.0398.
2-(5-Chlorobenzo[b]fur-2-yl)-6,7-dichloroquinoxaline
(16e). This compound was obtained from 3.89 g 13b and
3.54 g 15b in 56% yield as colorless needles, mp 256–
257 8C (dioxane); IR 3086, 1734, 1598, 1576, 1538, 1492,
1392, 1324, 1288, 1262, 1208, 1180, 1156, 1108, 1054, 966,
930, 918, 900, 874, 802, 736, 698, 680, 660, 622, 578, 558,
496, 426; 1H NMR(CDCl3): d 9.40, 8.29, 8.25 (s, 3H-quin.),
d 7.70–7.57 and 7.26–7.41 (m, 5H-benzf.); 13C NMR
(CDCl3/CH3OH, 315K): d 108.1, 112.6, 121.4, 126.7,
129.5, 129.6, 143.1 (7 tert.C), d 130.5, 134.6, 135.4,
140.4, 140.7, 144.3, 148.3, 153.2, 154.1 (9 quart. C).
1
745, 760, 750, 710, 630, 605, 560, 530, 420; H and 13C
NMR.28
hr-MS: m/z Calcd for C17H12N2O: 260.0950, found
260.0959.
2-(5-Chlorobenzo[b]fur-2-yl)-3-methylquinoxaline (16i).
This compound was obtained from the compound 17c in
92% yield as pale yellow needles, mp 157–159 8C (PrOH);
IR 3060, 1535, 1480, 1430, 1375, 1335, 1320, 1245, 1190,
1150, 1130, 1050, 1005, 950, 925, 890, 855, 820, 800, 775,
1
hr-MS: m/z Calcd for C16H7Cl3N2O: 347.9624, found
347.9611.
755, 715, 700, 690, 605, 450, 420; H NMR(CDCl3): d
8.15–7.96 and 7.76–7.67 (m, 4H-quin.), d 7.63 (d, 1H-
benzf.) d 7.54–7.30 (m, 3H-benzf.), d 3.12 (s CH3); 13C
NMR (CDCl3): d 129.1, 129.6, 140.6, 141.0, 143.4, 151.4,
153.7, 154.9 (8 quart.C), 109.3, 112.8, 121.2, 126.1, 128.3,
129.0, 129.4, 130.3 (8 tert.C), 25.0 (CH3).
2-(5-Chlorobenzo[b]fur-2-yl)-6,7-dimethylquinoxaline
(16f). This compound was obtained from 3.89 g 13b and
2.72 g 15c in 45% yield as yellow prisms, mp 221–222 8C
(nonane); IR 3098, 2976, 2948, 1854, 1726, 1624, 1580,
1536, 1484, 1444, 1362, 1328, 1294, 1282, 1262, 1208,
1178, 1156, 1110, 1054, 1022, 1002, 970, 920, 900, 866,
800, 760, 736, 696, 626, 578, 516, 488, 460, 426; 1H
NMR(CDCl3): d 9.31, 7.91, 7.86 (s, 3H-quin.) d 7.66–7.55
and 7.36–7.35 (m, 4H-benzf.), d 2.52 (s 2CH3), 13C
NMR(CDCl3): d 129.2, 129.8, 141.1, 141.4, 154.1, 156.2
(6 quart.C), 106.4, 112.9, 121.4, 126.2, 128.4, 128.5 (6
tert.C), 20.4 (2CH3).
hr-MS: m/z Calcd for C17H11ClN2O: 294.0560, found
294.0548.
2-(5-Bromobenzo[b]fur-2-yl)-3-methylquinoxaline (16j).
This compound was obtained from the compound 17d in
86% yield as pale yellow needles, mp 167–168.5 8C
(propanol); IR 3066, 2924, 1720, 1632, 1606, 1572, 1556,
1542, 1480, 1452, 1428, 1372, 1338, 1320, 1244, 1190,
1152, 1134, 1118, 1046, 1024, 1012, 960, 926, 900, 862,
826, 806, 780, 762, 720, 704, 674, 638, 610, 582, 568,
hr-MS: m/z Calcd for C18H13ClN2O: 308.0716, found
308.0707.
1
450, 426; H NMR (CDCl3): d 8.14–7.99 and 7.76–7.71

I. Starke et al. / Tetrahedron 60 (2004) 6063–6078
6075
(m, 4H-quin), d 7.81–7.80 and 7.52–7.45 (m, 4H benzf.), d
3.07 (s CH3); 13C NMR (CDCl3): d 116.54, 130.1, 140.6,
141.1, 143.4, 151.4, 154.1, 154.8 (8 quart.C), 108.9, 113.3,
124.4, 128.4, 128.8, 129.2, 129.6, 130.4 (8 tert.C), 25.0
(CH3); HR-MS: m/z Calcd for C17H11BrN2O: 338.0055,
found 338.0052.
(toluene); IR 3050, 1630, 1585, 1545, 1475, 1445, 1400,
1350, 1215, 1170, 1135, 1085, 1060, 1025, 990, 925, 855,
800, 780, 750, 700, 610, 590, 550, 520, 490, 420; 1H
NMR(CDCl3): d 8.29–8.26 and 8.16 and 8.12 (m for 2H-
quin.), d 7.90–7.40 (m, 13H-quin. and naphth.), d 7.05 (m
1H-phen); 13C NMR (CDCl3): d 123.5, 127.7, 129.3, 139.3,
140.1, 141.1, 143.2, 152.0, 153.0, 153.3 (10 quart.C), 109.8,
112.6, 123.1, 124.9, 126.7, 127.3, 127.71, 128.8, 128.9,
129.2, 130.27, 130.4 (12 tert.C).
2-(6-Methoxy-3-phenylbenzo[b]fur-2-yl)-3-methyl-
quinoxaline (16l). This compound was obtained from the
compound 17f in 73% yield as yellow needles, mp 115–
117 8C (EtOH); IR 3050, 2970, 2940, 2840, 1615, 1500,
1485, 1450, 1440, 1400, 1365, 1340, 1320, 1300, 1280,
1190, 1150, 1130, 1105, 1075, 1050, 1020, 1000, 960, 940,
920, 855, 820, 755, 745, 725, 700, 665, 630, 600, 580, 565,
550, 540, 430; 1H and 13C NMR and elemental analysis data
see Ref. 28.
hr-MS: Calcd for C26H16N2Oþ: 372.1263, found 372.1247.
4.2.9. General procedure for the synthesis of compounds
16h,k,l, 20a,b from compounds 1a,b and 12a–e, 18
(examples for a one-pot-method). The procedure is the
same as above for the synthesis of compounds 17 and 19
with one exception—after heating at reflux, another
equivalent of base (KOH or EtONa), dissolved in EtOH,
was added and the mixture was then heated further at reflux
for 2 h.
2-(Benzo[b]fur-2-yl)-3-phenylquinoxaline (16p). This com-
pound was obtained from the compound 17g in 84% yield as
yellow needles, mp 160–161 8C (EtOH); IR 3056, 1952,
1772, 1686, 1612, 1560, 1478, 1460, 1444, 1398, 1356,
1312, 1216, 1222, 1198, 1186, 1138, 1060, 1028, 990, 928,
2-(Benzo[b]fur-2-yl)-3-methylquinoxaline (16h).28 This
compound was obtained from the reaction of compound
1a with 12a in ethanolic KOH in 82% yield.
1
880, 822, 804, 758, 700, 656, 614, 564, 538, 512, 428; H
and 13C NMR-data.28
hr-MS: Calcd for C22H14N2Oþ: 322.1106, found 322.1104.
2-(3-Methylbenzo[b]fur-2-yl)-3-methylquinoxaline (16k).28
This compound was obtained from the reaction of compound
1a with 12d and in ethanolic EtONa in 58% yield as pale
yellow needles, mp 117–118 8C (EtOH); IR 3050, 2970,
2910, 1575, 1530, 1475, 1425, 1395, 1370, 1330, 1310, 1270,
1240, 1190, 1125, 1100, 1060, 990, 920, 900, 875, 750, 740,
2-(Benzo[b]fur-2-yl)-3-(4-chlorophenyl)quinoxaline (16s).
This compound was obtained from the compound 17h in
83% yield as yellow needles, mp 192–193 8C (EtOH); IR
3062, 3037, 1936, 1897, 1857, 1777, 1668, 1639, 1612,
1594, 1559, 1537, 1492, 1477, 1459, 1397, 1354, 1315,
1261, 1218, 1198, 1170, 1134, 1092, 1057, 990, 960, 928,
882, 836, 824, 807, 764, 748, 719, 658, 617, 590, 552, 539,
515, 485, 458, 446, 429; 1H NMR(CDCl3): d 8.28–8.12 and
7.83–7.79 (m, 4H-quin.), d 7.62–6.49 and d 6.79 (m and s
10H benzf. and phen); 13C NMR (CDCl3): d 127.8, 135.6,
137.6, 140.8, 141.0, 143.0, 151.8, 152.5, 155.3 (9 quart.C),
110.7, 111.9, 121.9, 123.4, 126.1, 128.9, 129.2, 129.3,
130.5, 130.6, 130.7 (11 tert.C).
1
715, 690, 620, 600, 590, 515, 450, 420; H, 13C NMR and
elemental analysis data see Ref. 15.
2-(6-Methoxy-3-phenylbenzo[b]fur-2-yl)-3-methyl-
quinoxaline (16l).29 This compound was obtained from the
reaction of compound 1a with 12e in ethanolic KOH in 61%
yield; 1H and 13C NMR and elemental analysis data see Ref.
15.
2-Methyl-3-(naphtho[2,1-b]fur-2-yl)quinoxaline (20a).
This compound30 was obtained from the reaction of
compound 1a with 18 in ethanolic KOH in 61% yield.
hr-MS: Calcd for C22H13N2OClþ: 356.0716, found
356.0694.
2-Methyl-3-(naphtho[2,1-b]fur-2-yl)quinoxaline (20a).
This compound25 was obtained from the compound 19a in
89% yield as yellow needles, mp 184–185 8C (toluene); IR
3050, 1580, 1570, 1510, 1470, 1435., 1370, 1330, 1300,
1245, 1215, 1200, 1145, 1120, 1070, 1025, 1010, 985, 950,
915, 860, 820, 795, 770, 750, 740, 710, 630, 605, 570, 550,
505, 465, 445; 1H NMR (CDCl3): d 8.20–8.17 and d 8.14–
8.11 and 8.02–7.97 and 7.93–7.90 (m, 4H-quin.), d 7.79–
7.67 and 7.62–7.40 (m, 6 H-naphth.) d 3.11 (s CH3); 13C
NMR (CDCl3): d 123.7, 127.7, 130.5, 140.6, 140.7, 143.8,
153.1, 153.4, 151.3 (9 quart.C), 108.9, 112.5, 123.4, 124.9,
126.7, 127.1, 128.3, 128.8, 129.0, 129.5, 129.8 (11 tert.C),
25.3 (CH3).
2-(Naphtho[2,1-b]fur-2-yl)-3-phenylquinoxaline (20b).
This compound21 was obtained from the reaction of
compound 1b with 18 in ethanolic KOH in 80% yield.
General procedure for preparing compounds 17 and 19.
Equimolar amounts of an o-hydroxy carbonyl compound
(12a-e, 18), a strong base (KOH or EtONa) and of
2-(halomethyl) compound (1a-c, 1g) were dissolved in
ethanol under heating and mixed in this sequence. The
mixture was heated at reflux for 2 h and then concentrated in
vacuo. It was often expedient to add little water at the end to
precipitate the product and to dissolve the KBr formed. The
mixture was cooled and kept in the refrigerator. Next day,
the solid was separated by filtering by suction and purified
by recrystalization.
hr-MS: Calcd for C21H14N2Oþ: 310.1106, found 310.1111.
2-(Naphtho[2,1-b]fur-2-yl)-3-phenylquinoxaline (20b).
This compound29,30 was obtained from the compound 19b
in 80% yield as yellow needles, mp 187.5–188.5 8C
2-(Quinoxalin-2-ylmethoxy)benzaldehyde (17a). This com-
pound was obtained from the reaction of 2-(chloromethyl)-
quinoxaline (1g) with compound 12a in 15% yield as

6076
I. Starke et al. / Tetrahedron 60 (2004) 6063–6078
colorless needles, mp 117.5–118.5 8C (heptane); IR 3072,
2920, 2854, 2752, 1924, 1668, 1600, 1554, 1490, 1446,
1414, 1378, 1308, 1282, 1234, 1202, 1124, 1106, 1058, 972,
910, 846, 816, 758, 648, 600, 532, 498, 448, 410. Anal.
Calcld for C16H12N2O2: C, 72.72; H, 4.58; N, 10.60; Found:
C, 72.55; H, 4.56; N, 10.45.
2766, 1958, 1690, 1598, 1542, 1482, 1454, 1400, 1378,
1365, 1320, 1284, 1238, 1188, 1156, 1132, 1098, 1078,
1040, 1012, 930, 904, 860, 832, 812, 874, 762, 716, 700,
648, 622, 602, 572, 554, 474, 440. Anal. Calcld for
C22H16N2O2: C, 77.63; H, 4.74; N, 8.23; Found: C, 77.69;
H, 4.81; N, 8.48.
2-(3-Methylquinoxalin-2-ylmethoxy)benzaldehyde (17b).
This compound was obtained from the reaction of
compound 1a with compound 12a in 89% yield as colorless
crystals, mp 129–131 (EtOH); IR 3060, 2950, 2875, 2775,
1690, 1600, 1580, 1560, 1480, 1460, 1430, 1400, 1375,
1350, 1295, 1255, 1220, 1200, 1165, 1130, 1100, 1045,
1025, 1000, 980, 900, 840, 810, 775, 755, 665, 645, 610,
565, 520, 475, 440, 405. Anal. Calcld for C17H14N2O2: C,
73.37; H, 5.07; N, 10.06; Found: C, 73.52; H, 5.16; N,
9.87.
2-(3-[4-Chlorophenyl]quinoxalin-2-ylmethoxy)benzalde-
hyde (17h). This compound was obtained from the reaction
of compound 1c with compound 12a in 74% yield as
colorless crystals, mp 167–168 8C (EtOH), IR 3066, 3041,
2957, 2932, 2862, 2758, 1907, 1686, 1597, 1546, 1481,
1455, 1398, 1382, 1356, 1284, 1230, 1193, 1160, 1125,
1093, 1043, 1031, 1015, 1000, 961, 902, 860, 840, 798, 763,
730, 703, 651, 633, 616, 601, 592, 564, 530, 501, 485, 459,
442. Anal. Calcld for C22H15ClN2O2: C, 70.50; H, 4.03; N,
7.47; Found: C, 70.28; H, 3.87; N, 7.22.
5-Chloro-2-(3-methylquinoxalin-2-ylmethoxy)benzalde-
hyde (17c). This compound was obtained from the reaction
of compound 1a with compound 12b in 46% yield as
colorless needles, mp 152–153 8C (toluene); IR 3040, 3000,
2970, 2945, 2880, 1690, 1595, 1485, 1455, 1405, 1390,
1365, 1325, 1265, 1230, 1200, 1180, 1125, 1020, 1000, 900,
890, 840, 805, 765, 750, 705, 680, 650, 610, 530, 435. Anal.
Calcld for C17H13Cl N2O2: C, 65.29; H, 4.19; N, 8.96;
Found: C, 64.98; H, 4.30; N, 8.78.
2-(3-Methylquinoxalin-2-ylmethoxy)naphthalen-1-carbal-
dehyde (19a). This compound was obtained from the
reaction of compound 1a with compound 18 in 67% yield
as colorless crystals, mp 175–177 8C (toluene, 2-ethoxy-
ethanol); IR 3054, 2992, 2943, 2803, 1911, 1828, 1658,
1618, 1589, 1511, 1493, 1498, 1434, 1418, 1399, 1368,
1344, 1300, 1265, 1230, 1180, 1160, 1144, 1063, 1027,
1005, 950, 913, 858, 820, 765, 707, 665, 637, 615, 597, 555,
520, 506, 438, 416. Anal. Calcld for C21H16N2O2: C, 76.81;
H, 4.91; N, 8.53; Found: C, 76.78; H, 5.21; N, 8.26.
5-Bromo-2-(3-methylquinoxalin-2-ylmethoxy)benzalde-
hyde (17d). This compound was obtained from the reaction
of compound 1a with compound 12c in 83% yield as
colorless needles, mp 160–161 8C (EtOH); IR 3040, 3000,
2945, 2880, 1690, 1590, 1510, 1485, 1465, 1425, 1400,
1390, 1370, 1325, 1260, 1230, 1200, 1185, 1110, 1020,
1000, 915, 890, 880, 830, 800, 765, 745, 680, 630, 610, 515,
435. Anal. Calcld for C17H13BrN2O2: C, 57.16; H, 3.67; N,
7.84; Found C, 57.15; H, 3.77; N, 7.88.
2-(3-Phenylquinoxalin-2-ylmethoxy)naphthalen-1-carbal-
dehyde (19b). This compound was obtained from the
reaction of compound 1b with compound 18 in 72% yield as
colorless crystals, mp 148–150 8C (toluene); IR 3050, 2925,
2885, 1650, 1610, 1585, 1560, 1500, 1480, 1455, 1435,
1365, 1345, 1320, 1285, 1220, 1160, 1150, 1120, 1085,
1050, 1025, 1000, 905, 855, 810, 760, 750, 710, 700, 670,
640, 615, 600, 560, 500. Anal. Calcld for C26H18N2O2: C,
79.98; H, 4.65; N, 7.17; Found: C, 80.34; H, 4.78; N,
6.93.
2-(3-Methylquinoxalin-2-ylmethoxy)acetophenone (17e).
This compound was obtained from the reaction of
compound 1a with compound 12d in 35% yield as pale
yellow crystals, mp 102–103 8C (heptane); IR 3060, 3030,
3000, 2925, 2885, 1665, 1595, 1485, 1455, 1405, 1375,
1360, 1325, 1290, 1240, 1170, 1165, 1125, 1065, 1045,
1025, 1000, 915, 900, 850, 820, 775, 765, 710, 675, 600,
590, 525, 435. Anal. Calcld for C18H16N2O2: C, 73.96; H,
5.52; N, 9.58; Found: C, 74.29; H, 5.62; N, 9.44.
4.2.10. General procedure for the synthesis of com-
pounds 21a–c. KOH solution (55 mmol, 3.08 g) in hot
EtOH (150 ml) was mixed with salicylic aldehyde
(60 mmol, 7.33 g). The resulting phenolate solution was
poured into the solution of the 2,3-bis(bromomethyl)-
quinoxaline 1d, 1e or 1f (25 mmol) in hot EtOH while
stirring. The mixture was heated at reflux for 3 h. The KBr
precipitate was removed by filtering from the boiling
mixture and washed with boiling EtOH (50 ml). The
ethanolic washings were combined with the reaction
solution. After adding 20 ml of water the solution was
concentrated in vacuo and kept in the refrigerator overnight.
The crystalized product was collected and recrystallized.
4-Methoxy-2-(3-methylquinoxalin-2-ylmethoxy)benzo-
phenone (17f). This compound was obtained from the
reaction of compound 1a with compound 12e in 63% yield
as colorless needles, mp 127–128 8C (CCl4); IR 3000, 2975,
2945, 2835, 1610, 1575, 1545, 1495, 1480, 1440, 1400,
1365, 1335, 1320, 1300, 1280, 1185, 1150, 1120, 1100,
1075, 1045, 1015, 995, 960, 935, 915, 900, 865, 840, 815,
760, 740, 720, 695, 660, 625, 600, 575, 560, 550, 530, 430.
Anal. Calcld for C24H20N2O3: C, 74.98; H, 5.24; N, 7.29;
Found: C, 74.85; H, 5.08; N, 7.42.
2,20-Quinoxalin-200,300-diylmethoxydibenzaldehyde (21a).
This compound was obtained from the reaction of 1d with
12a in ethanolic KOH in 62% yield as colorless needles
(ethanol), mp 150–151 8C; IR: 3070, 3010, 2896, 2774,
1978, 1684, 1600, 1582, 1478, 1458, 1404, 1356, 1202,
1242, 1220, 1200, 1164, 1126, 1102, 1042, 1012, 990, 908,
866, 834, 804, 754, 696, 648, 612, 598, 564, 528, 478, 444,
418; 1H NMR (CDCl3): d 10.32 (s, 2H, 2CHO), 8.16–7.00
(m, 12H, 2H-4, H-5, H-6, H-7; H-50, H-60, H-70, H-80), 5.70
2-(3-Phenylquinoxalin-2-ylmethoxy)benzaldehyde (17g).
This compound was obtained from the reaction of
compound 1b with compound 12a in 77% yield as colorless
crystals, mp 121.5–122.5 8C (BuOH); IR 3070, 2948, 2870,

I. Starke et al. / Tetrahedron 60 (2004) 6063–6078
6077
(s, 4H, 2CH2); 13C NMR (CDCl3): d 188.9 (2CHO), 160.2,
149.8, 141.3, 125.1 (4£2 quart. C); 135.9, 130.9, 129.3,
129.1, 121.5, 112.9 (6£2 tert. C); 70.6 (2CH2).
155.4, 152.2, 143.7, 143.0, 141.2 (2), 139.4 (2), 136.9 (2)
(11 quart.C); 131.9, 130.5, 128.2, 128.1, 126.2, 126.1,
123.5, 122.2, 122.0, 111.9 (2), 110.1, 110.0 (13 tert.C).
2,20-(600-Chloroquinoxalin-200,300-diyl)methoxydibenzalde-
hyde (21b). This compound was obtained from the reaction
of 1e with 12a in ethanolic KOH in 54% yield as colorless
needles (ethanol), mp 115–117 8C; IR: 3073, 2860, 2736,
1688, 1600, 1481, 1457, 1400, 1286, 1231, 1192, 1184,
1125, 1103, 1066, 1045, 1014, 942, 873, 834, 753, 646, 584,
489, 437; 1H NMR (CDCl3): d 10.30 (s, 2H, 2CHO), 8.12–
7.01 (m, 11H, 2H-2, H-3, H-4, H-5; H-50, H-60, H-80), 5.68
(s, 4H, 2CH2); 13C NMR (CDCl3): d 188.9 (2CHO); 160.1,
160.0, 150.9, 150.0, 141.6 (2), 139.8 (2), 136.8 (9 quart.C);
135.9 (2), 131.9, 130.3, 129.5, 128.4, 125.0, 121.6 (2), 112.9
(2) (11 tert.C); 70.4 (2CH2).
hr-MS: Calcd for C24H13N2O2Clþ: 396.0666, found
396.0668.
2,3-Bis(benzo[b]fur-2-yl)-6,7-dimethylquinoxaline (22c).
This compound was obtained from the dialdehyde 21c in
67% yield as pale yellow needles (toluene), mp 185–
186.5 8C; IR: 3393, 3061, 3038, 2980, 2919, 2366, 2343,
1945, 1782, 1683, 1561, 1544, 1478, 1451, 1417, 1350,
1326, 1309, 1256, 1229, 1204, 1161, 1144, 1111, 1060,
1023, 1000, 932, 907, 881, 820, 786, 751, 682, 655, 631,
1
612, 569, 492, 428; H NMR (CDCl3): d 7.93 (s, 2H, H-5,
H-8), 7.59 (d, J¼8.4 Hz, 2H0, H-40(2) or H-70(2)), 7.49 (d,
J¼8.7 Hz, 2H, H-70 or H-4 (2)), 7.32 (t, J¼8.0 Hz, 2H,
H-600(2) or H-50(2)), 7.24 (t, J¼8.0 Hz, 2H, H-50(2) or
H-6 (2)); 7.11 (s, 2H, H-30(2)); 2.48 (s, 6H, 2CH3); 13C
NMR (CDCl3): d 155.2, 152.8., 142.0, 141.8, 139.9, 128.3
(6£2 quart.C); 128.3, 125.5, 123.2, 121.7, 111.7, 108.9 (6£2
tert.C); 20.4 (2CH3).
2,20-(600,700-Dimethylquinoxalin-200,300-diyl)methoxydiben-
zaldehyde (21c). This compound was obtained from the
reaction of 1f with 12a in ethanolic KOH in 76% yield as
colorless needles (ethanol), mp 153–154 8C; IR: 3074,
2975, 2863, 2765, 1684, 1600, 1559, 1482, 1458, 1402,
1360, 1291, 1244, 1223, 1200, 1162, 1103, 1046, 1013, 986,
1
873, 833, 754, 649, 583, 528, 439; H NMR (CDCl3): d
hr-MS: Calcd for C26H18N2Oþ: 390.1368, found 390.1375.
10.34 (s, 2H, 2CHO); 7.89 (s, 2H, H-50, H-80), 7.80–7.01
(m, 8H, 2H-2, H-3, H-4, H-5), 2.53 (s, 6H, 2CH3); 13C NMR
(CDCl3): d 188.9 (2CHO); 160.3, 148.7, 141.7, 140.3, 125.0
(5£2 quart.C); 135.9, 129.1, 128.1, 121.4, 113.0 (5£2
tert.C); 70.6 (2CH2); 20.3 (2CH3).
5. Supporting information available
Tables 1a and b. Relative abundance (RA/%) of the most
important fragment ions of the aryloxymethyl quinoxalines
3, 4, 6, 8, 9, 11, 16, 20 and 22. Tables 2a and b. Elemental
compositions and accurate masses for diagnostic ions of
compounds 3, 4, 6, 8, 9, 11, 16, 20 and 22. This material is
available online alongside the electronic version of the
article in Elsevier web products including ScienceDirect:
http://www. Sciencedirect.com.
4.2.11. General procedure for the synthesis of com-
pounds 22a–c. The dialdehyde (21a,b or c) (10 mmol) was
dissolved in boiling ethanol, mixed with ethanolic solution
of potassium hydroxide (25 mmol) and heated at reflux for
2 h. The resulting mixture was kept in a refrigerator
overnight. The solid product was collected by filtering by
suction and recrystallized.
2,3-Bis(benzo[b]fur-2-yl)quinoxaline (22a). This com-
pound was obtained from the dialdehyde 21a in 64% yield
as pale yellow needles (toluene), mp 226–227 8C; IR: 3116,
3064, 3038, 2364, 1926, 1888, 1856, 1774, 1666, 1614,
1600, 1560, 1534, 1478, 1452, 1394, 1358, 1314, 1254,
1236, 1196, 1162, 1138, 1108, 1060, 1004, 974, 924, 884,
850, 824, 812, 776, 736, 690, 654, 634, 612, 570, 536, 508,
Acknowledgements
The skillfull assistance of Miss Sylvia Fu¨rstenberg in
collecting the MS data is gratefully acknowledged.
1
490, 460, 418; H NMR (CDCl3): d 8.24–8.18, 7.92–7.66
References and notes
(m, 4H, H-5, H-6, H-7, H-8), 7.62 (d, J¼0 7.8 Hz, 2H, H-40(2)
or H-70(2)), 7.55 (d, J¼7.9 Hz, 2H, H-7 (2) or H-40(2)), 7.35
(t, J¼8.0 Hz, 2H, H-60(2) or H-50(2)), 7.28 (t, J¼8.0 Hz, 2H,
H-50(2) or H-60(2)); 13C NMR (CDCl3): d 155.4, 152.5,
143.0, 140.9, 128.2 (5£2 quart.C), 130.9, 129.3, 125.9,
123.4, 121.9, 111.9, 109.5 (7£2 quart. C).
1. Starke, I.; Sarodnick, G.; Ovcharenko, V. V.; Pihlaja, K.;
Kleinpeter, E. Rapid Commun. Mass Spectrom. 2002, 16, 169.
2. (a) Karjalainen, A.; Krieger, H. Suomen Kemistilehti B 1970,
43, 273. (b) Kovacik, V.; Fedoronko, M.; Jezo, I. Org. Mass
Spectrom. 1973, 7, 449.
3. Part 12 Sarodnick, G.; Heydenreich, M.; Linker, T.;
Kleinpeter, E. Tetrahedron 2003, 59, 6311.
hr-MS: Calcd for C24H14N2Oþ2 : 362.1055, found 362.1046.
4. Mohrs, K. H.; Raddatz, S.; Matzke, M.; Fugmann, B.;
Fruchtmann, K.; Hatzelmann, A.; Mu¨ller-Peddinghaus, R. EP
574774 A1, 1993, Chem. Abstr. 1994, 120, 217737.
5. Sakata, G.; Makino, K.; Hashiba, K. Y. Heterocycles 1988, 27,
2481.
2,3-Bis(benzo[b]fur-2-yl)-6-chloroquinoxaline (22b). This
compound was obtained from the dialdehyde 21b in 72%
yield as pale yellow needles (toluene), mp 198–199 8C; IR:
3386, 3065, 2925, 1935, 1596, 1558, 1531, 1474, 1452,
1397, 1349, 1320, 1257, 1193, 1168, 1144, 1109, 1064,
1005, 933, 884, 830, 790, 748, 697, 650, 612, 579, 506, 423;
1H NMR (CDCl3): d 8.20–8.12 (m, 2H-quin.), d 7.62–7.20
(m, 10H-benzf., 1H-quin.); 13C NMR (CDCl3): d 155.5,
6. The Pesticide Manual, 12th edition produced and published
solely by the British Crop Protection Council (BCPC), 2000,
ISBN 1 901396 12 6.
7. Parg, A.; Berghaus, R.; Bratz, M.; Von-der-Heide, J.; Burgers,

6078
I. Starke et al. / Tetrahedron 60 (2004) 6063–6078
J. W.; Kober, R.; Fries, K. J.; Schneider, K. WO 2000035287
A1, DE 19857604 A1, Priority (US, DE) 1998, 1215.
20. Turecek, F.; Svetlik, J. Org. Mass Spectrom. 1981, 16, 285.
21. Van der Wel, H.; Nibbering, N. M. M.; Kingston, E. E.;
Beynon, J. H. Org. Mass Spectrom. 1985, 20, 535.
22. Madhusudanan, K. P.; Mittal, S.; Durani, S.; Kapil, R. S. Org.
Mass Spectrom. 1985, 20, 215.
8. Johnson, W. G.; Li, J. M.; Wait, J. D. Weed Technol. 2003, 17,
36.
9. Kramer, C. R.; Stache, J.; Sarodnick, G.; Kranz, L.; Ku¨hne,
S. DD 258 165 (v.13.07.1988); Chem. Abstr. 1989, I, 110, P
110132s.
23. Poradowska, H.; Kaniewska, A. Org. Mass Spectrom. 1981,
16, 5.
10. Bredereck, H.; Heck, H. Chem. Ber. 1958, 91, 1314.
11. Stoermer, R. Liebigs Ann. Chem. 1900, 312, 333.
12. Jeromin, G. E.; Orth, W.; Rapp, B.; Weiß, W. Chem. Ber.
1987, 120, 649.
24. Roche, J. V.; et, M.; Gore, J. Org. Mass Spectrom. 1977, 12,
751.
25. Kleinpeter, E.; Hilfert, L.; Koch, A. J. Phys. Org. Chem. 1999,
12, 725.
13. Sarodnick, G.; Kempter, G. Z. Chem. 1982, 22, 300.
14. Wegmann, J.; Dahn, H. Helv. Chim. Acta 1946, 29, 1247.
15. Sarodnick, G.; Hilfert, L.; Kempter, G.; Kleinpeter, E. J. Prakt.
Chem. 1997, 339, 714.
26. Sarodnick, G.; Vogt, K.; Kempter, G.; Jumar, A. DD258 226
A1 v. 13.07.1988, Chem. Abstr. 1989, 110, 114869k.
27. Vogt, K.; Sarodnick, G.; Kempter, G.; Ku¨hne, S. I. DD258 227
A1, v. 13.07.1988, Chem. Abstr. 1989, 110, P95276w.
28. Hilfert, L.; Sarodnick, G.; Kempter, G.; Kleinpeter, E. J. Mol.
Struct. 1998, 444, 199.
16. Webster, B. R. Chem. Commun. 1966, 124.
17. Bentley, T. W.; Johnstone, R. A. W.; Palying, D. W. Chem.
Commun. 1968, 1154.
29. Sarodnick, G.; Kempter, G.; Jumar, A. DD276 479 v.
28.02.1990, Chem. Abstr. 1991, 114, 6543y.
18. Jaeger, D. A.; Tomer, K. B.; Woodgate, P. D.; Gebreyesus, T.;
Dejerassi, C.; Shapiro, R. H. Org. Mass Spectrom. 1974, 9,
551.
30. Sarodnick, G.; Kempter, G.; Klepel, M. DD276 480
28.02.1990, Chem. Abstr. 1990, 113, 231411c.
19. Ramana, D. V.; Vairamani, M.; Kala, S. Org. Mass Spectrom.
1975, 10, 196.