N1-Allyl-3-substituted-6,7-dimethyl-1, 2-dihydro-2-quinoxalinone as key intermediate for new acyclonucleosides and their regioisomer O-analogues

Article abstract of DOI:10.1002/hc.20203

The key intermediates allyloxyquinoxaline 2a-c and N-allylquinoxaline 3a-c were used to synthesize a number of acyclonucleosides whose chemical modifications include quinoxaline ring and the acyclic part is either N ¹-propanediol or 3-hydroxypr

Full text of DOI:10.1002/hc.20203

Heteroatom Chemistry
Volume 17, Number 4, 2006
N1-Allyl-3-substituted-6,7-dimethyl-1,
2-dihydro-2-quinoxalinone as Key Intermediate
for New Acyclonucleosides and Their
Regioisomer O-Analogues
Ibrahim A. I. Ali1 and Walid Fathalla2
1Department of Chemistry, Faculty of Science, Suez Canal University, Ismailia, Egypt
2Department of Mathematical and Physical Sciences, Faculty of Engineering,
Suez Canal University, Port-Said, Egypt
Received 3 July 2005; revised 21 September 2005
ABSTRACT: The key intermediates allyloxyquinox-
aline 2a–c and N-allylquinoxaline 3a–c were used
to synthesize a number of acyclonucleosides whose
chemical modifications include quinoxaline ring and
the acyclic part is either N1-propanediol or 3-hydroxy-
propyl substituents and their O-analogues. These
compounds were characterized by elemental analysis,
ꢀ
C
MALDI MS, and NMR data. 2006 Wiley Periodicals,
Inc. Heteroatom Chem 17:280–288, 2006; Published online
in Wiley InterScience (www.interscience.wiley.com). DOI
10.1002/hc.20203
Conventional and common synthetic meth-
ods for the preparation of acyclic nucleosides
and nucleotides involve the coupling reaction
of heterocyclic bases with ꢀ-halo [5–7] or ace-
INTRODUCTION
The successful development of acyclovir I (ACV)
[1,2], 9-[(2-hydroxyethoxy)-methyl]guanine, and
ganciclovir II (DHPG) [3,4] as excellent antiviral
agents have stimulated the synthesis and biological
evaluation of a wide variety of acyclic nucleosides
modified either in the base moiety or the acyclic
part.
toxymethyl ethers catalyzed by various Lewis acids
or bases [7,8], e.g., HMDS [5,6], SnCl4, Hg(CN)2,
(CH3)3SiClO4, (CH3)3SiSO3C4F9 [9,10], and natural
phosphates (NP) [6] to afford the regioselective
N-alkylation of the nucleobases, i.e., acyclonucleo-
side.
Quinoxaline derivatives have attracted in-
terest as biologically active materials [11–13].
They also find considerable application as an-
giotensin II receptor antagonists [14], NMDA antag-
onists [15], anti-inflammatory [16], antidepressant-
tranquilizing agents [17], and antitumor drugs
[18,19]. El Ashry et al. [7] described the synthesis
Correspondence to: Walid Fathalla; e-mail: walid399@yahoo.
com.
Present address of Walid Fathalla: 4-Suez Canal Authority
Street, P.O. 41112, Ismailia, Egypt.
c
ꢀ
2006 Wiley Periodicals, Inc.
280

N1-Allyl-3-substituted-6,7-dimethyl-1,2-dihydro-2-quinoxalinone as Key Intermediate for New Acyclonucleosides 281
of some homoacyclovir analogues of 2-(1H)-
MALDI MS of both alkylated couples 2a–c and 3a–c
gave identical results agreed with the molecular for-
mula of these compounds. This made us conclude
that these compounds are isomeric alkylated prod-
ucts. Thus, the MALDI of 2a and 3a gave 237.4 and
237.5, respectively, corresponding to (M + Na)+. The
1H NMR spectra of compounds 2 and 3 gave small
evidence to deduce the site of alkylation. The 1H
NMR spectrum of 2a showed a doublet at δ 4.89 at-
tributed to OCH2, while that of 3a gave δ 5.00 at-
tributed to NCH2. The 13C NMR clearly deduce the
alkylation site; it shows a chemical shift at δ 66.7
corresponding to OCH2 for 2a while a shift at δ 43.4
quinoxalinone bases and their activity against Hep-
atitis B virus (HBV). The tested compounds showed
high viral replication inhibition with low cytotoxic-
ity. Therefore, a continuous need for new quinoxa-
line acyclonucleosides are still of great interest.
RESULTS AND DISCUSSION
In this paper, we report the results related
to the synthesis of the acyclonucleosides whose
chemical modifications include quinoxaline as the
heterocyclic base and the acyclic part (acyclic
sugar residue) is either N1-propanediol or 3-
hydroxypropyl substituents and their O-analogues.
The N-acyclonucleosides and the O-regioisomers
could be useful for the antiviral evaluation and SAR
study.
As part of our continuing interest toward the
regioselective reactions of ambident nucleophiles,
i.e., thioamides [20–22], we have studied the reac-
tion of quinoxalines 1a–c [23–25] with electrophiles.
Thus, the reaction of the ambident nucleophile 1a–c
with allyl bromide in the presence of NaH in N,N-
dimethylformamide always afforded a mixture of
O- and N-allyl substituted quinoxalines 2a–c and
3a–c, respectively (Scheme 1). The two alkylated iso-
mers were easily separated by column chromatog-
raphy using petroleum ether/ethylacetate (6:1) as
eluent to afford 2a–c in 27–33% yield and 3a–c in
56–62% yield. The elemental analysis together with
1
corresponding to NCH2 for 3a. The H NMR spec-
tra of the N-alkylated quinoxaline gave an inter-
esting pattern due to an anisotropy caused by the
adjacent alkyl substituent toward both methyl
groups and the aromatic protons. Thus, the 1H NMR
spectrum of 2a showed δ at 2.33, 7.48, and 7.65 at-
tributed to 2CH3, CHAr, and CHAr, respectively, while
the 13C NMR showed δ 19.8, 20.1, 118.1, 126.6, 128.2,
and 132.8 corresponding to (CH3), (CH3), (CH CH2),
(CHAr), (CHAr), and (CH CH2), respectively. On the
other hand, the 1H NMR spectrum of 3a gave δ 2.47,
2.53, 7.20, and 7.71 attributed to CH3, CH3, CHAr,
and CHAr, respectively, while the 13C NMR showed
δ 18.6, 20.1, 114.3, 117.3, 130.0, and 130.2, corre-
sponding to (CH3), (CH3), (CHAr), (CH CH2), (CHAr),
and (CH CH2), respectively.
The presence of the allyl group on oxygen rather
than on the nitrogen of the quinoxaline can be ex-
plained as being due to rearrangement of the N-allyl
group via a Claisen rearrangement to afford the
O-allyl derivative 2a–c [8]. The N/O alkylation prod-
ucts were once again produced in a similar manner
by the reaction of the ambident nucleophile 1 with
3-bromopropanol under the same reaction condition
to afford the O-substituted propanol 4a–c in 26–35%
yield and N-substituted propanol 5a–c in 58–62%
yield (Scheme 1).
The basic physicochemical features described
above for allyl derivatives 2 and 3 were also found
for compounds 4a–c and 5a–c. The O-alkylation site
were confirmed from the 13C NMR spectrum that
shows δ 58.6 and 60.7 attributed to two OCH2 groups
of compound 4a. The 13C NMR spectrum of 5a gave
δ 38.5 and 58.0 attributed to NCH2 and OCH2 groups,
respectively.
The structure of these compounds was chemi-
cally confirmed by an equivocal synthesis of these
compounds from the allyl derivatives 2a–c and 3a–c.
Thus, The borohydride hydroxylation of the allyl key
intermediate 2a–c and 3a–c using BH3·DMS under
inert atmosphere gave the N- and O-3-hydroxypropyl
derivatives 4a–c and 5a–c, respectively, in good
SCHEME 1 Reagents and conditions: (i) 3-bromopropanol,
NaH, DMF, 100◦C, 3 h; (ii) allyl bromide, NaH, DMF, 100◦C,
3 h.
Heteroatom Chemistry DOI 10.1002/hc

282 Ali and Fathalla
The key intermediate allyloxy quinoxaline 2a–c
and N-allyl quinoxaline 3a–c prepared in a single
step were designed to produce acyclonucleosides
mainly from the N-allyl quinoxaline, in addition to
O-regioisomer analogues. The allyl group is an ex-
cellent precursor for various chemical modifications
as described above.
Another type of acyclonucleoside classified as
tetra seco type, possessing a glycerol-1-yl side-chain
and their O-analogues were prepared. Thus, stirring
allyl derivatives 2a–c and 3a–c with AD-mix ꢁ in
tert-butyl alcohol for 2 days at ambient tempera-
ture afforded O- and N-propanediol 7a–c and 11a–c,
1
respectively, in moderate yield [26]. The H NMR
spectra of diol derivative 7a–c gave completely differ-
ent pattern compared to the N-substituted propane-
1
diol 11a–c (Schemes 2 and 3). The H NMR spec-
trum of 7b gave multiplet centered at δ 3.71, 4.12
and a doublet at δ 4.56 corresponding to CH2OH,
CHOH, and OCH2, respectively. On the other hand,
1
the H NMR of propanediol 11b gave two doublets
of doublets at δ 3.50 and 3.68 attributed to NCH2 and
two doublets of doublets at δ 4.23 and 4.51 attributed
to OCH2.
The selective tosylation of the primary alcohol of
the diol 7b afforded tosylate 8. Treatment of tosylate
with NaH failed to give the epoxide by smooth dis-
placement of the tosyl group and instead it afforded
the 2-allyloxyquinoxaline 2b.
SCHEME 2 Reagents and conditions: (i) AD-mix ꢁ, t BuOH,
H2O, 0◦C, 2 days; (ii) BH3·DMS, THF, 4 h, NaOH, H2O2,
0◦C; (iii) acetic anhydride, pyridine, 15 h; (iv) p-toluenesulfonyl
chloride, dichloromethane, pyridine, 0◦C, 1 h; (v) NaH, THF,
room temperature, 24 h.
yields 74–82% (Schemes 2 and 3). Acetylation of
compounds 4a–c and 5a–c afforded the propyl
acetate derivatives 6a–c and 10a–c, respectively,
in good to moderate yields, which gave an addi-
tional chemical evidence of the products formed
(Schemes 2 and 3).
EXPERIMENTAL
Solvents were purified and dried in the usual way.
The boiling range of the petroleum ether used was
35–65◦C. Thin layer chromatography (TLC): silica
gel 60 F254 plastic plates (E. Merck, layer thickness
0.2 mm) detected by UV absorption. Melting points
were determined on a Bu¨chi 510 melting-point ap-
paratus and the values are uncorrected. NMR spec-
tra measured with Bruker AC 250 (250 MHz). TMS
(0.00 ppm) or the signal of the deuterated sol-
vent was used as internal standard. FAB-MS mod-
ified Finningan MAT 312/AMD 5000 spectrometer at
790 eV and T = 70 MALDI-MS, the mass spectra were
measured with a KRATOS Analytical Kompact.
General Procedure of Allylation Reaction
A mixture of quinoxaline derivatives (14 mmol)
and NaH (0.30 g, 14 mmol) in dry DMF (20 mL)
was stirred at 100◦C for 0.5 h, and then cooled to
room temperature. Allyl bromide (1.4 mL, 16 mmol)
was added and the mixture was stirred at 100◦C
for 3 h. The reaction mixture was evaporated to
dryness under reduced pressure, and the residue
SCHEME 3 Reagents and conditions: (i) AD-mix ꢁ, t BuOH,
H2O, 0◦C, 2 days; (ii) BH3·DMS, THF, 4 h, NaOH, H2O2, 0◦C;
(iii) acetic anhydride, pyridine, 15 h.
Heteroatom Chemistry DOI 10.1002/hc

N1-Allyl-3-substituted-6,7-dimethyl-1,2-dihydro-2-quinoxalinone as Key Intermediate for New Acyclonucleosides 283
was chromatographed on silica gel column with
petroleum ether/ethylacetate as eluent to give the
products.
(s, 1H, Ar-H), 7.20 (s, 1H, Ar-H), 6.15–6.00 (m, 1H,
CH CH2), 5.46 (d, 1H, J = 10.4 Hz, CH), 5.29 (d, 1H,
J = 17.3 Hz, CH), 5.00 (d, 2H, J = 5.1 Hz, NCH2),
2.53 (s, 3H, CH3), 2.47 (s, 3H, CH3). 13C NMR (62.8
MHz): δ = 154.1 (C O), 148.4 (CH), 140.4 (C N),
132.1 (Cq), 131.5 (Cq), 130.2 (CH CH2), 130.0 (CHAr),
117.3 (CH CH2), 114.3 (CHAr), 43.4 (NCH2), 20.1
(CH3), 18.6 (CH3). (MALDI, positive mode, Matrix:
DHB): m/z = 237.5 (M + Na)+. C13H14N2O (214.27):
C, 72.87; H, 6.59; N, 13.07; Found: C, 73.11; H, 6.26;
N, 12.82.
2-(Allyloxy)-6,7-dimethylquinoxaline 2a. Yellow
powder (0.90 g, 30%); R = 0.73 (petroleum ether/
f
ethylacetate, 3:1); mp 45◦C. 1H NMR (CDCl3):
δ = 8.32 (s, 1H, CH), 7.65 (s, 1H, Ar-H), 7.48 (s,
1H, Ar-H), 6.17–6.00 (m, 1H, CH CH2), 5.43 (d, 1H,
J = 17.2 Hz, CH), 5.25 (d, 1H, J = 10.4 Hz, CH), 4.89
(m, 2H, OCH2), 2.33 (s, 6H, 2CH3). 13C NMR (62.8
MHz): δ = 156.6 (C N), 140.1 (C N), 138.7 (Cq),
138.2 (CH), 137.7 (Cq), 136.1 (Cq), 132.8 (CH CH2),
128.2 (CHAr), 126.6 (CHAr), 118.13 (CH CH2), 66.7
(OCH2), 20.1 (CH3), 19.8 (CH3). (MALDI, posi-
tive mode, Matrix: DHB): m/z = 237.4 (M + Na)+.
C13H14N2O (214.27): C, 72.87; H, 6.59; N, 13.07;
Found: C, 73.11; H, 6.63; N, 13.42.
1-Allyl-3,6,7-trimethyl-1,2-dihydro-2-quinoxalin-
one 3b. White powder (1.80 g, 56%); Rf = 0.33
(petroleum ether/ethylacetate, 3:1); mp 98◦C. 1H
NMR (CDCl3): δ = 7.73 (s, 1H, Ar-H), 7.22 (s, 1H,
Ar-H), 6.24–6.09 (m, 1H, CH CH2), 5.48 (d, 1H,
J = 10.4 Hz, CH), 5.38 (d, 1H, J = 17.2 Hz, CH),
5.07 (d, 2H, J = 5.2 Hz, NCH2), 2.79 (s, 3H, CH3),
2.59 (s, 3H, CH3), 2.53 (s, 3H, CH3). 13C NMR
(62.8 MHz): δ = 156.4 (C O), 154.2 (C N), 138.6
(Cq), 131.8 (Cq), 130.8 (Cq), 130.5 (CH CH2), 129.9
(Cq), 129.1 (CHAr), 117.3 (CH CH2), 114.1 (CHAr),
43.8 (NCH2), 20.9 (CH3), 20.0 (CH3), 18.7 (CH3).
(MALDI, positive mode, Matrix: DHB): m/z = 251.5
(M + Na)+. C14H16N2O (228.29): C, 73.66; H, 7.06; N,
12.27; Found: C, 73.76; H, 7.23; N, 12.01.
2-(Allyloxy)-3,6,7-trimethylquinoxaline 2b. White
powder (1.05 g, 33%); Rf = 0.78 (petroleum ether/
ethylacetate, 3:1); mp 72◦C. 1H NMR (CDCl3):
δ = 7.59 (s, 1H, Ar-H), 7.46 (s, 1H, Ar-H), 6.18–6.05
(m, 1H, CH CH2), 5.41 (d, 1H, J = 17.4 Hz, CH), 5.24
(d, 1H, J = 10.8 Hz, CH), 4.91 (m, 2H, OCH2), 2.56 (s,
3H, CH3), 2.33 (s, 6H, 2CH3). 13C NMR (62.8 MHz):
δ = 155.4 (C N), 146.5 (C N), 138.5 (Cq), 138.2
(Cq), 137.2 (Cq), 135.8 (Cq), 132.9 (CH CH2), 127.4
(CHAr), 126.2 (CHAr), 117.4 (CH CH2), 66.6 (OCH2),
20.1 (CH3), 19.9 (CH3), 19.7 (CH3). (MALDI, pos-
itive mode, Matrix: DHB): m/z = 251.2 (M + Na)+.
C14H16N2O (228.29): C, 73.66; H, 7.06; N, 12.27;
Found: C, 73.43; H, 6.98; N, 12.56.
1-Allyl-6,7-dimethyl-3-phenyl-1,2-dihydro-2-quin-
oxalinone 3c. Yellow powder (2.55 g, 63%);
Rf = 0.55 (petroleum ether/ethylacetate, 3:1); mp
129◦C. 1H NMR (CDCl3): δ = 8.26–8.22 (m, 2H, Ar-H),
7.52 (s, 1H, Ar-H), 7.34–7.31 (m, 4H, Ar-H), 6.86
(s, 1H, Ar-H), 5.90–5.75 (m, 1H, CH CH2), 5.13 (d,
1H, J = 10.3 Hz, CH), 5.04 (d, 1H, J = 17.0 Hz, CH),
4.76 (m, 2H, NCH2), 2.21 (s, 3H, CH3), 2.19 (s, 3H,
CH3). 13C NMR (62.8 MHz): δ = 154.3 (C O), 152.5
(C N), 140.2 (Cq), 136.3 (Cq), 132.6 (Cq), 131.7 (Cq),
131.0 (CHAr), 130.7 (Cq), 130.6 (CH CH2), 130.0
(CHAr), 129.6 (CHAr), 128.0 (CHAr), 117.9 (CH CH2),
114.6 (CHAr), 44.5 (NCH2), 20.7 (CH3), 19.2 (CH3).
(MALDI, positive mode, Matrix: DHB): m/z = 313.6
(M + Na)+. C19H18N2O (290.36): C, 78.59; H, 6.25; N,
9.65; Found: C, 79.01; H, 6.43; N, 9.36.
2-(Allyloxy)-6,7-dimethyl-3-phenylquinoxaline 2c.
Yellow powder (1.10 g, 27%); Rf = 0.82 (petroleum
1
ether/ethylacetate, 3:1); mp 55◦C. H NMR (CDCl3):
δ = 8.07–8.03 (m, 2H, Ar-H), 7.59 (s, 1H, Ar-H), 7.46
(s, 1H, Ar-H), 7.44–7.35 (m, 4H, Ar-H), 6.14–6.01 (m,
1H, CH CH2), 5.36 (d, 1H, J = 17.2 Hz, CH), 5.19
(d, 1H, J = 10.5 Hz, CH), 4.95 (d, 2H, J = 5.4 Hz,
OCH2), 2.31 (s, 6H, 2CH3). 13C NMR (62.8 MHz):
δ = 154.9 (C N), 145.2 (C N), 139.9 (Cq), 138.5 (Cq),
137.9 (Cq), 136.5 (Cq), 133.0 (Cq), 129.8 (CHAr),
129.4 (CH CH2), 129.04 (CHAr), 128.4 (CHAr), 128.1
(CHAr), 126.2 (CHAr), 117.7 (CH CH2), 67.1 (OCH2),
20.3 (CH3), 20.0 (CH3), 20.3 (CH3). (MALDI, pos-
itive mode, Matrix: DHB): m/z = 313.8 (M + Na)+.
C19H18N2O (290.36): C, 78.59; H, 6.25; N, 9.65; Found:
C, 78.13; H, 6.56; N, 10.2.
N- and O-Substituted Propanol Derivatives
Method A. A mixture of quinoxaline deriva-
tives (14 mmol) and NaH (0.30 g, 14 mmol) in dry
DMF (20 mL) was stirred at 100◦C for 0.5 h, and
then cooled to room temperature. 3-Bromopropanol
(14 mmol) was added and the mixture was stirred
at 100◦C for 3 h. The reaction mixture was evap-
orated to dryness under reduced pressure, and the
residue was chromatographed on silica gel column
1-Allyl-6,7-dimethyl-1,2-dihydro-2-quinoxalinone
3a. White powder (1.87 g, 62%); Rf = 0.27
(petroleum ether/ethylacetate, 3:1); mp 142◦C.
1H NMR (CDCl3): δ = 8.33 (s, 1H, CH), 7.71
Heteroatom Chemistry DOI 10.1002/hc

284 Ali and Fathalla
with petroleum ether/ethylacetate as eluent to give
the products.
29%); Rf = 0.32 (petroleum ether/ethylacetate, 2:1);
mp 185◦C. 1H NMR (CDCl3): δ = 8.06–7.97 (m,
2H, Ar-H), 7.81 (s, 1H, Ar-H), 7.54 (s, 1H, Ar-H),
7.49–7.39 (m, 3H, Ar-H), 4.70 (t, 2H, J = 5.8 Hz,
CH2), 3.72 (m, 2H, CH2), 3.11 (bs, 1H, OH), 2.41 (s,
6H, 2CH3), 2.12–2.00 (m, 2H, CH2). 13C NMR (62.8
MHz): δ = 155.7 (C N), 145.7 (C N), 140.6 (Cq),
138.3 (Cq), 138.1 (Cq), 137.1 (Cq), 130.5 (Cq), 129.8
(CHAr), 129.7 (CHAr), 128.7 (CHAr), 128.5 (CHAr),
126.1 (CHAr), 63.9 (CH2), 59.5 (CH2), 32.6 (CH2), 20.5
(CH3), 20.3 (CH3). (MALDI, positive mode, Matrix:
DHB): m/z = 347.6 (M + K)+. C19H20N2O2 (308.38):
C, 74.00; H, 6.54; N, 9.08; Found: C, 74.34; H, 7.01;
N, 9.21.
Method B. To a solution of allyl quinoxaline
derivatives (14 mmol) in dry THF (50 mL) at 0◦C un-
der argon atmosphere, BH3·DMS (7 mL, 14 mmol,
2 M solution in THF) was added and the reaction
mixture was allowed to warm to room temperature
and stirred for 4 h. The reaction flask was cooled to
0◦C and then a solution of NaOH (7 g, 28 mmol) in
EtOH/H2O (2:1, 18 mL) followed by H2O2 (4.7 mL,
42 mmol, 30%, w/v solution in water) were added
dropwise over 30 min. It was then allowed to stir at
room temperature for 3 h. The product was taken up
in EtOAc and aqueous layer extracted with EtOAc
(3 × 50 mL). The combined organic layers were
washed with brine, water, dried (Na2SO4), and con-
centrated. The crude product was chromatographed
using petroleum ether/ethylacetate (3:1) as eluent.
Method B: (3.19 g, 74%).
1-(3-Hydroxypropyl)-6,7-dimethyl-1,2-dihydro-2-
quinoxalinone 5a (Method A). White powder (1.68 g,
58%); Rf = 0.12 (petroleum ether/ethylacetate, 2:1);
1
3-((6,7-Dimethyl-2-quinoxalinyl)oxy)-1-propanol
4a (Method A). Yellow powder (0.84 g, 26%);
Rf = 0.21 (petroleum ether/ethylacetate, 2:1); mp
mp 125◦C. H NMR (CDCl3): δ = 8.25 (s, 1H, CH),
7.65 (s, 1H, Ar-H), 7.20 (s, 1H, Ar-H), 4.48 (t, 2H,
J = 5.9 Hz, OCH2), 3.72 (bs, 1H, OH), 3.56 (m,
2H, NCH2), 2.44 (s, 3H, CH3), 2.37 (s, 3H, CH3),
2.14–1.93 (m, 2H, CH2). 13C NMR (62.8 MHz):
δ = 155.7 (C O), 148.7 (CH), 141.3 (C N), 133.1
(Cq), 132.1 (Cq), 130.7 (CHAr), 129.9 (Cq), 114.2
(CHAr), 58.0 (OCH2), 38.5 (NCH2), 29.9 (CH2), 20.6
(CH3), 19.0 (CH3). (MALDI, positive mode, Matrix:
DHB): m/z = 255.4 (M + Na)+. C13H16N2O2 (232.28):
C, 67.22; H, 6.94; N, 12.06; Found: C, 67.01; H, 7.21;
N, 11.82.
1
79◦C. H NMR (CDCl3): δ = 8.27 (s, 1H, CH), 7.63
(s, 1H, Ar-H), 7.41 (s, 1H, Ar-H), 4.55 (m, 2H, CH2),
3.65 (m, 2H, CH2), 3.10 (bs, 1H, OH), 2.32 (s, 6H,
2CH3), 1.90 (m, 2H, CH2). 13C NMR (62.8 MHz):
δ = 157.1 (C N), 142.2 (Cq), 140.4 (Cq), 138.1 (Cq),
136.4 (Cq), 127.9 (CHAr), 126.2 (CHAr), 60.7 (CH2),
58.6 (CH2), 32.0 (CH2), 20.1 (CH3), 19.2 (CH3).
(MALDI, positive mode, Matrix: DHB): m/z = 269.5
(M + Na)+. C14H18N2O2 (246.31): C, 68.27; H, 7.37;
N, 11.37; Found: C, 68.11; H, 7.71; N, 10.98.
Method B: (2.30 g, 71%).
Method B: (2.56 g, 79%).
1-(3-Hydroxypropyl)-3,6,7-trimethyl-1,2-dihydro-
2-quinoxalinone 5b (Method A). White powder (2.05
g, 61%); Rf = 0.15 (petroleum ether/ethylacetate,
3-((3,6,7-Trimethyl-2-quinoxalinyl)oxy)-1-propa-
nol 4b (Method A). White powder (1.20 g, 35%);
Rf = 0.25 (petroleum ether/ethylacetate, 2:1); mp
104◦C. 1H NMR (CDCl3): δ = 7.59 (s, 1H, Ar-H), 7.42
(s, 1H, Ar-H), 4.56 (t, 2H, J = 5.9 Hz, CH2), 3.74 (t,
2H, J = 5.9 Hz, CH2), 3.50 (bs, 1H, OH), 2.51 (s, 3H,
CH3), 2.34 (s, 6H, 2CH3), 2.07–1.93 (m, 2H, CH2).
13C NMR (62.8 MHz): δ = 156.3 (C N), 146.8 (C N),
139.1 (Cq), 138.1 (Cq), 137.3 (Cq), 136.3 (Cq), 127.5
(CHAr), 126.1 (CHAr), 63.3 (CH2), 58.9 (CH2), 32.8
(CH2), 20.3 (CH3), 20.2 (CH3), 20.0 (CH3). (MALDI,
positive mode, Matrix: DHB): m/z = 269.5 (M + Na)+.
C14H18N2O2 (246.31): C, 68.27; H, 7.37; N, 11.37;
Found: C, 68.11; H, 7.71; N, 10.98.
1
2:1); mp 148◦C. H NMR (CDCl3): δ = 7.48 (s, 1H,
Ar-H), 7.07 (s, 1H, Ar-H), 4.33 (t, 2H, J = 6.5 Hz,
OCH2), 3.80 (bs, 1H, OH), 3.50 (m, 2H, NCH2),
2.49 (s, 3H, CH3), 2.33 (s, 3H, CH3), 2.26 (s, 3H,
CH3), 2.03–1.90 (m, 2H, CH2). 13C NMR (62.8 MHz):
δ = 156.3 (C O), 155.6 (C N), 139.4 (Cq), 132.7 (Cq),
131.5 (Cq), 129.9 (Cq), 129.7 (CHAr), 114.1 (CHAr),
58.2 (CH2OH), 38.8 (NCH2), 30.0 (CH2), 21.2 (CH3),
20.4 (CH3), 19.0 (CH3). (MALDI, positive mode,
Matrix: DHB): m/z = 268.1 (M + Na)+. C14H18N2O2
(246.31): C, 68.27; H, 7.37; N, 11.37; Found: C, 67.88;
H, 7.51; N, 11.13.
Method B: (2.82 g, 82%).
Method B: (2.34 g, 68%).
3-((6,7-Dimethyl-3-phenyl-2-quinoxalinyl)oxy)-1-
1-(3-Hydroxypropyl)-6,7-dimethyl-3-phenyl-1,2-
propanol 4c (Method A). Yellow powder (1.25 g,
dihydro-2-quinoxalinone 5c (Method A). Yellow
Heteroatom Chemistry DOI 10.1002/hc

N1-Allyl-3-substituted-6,7-dimethyl-1,2-dihydro-2-quinoxalinone as Key Intermediate for New Acyclonucleosides 285
powder (2.67 g, 62%); Rf = 0.19 (petroleum
3-((6,7-Dimethyl-3-phenyl-2-quinoxalinyl)oxy)-
propyl Acetate 6c. Yellow powder (0.47 g, 68%);
Rf = 0.52 (petroleum ether/ethylacetate, 2:1); mp
ether/ethylacetate, 2:1); mp 210◦C. 1H NMR (CDCl3):
δ = 8.32–8.25 (m, 2H, Ar-H), 7.72 (s, 1H, Ar-H),
7.47–7.44 (m, 3H, Ar-H), 7.16 (s, 1H, Ar-H), 4.47 (t,
2H, J = 6.1 Hz, CH2), 3.75 (bs, 1H, OH), 3.58 (m, 2H,
CH2), 2.35 (s, 3H, CH3), 2.17–2.03 (m, 2H, CH2), 2.42
(s, 3H, CH3). 13C NMR (62.8 MHz): δ = 155.3 (C O),
152.4 (C N), 140.5 (Cq), 136.1 (Cq), 133.1 (Cq),
132.1 (Cq), 130.7 (CHAr), 130.0 (CHAr), 129.4 (CHAr),
128.2 (Cq), 127.9 (CHAr), 114.0 (CHAr), 58.2 (CH2),
39.0 (CH2), 30.2 (CH2), 20.6 (CH3), 19.06 (CH3).
(MALDI, positive mode, Matrix: DHB): m/z = 331.4
(M + Na)+. C19H20N2O2 (308.38): C, 74.00; H, 6.54;
N, 9.08; Found: C, 74.21; H, 6.62; N, 9.42.
1
95◦C. H NMR (CDCl3): δ = 8.06 (s, 1H, Ar-H), 7.94–
7.89 (m, 2H, Ar-H), 7.79 (s, 1H, Ar-H), 7.62–7.49 (m,
3H, Ar-H), 4.63 (t, 2H, J = 6.2 Hz, CH2), 4.29 (t, 2H,
J = 6.2 Hz, CH2), 2.51 (s, 6H, 2CH3), 2.26–2.18 (m,
2H, CH2), 2.04 (s, 3H, OAc). 13C NMR (62.8 MHz):
δ = 168.5 (C O), 145.3 (C N), 141.1 (C N), 140.4
(Cq), 138.4 (Cq), 129.5 (CHAr), 128.9 (CHAr), 128.1
(CHAr), 127.3 (CHAr), 126.1 (CHAr), 63.2 (CH2), 61.6
(CH2), 28.2 (CH2), 21.1 (CH3), 20.3 (CH3), 19.9 (CH3).
(MALDI, positive mode, Matrix: DHB): m/z = 373.4
(M + Na)+. C21H22N2O3 (350.41): C, 71.98; H, 6.33;
N, 7.99; Found: C, 72.14; H, 6.52; N, 8.35.
Method B: (3.62 g, 84%).
3-(6,7-Dimethyl-2-oxo-1,2-dihydro-1-quinoxalin-
yl)propyl Acetate 10a. Yellow powder (0.41 g, 77%);
Rf = 0.2 (petroleum ether/ethylacetate, 2:1); mp
General Procedure of Acetylation Reaction
1
The quinoxaline derivatives (2 mmol) were treated
with acetic anhydride (20 mL) and pyridine (20 mL).
The reaction mixture was stirred for 15 h, and then
concentrated and purified by flash chromatography
(petroleum ether/ethylacetate, 2:1).
80◦C. H NMR (CDCl3): δ = 8.16 (s, 1H, CH), 7.58
(s, 1H, Ar-H), 7.12 (s, 1H, Ar-H), 4.35 (t, 2H, J = 6.0
Hz, OCH2), 4.20 (t, 2H, J = 6.0 Hz, NCH2), 2.43 (s,
3H, CH3), 2.35 (s, 3H, CH3), 2.15–2.09 (m, 5H, OAc,
CH2). 13C NMR (62.8 MHz): δ = 170.3 (C O), 154.4
(C O), 148.4 (CH), 140.6 (C N), 132.2 (Cq), 131.7
(Cq), 130.3 (Cq), 129.9 (CHAr), 113.1 (CHAr), 61.5
(OCH2), 38.5 (NCH2), 26.1 (CH2), 20.4 (CH3), 20.3
(CH3), 18.6 (CH3). (MALDI, positive mode, Matrix:
DHB): m/z = 297.2 (M + Na)+. C15H18N2O3 (274.32):
C, 65.68; H, 6.61; N, 10.21; Found: C, 65.73; H, 6.52;
N, 10.43.
3-((6,7-Dimethyl-2-quinoxalinyl)oxy)propyl Ac-
etate 6a. White powder (0.43 g, 81%); Rf = 0.35
(petroleum ether/ethylacetate, 2:1); mp 65◦C. 1H
NMR (CDCl3): δ = 8.15 (s, 1H, CH); 7.52 (s, 1H, Ar-
H), 7.35 (s, 1H, Ar-H), 4.35 (t, 2H, J = 6.2 Hz, CH2),
4.20 (t, 2H, J = 6.2 Hz, CH2), 2.23 (s, 6H, 2CH3),
2.04–2.00 (m, 2H, CH2), 1.92 (s, 3H, OAc). 13C NMR
(62.8 MHz): δ = 170.7 (C O), 156.8 (C N), 138.7
(Cq), 138.6 (Cq), 138.1(Cq), 136.1 (Cq), 128.2 (CHAr),
126.5 (CHAr), 62.6 (CH2), 61.1 (CH2), 28.0 (CH2),
20.7 (CH3), 20.0 (CH3), 19.7 (CH3). (MALDI, positive
mode, Matrix: DHB): m/z = 297.2 (M + Na)+ + 313.3
(M + K)+. C15H18N2O3 (274.32): C, 65.68; H, 6.61; N,
10.21; Found: C, 66.12; H, 6.32; N, 10.41.
3-(3,6,7-Trimethyl-2-oxo-1,2-dihydro-1-quinoxa-
linyl)propyl Acetate 10b. White powder (0.48 g,
85%); Rf = 0.22 (petroleum ether/ethylacetate, 2:1);
1
mp 121◦C. H NMR (CDCl3): δ = 7.48 (s, 1H, Ar-H),
6.99 (s, 1H, Ar-H), 4.26 (t, 2H, J = 6.1 Hz, OCH2),
4.14 (t, 2H, J = 6.1 Hz, NCH2), 2.49 (s, 3H, CH3), 2.34
(s, 3H, CH3), 2.27 (s, 3H, CH3), 2.08–1.99 (m, 5H,
OAc, CH2). 13C NMR (62.8 MHz): δ = 170.7 (C O),
156.8 (C O), 154.9 (C N), 139.1 (Cq), 132.3 (Cq),
131.3 (Cq), 130.2 (Cq), 129.8 (CHAr), 113.7 (CHAr),
61.8 (CH2), 39.1 (CH2), 26.5 (CH2), 21.2 (CH3),
20.7 (CH3), 20.5 (CH3), 19.0 (CH3). (MALDI, pos-
itive mode, Matrix: DHB): m/z = 311.6 (M + Na)+.
C16H20N2O3 (288.34): C, 66.65; H, 6.99; N, 9.72;
Found: C, 66.84; H, 7.22; N, 9.54.
3-((3,6,7-Trimethyl-2-quinoxalinyl)oxy)propyl Ace-
tate 6b. White powder (0.40 g, 71%); Rf = 0.41
(petroleum ether/ethylacetate, 2:1); mp 87◦C.
1H NMR (CDCl3): δ = 7.63 (s, 1H, Ar-H), 7.50 (s,
1H, Ar-H), 4.50 (t, 2H, J = 6.3 Hz, CH2), 4.25 (t,
2H, J = 6.3 Hz, CH2), 2.56 (s, 3H, CH3), 2.37 (s, 6H,
2CH3), 2.28–2.11 (m, 2H, CH2), 2.02 (s, 3H, OAc).
13C NMR (62.8 MHz): δ = 170.9 (C O), 155.8 (C N),
146.6 (C N), 138.7 (Cq), 138.3 (Cq), 137.2 (Cq),
135.9 (Cq), 127.5 (CHAr), 126.2 (CHAr), 62.7 (CH2),
61.4 (CH2), 28.2 (CH2), 20.8 (CH3), 20.1 (CH3), 20.0
(CH3), 19.8 (CH3). (MALDI, positive mode, Matrix:
DHB): m/z = 311.5 (M + Na)+. C16H20N2O3 (288.34):
C, 66.65; H, 6.99; N, 9.72; Found: C, 66.31; H, 7.21;
N, 9.43.
3-(6,7-Dimethyl-2-oxo-3-phenyl-1,2-dihydro-1-qui-
noxalinyl)propyl Acetate 10c. Yellow powder (0.56 g,
80%); Rf = 0.30 (petroleum ether/ethylacetate, 2:1);
1
mp 175◦C. H NMR (CDCl3): δ = 8.33–8.24 (m, 2H,
Ar-H), 7.65 (s, 1H, Ar-H), 7.48–7.41 (m, 3H, Ar-H),
7.06 (s, 1H, Ar-H), 4.36 (t, 2H, J = 5.9 Hz, OCH2),
4.21 (t, 2H, J = 5.9 Hz, NCH2), 2.39 (s, 3H, CH3),
Heteroatom Chemistry DOI 10.1002/hc

286 Ali and Fathalla
2.32 (s, 3H, CH3), 2.18 (m, 2H, CH), 2.10 (s, 3H,
OAc). 13C NMR (62.8 MHz): δ = 170.8 (C O), 154.5
(C O), 152.7 (C N), 140.3 (Cq), 136.2 (Cq), 132.6
(CHAr), 131.9 (Cq), 130.8 (CHAr), 130.5 (Cq), 129.5
(CHAr), 127.9 (CHAr), 62.1 (OCH2), 39.6 (NCH2),
26.6 (CH2), 20.8 (CH3), 20.2 (CH3), 19.1 (CH3).
(MALDI, positive mode, Matrix: DHB): m/z = 373.5
(M + Na)+. C21H22N2O3 (350.42): C, 71.98; H, 6.33;
N, 7.99; Found: C, 72.31; H, 6.29; N, 7.75.
3-((6,7-Dimethyl-3-phenyl-2-quinoxalinyl)oxy)-
1,2-propanediol 7c. White powder (0.12 g, 73%);
Rf = 0.63 (methanol/chloroform, 5%); mp 115◦C.
1H NMR (CDCl3): δ = 8.05–7.98 (m, 2H, Ar-H), 7.82
(s, 1H, Ar-H), 7.55 (s, 1H, Ar-H), 7.47–7.42 (m, 3H,
Ar-H), 4.56 (m, 2H, CH2), 4.19–4.12 (m, 1H, CHOH),
4.07 (bs, 1H, OH), 3.78–3.65 (m, 2H, CH2OH), 3.26
(bs, 1H, OH), 2.40 (s, 6H, 2CH3). 13C NMR (62.8
MHz): δ = 155.1 (C N), 145.4 (C N), 140.6 (Cq),
138.0 (Cq), 137.7 (Cq), 137.3 (Cq), 136.1 (Cq), 129.6
(CHAr), 128.4 (CHAr), 128.3 (CHAr), 125.8 (CHAr),
70.8 (CHOH), 68.4 (OCH2), 63.7 (CH2OH), 20.4
(CH3), 20.1 (CH3). EI-MS: m/z = 324.0; C19H20N2O3
(324.38): C, 70.35; H, 6.21; N, 8.64; Found: C, 70.41;
H, 6.32; N, 8.81.
General Procedure (O- and N-Propanediol
7 and 11)
To a mixture of AD-mix ꢁ (0.7 g), tert-butyl al-
cohol (3 mL) and water (5 mL) were added and
the mixture was stirred vigorously for 20 min be-
fore being cooled to 0◦C. Allyl quinoxaline deriva-
tives (0.5 mmol) in tert-butyl alcohol (2 mL) was
added and the mixture was stirred for 2 days.
Sodium sulfite (0.62 g, 5 mmol) and water (20 mL)
were added and crude product was extracted with
dichloromethane (3 × 20 mL). The solvent was re-
moved at reduced pressure and purified by flash
chromatography (methanol/chloroform, 3%).
1-(2,3-Dihydroxypropyl)-6,7-dimethyl-1,2-dihydro-
2-quinoxalinone 11a. White powder (0.08 g, 61%);
Rf = 0.32 (methanol/chloroform, 5%); mp 164◦C.
1H NMR (CDCl3): δ = 8.20 (s, 1H, CH), 7.58 (s, 1H,
Ar-H),), 7.25 (s, 1H, Ar-H), 4.89–4.78 (bs, 1H, OH),
ꢁ
4.47 (dd, 1H, Jgem = 12.0 Hz, J1,2 = 7.6 Hz, OCH2),
ꢁ
4.25 (dd, 1H, Jgem = 12.0 Hz, J1,2 = 6.2 Hz, OCH2),
4.16–4.02 (m, 1H, CHOH), 3.78–3.48 (bs, 1H, OH),
ꢁ
3.68 (dd, 1H, Jgem = 10.9 Hz, J1,2 = 3.6 Hz, NCH2),
ꢁ
ꢁ
3.53 (dd, 1H, Jgem = 11.0 Hz, J1 ,2 = 2.9 Hz, NCH2),
2.37 (s, 3H, CH3), 2.29 (s, 3H, CH3). 13C NMR (62.8
MHz): δ = 156.0 (C O), 148.1 (CH), 141.5 (C N),
133.4 (Cq), 132.3 (Cq), 130.4 (CHAr), 118.1 (Cq), 114.7
(CHAr), 69.5 (CHOH), 63.2 (OCH2), 44.3 (NCH2), 20.5
(CH3), 19.0 (CH3). EI-MS: m/z = 248.0; C13H16N2O3
(248.28): C, 62.89; H, 6.50; N, 11.28; Found: C, 63.09;
H, 6.63; N, 11.40.
3-((6,7-Dimethyl-2-quinoxalinyl)oxy)-1,2-propan-
ediol 7a. White powder (0.07 g, 55%); Rf = 0.53
(methanol/chloroform, 5%); mp 119◦C. 1H NMR
(CDCl3): δ = 8.40 (s, 1H, CH), 7.71 (s, 1H, Ar-H), 7.50
(s, 1H, Ar-H), 4.54 (d, 2H, J = 4.5 Hz, OCH2), 4.14–
4.10 (m, 1H, CHOH), 3.76–3.71 (m, 2H, CH2OH),
4.05 (bs, 1H, OH), 3.40 (bs, 1H, OH), 2.36 (s, 6H,
2CH3). 13C NMR (62.8 MHz): δ = 156.7 (C N), 140.7
(C N), 137.9 (CH), 137.5 (Cq), 136.8 (Cq), 127.9
(CHAr), 126.0 (CHAr), 70.5 (CHOH), 67.7 (OCH2),
63.1 (CH2OH), 20.0 (CH3), 19.7 (CH3). EI-MS:
m/z = 248.0; C13H16N2O3 (248.28): C, 62.89; H, 6.50;
N, 11.28; Found: C, 63.21; H, 6.59; N, 11.32.
1-(2,3-Dihydroxypropyl)-3,6,7-trimethyl-1,2-dihy-
dro-2-quinoxalinone 11b. White powder (0.08 g,
56%); Rf = 0.42 (methanol/chloroform, 5%); mp
211◦C. 1H NMR (CDCl3): δ = 7.56 (s, 1H, Ar-H),
7.23 (s, 1H, Ar-H), 4.51 (dd, 1H, Jgem = 12.6 Hz,
ꢁ
ꢁ
J1 ,2 = 7.6 Hz, OCH2), 4.23 (dd, 1H, Jgem = 12.6 Hz,
ꢁ
ꢁ
J1 ,2 = 5.8 Hz, OCH2), 4.18–4.00 (m, 1H, CHOH),
3-((3,6,7-Trimethyl-2-quinoxalinyl)oxy)-1,2-pro-
panediol 7b. White powder (0.08 g, 65%); Rf = 0.58
(methanol/chloroform, 5%); mp 178◦C. 1H NMR
(CDCl3): δ = 7.61 (s, 1H, Ar-H), 7.43 (s, 1H, Ar-H),
4.56 (d, 2H, J = 4.5 Hz, CH2), 4.18–4.08 (m, 1H,
CHOH), 4.04 (bs, 1H, OH), 3.77–3.66 (m, 2H,
CH2OH), 3.21 (bs, 1H, OH), 2.54 (s, 3H, CH3), 2.35
(s, 6H, 2CH3). 13C NMR (62.8 MHz): δ = 155.9 (C N),
146.7 (C N), 139.4 (Cq), 137.5 (Cq), 137.4 (Cq), 138.7
(Cq), 127.5 (CHAr), 125.8 (CHAr), 70.9 (CHOH), 68.2
(OCH2), 63.5 (CH2OH), 20.2 (CH3), 20.1 (CH3), 19.9
(CH3). EI-MS: m/z = 262.0; C14H18N2O3 (262.31): C,
64.11; H, 6.92; N, 10.68; Found: C, 64.43; H, 6.75; N,
11.01.
3.72–3.70 (bs, 2H, 2OH), 3.68 (dd, 1H, Jgem = 12.5 Hz,
ꢁ
ꢁ
J1 ,2 = 3.2 Hz, NCH2), 3.50 (dd, 1H, Jgem = 12.5 Hz,
ꢁ
ꢁ
J1 ,2 = 3.2 Hz, NCH2), 2.48 (s, 3H, CH3), 2.39 (s,
3H, CH3), 2.33 (s, 3H, CH3). 13C NMR (62.8 MHz):
δ = 156.3 (C O), 156.2 (C N), 139.9 (Cq), 133.3 (Cq),
131.6 (Cq), 130.3 (Cq), 129.8 (CHAr), 114.3 (CHAr),
69.5 (CHOH), 63.0 (CH2OH), 44.5 (NCH2), 21.3
(CH3), 20.5 (CH3), 19.1 (CH3). EI-MS: m/z = 262.0;
C14H18N2O3 (262.31): C, 64.11; H, 6.92; N, 10.68;
Found: C, 63.76; H, 6.74; N, 10.53.
1-(2,3-Dihydroxypropyl)-6,7-dimethyl-3-phenyl-
1,2-dihydro-2-quinoxalinone 11c. White powder
(0.05 g, 55%); Rf = 0.51 (methanol/chloroform, 5%);
Heteroatom Chemistry DOI 10.1002/hc

N1-Allyl-3-substituted-6,7-dimethyl-1,2-dihydro-2-quinoxalinone as Key Intermediate for New Acyclonucleosides 287
1
mp 130◦C. H NMR (CDCl3): δ = 8.29–8.19 (m, 2H,
Ar-H), 7.64 (s, 1H, Ar-H), 7.46–7.32 (m, 3H, Ar-H),
7.23 (s, 1H, Ar-H), 4.96–4.76 (bs, 1H, OH), 4.47 (dd,
was added slowly and the mixture was extracted
with dichloromethane (3 × 30 mL). The combined
extracts were washed with water (2 × 20 mL), brine
(2 × 30 mL), and dried over anhydrous magnesium
sulfate. The solvent was removed at reduced pressure
and the crude product was purified by flash chro-
matography. White powder (0.021 g, 75%); Rf = 0.78
(petroleum ether/ethylacetate, 3:1); mp 72◦C. 1H
NMR (CDCl3): δ = 7.59 (s, 1H, Ar-H), 7.46 (s, 1H, Ar-
H), 6.18–6.05 (m, 1H, CH CH2), 5.41 (d, 1H, J = 17.4
Hz, CH), 5.24 (d, 1H, J = 10.8 Hz, CH), 4.91 (m, 2H,
OCH2), 2.56 (s, 3H, CH3), 2.33 (s, 6H, 2CH3).
ꢁ
ꢁ
1H, Jgem = 12.5 Hz, J1 ,2 = 7.8 Hz, OCH2), 4.28 (dd,
ꢁ
ꢁ
1H, Jgem = 12.5 Hz, J1 ,2 = 6.5 Hz, OCH2), 4.18–3.95
(bs, 2H, CHOH, CHOH), 3.71 (dd, 1H, Jgem = 10.8 Hz,
ꢁ
ꢁ
J1 ,2 = 3.7 Hz, NCH2), 3.53 (dd, 1H, Jgem = 10.7 Hz,
ꢁ
ꢁ
J1 ,2 = 3.5 Hz, NCH2), 2.42 (s, 3H, CH3), 2.30 (s,
3H, CH3). 13C NMR (62.8 MHz): δ = 155.6 (C O),
154.3 (C N), 140.9 (Cq), 135.9 (Cq), 133.4 (Cq), 132.0
(Cq), 130.9 (Cq), 130.5 (CHAr), 130.0 (CHAr), 129.5
(CHAr), 127.9 (CHAr), 114.6 (CHAr), 69.5 (CHOH),
63.3 (OCH2), 44.6 (NCH2), 20.6 (CH3), 19.1 (CH3).
EI-MS: m/z = 324.0; C19H20N2O3 (324.38): C, 70.35;
H, 6.21; N, 8.64; Found: C, 69.87; H, 6.43; N, 8.54.
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2-Hydroxy-3-((3,6,7-trimethyl-2-quinoxalinyl)oxy)-
propyl-p-toluenesulfonate 8. To a mixture of diol
derivative 7b (0.15 g, 0.59 mmol) and p-toluenesul-
fonyl chloride (0.12 g, 0.65 mmol) in dichloro-
methane (10 mL) cooled to 0◦C, pyridine (0.2 mL,
2.5 mmol) was added with stirring for 1 h. The
mixture was allowed to warm to room tempera-
ture, stirred for 24 h, then poured into water. The
aqueous layer was extracted with dichloromethane
(3 × 20 mL) and the combined organic extracts
washed with hydrochloric acid (1 M), water, and
brine. After drying over anhydrous magnesium
sulfate, the solvent was removed at reduced pres-
sure and the crude product was purified by flash
chromatography using petroleum ether/ethyacetate
as eluent. White powder (0.18 g, 77%); Rf = 0.36
(petroleum ether/ethyacetate, 3:1); mp 83◦C. 1H
NMR (CDCl3): δ = 7.91 (d, 2H, J = 8.2 Hz, Ar-H),
7.61 (s, 1H, Ar-H), 7.50 (s, 1H, Ar-H), 7.35 (d, 2H,
J = 8.2 Hz, Ar-H), 6.23–6.03 (m, 1H, CH), 5.43 (d,
1H, J = 17.2 Hz, CH), 5.26 (d, 1H, J = 10.5 Hz,
CH), 4.94 (d, 2H, J = 5.4 Hz, OCH2), 2.58 (s, 3H,
CH3), 2.42 (s, 3H, CH3), 2.37 (s, 6H, 2CH3). 13C
NMR (62.8 MHz): δ = 155.6 (C N), 146.6 (C N),
141.7 (Cq), 138.7 (Cq), 138.3 (Cq), 137.3 (Cq), 135.9
(Cq), 133.0 (CHAr), 130.1 (CHAr), 127.5 (CHAr), 126.9
(CHAr), 126.3 (CH), 117.5 (CH2), 66.7 (CH2), 21.7
(CH3), 20.2 (CH3), 20.0 (CH3), 19.8 (CH3). EI-MS:
m/z = 416.0; C21H24N2O5S (416.49): C, 60.56; H, 5.81;
N, 6.70; Found: C, 60.75; H, 5.90; N, 6.83.
Attempted Cyclization of 8
2-(Allyloxy)-3,6,7-trimethylquinoxaline 2b. To a
solution of monotosylate derivative 8 (0.05 g,
0.11 mmol) in tetrahydrofuran (20 mL) at room
temperature, sodium hydride (20 mg, of a 60% dis-
persion in mineral oil, 0.4 mmol) was added and
the mixture was stirred for 24 h. Water (50 mL)
Heteroatom Chemistry DOI 10.1002/hc

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Heteroatom Chemistry DOI 10.1002/hc