Studies with aza-heterocyclic N-oxides: Synthesis of some new aromatic N-oxide derivatives

Abstract

Benzofuroxan derivative (1a) reacts with the cyanoacetanilides (2a-d) to give the benzimidazole derivatives (3a-d). Benzofuroxan (1b) reacts with rhodanine derivatives (4a,b) in presence of sodium ethoxide to give the arylaminobenzoimidazole derivatives (6a,b); while the last reaction afforded the thiazolidinone derivatives (8a,b) and the o-benzoquinone dioxime derivatives (9a,b) when it was repeated in the presence of sodium acetate. Moreover, a series of quinoxalinyl 1,4-di-N-oxide derivatives were prepared starting from quinoxalin-1,4-di-N-oxide derivatives (10a-c). Plausible mechanisms to account for the formation of the products are discussed.

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European?Journal?of?Chemistry?2?(1)?(2011)?51‐57?
European?Journal?of?Chemistry?
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European?Journal?of?Chemistry?
ISSN?2153‐2249?(Print)?/?ISSN?2153‐2257?(Online)??2011?EURJCHEM?
DOI:10.5155/eurjchem.2.1.51‐57.249?
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Journal?homepage:?www.eurjchem.com?
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Studies?with?aza‐heterocyclic?N‐oxides:?Synthesis?of?some?new?aromatic??
N‐oxide?derivatives?
Ahmed?Ali?Faddaa,?Fathy?Mohamed?Abdelrazekb,*?and?Ahmed?Mahmoud?Foudaa?
aChemistry?Department,?Faculty?of?Science,?Mansoura?University,?Mansoura,?EG‐35516,?Egypt?
bChemistry?Department,?Faculty?of?Science,?Cairo?University,?Giza,?EG‐12613,?Egypt??
*Corresponding?author?at:?Chemistry?Department,?Faculty?of?Science,?Cairo?University,?Giza,?EG‐12613,?Egypt.?Tel.:?+202.35676601;?fax:?+202.35727556.??
E‐mail?address:?prof.fmrazek@gmail.com??(F.M.?Abdelrazek).?
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?ABSTRACT
?Benzofuroxan? derivative? (1a)? reacts? with? the? cyanoacetanilides? (2a‐d)? to? give? the
benzimidazole? derivatives? (3a‐d).? Benzofuroxan? (1b)? reacts? with? rhodanine? derivatives
(4a,b)? in? presence? of? sodium? ethoxide? to? give? the? arylaminobenzoimidazole? derivatives
(6a,b);? while? the? last? reaction? afforded? the? thiazolidinone? derivatives? (8a,b)? and? the? o‐
benzoquinone?dioxime?derivatives?(9a,b)?when?it?was?repeated?in?the?presence?of?sodium
acetate.?Moreover,?a?series?of?quinoxalinyl?1,4‐di‐N‐oxide?derivatives?were?prepared?starting
from?quinoxalin‐1,4‐di‐N‐oxide?derivatives?(10a‐c).?Plausible?mechanisms?to?account?for?the
formation?of?the?products?are?discussed.?
?
?
ARTICLE?INFORMATION?
Received:?16?August?2010?
Received?in?revised?form:?04?October?2010?
Accepted:?28?October?2010?
Online:?31?March?2011?
KEYWORDS?
Heterocyclic?N‐oxides?
Benzofuroxan?
Rhodanine?
o‐Quinone?dioximes?
Thiocarbohydrazide??
Curtius?rearrangement??
?
1.?Introduction?
?
Over? the? last? three? decades? we? have? been? involved? in? a?
program? aiming? to? develop? new? simple? procedures? or? novel?
precursors? for? the? synthesis? of? heterocyclic? compounds? of?
biological? interest? from? cheap? laboratory? available? starting?
materials?to?be?evaluated?as?biodegradable?agrochemicals?[1‐
8].?
Benzofuroxans?display?
pharmacological?properties?and?specific?studies?were?devoted?
to?these?aspects?[9‐11].?Several?authors?have?reported?about?
the?biological?importance?of?quinoxaline?1,4‐dioxides?(QdNO's)?
since? 1940's.? Classical? and? more? recent? methods? of? the?
synthesis? of? the? quinoxaline? 1,4‐dioxides? and? some? of? their?
most?important?reactions?were?also?reported?[12,13].?
Furthermore? quinoxaline? 1,4‐di‐N‐oxide? derivatives? were?
reported?to?exhibit?hypoxia‐selective?cytotoxins?and?anticancer?
activities? [14,15]? as? well? as? mycobacterium? tuberculostatic?
activities?[16,17].?In?view?of?these?facts?and?in?continuation?of?
our?earlier?interest?[18‐20],?we?report?here?the?results?of?our?
investigations?on?benzofuroxans?
quinoxaline?1,4‐di‐N‐oxide??(10a‐c)?derivatives?(Scheme?1).??
?
O
several?biochemical?and?
1‐oxide?(1a‐b)?and?
N
O
N
N
O
N
O
R
R
1a-c
1a, R= 5-CH3
1b, R= H
1c, R= 6-CH3
10a, R= H, R'= COCH3
10b, R= CH3, R'= COCH3
10c, R= CH3, R'= COOC2H5
N
N
R'
CH3
O
O
R
?
?
Scheme?1?
2.?Experimental?
?
All? melting? points? are? recorded? on? Gallenkamp? electric?
melting?point?apparatus?and?are?uncorrected.?The?IR?spectra?(υ,?
cm‐1;? KBr)? were? recorded? on? Perkin? Elmer? Infrared?
Spectrophotometer? Model? 157,?Grating.? The?1H? NMR? spectra?
were?run?on?Varian?Spectrometer?at?200?MHz?using?TMS?as?an?
internal?reference?and?DMSO‐d6?as?solvent?and?chemical?shifts?
are?expressed?in?δ?(ppm).?The?mass?spectra?(EI)?were?run?at?70?
eV? with? Kratos? MS? equipment? and/or? a? Varian? MAT? 311? A?
Spectrometer.?Elemental?analyses?were?carried?out?at?the?micro?
analytical? center?of? Cairo?
Benzofuroxans?(1a,b)?were?prepared?according?to?a?procedure?
reported?previously?[21].?
?
2.1.?Synthesis?of?2‐(arylcarbamoyl)‐1‐hydroxy‐5‐methyl‐1H‐
benzo[d]imidazole‐3‐oxide?(3a‐d)?
?
A? mixture? of? benzofuroxan? (1a)? (0.45? g,? 3? mmol)? and?
cyanoacetanilide? derivatives? (2a)? (0.523? g,? 3? mmol),? (2b)?
(0.523?g,?3?mmol),?(2c)?(0.571?g,?3?mmol)?or?(2d)?(0.571?g,?3?
mmol)?was?stirred?in?ethanol?(30?mL)?with?piperidine?(3?mL)?
overnight.?The?obtained?precipitates?were?filtered?off,?dried?and?
recrystallized? from? ethanol? to? afford? the? benzimidazole?
derivatives?(3a‐d).?
3a,? Dirty?yellow? solid,?M.p.:? 217?oC.? Yield:? 70%.? IR? (KBr,?
max,?cm‐1):? 3430? (OH),?3250? (NH),? 1660? (C=O),? 1620? (C=N),?
1236,?1317?(N→O).?1H?NMR?(DMSO,?δ?ppm):?2.0?(s,?1H,?OH),?
2.12?(s,?3H,?CH3),?2.34?(s,?3H,?CH3),?7.06‐7.50?(m,?7H,?Ar‐H),?9.15?
(s,? 1H,? NH).? MS? (m/z,? %):? 296? (M+‐1,? 26).? Anal.? Calcd.? for?
C16H15N3O3?(297.31):?C,?64.64;?H,?5.09.?Found:?C?64.56;?H,?5.12.?
3b,? Dirty? yellow? solid,?M.p.:? 206?oC.? Yield:? 75%.? IR? (KBr,?
max,?cm‐1):? 3452? (OH),?3226? (NH),? 1691? (C=O),? 1618? (C=N),?
University,? Giza,?Egypt.?

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52?
?
1231,?1323?(N→O).?1H?NMR?(DMSO,?δ?ppm):?2.0?(s,?1H,?OH),?
2.34?(s,?6H,?2CH3),?7.06‐7.56?(m,?7H,?Ar‐H),?9.15?(s,?1H,?NH).?MS?
(m/z,?%):?297?(M+,?60).?Anal.?Calcd.?for?C16H15N3O3?(297.31):?C,?
64.64;?H,?5.09;?N,?14.13.?Found:?C?64.41;?H,?4.97;?N,?14.37.?
3c,?Yellowish?red?solid,?M.p.:?196?oC.?Yield:?60%.?IR?(KBr,?
max,?cm‐1):? 3448? (OH),?3248? (NH),? 1680? (C=O),? 1632? (C=N),?
1236,?1335?(N→O).?1H?NMR?(DMSO,?δ?ppm):?2.0?(s,?1H,?OH),?
2.34?(s,?3H,?CH3),?3.83?(s,?3H,?OCH3),?6.73‐7.50?(m,?7H,?Ar‐H),?
9.15?(s,?1H,?NH).?MS?(m/z,?%):?313?(M+,?33).?Anal.?Calcd.?for?
C16H15N3O4?(313.31):?C,?61.34;?H,?4.83;?N,?13.41.?Found:?C?61.19;?
H,?4.86;?N,?13.56.?
3d,?Reddish?yellow?solid,?M.p.:?300?oC.?Yield:?77%.?IR?(KBr,?
max,?cm‐1):? 3437? (OH),?3236? (NH),? 1687? (C=O),? 1627? (C=N),?
1234,?1314?(N→O).?1H?NMR?(DMSO,?δ?ppm):?2.34?(s,?3H,?CH3),?
3.83?(s,?3H,?OCH3),?7.07‐7.50?(m,?7H,?Ar‐H),?9.15?(br.,?s,?1H,?NH).?
MS? (m/z,? %):? 314? (M++1,? 43).? Anal.? Calcd.? for? C16H15N3O4?
(313.31):?C,?61.34;?H,?4.83.?Found:?C?61.37;?H,?4.88.?
?
2.2.?Synthesis?of?1‐hydroxy‐1H‐benzo[d]imidazole‐3‐oxides?
(6a,?b)?
?
A? mixture? of? benzofuroxan? (1b)? (0.45? g,? 3? mmol)? and?
rhodanine?derivatives?(4a)?(0.67?g,?3?mmol)?or?(4b)?(0.718?g,?3?
mmol)?was?heated?under?reflux?for?6?hours?in?ethanol?(30?mL)?
in? the? presence? of? sodium? ethoxide? (0.069? g,? 3? mmol).? The?
reaction?mixture?was?left?to?stand?at?room?temperature?for?3?
hours,?then?poured?into?crushed?ice?and?acidified?with?dilute?
HCl,? effervescence? with? evolution? of? CO2? was? observed.? The?
formed? precipitate? was? filtered,? dried? and? crystallized? from?
ethanol?to?give?benzimidazole?derivatives?(6a,b).??
6a,? Reddish? brown? crystals,? M.p.:? 254?oC.? Yield:? 70%.? IR?
(KBr,? max,? cm‐1):? 3250? (NH),? 1248,? 1343? (N→O).?1H? NMR?
(DMSO,?δ?ppm):?2.0?(s,?1H,?OH),?2.2?(s,?3H,?CH3),?4.10?(s,?1H,?
NH),?6.85‐8.56?(m,?8H,?Ar‐H).?MS?(m/z,?%):?239?(M+‐16,?15).?
Anal.?Calcd.?for?C14H13N3O2?(255.27):?C,?65.87;?H,?5.13.?Found:?C,?
65.53;?H,?5.32.?
6b,? Reddish? brown? crystals,? M.p.:? 160?oC.? Yield:? 60%.? IR?
(KBr,? max,? cm‐1):? 3250? (NH),? 1248,? 1343? (N→O).?1H? NMR?
(DMSO,?δ?ppm):?2.0?(s,?1H,?OH),?2.34?(s,?3H,?CH3),?3.83?(s,?3H,?
OCH3),?4.10?(s,?1H,?NH),?6.18‐7.50?(m,?8H,?Ar‐H).?MS?(m/z,?%):?
272?(M++1,?16).?Anal.?Calcd.?for?C14H13N3O3?(271.27):?C,?61.99;?
H,?4.83;?N,?15.49.?Found:?C,?61.74;?H,?5.11;?N,?15.56.?
?
2.3.?Synthesis?of?2,2'‐dithiano‐Δ5,5'‐bi‐4‐thiazolidinones?
(8a,b)?
?
A? mixture? of? benzofuroxan? (1b)? (0.45? g,? 3? mmol),?
rhodanine?derivatives?(4a)?(0.67?g,?3?mmol)?or?(4b)?(0.718?g,?3?
mmol),?and?catalytic?amount?of?anhydrous?sodium?acetate?(0.5?
g,?6?mmol)?in?acetic?acid?(20?mL)?was?heated?on?water?bath?at?
90?oC? for? 2‐3? hours.? The? reaction? mixture? was? then? filtered,?
dried?then?heated?with?hot?ethanol?filtered?while?hot?to?give?4‐
thiazolidinone?dimers?(8a,b).?
8a,?Dark?yellow?solid,?M.p.:?>?300?oC.?Yield:?82%.?IR?(KBr,?
max,?cm‐1):?3232?(NH),?1248,?1343?(N→O).?1H?NMR?(DMSO,?δ?
ppm):?2.42?(s,?6H,?2CH3),?6.89‐7.59?(m,?8H,?Ar‐H).?MS?(m/z,?%):?
442?(M+,?75).?Anal.?Calcd.?for?C20H14N2O2S4?(442.60):?C,?54.27;?H,?
3.19;?N,?6.33;?S,?28.98.?Found:?C,?54.40;?H,?3.26;?N,?6.25;?S,?29.08.?
8b,?Reddish?brown?solid,?M.p.:?>300?oC.?Yield:?90%.?IR?(KBr,?
max,?cm‐1):?3250?(NH),?1236,?1335?(N→O).?1H?NMR?(DMSO,?δ?
ppm):?3.80?(s,?6H,?2OCH3),?6.91‐7.50?(m,?8H,?Ar‐H).?MS?(m/z,?
%):? 474? (M+,? 12).? Anal.? Calcd.? for? C20H14N2O4S4? (474.60):? C,?
50.61;?H,?2.97.?Found:?C,?50.58;?H,?2.93.?
?
2.4.?Synthesis?of?3‐methyl‐E‐2‐(1‐(2‐(hydrazinecarbono?
thioyl)‐hydrazono)‐ethyl)‐?quinoxalin‐1,4‐dioxide?(12)?
?
To?a?boiling?solution?of?10a?(0.655?g,?3?mmol)?in?methanol?
(15? mL)? containing? 2? drops? of? conc.? HCl,? was? added? a?
methanolic? solution? of? thiocarbohydrazide? (11)? (0.318? g,? 3?
Fadda?et?al.?/?European?Journal?of?Chemistry?2?(1)?(2011)?51‐57?
mmol?in?10?mL?methanol)?with?stirring.?The?reaction?mixture?
was?refluxed?for?5?hours?and?then?allowed?to?stand?at?room?
temperature?overnight.?The?separated?product?was?filtered?off?
and?recrystallized?from?methanol?to?give?12.?Yellow?crystals,?
M.p.:?237?oC.?Yield:?72%.?IR?(KBr,?max,?cm‐1):?1250?(C=S),?1320?
(N→O),?1620?(C=N),?3220?(NH),?3410?(NH2).?1H?NMR?(DMSO,?δ?
ppm):?1.81?(s,?3H,?CH3),?2.01?(s,?2H,?NH2),?2.9?(s,?3H,?CH3),?8.2‐
8.6? (m,? 4H,? Ar‐H),? 8.68? (br.? s.,? 2H,? 2NH).? MS? (m/z,? %):? 308?
(M++2,?43).?Anal.?Calcd.?for?C12H14N6O2S?(306.34):?C,?47.05;?H,?
4.61;?N,?27.43;?S,?10.47.?Found:?C,?46.91;?H,?4.64;?N,?27.50;?S?
10.55. ?
?
2.5.?Reaction?of?12?with?formic?acid:?Formation?of?3‐methyl‐
E‐2‐(1‐(2‐(1,3,4‐thiadiazol‐2‐yl)‐hydrazono)‐ethyl)‐
quinoxaline?1,4‐dioxide?(15)?
?
A?mixture?of?12?(1?g,?3?mmol)?and?formic?acid?(15?mL)?was?
heated?under?reflux?for?4?hours.?The?reaction?mixture?was?then?
allowed?to?stand?overnight?at?room?temperature.?The?excess?
formic?acid?was?evaporated?under?vacuo?and?the?residue?was?
crystallized?from?ethanol?to?give?15.?Dark?yellow?crystals,?M.p.:?
80?oC.?Yield:?60%.?IR?(KBr,?max,?cm‐1):?3315?(NH),?1610?(C=N),?
1330?(N→O).?1H?NMR?(DMSO,?δ?ppm):?2.91?(s,?3H,?CH3),?2.95?(s,?
3H,?CH3),?7.0?(s,?1H,?NH),?7.5?(s,?1H,?CH),?8.1‐8.6?(m,?4H,?Ar‐H).?
MS? (m/z,? %):? 316? (M+,? 71).? Anal.? Calcd.? for? C13H12N6O2S?
(316.34):?C,?49.36;?H,?3.82.?Found:?C,?49.39;?H,?3.87.?
?
2.6.?Synthesis?of?2,6‐dimethyl‐3‐(2‐hydroxy‐2‐oxoindolin‐3‐
yl)acetyl)‐?quinoxaline‐1,4‐dioxide?(16)?
?
To?a?mixture?of?isatin?(0.397?g,?2.7?mmol)?and?2,6‐dimethyl‐
3‐acetylquinoxaline‐1,4‐dioxide?(10b)? (0.627? g,? 2.7? mmol)? in?
absolute?ethanol?(15?mL),?5?drops?of?piperidine?were?added?
and? the? reaction? mixture? was? allowed? to? stand? overnight? at?
room?temperature.?The?separated?crystals?was?filtered?off?and?
crystallized?from?ethanol?to?give?16.?Dark?yellow?powder,?M.p.:?
>300?oC.?Yield:?90%.?IR?(KBr,?max,?cm‐1):?1335?(N→O),?1700?
(cyclic?imide),?3447?(OH).?1H?NMR?(DMSO,?δ?ppm):?2.33?(s,?3H,?
CH3),?2.91?(s,?3H,?CH3),?3.65?(s,?1H,?OH),?4.13?(s,?2H,?CH2),?6.85‐
7.72?(m,?7H,?Ar‐H),?8.2?(s,?1H,?NH).?MS?(m/z,?%):?379?(M+,?14).?
Anal.?Calcd.?for?C20H17N3O5?(379.37):?C,?63.32;?H,?4.52;?N,?11.08.?
Found:?C,?63.25;?H,?4.47;?N,?11.00.?
?
2.7.?Synthesis?of?(E)‐2,6‐dimethyl‐3‐(2‐oxoindolin‐3‐
ylidene)acetyl)‐quinoxalin‐1,4‐dioxide?(17)?
?
A?mixture?containing?16?(1.897?g,?5?mmol),?(0.5?mL)?conc.?
HCl,?and?glacial?acetic?acid?(20?mL)?was?refluxed?for?2?hours?
and? then? left? to? stand? at? room? temperature? overnight,? fine?
needles?were?formed.?The?formed?precipitate?was?filtered?off?
and?recrystallized?from?acetic?acid?to?give?17.?Brownish?yellow?
powder,? M.p.:? 265?oC.? Yield:? 65%.? IR? (KBr,? max,? cm‐1):? 1725?
(α,β‐unsaturated? ketone),? 1330? (N→O).?1H? NMR? (DMSO,? δ?
ppm):?2.34?(s,?3H,?CH3),?2.91?(s,?3H,?CH3),?6.97‐8.74?(m,?7H,?Ar‐
H),?7.32?(s,?1H,?CH),?8.2?(s,?1H,?NH).?MS?(m/z,?%):?362?(M++1,?
35).?Anal.?Calcd.?for?C20H15N3O4?(361.35):?C,?66.48;?H,?4.18;?N,?
11.63.?Found:?C,?66.40;?H,?4.13;?N,?11.70.?
?
2.8.?Synthesis?of?3‐cinnamoyl‐2,6‐dimethyl‐quinoxalin‐1,4‐
dioxides?(18)?
?
A? mixture? of? 2‐methyl‐3‐acetyl‐quinoxalin‐1,4‐dioxide?
(10a)?(0.655?g,?3?mmol)?and?benzaldehyde?(0.318?g,?3?mmol)?in?
methanolic?sodium?hydroxide?(10?mL,?5%)?was?stirred?for?5‐10?
minutes? at? room? temperature.? The? formed? yellow? to? orange?
precipitate?was?filtered?off,?washed?with?water?and?crystallized?
from?the?appropriate?solvent?(acetic?acid)?to?give?the?cinnamoyl?
derivative?18.?Yellow?crystals,?M.p.:?197?oC.?Yield:?80%.?IR?(KBr,?
max,? cm‐1):? 1725? (C=O),? 1590? (C=C),? 1242,? 1325? (N→O).?1H?
NMR?(DMSO,?δ?ppm):?2.31?(s,?3H,?CH3),?2.9?(s,?3H,?CH3),?6.7?(d,?

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Fadda?et?al.?/?European?Journal?of?Chemistry?2?(1)?(2011)?51‐57?53?



1H,?CH),?7.7?(d,?1H,?CH),?7.2‐7.8?(m,?8H,?Ar‐H).?MS?(m/z,?%):?
321?(M++1,?23).?Anal.?Calcd.?for?C19H16N2O3?(320.34):?C,?71.24;?
H,?5.03.?Found:?C,?71.19;?H,?5.00.?
?
2.9.?Synthesis?of?2,6‐dimethyl‐3‐(5‐phenyl‐4,5‐dihydro‐1H‐
pyrazole‐3‐yl)quinoxalin‐1,4‐dioxide?(19)?
?
To?a?solution?of?18?(0.961?g,?3?mmol)?in?ethanol?(15?mL),?
hydrazine?hydrate?(98%,?0.0751?g,?1.5?mmol)?was?added.?The?
reaction?mixture?was?refluxed?for?3?hours?and?left?to?cool.?The?
crystalline? precipitate? was? filtered? off,? dried? and? crystallized?
from?ethanol?to?give?19.?Yellowish?crystals,?M.p.:?184?oC.?Yield:?
70%.?IR?(KBr,?max,?cm‐1):?3250?(NH),?1620?(C=N),?1320?(N→O).?
1H?NMR?(DMSO,?δ?ppm):?2.3?(s,?3H,?CH3),?2.9?(s,?3H,?CH3),?3.9?
(dd,? J=1.90? Hz,? 1H,? CH),? [3.19? (dd,? J=1.85? Hz,? 1H),? 3.44? (dd,?
J=1.85?Hz,?1H)?CH2],?7.06‐7.72?(m,?8H,?Ar‐H),?8.3?(s,?1H,?NH).?MS?
(m/z,?%):?333?(M+‐1,?63).?Anal.?Calcd.?for?C19H18N4O2?(334.37):?
C,?68.25;?H,?5.43.?Found:?C,?68.00;?H,?5.20.?
?
2.10.?The?reaction?of?18?with?phenyl?hydrazine:?Synthesis?of?
2,6‐dimethyl‐3‐(1,5‐diphenyl‐4,5‐dihydro‐1H‐pyrazol‐3‐yl)‐
quinoxaline‐1,4‐dioxide?(20)?
?
Compound?18?(0.961?g,?3?mmol)?was?boiled?with?phenyl?
hydrazine? (0.162? g,? 1.5? mmol)? in? acetic? acid? (10? mL)? for? 3?
hours.?The?reaction?mixture?was?left?to?cool?and?poured?into?
crushed? ice.? The? formed? precipitate? was? filtered,? dried? and?
crystallized? from? ethanol? to? give? 20.? Lemon? yellow? crystals,?
M.p.:?105?oC.?Yield:?67%.?IR?(KBr,?max,?cm‐1):?1620?(C=N),?1320?
(N→O).?1H?NMR?(DMSO,?δ?ppm):?2.34?(s,?3H,?CH3),?2.91?(s,?3H,?
CH3),?3.90?(dd,?J=1.95?Hz,?1H,?CH),?3.20?(dd,?J=1.88?Hz,?1H),?3.40?
(dd,?J=1.88?Hz,?1H)?CH2,?7.2‐7.5?(m,?13H,?Ar‐H).?MS?(m/z,?%):?
410?(M+,?62).?Anal.?Calcd.?for?C25H22N4O2?(410.47):?C,?73.15;?H,?
5.40;?N,?13.65.?Found:?C,?73.00;?H,?5.11;?N,?13.58.?
?
2.11.?The?reaction?of?18?with?hydroxylamine?hydrochloride:?
Synthesis?of?2,6‐dimethyl‐3‐(5‐phenyl‐4,5‐dihydroisoxazol‐3‐
yl)‐quinoxaline‐1,4‐dioxide?(21)?
?
A? mixture? of? 18? (0.961? g,? 3? mmol),? hydroxylamine?
hydrochloride?(0.104?g,?1.5?mmol),?sodium?hydroxide?(0.1?g,?2.5?
mmol)? and? ethanol? (15? mL)? was? refluxed? for? 4? hours.? After?
cooling,?the?separated?material?was?filtered?off?and?crystallized?
from? ethanol? to? give? 21.? Light? yellow? crystals,? M.p.:? 102?oC.?
Yield:?72%.?IR?(KBr,?max,?cm‐1):?1626?(C=N),?1340?(N→O).?1H?
NMR?(DMSO,?δ?ppm):?2.34?(s,?3H,?CH3),?2.91?(s,?3H,?CH3),?[3.13?
(dd,?J=2.03?Hz,?1H),?3.39?(dd,?J=2.03?Hz,?1H)?CH2],?5.96?(dd,?
J=2.09?Hz,?1H,?CH),?7.06‐7.70?(m,?8H,?Ar‐H).?MS?(m/z,?%):?335?
(M+,?18).?Anal.?Calcd.?for?C19H17N3O3?(335.36):?C,?68.05;?H,?5.11;?
N,?12.53.?Found:?C,?68.30;?H,?5.36;?N,?12.65.?
?
2.12.?Synthesis?of?2,6‐dimethyl‐3‐(2‐pyridinyl‐4,6‐
diphenyl)quinoxalin‐1,4‐dioxide?(24)?
?
To?a?solution?of?phenacyl?pyridinium?bromide?(22)?(0.834?
g,?3?mmol)?and?ammonium?acetate?(2?g)?in?glacial?acetic?acid?
(10?mL)?a?solution?of?18?(0.961?g,?3?mmol)?in?glacial?acetic?acid?
(10? mL)? was? added? gradually? with? continuous? stirring.? The?
reaction?mixture?was?refluxed?for?2?h?and?then?left?to?cool?and?
poured?into?crushed?ice.?The?formed?precipitate?was?filtered?
off,? dried? and? crystallized? from? methanol? to? afford? 24.?
Yellowish? brown? crystals,? M.p.:? 186?oC.? Yield:? 80%.? IR? (KBr,?
max,? cm‐1):? 3000‐3077? (CH? streching),? 1620? (C=N),? 1330?
(N→O).?1H?NMR?(DMSO,?δ?ppm):?2.35?(s,?3H,?CH3),?2.93?(s,?3H,?
CH3),?8.11?and?8.56?(2s,?2H,?Py?H`s),?7.06‐8.30?(m,?13H,?Ar‐H).?
MS? (m/z,? %):? 419? (M+,? 30).? Anal.? Calcd.? for? C27H21N3O2?
(419.47):?C,?77.31;?H,?5.05.?Found:?C,?77.09;?H,?4.89.?
?
2.13.?Synthesis?of?3‐(6‐amino‐5‐cyano‐4‐phenylpyridine‐2‐
yl)‐2,6‐dimethyl‐quinoxalin‐1,4‐dioxide?(25)?
?
A?mixture?of?18?(0.961?g,?3?mmol),?malononitrile?(0.198?g,?3?
mmol)?and?ammonium?acetate?(0.164?g,?2?mmol)?was?heated?at?
150?oC?for?4?hours.?The?solid?material?was?washed?with?water?
and? recrystallized? from? benzene? to? give? 25.? Coffee? Brown?
crystals,? M.p.:? 100?oC.? Yield:? 70%.? IR? (KBr,? max,? cm‐1):? 3470?
(NH2),?2220?(CN),?1640?(C=N),?1320?(N→O).?1H?NMR?(DMSO,?δ?
ppm):?2.30?(s,?3H,?CH3),?2.90?(s,?3H,?CH3),?7.05‐7.70?(m,?8H,?Ar‐
H),?7.60?(s,?2H,?NH2),?8.2?(s,?1H,?py‐H).?MS?(m/z,?%):?383?(M+,?
90).?Anal.?Calcd.?for?C22H17N5O2?(383.40):?C,?68.92;?H,?4.47;?N,?
18.27.?Found:?C,?69.03;?H,?4.53;?N,?18.45.?
?
2.14.?Synthesis?of?2,6‐dimethyl‐3‐(hydrazinecarbonyl)‐
quinoxalin‐1,4‐dioxide?(26)?
?
A? mixture? of? 2,6‐dimethyl‐3‐carboethoxyquinoxalin‐1,4‐
dioxide?(10c)?(0.787?g,?3?mmol)?and?hydrazine?hydrate?(80%,?3?
mL)?in?absolute?ethanol?(20?mL)?was?refluxed?for?6?hours?and?
left? to? stand? overnight? at? room? temperature.? The? separated?
crystals?were?filtered?off,?dried?and?crystallized?from?ethanol?to?
give?26.?Yellow?crystals,?M.p.:?218?oC.?Yield:?70%.?IR?(KBr,?max,?
cm‐1):? 3380? (NH2),? 3350? (NH),? 1650? (C=O),? 1330? (N→O).?1H?
NMR?(DMSO,?δ?ppm):?2.00?(s,?2H,?NH2),?2.30?(s,?3H,?CH3),?2.91?
(s,?3H,?CH3),?7.06?(s,?1H,?Ar‐H),?7.23?(d,?1H,?Ar‐H),?7.70?(d,?1H,?
Ar‐H),?8.00?(s,?1H,?NH).?Anal.?Calcd.?for?C11H12N4O3?(248.24):?C,?
53.22;?H,?4.87;?N,?22.57.?Found:?C,?53.07;?H,?4.91;?N,?22.64.?
?
2.15.?Synthesis?of?2,6‐dimethyl‐3‐(5‐thioxo‐1',3',4'‐
oxadiazolo‐2'‐yl)‐quinoxalin‐1,4‐dioxide?(27)?
?
A? mixture? of? 26? (1.201? g,? 5? mmol)? in? ethanol? (10? mL),?
potassium?hydroxide?(0.281?g,?5?mmol)?in?water?(3?mL)?and?
carbon?disulfide?(0.381?g,?5?mmol)?was?heated?under?reflux?for?
7? hours? or? until? the? evolution? of? H2S? ceased.? The? reaction?
mixture?was?left?to?cool,?poured?into?crushed?ice?and?acidified?
with?conc.?HCl.?The?precipitate?was?filtered?off,?washed?with?
water,?dried?and?crystallized?from?ethanol?to?give?27.?Brownish?
crystals,? M.p.:? 210?oC.? Yield:? 85%.? IR? (KBr,? max,? cm‐1):? 1595?
(C=N),? 1330? (N→O),? 1300‐1100? (C=S),? 2600‐2620? (SH).?1H?
NMR?(DMSO,?δ?ppm):?2.34?(s,?3H,?CH3),?2.90?(s,?3H,?CH3),?7.00?
(s,?1H,?NH),?7.06?(s,?1H,?Ar‐H),?7.23?(d,?1H,?Ar‐H),?7.70?(d,?1H,?
Ar‐H).?MS?(m/z,?%):?290?(M+,?33).?Anal.?Calcd.?for?C12H10N4O3S?
(290.30):?C,?49.65;?H,?3.47.?Found:?C,?49.77;?H,?3.54.?
?
2.16.?Synthesis?of?3,7‐dimethyl‐1,4‐dioxyquinoxaline‐2‐
carboxylic?acid?N`‐(3,7‐dimethyl‐1,4‐dioxyquinoaline‐2‐
carbonyl)hydrazide?derivative?(29)?
?
A?mixture?of?26?(0.721?g,?3?mmol),?acetoacetanilide?(0.532?
g,?3?mmol)?in?glacial?acetic?acid?(15?mL)?was?refluxed?for?3?h.?
After? cooling,? the? precipitate? was? filtered? off,? dried? and?
recrystallized?from?acetic?acid?to?give?29.?Dark?yellow?powder,?
M.p.:? >300?oC.? Yield:? 60%.? IR? (KBr,? max,? cm‐1):? 3250,? 3280?
(NH/NH),? 1700? (two? C=O),? 1327? (N→O).?1H? NMR? (DMSO,? δ?
ppm):?2.55?(s,?6H,?2CH3),?2.91?(s,?6H,?2CH3),?6.80‐7.60?(m,?6H,?
Ar‐H),?9.50?(br.?s.,?2H,?NH/NH).?MS?(m/z,?%):?432?(M+‐32,?20).?
Anal.?Calcd.?for?C22H20N6O6?(464.43):?C,?56.89;?H,?4.34;?N,?18.10.?
Found:?C,?56.97;?H,?4.42;?N,?18.36.?
?
2.17.?Synthesis?of?3‐(3‐carboxamido‐2,6‐dimethyl‐1‐
phenylquinoxalin‐1,4‐dioxide)thiourea?(30)?
?
Phenylisothiocyanate? (0.406? g,? 3? mmol)? was? added? to? a?
solution?of?26?(0.721?g,?3?mmol)?in?ethanol?(20?mL)?and?the?
reaction?mixture?was?heated?for?4?hours?on?water?bath?then?left?
to? cool.? The? precipitated? solid? product? was? filtered? off? and?

Page 4

54?
?
crystallized?from?ethanol?to?give?30.?Orange?crystals,?M.p.:?192?
oC.?Yield:?88%.?IR?(KBr,?max,?cm‐1):?3250,?3300,?3350?(NH/NH),?
1220?(C=S),?1350?(N→O).?1H?NMR?(DMSO,?δ?ppm):?2.00?(s,?1H,?
NH),?2.34?(s,?3H,?CH3),?2.90?(s,?3H,?CH3),?4.20?(s,?1H,?NH),?6.80‐
7.70?(m,?8H,?Ar‐H),?9.35?(s,?1H,?NH),?9.55?(s,?2H,?NH/NH).?MS?
(m/z,?%):?383?(M+,?80).?Anal.?Calcd.?for?C18H17N5O3S?(383.42):?C,?
56.38;?H,?4.47;?N,?18.27.?Found:?C,?56.32;?H,?4.41;?N,?18.38.?
??
2.18.?Synthesis?of?3‐(2,6‐dimethylquinoxalin‐1,4‐dioxide)‐5‐
mercapto‐4‐phenyl‐4H‐1,2,4‐triazole?(31)?
?
A?solution?of?30?(1.15?g,?3?mmol)?in?potassium?hydroxide?
(10%,?20?mL)?was?refluxed?for?8?hours.?The?reaction?mixture?
was?kept?to?stand?overnight?at?room?temperature,?then?poured?
into?crushed?ice?and?acidified?with?dilute?acetic?acid.?The?solid?
product? was? filtered? off,? washed? with? water,? dried? and?
crystallized?from?ethanol?to?give?31.?Orange?powder,?M.p.:?248?
oC.? Yield:? 70%.? IR? (KBr,? max,? cm‐1):? 2600‐2550? (SH),? 1600?
(C=N),?1337?(N→O),?1300‐1100?(C=S).?1H?NMR?(DMSO,?δ?ppm):?
2.35?(s,?3H,?CH3),?2.91?(s,?3H,?CH3),?3.42?(s,?1H,?SH),?7.05‐7.55?
(m,?8H,?Ar‐H).?MS?(m/z,?%):?365?(M+,?5),?366?(M++1,?10).?Anal.?
Calcd.?for?C18H15N5O2S?(365.41):?C,?59.16;?H,?4.14;?N,?19.17;?S,?
8.78.?Found:?C,?59.32;?H,?4.27;?N,?19.10;?S,?8.85.?
?
2.19.?Synthesis?of?3‐(2,6‐dimethylquinoxalin‐1,4‐dioxide)‐2‐
phenylimino‐4‐thiazolidinone?(32)?
?
To?a?solution?of?30?(1.15?g,?3?mmol)?in?glacial?acetic?acid?
(20?mL)?was?added?monochloroacetic?acid?(0.284?g,?3?mmol)?
and? anhydrous? sodium? acetate? (0.3? g).? The? reaction? mixture?
was?refluxed?for?8?hours,?then?left?to?cool?at?room?temperature?
and? then? poured? into? crushed? ice.? The? separated? solid? was?
filtered? off,? washed? thoroughly? with? water,? dried? and?
crystallized?from?ethanol?to?give?32.?Light?yellow?crystals,?M.p.:?
86?oC.?Yield:?60%.?IR?(KBr,?max,?cm‐1):?3250?(NH),?1680,?1600?
(C=O),?1535?(C=N),?1335?(N→O).?1H?NMR?(DMSO,?δ?ppm):?2.34?
(s,?3H,?CH3),?2.90?(s,?3H,?CH3),?4.10?(s,?2H,?CH2),?7.06‐7.70?(m,?
8H,? Ar‐H).? MS? (m/z,? %):? 423? (M+,? 20).? Anal.? Calcd.? for?
C20H17N5O4S? (423.45):? C,? 56.73;? H,? 4.05;? N,? 16.54;? S,? 7.57.?
Found:?C,?56.68;?H,?4.08;?N,?16.45;?S,?7.60.?
?
2.20.?Synthesis?of?3‐carbazido‐2,6‐dimethylquinoxalin‐1,4‐
dioxide?(33)?
?
To?a?suspension?of?26?(0.721?g,?3?mmol)?in?dioxane?(10?mL)?
and?acetic?acid?(10?mL),?sodium?nitrite?(0.5?g)?in?water?(1.3?mL)?
was?added?with?stirring?at?0‐2?oC.?Stirring?was?continued?for?
further?30?minutes?after?complete?addition?of?sodium?nitrite?
solution.?The?separated?material?was?filtered?off,?washed?with?
water? and? crystallized? from? acetic? acid? to? give? 33.? Yellow?
crystals,? M.p.:? 78?oC.? Yield:? 55%.? IR? (KBr,? max,? cm‐1):? 2157?
(strong?N3),?1691?(CO),?1341?(N→O).?1H?NMR?(DMSO,?δ?ppm):?
2.35?(s,?3H,?CH3),?2.93?(s,?3H,?CH3),?7.08?(s,?1H,?Ar‐H),?7.21?(d,?
J=7.5?Hz,?1H,?Ar‐H),?7.65?(d,?J=7.5?Hz,?1H,?Ar‐H).?MS?(m/z,?%):?
259?(M+,?35).?Anal.?Calcd.?for?C11H9N5O3?(259.22):?C,?50.97;?H,?
3.50;?N,?27.02.?Found:?C,?51.02;?H,?3.56;?N,?27.17.?
?
2.21.?Synthesis?of?2,6‐dimethyl‐3‐ethoxycarbonylamino?
quinoxalin‐1,4‐dioxide?(34)?
?
?The?azide?33?(0.778?g,?3?mmol)?in?absolute?ethanol?(30?
mL)? was? refluxed? for? 5? hours? and? the? reaction? mixture? was?
filtered?while?hot?to?remove?any?insoluble?material.?The?filtrate?
was?evaporated?and?the?residue?crystallized?from?ethanol?to?
give?34.?Yellow?crystals,?M.p.:?200?oC.?Yield:?72%.?IR?(KBr,?max,?
cm‐1):? 3382? (NH),? 1723? (CO,? ester),? 1339? (N→O).?1H? NMR?
(DMSO,?δ?ppm):?1.80?(t,?J=13.7?Hz,?3H,?CH3),?2.30?(s,?3H,?CH3),?
2.90?(s,?3H,?CH3),?3.50?(q,?J=13.7?Hz,?2H,?CH2),?6.70‐7.30?(m,?3H,?
Ar‐H),?8.00?(s,?1H,?NH).?MS?(m/z,?%):?277?(M+,?13).?Anal.?Calcd.?
Fadda?et?al.?/?European?Journal?of?Chemistry?2?(1)?(2011)?51‐57?
for?C13H15N3O4?(277.28):?C,?56.31;?H,?5.45;?N,?15.15.?Found:?C,?
56.43;?H,?5.57;?N,?15.27.?
?
2.22.?Synthesis?of?2,6‐dimethyl‐3‐isocyanatoquinoxalin‐1,4‐
dioxide?(35)?
?
The?azide?33?(0.778?g,?3?mmol)?in?dry?toluene?(20?mL)?was?
refluxed?for?3?hours.?After?cooling,?the?separated?material?was?
filtered? off,? dried? and? crystallized? from? benzene? to? give? 35.?
Reddish?crystals,?M.p.:?244?oC.?Yield:?66%.?IR?(KBr,?max,?cm‐1):?
1700?(C=O),?1330?(N→O).?1H?NMR?(DMSO,?δ?ppm):?2.38?(s,?3H,?
CH3),? 2.91? (s,? 3H,? CH3),? 7.30? (d,?J=8.30? Hz,? 1H,? H7),? 7.70? (d,?
J=8.30?Hz,?1H,?H8),?7.06?(s,?1H,?H5).?MS?(m/z,?%):?230?(M+‐1,?
70).? Anal.? Calcd.? for? C11H9N3O3? (231.21):? C,? 57.14;? H,? 3.92.?
Found:?C,?57.01;?H,?3.80.?
?
2.23.?Synthesis?of?3‐amino‐2,6‐dimethylquinoxalin‐1,4‐
dioxide?(36)?
?
The?carbazide?33?(0.778?g,?3?mmol)?in?acetic?acid?(5?mL)?
and?dioxane?(5?mL)?was?heated?for?30?minutes?and?then?left?to?
cool.?The?reaction?mixture?was?poured?into?water?(30?mL)?and?
then?extracted?with?ether?(three?times),?dried?over?anhydrous?
magnesium?sulfate;?the?solvent?was?evaporated?under?vacuo?to?
afford?36.?Greyish?crystals,?M.p.:?202?oC.?Yield:?70%.?IR?(KBr,?
max,?cm‐1):?3480‐3440?(NH2),?1350?(N→O).?1H?NMR?(DMSO,?δ?
ppm):?2.34?(s,?3H,?CH3),?2.90?(s,?3H,?CH3),?6.90?(s,?2H,?NH2),?
6.06‐7.70?(m,?3H,?Ar‐H).?MS?(m/z,?%):?189?(M+‐16,?50),?173?
(100).?Anal.?Calcd.?for?C10H11N3O2?(205.21):?C,?58.53;?H,?5.40.?
Found:?C,?58.62;?H,?5.52.?
?
2.24.?Diazotization?and?coupling?of?40?with?β–naphthol:?
Synthesis?of?2,6‐dimethyl‐E‐3((2‐hydroxynaphthalen‐1‐
yl)diazenyl)‐quinoxalin‐1,4‐dioxide?(37)?
?
2,6‐Dimethyl‐3‐aminoquinoxalin‐1,4‐dioxide?(36)?(0.616?g,?
3?mmol)?was?dissolved?in?conc.?hydrochloric?acid?(6?mL)?and?
cooled? to? 0?oC? in? ice? bath.? Cold? aqueous? solution? of? sodium?
nitrite?(0.3?g?in?5?mL?water)?was?added?in?small?portions?to?the?
above?amine?hydrochloride?solution.?To?the?resulting?sodium?
salt?solution?was?added?a?cold?solution?of?β–naphthol?(0.433?g,?
3?mmol)?in?sodium?hydroxide?(10%,?10?mL),?the?precipitated?
solid? material? was? filtered? off,? washed? with? water? and?
crystallized?from?ethanol?to?give?37.?Orange?powder,?M.p.:?238?
oC.? Yield:? 80%.? IR? (KBr,? max,? cm‐1):? 3500? (OH),? 1618? (C=N),?
1495?(N=N),?1345?(N→O).?1H?NMR?(DMSO,?δ?ppm):?2.30?(s,?3H,?
CH3),?2.96?(s,?3H,?CH3),?5.40?(s,?1H,?OH),?7.06‐8.07?(m,?9H,?Ar‐
H).? MS? (m/z,? %):? 360? (M+,? 27).? Anal.? Calcd.? for? C20H16N4O3?
(360.37):?C,?66.66;?H,?4.48;?N,?15.55.?Found:?C,?66.57;?H,?4.53;?N,?
15.68.?
?
3.?Results?and?discussion??
?
It?is?well?established?that?Benzofuroxan?derivatives?exist?at?
room?temperature?as?a?mixture?of?tautomers.?The?substituents?
in?the?benzene?ring?could?occupy?the?5‐?or?6‐position?and?the?
proportion?of?both?tautomers?in?the?equilibrium?depends?on?
the?electronic?characteristics?of?the?substituents?[22].?
The? reaction? of? benzofuroxan? (BFO)? 1a? with? the? cyano‐
acetanilides?2a‐d?in?the?presence?of?piperidine?as?catalyst?at?
room?temperature?afforded?the?2‐(arylcarbamoyl)‐1‐hydroxy‐
5‐methyl‐1H‐benzo[d]imidazol‐3‐oxide?
respectively;?(Scheme?2).?
?
?
derivatives? 3a‐d,?
Scheme?2?

Page 5

Fadda?et?al.?/?European?Journal?of?Chemistry?2?(1)?(2011)?51‐57?55?



A? probable? mechanism,? in? line? with? other? carbanion?
reactions?of?BFO's?is?outlined?in?(Scheme?3).?
?
N
O
N
O
H3C
1a
CNCHCONHAr
N
O
O
N
H3C
H
C
NC CONHAr
H3C
N
O
N
O
CN
H
CONHAr
N
O
N
H3C
O
H
CONHAr
N
OH
N
H3C
O
CONHAr
3a-d
?
Scheme?3?
?
The?structures?of?3a‐d?were?elucidated?from?their?spectral?
and?elemental?analysis.?Thus,?the?IR?spectra?of?3a‐d?reveal?the?
presence? of? OH? and? NH? groups? (3430? and? 3250? cm‐1),?
respectively,?amide?carbonyl?(1660?cm‐1),?C=N?(1620?cm‐1)?and?
(N→O)?functions?(1236,?1317?cm‐1).?The?1H?NMR?spectrum?of?
3d?shows?two?singlets?each?integrated?for?3H?at?δ?2.34?and?3.83?
attributable?to?methyl?and?methoxy?protons,?respectively,?and?
the? aromatic? protons? appears? at? δ? 7.07‐7.50? (m,? 7H,? Ar‐H),?
while?the?NH?proton?appears?as?a?broad?singlet?at?δ?9.15?ppm.?
Moreover,? rhodanines? are? important? anticonvulsant? [16],?
anti‐inflammatory? [17],? antitubercular? [18],? and? antibacterial?
agents? [19].? So,? compounds? having? a? combination? of?
benzofuroxan?with?rhodanine?moieties?are?expected?to?posses?
marked? biological? properties.? Unexpectedly? when? 1b? was?
reacted?with?rhodanines?4a,b?as?active?methylene?compounds,?
in?the?presence?of?sodium?ethoxide,?1‐hydroxy‐2‐(arylamino)‐
1H‐benzo[d]imidazole‐3‐oxide? 6? was? obtained? instead? of? the?
thioxospirobenzoimidazole‐thiazolidine‐1,3‐dioxide?5?(Scheme?
4).?
?

?
Scheme?4?
?
The?IR,?1H?NMR?and?mass?spectra?of?6a,b?are?in?agreement?
with?their?proposed?structures?(Scheme?5).?
If?the?above?reaction?afforded?compound?5,?so,?it?would?not?
have?shown?bands?in?both?the?IR?and?1H?NMR?spectrum?for?NH?
group.?
On?the?other?hand,?we?report?here?the?reaction?of?BFO's?
with? rhodanine? in? the? presence? of? a? weaker? base,? such? as?
freshly? fused? sodium? acetate? and? drops? of? acetic? acid.? This?
versatile? synthesis? has? afforded? novel? compounds? hitherto?
inaccessible?by?classical?synthetic?methods.?Thus,?surprisingly,?
the?reaction?of?rhodanines?4a,b?with?benzofuroxan?1a,b?and?
catalytic?amount?of?freshly?fused?sodium?acetate?does?not?give?
the? expected? spiro? benzimidazolyl‐4‐thiazolidinone? 5,? but?
resulted? in? the? formation? of? 2,2'‐dithiano‐Δ5,5'‐bi‐4‐thiazo?
lidinones?7a,b?which?are?auto‐oxidized?to?2,2'‐dithiano‐Δ5,5'‐bi‐
4‐thiazolidinones? 8a,b,? in? which? the? benzofuroxan? acts? as?
oxidizing? agent? and? in? the? same? time? it? was? reduced? to????????????????
o‐quinone? dioxime? 9.? The? oxidizing? capacity? [21]? of?
benzofuroxan?and?its?ability?to?oxidize?rhodanine?to?the?dimer?
derivatives?8a,b?via?the?formation?of?7?based?on?initial?one?or?
two? electron? oxidation? and? the? subsequent? formation? of? o‐
quinone? dioximes? 9a,b? as? side? products? are? illustrated? in?
(Scheme? 6).? The? structures? were? assigned? to? the? bi‐
thiazolidinones?class?on?the?basis?of?the?chemical?shift?of?the?
methyl?groups?and?aromatic?rings?in?the?1H?NMR?spectra.?
?

?
Scheme?5?
?

?
Scheme?6?
?
In?addition,?thiocarbohydrazide?has?been?reported?to?show?
tubercular?activities?[30],?in?vitro?and?high?insecticidal?activity?
towards?the?house‐fly?in?comparison?with?DDT?[31].?Thus,?the?
quinoxaline?N‐dioxide?10a?reacts?with?the?thiocarbohydrazide?
11?to?afford?the?condensation?product?12?which?reacts?with?
excess?formic?acid?to?give?3‐methyl‐E‐2‐(1‐(2‐(1,3,4‐thiadiazol‐
2‐yl)hydrazono)ethyl)‐quinoxaline‐1,4‐dioxide? 15? presumably?
via? the? intermediates? 13? and? 14.? Here,? formic? acid? was?
expected? to? reduce? the? C=N? to? the? corresponding? secondary?
amine,?however,?formylation?of?NH2?group?took?place?and?the?
intermediate? 14? was? formed,? which? then? loses? a? water?
molecule?to?give?15.?All?attempts?to?isolate?the?intermediate?14?
failed?(Scheme?7).?
Structures? 12? and? 15? were? established? on? the? basis? of?
analytical?and?spectral?data?(see?experimental?part).??
On?the?other?hand,?it?has?been?found?that?the?reaction?of?
isatin?with?quinoxaline?derivatives?10b?[29],?in?the?presence?of?
piperidine,? afforded? 3‐(2‐hydroxy‐2‐oxoindolin‐3‐yl)acetyl)‐
2,6‐dimethyl‐quinoxalin‐1,4‐dioxide? 16,? in? quantitative? yield?
(Scheme?8).?The?structure?of?16?was?established?from?micro?
analytical?data?as?well?as?the?IR?spectrum?which?showed?well?
defined? bands? in? the? region? 3447? cm‐1? (OH)? and? 1700? cm‐1?
(cyclic? imide).? Dehydration? of? 16? by? dilute? alcoholic? hydro‐
chloric?acid?or?by?hydrochloric?acid?in?the?presence?of?acetic?
acid? gave? (E)‐2,6‐dimethyl‐3‐(2‐oxoindolin‐3‐ylidene)acetyl)?
quinoxaline‐1,4‐dioxide? 17? in? good? yield.? IR? spectrum? of? 17?