Dihydro-1,2,4-triazin-6(1H)-ones. III oxidation products of 1-Methyl-3-phenyl-4,5-dihydro-1,2,4-triazin-6(1H)-one

Article abstract of DOI:10.1071/CH99047

1-Methyl-3-phenyl-4,5-dihydro-1,2,4-triazin-6(1H)-one (1) undergoes aerial oxidation to give a mixture of 1-methyl-3-phenyl-1,2,4-triazin-6(1H)-one (2) and 1-methyl-3-phenyl-1,4-dihydro-1,2,4-triazine-5,6-dione (3). The dehydro derivative (2) was cleanly

Full text of DOI:10.1071/CH99047

C S I R O P U B L I S H I N G
Australian Journal
of Chemistry
Volume 52, 1999
© CSIRO Australia 1999
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Aust. J. Chem., 1999, 52, 971–975
Dihydro-1,2,4-triazin-6(1H)-ones. III*
Oxidation Products of 1-Methyl-3-phenyl-
4,5-dihydro-1,2,4-triazin-6(1H)-one
David J. Collins,A Timothy C. HughesA,B and Wynona M. Johnson B
A Department of Chemistry, Monash University, Clayton, Vic. 3168.
B CSIRO Molecular Science, Private Bag 10, Rosebank MDC, Clayton, Vic. 3169.
1-Methyl-3-phenyl-4,5-dihydro-1,2,4-triazin-6(1H)-one (1) undergoes aerial oxidation to give a mixture of 1-
methyl-3-phenyl-1,2,4-triazin-6(1H)-one (2) and 1-methyl-3-phenyl-1,4-dihydro-1,2,4-triazine-5,6-dione (3). The
dehydro derivative (2) was cleanly prepared by the oxidation of (1) with 2,3-dichloro-5,6-dicyano-1,4-benzo-
quinone (ddq). The dehydro derivative (2) underwent a surprising rearrangement to the triazole (12) upon oxida-
tion with OxoneR. Several attempts at unambiguous synthesis of the ␣-dicarbonyl derivative (3) were unsuccessful;
it was obtained, together with the 1,4-dimethyl derivative (13) by methylation of 3-phenyl-1,4-dihydro-1,2,4-tri-
azine-5,6-dione (4) with sodium hydride and methyl iodide.
Introduction
consistent with the structures (2) and (3). Aerial oxidation of
crystalline (1) to the dehydro derivative (2) also occurred
partially during radial chromatography. Aerial oxidation of
the solid material is probably due to a photochemical process
in which a trace of the u.v. indicator eluted from the silica gel
during radial chromatography has acted as a photosensitizer.
When compound (1) was purified by flash column chro-
matography over pure silica gel without the u.v. indicator, or
simply by recrystallization, it was stable to aerial oxidation
in the solid state.
During exploration of novel heterocycles1 for use as
potential crop protection agents, we became aware that the
4,5-dihydro-1,2,4-triazin-6(1H)-one ring system is readily
susceptible to aerial oxidation. In this paper we report that
aerial oxidation of 1-methyl-3-phenyl-4,5-dihydro-1,2,4-
triazin-6(1H)-one (1) gives a dehydro derivative and a dicar-
bonyl derivative, and independent syntheses of them is
described. Since these oxidative transformation products
exhibited different levels and types of biological activity
when they were separately tested as crop protection chemi-
cals it became desirable to establish convenient and general
synthetic routes to these materials for further biological
studies.
Results and Discussion
Aerial Oxidation of the 1-Methylated Dihydrotriazinone (1)
When air was bubbled through a chloroform solution of 1-
methyl-3-phenyl-4,5-dihydro-1,2,4-triazin-6(1H)-one1 (1) it
was readily oxidized to a mixture of the new dehydro ana-
logue (2)† (56%) and the new dicarbonyl compound (3)
(44%) (Scheme 1). The dehydro derivative (2) was identi-
fied by its methine resonances at ␦ 8.41 and 157.5 in the 1H
and 13C n.m.r. spectra, respectively. The dicarbonyl deriva-
tive (3) was identified by the lack of a methylene resonance
We next investigated the stability of (2) to aerial oxida-
tion. Compound (2) was subjected to the original oxidation
conditions (CHCl3, air). No additional products were formed
and compound (2) was recovered unchanged. Hence, the
dehydro derivative (2) and the dicarbonyl compound (3)
appear to be formed by independent routes, perhaps via a
common intermediate, during aerial oxidation of 1-methyl-
3-phenyl-4,5-dihydro-1,2,4-triazin-6(1H)-one (1).
1
in its H n.m.r. spectrum, and two carbonyl carbon reso-
nances at ␦ 154.0 and 155.1 in the 13C n.m.r. spectrum.
Elemental analyses and accurate mass measurements were
* Part II, Aust. J. Chem., 1999, 52, 379.
† The dehydro compound (2) has the systematic name 1-methyl-3-phenyl-1,2,4-triazin-6(1H)-one, but use of the term ‘dehydro’ is appropriate in
the present context.
Manuscript received 14 April 1999
© CSIRO 1999
0004-9425/99/100971
10.1071/CH99047

972
D. J. Collins, T. C. Hughes and W. M. Johnson
(4). Also, the use of N-methyl carbazates1 in such reactions
should regiospecifically provide the 1- or 2-methyl deriva-
tives of (4).
Not surprisingly, the pure compounds (1), (2) and (3) pos-
sessed different biological activities when tested as potential
crop protection agents.* It is plausible that other 4,5-
dihydro-1,2,4-triazin-6(1H)-ones may be at least partly oxi-
dized to the corresponding 5,6-dicarbonyl compound and/or
dehydro derivative(s) while undergoing biological testing,
and the net biological activity observed may not be that of
the original compound. It was therefore desirable to explore
other synthetic routes to the dicarbonyl compound (3) and
the dehydro compound (2) which may be applicable to the
efficient generation of a range of analogues for measurement
of their intrinsic biological activities.
Oxidation of the 1-Methylated Dihydrotriazinone (1)
with 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone
There are several reports of 4,5-dihydro-1,2,4-triazin-
6(1H)-ones being oxidized to the corresponding dehydro,
aromatic derivatives;2 these reactions were generally low-
yielding and often entailed difficult workup procedures. To
the best of our knowledge, no one has described the success-
ful oxidation of a 4,5-dihydro-1,2,4-triazin-6(1H)-one to the
corresponding dehydro 1,2,4-triazin-6(1H)-one using 2,3-
dichloro-5,6-dicyano-1,4-benzoquinone (ddq) as the
oxidant. Despite a claim by Taylor and Macor3 that ddq
failed to oxidize some dihydrotriazinones to their corre-
sponding dehydro derivatives, we found that ddq can be used
to effect this transformation cleanly. Treatment of 1-methyl-
3-phenyl-4,5-dihydro-1,2,4-triazin-6(1H)-one (1) with ddq
in dry dichloromethane afforded 94% of 1-methyl-3-phenyl-
1,2,4-triazin-6(1H)-one (2) which was identical with the
material prepared by aerial oxidation of (1).
Methyl benzimidate10 (8) was treated with t-butyl car-
bazate to give the new amidrazone derivative (9)† in 82%
yield. The 1H n.m.r. spectrum of (9) showed a resonance for
the t-butyl group at ␦ 0.99, and signals for the amino protons
at ␦ 5.42 (2H) and 8.38. The 13C n.m.r. spectrum of (9)
showed imine and carbonyl carbon resonances at ␦ 146.6 and
153.7, respectively. Upon being heated, (9) cyclized to give
5-phenyl-2,4-dihydro-3H-1,2,4-triazol-3-one (10) which
was identified by comparison of its spectra with the reported
data11 (Scheme 2). Not surprisingly, the mass spectrum of
(9) did not show the parent molecular ion, but gave the
molecular ion of the triazolone (10); however, elemental
analysis of (9) was consistent with the molecular formula
C12H17N3O2.
Attempted Synthesis of the 1-Methylated
Dihydrotriazinedione (3)
Synthesis of 3-phenyl-1,4-dihydro-1,2,4-triazine-5,6-
dione (4) and its 1-methyl analogue (3) proved to be a much
more difficult problem. Indeed, relatively few syntheses of
1,2,4-triazine-5,6-diones have been reported in the litera-
ture.4–7 Two general approaches have been used: (i) cycload-
dition of an oxalate derivative with an amidrazone
derivative; and (ii) oxidation of the preformed ring system to
the 5,6-dione system.
Treatment of the protected amidrazone (9) with dimethyl
oxalate or ethyl oxalyl chloride failed to yield any of the
desired products (6) or (4). Interestingly, when the amidra-
zone (9) was treated with dimethyl oxalate at 200°C in a
microwave reactor12 for 5 min, the triazolone (10) was
obtained in quantitative yield. This constitutes an efficient
microwave conversion of the amidrazone derivative (9) into
the triazolone (10).
Cyclization Reactions
The attempted cyclocondensation13,14 of oxamic
hydrazide (5; Z = NH2, Z = NHNH2) with trimethyl
orthobenzoate failed to yield the desired 5,6-dione com-
pound (4). Reaction of hydrazine with the oxalyl chloride
derivative (7) was also considered. However, the oxalyl
chloride derivative (7) was unable to be isolated from the
reaction of methyl benzimidate hydrochloride15 with oxalyl
chloride.16
Several 1,2,4-triazine-5,6-diones have been prepared by
cyclization of amidrazone derivatives with diethyl oxalate
(or other oxalic acid derivatives).5,6 However, reaction of
benzamidrazone8 with either dimethyl oxalate or oxalyl
chloride failed to afford any of the desired product (4).
To avoid problems associated with benzamidrazone,
including its tendency towards self-condensation reactions,9
the masked amidrazone derivative (9) was prepared. It was
expected that compound (9) could react with an oxalate
derivative (5) to give compounds of the type (6), which upon
deprotection should cyclize to give the triazine-5,6-dione
Oxidation Reactions
Attempted oxidations of the preformed triazinone system
using bromine water, selenium dioxide or selenium dioxide/
* The results of biological testing of the compounds reported in this work will be published elsewhere.
† The compounds (9) and (10) may exist in different tautomers to the ones illustrated.

Dihydro-1,2,4-triazin-6(1H)-ones. III
973
90% t-butyl hydroperoxide or Oxone17* failed to generate
the desired 5,6-dione ring system.
However, we wish to report here an oxidative rearrange-
ment of the 1-methyl dehydro triazinone (2) observed when
OxoneR was used as the oxidizing agent.
Hajipour and Pyne18 have described a general method of
synthesizing oxaziridines from the corresponding imine with
OxoneR. It was expected that the oxaziridine (11), poten-
tially available from the corresponding triazinone (2), could
be rearranged into the desired 1-methyl-3-phenyl-1,4-
dihydro-1,2,4-triazine-5,6-dione (3). However, attempts to
generate the oxaziridine (11) by reaction of OxoneR (cf.
Corey and Ward19) with the dehydro 1,2,4-triazin-6(1H)-one
(2) and sodium hydrogen carbonate in aqueous acetone gave
1-methyl-3-phenyl-1H-1,2,4-triazole (12) in 85% yield
(Scheme 3). The melting point and the 1H n.m.r. spectrum of
(12) were consistent with the data reported.20 The triazole
(12) could result from a base-catalysed transformation of the
oxaziridine (11); a possible rationalization of this is shown in
Scheme 4. The dehydro triazinone (2) was stable under
similar basic conditions, therefore ruling out an alternative
base-catalysed mechanism for the rearrangement of (2) to
(12).
Reaction of the 1-methyl-1,2,4-triazin-6(1H)-one (2) with
hydrogen peroxide and sodium hydroxide under the condi-
tions described by Felix et al.21 gave a mixture of 12% of the
methyl triazole (12) and 74% of starting material. However,
oxidation of (2) with 3-chloroperbenzoic acid in dichloro-
methane (i.e. under non-aqueous and non-basic conditions)
gave a mixture containing 40% of the methyl triazole (12),
the remainder being some starting material and several other
minor unidentified products.
Methylation of the Dihydrotriazinedione (4)
Since attempts to prepare 1-methyl-3-phenyl-1,4-
dihydro-1,2,4-triazine-5,6-dione (3) by cyclocondensation
or oxidation procedures had failed, methylation of the dicar-
bonyl compound (4) was attempted. Treatment of 3-phenyl-
1,4-dihydro-1,2,4-triazine-5,6-dione (4), which has two
acidic (amidic) NH groups, with sodium hydride and methyl
iodide gave a mixture of the 1-monomethylated derivative
(3) (68%), and the 1,4-dimethylated compound (13) (32%)
(Scheme 5). The monomethylated product was identified by
comparison of its resonances in the 1H and 13C n.m.r. spectra
of the mixture with those of an authentic sample of (3) pre-
pared by aerial oxidation of 1-methyl-3-phenyl-4,5-dihydro-
1,2,4-triazin-6(1H)-one (1). The mass spectrum of the
mixture showed parent molecular ions of both products and
an accurate mass measurement confirmed the presence of the
dimethylated compound (13). The 1H n.m.r. spectrum of the
mixture showed resonances at ␦ 3.08 and 3.52 consistent
with the N-methyl groups of the dialkylated product (13),
and the 13C n.m.r. spectrum showed two carbonyl resonances
for (13) at ␦ 153.0 and 157.2. Compound (3), in the form of
its enolate, could be readily separated from the mixture by
base extraction.
The failure of several possible cyclocondensation and
oxidative procedures to give the 5,6-triazinedione (4) may be
due to electronic and/or steric effects. While the dione (3)
was readily obtainable (together with (2)) by aerial oxidation
of (1), the failure of the latter to undergo oxidation to (3) with
bromine water, or selenium dioxide/t-butylhydroperoxide is
surprising. From the point of view of developing potential
Although the transformation of the 1-methyl triazinone
(2) into the 1-methyl triazole (12) was unexpected, 1,2,4-tri-
azines are known to undergo ring contractions to give 1,2,4-
triazoles, 1,2,3-triazoles and imidazoles.22–25 For example,
Lee and Paudler22 reported the ring contraction of some 1-
methyl-1,2,4-triazinium iodides to the corresponding 1,2,4-
triazoles upon attempted base-catalysed hydrolysis.
* Oxone is a registered trademark of E. I. Du Pont de Nemours & Co. Potassium peroxymonosulfate can be prepared by the method in ref. 17.

974
D. J. Collins, T. C. Hughes and W. M. Johnson
C, 61.5; H, 7.5; N, 17.9. C12H17N3O2 requires C, 61.3; H, 7.3; N,
crop protection agents, the facile aerial oxidation of com-
pounds of the type (1) may be blocked by appropriate disub-
stitution at C 5.
17.9%). ␯
(KBr) 3484m, 3344m, 1704s, 1633s, 1520m, 1255m,
max
778m, 710m cm–1. G.c.m.s. Rt 21.76 min, 100%. Mass spectrum: m/z
(e.i.) 161 (95%), 118 (100), 130 (27), 91 (100), 77 (73), 51 (50). 1H
n.m.r. ␦ (CDCl3/(CD3)2SO) 0.99, s, CH3; 5.42, br s, NH2; 6.72–6.88, m,
3H, Ar; 7.18–7.30, m, 2H, Ar; 8.38, br s, NH. 13C n.m.r. ␦
(CDCl3/(CD3)2SO) 28.2, C(CH3)3; 78.8, C(CH3)3; 125.9, C 2Ј, C 6Ј or
C 3Ј, C 5Ј; 127.6, C 2Ј, C 6Ј or C 3Ј, C 5Ј; 128.7, C 4Ј; 134.6, C 1Ј; 146.6,
C=O or C=N; 153.7, C=O or C=N. The mass spectrum was identical to
that of 5-phenyl-2,4-dihydro-3H-1,2,4-triazol-3-one (10)
Attempted Synthesis of 3-Phenyl-1,4-dihydro-1,2,4-triazine-
5,6-dione (4)
(i) Reaction of benzamidrazone with oxalate derivatives.
A
mixture of benzamidrazone8 and 1 mole equiv. of dimethyl oxalate in
dichloromethane was stirred at room temperature overnight, and the
1
mixture was then evaporated to dryness at reduced pressure. H and 13
C
Experimental
n.m.r. and mass spectroscopy of the residue showed, by comparison
with data for an authentic sample of (4), that no 3-phenyl-1,4-dihydro-
1,2,4-triazine-5,6-dione (4) had been formed. Similarly, 1 mole equiv.
of either ethyl oxalyl chloride or oxalyl chloride was added to a solu-
tion of benzamidrazone and 1 mole equiv. of triethylamine (for the acid
chloride reactions) in dichloromethane at –20°C and the mixture was
allowed to warm to room temperature, and stirred overnight. 1H and
13C n.m.r. and mass spectroscopic examination of the residue showed
that none of the desired 3-phenyl-1,4-dihydro-1,2,4-triazine-5,6-dione
(4) had been formed.
General experimental details were as previously described.1
1-Methyl-3-phenyl-1,2,4-triazin-6(1H)-one (2)
(i) By oxidation of 1-methyl-3-phenyl-4,5-dihydro-1,2,4-triazin-
6(1H)-one (1) with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone.
2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (923 mg, 4.06 mmol) was
added to a solution of 1-methyl-3-phenyl-4,5-dihydro-1,2,4-triazin-
6(1H)-one1 (1) (769 mg, 4.06 mmol) in dry dichloromethane (50 ml)
under an argon atmosphere. The mixture was stirred overnight at room
temperature, and then poured onto a short column of silica gel and
eluted with dichloromethane. Recrystallization of the eluate from ethyl
acetate/light petroleum afforded 1-methyl-3-phenyl-1,2,4-triazin-
6(1H)-one (2) (713 mg, 93%) as a white solid, m.p. 145–145.5°C.
G.l.c. Rt 13.48 min, 100% (Found: C, 64.2; H, 5.1; N, 22.4%; [M+1]+•,
188.083. C10H9N3O requires C, 64.2; H, 4.9; N, 22.5%; [M+1]+•,
(ii) Reaction of t-butyl NЈ-[imino(phenyl)methyl]hydrazinecarboxy-
late (9) with oxalyl derivatives. When a solution of the amidrazone
derivative (9) (563 mg, 2.39 mmol) and dimethyl oxalate (282 mg, 2.39
mmol) in dichloromethane (or methanol) (20 ml) was allowed to stand
at room temperature, or heated under reflux, n.m.r., mass spectroscopic,
and t.l.c. analysis showed only starting materials. Heating the mixture
to 200°C for 5 min in a microwave reactor gave triazol-3-one (10) in
quantitative yield. Reaction of the amidrazone derivative (9) (500 mg,
2.13 mmol), ethyl oxalyl chloride (240 ␮l, 2.55 mmol) and anhydrous
triethylamine (300 ␮l, 2.55 mmol) in anhydrous dichloromethane at
–78°C gave a complex mixture but n.m.r. and mass spectroscopic anal-
ysis indicated that none of the desired product (4), or its possible
cyclization products were present.
188.082). ␯
(KBr) 1669s, 1585m, 1566m, 1446m, 1271w, 745m,
max
693m, 608m cm–1. 1H n.m.r. ␦ 3.77, s, CH3; 7.37–7.53, m, 3H, Ar;
8.05–8.18, m, 2H, Ar; 8.41, s, CH=N. 13C n.m.r. ␦ 39.6, CH3; 126.5,
C 2Ј, C 6Ј or C 3Ј, C 5Ј; 128.6, C 2Ј, C 6Ј or C 3Ј, C 5Ј; 130.2, C 4Ј;
133.3, C 1Ј; 148.1, C 3; 153.6, C=O; 157.5, C 5. Mass spectrum: m/z
(c.i.) 188 ([M+1]+•, 100%), 144 (8), 116 (9).
(ii) By aerial oxidation of 1-methyl-3-phenyl-4,5-dihydro-1,2,4-
triazin-6(1H)-one (1). Air was vigorously bubbled through a solu-
tion of 1-methyl-3-phenyl-4,5-dihydro-1,2,4-triazin-6(1H)-one (1)
(553 mg, 2.91 mmol) in chloroform (20 ml) overnight. The solvent was
evaporated and the residue was triturated with dichloromethane.
Recrystallization of the residue from methanol gave 1-methyl-3-
phenyl-1,4-dihydro-1,2,4-triazine-5,6-dione (3) (259 mg, 44%) as a
white solid, m.p. 240–242°C (Found: [M+1]+•, 204.076. C10H9N3O3
requires [M+1]+•, 204.077). ␯max (KBr) 3576m, 3338m, 3120m, 1710s,
1613m, 1386m, 923m, 776m cm–1. 1H n.m.r. ␦ ((CD3)2SO) 3.40, s,
CH3; 7.12–7.34, m, 4H, Ar, NH; 7.54–7.75, m, 2H, Ar. 13C n.m.r. ␦
((CD3)2SO) 38.1, CH3; 126.3, C 2Ј, C 6Ј or C 3Ј, C 5Ј; 128.2, C 2Ј, C 6Ј
or C 3Ј, C 5Ј; 129.7, C 1Ј; 130.3, C 4Ј; 140.2, C 3; 154.0, C 5 or C 6;
155.1, C 5 or C 6. Mass spectrum: m/z (c.i.) 204 ([M+1]+•, 100%), 188
(93). The filtrate was evaporated to dryness at reduced pressure and the
residue was recrystallized from ethyl acetate/light petroleum to afford
1-methyl-3-phenyl-1,2,4-triazin-6(1H)-one (2) (306 mg, 56%), as a
white solid, m.p. 145–145.5°C, which was identical with the material
obtained by method (i).
1-Methyl-3-phenyl-1H-1,2,4-triazole (12)
According to a modified version of the procedure described by
Corey,19 a solution of OxoneR (2KHSO5·KHSO4·K2SO4; 2.82 g, 4.59
mmol) in water (15 ml) was added dropwise to a solution of sodium
hydrogen carbonate (0.9 g, 10.38 mmol) and 1-methyl-3-phenyl-1,2,4-
triazin-6(1H)-one (2) (452 mg, 2.42 mmol) in water (2.5 ml) and
acetone (5 ml). The mixture was stirred at room temperature for 42 h,
and then extracted with ethyl acetate (3×30 ml). The combined extract
was washed with an equal volume of saturated sodium chloride solu-
tion, dried over anhydrous sodium sulfate, and concentrated to afford
an oil. Distillation of this under reduced pressure gave 1-methyl-3-
phenyl-1H-1,2,4-triazole (12) (325 mg, 84%), b.p. 70°C/0.05 mmHg
(lit.26 94°C/0.5 mmHg), which slowly crystallized, m.p. 22°C (lit.20
23°C). G.l.c. Rt 11.88 min, 98%. ␯ (film) 3066w, 1676m, 1577w,
max
1
1522w, 1502m, 1440m, 728s, 696m cm–1. H n.m.r. ␦ 3.96, s, CH3;
7.31–7.50, m, 3H, Ar; 7.97–8.18, m, 3H, Ar and H5. 13C n.m.r. ␦ 36.2,
CH3; 126.2, C 2Ј, C 6Ј or C 3Ј, C 5Ј; 128.6, C 2Ј, C 6Ј or C 3Ј, C 5Ј;
129.2, C 4Ј; 130.8, C 1Ј; 144.3, C 3; 162.5, C 5. Mass spectrum: m/z
(c.i.) 160 ([M+1]+•, 100%); (e.i.) 159 (M+•, 100%), 131 (38), 104 (30),
89 (5), 77 (10), 63 (5).
t-Butyl NЈ-(Imino(phenyl)methyl)hydrazinecarboxylate (9)
A solution of t-butyl carbazate (978 mg, 7.4 mmol) and methyl ben-
zimidate10 (8) (1.00 g, 7.4 mmol) in anhydrous ethanol (20 ml) was
stirred overnight at room temperature under an argon atmosphere. The
mixture was then evaporated to dryness under reduced pressure and the
residue was recrystallized from ethyl acetate/light petroleum to afford
the amidrazone derivative (9)* (1.34 g, 77%), m.p. >300°C† (Found:
1-Methyl-3-phenyl-1,4-dihydro-1,2,4-triazine-5,6-dione (3):
Methylation of 3-Phenyl-1,4-dihydro-1,2,4-triazine-5,6-dione (4)
A solution of 3-phenyl-1,4-dihydro-1,2,4-triazine-5,6-dione27 (4)
(535 mg, 2.8 mmol) in anhydrous dimethylformamide (10 ml) was
* Compound (9) may exist in different tautomeric forms to the one shown.
† The compound (9) cyclizes to compound (10) with loss of t-butyl alcohol when heated (see also m/z 161 in mass spectrum).

Dihydro-1,2,4-triazin-6(1H)-ones. III
975
added dropwise with stirring to an ice-cold suspension of sodium
hydride (171 mg, 6.0 mmol, 80%) in anhydrous dimethylformamide (2
ml) under an argon atmosphere. The cooling bath was then removed
and the mixture was stirred for 1 h, then recooled to 0°C and a solution
of freshly distilled methyl iodide (176 ␮l, 2.8 mmol) in anhydrous
dimethylformamide (5 ml) was added dropwise. The mixture was
stirred for 2 h at 0°C, and then evaporated to dryness (eventually
25°C/0.05 mmHg). 1H and 13C n.m.r. spectroscopy and t.l.c. analysis
indicated that the crude product was a mixture of 1-methyl-3-phenyl-
1,4-dihydro-1,2,4-triazine-5,6-dione (3) (68%) and 1,4-dimethyl-3-
phenyl-1,4-dihydro-1,2,4-triazine-5,6-dione (13) (32%). No starting
material, and no other methylation products were observed. The spec-
troscopic data for (13) are as follows (Found: [M+1]+•, 218.094.
C10H9N3O3 requires [M+1]+•, 218.093). 1H n.m.r. ␦ ((CD3)2SO) 3.08, s,
1-CH3 or 4-CH3; 3.52, s, 1-CH3 or 4-CH3; 7.56, s, Ar. 13C n.m.r. ␦
((CD3)2SO) 33.6, 1-CH3 or 4-CH3; 38.5, 1-CH3 or 4-CH3; 126.6, C 2Ј,
C 6Ј or C 3Ј, C 5Ј; 128.2, C 2Ј, C 6Ј or C 3Ј, C 5Ј; 128.9, C 4Ј; 131.5,
C 1Ј; 136.7, C 3; 153.0, C 5; 157.2, C 6. Mass spectrum: m/z (c.i.) 218
([M+1]+•, 100%).
A., Shklyaev, V. S., and Shklyaev, Y. V., Chem. Heterocycl. Compd.
(Engl. Transl.), 1994, 30, 449.
7
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9
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Acknowledgments
We thank Marianne Bliese (CSIRO) for the preparation of
3-phenyl-1,4-dihydro-1,2,4-triazine-5,6-dione (4).
21
22
23
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