A synthesis of 1-hydroxy-5-(2-substituted aryl)tetrazoles by directed lithiation

Article abstract of DOI:10.1071/CH00073

Dilithiation of 1-hydroxy-5-aryltetrazoles with 2 equiv. of butyllithium in the presence of N,N,N′N′-tetramethylethylenediamine enables the introduction of ortho-substituents into the aryl ring to form compounds (6a-e). The hydroxy group of 1-hydroxy-5-ph

Full text of DOI:10.1071/CH00073

C S I R O P U B L I S H I N G
Australian Journal
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Volume 53, 2000
© CSIRO 2000
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Aust. J. Chem., 2000, 53, 619–622
A Synthesis of 1-Hydroxy-5-(2-substituted
aryl)tetrazoles by Directed Lithiation
Andris J. Liepa,A,B Dionne A. Jones,A Thomas D. McCarthy A and
Roland H. Nearn A
A CSIRO Molecular Science, Private Bag 10, Clayton South MDC, Vic. 3169.
B Author to whom correspondence should be addressed.
Dilithiation of 1-hydroxy-5-aryltetrazoles with 2 equiv. of butyllithium in the presence of N,N,N ´N ´-tetra-
methylethylenediamine enables the introduction of ortho-substituents into the aryl ring to form compounds (6a–e).
The hydroxy group of 1-hydroxy-5-phenyltetrazole may be masked by alkylation with 9-anthrylmethyl chloride.
The masking group is removed with 1,4-diazabicyclo[2.2.2]octane or migrated to N3 by treatment with trifluoro-
acetic acid to form the N-oxide (10).
Keywords. 1-Hydroxy-5-aryltetrazoles; lithiation; alkylation; ortho-substituent.
Introduction
During a program directed at the discovery of new crop
protection chemicals, 1-hydroxytetrazoles were found to
provide precursors for a group of highly active herbicides.1
Subsequent analoging and structure–activity studies sug-
gested that certain 1-hydroxy-5-aryltetrazoles were more
likely to provide active compounds, particularly those
derivatives where the pendent aryl ring bore a substituent in
the 2-position.
In principle, a large number of variations in substitution of
the aryl ring are available by adopting the original synthetic
pathway devised by Plenkiewicz2 (Scheme 1, R = H). This
procedure utilizes aldoximes (1) as starting materials which in
turn are readily obtained from numerous commercially avail-
able aryl aldehydes. Chlorination to the hydroximoyl chloride
(2) followed by displacement with the azide anion provides
azidoximes (3) which can be cyclized to 1-hydroxytetrazoles
(4) with acetyl chloride. With some minor modifications to
avoid isolation of the hydroximoyl chloride and the potentially
hazardous azidoximes, a range of 5-substituted 1-hydroxy-
tetrazoles (4) were obtained without difficulty.
Even so, it was desirable to increase the number of tetra-
zoles bearing ortho-substituents in the aryl ring beyond the
realms accessible from commercial aldehydes. To this end it
seemed more efficient to investigate methodology which
could enable introduction of a variety of substituents by
using a few key 5-aryltetrazole precursors rather than pursue
a plethora of ortho-substituted aryl aldehydes as individual
synthetic targets.
adjacent to the location of the heterocyclic ring as a conse-
quence of stabilization of the lithiated product by a proxi-
mate heteroatom. Indeed, encouraging results have been
obtained following dilithiation of 5-phenyltetrazole3 as well
as with benzoic acids.4 In addition there was the attractive
prospect of obtaining compounds bearing 2,6-disubstitution
on the phenyl ring. This structural type was found not to be
accessible by the Plenkiewicz procedure as a result of resis-
tance to cyclization by the azidoxime intermediate.
Thus, with the present heterocycle there was the possibil-
ity that, following the formation of a lithium salt of the highly
acidic hydroxy group, further treatment with butyllithium
might abstract an ortho-proton from the phenyl substituent.
Subsequent reaction with suitable electrophiles should then
introduce an ortho-substituent (Scheme 2).
Results and Discussion
It has been observed that lithiation of aryl-substituted het-
erocycles often leads to lithiation of the aryl ring at a position
Manuscript received 23 May 2000
© CSIRO 2000
10.1071/CH00073
0004-9425/00/070619

620
Short Communications
In the event it was found that treatment of 1-hydroxy-5-
phenyltetrazole (4; R = H) with 2 equiv. of n-butyllithium in
tetrahydrofuran at –77° for 1 h followed by addition of an
electrophile and subsequent acidification returned only the
starting tetrazole. On the other hand, inclusion of N,N,N´,N´-
tetramethylethylenediamine (TMEDA) in the reaction mixture
led to formation of coloured solutions during the addition of
the second equivalent of butyllithium. These solutions then
readily gave 2-substituted products following reaction with
dimethyl disulfide (6a), methyl iodide (6b), and trimethylsi-
lyl chloride (6c) respectively.A2,6-disubstituted product (6d)
was prepared without difficulty by methylation of the dianion
from 5-(2-chlorophenyl)-1-hydroxytetrazole (4; R = 2-Cl).
On the other hand, thioalkylation of the dianion from 5-(3-
chlorophenyl-1-hydroxytetrazole (4; R = 3-Cl) with dimethyl
disulfide resulted in insertion of the introduced group
between the existing substituents4 to afford (6e).
It was expected that instances would occur where conver-
sion was incomplete and the product would consist of two or
more highly polar tetrazoles which could prove difficult to
separate. It seemed prudent, therefore, to investigate the fea-
sibility of forming some less polar derivative amenable to
chromatographic purification yet susceptible to facile cleav-
age to restore the parent tetrazole. For such a purpose, O-
alkylated derivatives seemed potentially useful. With ease of
subsequent cleavage in mind, the possibility of employing a
9-anthrylmethyl group was considered since derivatives of
this type have been previously advocated5 for the protection
of carboxylic acids, phenols and some other classes of com-
pounds. They have been shown to be easily cleaved by the
sodium salt of methyl mercaptan in N,N-dimethylformamide
at room temperature or, in some instances, by trifluoroacetic
acid in methylene chloride.5
several alternatives.5 In due course it was found that the model
compound could be cleaved efficiently by brief heating with
an excess of 1,4-diazabicyclo[2.2.2]octane (DABCO) in aceto-
nitrile. Apparently under these conditions DABCO is readily
quaternized by transfer of the 9-anthrylmethyl group to give a
water-soluble quaternary salt together with the DABCO salt of
the 1-hydroxy-5-phenyltetrazole from which the tetrazole
(70% yield) was easily liberated by acidification.
Surprisingly, treatment of (9) with trifluoroacetic acid5
induced rapid transformation to an isomeric product (10) in
high yield. Evidently the acid causes protonation of the
oxygen atom and this is followed by dissociation into the
starting hydroxytetrazole together with the anthrylmethyl
cation. Recombination occurs to a significant extent at nitro-
gen to give a product stable to trifluoroacetic acid. After
several cycles, much of the substituent is redistributed to
form a thermodynamically favoured N-oxide product (10)
(60%). In addition, some 1-hydroxy-5-phenyltetrazole (7)
(16%) is generated, possibly as a consequence of a minor
pathway whereby the carbenium ion is trapped by the
weakly nucleophilic trifluoroacetate anion. The observed
shift of the methylene carbon in its 13C n.m.r. spectrum from
75.6 in the O-alkylated material (9) to 50.9 in the N-oxide
(10) is consistent with this interpretation. Thermal migration
of substituents from oxygen to nitrogen in 1-alkoxy-5-aryl-
tetrazoles to form 3-alkyl-5-aryltetrazole 1-oxides has been
observed previously,6 apparently arising by an intermolecu-
lar transfer mechanism.
Alkylation of 1-hydroxy-5-phenyltetrazole (7) with 9-
anthrylmethylchloride (8) in N,N-dimethylformamide in the
presence of potassium carbonate readily gave the crystalline
ether (9) in 90% yield (Scheme 3).
Conditions for efficient recovery of the tetrazole from this
derivative proved more difficult to establish than expected. In
our hands, treatment of (9) with sodium methyl mercaptide in
N,N-dimethylformamide produced irksome mixtures as did

Short Communications
621
5-(3-Chlorophenyl)-1-hydroxytetrazole (4; R = 3-Cl)
Experimental
The tetrazole (4; R = 3-Cl) was obtained (51% yield) by a similar
procedure as above from 3-chlorobenzaldehyde. Colourless prisms
were obtained from ethyl acetate/light petroleum, m.p. 122–124°
(Found: C, 42.6; H, 2.4; N, 28.3. C7H5ClN4O requires C, 42.8; H, 2.6;
N, 28.5%). 1H n.m.r. ((CD3)2SO) 7.42–7.61, m, 2ArH; 7.94–8.08, m,
2ArH. 13C n.m.r. ((CD3)2SO) 125.2, 125.4, 126.2, 130.4, 130.8, 133.5,
143.6.
Melting points were determined on a Reichert Kofler hot-stage
micro-melting point apparatus and are uncorrected. Microanalyses
were performed by Campbell Microanalytical Laboratory, University
of Otago, New Zealand. Infrared spectra were recorded on a
Perkin–Elmer 842 spectrophotometer (cm–1) and refer to paraffin mulls.
1H and 13C n.m.r. spectra were recorded at 200 and 50.3 MHz, respec-
tively, on a Bruker AC-200 spectrometer. Chemical shifts ( ) are mea-
sured in ppm with tetramethylsilane as an internal standard. Radial
thin-layer chromatography was performed on a Harrison Research
Chromatron (7924T) by using 4 mm thick silica plates (silica gel 60
PF254, Merck No. 7749). All reactions involving organometallic
reagents and intermediates were performed under an atmosphere of
argon. The butyllithium solution was standardized by using 2,5-
dimethoxybenzyl alcohol as an indicator7 and N,N,N ´,N ´-tetra-
methylethylenediamine (TMEDA) was distilled from potassium
hydroxide. Tetrahydrofuran was freshly distilled from sodium/benzo-
phenone under argon immediately prior to use. All other commercially
available reagents were used without further purification. Light
petroleum refers to the fraction with a b.p. of 40–60°.
5-(4-Chlorophenyl)-1-hydroxytetrazole (4; R = 4-Cl)
The tetrazole (4; R = 4-Cl) was obtained by a similar procedure as
above (57% yield) from 4-chlorobenzaldehyde. Colourless needles
were obtained from ethyl acetate, m.p. 207–208° (Found: C, 42.9; H,
1
2.4; N, 28.3%. C7H5ClN4O requires C, 42.8; H, 2.6; N, 28.5 %) H
n.m.r. ((CD3)2SO) 7.61, d, J 8.8 Hz; 8.20, d, J 8.8 Hz. 13C n.m.r.
((CD3)2SO) 123.0; 128.1, 2×C; 128.7, 2×C; 134.7; 143.0.
1-Hydroxy-5-(2-methylphenyl)tetrazole (6b)
The tetrazole (4; R = 2-Me) was prepared (41% yield) in a similar
manner from 2-methylbenzaldehyde. Fawn plates were obtained from
benzene, m.p. 122–124° (Found: C, 54.2; H, 4.8; N, 31.6 . C8H8N4O
requires C, 54.5; H, 4.6; N, 31.8 %). 1H n.m.r. ((CD3)2SO) 2.31, s, Me;
7.25–7.66, m, 4ArH. 13C n.m.r. ((CD3)2SO) 19.5, 122.2, 126.0, 129.8,
130.7, 131.0, 137.7, 146.9.
1-Hydroxy-5-phenyltetrazole (4; R = H)
1-Hydroxy-5-phenyltetrazole (4; R = H) was prepared as described,2
1
m.p. 154–156° (lit.2 151–152°). H n.m.r. ((CD3)2SO) 7.3, m, 3H,
ArH; 8.05, m, 2H, ArH. 13C n.m.r. ((CD3)2SO) 122.6, 127.4, 129.1,
131.3, 145.7.
1-Hydroxy-5-(2-methylsulfanylphenyl)tetrazole (6a)
To a stirred solution of 1-hydroxy-5-phenyltetrazole (4; R = H)
(1.0 g, 6.2 mmol) in dry tetrahydrofuran (100 ml) cooled to –77° in a
dry ice/acetone bath was added TMEDA (2.0 ml, 13.3 mmol) followed by
n-butyllithium (6.5 ml, 13.6 mmol, 2.1 M solution in hexane) added
dropwise. After stirring for a further 1 h at –77°; the reaction mixture
was allowed to slowly warm to between –20 to –30° and held at this
temperature for a further 20 min after the addition of dimethyl disulfide
(1.2 ml, 13.6 mmol). The reaction mixture was quenched with dilute
hydrochloric acid and water (50 ml) was then added. The resulting solu-
tion was then adjusted to pH 7 by the addition of solid NaHCO3. After
the organic and aqueous phases were separated, the organic phase was
extracted with saturated NaHCO3 (20 ml). The aqueous phase and
extract were combined and acidified with concentrated hydrochloric
acid and extracted with ether (2×40 ml). The combined ether extracts
were washed with water (3×40 ml), dried (MgSO4), and evaporated
under vacuum to give a colourless oil which crystallized slowly on
standing (1.1 g, 85%). Recrystallization from methanol/water gave the
product (6a) as colourless needles, m.p. 118–120° (Found: C, 45.8; H,
3.7; N, 26.8; S, 15.3. C8H8N4OS requires C, 46.1; H, 3.9; N, 26.9; S,
15.4%). 1H n.m.r. ((CD3)2SO) 2.45, s, Me; 7.24–7.40, m, 1ArH;
7.50–7.77, m, 3ArH. 13C n.m.r. ((CD3)2SO) 15.5, 121.4, 124.9, 126.6,
130.4, 131.7, 139.8, 146.1.
5-(2-Chlorophenyl)-1-hydroxytetrazole (4; R = 2-Cl)
To a solution of 2-chlorobenzaldoxime (7.8 g, 0.05 mol) in acetoni-
trile (40 ml) containing 5 drops of concentrated hydrochloric acid was
added N-chlorosuccinimide (7.3 g, 0.055 mol) in portions (c. 1 g) at a
rate which allowed a transient blue-green colour to fade before each
subsequent addition. Following the final addition, the solution was
allowed to stand for 30 min, and then diluted with water (80 ml) and
extracted with benzene (2×40 ml). The combined benzene extracts con-
taining the hydroxamoyl chloride were subsequently used to prepare a
solution of the azidoxime without any further purification.
A solution of sodium azide (6.5 g, 0.1 mol) in water (33 ml) was
added in a thin stream with stirring to the benzene solution of the
hydroxamoyl chloride (obtained as described above) cooled in an ice
bath. The mixture was then stirred at room temperature for 48 h. The
aqueous layer was then separated and the organic phase was washed
with water (2×100 ml). The extract was dried over sodium sulfate and
used in the cyclization without undue delay. Drying the solution over
anhydrous magnesium sulfate sometimes led, after a brief delay, to
commencement of a brisk effervescence with decomposition of the
azidoxime. A similar phenomenon was on rare occasions observed
during drying with anhydrous sodium sulfate, but only after a much
longer delay.
1-Hydroxy-5-(2-methylphenyl)tetrazole (6b) by Methylation
Following the same procedure as outlined for (6a), 1-hydroxy-5-
phenyltetrazole (4; R = H) (1.0 g, 6.2 mmol) in dry tetrahydrofuran (100
ml) was treated with n-butyllithium (6.5 ml, 13.6 mmol, 2.1 M solution
in hexane) in the presence of TMEDA (2.0 ml, 13.3 mmol). Methyl iodide
(0.5 ml, 7.4 mmol) was added in place of dimethyl disulfide. The crude
product (918 mg, 83%) was obtained as a pale yellow solid on acidifi-
cation and extraction of the basic aqueous phase with ether. The product
was recrystallized from benzene to give colourless needles (m.p.
The benzene solution containing crude azidoxime (obtained as
described above) was added in a thin stream to an excess of acetyl chlo-
ride (20 ml) in benzene (20 ml) cooled in ice; the mixture was allowed
to warm over 2 h to room temperature and then allowed to stand for
48 h. The mixture was partially evaporated (to about 30 ml), cautiously
diluted with water (10 ml) and stirred for 10 min and then simmered for
2 h. The cooled mixture was diluted with water (100 ml) and extracted
with diethyl ether (100 ml). The ether extract was washed with water
and then extracted with two portions of saturated sodium bicarbonate
(100 ml each). The combined sodium bicarbonate extracts were acidi-
fied to pH 1 by the addition of concentrated hydrochloric acid and the
precipitate was collected by filtration and washed on the filter with
water to give the tetrazole (4; R = 2-Cl) (5.3 g, 54%) as colourless
needles, m.p. 187–190°. A portion was recrystallized from ethyl acetate
to give colourless prisms, m.p. 189–192° (Found: C, 43.0; H, 2.3; N,
1
121–123°) identical (m.p., mixture m.p. and H n.m.r.) with material
prepared by total synthesis.
1-Hydroxy-5-(2-trimethylsilylphenyl)tetrazole (6c)
Following the same procedure as outlined above, the hydroxytetra-
zole (4; R = H) (1.0 g, 6.2 mmol) in dry tetrahydrofuran (100 ml) was
treated with n-butyllithium (6.5 ml, 13.6 mmol, 2.1 M solution in
hexane) in the presence of TMEDA (2.0 ml, 13.3 mmol) followed by
chlorotrimethylsilane (1.2 ml, 9.3 mmol). The reaction mixture was
quenched with water (20 ml) and extracted with ether (30 ml). The
1
28.5. C7H5ClN4O requires C, 42.8; H, 2.6; N, 28.5 %). H n.m.r.
((CD3)2SO) 7.83–7.45, m . 13C n.m.r. ((CD3)2SO) 122.4, 2×C; 127.5;
130.0; 132.1; 133.0; 145.5.

622
Short Communications
H, 4.6; N, 15.9%). 1H n.m.r. (CDCl3) 6.42, s, CH2 7.09, m, 2H; 7.25,
;
aqueous phase was cooled in an ice bath, acidified with concentrated
hydrochloric acid, and extracted with ether (2×30 ml). The combined
ether extracts were washed with water (4×30 ml), dried (MgSO4) and
evaporated under vacuum to give the crude product as a colourless solid
(0.89 g, 62%), m.p. 156–160°. Recrystallization of a sample from
methanol/water gave the tetrazole (6c) as colourless prisms, m.p.
158.5–160.0° (Found: C, 51.1; H, 5.9; N, 23.9. C10H14N4OSi requires
m, 2H; 7.49, m, 5H; 7.91, m, 2H; 8.13, m, 2H; 8.42, s, 1H. 13C n.m.r.
((CD3)2SO) 75.6, OCH2; 120.0–133.0, aromatic C.
Cleavage of (9) by 1,4-Diazabicyclo[2.2.2]octane
To a solution of the ether (9) (0.5 g, 1.4 mmol) in acetonitrile (10 ml)
was added 1,4-diazabicyclo[2.2.2]octane (0.5 g, 4.5 mmol) and the
whole was simmered for 25 min. After this time, t.l.c. showed an
absence of starting material and a drop of the solution added to water
gave a clear solution. The solvent was removed by evaporation, the
residue was stirred with hydrochloric acid (5 N, 10 ml) and extracted
with ether. Evaporation of the organic phase gave a pale yellow, crys-
talline residue which was stirred with water (5 ml) and sodium bicar-
bonate. A small amount of yellow flocculent material was filtered off
and the aqueous filtrate was acidified with concentrated hydrochloric
acid to precipitate 1-hydroxy-5-phenyltetrazole as colourless needles
(168 mg, 70%) identical (m.p., mixture m.p.) with authentic material.
1
C, 51.3; H, 6.0; N, 23.9%). H n.m.r. ((CD3)2SO) 0.03, 9H, SiMe3;
7.42–7.59 and 7.63–7.73, m, 3H. 13C n.m.r. ((CD3)2SO) –0.5, 128.0,
129.0, 129.8, 130.0, 135.0, 140.9, 148.3.
5-(2-Chloro-6-methylphenyl)-1-hydroxytetrazole (6d)
Following the same procedure as outlined for (6a), the hydroxy-
tetrazole (4; R = 2-Cl) (2.0 g, 10.2 mmol) in dry tetrahydrofuran (150
ml) was treated with n-butyllithium (10.7 ml, 22.4 mmol, 2.1 M solution
in hexane) in the presence of TMEDA (3.4 ml, 22.4 mmol) followed by
methyl iodide (0.8 ml, 12.8 mmol). The crude product (1.8 g) was
obtained as a pale yellow solid on acidification and extraction of the
basic aqueous phase with ether. The corresponding organic phase did
not contain any O-alkylated hydroxytetrazole, as judged by the absence
of any signal attributable to a methoxy group in the proton magnetic
resonance spectrum. Recrystallization from aqueous methanol gave the
product (6d) as colourless prisms (1.4 g, 68%), m.p. 233–235° (dec.)
(Found: C, 45.5; H, 3.1; N 26.4. C8H7ClN4O requires C, 45.6; H, 3.4;
3-(Anthracen-9-ylmethyl)-5-phenyltetrazole 1-Oxide (10)
Trifluoroacetic acid (2 ml) was added dropwise to a solution of the
9-anthrylmethyl ether (9) (600 mg, 1.7 mmol) in dichloromethane (10
ml) maintained at 0°. After 10 min the volatile components were
removed by evaporation and the residue was taken up in benzene
(20 ml) and the solution was extracted with aqueous sodium bicarbon-
ate. Acidification of the aqueous extract with concentrated hydrochlo-
ric acid followed by extraction with ether gave a small quantity (44 mg,
16%) of tetrazole after evaporation of the ethereal solution. On stand-
ing for several hours, the original benzene solution deposited a yellow
solid which was collected by filtration to give the product (10) (360 mg,
60%). Recrystallization from dichloromethane/methanol gave yellow
plates, m.p. 176–178° (Found: C, 74.7; H, 4.8; N, 15.7. C22H16N4O
N, 26.6%). 1H n.m.r. ((CD3)2SO) 2.06, s, Me; 7.4–7.8, m, 3ArH. 13
C
n.m.r. ((CD3)2SO) 19.3, 122.1, 126.6, 128.5, 131.9, 133.8, 140.6,
144.8.
5-(3-Chloro-(2-methylsulfanylphenyl)-1-hydroxytetrazole (6e)
Following the same procedure as outlined above, the 1-hydroxy-
tetrazole (4; R = 3-Cl) (1.5 g, 7.7 mmol) in dry tetrahydrofuran (120 ml)
was treated with n-butyllithium (8.8 ml, 16.8 mmol, 2.1 M solution in
hexane) in the presence of TMEDA (2.5 ml, 16.8 mmol), followed by
dimethyl disulfide (1.5 ml, 16.8 mmol). The crude product (1.5 g, 80%)
was obtained as a pale yellow oil which crystallized slowly on standing.
5-(3-Chloro-1-hydroxy-(2-methylsulfanylphenyl)tetrazole (6e) was
obtained as colourless needles from ether/benzene, m.p. 163–164°
(Found: C, 39.5; H, 3.1; N, 23.1; S, 12.9. C8H7ClN4OS requires C, 39.6;
H, 2.9; N, 23.1; S, 13.2%). 1H n.m.r. ((CD3)2SO) 2.39, s, SMe; 7.60,
t, J 7.7 Hz, H 5; 7.62, dd, J 1.8, and 7.7 Hz, H4; 7.87, dd, J 1.8 and
7.7 Hz, H 6. 13C n.m.r. ((CD3)2SO) 18.4, 129.9, 130.0, 130.3, 132.8,
135.3, 139.6, 146.9.
1
requires C, 75.0; H, 4.7; N, 15.9%). H n.m.r. (CDCl3) 6.58, CH2;
7.32–7.70, m, 7H, ArH; 8.08, m, 2H; 8.33, m, 2H; 8.53, m, 2H; 8.58, s,
1H. 13C n.m.r. ((CD3)2SO) 50.9, NCH2; 122.0–131.0, aromatic C.
Acknowledgments
We thank E. I. DuPont de Nemours and Co., Agricultural
Products Department, for the evaluation of herbicidal activ-
ity. We are also indebted to Mr Ian Willing for the determi-
nation of n.m.r. spectra.
1-(Anthracen-9-ylmethoxy)-5-phenyltetrazole (9)
References
1
Anthracen-9-ylmethyl chloride (460 mg, 2.0 mmol) was added to a
solution of 5-phenyl-1-hydroxytetrazole (300 mg, 1.9 mmol) dissolved
in N,N-dimethylformamide (5 ml) containing potassium carbonate (643
mg, 4.6 mmol) and the mixture was stirred overnight at room tempera-
ture. The next day the mixture was diluted with water (5 ml), stirred for
20 min and the product was collected by filtration and washed with
water on the filter to afford yellow needles (631 mg, 90%) showing
only one spot by t.l.c. The compound (9) was recrystallized from
dichloromethane/cyclohexane to give pale yellow needles, m.p.
144–146° (Found: C, 74.8; H, 4.7; N, 15.6. C22H16N4O requires C, 75.0;
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