This disclosure describes novel compounds of the formula ##STR1## wherein R.sub.1 and R.sub.2 each independently represent hydrogen, halo having an atomic weight of about 19 to 36, lower alkyl, straight chain lower alkoxy, amino, nitro or trifluoromethyl, and PA1 X represents ##STR2## which are useful as minor tranquilizers and sleep inducers.

This invention relates to 3-substituted or unsubstituted 
phenyl-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3-e]-as-triazine 
s and corresponding 4-oxides which exhibit minor tranquilizer and sleep 
inducer activity. In particular, it relates to pyrano[4,3-e]-as-triazines 
and corresponding 4-oxides, pharmaceutically acceptable salts, their 
preparation and intermediates thereof. 
The compounds of this invention may be represented by the following 
structural formula: 
##STR3## 
wherein R.sub.1 and R.sub.2 each independently represent hydrogen, halogen 
having an atomic weight of about 19 to 36, lower alkyl, i.e., alkyl having 
1 to 4 carbon atoms, e.g., methyl, ethyl, isopropyl and the like, straight 
chain lower alkoxy, i.e., alkoxy having 1 to 4 carbon atoms, e.g., 
methoxy, ethoxy and the like, amino, nitro or trifluoromethyl, and 
X represents 
##STR4## 
provided that (i) when one of R.sub.1 and R.sub.2 represents nitro, the 
other is other than nitro or trifluoromethyl; 
(ii) when R.sub.1 and R.sub.2 represent trifluoromethyl, they are on other 
than adjacent carbon atoms; an 
(iii) when R.sub.1 and R.sub.2 represent t-butyl, they are on other than 
adjacent carbon atoms; and 
(iv) when one of R.sub.1 and R.sub.2 is trifluoromethyl and the other is 
t-butyl, they are on other than adjacent carbon atoms. 
The compounds of formula (I) in which X represents 
##STR5## 
may be prepared according to the following reaction scheme: 
##STR6## 
where R.sub.3 represents lower alkyl having 1 to 2 carbon atoms, i.e., 
methyl or ethyl, and 
R.sub.1, R.sub.2 and the provisos are as defined above. 
The compounds of formula (Ia) are prepared by treating a compound of the 
formula (II) with a compound of the formula (III) in the presence of an 
inert atmosphere, e.g., nitrogen, helium or argon and in the presence of 
an inert organic solvent. Although the particular solvent employed is not 
critical, the preferred solvents include the aromatic hydrocarbons such as 
benzene, toluene and the like, the lower alkanols such as methanol, 
ethanol and the like, or an excess of the ortho ester of formula (III), 
the latter being especially preferred. The temperature of the reaction is 
not critical, but it is preferred that the reaction be run from about 
70.degree. to 200.degree. C., preferably from about 130.degree. to 
150.degree. C. The reaction is run from about 12 to 36 hours, preferably 
from about 15 to 20 hours. The product is recovered using conventional 
techniques, e.g., filtration. 
Another aspect of this invention and the preferred method of preparing the 
compounds of formula (I) in which X represents 
##STR7## 
and one of R.sub.1 and R.sub.2 is nitro and the other is other than nitro 
or trifluoromethyl may be illustrated by the following reaction scheme: 
##STR8## 
where R.sub.1 ' is hydrogen, halo having an atomic weight of about 19 to 
36, lower alkyl, i.e., alkyl having 1 to 4 carbon atoms, e.g., methyl, 
ethyl and the like, straight chain lower alkoxy, i.e., alkoxy having 1 to 
4 carbon atoms, e.g., methoxy, ethoxy and the like, or amino. 
The compounds of formula I(a") may be prepared by treating a compound of 
formula I(a') with a nitronium ion-forming reactant in the presence of an 
inert organic solvent. The nitronium ion-forming reactant may be prepared, 
for example, from a mixture of sulfuric acid and nitric acid, a mixture of 
trifluoromethanesulfonic acid with fuming nitric acid, or a mixture of 
hydrogen fluoride, and dinitrogen peroxide in nitromethane at -20.degree. 
C. saturated with boron fluoride, preferably trifluoromethane sulfonic 
acid with fuming nitric acid, in a ratio of 2 moles 
trifluoromethanesulfonic acid to one mole of fuming nitric acid. Although 
the particular solvent used is not critical, the preferred solvents 
include the aromatic hydrocarbons such as benzene, toluene and the like or 
the halogenated hydrocarbons such as methylene chloride chloroform and the 
like, preferably methylene chloride. The temperature of the reaction is 
not critical, but it is preferred that the reaction be run from about 
-80.degree. C. to +70.degree. C., preferably from about -35.degree. C. to 
+30.degree. C. The reaction is run from about 19 to 96 hours, preferably 
from about 60 to 75 hours. The product is recovered using conventional 
techniques, e.g., recrystallization. 
The compounds of formula (I) in which X represents 
##STR9## 
may be prepared according to the following reaction scheme: 
##STR10## 
where R.sub.1, R.sub.2 and the provisos are as defined above. 
The compounds of formula (Ib) are prepared by treating a compound of the 
formula (Ia) with cyclohexene (IV) in an inert atmosphere, e.g., nitrogen, 
helium, or argon, preferably nitrogen, and in the presence of a noble 
metal catalyst such as palladium, platinum, rhodium and the like, 
preferably palladium, optionally neat or on a support such as charcoal, in 
an inert organic solvent. Although the particular solvent used is not 
critical, it is preferred that the reaction be carried out in the presence 
of the lower alkanols, e.g., methanol, ethanol, and the like, preferably 
ethanol. Temperature of the reaction is not critical but it is preferred 
that the reaction be carried out between 20.degree. to 200.degree. C., 
preferably from about 70.degree. to 110.degree. C. The reaction is run 
from about 5 to 72 hours, preferably from about 15 to 30 hours. The 
product is recovered using conventional techniques, e.g., crystallization. 
The compounds of formula (II) may be prepared according to the following 
reaction scheme: 
##STR11## 
The compounds of formula (II) are prepared by treating a compound of the 
formula (V) with hydrazine (VI) in an inert atmosphere, e.g., nitrogen, 
helium or argon, preferably nitrogen in the presence of an inert organic 
solvent. Although the particular solvent employed is not critical, it is 
preferred that the reaction be carried out in the presence of the lower 
alkanols, e.g., methanol, ethanol and the like, preferably ethanol. The 
temperature of the reaction is not critical, but it is preferred that the 
reaction be carried out between 0.degree. to 150.degree. C., preferably 
from about 75.degree. to 85.degree. C. The reaction is run from about 1 to 
18 hours, preferably from about 2 to 8 hours. The product is recovered 
using conventional techniques, e.g., crystallization. 
Another preferred aspect of this invention concerns a process for preparing 
certain of the compounds of formula (I) in accordance with the following 
reaction scheme: 
##STR12## 
wherein R.sub.1, R.sub.2 and the provisos are as defined above. 
The compounds of formula (Id) are prepared by reacting a compound of the 
formula (Ic) with phosphorous trichloride in the presence of an inert 
atmosphere, e.g., nitrogen, helium or argon and in the presence of an 
inert organic solvent. The particular solvent employed is not critical, 
however, it is preferred that the reaction be run in the presence of 
chloroform, tetrachloroethane or 1,2-dichloroethane, the latter being 
especially preferred. The temperature of the reaction is not critical, but 
it is preferred that the reaction be run from 50.degree. to 150.degree. 
C., preferably the reflux temperature of the solvent. The reaction is run 
from about 4 to 18 hours, preferably from about 6 to 9 hours. The product 
is recovered using conventional techniques, e.g., recrystallization. 
The compounds of formula (Ic) are prepared in accordance with the following 
reaction scheme: 
##STR13## 
wherein R.sub.1, R.sub.2 and the proviso are as defined above. 
The compounds of formula (Ic) are prepared by reacting a compound of the 
formula (VII) with a compound of the formula (II) in the presence of a 
base such as sodium carbonate, potassium carbonate, sodium hydroxide, 
potassium hydroxide and the like, preferably potassium carbonate and in 
the presence of an inert organic solvent. Although the particular solvent 
used is not critical, the preferred solvents include the aromatic 
hydrocarbons such as benzene, toluene and the like, preferably toluene. 
The temperature of the reaction is not critical, but it is preferred that 
the reaction be run from about 75.degree. to 150.degree. C., preferably 
the reflux temperature of the solvent. The reaction is run from about 3 to 
15 hours, preferably from about 4 to 6 hours. The product is recovered 
using conventional techniques, e.g., recrystallization. 
Certain of the compounds of formulae (III), (IV), (V), (VI) and (VII) are 
known and may be prepared by methods described in the literature. Those 
compounds of formulae (III), (IV), (V), (VI) and (VII) not specifically 
disclosed may be prepared by analogous methods from known starting 
materials. 
It will be understood that the compounds of formula (I) may exist in the 
form of optically active isomers and can be separated and recovered by 
conventional techniques, and that such isomeric forms are included within 
the scope of this invention. They also can be prepared starting with one 
of the optically active isomers of compound (II). The following isomers 
have been separated and recovered and represent a preferred embodiment of 
this invention: 
(a) 
(+)-3-(m-trifluoromethylphenyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H- 
pyrano[4,3-e]-as-triazine-4-oxide, 
(b) 
(+)-3-(m-trifluoromethylphenyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H- 
pyrano[4,3-e]-as-triazine, 
(c) 
(+)-3-(m-nitrophenyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3 
-e]-as-triazine-4-oxide, 
(d) 
(+)-3-(m-nitrophenyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3 
-e]-as-triazine, 
(e) 
(-)-3-(m-nitrophenyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3 
-e]-as-triazine-4-oxide, or 
(f) 
(-)-3-(m-nitrophenyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3 
-e]-as-triazine. 
The compounds which are particularly preferred are compounds (a) and (f) 
set out above. 
The compounds of formula (I) are useful because they possess 
pharmacological activity in animals as sleep inducers and minor 
tranquilizers as indicated (1) by the hexobarbital reinduction method of 
Winter, J. Pharmacol. and Exp. Therap., 94, 7-11, 1948; (2) by their 
ability to produce docility in behavior tests in mice given 10 to 200 
mg/kg of animal body weight, i.p. of the test compound according to the 
30-word adjective check sheet system basically as described by Irwin S. 
(Gordon Research Conference, Medicinal Chemistry, 1959) and Chen 
(Symposium on Sedative and Hypnotic Drugs, Williams and Wilkins, 1954); 
(3) by their ability to antagonize chronic convulsions and death in mice 
given 20 to 250 mg/kg i.p. of N-sulfamoylazepine; (4) by scoring for loss 
of righting reflex according to the method of Reed-Muench (American 
Journal of Hygiene, 27: 493-497, 1938), in which mice are administered 
12.5 mg/kg, i.p. Thioridazine, immediately after which test compound is 
administered at dosages of 5 to 100 mg/kg in a volume of 0.1 ml/10 g. 
body weight. Sixty minutes after dosing, the mice are scored for loss of 
right reflex; (5) in the Cebus monkey using chronically implanted 
electrodes. Brain readings are obtained via a ten or sixteen channel 
electroencephalograph. For the recording sessions, the monkeys are 
restrained by neck and waist plates in chairs in full side observation 
cages, at the same time every night, for thirteen and one half hours, 
Monday through Thursday. Gross behavior is monitored via closed circuit 
television and video tape recordings. The compounds of formula (I) are 
administered p.o. immediately on placing the monkey in the observation 
cages with at least seven days intervening between drug administration. 
Physiological saline is administered via a similar route and at the same 
time on all control runs. Control data are collected at least three days 
per week and accumulated to give control data for fifteen sessions per 
monkey. Data from each session are statistically compared via computer 
analysis to the previous 5-15 control sessions for the particular animal, 
with particular emphasis being given to the following phases of the 
sleep-wakefulness cycle: resting awake, light sleep, deep sleep, 
paradoxical (REM) sleep, "pseudo-" paradoxical sleep, latency to onset of 
deep sleep, and latency to onset of first epoch of paradoxical sleep; and 
(6) by their ability to reduce conflicts as defined in the Gellar Conflict 
Test [Irving Geller, Psychopharmacologia, I, 42-492, (1960)]. 
The sleep inducing effective dosage of the compounds of formula (I) will 
vary depending on the particular compound employed. However, in general, 
satisfactory results are obtained when the compounds are administered 
orally at a daily dosage of from about 0.1 milligram to about 75 
milligrams per kilogram of animal body weight, typically given in a single 
dose at bedtime. For most large mammals, the total daily dosage is from 
about 1 to about 300 milligrams, preferably at bedtime and dosage forms 
suitable for internal administration comprise from about 0.25 to about 150 
milligrams of the compound in admixture with a solid or liquid 
pharmaceutical carrier or diluent. The preferred pharmaceutical 
compositions from the standpoint of preparation and ease of administration 
are solid compositions, particularly hard-filled capsules and tablets. 
For minor tranquilizer use, the effective dosage will vary depending on the 
particular compound employed. However, in general, satisfactory results 
are obtained when the compounds are administered orally at a daily dosage 
of from about 1.0 milligram to about 75 milligrams per kilogram of animal 
body weight, typically given in divided doses two to four times per day. 
For most large mammals, the total daily dosage is from about 5 to 500 
milligrams, and dosage forms suitable for internal administration comprise 
from about 1.25 to about 250 milligrams of the compound in admixture with 
a solid or liquid pharamceutical carrier or diluent. 
For the uses mentioned above, the compound may be administered orally in 
such forms as tablets, capsules, elixirs, suspensions and the like, or 
parenterally in the form of injectable solutions or suspensions. The 
dosage will vary depending upon the mode of administration utilized and 
the compound employed. 
The compounds of formula (I) may be similarly administered in the form of 
their non-toxic pharmaceutically acceptable salts. Such salts possess the 
same order of activity as the free base and are readily prepared by 
reacting the base with an appropriate acid by conventional technique and, 
accordingly, are included within the scope of this invention. 
Representative of such salts are the mineral acid salts, e.g., 
hydrochloride, hydrobromide, sulfate and the like, and the organic acid 
salts such as succinate, benzoate, maleate and the like. 
Tablets and capsules containing the ingredients indicated below may be 
prepared by conventional techniques and are useful as sleep inducers at a 
dose of one or two tablets just before bedtime. Tablets and capsules 
containing the ingredients indicated below may also be useful as minor 
tranquilizers in divided doses two to four times per day. 
______________________________________ 
Weight (mg.) 
Ingredients Tablet Capsule 
______________________________________ 
3-phenyl-5,8-dihydro-6,6,8-tri- 
methyl-5,8-ethano-6H-pyrano 
[4,3-e]-as-triazine 
200 200 
tragacanth 10 -- 
lactose 247.5 300 
corn starch 25 -- 
talcum 15 -- 
magnesium stearate 2.5 -- 
Total 500 mg. 500 mg. 
______________________________________

EXAMPLE 1 
1,3,3-Trimethyl-2-oxabicyclo[2,2,2]octan-5,6-dione-5-oxime-6hydrazone 
A mixture of 1.97 g. (0.01 mole) 
1,3,3-trimethyl-2-oxabicyclo[2,2,2]octan-5,6-dione-5-oxime and 0.35 ml. 
(0.011 mole) anhydrous hydrazine (98%) in 25 ml. absolute ethanol is 
refluxed under nitrogen at a bath temperature of 80.degree. C. for 1 hour. 
After evaporation of the solvent, the residue is recrystallized from ether 
to give 1,3,3-trimethyl-2-oxabicyclo 
[2,2,2]octan-5,6-dione-5-oxime-6-hydrazone; mp. 138.degree. to 142.degree. 
C. 
EXAMPLE 2 
3-Phenyl-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano 
[4,3-e]-as-triazine-4-oxide 
A solution of 2.11 g. (0.01 mole) 
1,3,3-trimethyl-2-oxabicyclo[2,2,2]octan-5,6-dione-5-oxime-6-hydrazone in 
10 ml. trimethylorthobenzoate is refluxed under nitrogen for 18 hours at a 
bath temperature of 140.degree. C. during which time all distillate is 
removed. The resulting mixture is cooled and evaporated to dryness in 
vacuo. After filtering the residue dissolved in 2% methanol-chloroform 
through silica gel, and evaporation of the filtrate the resulting solid is 
triturated with ether, giving 
3-phenyl-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano 
[4,3-e]-as-triazine-4-oxide; m.p. 186.5.degree. to 189.degree. C. 
Following the above procedure and using in place of trimethylorthobenzoate 
an equivalent amount of 
(a) p-chloro-trimethylorthobenzoate, 
(b) p-fluoro-trimethylorthobenzoate, 
(c) p-methyl-trimethylorthobenzoate, 
(d) p-methoxy-trimethylorthobenzoate, 
(e) m-trifluoromethyl-trimethylorthobenzoate, 
(f) p-amino-trimethylorthobenzoate, 
(g) p-nitro-trimethylorthobenzoate, 
(h) m-nitro-trimethylorthobenzoate, 
(i) m-chloro-trimethylorthobenzoate, or 
(j) 3,4-dimethoxy-trimethylorthobenzoate, 
there is obtained 
(a) 
3-(p-chlorophenyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3-e] 
-as-triazine-4-oxide, 
(b) 
3-(p-fluorophenyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3-e] 
-as-triazine-4-oxide, 
(c) 
3-(p-tolyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3-e]-as-tri 
azine-4-oxide, 
(d) 
3-(p-anisyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3-e]-as-tr 
iazine-4-oxide, 
(e) 
3-(m-trifluoromethylphenyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyra 
no[4,3-e]-as-triazine-4-oxide, 
(f) 
3-(p-aminophenyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3-e]- 
as-triazine-4-oxide, 
(g) 
3-(p-nitrophenyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3-e]- 
as-triazine-4-oxide, 
(h) 
3-(m-nitrophenyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3-e]- 
as-triazine-4-oxide, 
(i) 
3-(m-chlorophenyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3-e] 
-as-triazine-4-oxide, or 
(j) 
3-(3,4-dimethoxyphenyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4 
,3-e]-as-triazine-4-oxide, respectively. 
EXAMPLE 3 
3-Phenyl-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano 
[4,3-e]-as-triazine 
To a solution of 1.80 g. (0.006 mole) 
3-phenyl-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3-e]-as-triazi 
ne-4-oxide and 1.50 g. (0.018 mole) cyclohexene in 30 ml. absolute ethanol 
there is added 60 mg. 10% palladium on charcoal. The resulting mixture is 
refluxed under a nitrogen atmosphere for 18 hours. The catalyst is then 
removed by filtration and the filtrate evaporated to give 
3-phenyl-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3-e]-as-triazi 
ne; m.p. 180.degree. to 189.degree. C. 
Following the above procedure and using in place of 
3-phenyl-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3-e]-as-triazi 
ne-4-oxide an equivalent amount of 
(a) 
3-(p-chlorophenyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3-e] 
-as-triazine-4-oxide, 
(b) 
3-(p-fluorophenyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3-e] 
-as-triazine-4-oxide, 
(c) 
3-(p-tolyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3-e]-as-tri 
azine-4-oxide, 
(d) 
3-(p-anisyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3-e]-as-tr 
iazine-4-oxide, 
(e) 
3-(m-trifluoromethylphenyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyra 
no[4,3-e]-as-triazine-4-oxide, 
(f) 
3-(p-aminophenyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3-e]- 
as-triazine-4-oxide, 
(g) 
3-(p-nitrophenyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3-e]- 
as-triazine-4-oxide, 
(h) 
3-(m-nitrophenyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3-e]- 
as-triazine-4-oxide, 
(i) 
3-(m-chlorophenyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3-e] 
-as-triazine-4-oxide, or 
(j) 
3-(3,4-dimethoxyphenyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4 
,3-e]-as-triazine-4-oxide, 
there is obtained 
(a) 
3-(p-chlorophenyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3-e] 
-as-triazine, 
(b) 
3-(p-fluorophenyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3-e] 
-as-triazine, 
(c) 
3-(p-tolyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3-e]-as-tri 
azine, 
(d) 
3-(p-anisyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3-e]-as-tr 
iazine, 
(e) 
3-(m-trifluoromethylphenyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyra 
no[4,3-e]-as-triazine, 
(f) 
3-(p-aminophenyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3-e]- 
as-triazine, 
(g) 
3-(p-nitrophenyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3-e]- 
as-triazine, 
(h) 
3-(m-nitrophenyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3-e]- 
as-triazine, 
(i) 
3-(m-chlorophenyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3-e] 
-as-triazine, or 
(j) 
3-(3,4-dimethoxyphenyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4 
,3-e]-as-triazine, respectively. 
EXAMPLE 4 
3-(m-nitrophenyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3-e]-a 
s-triazine-4-oxide 
To a mixture of 0.2 ml. (0.005 mole) fuming nitric acid and 1.5 g. (0.01 
mole) trifluoromethanesulfonic acid in 15 ml. anhydrous methylene chloride 
maintained at a temperature of -30.degree. C. there is added dropwise a 
solution of 0.60 g. (0.002 mole) 
3-phenyl-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3-e]-as-triazi 
ne-4-oxide in 15 ml. methylene chloride, maintaining the temperature at 
-30.degree. C. throughout the addition. The resulting mixture is allowed 
to stir at ambient temperature for 72 hours, then poured onto ice and 
neutralized with solid sodium bicarbonate. The organic layer is removed, 
washed with saturated brine solution, dried over magnesium sulfate and 
evaporated. Trituration of the resulting residue with ether gives 
3-(m-nitrophenyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3-e]- 
as-triazine-4-oxide-monohydrate; m.p. 150.degree. (d). 
Following the above procedure but using in place of 
3-phenyl-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3-e]-as-triazi 
ne-4-oxide, an equivalent amount of 
(a) 
3-(p-tolyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3-e]-as-tri 
azine-4-oxide, or 
(b) 
3-(p-anisyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3-e]-as-tr 
iazine-4-oxide 
there is obtained 
(a) 
3-(4-methyl-3-nitrophenyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyran 
o[4,3-e]-as-triazine-4-oxide, or 
(b) 
3-(4-methoxy-3-nitrophenyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyra 
no[4,3-e]-as-triazine-4-oxide, respectively. 
The 
3-(m-nitrophenyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3-e]- 
as-triazine-4-oxide of this example is a particularly effective sleep 
inducer when orally administered to an animal in need of said treatment at 
a dosage of 200 mg. just before bedtime. 
EXAMPLE 5 
(-)-3-(m-nitrophenyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3- 
e]-as-triazine 
(a) Preparation of 
(+)-3-(m-nitrophenyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3 
-e]-as-triazine-4-oxide 
To a flask equipped with a reflux condenser, there is added 10.2 g. (0.048 
mole) of 3-nitro-benzenecarboximidic acid ethyl ester hydrochloride, 11.7 
g. (0.048 mole) of 
(+)-1,3,3-trimethyl-2-oxabicyclo[2,2,2]octan-5,6-dione-5-oxime-6-hydrazone 
, 3.6 g. (0.024 mole) of potassium carbonate and 300 ml. of toluene. The 
resulting mixture is refluxed for 5 hours, then cooled to room 
temperature. The excess solvent is then removed at reduced pressure on a 
rotary evaporator. Methylene chloride is then added to dissolve the 
product and the resulting solution is then filtered. The filtrate is then 
evaporated and the residue recrystallized from absolute ethanol to yield 
(+)-3-(m-nitrophenyl)-5,8-dihydro-6,6,8-ethano-6H-pyrano[4,3-e]-as-triazin 
e-4-oxide; m.p. 217.5.degree. C. to 218.5.degree. C.; ORD+7.8.degree.. 
(b) 
(-)-3-(m-nitrophenyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3 
-e]-as-triazine 
To a flask equipped with stirrer, reflux condenser and gas inlet there is 
added under nitrogen a mixture of 6.9 g. (0.020 mole) of 
(+)-3-(m-nitrophenyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3 
-e]-as-triazine-4-oxide, 20 ml. (0.23 mole) of phosphorous trichloride in 
300 ml. of 1,2-dichloroethane. The resulting mixture is refluxed for 6.5 
hours and then cooled to room temperature, and poured into a beaker 
containing 500 g. of ice. To this mixture there is added cautiously 60 ml. 
of 50% aqueous sodium hydroxide while maintaining stirring for 1 hour. The 
resulting mixture is then transferred to a separatory funnel and permitted 
to separate. The layers are partitioned and the aqueous phase extracted 
twice with 300 ml. of methylene chloride and the extracts combined with 
the organic phase. The resulting solution is washed once with brine, dried 
over anhydrous magnesium sulfate, and then concentrated to yield a residue 
which is then recrystallized from absolute ethanol to give 
(-)-3-(m-nitrophenyl)-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano[4,3 
-e]-as-triazine; m.p. 184.degree. to 185.degree. C.; ORD-1.8.degree..