Disclosed are certain 3-phenylpyridazines, compositions thereof which are herbicidal and methods of using such compositions for controlling undesired plants. Intermediates useful in preparing the 3-phenylpyridazines are disclosed.

FIELD OF THE INVENTION 
The present invention relates to novel compounds useful for controlling 
undesired plants and for retarding plant growth. More particularly, the 
present invention relates to certain 3-phenylpyridazines useful for 
controlling undesired plants and for retarding plant growth. 
PRIOR ART 
In U.S. Pat. No. 4,623,376, certain substituted 3-phenylpyridazines have 
been disclosed as being useful as herbicides. 
In Auer et al, "The Chemistry and Properties of New and Herbicidal 
Derivatives of 3-Phenylpyridazine", Environ. Qual. Saf. Suppl., (1975), pp 
680-685, certain substituted 3-phenylpyridazines have been disclosed as 
being useful as herbicides. 
There is a continuing need in the art for herbicides which provide a broad 
spectrum of control of weeds and which may be better tolerated by crops. 
The present invention produces such kind of improved and useful 
herbicides. 
SUMMARY OF THE INVENTION 
The novel compounds of the present invention may be depicted by the 
following structural formula (W): 
##STR1## 
wherein: A and E are each hydrogen; 
B and D are each independently hydrogen, C.sub.1 -C.sub.3 haloalkyl, 
C.sub.1 -C.sub.3 haloalkyl, nitro, amino, halo, C.sub.1 -C.sub.7 
alkylsilyl, C.sub.1 -C.sub.7 alkyl, C.sub.1 -C.sub.7 haloalkoxy, phenyl 
C.sub.1 -C.sub.7 alkylsilyl, or halo C.sub.1 -C.sub.7 alkylthio; 
C is hydrogen, nitro or amino; 
F is hydrogen, halo, C.sub.1 -C.sub.7 alkoxy, hydroxy, C.sub.1 -C.sub.7 
alkyl, C.sub.1 -C.sub.7 alkynyl, C.sub.1 -C.sub.7 alkenyl, C.sub.1 
-C.sub.7 alkylthio, C.sub.1 -C.sub.7 alkylamino, C.sub.1 -C.sub.7 
alkylsulfonyl, or C.sub.1 -C.sub.7 alkylsulfinyl; 
G is hydrogen, hydroxycarbonyl, hydroxycarbonylamino, amino, halo, C.sub.1 
-C.sub.7 alkyl, cyanothio, thio, formylamino, C.sub.1 -C.sub.7 alkylamino, 
C.sub.1 -C.sub.7 alkoxy, C.sub.1 -C.sub.7 alkylamino, C.sub.1 -C.sub.7 
alkylthio, C.sub.1 -C.sub.7 alkynloxy, C.sub.1 -C.sub.7 alkenyloxy, 
hydroxy, hydroxycarbonyl C.sub.1 -C.sub.7 alkoxy, halo C.sub.1 -C.sub.7 
alkylthio, C.sub.1 -C.sub.7 alkoxy C.sub.1 -C.sub.7 alkoxy, C.sub.1 
-C.sub.7 alkoxy C.sub.1 -C.sub.7 alkoxy C.sub.1 -C.sub.7 alkoxy, 
aminocarbonyl, C.sub.1 -C.sub.7 alkylthio C.sub.1 -C.sub.7 alkoxy, C.sub.1 
-C.sub.7 alkylaminooxy, C.sub.1 -C.sub.7 alkylcarbonylamino, halo C.sub.1 
-C.sub.7 alkoxy, aminocarbonyl, C.sub.1 -C.sub.7 alkylsulfinyl, C.sub.1 
-C.sub.7 alkylsulfonyl, C.sub.1 -C.sub.7 alkoxycarbonylamino, C.sub.1 
-C.sub.7 alkylaminocarbonylamino, C.sub.1 -C.sub.7 alkylthio, cyano, 
C.sub.1 -C.sub.7 alkoxy, or C.sub.1 -C.sub.7 alkylaminocarbonylamino; and 
H is hydrogen, halo, C.sub.1 -C.sub.7 alkoxy C.sub.1 -C.sub.7 alkylthio, 
C.sub.1 -C.sub.7 alkyl, C.sub.1 -C.sub.7 alkynyl, C.sub.1 -C.sub.7 
alkenyl, C.sub.1 -C.sub.7 alkylamino, hydroxy, C.sub.1 -C.sub.7 
alkylsulfinyl, C.sub.1 -C.sub.7 alkylsulfonyl, or cyano; 
Either nitrogen of the pyridazine ring may be substituted with an oxide. G 
and H together may form a 5-member hetero oxygen ring. Herbicidal salts 
and esters of the compounds are also included. 
The present invention provides novel compounds of the general Formula W 
depicted above which exhibit desirable herbicidal properties and further 
provides herbicidal compositions for the selective controlling of weeds in 
crop plants. The compositions comprise one or more compounds of Formula W 
herein by themselves or admixed with one or more carriers, such as solid 
and/or liquid inert extenders or diluents and/or wetting agents and 
optionally other active herbicides, insecticides, growth regulators, plant 
nutrients and like additaments. The invention also provides an effective 
method of controlling undesirable plants, such as grasses, perennial and 
annual broad-leafed weeds and so on which comprises applying to the locus 
of the plants to be controlled on herbicidally effective amount of at 
least one 3-phenylpyridazine compound. 
These novel 3-phenylpyridazine compounds which may be employed as an active 
ingredient in this invention can be prepared by a variety of processes 
such as one of the general procedures as will be described below. 
The present invention also provides new and useful processes for making 
3-phenylpyridazine compounds and intermediates thereof. 
DETAILED DESCRIPTION OF THE INVENTION 
It has been shown that the phenyl substituted pyridazine compounds within 
the above depicted general Formula W are not only herbicidal but also have 
good herbicidal tolerance by certain crop plants, especially corn. The 
preferred compounds herein provide a broader spectrum of weed control and 
show good perennial broad-leaf activity. The field soil half-life of the 
preferred compounds provide longer residual control than alachlor but is 
normally short enough that any carryover problems are environmentally 
acceptable. 
In this specification and claims, numerical values are not critical unless 
otherwise stated. That is, the numerical values may be read as if prefaced 
with the word "about" or "substantially". 
The following defines the various terms used in the application. 
The term "C.sub.1 -C.sub.7 alkyl" or in the shortened cognate form "C.sub.1 
-C.sub.7 alk" as used herein include the straight and branched aliphatic 
groups of one to ten carbon atoms, such as methyl, ethyl, propyl, 
isopropyl (1-methyl-ethyl), butyl, isobutyl (2-methylpropyl), sec-butyl, 
(1-methylpropyl), tert-butyl, (1,1-dimethylethyl), pentyl, isopentyl, 
(3-methylbutyl), sec-pentyl (1-methylbutyl), 1,1-dimethylpropyl, 
1-2-dimethylpropyl, neopentyl, (2,2-dimethylpropyl), hexyl, isohexyl 
(4-methylpentyl), sec-hexyl, (1-methylpentyl), 2-methylpentyl, 
3-methylpentyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 
1,2-dimethylbutyl, 1,3-dimethylbutyl, 1,2,2-trimethylpropyl, 
1,1,2-trimethylpropyl, and the like. The terms, such as "C.sub.1 -C.sub.3 
" and "C.sub.1 -C.sub.5 " are included in the term C.sub.1 -C.sub.10 but 
with a corresponding lesser number of carbon atoms as indicated. 
The term "C.sub.1 -C.sub.3 haloalkyl" as used herein includes such radicals 
as trifluoromethyl, trichloromethyl, difluoromethyl, chlorodifluoromethyl, 
fluoromethyl, bromomethyl, .alpha.,.alpha.-difluoromethyl, 
pentafluoroethyl, heptafluoro-n-propyl, pentachloroethyl, iodomethyl, 
etc., where the number of carbon atoms in the alkyl is 1-3, inclusive. 
The tern "halogen" either alone or in compound words such as "haloalkyl" 
denotes fluorine, chlorine, bromine or iodine. 
The term "alkoxy" denotes methoxy, ethoxy, n-propyloxy, isopropyloxy and 
the different butoxy, pentoxy, hexyloxy isomers, etc. 
The term "alkenyl" denotes straight or branched alkenes, e.g., vinyl, 
1-propenyl, 2-propenyl, 3-propenyl and the different butenyl, pentenyl, 
hexenyl isomers, etc. 
The term "alkynyl" denotes straight chain or branched alkynes, e.g., 
ethynyl, 1-propynyl, 3-propynyl, etc., including the different butynyl, 
pentynyl and hexynyl isomers. 
The term "alkylthio" denotes methylthio, ethylthio and the various 
propylthio, butylthio, pentylthio and hexylthio isomers. 
Alkylsulfinyl, alkylsulfonyl, alkylamine, etc., are defined analogously to 
above terms as will be understood by those skilled in the art. 
Processes for preparing the compounds of the present invention are 
disclosed in the schematic diagrams and written descriptions which follow 
below. 
The compounds which can be prepared by the new and useful process of the 
present invention include those of the following general formula (W'): 
##STR2## 
In broad aspect, the preferred overall process for preparing the compounds 
of Formula W' is best viewed in the separate process steps required to 
prepare the necessary intermediates, immediate precursors and end products 
of the above formula. The products of. "Processes I, III and IV", provide 
the intermediates necessary for "Processes II and V". The compounds 
according to Formula W' are prepared by either a single process "I, II, or 
V" or any suitable combination of "Processes I-V". It is expressly 
understood that various modifications obvious to those skilled in the art 
are contemplated. Specific embodiments of the preparation of the compounds 
herein are described in Examples 1-19 below. 
In the sequence of process steps described below, the various symbols 
defining radical substituents and the number of such substituents, e.g., 
X, Y, Z, m, n, R.sub.1 -R.sub.7, etc., have the same meaning as defined 
for the compounds of Formula W and compounds related thereto, unless 
otherwise qualified or limited. The symbol m is zero or an integer of 1-5, 
inclusive, and n is zero or an integer of 1-3, inclusive. X is selected 
from substituents A, B, C, D and E as above defined and Y is selected from 
substituents F, G and H as above defined. 
Process I 
This process describes the preparation of compounds of Formula E of the 
following schematic which in many cases are equivalent to compounds of 
Formula W'. Process I also describes the preparation of important 
intermediate compounds of Formula E, which are useful for the preparation 
of compounds of Formula W'. X is a substituent including A-E radicals as 
above defined; Y is a substituent including F-H radicals as above defined. 
The subscript m is zero or an integer of 1-4; subscript n is zero or an 
integer of 1-3. 
The first step of Process I involves the conversion of acetophenones of 
Formula A, which are either known in the art, commercially available, or 
whose preparation is described herein, to hydrazones of Formula B. The 
reaction is carried out by admixing the aCetophenone with ethyl carbazate 
in the presence of a catalytic amount of an acid chosen from 
.rho.-toluenesulfonic acid, sulfuric acid, methanesulfonic acid or the 
like in any anhydrous solvent or mixture of solvents with the preferred 
solvents being chosen from benzene, toluene, ether, tetrahydrofuran, or 
methylene chloride. This is followed by removal of the water that is 
generated with a drying agent, such as sodium sulfate, magnesium sulfate, 
or molecular sieves or by refluxing the mixture over a "Dean-Stark" trap. 
The reaction temperature may range from 0.degree. C. to 150.degree. C., 
preferably 25.degree. C. to 120.degree. C. The reaction time may vary from 
a few minutes to several weeks depending on the selected reagents, the 
amounts of the reagents, reaction temperature, etc. The compounds of 
Formula B are isolated by removal of the reaction solvent followed by 
recrystallization from an appropriate inert organic solvent. 
##STR3## 
The second step in Process I involves the conversion of hydrazones of 
Formula B to dichlorohydrazones of Formula C by treatment with a suitable 
chlorinating agent, preferably chosen from N-chlorosuccinimide, sulfuryl 
chloride, oxalyl chloride, thionyl chloride, 
1,3-dichloro-5,5-dimethylhydantoin, chlorine gas, or trichlorotriazinone. 
The reaction can be carried out in any nonreactive solvent or mixture of 
solvents, preferably carbon tetrachloride, chloroform, methylene chloride, 
or dichloroethane. The reaction temperature may range from -78.degree. C. 
to 150.degree. C., preferably -20.degree. C. to 100.degree. C. The 
reaction period may be chosen from a few minutes to several weeks 
depending on the amounts of reagents, reaction temperature, etc. The 
resulting reaction mixture containing the compounds of Formula C are 
filtered and then concentrated and may be used as is or recrystallized 
from an appropriate solvent. 
The third step in Process I involves the conversion of compounds of Formula 
C to compounds of Formula D by treatment of compounds of Formula C with a 
hindered amine base, preferably chosen from triethylamine, 
diisopropylethylamine, tributylamine, DBU or DBN and an electron rich 
enamine or enol ether (electron rich olefins). The electron rich olefins 
depicted in Scheme I are either known in the art or are prepared as 
described herein from an appropriate ketone, aidehyde, or acetylene and 
may have ZR.sub.3 equal to morpholine, methoxy, or ethoxy and R.sub.1 
and/or R.sub.2 equal to hydrogen, lower alkyl or haloalkyl, methoxy, or 
carboxylate. The reaction may be carried out in any anhydrous solvent or 
mixtures of solvents, which includes preferablymethylene chloride, 
tetrahydrofuran, chloroform, carbontetrachloride, dichloroethane, or 
benzene. The reaction temperature may range from -78.degree. C. to 
150.degree. C., preferably -20.degree. C. to 100.degree. C. The reaction 
period may be chosen from a few minutes to several weeks depending on the 
selected reagents, the amounts of the reagents, reaction temperature, etc. 
The resulting reaction mixture containing the compounds of Formula D is 
then diluted with water and extracted several times with an appropriate 
organic solvent. The organic solvent is then dried, filtered and 
evaporated in vacuo. The resulting compounds of Formula D are then 
purified by standard methods, such as crystallization or chromatography 
and are usually isolated as a mixture of one or more diastereomers. 
The fourth step in Process I involves the conversion of compounds of 
Formula D to compounds of Formula E by treatment with a base preferably 
chosen from NaOH, KOH, t-BuOK, NaOMe, NaOEt, or LDA or by heating the 
compounds of Formula D at an elevated temperature in a appropriate 
solvent. The reaction may be performed in any appropriate solvent, 
preferably chosen from methanol, ethanol, THF, DMSO or DMF. The reaction 
temperature may range from -78.degree. C. to 150.degree. C., preferably 
-20.degree. C. to 100.degree. C. The reaction period may be chosen from a 
few minutes to several weeks depending on the selected reagent, the 
amounts of the reagents, reaction temperature, etc. The reaction mixture 
containing the compounds of Formula E is then diluted with water, made 
acidic, and then extracted with an appropriate organic solvent. The 
organic solvent is then dried, filtered and evaporated in vacuo. The 
resulting compounds of Formula E are then used as is or are purified by 
standard methods, such as crystallization or chromatography. 
Process II 
This process describes the preparation of compounds of Formulas G-L 
inclusive, which are depicted below and are included in the compounds of 
Formula W'. 
The first step in Process II involves the conversion of compounds of 
Formula F-G inclusive where R.sub.4 is OH or NH.sub.2. When R.sub.4 is OH 
the compounds of Formula F are treated with diphenylphosphorylazide, an 
organic base most preferably chosen from triethylamine, DBU or 
N,N-diisopropylethylamine. The reaction may be carried out in any suitable 
alcoholic solvent, such as methanol, ethanol, t-butanol or i-propanol. The 
reaction temperature may range from 25.degree. C. to 100.degree. C., 
preferably 75.degree. C. to 80.degree. C. 
##STR4## 
The reaction time may range from a few minutes to several weeks depending 
on the selected reagents, the reaction temperature, amounts of the 
reagents, etc. The intermediate carbamate that is formed is converted to 
compounds of Formula G by removal of the above mentioned alcoholic solvent 
in vacuo followed by stirring the mixture in an aqueous acid chosen from 
hydrochloric acid, sulfuric acid, nitric acid, or acetic acid. The 
reaction temperature may range from 25.degree. C. to 100.degree. C., 
preferably 50.degree. C. to 100.degree. C. The reaction time may range 
from a few minutes to several weeks depending on the selected reagents, 
the reaction time, amount of the reagents, etc. The compounds of Formula G 
are isolated by neutralizing the aqueous acid solution with a base 
followed by extraction with an appropriate organic solvent. The organic 
solvent is removed in vacuo and the compounds of Formula G are purified by 
standard methods, such as recrystallization or chromatography. 
In the first step of Process II when R.sub.4 is NH.sub.2, the compounds of 
Formula F are treated with an aqueous sodium hypochlorite solution in the 
presence of a base such as potassium carbonate, sodium hydroxide, or 
potassium hydroxide. The reaction temperature may range from 25.degree. C. 
to 100.degree. C. The reaction time may vary from a few minutes to several 
weeks depending on the selected reagents, the amounts of the reagents, 
reaction temperature, etc. The compounds of Formula G are isolated by 
extraction of the aqueous solution with an appropriate organic solvent 
followed by evaporation in vacuo. The compounds of Formula G may be 
purified by standard methods, such as recrystallization or chromatography. 
The second step of Process II involves the conversion of compounds of 
Formula G-H, inclusive, by treatment of G with an alkylnitrite and a 
halogenating reagent such as CuX.sub.2, CuX or X.sub.2. In these cases 
X=Cl, Br or I. The reaction may be carried out in any anhydrous organic 
solvent or mixture of solvents, preferably THF, chloroform, methylene 
chloride, acetonitrile or dimethoxyethane. The reaction temperature may 
range from -20.degree. C. to 100.degree. C., preferably 40.degree. C. to 
75.degree. C. The reaction time may range from a few minutes to several 
weeks depending on the selected reagents, the reaction temperature, 
amounts of reagents, etc. The compounds of Formula H are isolated by 
pouring the reaction mixture into dilute aqueous acid followed by 
extraction with an organic solvent which is dried, filtered and evaporated 
in vacuo. The compounds of Formula H may be purified by standard methods, 
such as crystallization or chromatography. 
The third step in Process II involves the conversion of compounds of 
Formulas H and I by treatment of H with an alkyl alcohol, thiol or amine 
and a base, preferably chosen from KOH, NaOH, NaH, K.sub.2 CO.sub.3, LDA 
or t-BuOK. The reaction may be carried out in any anhydrous solvent or 
mixture of solvents, preferably the neat alkyl alcohol, thiol, amine, THF, 
DMF, DMSO, or di-methoxyethane. The reaction temperature may vary from 
-78.degree. C. to 150.degree. C., preferably -20.degree. C. to 100.degree. 
C. The reaction time may vary from several minutes to several weeks 
depending on the amounts of the reagents, reaction temperatures, etc. The 
compounds of Formula I are isolated by pouring the mixture into water and 
extracting with an organic solvent. The compounds of Formula I are 
purified after removal of the organic solvent in vacuo by standard 
methods, such as recrystallization or chromatography. 
The fourth step in Process II involves the conversion of compounds of 
Formula G-J, inclusive, where X is in the 5- and the 6-positions of the 
pyridazine of Formula J or X is in the 4- and the 5-positions of the 
pyridazine of Formula J. 
To prepare compounds of Formula J where X is in the 5- and the 6-positions 
of the pyridazine, compounds of Formula G are first converted to compounds 
of Formula H as described above. The compounds of Formula H are then 
treated with a peracid, preferably chosen from m-chloroperbenzoic acid, 
peracetic acid, trifluoroperacetic acid or hydrogen peroxide to give an 
intermediate 1-pyridazine N-oxide. The reaction solvent may be chosen from 
any inert organic solvent, preferably chloroform, benzene or methylene 
chloride. The reaction temperature may vary from -20.degree. C. to 
100.degree. C., preferably 25.degree. C. to 80.degree. C. The reaction 
time may vary from a few minutes to several weeks depending on the 
reaction temperature, amounts of the reagents, etc. The N-oxide may be 
isolated by pouring the reaction mixture into water and extracting with an 
appropriate organic solvent. After the solvent is removed in vacuo the 
product may be purified by standard methods, such as recrystallization or 
chromatography. The N-oxide is then treated with a halogenation reagent, 
preferably chosen from POX.sub.3, SOX.sub.2, SO.sub.2 X.sub.2, PX.sub.5, 
PX.sub.3 or (CO).sub.2 X.sub.2. The reaction is done neat with the 
halogenation reagent as a solvent or preferably in a solvent chosen from 
benzene, chloroform, methylene chloride or carbon tetrachloride. The 
reaction temperature may vary from -20.degree. C. to 100.degree. C., 
preferably 25.degree. C. to 80.degree. C. The reaction time may vary from 
a few minutes to several weeks depending on the reaction temperature, 
amounts of the reagents, etc. The compounds of Formula J where X is in the 
5- and the 6-positions of the pyridazine are isolated by removal of the 
solvent in vacuo followed by purification by standard methods, such as 
recrystallization or chromatography. 
To prepare compounds of Formula J where X is in the 4- and the 5-positions 
of the pyridazine, compounds of Formula G are treated with a halogenation 
reagent chosen from N-halosuccinimide, X.sub.2, 
1,3-dihalo-4,4-dimethylhydantoin, SO.sub.2 X.sub.2 or (CO).sub.2 X.sub.2. 
The reaction may be performed in any nonreactive organic solvent or 
mixtures of solvents, preferably acetonitrile, chloroform, methylene 
chloride or benzene. The reaction temperature may vary from -20.degree. C. 
to 100.degree. C., preferably 25.degree. C. to 80.degree. C. The reaction 
time may vary from a few minutes to several weeks depending on the 
reaction temperature, amounts of the reagents, etc. The intermediate 
4-halo-5-aminopyridazine may be isolated by removal of volatiles in vacuo 
followed by purification by standard methods, such as recrystallization or 
chromatography. The intermediate 4-halo-5-aminopyridazine is then 
converted to compounds of Formula J where X is in the 4- and the 
5-positions of the pyridazine by the same procedure described above for 
the preparation of compounds of Formula H. 
The fifth step in Process II involves the conversion of compounds of 
Formulas J to K or L by treatment of compounds of Formula J with either 
one or two equivalents of an alkyl alcohol, thiol or amine and a base. In 
these sequences R.sub.5 and R.sub.6 may be the same or different depending 
on the nucleophile utilized for the reaction. The procedure for the 
conversion of J to either K or L is identical to that utilized for 
preparation of compounds of Formula I. 
The sixth step in Process II involves the conversion of compounds of 
Formula K to compounds of Formula L by treatment of compounds of Formula K 
with a tetraalkyl tin reagent, preferably chosen from tetramethyltin or 
vinyltributyltin and a palladium catalyst, such as 
bis(triphenylphosphine)palladium(II) chloride or 
trans-benzyl(chloro)bis(triphenylphosphine)palladium(II). The reaction may 
be performed in any suitable anhydrous inert organic solvent or mixture of 
solvents, preferably DMF, DMSO, dimethoxyethane, benzene or toluene. The 
reaction temperature may vary from 0.degree. C. to 150.degree. C., 
preferably 25.degree. C. to 100.degree. C. The reaction time may vary from 
a few minutes to several weeks depending on the reaction temperature, 
amounts of the reagents, etc. The compounds of Formula L are isolated by 
pouring the reaction mixture into water followed by extraction with a 
suitable organic solvent. The solvent is then dried and evaporated in 
vacuo to give the compounds of Formula L which may be purified by standard 
methods, such as recrystallization or chromatography. 
Process III 
This process involves the preparation of important intermediate compounds 
of Formula R which are useful in the overall process scheme for producing 
compounds of Formula W. 
The first step in the process for the preparation of compounds of Formula R 
proceeds from 3,4-dichloro-3-hydroxypyridazine M, which is commercially 
available and known in the art. Treatment of compounds of Formula M with 
an appropriate protecting group chosen preferably from chloromethylmethyl 
ether, chloromethylthiomethyl ether, dihydropyran or 2-methoxyethoxymethyl 
chloride and an organic or inorganic acid, such as p-toluenesulfonic acid 
or sulfuric acid or a base chosen from triethylamine or 
N,N-diisopyropylethylamine gives a compound of Formula N. In compounds of 
Formula N, R.sub.7 is derived from one of the protecting groups mentioned 
above. The reaction can be carried out in any anhydrous solvent or mixture 
of solvents with the preferred solvents being chosen from ether, 
tetrahydrofuran, benzene, toluene or methylene chloride. The reaction 
temperatures may range from -78.degree. C. to 150.degree. C., preferably 
0.degree. C. to 100.degree. C. The reaction period may be chosen from a 
few minutes to several weeks depending on the selected reatents, the 
amounts of reagents, reaction temperature, etc. After the reaction is 
complete, the mixture containing the compounds of Formula N are diluted 
with an appropriate organic solvent and extracted with an aqueous base 
such as sodium bicarbonate. The compounds of Formula N are isolated by 
drying the organic solvent, filtration and then removal of the solvent in 
vacuo. The compounds of Formula N are utilized as is or if necessary the 
product is purified by standard methods, such as crystallization or column 
chromatography. 
The second step in Process III involves the conversion of compounds of 
Formula N-O, inclusive, by treatment of N with an alkyl alcohol, thiol, or 
amine and an appropriate base, such as sodium hydroxide, potassium 
hydroxide, sodium hydride, potassium hydride, sodium bicarbonate, 
potassium carbonate, triethyl amine, N,N-diisopyropylethylamine or DBU to 
give compounds of Formula O. 
##STR5## 
In compounds of Formula O, R.sub.5 is derived from the alkyl alcohol, thiol 
or amine mentioned above and in many cases would be equivalent to Y.sub.n 
of Formula W'. The reaction can be carried out neat with the above 
mentioned alcohol, thiol or amine as solvent or in any suitable anhydrous 
solvent or mixture of solvents with the preferred solvents being chosen 
from ether, tetrahydrofuran, benzene, N,N-dimethylformamide or 
dimethylsulfoxide. The reaction temperatures may range from -78.degree. C. 
to 150.degree. C., preferably -20.degree. C. to 100.degree. C. The 
reaction period may be chosen from a few minutes to several weeks 
depending on the amounts of reagents, reaction temperature, etc. The 
mixture containing the compounds of Formula O are then diluted with an 
organic solvent and extracted several times with water. The compounds of 
Formula O are isolated by removal of the organic solvent in-vacuo and may 
be used as is or if necessary may be purified by standard methods, such as 
crystallization or column chromatography. 
The third step in Process III involves the conversion of compounds of 
Formula O to compounds of Formula P by treatment of compounds of Formula O 
with hydrogen, an appropriate transition metal catalyst, such as Pd-C, 
Pt-C, or PtO.sub.2, and an appropriate base such as triethyl amine, 
N,N-diisopyropylethylamine, or DBU to give compounds of Formula P. The 
reaction can be carried out in any anhydrous solvent or mixture of 
solvents with the preferred solvents being chosen from methanol, ethanol, 
benzene, or ethyl acetate, preferably methanol or ethanol. The reaction 
temperatures may range from -78.degree. to 150.degree. C., preferably 
0.degree. C. to 40.degree. C. The reaction period may be chosen from a few 
minutes to several weeks depending on the selected reagents, the amounts 
of reagents, reaction temperature, etc. The compounds of Formula P are 
isolated by filtration and removal of the solvent in vacuo. The compounds 
of Formula P are used as is or may be purified by standard methods, such 
as crystallization or column chromatography. 
The fourth step in Process III involves the conversion of compounds of 
Formula P to compounds of Formula Q by treatment of P with an aqueous 
acid, such as hydrochloric acid, phosphoric acid, sulfuric acid, or nitric 
acid to give compounds of Formula Q. The reaction is carried out in the 
aqueous acid as solvent in the presence of a co-solvent, such as methanol, 
ethanol or tetrahydrofuran with the reaction temperatures ranging from 
0.degree. C. to 100.degree. C., preferably 25.degree. C. to 100.degree. C. 
The reaction period may be chosen from a few minutes to several weeks 
depending on the selected reagents, the amounts of reagents, reaction 
temperature, etc. The compounds of Formula Q are isolated by making the 
reaction mixture basic with sodium hydroxide, extracting with a 
chlorinated solvent, such as methylene chloride, chloroform, or carbon 
tetrachloride to remove contaminants, then acidifying with concentrated 
acid to precipitate the product. The products of Formula Q are then 
collected by filtration and dried and may be used as is or if necessary 
purified by standard methods, such as crystallization or column 
chromatography. 
The fifth step in Process III involves the conversion of compounds of 
Formula Q to compounds of Formula R by treatment of compounds of Formula Q 
with a chlorinating agent, such as thionyl chloride, oxalyl chloride, 
sulfuryl chloride or phosphorous oxychloride to give compounds of Formula 
R. The reaction is carried out neat in the chlorinating agent as solvent 
or with the chlorinating agent and a co-solvent, such as methylene 
chloride, chloroform or carbon tetrachloride. The reaction temperature may 
range from 0.degree. C. to 100.degree. C., preferably 25.degree. C. to 
100.degree. C. The reaction period may be chosen from a few minutes to 
several weeks depending on the selected reagents, the amounts of reagents, 
reaction temperature, etc. The compounds of Formula R are isolated by 
removal of the solvents in vacuo to give the products which can be used as 
is or purified by standard methods, such as crystallization or column 
chromatography. 
Process IV 
This process describes the preparation of important intermediate compounds 
of Formula T which are useful in the overall process scheme for producing 
compounds of Formula W. 
##STR6## 
The first step of Process IV involves the conversion of 
3,5-dichloropyridazine S, which is known in the art (W. Deinhammer et al., 
German Patent No. 2,706,701), to compounds of Formula T by treatment with 
one equivalent of an alkyl alcohol, thiol, or amine and an appropriate 
base such as sodium hydroxide, potassium hydroxide, sodium hydride, 
potassium hydride, sodium bicarbonate, potassium carbonate, triethyl 
amine, N,N-diisopropylethylamine or DBU. In compounds of Formula T, 
R.sub.5 is derived from the alkyl alcohol, thiol, or amine mentioned above 
and in many cases can be equivalent to Yn of Formula W. The reaction can 
be carried out neat with the above mentioned alcohol, thiol, or amine as 
solvent or in any anhydrous solvent or mixture of solvents with the 
preferred solvents being chosen from ether, tetrahydrofuran, benzene, 
N,N-di-methylformamide, or dimethylsulfoxide. The reaction temperatures 
may range from -78.degree. C. to 150.degree. C., preferably -20.degree. C. 
to 100.degree. C. The reaction period may be chosen from a few minutes to 
several weeks depending on the selected reagents, the amounts of reagents, 
reaction temperature, etc. The mixture containing the compounds of Formula 
T are then diluted with an organic solvent and extracted several times 
with water. The compounds of Formula T are isolated by removal of the 
organic solvent in vacuo and may be used as is or if necessary may be 
purified by standard methods, such as crystallization or column 
chromatography. 
Process V 
This process describes the preparation of compounds of Formula W from 
compounds of Formulas U and V. 
##STR7## 
compounds of Formula U which are either known in the art, commercially 
available, or prepared as described herein are treated with magnesium 
metal or a palladium(0) catalyst followed by a tin reagent in an 
appropriate solvent, preferably chosen from ether, THF, toluene, or 
dimethoxyethane to generate a "Grignard Reagent" or an "organotin 
reagent". To this is added a transition metal catalyst, preferably chosen 
from bis(triphenylphosphine)nickel(II) chloride, 
1,2-bis(diphenylphosphinoethane)nickel(II) chloride, or 
tetrakis(triphenylphosphine)palladium(0) and compounds of Formula V. The 
mixture is allowed to react at a temperature from -20.degree. C. to 
100.degree. C., preferably 0.degree. C. to 80.degree. C. The reaction 
period may be chosen from a few minutes to several weeks depending on the 
amounts of reagents, reaction temperature, etc. The mixture containing the 
compounds of Formula W are then poured into water and extracted with an 
appropriate organic solvent. After drying, the solvent is removed in vacuo 
to give the compounds of Formula W which can be purified by standard 
methods, such as recrystallization or chromatography. 
The acid addition salts useful in the present composition can be prepared 
by admixing a suitable compound of Formula W with a suitable acid to form 
the corresponding acid addition salt. Examples of those acids which may be 
employed include inorganic acids, such as hydrochloric acid, sulfuric 
acid, nitric acid, phosphoric acid and an organic acid, such as 
trichloroacetic acid. It is to be noted that certain compounds of Formula 
W may not be converted conveniently to a corresponding suitable acid 
addition salt. 
Preparation of some of the intermediates of the compounds of this invention 
and the compounds of this invention are illustrated by the following 
examples. In the examples which follow, all percentages are given on a 
weight basis unless otherwise indicated.