Synthesis of acetyl-T-alkanes

Acetyl-tertiary-alkanes are prepared by hydrolytic decarboxylation of tertiary-alkanoylacetonitriles with hydrochloric acid.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
This invention belongs to the field of synthetic organic chemistry and 
provides a process for preparing acetyl-tertiary-alkanes. The compounds 
are particularly useful as intermediates for preparing a group of 
3-alkylpyridazin-6-ylbenzamides which have recently been identified as 
valuable herbicides. The acetyl-t-alkanes have been difficult to prepare, 
because of the bulk of the tertiary alkyl group attached to the carbonyl, 
and the present invention provides a convenient synthesis of these 
intermediates. 
2. State of the Art 
Various processes have been used in the art to make acetylalkanes. Corey 
and Durst, J. Am. Chem. Soc. 90, 5548-52 (1968) made acetylcyclohexane and 
pinacolone by reacting the appropriate ethyl ester with lithium 
N-(p-tolyl)lithiomethanesulfinamide. House and Larson, J. Org. Chem. 33, 
61-65 (1968), made acetylheptadecane by reacting the corresponding methyl 
ester with dimethylsulfone and sodium hydride to obtain the 
methylsulfonylacetyl intermediate, and reducing off the methylsulfonyl 
with aluminum amalgam. Phenylacetone, a related compound, was prepared by 
Oishi et al., Chem. Pharm. Bull. 17, 2314-18 (1969), by reacting ethyl 
phenylacetate with 1-ethoxy-N,N-dimethylvinylamine, deaminating the 
product on silica gel, and hydrolyzing in hot dilute acid. 
SUMMARY OF THE INVENTION 
The present invention provides a process for preparing an acetyl-t-alkane 
of the formula 
##STR1## 
wherein R is of the formula 
##STR2## 
R.sup.1 is C.sub.1.sbsb.3 -C.sub.4 alkyl; 
R.sup.2 and R.sup.3 are independently C.sub.1 -C.sub.13 alkyl, or 
halo-C.sub.1 -C.sub.13 alkyl; 
n is 0-4; 
R.sup.4 and R.sup.5 are independently hydrogen, halo or C.sub.1 -C.sub.4 
alkyl; comprising hydrolytically decarboxylating a t-alkanoylacetonitrile 
of the formula 
##STR3## 
with hydrochloric acid. 
DESCRIPTION OF THE PREFERRED EMBODIMENTS 
In this document, all temperatures are described in degrees Celsius. 
The general chemical names above are used in their ordinary meanings in 
organic chemistry. Thus, the term C.sub.1 -C.sub.4 alkyl includes such 
groups as methyl, ethyl, propyl, isopropyl, butyl, s-butyl and t-butyl. 
C.sub.1 -C.sub.13 alkyl includes the groups just mentioned, as well as 
such larger groups as pentyl, heptyl, undecyl, dodecyl, tridecyl, 
neopentyl, 1-methylbutyl, 2ethylbutyl, 3-methylbutyl, 4-methylhexyl, 
2,2-diethylpentyl, 3-propylhexyl, 1,3-diethylpentyl, 2-methyloctyl, 
3-propyloctyl, 4-ethylheptyl, 2-butylheptyl, 3-methyldecyl, 
1-ethylundecyl, 2,4-diethylnonyl, 1-pentylhexyl, 5-propyldecyl and the 
like. 
The halo-C.sub.1 -C.sub.13 alkyl groups of the compounds prepared by this 
invention include C.sub.1 -C.sub.13 alkyl groups as described above 
substituted with chlorine, bromine and fluorine atoms in any desired 
manner, from a single halogen atom on the alkyl group up to and including 
full halogen substitution. Exemplary haloalkyl groups are further 
illustrated below. 
Similarly, the halogen atoms which may constitute the R.sup.4 and R.sup.5 
substituents of the compounds may be chlorine, bromine or fluorine atoms. 
It will be seen that the tertiary alkyl groups of the compounds may be 
simple groups where the adjacent carbon atom is substituted with 3 alkyl 
(or haloalkyl) groups, or two of the groups may combine to form a 
cycloalkyl group, which may optionally be substituted. The cycloalkyl 
groups may be of from 3 to 7 carbons, as defined by the integer n in the 
formula above. 
Certain categories of the acetyl-t-alkanes constitute preferred products of 
this invention. The definitions below define the preferred classes of 
products; it will be understood that various of the definitions may be 
combined as desired to define further, more limited preferred classes. 
A. Compounds of formula I; 
B. Compounds of formula I wherein R.sup.2 is C.sub.1 -C.sub.4 alkyl or 
halo-C.sub.1 -C.sub.4 alkyl; 
C. Compounds of formula I wherein R.sup.3 is C.sub.1 -C.sub.4 alkyl or 
halo-C.sub.1 -C.sub.4 alkyl; 
D. Compounds of formula I wherein R.sup.2 is C.sub.1 -C.sub.4 alkyl; 
E. Compounds of formula I wherein R.sup.3 is C.sub.1 -C.sub.4 alkyl; 
F. Compounds of formula I wherein R.sup.1 is unbranched; 
G. Compounds of formula I wherein R.sup.2 is unbranched; 
H. Compounds of formula I wherein R.sup.3 is unbranched; 
I. Compounds of formula II; 
J. Compounds of formula II wherein n is 2-4; 
K. Compounds of formula II wherein n is 3; 
L. Compounds of formula II wherein R.sup.4 and R.sup.5 are the same; 
M. Compounds of formula II wherein R.sup.4 and R.sup.5 are hydrogen; 
N. Compounds of formula II wherein R.sup.1 is unbranched. 
The products of the process of this invention are further explained by the 
following group of specific products prepared thereby. 
1-acetyl-6,6,6-trifluoro-1-methyl-1-propylhexane 
1-acetyl-2-(2,2-dibromoethyl)-1-ethyl-1-methylbutane 
1-acetyl-2-fluoro-1-isobutyl-1-isopropyl-3-methylpentane 
1-acetyl-1-butyl-3-chloro-1-ethylhexane 
1-acetyl-1-s-butyl-3-fluoro-1-pentylheptane 
1acetyl-1-(3,3-dichloro-1-ethylbutyl)-1-ethyl-3-methylhexane 
1-acetyl-4,5,5-trichloro-2-ethyl-1-(1-ethylpropyl)-1-methylpentane 
1-acetyl-1-ethyl-3,3,4-trifluoro-1-hexyloctane 
1-acetyl-1-(2-ethylbutyl)-1-isopropyl-4-trifluoromethylheptane 
1-acetyl-3-bromo-1-butyl-3-ethyl-1-(1-ethylbutyl)hexane 
1-acetyl-9-bromo-1-heptyl-1-methylnonane 
1-acetyl-3,3-difluoro-1,5-dimethyl-1-(5-methylhexyl)heptane 
1-acetyl-6-chloro-1-(2-ethylpentyl)-1-ethyl-2-propylhexane 
1-acetyl-6-bromo-1-isopropyl-1-(1-propylbutyl)decane 
1-acetyl-1-t-butyl-10,10,10-trifluoro-1-octyldecane 
1-acetyl-5-chloro-1-methyl-2-proply-1-(1-propylpentyl)heptane 
1-acetyl-2-butyl-2,3-dichloro-1-(4-ethylhexyl)-1-isopropylhexane 
1-acetyl-5,5,6,6-tetrabromo-1-s-butyl-1-(3-methylnonyl)undecane 
1-acetyl-1-[4(3-chloropropyl)heptyl]-1-isopropyldecane 
1-acetyl-1-(2-butylpentyl)-1-propyl-6-trifluoromethyldecane 
1-acetyl-12,12,12-trichloro-1-isopropyl-1-(3-propylhexyl)dodecane 
1-acetyl-1-[2-(5,5-dibromopentyl)hexyl]-1-propylundecane 
1-acetyl-1-(2-butylhexyl)-7-(2-fluoroethyl)-1-methyldecane 
1-acetyl-2-butyl-7,7-dichloro-1-(2,4-diethylhexyl)-1-methyloctane 
1-acetyl-2,2-dichloro-1-(1,5-dimethylhexyl)-1-methyltridecane 
1-acetyl-1-[4-(3,3,4,4,4-pentafluorobutyl)-octyl]-1-methyldodecane 
1-acetyl-8,8,8-trifluoro-1-methyl-2-pentyl-1-(1-pentylhexyl)octane 
1-acetyl-14-bromo-1-methyl-1-(2,6-dimethylnonyl)tetradecane 
1-acetyl-1-(1,4-dibromo-2,5-diethylnonyl)-1-ethyltridecane 
1-acetyl-2-bromo-5-chloro-2-pentyl-1-propyl-1-(2-pentylheptyl)nonane 
1-acetyl-1,2,4,8-tetramethyl-1-propyldecane 
1-acetyl-1,1-dimethyltetradecane 
1-acetyl-2-butyl-1-isobutyl-1-methyldecane 
1-acetyl-1,1-diethyl-5-pentylundecane 
1-acetyl-11-methyl-1-pentyl-1-propyldodecane 
1-acetyl-1-chloromethyl-1-ethyl-3-methylpentane 
1-acetyl-1-isobutyl-1-(2-fluoroethyl)-2-ethylbutane 
1-acetyl-1-(2,2-dibromopropyl)-1-methylheptane 
1-acetyl-1-(4-bromobutyl)-1-t-butyl-3-ethylpentane 
1acetyl-1-(1-chloromethylpropyl)-1-ethyl-2-propylbutane 
1acetyl-1-pentachloroethyl-1-isopropyloctane 
1-acetyl-1-(2,2,3-tribromobutyl)-1-ethyl-6-methylheptane 
1-acetyl-1-(5-fluoropentyl)-3-ethyl-1-methylhexane 
1-acetyl-1-(2,2-dichloropentyl)-1-methyl-2-propylpentane 
1-acetyl-1-(2,2-dibromopropyl)-6,6,6-trifluoro-1-methylhexane 
1-acetyl-1-[1-(2,2-dibromoethyl)propyl]-5-bromo-1-ethylpentane 
1-acetyl-1-[1-(chloromethyl)propyl]-2-fluoro-1-isopropyl-3-methylpentane 
1-acetyl-1-pentachloroethyl-3-chloro-1-propylhexane 
1-acetyl-1-(3,4,4-tribromobutyl)-1-s-butyl-3-fluoroheptane 
1-acetyl-1-(3,3-dichloro-2-ethylbutyl)-6-fluoro-1-methylhexane 
1-acetyl-2,2-dibromo-1-[1-(1,1,2-trichloropropyl)propyl]-1-ethylhexane 
1-acetyl-3,3,4-trifluoro-1-methyl-1-octyloctane 
1-acetyl-1-methyl-1-(2-propylpentyl)-4-trifluoromethylheptane 
1-acetyl-3-bromo-2-ethyl-1-(3-ethylhexyl)-1-methylhexane 
1-acetyl-8-bromo-1-methyl-1-(3-methylnonyl)-nonane 
1-acetyl-1-(1,1-difluoro-4-methylhexyl)-1-methyldecane 
1-acetyl-3-butyl-1-(5-chloro-2-propylpentyl)-1-methylhexane 
1-acetyl-6-bromo-1-methyl-1-(3-propylhexyl)-decane 
1-acetyl-1-decyl-10,10,10-trifluoro-1-methyldecane 
1-acetyl-3-butyl-1-(4-chloro-3-propylhexyl)-1-ethylheptane 
1-acetyl-1-(1-butyl-1,4-dichloropentyl)-1,3,5-triethylheptane 
1-acetyl-9,9,10,10-tetrabromo-1-(1,3-dimethylhexyl)-1-methylundecane 
1-acetyl-1-[3-(2-chloropropyl)heptyl]-1-methyldodecane 
1-acetyl-6-trifluoromethyl-1-methyl-1-(1-pentylhexyl)decane 
1-acetyl-3,3,4-trichloro-1-methyl-1-(2,6-dimethylnonyl)dodecane 
1-acetyl-1-[2-(5-bromopentyl)hexyl]-1-ethyltridecane 
1-acetyl-1-ethyl-7-(2-fluoroethyl)-1-(2-pentylheptyl)decane 
1-acetyl-1-(1-butyl-4,5-dichloroheptyl)-1-isopropyl-2,3,4-trimethyldecane 
1-acetyl-1-(12,12-dichlorododecyl)-1-methyltetradecane 
1-acetyl-3-butyl-1-[2-(1,1,2,2-tetrafluorobutyl)octyl]-1-methyldecane 
1-acetyl-5-pentyl-1-(2,2,3-trifluoro-1-pentylheptyl)-1-propylundecane 
1-acetyl-12-bromo-1-(6-methylundecyl)-1-methyltetradecane 
1-acetyl-2,6-dibromo-1-chrlormethyl-4,8-diethyl-1-methyldecane 
1-acetyl-2-bromo-4-chloro-1-(1-fluoroethyl)-1-methyl-2-pentylnonane 
1-acetyl-1,2-dimethylcyclopropane 
1-acetyl-3-t-butyl-1-ethyl-2-fluorocyclobutane 
1-acetyl-2-chloro-4-ethyl-1-propylcyclopentane 
1-acetyl-2-bromo-4-butyl-1-isopropylcyclohexane 
1-acetyl-1-butyl-3-methyl-4-isopropylcycloheptane 
1-acetyl-1-t-butyl-3-s-butyl-2-ethylcyclopentane 
1-acetyl-1-s-butyl-2-isopropyl-3-propylcyclohexane 
1-acetyl-1,4-diisobutyl-3-propylcycloheptane 
1-acetyl-2-isobutyl-1-methylcyclobutane 
1-acetyl-2-bromo-4-s-butyl-1-ethylcyclopentane 
1-acetyl-4-butyl-3-chloro-1-ethylcyclohexane 
1-acetyl-3-t-butyl-5-fluoro-1-methylcycloheptane 
The alkanoylacetonitriles which are the starting compounds for the process 
of this invention are obtained readily by reacting acetonitrile in the 
presence of sodium hydride with the methyl carboxylate of the acid which 
provides the desired alkanoyl group. For example, if the R group is to be 
t-butyl (R.sub.1, R.sub.2 and R.sub.3 are all methyl) the ultimate 
starting compound is methyl pivalate. The reaction of the methyl ester 
with acetonitrile is a standard literature method for the preparation of 
alkanoylacetonitriles such as the starting compounds used in this process. 
The synthesis of the acetonitriles is preferably carried out by first 
suspending sodium hydride in a suitable amount of tetrahydrofuran at 
ambient temperature, and adding the methyl carboxylate and acetonitrile to 
the suspension. The mixture is warmed slowly to obtain a gentle reflux, 
and stirred at that temperature for several hours or overnight. The 
reaction is an efficient one and produces good yields of the starting 
compounds. Synthesis of the alkanoylacetonitriles is further explained in 
the preparations below. 
The process of this invention is carried out under mild conditions, and 
quite unexpectedly produces the desired tertiary acetylalkanes without the 
undesired rearrangement of the tertiary alkyl groups which would be 
expected to occur. The rearrangement, properly described as a 
Wagner-Meerwein rearrangement, is understood to occur in similar reactions 
in the field of branched alkane chemistry and to be a major problem. See, 
for example, Banthorpe and Whittaker, Quart. Revs. 20, 373 (1966); Dutler 
et al., Helv. Chim. Acta. 38, 1268 (1955); and Brownlie et al., J. Chem. 
Soc. 2419 (1956). 
The reagent for the synthesis of this invention is hydrochloric acid. 
Concentrations in the range of from about 6-normal up to the maximum 
obtainable concentration (which is about 12-normal) are particularly 
useful. It is most preferred to use commercial concentrated hydrochloric 
acid containing about 36-38% by weight of HCl. 
When concentrated hydrochloric acid is used, the process of this invention 
occurs efficiently at temperatures in the range of about 
80.degree.-110.degree., in about 2 hours. The most preferred condition for 
the process is about the reflux temperature of the reaction mixture, 
especially when using commercial concentrated hydrochloric acid. 
It will be understood that the necessary reaction time will increase 
markedly when lower temperatures are used, and also when lower 
concentrations of hydrochloric acid are used. The necessary reaction times 
are easily identified for each combination of conditions. The optimum time 
in a given case, of course, is found by a balance between the maximum 
throughput, obtained by short reaction times, and the maximum yield, 
obtained by long reaction times. 
The products of the present invention are used as intermediates in the 
synthesis of a series of N-pyridazinylbenzamides which are taught in U.S. 
patent application Ser. No. 302,323, of Burow. The herbicides are of the 
formula 
##STR4## 
wherein Z is oxygen or sulfur; 
R.sup.6 is hydrogen, halogen, C.sub.1 -C.sub.4 alkyl, or C.sub.1 -C.sub.4 
alkoxy; 
R.sup.7 hydrogen, halogen, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, 
C.sub.1 -C.sub.4 alkylthio or trifluoromethyl; 
R.sup.8 is hydrogen, halogen, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 
alkoxy or C.sub.1 -C.sub.4 alkylthio; provided that when one of R.sup.6, 
R.sup.7 or R.sup.8 is alkyl, one or both of the other phenyl substituents 
is other than hydrogen; and when R.sup.7 is trifluoromethyl, one or both 
of R.sup.6 and R.sup.8 is other than hydrogen. 
The products of the process of this invention are transformed to the 
herbicidal benzamides in a simple step-wise process. In the first step, 
the acetylalkane is reacted with chloral (trichloroacetaldehyde) or its 
hydrate to obtain a 3-alkanoyl-2-hydroxy compound of the formula 
##STR5## 
The above intermediate is hydrolyzed with base, preferably in aqueous 
ethanol, to obtain the corresponding unsaturated acid of the formula 
##STR6## 
In some preparations the above unsaturated acid is obtained as a mixture 
with the corresponding keto-hydroxy acid 
##STR7## 
The above acid represents merely incomplete dehydration. The presence of a 
mixture of this type is not a disadvantage, because the keto-hydroxy acid 
reacts in the following step just as does the unsaturated acid. 
The corresponding pyridazinone is prepared in a process step which is the 
subject of an application for patent, entitled Synthesis of 
6-t-alkyl-3-Pyridazinones, of Riaz F. Abdulla, filed on the same day with 
this application. The acid is first irradiated with strong light to 
convert the acid to the corresponding cyclic form, 
##STR8## 
which intermediate is reacted with hydrazine in the presence of ethanol 
and hydrochloric acid to form the pyridazinone of the formula 
##STR9## 
Finally, the pyridazinone is reacted with a chlorinating agent such as 
phosphorus oxychloride to replace the oxo atom with chlorine, is aminated 
with ammonia under pressure to prepare the 4-aminopyridazine, and is 
finally reacted with the appropriate benzoyl (or thiobenzoyl) compound to 
form the herbicidal benzamide. 
Synthesis of the benzamides is further explained in the preparations below. 
The benzamide herbicides are used in agriculture as herbicides have often 
been used in the past. Many of them are so active that application rates 
in the range of from about 0.1 to about 2 kg. per hectare are adequate. In 
general, they are used at rates from about 0.05 to about 15 kg. per 
hectare. When the compounds are used for post-emergence control of weeds, 
higher application rates, such as from about 1 to about 20 kg. per 
hectare, are preferred. 
It is not necessary to incorporate the herbicides in the soil. The 
compounds are more potent when incorporated than when applied on the 
surface of the soil, however, and incorporation is therefore preferred. 
The compounds are effective when applied either before or after the 
emergence of weeds; the pre-emergence use of them is more effective and is 
accordingly preferred. The compounds are effective against a wide range of 
undesirable vegetation, including most of the herbaceous weeds and grasses 
which afflict agriculture. Accordingly, the herbicidal benzamides are 
widely usable. 
The benzamides are particularly and notably safe to cereal crops, such as 
corn, rice and especially wheat, and their use as herbicides in cropland 
in which such crops are grown is particularly preferred. They may also 
safely be used, however, in many other crops, such as soybeans, peanuts, 
cotton, peas and related crops. The compounds are also useful for the 
control of unwanted vegetation in non-cropland, such as in fallow wheat 
land and the like. It is often convenient to apply herbicides in 
combination with other herbicides or with crop protection chemicals such 
as fungicides, insecticides and the like. The benzamides may conveniently 
be applied in the form of such combinations when it is desired to do so.

The first preparation below illustrates the synthesis of the 
alkanoylacetonitriles which are the starting compounds for the process of 
the present invention. 
Preparation 1 
(2-ethyl-2-methylbutyryl)acetonitrile 
To a suspension of 96 g. of sodium hydride, as a 50% dispersion in mineral 
oil, in 300 ml. of dry tetrahydrofuran was added, with stirring, 63 g. of 
acetonitrile and 114 g. of methyl 2-ethyl-2-methylbutyrate. The mixture 
was then heated gently to 60.degree.-65.degree. and allowed to reflux 
gently at that temperature overnight. It was then cooled to ice bath 
temperature, and 2 ml. portions of ethanol were added to decompose the 
remaining hydride. When the mixture did not foam on further ethanol 
addition, the mixture was evaporated under vacuum to dryness, and the 
residue was dumped into 4 liters of water. The aqueous mixture was 
extracted with hexane to remove the mineral oil, and it was then made acid 
to pH 2 and was extracted with two 1 liter portions of diethyl ether. The 
ether was dried over magnesium sulfate and evaporated under vacuum to 
obtain 122 g. of the desired acetonitrile. 
The examples below illustrate the process of this invention. 
EXAMPLE 1 
1-acetyl-1-ethyl-1-methylpropane 
To the 122 g. of alkanoylacetonitrile obtained in Preparation 1 was added 1 
liter of 12 N hydrochloric acid. The mixture was heated to reflux, and was 
stirred under reflux for 2 hours. It was then cooled and extracted with 1 
liter of pentane. The organic layer was dried over magnesium sulfate and 
evaporated under vacuum at 35.degree. to obtain 93 g. of crude product. 
EXAMPLE 2 
1-acetyl-1-ethylcyclohexane 
To 180 g. of (1-ethylcyclohexylcarbonyl)-acetonitrile was added 1 liter of 
12 N hydrochloric acid, and the mixture was stirred under reflux for 2.5 
hours and was cooled. The mixture was then extracted with one 1000 ml. and 
one 500 ml. portion of pentane, and the organic layers were combined, 
dried over magnesium sulfate and concentrated under vacuum at a 
temperature near 30.degree.. The desired product was found to co-distill, 
in part, with the solvent, and so the vacuum and temperature were 
carefully watched to avoid excessive loss of the product, which was 
identified by its molecular ion in mass spectroscopic analysis, 154. Its 
boiling point was 44.degree.-45.degree. at 0.4 torr. 
The following series of preparations illustrates the manner in which the 
acetylalkanes prepared by the process of this invention are converted to 
the herbicidal pyridazinylbenzamides. 
Preparation 2 
1,1,1-trichloro-5-ethyl-2-hydroxy-5-methyl-4-oxoheptane 
A 30 g. portion of the product of Example 1, 
1-acetyl-1-ethyl-1-methylpropane, was combined with 38.4 g. of chloral and 
36 ml. of acetic acid, and was stirred under reflux, under nitrogen, for 4 
days. The solvent was then carefully removed under vacuum to obtain 39 g. 
of the crude product as an amber, viscous oil. 
Preparation 3 
5-ethyl-5-methyl-4-oxo-2-heptenoic acid 
The product of the preparation immediately above was dissolved in 400 ml. 
of ethanol and brought to a boil. To it was quickly added 40 g. of 
potassium hydroxide in 360 ml. of water, and the temperature was held at 
72.degree. for 2 minutes. The mixture was then poured immediately into 1 
liter of ice-water, and 50 g. of sodium chloride was added. The aqueous 
mixture was extracted with 1000 ml. of diethyl ether, and the aqueous 
layer was made acid to pH 1 with concentrated hydrochloric acid. It was 
then extracted 4 times with 500 ml. portions of dichloromethane, and the 
organic layers were combined, dried over magnesium sulfate and evaporated 
under vacuum to obtain 20 g. of the desired acid, as a mixture with 
5-ethyl-2-hydroxy-5-methyl-4-oxoheptanoic acid, the presence of which was 
indicated by nuclear magnetic resonance signals, .delta.4.35 (q, 1H); 
2.6-3.8 (m, 2H). 
Preparation 4 
6-(1-ethyl-1 -methylpropyl)pyridazine-3-one 
The 20 grams of product mixture obtained in Preparation 3 above was added 
to 200 ml. of ethanol, and 3.6 g. of hydrazine was added. The mixture was 
stirred under reflux for 3 days, while being irradiated with light from a 
300-watt sunlamp. The mixture was in a Pyrex flask, and the lamp was 
placed 5 cm. from the flask wall. The light emitted by the lamp was 
primarily of wave length 200-800 m.mu.. The mixture was then evaporated to 
an oil under vacuum, and the oil was chromatographed on a 500 g. silica 
gel column, eluting with 1:1 ethyl acetate:dichloromethane. The 
product-containing fractions were combined and evaporated under vacuum to 
obtain a solid residue, which was crystallized from hexane to obtain 4.3 
g. of the desired product, m.p. 97.degree.-99.degree.. 
Preparation 5 
3-chloro-6-(1-ethyl-1-methylpropyl)pyridazine 
To 34 g. of 6-(1-ethyl-1-methylpropyl)pyridazin-3-one was added 175 ml. of 
phosphorus oxychloride, and the mixture was stirred under reflux for 30 
minutes. It was then cooled, excess phosphorus oxychloride was removed 
under vacuum, and the residual oil was poured into ice water. The residue 
was made basic to pH 9 with ammonia, and triturated. The aqueous mixture 
so prepared was extracted with two one-liter portions of diethyl ether, 
and the combined organics were dried and evaporated under vacuum to obtain 
35 g. of the desired product, identified by mass spectroscopy, which 
showed a molecular ion having a weight of 198. 
Preparation 6 
3-amino-6-(1-ethyl-1-methylpropyl)pyridazine 
To the product obtained from the preparation immediately above was added 
1000 ml. of liquid ammonia in a pressure vessel, and the mixture was 
heated at 200.degree. for 50 hours. The mixture was cooled and the 
volatiles were allowed to evaporate, and the residue was dissolved in 500 
ml. of denatured ethanol. The insoluble matter was removed and the solvent 
was evaporated under vacuum. The residue was purified by chromatography on 
a 700 g. silica gel column, using ethyl acetate as the eluting solvent. 
The product-containing fractions were combined and evaporated to obtain an 
oil which crystallized on standing. The yield was 24 g. of the desired 
product, m.p. 56.degree.-58.degree. after recrystallization from hexane. 
Preparation 7 
N-[6-(1-ethyl-1-methylpropyl)pyridazin-3-yl]-2,6-dimethoxybenzamide 
A mixture of 21 g. of the product of the preparation immediately above and 
23.5 g. of 2,6-dimethoxybenzoyl chloride was dissolved in 500 ml. of 
benzene, and the mixture was stirred under reflux overnight. The solvent 
was removed under vacuum, and to the residue was added a solution of 20 g. 
of potassium hydroxide in 500 ml. of ethanol. The mixture was stirred 
under reflux for 3 hours, cooled and evaporated under vacuum. To the 
residue was added 500 ml. of saturated sodium chloride solution, and the 
aqueous mixture was extracted 3 times with 500 ml. portions of diethyl 
ether. The organic layers were combined and dried over magnesium sulfate, 
and the solution was evaporated under vacuum. The crude product was then 
dissolved in 1000 ml. of diethyl ether and washed with 0.1 N hydrochloric 
acid. The organic layer was dried and evaporated under vacuum. The oil was 
treated with 300 ml. of water containing 5 g. of hydroxylamine 
hydrochloride and 1 liter of diethyl ether, and the 2-phase mixture was 
stirred for 1 hour. The organic layer was then separated and washed with 2 
N sodium hydroxide, dried and evaporated under vacuum to obtain 23 g. of 
crude product, which was then dissolved in 500 ml. of ethanol containing 
40 g. of potassium hydroxide. That mixture was stirred under reflux for 14 
hours, cooled and evaporated under vacuum. A 1.5 liter portion of water 
was added, and the resulting suspension was filtered. The solids were 
dissolved in ethyl acetate, treated with charcoal and filtered. The 
filtrate was evaporated under vacuum to obtain a solid which was 
crystallized from benzene/hexane to obtain the desired product, m.p. 
145.degree.-147.degree..