JPH0128755B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention provides novel 2-(2-imidazoline-2-
The present invention relates to pyridine and quinoline compounds, methods of preparing the pyridine and quinoline compounds, and methods of using them to control undesirable annual and perennial plant species. More particularly, the present invention relates to the structural formula [wherein R ₁ is C ₁ -C ₄ alkyl; R ₂ is C ₁ -C ₄ alkyl or C ₃ -C ₆ cycloalkyl, and when R ₁ and R ₂ are taken together they are A can also represent _C3 - _C6 cycloalkyl optionally substituted by methyl; A is _COOR3 , _CONHR6 , CHO, _CH2OH ,
COCH ₃ , COC ₆ H ₅ , CN, CH ₃ , CH=NOH,
CH ₂ COOH, CONHOH, CH ₂ CH ₂ COOH,
_CHR8OH ,

[Formula] or

[Formula], _R3 is hydrogen, di-lower alkylimino, optionally the following groups: _C1 - _C3 alkoxy, halogen, hydroxyl, _C3 - _C6 cycloalkyl, benzyloxy, furyl, phenyl, halophenyl, May be substituted with one of the following: lower alkyl phenyl, lower alkoxyphenyl, nitrophenyl, carboxyl, lower alkoxycarbonyl, cyano or tri-lower alkylammonium
_C1 - _C12 alkyl; optionally substituted with one of the following groups: _C1 - _C3 alkoxy, phenyl, halogen or lower alkoxycarbonyl or with two _C1 - _C3 alkoxy groups or two halogen groups C ₃
~ _C12 alkenyl; _C3 - _C6 cycloalkyl optionally substituted with one or two _C1 - _C3 alkyl groups; optionally one or two _C1 - _C3 alkyl groups _C3 - _C10 alkynyl optionally substituted with; or alkali metal, alkaline earth metal, manganese,
a cation selected from the group consisting of copper, iron, zinc, cobalt, lead, silver, nickel, ammonium and organic ammonium; R ₆ is hydrogen, hydroxyl, C ₃ -alkenyl,
C ₃ -alkynyl or optionally substituted with one hydroxyl or one chlorine group
_C1 - _C4 alkyl; B is _COR4 or _SO2R5 , provided that when _B is _COR4 or _{SO2R5 ,} A is _COOR3
(where R ₃ is H or other than a salt-forming cation), CH ₃ or CN, W is O, and Y and Z are not alkylamino, hydroxyl or hydroxy-lower alkyl; R ₄ is _C1 - _C11 alkyl, chloromethyl or phenyl optionally substituted with one chloro, one nitro or one methoxy group; _R5 is _C1 - _C4 alkyl or optionally is phenyl optionally substituted with one methyl group; W is O or S; _R8 is _C1 - _C4 alkyl or phenyl; X is hydrogen, halogen, hydroxyl or methyl; However, as a condition, when Y and Z are taken together to form a ring and YZ is represented by the structural formula -( _CH2 )n- (where n is 3 or 4), X is hydrogen. ; Y and Z are hydrogen, halogen, C ₁ ~
C ₆ alkyl, hydroxy-lower alkyl, C ₁ ~
_C6 alkoxy, _C1 - _C4 alkylthio, phenoxy, _C1 - _C4 -haloalkyl, nitro, cyano,
_C1 - _C4 alkylamino, di-lower alkylamino or _C1 - _C4 alkylsulfonyl group, or optionally substituted with one _C1 - _C4 alkyl, _C1 - _C4 alkoxy or halogen represents a member selected from the group consisting of phenyl, and Y and Z can form a ring and YZ has the structure -( _CH2 )n-, where is an integer) or

[Formula], where L, M, Q and R ₇ are hydrogen, halogen, C ₁ -C ₄ alkyl, C ₁ -
_C4 alkoxy, _C1 - _C4 -alkylthio, _C1 - _C4
Alkylsulfonyl, _C1 - _C4 haloalkyl,
_NO2 , CN, phenyl, phenoxy, amino, _C1
~ _C4 alkylamino, di-lower alkylamino,
chlorophenyl, methylphenyl or 1 Cl,
represents a member selected from the group consisting of phenoxy substituted with CF ₃ , NO ₂ or CH ₃ groups, provided that only one of L, M, Q or R ₇ is hydrogen, halogen, C ₁ ~ _C4 alkyl or _C1 ~
can represent substituents other than C ₄ -alkoxy, and with the proviso that R ₃ cannot be unsaturated alkyl when W is O and A is CB, CH ₃ or COOR ₃ ;
and Y and Z cannot be alkylamino, dialkylamino or alkylthio] and their N-oxides, R ₁ and R ₂ are not the same Sometimes it concerns its optical isomers and its acid addition salts except when R ₃ is a salt-forming cation. A preferred group of 2-(2-imidazolin-2-yl)pyridine compounds is where R ₁ is methyl, R ₂ is methyl, ethyl, isopropyl or cyclopropyl, W is oxygen and B is hydrogen. , CO−
alkyl C ₁ -C ₆ or CO-phenyl optionally substituted with chloro, nitro or methoxy, and A is COOR ₃ , CH ₂ OH or CHO, where R ₃ is defined in the above formula. like)
, X is hydrogen, Y and Z are each
selected from the group consisting of hydrogen, _C1 - _C6 alkyl, _C1 - _C6 alkoxy, halo, phenyl, nitro, cyano, trifluoromethyl or methylsulfonyl, and when Y and Z are taken together, YZ is -( It has the above formula such that _CH2 ) ₄ . These 2-(2-imidazolin-2-yl)
A further preferred group of pyridines is the formula (a) [Wherein, B is hydrogen, CO-alkyl C ₁ to C ₆ or CO
- phenyl, A is COOR ₃ (where R ₃ is as described in formula () above), X is hydrogen, and Y and Z are each hydrogen, C ₁ - _C6 alkyl, _C1 - _C4 -alkoxy,
halo, C ₁ -C ₄ -represents haloalkyl or phenyl, and when taken together YZ is -
(CH ₂ ) ₄ -] The most preferred 2-(2-imidazolin-2-yl)pyridine compounds of formula (a) are those in which B, X, Y and Z are each hydrogen and A is _COOR3 ;
And R ₃ is as described in the above formula (). The 2-(2-imidazolin-2-yl)quinoline compound is represented by the following formula (): [In the formula, R ₁ , R ₂ , W, B, A, X, L, M, Q
and R ₇ are as defined for formula () above]. Suitable herbicides are 2-(2-imidazolin-2-yl)quinoline compounds of formula () in which R ₁ is methyl, R ₂ is methyl, ethyl, isopropyl or cyclopropyl, and W is oxygen. Yes, B is hydrogen, CO-alkyl C ₁ to C ₆ , optionally 1
CO-phenyl optionally substituted with chloro, nitro or methoxy; A is
COOR ₃ , CH ₂ OH or CHO, and R ₃ is of the formula ()
X is hydrogen, and L, M, Q and R ₇ are each hydrogen,
halogen, methoxy, nitro, alkyl C1 _{- C4} ,
CF ₃ , CN, N(CH ₃ ) ₂ , NH ₂ , SCH ₃ or
selected from the group consisting of SO ₂ CH ₃ , provided that only one of L, M, Q or R ₇ is nitro,
CF ₃ , CN, N(CH ₃ ) ₂ , NH ₂ , SCH ₃ or
_It 's like it could be _SO2CH3 . 2-(2-imidazolin-2-yl) of formula ()
A further preferred group of quinoline compounds are X, L and
R ₇ is each hydrogen, R ₁ is methyl,
_R2 is methyl, ethyl, isopropyl or cyclopropyl, B is hydrogen or _COCH3 ,
A is COO ₃ , CH ₂ OH or CHO, where R ₃
is as defined in formula (), W is oxygen, and M and Q are hydrogen, halogen, methyl, methoxy, nitro, CF ₃ , CN,
Represents a member selected from N(CH ₃ ) ₂ , NH ₂ , SCH ₃ or SO ₂ CH ₃ with the proviso that only one of M or Q is a substituent other than hydrogen, halogen, methyl or methoxy. It's like being able to do something. 2-(2-imidazolin-2-yl) of formula ()
An even more preferred group of quinolines is R ₁ is methyl, R ₂ is isopropyl, W is oxygen, B, X, L, M, Q and R ₇ are hydrogen;
A is _COOR3 , where _R3 is _C1 - _C8 alkyl, hydrogen, _C3 - _C8 alkenyl, _C3 - _C8 alkynyl, _C3 - _C6 cycloalkyl or an alkali metal;
A cation selected from alkaline earth metals, manganese, copper, iron, zinc, cobalt, lead, silver, nickel, ammonium and aliphatic ammonium. In formulas, a and above, alkali metals include sodium, potassium and lithium, with sodium generally preferred. moreover,
The term "organic ammonium" is defined as a group consisting of positively charged nitrogen atoms bonded to 1 to 4 aliphatic groups, each having 1 to 20 carbon atoms. Representative organic ammonium groups for the preparation of aliphatic ammonium salts of imidazolinyl nicotinic acids and esters of formula () are monoalkylammonium, dialkylammonium, trialkylammonium, tetraalkylammonium, monoalkenylammonium, dialkylammonium, Trialkenyl ammonium, monoalkynylammonium, dialkynylammonium, trialkynylammonium, monoalkanol ammonium, dialkanol ammonium, trialkanol ammonium,
_C5 - _C6 -cycloalkylammonium, piperidinium, morpholinium, pyrrolidinium, benzylammonium, and the like. Examples of the above halogens are chlorine, fluorine, bromine and iodine, with chlorine and bromine being preferred. As mentioned above, the present invention relates to 2-(2-imidazolin-2-yl)pyridine and 2-(2-imidazolin-2-yl)quinoline compounds and their use as herbicides. These new pyridine and quinoline compounds are represented by the general formula () for both groups of compounds. Formula () is more specific and indicates 2-(2-imidazolin-2-yl)quinoline. Although many of the process steps described below are common for the production of both the pyridine and quinoline derivatives of the present invention,
For simplicity, process steps specific to the production of quinoline derivatives are discussed separately following the discussion of the production of pyridine derivatives. According to the process of the invention, formula () where A is COOR ₃ and R ₃ represents hydrogen or a substituent other than a salt-forming cation and R ₁ , R ₂ , X, Y and Z are as above The 2-(2-imidazolin-2-yl)pyridine ester of 2-(2-imidazolin-2-yl)pyridine ester is prepared by preparing an imidazopyrrolopyridinedione represented by the following formula () with a suitable alcohol and the corresponding alkali metal alkoxide at a temperature between about 20°C and about 50°C. It can be produced by reacting at a temperature within a range. In these reactions, alcohols can act as both reactants and solvents. In this case, no co-solvent is necessary. However, when expensive alcohols are used in the reaction, e.g. dioxane,
Relatively inexpensive co-solvents such as tetrahydrofuran or other aprotic solvents can also be added to the reaction mixture. The amount of aprotic solvent added to the reaction mixture can vary widely. The overall reaction can be described by the equation as follows: [wherein M ₁ is an alkali metal, and X,
Y, Z, R ₁ , R ₂ and R ₃ are as defined above]. Advantageously, the 2-(2-imidazolin-2-yl)pyridine ester of formula (b) has R ₁ , R ₂ ,
From a dioxopyrrolopyridine acetamide of formula () in which X, Y and Z are as above, in the presence of an inert organic solvent such as xylene or toluene, a strong base such as 1,5-diazabicyclo[5.4.0] It can be prepared by cyclizing it with undec-5-ene (DBU) to give the crude imidazopyrrolopyridine of formula (). The reaction mixture is heated to a temperature between 100°C and 150°C, and water is removed from the reaction mixture during the reaction using conventional means such as a Dean Stark water separator. Then at least one equivalent of R ₃ OH of formula ()
An alcohol represented by: [wherein R ₃ is a member other than hydrogen or a salt-forming cation, and R ₁ , R ₂ , X, Y and Z are as described above] is added to the reaction mixture, and thus The mixture prepared above is heated to reflux to a temperature between 100°C and 150°C to give the 2-(2-imidazolin-2-yl)pyridine ester of formula (b). The overall reaction can be described by the equation as follows: [In the formula, X, Y, Z, R ₁ , R ₂ and R ₃ are as described above]. In another embodiment for the preparation of the 2-(2-imidazolin-2-yl)pyridine ester of formula (b), the carbamoyl nicotinate ester of formula () is heated with phosphorus pentachloride at an elevated temperature, generally Cyclization occurs at between about 60°C and 100°C. The reaction is preferably carried out in the presence of an inert organic solvent, such as toluene or benzene.
The desired hydrochloride of the ester of formula (b) is obtained in good yield. By then dissolving the acid addition salt in water and neutralizing the solution produced with a base, such as sodium or potassium carbonate,
The hydrochloride salt is easily converted to the ester of formula (b). The overall reaction is explained as follows: [wherein A is COOR ₃ and R ₃ is hydrogen or a substituent other than a salt-forming cation, and
R ₁ , R ₂ , X, Y and Z are as described above]. In another embodiment for the preparation of 2-(2-imidazolin-2-yl)pyridine esters of formula (b) of the invention, represented by formula () using a mixture of phosphorus pentachloride and phosphorus oxychloride, Cyclization of the carbamoyl nicotinate ester takes place. The reaction mixture is stirred at room temperature for about 4-8 hours, then the POCl ₃ is removed in vacuo. The remaining residue is dispersed in an organic solvent such as toluene. The solvent is removed and the residue is dispersed in water and heated between 80°C and 100°C. After cooling, the pH of the aqueous mixture is adjusted to 5-6 using sodium bicarbonate and the product is extracted in methylene chloride to obtain the desired 2-(2
-imidazolin-2-yl)pyridine ester. The reaction is represented by the formula: [wherein A is COOR ₃ and R ₃ is hydrogen or a substituent other than a salt-forming cation, and R ₁ ,
R ₂ , X, Y and Z are as above]. A is COOR ₃ and R ₃ is alkyl C ₁ ~
_C12 , alkenyl _C3 - _C12 , alkynyl _C3 - _C10 ,
cycloalkyl C ₃ to _{C 6} or substituted derivatives of these groups, and X, Y, Z, R ₁ and
R ₂ is obtained by reacting a 2-(2-imidazolin-2-yl)pyridine ester of formula (b) as described above with ammonia at a temperature between about 25 and 125° C. under excess pressure. It can be converted to the corresponding amide which is CONH ₂ . This reaction can be carried out in a protic solvent such as a lower alkanol or an aprotic solvent such as tetrahydrofuran, dioxane, etc. Similarly, using similar conditions replacing ammonia with hydroxylamine in the above reaction gives hydrooxamic acid. These reactions can be explained by the following equations: The above-mentioned primary amide thus prepared is treated with titanium tetrachloride and triethylamine, preferably in the presence of an inert aprotic solvent, such as tetrahydrofuran, to give the corresponding nitrile. The reaction is generally carried out under an atmosphere of an inert gas, such as nitrogen, at a temperature between about 0°C and 10°C. The reaction can be explained as follows: [In the formula, X, Y, Z, R ₁ and R ₂ are as described above]. B is _{COR4 or SO2R5} , A is _CH3 , CN or _COOR3 , W is O, _R1 , _R2 , _R3 ,
X, Y and Z are as above, provided that Y and Z
cannot be alkylamino, hydroxy or hydroxy lower alkyl.
-yl)pyridine with excess acyl halide, acyl anhydride or sulfonyl halide, either alone or in a solvent such as pyridine or toluene, at elevated temperatures between about 50°C and 125°C. It will be done. The reaction can be described by the equation as follows: [Wherein A is CH ₃ , CN or COOR ₃ , R ₁ ,
R ₂ , R ₃ , R ₄ , R ₅ , X, Y and Z are as described above, provided that Y and/or Z cannot be alkylamino, hydroxyl, hydroxy-lower alkyl]. A is CH ₃ , CN or COOR ₃ as above except that R ₃ cannot be an unsaturated alkyl group, and B is R ₄ CO or R ₅ SO ₂
2-(2-imidazolin-2-yl)pyridine of formula () or as written and illustrated immediately above, such that Y or Z cannot be alkylamino, alkylthio or dialkylamino The N-substituted imidazoline derivative of , when reacted with an excess of m-chloroperbenzoic acid at reflux temperature in the presence of an inert solvent such as methylene chloride, gives a reaction with an excess of m-chloroperbenzoic acid corresponding to the pyridine derivative used as starting material. The N-oxide is produced. The reaction can be explained as follows: [wherein A is CH ₃ , CN or COOR ₃ , R ₃ is as above except that it cannot be an unsaturated alkyl group, B is COR ₄ or SO ₂ R ₅ , R ₁ ,
R ₂ , R ₄ , R ₅ , X, Y and Z are as described above, with the proviso that Y and Z cannot be alkylamino, alkylthio or dialkylamino]. Hydrolysis of the N-oxide thus prepared in a lower alcohol using a strong base such as sodium hydroxide produces the corresponding N-oxide in which B is H. Advantageously, B is hydrogen and W is oxygen;
A is _COOR3 , where _R3 is a saturated _C1 - _C12 alkyl, _C3 - _C6 cycloalkyl or benzyl substituent, and _R1 , _R2 , X, Y and Z are as defined above The ester of formula () as shown above can be prepared by adding the corresponding acid, i.e. where A is COOH, to a catalytic amount of a strong mineral acid, such as hydrochloric acid, sulfuric acid, etc.
at a temperature between about 50°C and 100°C in the presence of
It can be produced by reacting with an appropriate alcohol. The reaction can be explained as follows: [wherein _R3 is _C1 - _C12 alkyl, _C3 - _C6 cycloalkyl or benzyl, and _R1 , _R2 , X,
Y and Z are as defined above]. The formula () shown immediately above where A is COOH, B is hydrogen, W is oxygen, and R ₁ , R ₂ , X, Y and Z are as defined above can be readily converted to the corresponding methyl ester by reaction with diazomethane at temperatures between about 0°C and 25°C. The methyl ester thus prepared is then combined with an alkali metal alkoxide, such as a sodium or potassium alkoxide (designated simply as R ₃ ONa) and a compound of the structure R ₃ OH, where R ₃ is optional. 1
_C1 - _C4 alkoxy, _C3 - _C6 cycloalkyl,
_C1 - _C12 alkyl optionally substituted with benzyloxy, furyl, phenyl, halophenyl, lower alkyl phenyl, lower alkoxyphenyl, nitrophenyl or cyano; optionally one or two _C1 - _C3 alkoxy , _C3 - _C12 alkenyl optionally substituted with phenyl or halogen groups; _{C3 -C6 cycloalkyl optionally substituted with one or two C1-C3 alkyl groups} ; _{C3 - C10} alkynyl optionally substituted with one or two C1- _C3 alkyl groups]
can be reacted with a suitable alcohol represented by The above reaction can be explained as follows: [wherein R ₁ , R ₂ , R ₃ , X, Y and as defined above]. Conversion of the esters of formula () above into the corresponding acid addition salts involves converting the esters into strong acids, especially strong mineral acids.
This can be easily carried out by treatment with, for example, hydrochloric acid, sulfuric acid or hydrobromic acid. If you want a hydrohalogenated acid addition salt, A is
COOR ₃ , R ₃ is other than hydrogen or a salt-forming cation, and R ₁ , R ₂ , X, Y and Z are as described above, such as methylene chloride, chloroform, ether, etc. Dissolve in an organic solvent such as At least one equivalent of acid is then added to the solution thus prepared to form the desired acid addition salt. The reaction is explained as follows: When a sulfate salt of an ester is desired, the ester of formula () is generally dissolved in a lower aliphatic alcohol such as methanol, ethanol, isopropanol, etc. or a mixture thereof with water. Treatment of the mixture with at least one equivalent of sulfuric acid produces the sulfuric acid addition salt of the ester of formula (). In another embodiment of the invention, A is COOR ₃ , R ₃ is hydrogen and R ₁ , R ₂ , X, Y and Z are as defined above, with the proviso that X, Y and Compounds of formula () such that Z cannot be NO ₂ or halogen are of formula ()
The benzyl ester of imidazolinylpyridine shown in the formula: [wherein R ₁ , R ₂ , X, Y and Z are as defined above] is hydrolyzed using a palladium or platinum catalyst. It can be manufactured by In this reaction, the benzyl ester of formula () is dissolved or dispersed in an organic solvent such as a lower alcohol, an ether such as dioxane, tetrahydrofuran, toluene or xylene. A catalyst, preferably palladium on a carbon support, is added to the mixture and the mixture is heated between 20°C and 50°C.
Heat between ℃. The heated mixture is then treated with hydrogen gas to produce the desired acid. The reaction can be described by the equation as follows: On the other hand, an acid of formula () in which A is COOH can be produced by treating an aqueous solution of an ester of formula () with a strong acid group. In practice, the ester of formula () is generally treated with one equivalent of base in aqueous solution and the mixture heated to between 20<0>C and 50<0>C. Then cool the mixture and use strong mineral salt to
Adjust the pH to 6.5-7.5, preferably 7. Such treatment produces the desired acid. The reaction can be explained as follows: [wherein R ₃ is other than hydrogen or a salt-forming cation and R ₁ , R ₂ , X, Y and Z are as described for formula ()]. Acids of formula () in which A is COOH, B is hydrogen, W is oxygen, and X, Y, Z, R ₁ and R ₂ are as above, are preferably prepared in an inert solvent, For example, it can be prepared by reacting a suitably substituted imidazolinone of formula () with an alkyllithium in the presence of tetrahydrofuran under a nitrogen atmosphere at a temperature between about -70°C and -80°C. The mixture thus prepared is then suitably treated with hexamethylphosphoramide and carbon dioxide in an inert solvent such as tetrahydrofuran to give the desired product. A is CH ₃
and if it is desired to obtain a pyridine derivative of formula () in which X, Y, Z, R ₁ and R ₂ are as above, the imidazoline of formula ( The same method as described, but using methyl iodide instead of carbon dioxide. Substituting dimethylformamide for methyl iodide gives the corresponding formyl derivative. These reactions can be explained as follows: Advantageously, the acid of formula () is converted into a compound of formula () by reaction with dicyclohexylcarbodiimide (DCC).
can be converted to 5-H-imidazo[1',2':1,2]-pyrrolo[3,4-b]pyridine-3(2H), 5-dione. The reaction is carried out using approximately equimolar amounts of carbodiimide in the presence of a chlorinated hydrocarbon solvent at a temperature between about 20°C and 32°C. The reaction can be described by the equation as follows: 5H-imidazo[1',2':1,2]- of formula ()
Pyrrolo[3,4-b]pyridine-3(2H),5-
The diones are isomers of imidazopyrrolopyridinediones of formula () above, and as will be apparent from the discussion below, the 2-
It is particularly useful in the production of (2-imidazolin-2-yl)-pyridine derivatives. In fact, the 3(2H),5-dione of formula () can be reacted with at least one equivalent of an appropriate R ₃ OH alcohol of formula () in the presence of triethylamine as a catalyst to form the alcohol corresponding to the used alcohol ( )
It has been found that pyridine esters can be produced. The reaction is suitably carried out at a temperature between about 20<0>C and 50<0>C in the presence of an inert aprotic solvent such as tetrahydrofuran, dioxane, and the like. The reaction can be explained as follows: [In the formula, R ₃ represents a substituent as described above, but hydrogen and salt-forming cations are excluded, and R ₁ ,
R ₂ , X, Y and Z are as above]. 3(2H), 5-dione of formula () can also be converted to R ₁ , R ₂ , X, Y and Z by reaction with methylmagnesium bromide, phenyllithium, sodium trimethylphosphonoacetate or sodium borohydride, respectively. is as above, W is oxygen, B is hydrogen, and A is acetyl, benzoyl,
2-(2-imidazoline-2 of formula (b) which is trimethylphosphonoacetate or hydroxymethyl
-yl)-pyridine derivatives.
The methylmagnesium bromide, phenyllithium and sodium trimethylphosphonoate acetate reaction is preferably carried out at a temperature between about -50°C and -80°C, in the presence of an inert solvent such as tetrahydrofuran or dioxane, and an inert gas. For example, it is carried out under a nitrogen atmosphere. The reaction between the dione of formula () above and sodium borohydride is relatively slow. The reaction does not require an atmosphere of inert gas and can be carried out at temperatures between about -10°C and +15°C. When the dione of formula () is reacted with at least one equivalent of acetone oxime, A becomes COON=C
( _CH3 ) ₂ , B is hydrogen, and _R1 ,
2- of formula () where R ₂ , X, Y and Z are as described for the pyridine derivative of formula ()
Acetone oxime of (2-imidazolin-2-yl)pyridine is produced. The above reaction is generally carried out in the presence of an inert organic solvent such as toluene, benzene, xylene, etc. at a temperature between about 40<0>C and 80<0>C. The above reaction is explained by the equation as follows: [In the formula, R ₁ , R ₂ , X, Y and Z are as described above]. A is COOR ₃ , R ₃ represents a salt-forming cation, such as an alkali metal alkaline earth metal, ammonium or aliphatic ammonium; and
A compound of formula () in which R ₁ , R ₂ , X, Y and Z are as described above can be prepared by dissolving 2-(2-imidazolin-2-yl)pyridine acid of formula () in a suitable solvent; It can then be prepared by treating this acid solution with one equivalent of a salt-forming cation. If the salt-forming cation is an inorganic salt, such as sodium, potassium,
For compounds that are calcium, barium, etc., the acid of formula () can be dissolved or dispersed in water or lower alcohols or mixtures thereof. One equivalent of the salt-forming cation, generally in the form of hydroxide, carbonate, bicarbonate, etc., but preferably the hydroxide, is mixed with a solution of the acid of formula (). After 5 to 6 minutes, the compound of formula () in which R ₃ is the salt-forming cation generally precipitates and can be recovered by filtration or by azeotropic distillation using an organic solvent such as dioxane. To prepare compounds of formula () where A is COOR ₃ and R ₃ is ammonium or organic ammonium, an acid of formula () is dissolved or dispersed in an organic solvent such as dioxane, tetrahydrofuran, etc. , and the mixture is treated with one equivalent of ammonia, amine or tetraalkylammonium hydroxide. Amines that can be used in the above reaction are: methylamine, ethylamine, n-propylamine, isopropylamine, n-butylamine, isobutylamine, secondary-butylamine, n-amylamine,
Iso-amylamine, hexylamine, heptylamine, octylamine, nonylamine, decylamine, undecylamine, dodecylamine, tridecylamine, tetradecylamine, pentadecylamine, hexadecylamine, heptadecylamine, octadecylamine, methylethylamine, Methylisopropylamine, methylhexylamine, methylnonylamine, methylpentadecylamine, methyloctadecylamine, ethylbutylamine, ethylheptylamine, ethyloctylamine, hexylheptylamine, hexyloctylamine, dimethylamine, diethylamine, di-n- Purpylamine, diisopropylamine, di-n-amylamine, diisoamylamine, dihexylamine, diheptylamine, dioctylamine, trimethylamine, triethylamine, tri-n-propylamine, triisopropylamine, tri-n-butylamine, triisobutylamine, Tri-secondary-butylamine, tri-n-amylamine, ethanolamine, n-propanolamine, isopropanolamine, diethanolamine, N,N-diethylethanolamine, N-ethylpropanolamine, N-butylethanolamine, allylamine, n-utenyl -2-amine, n-pentenyl-2-amine, 2,3-dimethylbutenyl-2-
Amines, dibutenyl-2-amine, n-hexenyl-2-amine, propylene diamine, tallowamine, cyclopentylamine, cyclohexylamine, dicyclohexylamine, piperidine, morpholine and pyrrolidine. Tetraalkylammonium hydroxy includes methyl, tetraethyl, trimethylbenzylammonium hydroxide. In practice, after 5-6 minutes the ammonium or organic ammonium salt precipitates and can be separated from the solution by conventional means such as filtration or centrifugation. Additionally, the reaction mixture can be concentrated and the remaining solution removed using hexane and the residue then dried to recover the ammonium or organic ammonium salt of formula (). The above reaction can be explained by the following equation: [wherein R ₁ , R ₂ , X, Y and Z are as described above and b is a salt-forming cation]. When R ₁ and R ₂ represent different substituents,
The carbon to which R ₁ and R ₂ are attached is an asymmetric center, and the products (and their intermediates) exist in the d- and 1-forms as well as the d1-form. 2- expressed by the formula () where B=H
(2-Imidazolin-2-yl)pyridine and quinoline are described by one structural formula, identified as formula () for simplicity, but it is understood that they can also be in tautomeric forms. and they can exist in any of the isomeric forms described below: or [where A, W, X, Y, Z, R ₁ and R ₂ are as defined above and B is H]. Both isomeric forms of 2-(2-imidazolin-2-yl)pyridine and 2-(2-imidazolin-2-yl)quinoline are also meant to be included in the definition of formula (). One common method for preparing compounds of formula () is to react quinoline anhydride of formula () below with an appropriately substituted α-aminocarbonyltolyl of formula () below to form compounds of formula () and formula (). The method includes a step of producing a monoamide of quinolinic acid. The reaction is carried out at temperatures between about 20°C and 70°C, preferably at about 35°C.
It is carried out in an inert solvent such as tetrahydrofuran, methylene chloride, ether, chloroform, toluene, etc., at a temperature between 0.degree. C. and 40.degree. The acid thus prepared is then cyclized by heating the reaction mixture with an excess of acetic anhydride in the presence of a catalytic amount of sodium or potassium acetate to give the acid described by formula (). It becomes the corresponding pyrrolopyridine acetonitrile. Generally, the above reactions are carried out by treating the reaction mixture with acetic anhydride, acetyl chloride, thionyl chloride, etc. and heating the mixture to a temperature between about 20<0>C and 100<0>C. Hydration of the pyrrolopyridine acetonitrile of formula (XI) thus prepared is carried out by treating the acetonitrile with a strong acid such as, for example, sulfuric acid. This reaction produces pyrrolopyridine acetamide of formula (). Although the addition of immiscible solvents, such as methylene chloride, chloroform, etc., is not essential to carrying out the above reactions, it is generally preferred to add such solvents to the reaction mixture. The reaction is normally carried out at a temperature between about 10°C and 70°C. Cyclization of pyrrolopyridine acetamides of formula () below produces tricyclic imidazopyrrolopyridinediones of formula (), which are imidazolinylnicotinic acids of the invention represented by formula (b) above. and intermediate products for esters. The products of this reaction are primarily the desired imidazopyrrolopyridinedione (85%) as well as the formula (
It is an isomer of a). A mixture of the two isomers in this ratio generally provides a substantially isomerically pure product. The cyclization reaction is preferably carried out at a temperature between 80°C and 150°C in the presence of a base, such as sodium or potassium hydride, or an acid, such as an aromatic sulfonic acid, and a solvent which forms an azeotrope with water. The mixture is removed from the reaction mixture virtually as soon as it is formed. Solvents that can be used are toluene, benzene, xylene and cyclohexane. Bases that can be used include alkali metal hydroxides, alkali metal hydrides, alkali metal oxides, tertiary amines such as diisopropylethylamine, 1,5-diazabicyclo[3.4]
Nonene-5,1,5-diazodicyclo [5.4.0]
Included are undecene-5,1,4-diazabicyclo[2.2.2]octane, tetramethylguanidine, potassium fluoride and quaternary ammonium hydroxides such as trimethylbenzylammonium hydroxide and strongly basic ion exchange resins. Finally, acidic reagents that can be used here include aromatic sulfonic acids such as p-toluenesulfonic acid,
Includes β-naphthalene sulfonic acid, naphthalene disulfonic acid, etc. The mixture of compounds of formula () and formula (a) is then converted to formula (b) above using an alkali metal alkoxide and an alcohol. When X, Y, Z, R ₁ , R ₂ and R ₃ are as defined above, the above reaction is illustrated by the formula in the following flow diagram: Another common method for preparing pyridine derivatives of formula () is to prepare a quinoline anhydride of formula (), preferably in a ketone solvent such as acetone, under a nitrogen atmosphere, to prepare a pyridine derivative represented by formula (). () and formula (
XI) producing a mixture of isomers of the acid. The mixture is then treated with acetic anhydride and a catalytic amount of sodium acetate at elevated temperature to provide dihydrodioxopyrrolopyridic acid of formula (XII). The acid thus prepared is heated at elevated temperature, i.e. from 80°C to
Reaction at 150° C. with a thionyl halide, such as thionyl chloride or thionyl bromide, gives the acid halide of formula () corresponding to the acid of formula (XII). The acid halide is then treated with excess ammonia to produce the dihydrodioxopyrrolopyridine acetamide of formula (). The reaction is preferably carried out in the presence of an aprotic solvent. An acetamide of formula () is prepared in an inert organic solvent such as toluene or xylene at a temperature of about 80°C to
Reaction with 1,8-diasabicyclo[5,4,0]undec-7-ene at elevated temperatures between 125°C gives the imidazopyrrolopyridinone of formula (), which can be reacted with morpholine or a suitable
Heating with _NH2R6 amine produces 2-(2-imidazolin-2 _- yl)nicotinamide. These reactions are illustrated as a process diagram: In another general method, 2-(2-imidazolin-2-yl)pyridic acid and esters of formula () are prepared from 2-carboalkoxynicotinoyl chloride of formula () below, preferably as the methyl ester and Preferably in the form of the hydrochloride, with the formula (
) can be prepared by reacting with a suitable amine carboxide as described by ). This reaction produces a carbamoyl picolinate of formula (), and the reaction is preferably carried out in an inert atmosphere of gas, such as nitrogen. The reaction mixture is generally kept at a temperature below 30° C. during the reaction period. The carbamoyl picolinate of formula () thus prepared is dispersed in an inert solvent, such as xylene or toluene, and 1,5-diazabicyclo-[5.4.0]undec-5
-Can be heated to about 50℃ to 130℃ with ene. This reaction produces a mixture of imidazopyrrolopyridinedione isomers of formula () and formula (a),
It can be used without separation in a subsequent reaction in which the reaction mixture is treated with an alkali metal alkoxide in the presence of an alcohol to produce a mixture of imidazolinyl nicotinate and imidazolinyl picolinate. The desired nicotinate of formula (b) is prepared by neutralizing the reaction mixture, preferably using glacial acetic acid, concentrating the neutralized solution, and chromatographing the resulting residue on silica gel in ether. can be easily separated from picolinate. Conversion of imidazolinyl nicotinate esters to the corresponding acids or acid addition salts can be easily carried out by the methods described above. Similarly, imidazolinylnicotinic acid is converted to the corresponding alkali metal, ammonium or organic ammonium salt by the methods described above. The production of acids and esters of formula () by the above method will be explained by formulas in the process diagrams below. Advantageously, many of the 2-(2-imidazolin-2-yl)quinoline derivatives of formula () according to the invention are
2-(2-imidazoline-2- of the above formula ())
It can be produced by a method for producing a pyridine compound. For example, R ₃ represents hydrogen or a substituent other than a salt-forming cation, and R ₁ , R ₂ , X, L, M, Q
2 of the formula () where and R ₇ is as above
-(2-imidazolin-2-yl)quinoline carboxylate esters can be prepared by reacting diones of formula () with appropriate alcohols and alkali metal alkoxides at temperatures between about 20°C and 50°C. In these reactions, similar reactions produce pyridine of formula (),
Alcohols can act as both reactants and solvents. In that case, a co-solvent is not required, but can be used if desired. When a co-solvent is used, it is preferred to use an aprotic solvent, such as tetrahydrofuran or dioxane.
The reaction can be explained as follows: [In the formula, M is an alkali metal, X is hydrogen, halogen, hydroxyl or methyl, provided that one of L, M, Q or R ₇ is hydrogen,
When it is a substituent other than halogen, _C1 - _C6 alkyl or _C1 - _C4 alkoxy, L, M, Q and
_R7 is hydrogen, halogen, _C1 - _C4 alkyl,
_C1 ~ _C4 alkoxy, _C1 ~ _C4 alkylthio, C1 _~
C4 alkylsulfonyl, _C1 - _C4 haloalkyl,
_NO2 , CN, phenyl, phenoxy, amino, _C1
~ _C4 alkylamino, di-lower alkylamino,
chlorophenyl, methylphenyl or 1 Cl,
Represents phenoxy substituted with CF ₃ , NO ₂ or CH ₃ groups, with the proviso that L, M, Q or R ₇
only one of which may represent a substituent other than hydrogen, halogen, _C1 - _C4 alkyl or _C1 - _C4 alkoxy, and _R1 , _R2 and _R3 are as above] . From a dioxopyrroquinoline acetamide of formula () in which R ₁ , R ₂ , X, Y and Z are as above, a strong base, e.g. 1,5- It can be prepared by cyclizing it with diazabicyclo[5.4.0]undec-5-ene (DBU) to give the crude imidazopyrroloquinolinedione of formula (). The reaction mixture is heated to a temperature between 100°C and 150°C, and water is removed from the reaction mixture during the reaction using, for example, a Dean Stark water separator. Then at least one equivalent of the formula ()
An alcohol represented by R ₃ OH, where R ₃ is a member other than hydrogen or a salt-forming cation, is added to the reaction mixture and the mixture thus prepared is heated at between 100°C and 150°C. Heating to reflux temperature gives the ester of formula (). The reaction can be described by the equation as follows: [In the formula, R ₁ , R ₂ , R ₃ , X, L, M, Q and R ₇ are as described above]. 2-(2-imidazoline-2 of formula ()
-yl)quinoline-carboxylate esters can be prepared by cyclizing carbamoylquinoline carboxylate esters of formula () with phosphorus pentachloride at elevated temperatures between about 60°C and 100°C. The reaction is suitably carried out in the presence of an inert organic solvent, such as toluene or benzene, and is of the formula ()
to produce the hydrochloride salt of 2-(2-imidazolin-2-yl)quinoline carboxylate ester.
The hydrogen halide salt thus prepared is treated with a base such as sodium or potassium carbonate to produce the 2-(2-imidazolin-2-yl)quinoline carboxylate ester of formula (). The formula used in the above reaction (
The carbamoylquinoline carboxylate ester of ) is shown below: [wherein R ₃ is a substituent as described above, but hydrogen or a salt-forming cation is excluded, and R ₁ , R ₂ , X,
L, M, Q and _R7 are as above]. 2-(2-imidazoline-2 of formula ()
-yl) quinoline carboxylate ester is
It is also produced by cyclization of carbamoylquinoline carboxylate esters having the structure represented by formula (): [wherein R ₃ is as above, but hydrogen and salt-forming cations are excluded, and R ₁ , R ₂ , X,
L, M, Q and _R7 are as above]. Cyclization of the carbamoylquinoline carboxylate ester is carried out by reacting it with a mixture of phosphorus pentachloride and phosphorus oxychloride.
The reaction mixture is stirred for several hours at about 15°C to 35°C and then the POCl ₃ is removed in vacuo. The remaining residue is dispersed in an organic solvent such as toluene. The solvent is removed and the residue is dispersed in water and heated between 80°C and 100°C. After cooling, the PH of the aqueous mixture is adjusted to 5-6 using sodium or potassium bicarbonate and the product is extracted in methylene chloride to obtain the desired 2-(2-imidazolin-2-yl of formula ()). ) gives quinoline carboxylate ester. R ₃ is hydrogen or any of the above other than a salt-forming cation, and R ₁ , R ₂ , X, L, M, Q and
A quinoline ester of formula (), where R ₇ is as defined above, is readily converted to its corresponding acid addition salt by reacting the ester with at least one equivalent of a strong acid. Strong mineral acids such as hydrochloric, sulfuric and hydrobromic acids are used, but organic acids can also be used. In practice, it has been found that the reaction proceeds most satisfactorily when carried out in the presence of an inert organic solvent such as, for example, ether, chloroform, methylene chloride or mixtures thereof. Generally, a phylate is produced by this method, but a lower aliphatic alcohol is used in place of the above-mentioned solvent. A is COOH, B is hydrogen, W is oxygen, and R ₁ , R ₂ , X, L, M, Q and
2-(2-imidazolin-2-yl)quinoline of formula () where R ₇ is as defined above, with the proviso that X, L, M, Q and R ₇ are not halogen or nitro. The production of derivatives is
2-(2-imidazoline-2- of formula ()
It is carried out by hydrolysis of the benzyl ester of quinoline carboxylate. The reaction is carried out by dispersing the benzyl ester in an organic solvent, for example as described above for the hydrolysis of benzyl esters of formula () based on 2-(2-imidazolin-2-yl)pyridine, and The reaction mixture prepared may include a step of treatment with hydrogen gas in the presence of palladium or platinum on a carbon support, for example. Hydrolysis is generally carried out at temperatures between about 20°C and 50°C. A is COOH, B is hydrogen, W is oxygen, and R ₁ , R ₂ , X, L, M, Q and
The acid of the 2-(2-imidazolin-2-yl)quinoline derivative of formula () in which R ₇ is as above,
R ₃ is a substituent as defined above other than hydrogen and a salt-forming cation, and R ₁ , R ₂ , X, L, M, Q and R ₇
It is also prepared by reacting an ester of formula (), in which is as described above, with at least one equivalent of a strong aqueous base, such as an aqueous solution of an alkali metal hydroxide, at a temperature of 20°C to 50°C. Cool the mixture and then adjust to PH6.5 using strong mineral acid
Adjust to ~7.5. Such treatment produces the desired acid. A is _COOR3 , _R3 is a salt forming cation, B is hydrogen, W is oxygen, and
2-(2-imidazolin-2-yl)quinoline derivatives of formula () in which R ₁ , R ₂ , X, L, M, Q and R ₇ are as above, A is COOH and B
is hydrogen, W is oxygen, and R ₁ , R ₂ ,
An acid of formula () in which X, L, M, Q and R ₇ are as above is dissolved in a suitable solvent and the mixture thus prepared is treated with at least one equivalent of salt-forming cation. It can be manufactured by processing. The reaction essentially means that A is
Identical to the description for the preparation of pyridine of formula () where COOR ₃ and R ₃ is the salt-forming cation. It is also to be understood that the imidazolinylquinoline carboxylic acids described by formula () where B is H may be in tautomeric forms. 2-(2-imidazolin-2-yl) of formula ()
When R ₁ and R ₂ represent different substituents on the quinoline derivatives and imidazopyrroloquinolinediones of formula (), the carbons to which R ₁ and R ₂ are attached are asymmetric centers and the products (as well as their intermediate products) in d- and 1-forms and dl
It should also be understood that it exists in a form. Cyclization of imidazopyrroloquinoline acetamides of formula () produces tetracyclic imidazopyrroloquinolinediones of formula () and formula (a), which are 2-(2-
imidazolin-2-yl) quinoline carboxylate acids and esters. The products of this reaction are primarily the desired imidazopyrroloquinolinedione as well as a small amount of the formula (
It is an isomer of a). Treatment of the mixture of isomers with an alkali metal alkoxide provides a substantially isomerically pure quinoline carboxylate product. The cyclization reaction is preferably carried out at a temperature between 80°C and 150°C in the presence of a base, such as sodium or potassium hydride, or an acid, such as an aromatic sulfonic acid, and a solvent which forms an azeotrope with water. The mixture is removed from the reaction mixture virtually as soon as it is formed. Solvents that can be used are toluene, benzene, xylene and cyclohexane. Bases that can be used include alkali metal hydroxides, alkali metal hydrides, alkali metal oxides, tertiary amines such as diisopropylethylamine, 1,5-diazabicyclo[3.4]
Nonene-5,1,5-diazodicyclo [5.4.0]
Included are undecene-5,1,4-diazabicyclo[2.2.2]octane, tetramethylguanidine, potassium fluoride and quaternary ammonium hydroxides such as trimethylbenzylammonium hydroxide and strongly basic ion exchange resins. Finally, acidic reagents that can be used here include aromatic sulfonic acids such as p-toluenesulfonic acid,
Includes β-naphthalene sulfonic acid, naphthalene disulfonic acid, etc. Reactions are explained by formulas in process diagrams. Several methods are used to produce pyrroloquinoline acetamide represented by formula (). Preferably, hydration of the pyrroloquinoline acetonitrile of formula () is carried out by treatment with a mineral acid, such as sulfuric acid. This reaction produces pyrroloquinoline acetamide of formula (). Although the addition of immiscible solvents such as methylene chloride, chloroform, etc. is not essential to carrying out the above reactions, such solvents can also be added to the reaction mixture. The reaction is generally 10
It is usually carried out at temperatures between 70°C and 70°C. On the other hand, pyrroloquinoline acetamide of formula () can be obtained by a Diels-Alder cycloaddition reaction between a substituted anthranyl of formula (XI) and dioxopyrroline acetamide of formula (XII). These reactions are carried out within a wide temperature range below 130°C, and the intermediate product, formula (
) aldehyde can be obtained, but from 130℃
At 200°C, pyrroloquinoline acetamide of formula () is produced. Alternatively, the intermediate aldehyde of formula () is isolated and cyclized in refluxing xylene in the presence of an acid catalyst such as p-toluenesulfonic acid. This reaction produces the desired pyrroloquinoline acetamide of formula (). These reactions are illustrated schematically in the flow diagrams below. Various methods can be used to obtain the pyrroloquinoline acetonitrile of formula () depending on the nature of the L, M, Q and R ₇ substituents. Pyrroloquinoline acetonitrile of formula () can be prepared by reacting a suitably substituted anhydride (XI) with a suitably substituted α-aminocarbonitrile of formula () to form acids of formula (a) and formula (b). can be prepared by forming a mixture of monoamides. The reaction is carried out between 20°C and 70°C, preferably around 35°C.
It is carried out in an inert solvent such as tetrahydrofuran, methylene chloride, ether, chloroform, toluene, etc., at a temperature between -40<0>C. The acid thus prepared is then cyclized to the corresponding pyrroloquinoline acetonitrile described by formula (). This prepares the reaction mixture with excess acetic anhydride in the presence of a catalytic amount of sodium acetate or potassium acetate from about 75°C to
This is done by heating to a temperature between 150°C. Generally, the above reaction is carried out by treating the reaction mixture with acetic anhydride, acetyl chloride, thionyl chloride, etc.
The mixture is then heated to a temperature between about 20°C and 100°C. The above reaction is explained by formula in the process diagram below. In the formula, R ₁ , R ₂ ,
X, L, M, Q and R ₇ are as described above. A preferred method to give pyrroloquinoline acetonitrile of formula () is a Diels-Alder thermal cycloaddition reaction of a suitably substituted maleimide of formula () with a suitably substituted anthranyl. In this method, X must be hydrogen. The outcome of this reaction is dependent on the reaction temperature. ~
At 55°C, an intermediate product of formula () is obtained. Further heating of the reaction mixture to a temperature between 55°C and 130°C provides an aldehyde intermediate of formula (). If the reaction is carried out in the presence of an aprotic solvent such as o-dichlorobenzene and the reaction mixture is heated between 140 DEG and 200 DEG C., the reaction produces pyrroloquinoline acetonitrile of formula (). The reaction is illustrated in the flow diagram below: In the above method, the L, M, Q and R ₇ groups are electronegative groups, such as halogen, nitro, CF ₃ , SO ₂ CH ₃ ,
This is particularly effective when CN. A variation of this process is to prepare the o-aminoacetal of formula () in the presence of an abrotic solvent, such as xylene or toluene, at a temperature of about 50°C to 130°C.
At temperatures between ℃ and the appropriately substituted formula (
) with maleimide. These reactions are explained by the equations as follows. Other variants that can be used for the synthesis from anilines with electron donor substituents or one halogen or CF ₃ function in the L, M, Q and R ₇ positions are o-alkyl or aryl of formula (). This is a step in which ruthiomethylaniline is reacted with bromomaleimide of formula () to give maleimide of formula (XI), which is oxidized to maleimide of formula (XII). Then the expression ()
The maleimide of is cyclized in an acid-catalyzed reaction to produce pyrroloquinoline acetonitrile of formula (). The reaction is explained below using the formula. _R1 ,
R ₂ , L, M, Q and R ₇ are as defined above. Compounds of formula () containing electron-donor substituents in the L, M, Q and R ₇ positions, such as alkyl, alkoxy, alkylthio, dialkylamino, hydroxy and one halogen, may have the formula (
) or anthranilic acid of formula (XI) with a bromo(or chloro)maleimide of formula (). The reaction is carried out in the presence of a non-polar solvent, such as isopropyl or t-butyl alcohol, from 0°C to 30°C.
are carried out in the formula (
) to produce hydroxymethylanilinomaleimide or dioxoprolinyl anthranilic acid of formula (). Various base acceptors can be used in the above reaction, such as alkaline earth metal hydroxides, such as Ba(OH) ₂ , BaO or sodium acetate. However, in many cases the reaction proceeds satisfactorily without a base acceptor. The alcohol formula () of the formula ()
) to aldehydes can be oxidized using a variety of oxidizing agents,
For example, chlorochromate or t in methylene chloride
- activated manganese dioxide in butanol,
It can be implemented using The cyclization of aldehydes of formula () to pyrroloquinoline acetonitrile of formula () can be carried out by one of the methods described above, e.g.
This is done by heating between 140°C and 200°C. The cyclization of the o-anilinocarboxylic acid of formula () to the acetoxyquinoline of formula () is carried out using acetic anhydride, triethylamine and 4-dimethylaminopyridine at room temperature. By removal by slow reduction, the expression (
) pyrroloquinoline acetonitrile is obtained. Upon hydrolysis in warm aqueous acetic acid, X=
A formula () is obtained which is OH, which is further reacted with phosphorus oxychloride and pyridine to give a compound where X is chlorine. These reactions are illustrated in the flow diagrams below. Another method for obtaining 2-(2-imidazolin-2-yl)quinoline compounds of formula (), which is particularly useful in the synthesis of congeners where the A group is varied, involves
) 2-(2-imidazolin-2-yl)quinoline is used. This intermediate product is converted to the acid chloride or anhydride of the formula (
) is produced from quinoline carboxylic acid,
It is then reacted with a suitably substituted α-aminocarbonitrile of formula () to form a compound of formula (
) or the formula (
XI) with the aminoamide of the formula (
XII) gives the carboxamide amide. The cyclization of the carboxamide amide is carried out by the methods described above, but cyclization with sodium hydride in the presence of xylene is preferred. Introduction of various groups A can also be carried out by treating 2-(2-imidazolin-2-yl)quinoline of formula () with a metallizing reagent. Although many organometallic reagents have some effect when using two moles of dianion, the yield and reaction composition depend on the organometallic reagent, reaction solvent, reaction temperature, and demand used to quench the reaction. Relies on electronic reagents. In practice, organometallic reagents such as alkyl lithiums are preferred, and methyl, n-butyl, sec-butyl and tertiary-butyl lithium are used to form anions. Phenyllithium and lithium diisopropylamide can be used. The solvent must be aprotic and diethyl ether is preferred. The reaction temperature used to produce the dianion ranges from -78°C to 0°C, preferably -30°C to -10°C. Cooling using electrophiles typically ranges from -78°C
Performed at +20°C. If necessary, acid treatment is then performed. All reactions are carried out under an inert atmosphere. Examples of reactive electrophiles include _CO2 ,
_{ClCO2CH3 ,} ( _CH3 ) _2NCHO , _CH3HCO ,
Includes _CH3HCO , _C6H5CHO , _{CH3I .} The corresponding value for A in formula (a) is COOH,
_COOCH3 ,CHO,CH(OH) _CH3 ,CH(OH)
_{C6H5 , CH3} . Additionally, the product can be modified after quenching the electrophile. In this way
Aldehydes produced from DMF cooling (A=
CHO) reacts with hydroxylamine to give oxime. The above method is also useful for the synthesis of A=COOH compounds by treating the dianion with carbon dioxide. Not all X, L, M, Q and R ₇ substituents are compatible with this organometallic method. Therefore, if the above-mentioned substituents are Br, I or sometimes fluorine, a comparable loss of these groups as well as a displacement of the 3-proton of the quinoline results. However, chlorine is compatible with this method. L, M, Q or
When R ₇ is methoxy, a comparable anion formation can occur with otol for the methoxy group. The above reaction is illustrated by the formula in the process diagram below. The various functional groups A are produced by different methods.
Reaction of the imidazopyrroloquinolinedione of formula () with R ₃ OM ⁺ provides the 2-(2-imidazolin-2-yl)quinoline ester of formula (). In the case of compounds of formula () in which A is a CONHCH ₂ CH ₂ OH group, this can be cyclized to an oxazoline group by reacting the above compound with triethyl phosphite in refluxing xylene. A is-
The derivative of formula () which is CONH ₂ can be converted into the corresponding cyano derivative, i.e. that of A=CN, by dehydration of the -CONH ₂ functional group. Although a large number of compounds containing L, M, Q and R ₇ substituents can be prepared by the method described above, amino, alkylamino and dialkylamino compounds can be prepared using the appropriate nitro at the L, M, Q or R ₇ positions. It is easily prepared by reductive alkylation of substituents. The alkylsulfonyl compound is L, M, Q or
The alkylsulfonyl group at the R ₇ position is 0℃~
It is most easily produced by mild oxidation with m-chloroperbenzoic acid at 20°C.
Under these conditions, N-oxidation of the quinoline nitrogen is minimized. The oxidation of the quinoline to the N-oxide can be carried out by prior N-protection of the imidazolone ring, for example with a COCH ₃ group, and the N-oxidation can be carried out with peracetic acid or trifluoroperacetic acid, if necessary at elevated temperature. 2-(2-imidazolin-2-yl)pyridine and 2-(2-
Imidazolin-2-yl)quinoline and the imidazopyrrolopyridinediones and imidazopyrroloquinolinediones of the formulas () and () are useful for the control of a very wide variety of grassy and tree-like annual and perennial nest cotyledonous and dicotyledonous plants. It is a useful and highly effective herbicide. Additionally, these compounds are effective as herbicides to control weeds indigenous to both dryland and wetland areas. They are also useful as aqueous herbicides and are added to the soil or water containing the leaves or seeds of the plants mentioned above or other reproductive organs of the plants, such as tubers, rhizomes or stolons, at about 0.016 to 4.0 Kg/ ha and preferably at a rate of about 0.032 to 2.0 Kg/ha. Of course, it is clear that application rates higher than 4.0 Kg/ha can be used to effectively kill undesirable plant species, but the application of excessive amounts of poison is costly and has no environmentally beneficial effect. Application of poisons at rates higher than those necessary to kill undesirable plants should be avoided. Plants that can be controlled using the compounds of the invention include: Elatine tri-
andra), Sagittaria pygmaea, Seirpus hotarui, Cyperus serotinus, Eclipta alba, Cyperus
difformis), Rotala indica, Lindernia dyri-
doria), Golden millet (Echinochloa crus-galli),
Digitaria agnguina-lis, Setaria viridis, Cyperus
rotundus), Convolvulus arvensis, Azropyron
repens), Datura (Datura)
stramonium), Alopecurus myosuro-ides, morning glory (Ipomoea spp.), Sida spinosa (Sida
spinosa), ragweed (Ambrosia
artemisiifolia), Eichhornia cra−ssipes, Xanthium pensylva−nicum, Sesbania cra−ssipes
Exaltata (Sesba-nia exaltata), oat (Avenafatua), velvet leaf (Abutilon theophrasti), Bromus tectorum, Sorghum grass, ryegrass (Lolium)
spp.), Panicum dichotomiflorum (Panicum
dichotomiflorum), Matricaria (Matricaria)
spp.), Amara-nthus retroflexus,
Cirsium arvense and Rumex japonicus
japonicus). Surprisingly, some of the compounds of formula ( ) and formula ( It has now been found that it is a selective herbicide when applied at application rates, i.e. from 0.016 to about 2.0 Kg/ha. In fact, 2-(2-imidazoline-
2-yl)pyridine is generally found to be best suited for use as a broad spectrum herbicide when used either pre-emergent or post-emergent where weed control is desired. Served. However, this does not mean that all pyridines of formula () are non-selective. fact,
Certain 2-(2-imidazolin-2-yl)pyridines, especially penta-substituted compounds of formula () and formula (
Pyridine in a) is selective in leguminous crops, especially in crops such as, for example, soybean. Similarly, 2-(2-imidazoline-2-
Quinoline is a general selective herbicide that is particularly effective for the control of undesirable weeds in the presence of legume crops such as, for example, soybeans. However, some of the compounds of formula () and formula () are less selective than others in this series. Formula () and some of the 2-(2-imidazolin-2-yl)pyridine and 2-(2-imidazolin-2-yl)quinoline of formula () are about 0.016 to
It has also been found to be effective as a defoliant for cotton when applied at application rates between 4.0 Kg/ha. At application rates not exceeding about 0.01 Kg/ha, the pyridine seeds of formulas () and () are effective for increasing branch growth in legume crops and for obtaining early grain ripening. has also been found. Pyrrolopyridine acetonitrile of formula (XI), pyrrolopyridine acetamide of formula (), pyrrolopyridine acetamide of formula ()
Pyrroloquinoline acetonitrile of formula () and pyrroloquinoline acetamide of formula () are
The above herbicide formula () and formula () 2-
(2-imidazolin-2-yl)pyridine and quinoline and the herbicides formula () and formula (
) is useful as an intermediate for the production of imidazopyrrolopyridinediones and imidazopyrroloquinolinediones. Since the imidazolinylpyridine and quinoline derivatives of formula () and formula () in which R ₃ is a salt-forming cation are water-soluble, these compounds can be easily dispersed in water and leave the leaves of plants or the reproductive organs of plants. It can be applied as a diluted aqueous spray to the containing soil. These salts can also be formulated into concentrated flowable liquids. 2-(2-imidazolin-2-yl)pyridine and quinoline of formula () and formula () and imidazopyrrolopyridinedione and isodazopyrroquinolinedione of formula () and formula () can be used as wettable powders, concentrated fluids, It can also be formulated as a concentrated emulsion, granular composition, etc. Wettable powders contain about 20-45% by weight of a finely divided carrier, such as kaolin, bentonite, diatomaceous earth, attapulgite, etc., 45-80% by weight of active compound, 2-
5% by weight of a dispersant, e.g. sodium lignosulfonate, and 2-5% by weight of a nonionic surfactant, e.g. octylphenoxypolyethoxyethanol, nonylphenoxypolyethoxyethanol, etc., are ground to a pulp. It can be manufactured by A typical flowable liquid contains about 40% by weight of active ingredient and about 2% by weight of a gelling agent, such as bentonite.
3% by weight of a dispersant such as sodium lignosulfonate, 1% by weight of polyethylene glycol and
It can be produced by mixing with 54% water by weight. A typical concentrated emulsion contains about 5-25% by weight of active ingredient, about 65-90% by weight of N-methyl-pyrrolidone,
It can be prepared by dissolving in isophorone, butyl cellosolve, methyl acetate, etc., and dispersing therein about 5 to 10% by weight of a nonionic surfactant, such as an alkyl phenoxy polyethoxy alcohol. This concentrated emulsion is dispersed in water for application as a liquid spray. When the compounds of the present invention are used as herbicides, including soil treatments, the compounds can be prepared and applied as granular products. The production of granular products involves dissolving the active compound in a solvent such as methylene chloride,
N-methylpyrrolidone, etc., and the solution thus prepared is applied to a granular carrier,
For example, corn cob flour, sand, attapulgite,
This is done by spraying on kaolin, etc. The granular products thus produced generally consist of about 3-20% by weight of active ingredient and about 97-80% by weight of granular carrier. To further facilitate an understanding of the invention, the following examples are presented primarily for the purpose of further illustration. The present invention is not limited by the examples except in the scope of the claims. All parts are parts by weight unless otherwise indicated. Reference example 1 5,7-dihydro-α-isopropyl-α-methyl-5,7-dioxo-6H-pyrrolo[3,
4-b] Preparation of pyridine-6-acetonitrile To a stirred solution containing 212 g of quinoline anhydride in 950 ml of methylene chloride, 167 g
of 2-amino-2,3-dimethylbutyronitrile was added at a suitable rate. Approximately 1/4 of aminonitrile
is added, the mixture reaches the boiling point of the solution,
The addition rate was then adjusted to maintain this temperature. After the addition, the solution was heated under reflux for an additional 4 hours. The solution was cooled, filtered, and concentrated to a thick oil. Dissolve this oil in 950 ml of acetic anhydride, add 6 g of anhydrous sodium acetate and
When heating is continued under reflux for 3 hours, the steam temperature is
The mixture was distilled until reaching 118°C. The mixture was concentrated under reduced pressure and the residue was dissolved in 500ml of toluene and concentrated again. This was repeated. The residue was slurried with a mixture of ether and hexane and the crude product which crystallized was collected (349 g). This was dissolved in 700 ml of methylene chloride, passed through a column containing 700 g of silica gel, and the product was eluted with methylene chloride. Concentration of the eluent gave 258 g of desired product. Recrystallization of the product from ether-methylene chloride gave an analytically pure sample with a melting point of 95-96°C. Using the appropriate aminonitrile and quinoline anhydride in the above process, the following pyrrolopyridine was prepared:

[Table] Reference example 2 5,7-dihydro-α-isopropyl-α-methyl-5,7-dioxo-6H-pyrrolo[3,
4-b] Preparation of pyridine-6-acetamide 298 g of finely divided nitrile was added dropwise to 330 ml of concentrated sulfuric acid with thorough stirring, making sure the temperature did not exceed about 72°C. After addition, increase the temperature to 60~
Adjusted to 65°C and held there for 1 1/2 hours.
The mixture was cooled, quenched with ice, and finally diluted to ca. After adding 454 g of sodium acetate and cooling to 0°C for 2 hours, the mixture was filtered.
The solid was collected and washed twice with 500 ml of water containing sodium acetate, then with water,
All sulfuric acid was removed. Dry the solid, 289g
gave a product of Melting point 176-178℃. A material produced in a similar manner and analytically pure has a melting point of 188
It had a temperature of ~190°C. Using the appropriate pyrrolopyridine-acetonitrile in the above step, the following pyrrolopyridine acetamide was prepared.

[Table] Example 1 3-isopropyl-3-methyl-5H-isodazo[1',2':1,2]pyrrolo[3,4-b]
Preparation of pyridine-3(2H),5-dione A mixture of 50 g of amide and 450 ml of toluene was heated under a Dean-Stark water separator to remove trace amounts of water. To the cooled mixture was added 10.1 g of a 50% suspension of sodium hydride in mineral oil, and the mixture was heated under reflux for 23 hours. The hot solution was filtered and concentrated under reduced pressure to crystallize the residue. The mineral oil was removed by decanting, the solid was washed with hexane, and dried under reduced pressure to give 44.5 g of product, which by NMR analysis was approximately 90% desired isomer and 10% undesired isomer. It was a. Isomerically pure samples were obtained by recrystallization of the crude product from hexane-methylene chloride. Melting point 107-115℃. The cyclization could be carried out in toluene solution with the basic reagents sodium and sodium hydroxide or the acidic reagent p-toluenesulfonic acid. It should be understood that mixtures of products corresponding to the above structural formula and a are obtained and are generally used directly for the preparation of the derived nicotinic acid esters without purification. The imidazopyrrolopyridine described below was prepared using the appropriate pyrrolopyridine carboxamide.

[Table] Example 2 3-isopropyl-5-H-imidazo[2',
Preparation of 2':1,2]-pyrrolo[3,4-b]pyridine-3(2H),5-dione 52 g of 3-[(1-carbamoyl-1,2-dimethylpropyl)] in 400 ml of xylene A mixture containing picolinate, 1.77 ml of 1,2-diazabisic-[5.4.0]-undec-5-ene (DBU) was heated under reflux under a Dean Stark water separator for 2 hours. The mixture was concentrated under reduced pressure and the residue was chromatographed on 400 g of basic alumina. The desired product mixture was eluted with methylene chloride and used without further purification. Example 3 Methyl-2-(isopropyl-5-methyl-4
Preparation of -oxo-2-imidazolin-2-yl)nicotinate To 20 ml of dry methanol in which 10 mg of sodium hydride had already reacted, a mixture of 2.0 g of imidazopyrrolopyridine was added. After stirring for 16 h, 0.03 g of glacial acetic acid was added (to neutralize the base), the solution was concentrated under reduced pressure, and the residue was chromatographed on silica gel in ether, moving relatively quickly. The desired ester material is obtained in several fractions, which are combined, concentrated and crystallized from acetonitrile,
Imidazolinyl nicotinate, melting point 121-123.5℃
gave. An analytically pure sample crystallized from methylene chloride-hexane showed a melting point of 121-122°C. Example 4 Methyl 2-(5-isopropyl-5-methyl-
Preparation of 4-oxo-2-imidazolin-yl) nicotinate This process involves the preparation of the tricyclic compounds of Examples 1 and 2 with the direct preparation of the nicotinic acid ester without isolation: 25 g of amide and 1 ml of 1,5-diaza-bicyclo[5.4.0]undec- in 500 ml of xylene
The mixture of 5-ene (DBU) was heated under reflux for 1 hour under a Dean-Stark water separator. Cool the mixture somewhat, remove the water separator, and add 100
ml of anhydrous methanol was added and the mixture was heated under reflux for 1 hour. The solvent was then removed under reduced pressure and the product was isolated by chromatography as described in Example 3 to give 13.65 g of product, mp 120-122°C. It was identical to that described in Example 3 above. Example 5 Methyl 2-(5-isopropyl 5-methyl-4
-Oxo-2-imidazolin-2-yl) Nicotinate, Method A (Step 11) A mixture of 13.65 g nicotinate and 9.69 g phosphorus pentachloride in 100 ml dry toluene was heated to 80° C. with stirring. . After 1 1/2 hours the thick mixture was cooled, filtered, and the solids were washed with ether and dried. This was the hydrochloride salt of the desired product. This salt was dissolved in 60 ml of water, neutralized with sodium bicarbonate, the precipitate formed was removed by filtration, washed with water and air-dried, resulting in a product identical to that produced by the process of Example 3. gave something. A mixture of 5.0 g nicotinate and 7.1 g phosphorus pentachloride in 40 ml phosphorus oxychloride was stirred at room temperature overnight. The phosphorus oxychloride was removed under reduced pressure and the residue was suspended in 40 ml of toluene and concentrated again. This was repeated. Water (40ml) was added to the residue and the mixture was heated to reflux and kept there for 1 hour. After cooling, the mixture was extracted with methylene chloride, the extracts were dried and concentrated to give 1.05 g of the desired product. The pH of the aqueous phase obtained from the methylene chloride extraction was adjusted to 5 using sodium bicarbonate.
-6 and the mixture was extracted again with methylene chloride. The dried extract was concentrated and the residue was crystallized to give an additional 2.65 g of the desired product identical to that described in Example 3. The following nicotinic acid esters were prepared by one or more of the above methods:

【table】

【table】

【table】

[Table] Example 6 Methyl-2-(5-isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl)
- Preparation of Nicotinate Hydrochloride To a stirred suspension of 3.0 g of the ester of Example 3 in 40 ml of ether was added sufficient methylene chloride to obtain a solution. Dry hydrogen chloride was then passed through the solution for about 20 minutes. 1 hour later
The mixture was filtered to remove the product, which was washed with ether and dried to give 1.90 g of analytically pure hydrochloride salt. It had a melting point equal to 195-196 °C. Example 7 Preparation of 2-(5-isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl)nicotinic acid 22.63 g of the ester of Example 3 in 100 ml of water was charged with 3.29 g in 25 ml of water. of sodium hydroxide was added and the mixture was heated under reflux with stirring for 1.5 hours. After standing overnight at room temperature, 6.8 ml of concentrated hydrochloric acid was added and a heavy precipitate formed. This was removed by filtration, washed with 20 ml of water, then 30 ml of ether and dried to give 19.27 g of acid. Melting point 168-170
℃. This material was dissolved in 350 ml of methylene chloride and filtered (to remove a small amount of isomeric 2-acid).
It was then concentrated to give 17.91 g of pure acid.
Melting point 170-172℃. Analytically pure acid was prepared by recrystallizing the material from acetone-hexane. Melting point 170-172.5℃. Example 8 Preparation of 2-(5-isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl)nicotinic acid To 1.0 g of benzyl ester in 2.0 ml of ethanol was added 50 mg of 5% palladium on carbon. Add catalyst,
The mixture was then shaken under a hydrogen atmosphere until 1 equivalent of hydrogen was absorbed. The catalyst was removed by filtration, the solvent was removed under reduced pressure, and the residue was crystallized from acetone-hexane to give the acid described in Example 7. The following acids were prepared by the above method:

Table Example 9 Preparation of calcium 2-(5-isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl)nicotinate 0.98 g of Example 7 partially dissolved in 10 ml of water 0.18 g of calcium carbonate was added to the acid with stirring. After 10 minutes the solution was filtered, concentrated and the residue treated with ether to give a crystalline product which was dried at 40° C. and 25 mm pressure to give 0.88 g of calcium salt. Melting point 265℃. Sodium, diisopropylammonium and triethylammonium salts were prepared in a similar manner. By the method described above, the following salts can be prepared using suitable acids and selected oxides, carbonates, carbonates or hydroxides of metals, alkali metals, alkaline earth metals, ammonia or aliphatic amines. Ta.

【table】

【table】

[Table] Reference Example 3 Production of methyl 2-[(carbamoyl-1,2-dimethyl-propyl)carbamoyl]nicotinate Sodium hydride (0.47 g of a 50% suspension in mineral oil) was reacted with 500 ml of dry methanol under nitrogen. To this was added 51.4 g of the amide of Example 2,
The mixture was then stirred at room temperature overnight. The mixture was concentrated, the residue was dissolved in methylene chloride, and the solution was washed first with 150 ml of water and then with 150 ml of brine. After drying (Na ₂ SO ₄ ), the organic phase was concentrated and the residue was crystallized to give 47.85 g of product, which was analytically pure. melting point 108
~145℃ (decomposition). Reference Example 4 Production of methyl 3-[1-carbamoyl-1,2-dimethylpropyl)carbamoyl]picolinate 25.5 g of acid chloride [(Helv.Chem.Acta, 34, 488 (1951)]) in 200 ml of methylene chloride and 29.7 ml
13.93 g of U.S. Pat. No. 4,017,510 under nitrogen to a stirred mixture containing triethylamine.
A solution containing an aminoamide, such as that disclosed in , was added dropwise at such a rate that the temperature of the reaction mixture was maintained below 30°C. After 1 hour, the mixture was filtered, the solids washed with methylene chloride and dried to give 19.8 g of product. melting point
176-177℃ (decomposition). The sample recrystallized from nitromethane had a temperature of 196-196.5°C (decomposed) and was analytically pure. Reference example 5 5,7-dihydro-α-isopropyl-α-methyl-5,7-dioxo-6-H-pyrrolo[3,4-b]pyridine-6-acetic acid (-isomer)
Manufacturing of To a stirred suspension of 18.4 g of anhydride in 760 ml of dry acetone was added 16.2 g of (+)− under nitrogen.
Methylvaline was added. After stirring at room temperature for 48 hours, the mixture was filtered and the liquid was concentrated to give the crude intermediate product. This material was dissolved in 500 ml of acetic anhydride, a catalytic amount of sodium acetate was added and the mixture was stirred at room temperature for 5 hours. After heating under reflux for 1.5 hours, the mixture was concentrated.
The residue was dissolved in ethyl acetate and washed with water. The dried extract was concentrated to give a thick syrup. The sample was dissolved in ethyl acetate, treated with charcoal, filtered, and concentrated. The residue was crystallized from methylene chloride to give the product. Melting point 122-125℃ [α] ²⁵ _D = -7.73℃ (c = 0.100,
THF). By essentially the same process and using the appropriate starting quinoline anhydride and amino acid, the following amide was prepared.

[Table] Reference example 6 5,7-dihydro-α-isopropyl-α-methyl-5,7-dioxo-6H-pyrrolo[3,
Production of 4-b]-pyridine-6-acetamide To a mixture containing 32 g of (-)-acid in 375 ml of toluene were added 2 ml of dimethylformamide followed by 13 ml of thionyl chloride. After heating under reflux for 1.25 hours, the mixture was concentrated under reduced pressure. The residue was dissolved in 350ml of tetrahydrofuran, cooled to 0°C and a slight excess of gaseous ammonia was bubbled into the mixture. The solvent was removed under reduced pressure leaving a solid that was washed with water and air dried. A portion of this solid was crystallized twice from ethyl acetate (with charcoal treatment) to give the desired product as a white crystalline solid. Melting point 188-189℃, [α] ²⁵ _D = +3.59 (c =
0.79, DMSO). The following amides were prepared by essentially the same method and using the appropriate acids.

[Table] Reference example 7 5-Butyl-N-(1-carbamoyl-1,2
-Production of dimethylpropyl)picolinamide To a suspension of 20 g of acid in 200 ml of dry tetrahydrofuran was added 10.7 ml of ethyl chloroformate with stirring. Cool the mixture to −10 °C and 17.1
ml of triethylamine was added dropwise in such a way that the temperature did not exceed 0°C. After 10 minutes, a solution containing 14.3 g of aminoamide in 150 ml of dry tetrahydrofuran was added dropwise at 0° C. with stirring. The mixture was allowed to reach room temperature and after 2 hours enough water was added to dissolve the solids. Tetrahydrofuran was removed under reduced pressure.
The aqueous residue was extracted with ethyl acetate and again after saturation with salts. The organic phases were combined, washed with brine, dried and concentrated. The remaining oil crystallized. A portion was crystallized first from methylene chloride-hexane and then from ether-hexane to give analytically pure product. Melting point, 83-86°C. The following picolinic acid was prepared using essentially the same method as described above.

[Table] Reference example 8 2-(5-butyl-2-pyridyl)-5-isopropyl-5-methyl-2-imidazoline-4-
on manufacturing A stirred suspension of sodium hydride (2.4 g) in 250 ml of dry toluene was heated under reflux with stirring under a Dean Stark water separator. To this mixture was slowly added 26.52 g of diamide. Heating was continued for 1.5 hours after addition. After standing overnight, the reaction was quenched with water, the PH was adjusted to 5 using hydrochloric acid, and the phases were separated. The aqueous phase was extracted twice more with ethyl acetate and the organic extracts were combined, washed with brine, dried and concentrated. The residue was recrystallized from hexane to give the pure product. Melting point 60-62℃. The following imidazolinones were prepared using essentially the same process.

[Table] Example 10 Production of 5-butyl-2-(5-isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl)nicotinic acid To a stirred solution containing 10.0 g of imidazolinone in 100 ml of dry tetrahydrofuran at -76° and under nitrogen, 47.3 ml of a 1.7 M solution of methyllithium in ether was added dropwise.
The mixture began to become very thick and then 2 ml of hexamethylphosphoramide and about 150 ml of tetrahydrofuran were added. The mixture was warmed to -10°C and held at this temperature for 0.75 hours. The mixture was cooled to -70° and added to a slurry of carbon dioxide in tetrahydrofuran. After stirring for 0.5 hours,
Water was added to the mixture, the PH was adjusted to 2 using dilute sulfuric acid, and the product was extracted into methylene chloride.
The extracts were washed with brine, dried, and concentrated to give the product as a yellow solid. Recrystallization from methylene chloride-hexane gave an analytically pure sample. Melting point 152-154℃. Using essentially the same steps as above, but with 2-(5
-butyl-2-pyridyl)-5-isopropyl-
Substituting the appropriate imidazolinone for 5-methyl-2-imidazolinone and using dimethylformamide and methyl iodide and carbon dioxide as subreagents, the following imidazolinone was prepared.

[Table] Example 11 Production of 2-(5-isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl)-3-pyridineacetic acid Using essentially the same process as described in Example 10, but with 5-isopropyl-5-methyl-
5-isopropyl-instead of 2-(5-n-butyl-2-pyridyl)-2-imidazolin-4-one
5-Methyl-2-(3-methyl-2-pyridyl)-
Using 2-isodazolin-4-one, the desired pyridine acetic acid was obtained. Melting point 173 (decomposed). Example 12 Methyl-2-(5-isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl)
-Production of 6-phenoxy nicotinate A solution of the acid in ether was treated with excess diazomethane. After a few minutes, excess diazomethane was removed by warming. The solvent was removed and the residue was crystallized from ether-hexane to give the desired methyl ester. Melting point 128-131℃. The following methyl esters were prepared starting from the appropriate acids using essentially the same conditions as above.

[Table] Reference example 9 4-[2-(5-isopropyl-5-methyl-4
-Production of oxo-2-imidazolin-2-yl)nicotinoyl]morpholine 150 ml toluene and 0.45 ml 1,8-diazabicyclo[5,4,
0] The amide was cyclized by heating 7.83 g of the amide in undec-7-ene under a Dean-Stark water separator for 2 hours. 4ml excluding separator
of morpholine was added and heating continued for 3 hours. The mixture was concentrated and the residue was chromatographed on silica gel in ethyl acetate. The product was first eluted and this material was recrystallized from ether-hexane to give the pure amide. Melting point 143-145.5℃. Example 13 The following amide was prepared by using an appropriate ammonium in place of morpholine in Reference Example 9.

[Table] Example 14 Production of N-(2-chloroethyl)-2-(5-isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl)nicotinamide A mixture containing 4.04 g hydroxyethylamine and 8.2 ml thionyl chloride in 250 ml methylene chloride was heated under reflux for 3.5 hours. The mixture was cooled, poured into water, and the aqueous phase was made basic with sodium carbonate. The mixture was shaken, the organic phase was separated, washed with water, dried, and concentrated to leave a white solid that was recrystallized from toluene to give the desired chloroethylamide in the form of a white crystalline solid. Ta. It partially catalyzed at 128.5°C and completely melted at 157°C. Example 15 Preparation of 2-(5-isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl)nicotinamide A solution containing 10.0 g of ester in 50 ml of tetrahydrofuran was added to 100 ml of a glass bomb.
of liquid ammonia. The bomb was sealed and the contents heated to 100°C for 16 hours. After cooling,
Ammonia was evaporated and the residue was concentrated.
This residue was combined with material from a similar reaction using 5g and 7g of ester. These were crystallized from ethyl acetate to give 5g of product.
The liquid is concentrated after treatment with charcoal and further
It gave 15.7g of product. Recrystallizing the sample twice from ethyl acetate gives
Pure nicotinamide was provided as a white crystalline solid. Melting point 178-182℃. Example 16 Preparation of 2-(5-isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl)nicotinonitrile To 75 ml of ice-cold tetrahydrofuran was added 12 ml of titanium tetrachloride in 20 ml of carbon tetrachloride with stirring under nitrogen at a rate such that the temperature did not exceed 5°C. Then 5.2 g of amide in 75 ml of tetrahydrofuran were added, again keeping the temperature <5°C.
Finally, 17 ml of triethylamine in 5 ml of tetrahydrofuran was added to the mixture under the same conditions.
After 1.5 hours at 5°C, the mixture was stirred at room temperature overnight. Water (100ml) was carefully added at 0°C, the upper organic phase was separated and the aqueous phase was extracted with methylene chloride (4 x 100ml). The extracts were combined, washed with brine, dried, and concentrated. The solid residue was recrystallized from hexane-methylene chloride to give nicotinonitrile as a brown solid. Melting point 144-148°C The analytically pure compound had a melting point of 148-150°C. Reference example 10 2-[5-(hydroxymethyl)-2-pyridyl]
-Production of 5-isopropyl-5-methyl-2-imidazolin-4-one To a stirred slurry of 23 g of lithium aluminum hydride in 250 ml of tetrahydrofuran was added dropwise under nitrogen at -70 DEG C. 46.8 g of the ester in 350 ml of tetrahydrofuran. The mixture was warmed to room temperature, 73 ml of saturated ammonium chloride solution was carefully added with vigorous stirring, the mixture was filtered and the solid was washed with tetrahydrofuran. When the liquid was condensed, rubber remained. This was chromatographed on silica gel and the product was eluted with ethyl acetate. Melting point 101-104℃. Reference Example 11 Production of 2-[5-(tertiary-butyldimethylsiloxy)-methyl-2-pyridyl]-5-isopropyl-5-methyl-2-imidazolin-4-one To a stirred solution containing 2.03 g alcohol in 3.5 ml dimethylformamide under nitrogen was added 0.68 g imidazole, then 3.1 g
of t-butyl-dimethylsilyl chloride was added. The mixture was kept at 35°C for 10 hours and at room temperature for 10 hours. Saturated sodium sulfate was added and the aqueous mixture was extracted with ether. The extracts were washed with brine, dried and evaporated. The pure product was isolated by chromatography of the crude product on silica gel and eluting with methylene chloride and then ether. Example 17 Preparation of 5-(hydroxymethyl)-2-(5-isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl)nicotinic acid A solution containing 0.29 g of silyl ether in 10 ml of 80% aqueous acetic acid was heated on a steam bath for 0.5 h. The mixture was concentrated and the residue was dried azeotropically using toluene. The gummy residue was crystallized from methylene chloride-hexane. The pure product had a melting point of 170-171.5°C. Example 18 Preparation of methyl 2-(1-acetyl-4-isopropyl-4-methyl-5-oxo-2-imidazolin-2yl)nicotinate A solution containing 10 g of methyl 2-(5-isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl)nicotinate in 100 ml of acetic anhydride was heated under reflux for 16 hours. The mixture was concentrated and the residue was crystallized from ether-hexane to give the N-acetyl derivative. Melting point 88-90
°C, which was the melting point of analytically pure material. Using essentially the same conditions as described above, the appropriate imidazolinyl nicotinate is converted to the appropriate acyl anhydride, acyl halide, sulfonyl halide,
The following N-substituted imidazolinones were prepared by reacting with alkyl halides or sulfates either alone or in a solvent such as pyridine or toluene.

【table】

[Table] Example 19 Production of methyl 2-(1-acetyl-4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)nicotinate-1-oxide 40 g (126 mmol) in 500 ml methylene chloride
of nicotinate in a solution containing 30 g of 80
~90% pure m-chloroperbenzoic acid (139 mmol based on 80% purity) was added. After heating under reflux overnight, excess peracid was destroyed by addition of excess 1-hexene. The solution was washed with saturated sodium bicarbonate solution, dried, and concentrated. The residue was crystallized from methylene chloride-hexane-ether to give 18.3 g of the desired N-oxide.
Melting point 92-100℃. The analytically pure N-oxide had a melting point of 95-99°C. Example 20 Methyl 2-(5-isopropyl-5-methyl-
Production of 4-oxo-2-imidazolin-2-yl)nicotinate-1-oxide About 0.5 g of sodium methoxide was added to a solution of 30 g of N-acetyl compound in 200 ml of methanol. After stirring for 2 hours, the product was filtered off and air dried. Melting point 197-201℃. Acetone-
An analytically pure sample recrystallized from hexane had a melting point of 200-201°C. Example 21 Methyl 6-chloro-2-(5-isopropyl-
5-Methyl-4-oxo-2-imidazoline-
Production of 2-yl) nicotinate A solution containing 22.0 g of N-oxide in 135 ml of phosphorus oxychloride was heated under reflux for 4 hours. After standing overnight at room temperature, excess phosphorous oxychloride was removed under reduced pressure and the residue was treated with xylene and concentrated again. The residue was dissolved in methylene chloride, treated with water, the PH was adjusted to 5 with sodium carbonate, and ether was added to top the organic phase. The phases were separated and the aqueous phase was re-extracted twice with ether. The organic phases were combined, washed with brine, dried and concentrated. The residue was chromatographed on 250 g of silica gel in a mixture of ether and hexane to give 10.6 g of the desired product. This was recrystallized from ether hexane to give 8.95 g of 6-chloro derivative. Melting point 104-106℃. An analytically pure sample is
Melted at 102.5-104.5°C. Example 22 Preparation of 6-chloro-2-(5-isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl)nicotinic acid A suspension of 3.0 g of ester in 5.8 ml of 2N sodium hydroxide, 5 ml of water and 3 ml of methanol was
Warming to °C gave a clear solution. After stirring the solution for 3 hours it was cooled, extracted with ether and the organic phase was discarded. Adjust the pH of the aqueous phase to 2 using 6N hydrochloric acid.
and then add sodium bicarbonate solution
The pH was set to 4. The aqueous phase was extracted twice with methylene chloride, the pH of the aqueous phase was adjusted to 2, and extracted again twice with methylene chloride. The organic phases were combined, dried, concentrated and the residue was crystallized from methylene chloride-hexane to give analytically pure acid. Melting point 154-157℃. Following the above process but using 5-bromoester instead of 6-chloroester, 5-bromo-2-(5-isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl)nicotinic acid was generated. Melting point 211-213℃. Reference Example 12 Production of 6-(benzyloxy)-2-(5-isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl)nicotinic acid To 2 ml of sodium hydride (from 0.34 g of 50% sodium hydride in oil) in 2 ml of N-methylpyrrolidone was added 2 ml of benzyl alcohol under nitrogen with stirring. After the alkoxide formation is complete, add 0.6 g of chloroacid and mix the mixture.
It was heated to 165-175° for 5 hours. After cooling, dilute the mixture with water and adjust its PH to
The pH was adjusted to 1 using 1N hydrochloric acid and then brought back to 8 using saturated sodium bicarbonate. The mixture was extracted twice with ether and the ether was discarded. Adjust the pH of the aqueous phase to 5 and use methylene chloride to
Extracted 6 times. The extracts were combined, dried, and concentrated. Crystallization from ether-hexane gave the 6-benzyloxy derivative. melting point 205
~207℃. Example 23 Using essentially the same conditions as above, and using the appropriate 4- or 6-chloro-2-(5-isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl)nicotinic acid and Using the appropriate sodium alkoxide, phenoxide or thioalkoxide, the following imidazolinylnicotinic acid was prepared.

[Table] Example 24 4-hydroxy-2-(5-isopropyl-5
-Methyl-4-oxy-2-imidazoline-2
-yl)nicotinic acid production 1.55 g of benzyloxy derivative was slowly added to 15 ml of concentrated sulfuric acid while stirring. To this mixture was added 7 ml of ethylene dichloride. After 16 hours at room temperature, the mixture was poured onto ice, the PH was adjusted to 4 with dilute sodium hydroxide, and extracted with ethyl acetate. The extracts were dried and concentrated to give a brown solid, which was recrystallized from methylene chloride-ether. Melting point 210-211℃. Example 25 2-isopropyl-2-methyl-5H-imidazo-[1',2':1,2]pyrrolo[3,4-b]
Production of pyridine-3(2H), 5-dione To a solution containing 50.9 g of dicyclohexylcarbodiimide in 600 ml of dry methylene chloride was added, with stirring, 60 g of acid at a rate such that the temperature did not exceed 32°C. After stirring for 2.5 hours at room temperature, the mixture was filtered and the liquid was concentrated to give a white solid. This solid was recrystallized from methylene chloride to give 57.4 g of dione. Melting point 125~
128.5℃. The analytically pure dione melted at 132-134°C. Reference Example 13 Production of acetone oxime ester of 2-(5-isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl)nicotinic acid 0.6 g of acetoxime was added to a solution containing 2.0 g of 3,5-dione in 15 ml of toluene. The mixture was heated to 50-60°C for 2.75 hours and stirred. After stirring overnight at room temperature, the solvent was removed and the residue was purified on silica gel with 10% acetonitrile in methylene chloride and then in methylene chloride.
Chromatographed using 30% acetonitrile as eluent. The toluene was removed from the fraction containing the product and the product was collected. This was recrystallized from methylene chloride-hexane to give the oxime ester analytically. melting point
117-119.5℃. 2,2,2− in essentially the same way
An ester was prepared from trichloroethanol. Melting point 114-116. Example 26 2-(3-acetyl-2-pyridyl)-5-isopropyl-5-methyl-2-imidazoline-4
- Manufacture of on To a stirred solution containing 10.0 g of dione in 100 ml of dry tetrahydrofuran under nitrogen and at -78°C was added dropwise 15.1 ml of a 3M solution of methylmagnesium bromide in ether. A temperature of <-60°C was maintained during the addition.
After the addition, stirring was continued at −78° C. and the mixture was then slowly warmed to room temperature. The mixture was diluted with an equal volume of water, the PH was adjusted to 4 using glacial acetic acid, and extracted three times with methylene chloride. The extracts were combined, dried, and concentrated. The residue was chromatographed on silica gel with ether. Concentration of the appropriate fractions gave 6.1 g of product in the form of a crystalline solid. Melting point 104-108℃. Analytically pure samples had melting points of 103-105°C. Using essentially the same process as above but substituting phenyllithium or sodium trimethylphosphonoacetate for methylmagnesium bromide, the following imidazolinones were prepared.

【table】 \
p( _OCH3 ) ₂ 131.5−134
‖
O
Example 27 2-[3-[hydroxymethyl)-2-pyridyl]
-Production of 5-isopropyl-5-methyl-2-imidazolin-4-one Add 0.32 g of sodium borohydride to a stirred solution of 25 ml of absolute ethanol at 0°C.
A solution containing 2.0 g of dione in 25 ml of dry tetrahydrofuran was added with stirring over a period of 10 minutes. The mixture was then stirred for a further 3 hours at room temperature. The mixture was poured into 200ml of ice water, extracted with methylene chloride, the extracts were dried and concentrated. The residue was crystallized from methylene chloride-hexane to give the desired product. The analytically pure sample had a melting point of 145-149°C. Reference example 14 1,3-dihydro-α-isopropyl-α-methyl-1,3-dioxo-2-H-pyrrolo-
[3,4-b] Production process A of quinoline-2-acetonitrile Anthranyl (59.6 g, 0.5 mol) was treated with α-isopropyl-α-methyl-2,5-dioxo-3-pyrroline-1-acetonitrile in o-dichlorobenzene (450 ml) over 45 minutes with stirring under nitrogen. was added dropwise to the refluxing solution. After 18 hours the reaction mixture was cooled and methylene chloride was added. This solution was passed through a 3 inch silica gel column by elution with methylene chloride. The eluent was concentrated to 500ml and hexane was added.
A precipitate forms, which is separated and air-dried.
110.6 g (75%) of product was produced as a light brown solid. Crystallization from ethyl acetate-hexane gave flame yellow crystals. Melting point 195-196℃. Analysis: Calculated _{for C17H15N3O2 :} C, _69.61 ;
H, 5.15; N, 14.33. Actual value: C, 69.37; H,
5.15; N, 14.43. Compounds in Table 1 were prepared using similar conditions. Step B Cyclization of o-formylanilino-maleimide p-Toluenesulfonic acid (0.3g, 0.0016mol)
N-(1-
Cyano-1,2-dimethylpropyl)-2-(o-
formylanilino) maleimide (7.19g, 0.023
mol) solution was heated to reflux for 4 hours using a Dean-Stark trap to collect the removed water. The reaction was cooled, evaporated under reduced pressure, and dissolved in hot ethyl acetate, which was passed through a 3 inch silica gel column. The eluted ethyl acetate fractions were combined to yield 5.51 g (81%) of a solid 1,3-dihydro-α-isopropyl-α-methyl-1,3-dioxo-2-H-pyrrolo[3,4
-b] gave quinoline-2-acetonitrile.
Melting point 195-195.5℃. Other compounds prepared by this method are shown in the table. Reference Example 15 Step C 1,3-dihydro-α-isopropyl-α-methyl-1,3-dioxo-2-H-pyrrolo[3,4-b]-4-acetoxyquinoline-2-
Production of acetonitrile N-[1-(1-cyano-1,2-dimethylpropyl)-2,5-dioxo-3-pyrroline-3-
A solution of ylanthranilic acid (3.27 g, 0.01 mol) in acetic anhydride (20 ml) was treated all at once with triethylamine (10 ml) and dimethylaminopyridine (0.122 g, 0.001 mol). 2.5 under nitrogen
After stirring for 1 hour at °C, the reaction was poured into ice water. A solid formed and passed. Purification was accomplished by resuspending in ether, filtering and drying. Yield 2.54 g (72%) product. Melting point 145-151℃. m+l/e=352.

【table】

[Table] Reference Example 16 Production of 1,3-dihydro-α-isopropyl-α-methyl-1,3-dioxo-2-H-pyrrolo[3,4-b]quinoline-2-acetamide 1,3-dihydro-α-isopropyl-α-methyl-1,3-dioxo-2-H-pyrrolo[3,
4-b] Quinoline-2-acetonitrile (0.44
g, 0.0015 mol) in concentrated sulfuric acid (5 ml) at room temperature.
and stirred overnight. When the reaction mixture was poured onto crushed ice (50 ml), a white precipitate formed, which was separated and washed with water, aqueous bicarbonate solution and water.
Next, it was dried under reduced pressure. This gave 0.34 g (74%) of product. Melting point 237-239°C (decomposition). Analysis, calculated _{value for C17H17H3O3} : C, _65.58 ;
H, 5.50; N, 13.50, Actual value: C, 65.03; H,
5.63; N, 13.19. The following compounds were prepared in the same manner as above.

【table】

[Table] Example 28 Production process A of 2-(5-isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl)-3-quinolinecarboxylic acid 1,3-dihydro-α-isopropyl-α-methyl-1,3-dioxo-2-H-pyrrolo[3,
4-b] Quinoline-2-acetamide [5.76g,
sodium hydride (1.33 g, 0.0278 mol) in dry xylene (600 ml)
50% oil dispersion was added and the mixture was heated to reflux and the reaction mixture began to become homogeneous. After 3 hours under reflux, the reaction was left at room temperature overnight, then methanol (15 ml) containing sodium methoxide (0.1 g) was slowly added and warmed under reflux for 1 hour. The mixture was filtered hot and the organic solvent was stripped to give an oil and solid. A methylene chloride-water mixture was shaken with the above residues until they were dissolved. The aqueous layer (200ml) was separated and slowly acidified using acetic acid (5ml). A precipitate of product formed and was collected by filtration to give 3.91 g (72%).
Melting point 219-224℃. Recrystallization from hexane-ethyl acetate gave mp 219-222°C (decomposed). Analysis, calculated values for C ₁₇ H ₁₇ N ₃ O ₃ : C,
65.58; H, 5.50; N, 13.50, Actual value: C,
65.09; H, 5.50; N, 13.59. This example was used to prepare the examples below. However, it is also possible to simply add methanol and water (be careful of hydrogen evolution) to the xylene layer without stripping the xylene through the insolubles to avoid ester formation.

【table】

【table】

[Table] Example 29 Ethyl-2-(5-isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl)
-Production process A of 3-quinolinecarboxylic acid 2-isopropyl-2-methyl-5-H-imidazo[1',2':1,
2=pyrazolo[3,4-b]quinoline-3H
(2H), 5-dione (2 g, 0.0068 mol) under nitrogen was added 50% sodium hydride (0.34 g, 0.00716 mol) with ice cooling. Gas generation was observed. After 10 minutes, the reaction was neutralized with aqueous ammonium chloride, stripped, and partitioned between water and ethyl acetate. Separate the organic layer;
Dry over anhydrous magnesium sulfate, filter, strip, and the residue crystallize from ethyl acetate-hexane to give 1.38 g (60%) of a white solid. Melting point 146-147.5℃. The esters listed in the table below were produced in a similar manner. Example 30 Methyl-2-(5-isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl)
-Production process B of 3-quinolinecarboxylic acid 50% sodium hydride oil dispersion (1.4g,
1,3-dihydro-α-isopropyl-α-methyl-1,3-dioxo-2-H-pyrrolo[3,4
-b] Quinoline-2-acetamide (6 g,
0.0193 mol). The mixture was heated and stirred under reflux for 6 hours, cooled and slowly quenched with a solution of sodium methoxide (0.1 g) in methanol (20 ml). After heating to 60°C for 3 hours, the mixture was filtered and the liquid was stripped to give a white solid, which was dissolved in the methylene chloride-water mixture. The organic layer was separated and stripped to give 0.48 g of solid, which was purified by passing through a pad of silica gel using ethyl acetate as the solvent. After removal of the solvent, the solid residue is crystallized from ethyl acetate-hexane.
This gave 0.4 g of white needles of the desired ester. Melting point 145-154℃. Analyzed, calcd _{for C18H19N3O3} : C, _66.44 ; _H , 5.89; N, 12.92. Actual value, C, 66.35; H, 5.93; N, 12.83.

[Table] Example 31 Acid salt of quinoline carboxylic acid ester: Methyl 2-(5-isopropyl-5-methyl-
4-oxo-2-imidazolin-2-yl)-
Preparation of the hydrochloride salt of 3-quinolinecarboxylic acid A solution of the ester is dissolved in an ether-methylene chloride solution, and dry hydrogen chloride is passed through the solution until all the solid hydrochloride salt is formed, and the ether and dried under reduced pressure. Melting point 226-270℃. In a similar manner, substituting the appropriate acid, but partially hygroscopic oil, and using ethyl acetate as the preferred solvent for the acid salt, the following salts can be prepared.

[Table] Example 32 Production of sodium 2-(5-isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl)-3-quinolinecarboxylic acid 2-(5-isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl)-3-quinolinecarboxylic acid (2.33 g, 0.0075 mol) containing sodium hydride (0.3 g, 0.0075 mol) The solution in water (22 ml) was stirred at room temperature overnight, then washed with methylene chloride, the aqueous layer was separated and
It was then evaporated to an orange solid, which was washed with ether and air dried. The dihydrate salt product was obtained as a cream colored solid. Melting point 235-250℃
(Disassembly). Analysis, calculated values for C ₁₇ H ₁₆ N ₃ O ₃ Na + 2H ₂ O: C, 55.27; H, 5.45; N, 11.37; Na,
6.22. Actual value: C, 55.56; H, 5.31; N,
11.35; Na, 6.30. The following salts were prepared in a similar manner substituting sodium hydroxide. The compounds produced by this method are listed in the table.

[Table] Example 33 2-isopropyl-2-methyl-5-H-imidazo[1',2':1,2]-pyrazolo3,4-b
Production process A of quinoline 3(2H), 5-dione, 2-isopropyl-2-methyl Dicyclohexylcarbodiimide (3.47 g, 0.0168 mol) in methylene chloride was diluted with 2-
(5-isopropyl-5-methyl-4-oxo-
2-Imidazolin-2-yl)-3-quinolinecarboxylic acid (5.24 g, 0.0168 mol) was added to a stirred suspension of methylene chloride at room temperature overnight. Since the reaction was incomplete, further
Add 0.3 g of dicyclohexylcarbodiimide,
The mixture was then stirred for an additional 48 hours. The reaction mixture was evaporated to a yellow solid and purified by chromatography on a silica gel column. The product was eluted with acetonitrile-methylene chloride to give a white solid which was crystallized from toluene. Melting point, 225-227°C. Analysis, calculated values _{for C17H15N3O2} : C, _69.61 ; _H , 5.15; N, 14.33;
Actual values: C, 69.76; H, 5.31; N, 14.13. Reference example 17 Step B Cis and trans 1,11b-dihydro-11b-
Hydroxy-3-isopropyl-3-methyl-
Production of 5-H-imidazo[1',2':1,2]pyrrolo[3,4-b]quinoline-2(3H), 5-dione 1,3-dihydro-α-isopropyl-α-methyl-1,3-dioxo-2-H-pyrrolo[3,
4-b] Quinoline-2-acetamide (0.5g,
A solution of 0.0016 mol) was heated to reflux in xylene for 23 hours. Upon cooling, 0.17 g white solid, mp 191-192°C. precipitates, and by diluting the liquid with hexane an additional 0.1 g, melting point
187-189°C was obtained. Analysis, calculated values _{for C17H17N3O3} : C, _65.58 ; _H , 5.50; N, 13.50;
Actual values: C, 66.08; H, 5.65; N, 13.00. Example 34 Other tricyclic compounds were obtained in a manner similar to steps A and B above. Examples of tricyclic compounds:

[Table] Reference Example 18 Production process A of N-(1-cyano-1,2-dimethylpropyl-2-(o-formylanilino)maleimide) anthranyl (3.55 g, 0.0298 mol) and α-
Isopropyl-α-methyl-2,5-dioxo-
3-pyrroline-1-acetonitrile (5.73g,
A solution of 0.0298 mol) in xylene (20 ml) was heated to reflux under nitrogen for 39 hours. Upon cooling, a yellow precipitate formed which was separated to give 2.78 g of product, mp 191-192°C. Analyzed, calcd _{for C17H17N3O3} : C, _65.58 ; _H , 5.50; N, 13.50. Actual values: C, 65.33; H, 5.44; N, 13.36. Reference example 19 Step B N-(1-cyano-1,2-dimethylpropyl)
-2-(2-formyl-5-chloroanilino)
Manufacture of maleimide Pyridinium chlorochromate (4.4 g, 0.0204 mol) in methylene chloride (20 ml) was dissolved in N-(1-
Cyano-1,2-dimethylpropyl)-2-(5-
Chloro-2-hydroxymethylanilino)maleimide (4.75 g, 0.0136 mol) in methylene chloride (20
ml) solution. After 2 hours the thick reaction mixture was diluted with ether (20ml) and a yellow precipitate formed which was separated. This solid was redissolved in ethyl acetate:methylene chloride (1:1) and passed through a silica gel column, 4.31 g (92
%) of a yellow solid. Melting point: 80℃ (decomposition). The following aldehydes shown in the table were prepared according to steps A or B.

【table】

[Table] Reference example 20 N-(1-cyano-1,2-dimethylpropyl)
-Production of 2-(2-hydroxymethylanilino)maleimide o-Aminobenzyl alcohol (2g, 0.0125
mole) and 3-bromo-α-isopropyl-α-
Methyl-2,5-dioxo-3-pyrroline-1-
In acetonitrile (2.7 g, 0.01 mol), 3 g
Absolute ethanol (100 ml) containing a 5A grinding sieve was added. The mixture was stirred at room temperature for 20 hours. The solvent was removed and the residue was passed through a silica gel drying column with eluent ether-hexane (2:
1). The starting bromomaleimide was recovered first, followed by 1.89 g (60%) of a bright yellow solid, mp 39-45°C. Analysis, calcd for C ₁₇ H ₁₉ N ₃ O ₃ : C, 65.16;
H, 6.11; N, 13.41. Actual value: C, 65.94; H,
6.21; N, 12.87. Other compounds were prepared using various substituted o-aminobenzyl-alcohols by the method described above. Substituting i-propanol or t-butanol for ethanol generally improves product yields and also allows the use of bases as acid acceptors.

[Table] Reference example 21 3-bromo-α-isopropyl-α-methyl-
Production of 2,5-dioxo-3-pyrroline-1-acetonitrile α-isopropyl-α-methyl-2,5-dioxo-3-pyrroline-1-acetonitrile (50 g, 0.25 mol) in acetic acid (500 ml) heated to 75°C
Bromine (40.76 g,
0.255 mol) was added dropwise with stirring. The reaction was kept at 85° overnight and evaporated to syrup.
Dissolve this in methylene chloride (300ml) and
Cool to °C and add triethylamine (34.78ml) to it.
added. After stirring for 2 hours, the brown methylene chloride solution was diluted with ether and a white precipitate formed. This was extracted with water (400ml) and the organic layer was dried over anhydrous magnesium sulfate and then passed through a 2 inch bed of silica gel eluting with methylene chloride.
The eluent was obtained as a dark brown oil. analysis,
Calculated value for C ₁₀ H ₁₀ N ₂ O ₂ Br: C, 44.29; H,
4.09; N, 10.33. Actual value: C, 43.37:H,
4.05; N, 10.07. Other bromomaleimides were prepared in a similar manner.

【table】

[Table] Reference Example 22 Production of α-isopropyl-α-methyl-2,5-dioxo-3-pyrroline-1-acetonitrile N-(1-cyano-1,2-dimethylpropyl)
- A solution of maleic acid (595 g, 2.83 mol) in acetic anhydride (3.96) containing sodium acetate (13.72 g, 0.167 mol) is heated under reflux for 1 hour, cooled and the solvent removed under reduced pressure. Removed. Distill the product at 120-130℃/0.1mm ^* ,
Yielded 337g (63%) of product. *The container temperature is
Do not exceed 200°. Analyzed _{, calcd for C10H12N2O2} : C, 62.49; H, 6.29; N, 14.57.
Actual values: C, 62.32; H, 6.36; N, 14.59. The following compounds were prepared in a similar manner.

【table】

[Table] Reference example 23 N-[1-(1-cyano-1,2-dimethylpropyl)-2,5-dioxo-3-pyrroline-3
-yl]anthranilic acid production Anthranilic acid (13.7 g, 0.1 mol), 3-bromo-α-isopropyl-α-methyl-2,5-dioxo-3-pyrroline-1-acetonitrile (27
g, 0.1 mol), isopropanol (200 ml) and sodium acetate (8.2 g) was stirred at room temperature for 3 days and then heated to reflux for 1 hour. Cooling and addition of ether gave 31.6 g (97.7%) of a yellow solid, mp 262-266° C., after crystallization from acetic acid. Analysis, calculated values for C ₁₇ H ₁₇ N ₃ O ₄ : C,
62.37; H, 5.24; N, 12.84. Actual value: C,
62.24; H, 5.19; N, 12.70. Other maleimides could also be produced in a similar manner.

[Table] Reference Example 24 Production of N-(1-carbamoyl-1,2-dimethylpropyl)-quinaldamide Quinaldic acid (20g,
methyl chloroformate (8.92 ml, 0.116 mol) in tetrahydrofuran (500 ml)
and then triethylamine (18.4ml, 0.139mol) was added. After 20 minutes α-isopropyl-α-
Methyl-3-pyrroline-1-acetamide (15.1
g, 0.116 mol) was added and the mixture was stirred at room temperature overnight. Water was added and the solution was reduced to 200ml on a rotorvap. A white solid precipitated and was separated, washed with water and dried. Recrystallization from absolute ethanol gave 26.86 g (87%) of product. Melting _point 179-180<0>C, anal. _calcd for _C16H19N3O2 : C, 67.34; _H , 6.73; N, 14.72. Actual values: C, 67.14; H, 6.17; N, 14.72. Other quinoline carboxamides could also be produced in a similar manner.

[Table] Reference Example 25 Production of α-isopropyl-α-methyl-2,5-dioxo-3-pyrroline-1-acetamide α-isopropyl-α-methyl-2,5-dioxo-3-pyrroline-1-acetonitrile (2.0
g, 0.104 mol) in methylene chloride (30 ml) was added in a fine stream to the concentrated sulfuric acid at room temperature. After stirring overnight at room temperature for 16 hours, the mixture was poured onto ice containing sodium chloride and ethyl acetate. The organic layer was washed with aqueous sodium bicarbonate solution, brine, and dried. After washing with etherpentane and evaporation, a solid (72
%) was given. Melting point 138.5-140℃. analysis,
Calculated value for C ₁₀ H ₁₄ N ₂ O ₃ : C, 57.13; H,
6.71; S, 13.33. Actual value: C, 56.89; H,
6.64; N, 13.16. Other imidoamides were prepared in a similar manner.

[Table] Reference Example 26 Production of 5-isopropyl-5-methyl-2-(2-quinolyl)-2-imidazolin-4-one N-(1-carbamoyl-1,2-dimethyl-
propyl)-2-quinolinecarboxamide (16.04
To a slurry of sodium hydride (2.7 g, 0.056 mol) in xylene (610 ml) under nitrogen was added a 50% oil dispersion of sodium hydride (2.7 g, 0.056 mol) at 20°C. The reaction was heated to reflux for 2 hours, cooled and treated with water (50
ml) was added. The aqueous layer was extracted with methylene chloride, the organic layers were combined and evaporated to give 17 g of a yellow oil. Purification was carried out by passing through a silica gel column using hexane-ethyl acetate as a solvent. A flame yellow solid was obtained which was recrystallized from ethyl acetate to yield 11.77 g (78%).
gave a white product. Melting point 112-117℃. analysis,
Calculated value for C ₁₆ H ₁₇ N ₃ O: C, 71.88; H,
6.41; N, 15.72. Actual value: C, 71.91; H,
6.47; N, 15.70. Other compounds prepared in a similar manner are shown in the table.

[Table] Example 35 Production of 2-(5-isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl)-3-quinolinecarboxaldehyde 5-isopropyl-5-methyl-2-(2-quinolyl)-2-imidazolin-4-one (3 g,
0.0112 mol) in ether (150 ml),
Tetramethylethylenediamine (3.4g, 0.00225
mol) was added. The reaction mixture cooled to -63°C was charged with n-butyllithium (17 ml,
0.027 mol) was added dropwise. A strong red color appears,
The mixture was then kept at -10 to -20°C for 2 1/2 hours after the addition. Dry DMF (5ml) was added at -10°C and the mixture was allowed to reach room temperature with stirring overnight. The mixture was diluted with water (75ml) and neutralized with acetic acid. 2.57g (78%) pale yellow solid, mp 226 ~
227°C was obtained after crystallization ^* from 95% ethanol. Analysis, calculated values for C ₁₇ H ₁₇ N ₃ O ₂ : C,
69.13; H, 5.80; N, 14.23. Actual value: C,
68.98; H, 5.88; N, 14.25. Diluting the 95% ethanol with 5-10 ml of water gave a new solid that was separated. The solid was washed with 95% ethanol to remove the yellow color and had a melting point of 168
gave material at ~169°C. Tricyclic structure A or B was confirmed by m+l/e. or Another group A was prepared in a similar manner.

[Table] Example 36 2-3-(hydroxymethyl)-2-quinolyl-
Production of 5-isopropyl-5-methyl-2-imidazolin-4-one Powdered sodium borohydride (0.5 g, 0.013 mol) was suspended in ethanol (150 ml).
-(5-isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl)-3-quinolinecarboxaldehyde (0.78 g, 0.00264 mol) was added under nitrogen. A clear yellow solution resulted. After 20 minutes, the reaction was concentrated to 40 ml and water (75 ml)
diluted with Extraction with methylene chloride and evaporation gave a solid which was crystallized from hexane-ethyl acetate to give flame yellow crystals, mp 138-149.
℃, M/e298 was given. Quinoline appropriately substituted by the above method
Other compounds could be prepared using carboxaldehyde. Such compounds are shown in Table X.

[Table] Example 37 Evaluation of post-emergence herbicidal activity of test compounds The post-emergence herbicidal activity of the compounds of the present invention is shown by the following test. There, various monocotyledonous and dicotyledonous plants were treated with test compounds dispersed in an aqueous acetone mixture. In the test, seedling plants were grown in Jiffy flats for approximately two weeks. Test compounds were incubated at 40 psi in a 50/50 acetone/water mixture containing 0.5% TWEEN20, a polyoxyethylene sorbitan monolaurate surfactant from Atlas Chemical Industries.
The active compound was dispersed in an amount sufficient to reach about 0.016 Kg to 10 Kg/ha of active compound when applied to the plants through a spray nozzle operated over a predetermined period of time. After spraying, the plants were placed on greenhouse benches and cared for in the usual manner and according to standard greenhouse construction. Treatment 4
At ~5 weeks, seedling plants were tested and rated according to the rating system described below. The data obtained are listed in Table XI below. Growth difference (%) ^from evaluation system control* 0-No effect 0 1-Possible effect 1-10 2-Slight effect 11-25 3-Moderate effect 26-40 5-Severe damage 41-60 6-Herbicidal effect 61-75 7-Good herbicidal effect 76-90 8-Near complete eradication 91-99 9-Complete eradication 100 4-Abnormal growth, i.e. sharp deformity, but overall Efficacy is less than the rating scale of 5. In most cases the data relate to a single trial, but in some cases they are average values obtained from more than one trial. Plant species used: Echinochloa crusgalli, Setaria Viridis, Cyperus rotundus L., AVena Fatua, Agropyron repens, field vineweed
(Convolvulus arvensis L.) Xanthium Pensvlvanicum Morning glory (Ipomoea purpurea) Ragweed (Ambrosia artemisiifolia) Abutilon Theophrasti Barley (Hordeum vulgare) Corn (Zea mays) Rice (Oryza Sativa) Soybean (Glycine max) Sunflower ( Helianthus annus) Wheat (Triticum aestivum)

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[Table] Nicotinic acid Example 38 Evaluation of pre-emergence herbicidal activity of test compounds The pre-emergence herbicidal activity of the compounds of the present invention is illustrated by the following test. There, seeds of various monocots and dicots were mixed separately with container soil and planted approximately 1 inch from the soil in separate pint containers. After planting, the containers were sprayed with a selected acetone aqueous solution containing the test compound in an amount sufficient to provide approximately 0.016-10 Kg/ha of test compound per container. The treated containers were then placed on greenhouse benches, watered, and cared for according to standard greenhouse procedures. Treatment 4-5
After a week, the test was terminated and each container was inspected and rated according to the rating system described above. The herbicidal efficacy of the active ingredients of the invention is evident from the test results described in section XII below. When more than one test was performed for a compound, the data were averaged.

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[Table] Example 39 Evaluation of the defoliation effect of compounds of the present invention on cotton In the following tests, appropriate compounds were mixed with acetone, -
It was dissolved or dispersed in a water (1:1) mixture at a final concentration corresponding to the proportions in Kg/ha indicated in the table below. The solution also contains 0.1% to 0.25% v/v colloidal BIOFILN (a product manufactured by Colloidal Products Corporation), which includes alkylaryl polyoxyethanol, free and bound aliphatics, glycol ethers, dialkylbenzenes. It was a mixture of carboxylate and 2-propanol. The plant species used in these tests was cotton (Gossypium hirsutum, Stoneville 213 variety). In the test, a solution or dispersion of the compound was applied to the leaves by spraying at a rate of 40 ml/container (one plant/container).
The plants were mature seedlings at the fourth leaf stage at the time of testing. Immediately before the procedure, the container was filled with water. After treatment, plants were placed on benches in a greenhouse in an irregular arrangement. Regular watering and fertilization (insecticides were applied to the plants as necessary) maintained a minimum daytime and nighttime temperature of 18.3° during the cold period of the year.
Normal diurnal temperature variations occurred during the summer. Plants were sprayed to provide the Kg/ha rate shown in the table below. Each treatment was repeated 6 times and the control was repeated 12 times. Plants were harvested 15 days after pre-emergence application of the test solution and the number of defoliated, dried and senesced leaves were counted for each plant. The plants were also tested for bud growth. The data obtained are shown in the table below as mean values for each treatment.

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[Table] Example 40 Aqueous hyacinth Eichhornia as a plant species
Evaluation of test compounds as aqueous herbicides when using crassipes In these tests, test rice fields with aqueous hyacinth populations sown and grown with 5 tilapia seeds 11 months prior to compound evaluation were tested.
333/ha of test solution containing 0.5% by weight surfactant and sufficient test compound to give 0.125-1.0 Kg/ha of test compound was sprayed. After 44 days of post-emergence treatment, the test rice fields were inspected and the results were recorded and they are listed in the table below.

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Claims (1)

[Claims] 1. The following formula Here, A is COOR ₃ , CONHR ₆ , CHO, CH ₂ OH,
COCH ₃ , COC ₆ H ₅ , CN, CH ₃ , CH=NOH,
CH ₂ COOH, CONHOH, CH ₂ CH ₂ COOH,
CHR ₈ OH, [formula] or [formula] and E is [formula], or A and E taken together as a group represented by [formula], [formula] or [formula] represents a group represented by R ₁ is C ₁ -C ₄ alkyl; R ₂ is C ₁ -C ₄ alkyl or C ₃ -C ₆ cycloalkyl; and R ₁ and R ₂ taken together Sometimes they can also represent _C3 - _C6 cycloalkyl optionally substituted by methyl; _R3 is hydrogen, di-lower alkylimino, optionally the following groups: _C1 - _C3 alkoxy, halogen , hydroxyl, _C3 - _C6 cycloalkyl, benzyloxy, furyl, phenyl, halophenyl, lower alkyl phenyl, lower alkoxyphenyl, nitrophenyl, carboxyl, lower alkoxycarbonyl, cyano or tri-lower alkyl ammonium. may have been
_C1 - _C12 alkyl; optionally substituted with one of the following groups: _C1 - _C3 alkoxy, phenyl, halogen or lower alkoxycarbonyl or with two _C1 - _C3 alkoxy groups or two halogen groups C ₃
~ _C12 alkenyl; _C3 - _C6 cycloalkyl optionally substituted with one or two _C1 - _C3 alkyl groups; optionally one or two _C1 - _C3 alkyl groups _C3 - _C10 alkynyl optionally substituted with; or a cation; _R6 is hydrogen, hydroxyl, _C3 -alkenyl,
C ₃ -alkynyl or optionally substituted with one hydroxyl or one chlorine group
C ₁ -C ₄ alkyl; B is H, COR ₄ or SO ₂ R ₅ , provided that when B is COR ₄ or SO ₂ R ₅ , A is
COOR ₃ (where R ₃ is H or other than a salt-forming cation), CH ₃ or CN, W is O, and Y and Z are not alkylamino, hydroxyl or hydroxy-lower alkyl; R ₄ is _C1 - _C11 alkyl, chloromethyl or phenyl optionally substituted with one chloro, one nitro or one methoxy group; _R5 is _C1 - _C4 alkyl or phenyl optionally substituted with one methyl group; W is O or S; _R8 is _C1 - _C4 alkyl or phenyl; X is hydrogen, halogen, hydroxyl or methyl; Yes, provided that when Y and Z are taken together to form a ring and YZ is represented by the structural formula -(CH ₂ ) n- (where n is 3 or 4), X is hydrogen. and Y and Z are hydrogen, halogen, C ₁ ~
C ₆ alkyl, hydroxy-lower alkyl, C ₁ ~
_C6 alkoxy, _C1 - _C4 alkylthio, phenoxy, _C1 - _C4 haloalkyl, nitro, cyano, _C1
~ _C4 alkylamino, di-lower alkylamino or _C1 - _C4 alkylsulfonyl group, or optionally 1
represents a member selected from the group consisting of _C1 - _C4 alkyl, _C1 - _C4 alkoxy or phenyl optionally substituted with halogen;
can come together to form a ring, and YZ is
is hydrogen, then the structural formula -(CH ₂ )n- (where n
is an integer selected from 3 and 4) or [Formula], where L, M, Q and R ₇ are hydrogen, halogen,
_C1 - _C4 alkyl, C1 _- C4 alkoxy, C1- _C4 alkylthio, _{C1 - C4 alkylsulfonyl} , C1- _C4
C ₄ haloalkyl, NO ₂ , CN, phenyl, phenoxy, amino, C ₁ -C ₄ alkylamino, di-lower alkylamino, chlorophenyl, methylphenyl or substituted with one Cl, CF ₃ , NO ₂ or CH ₃ group represents a member selected from the group consisting of phenoxy, with the proviso that L, M, Q or
Only one of R ₇ is hydrogen, halogen, C ₁ to C ₄
may represent a substituent other than alkyl or _C1 - _C4 alkoxy, and W is O and A is CN, _CH3 or
COOR ₃ , with the proviso that R ₃ cannot be an unsaturated alkyl, and Y and Z cannot be alkylamino, dialkylamino or alkylthio] , their N-oxides, and their optical isomers when R ₁ and R ₂ are not the same, and their acid addition salts except when R ₃ is a salt-forming cation. 2 Structural formula [wherein R ₁ , R ₂ , B, W and A are as above; X is hydrogen, halogen, hydroxyl or methyl, with the proviso that Y and Z taken together form a ring and When YZ is represented by the structural formula -( _CH2 )n-, where n is 3 or 4, X is hydrogen; Y and Z are each hydrogen, halogen, _C1-
C ₆ alkyl, hydroxy-lower alkyl, C ₁ ~
_C6 alkoxy, _C1 - _C4 alkylthio, phenoxy, haloalkyl, nitro, cyano, _C1 - _C4 alkylamino, di-lower alkylamino or
represents a member selected from the group consisting of a _C1 - _C4 alkylsulfonyl group, or phenyl optionally substituted with one C1- _C4 alkyl _{, C1} - _C4 alkoxy or halogen, and Y and Z
can come together to form a ring, and YZ is
is hydrogen, then the structural formula -(CH ₂ )n- (where n
is an integer selected from 3 and 4); and W is O and A is CN, CH ₃ or
COOR ₃ , with the proviso that R ₃ cannot be an unsaturated alkyl, and Y and Z cannot be alkylamino, dialkylamino, or alkylthio. Compounds according to claim 1, their N-oxides, and their optical isomers when R ₁ and R ₂ are not the same, and their acid addition salts other than when R ₃ is a salt-forming cation. . 3 Structural formula [In the formula, R ₁ , R ₂ , B, W, A, X, L, M, Q
and R ₇ are as above; and W is O and A is CN, CH ₃ or
When R 3 is COOR ₃ , R ₃ cannot be an unsaturated alkyl], their N-oxides, and their optical isomerism when R ₁ and R ₂ are not the same. and acid addition salts thereof except when R ₃ is hydrogen or a salt-forming cation. 4. A herbicidally effective amount of the following formula to the soil or water containing the leaves of monocotyledonous and dicotyledonous, annual, perennial and aquatic plants, or their seeds or other propagating organs: Here, A is COOR ₃ , CONHR ₆ , CHO, CH ₂ OH,
COCH ₃ , COC ₆ H ₅ , CN, CH ₃ , CH=NOH,
CH ₂ COOH, CONHOH, CH ₂ CH ₂ COOH,
CHR ₈ OH, [formula] or [formula] and E is [formula], or A and E taken together as a group represented by [formula], [formula] or [formula] represents a group represented by R ₁ is C ₁ -C ₄ alkyl; R ₂ is C ₁ -C ₄ alkyl or C ₃ -C ₆ cycloalkyl, and R ₁ and R ₂ taken together Sometimes they can also represent _C3 - _C6 cycloalkyl optionally substituted by methyl; _R3 is hydrogen; di-lower alkylimino; optionally the following groups: _C1 - _C3 alkoxy, halogen , hydroxyl, _C3 - _C6 cycloalkyl, benzyloxy, furyl, phenyl, halophenyl, lower alkyl phenyl, lower alkoxyphenyl, nitrophenyl, carboxyl, lower alkoxycarbonyl, cyano or tri-lower alkyl ammonium. may have been
_C1 - _C12 alkyl; optionally substituted with one of the following groups: _C1 - _C3 alkoxy, phenyl, halogen or lower alkoxycarbonyl or with two _C1 - _C3 alkoxy groups or two halogen groups C ₃
~ _C12 alkenyl; _C3 - _C6 cycloalkyl optionally substituted with one or two _C1 - _C3 alkyl groups; optionally one or two _C1 - _C3 alkyl groups _C3 - _C10 alkynyl optionally substituted with; or a cation; _R6 is hydrogen, hydroxyl, _C3 -alkenyl,
C ₃ -alkynyl or optionally substituted with one hydroxyl or one chlorine group
C ₁ -C ₄ alkyl; B is H, COR ₄ or SO ₂ R ₅ , provided that when B is COR ₄ or SO ₂ R ₅ , A is
COOR ₃ (where R ₃ is H or other than a salt-forming cation), CH ₃ or CN, W is O, and Y and Z are not alkylamino, hydroxyl or hydroxy-lower alkyl; R ₄ is _C1 - _C11 alkyl, chloromethyl or phenyl optionally substituted with one chloro, one nitro or one methoxy group; _R5 is _C1 - _C4 alkyl or phenyl optionally substituted with one methyl group; W is O or S; _R8 is _C1 - _C4 alkyl or phenyl; X is hydrogen, halogen, hydroxyl or methyl; Yes, provided that when Y and Z are taken together to form a ring and YZ is represented by the structural formula -(CH ₂ ) n- (where n is 3 or 4), X is hydrogen. and Y and Z are hydrogen, halogen, C ₁ ~
C ₆ alkyl, hydroxy-lower alkyl, C ₁ ~
_C6 alkoxy, _C1 - _C4 alkylthio, phenoxy, _C1 - _C4 -haloalkyl, nitro, cyano,
_C1 - _C4 alkylamino, di-lower alkylamino or _C1 - _C4 alkylsulfonyl group, or optionally substituted with one _C1 - _C4 alkyl, _C1 - _C4 alkoxy or halogen represents a member selected from the group consisting of phenyl, and Y and Z can form a ring and YZ has the structure -( _CH2 )n-, where is an integer) or [Formula], where L, M, Q and R ₇ are hydrogen, halogen,
_C1 - _C4 alkyl, _C1 - _C4 alkoxy, _C1 - _C4 −
Alkylthio, _C1 - _{C4alkylsulfonyl} , _C1
~ _C4 haloalkyl, _NO2 , CN, phenyl, phenoxy, amino, _C1 - _C4 alkylamino, di-lower alkylamino, chlorophenyl, methylphenyl or substituted with one Cl, _CF3 , _NO2 , or _CH3 represents a member selected from the group consisting of phenoxy, with the proviso that L, M, Q or
Only one of R ₇ is hydrogen, halogen, C ₁ to C ₄
can represent substituents other than alkyl or _C1 - _C4 -alkoxy, and W is O and A is CN, _CH3 or
COOR ₃ , with the proviso that R ₃ cannot be an unsaturated alkyl, and Y and Z cannot be alkylamino, dialkylamino or alkylthio] , their N-oxides, and their optical isomers when R ₁ and R ₂ are not identical, and their acid addition salts, except when R ₃ is a salt-forming cation. How to get rid of seeds. 5. Claims in which the compound is applied to the leaves of the plant or to the soil or water containing the seeds or other propagating organs of the plant at a rate between 0.016 Kg/ha and 4.0 Kg/ha The method described in Section 4. 6. Approximately 5 to 15 days before the expected harvest time, the structural formula of the leaves of cotton trees is [wherein R ₁ is C ₁ -C ₄ alkyl; R ₂ is C ₁ -C ₄ alkyl or C ₃ -C ₆ cycloalkyl, and when R ₁ and R ₂ are taken together they are A can also represent _C3 - _C6 cycloalkyl optionally substituted by methyl; A is _COOR3 , _CONHR6 , CHO, _CH2OH ,
COCH ₃ , COC ₆ H ₅ , CN, CH ₃ , CH=NOH,
CH ₂ COOH, CONHOH, CH ₂ CH ₂ COOH,
CHR ₈ OH, [Formula] or [Formula]; R ₃ is hydrogen; di-lower alkylimino; optionally the following groups: C ₁ -C ₃ alkoxy, halogen, hydroxyl, C ₃ -C ₆ cycloalkyl, benzyl May be substituted with one of the following: oxy, furyl, phenyl, halophenyl, lower alkyl phenyl, lower alkoxy phenyl, nitrophenyl, carboxyl, lower alkoxy carbonyl, cyano or tri-lower alkyl ammonium
_C1 - _C12 alkyl; optionally one of the following groups: _C1 - _C3 alkoxy, phenyl, halogen or lower alkoxycarbonyl, or two _C1 - _C3 alkoxy groups or two halogen groups; May be replaced
_C3 - _C12 alkenyl; C3 _{- C6} cycloalkyl optionally substituted with one or two _C1 - _C3 alkyl groups; optionally one or two C1 _{- C3 C3} - _C10 alkynyl optionally substituted with an alkyl group; or a cation; _R6 is hydrogen, hydroxyl, _C3 -alkenyl,
C ₃ -alkynyl or optionally substituted with one hydroxyl or one chlorine group
C ₁ -C ₄ alkyl; B is H, COR ₄ or SO ₂ R ₅ , provided that when B is COR ₄ or SO ₂ R ₅ , A is
COOR ₃ (where R ₃ is H or other than a salt-forming cation), CH ₃ or CN, W is O, and Y and Z are not alkylamino, hydroxyl or hydroxy-lower alkyl; R ₄ is _C1 - _C11 alkyl, chloromethyl or phenyl optionally substituted with one chloro, one nitro or one methoxy group; _R5 is _C1 - _C4 alkyl or phenyl optionally substituted with one methyl group; W is O or S; _R8 is _C1 - _C4 alkyl or phenyl; X is hydrogen, halogen, hydroxyl or methyl; Yes, provided that when Y and Z are taken together to form a ring and YZ is represented by the structural formula -(CH ₂ ) n- (where n is 3 or 4), X is hydrogen. and Y and Z are hydrogen, halogen, C ₁ ~
C ₆ alkyl, hydroxy-lower alkyl, C ₁ ~
_C6 alkoxy, _C1 - _C4 alkylthio, phenoxy, _C1 - _C4 -haloalkyl, nitro, cyano,
_C1 - _C4 alkylamino, di-lower alkylamino or _C1 - _C4 alkylsulfonyl group, or optionally substituted with one _C1 - _C4 alkyl, _C1 - _C4 alkoxy or halogen represents a member selected from the group consisting of phenyl, and Y and Z can form a ring and YZ has the structure -( _CH2 )n-, where is an integer) or [Formula], where L, M, Q and R ₇ are hydrogen, halogen,
_C1 - _C4 alkyl, _C1 - _C4 alkoxy, _C1 - _C4 −
Alkylthio, _C1 - _{C4alkylsulfonyl} , _C1
~ _C4 haloalkyl, _NO2 , CN, phenyl, phenoxy, amino, _C1 - _C4 alkylamino, di-lower alkylamino, chlorophenyl, methylphenyl or substituted with one Cl, _CF3 , _NO2 or _CH3 group represents a member selected from the group consisting of phenoxy, with the proviso that L, M, Q or
Only one of R ₇ is hydrogen, halogen, C ₁ to C ₄
can represent substituents other than alkyl or _C1 - _C4 -alkoxy, and W is O and A is CN, _CH3 or
COOR ₃ , with the proviso that R ₃ cannot be an unsaturated alkyl, and Y and Z cannot be alkylamino, dialkylamino or alkylthio] , their N-oxides, and their optical isomers when R ₁ and R ₂ are not identical, and their acid addition salts except when R ₃ is a salt-forming cation. How to defoliate trees. 7 Inert solid or liquid diluent and herbicidally effective amount of the following formula: Here, A is COOR ₃ , CONHR ₆ , CHO, CH ₂ OH,
COCH ₃ , COC ₆ H ₅ , CN, CH ₃ , CH=NOH,
CH ₂ COOH, CONHOH, CH ₂ CH ₂ COOH,
CHR ₈ OH, [formula] or [formula] and E is [formula], or A and E taken together as a group represented by [formula], [formula] or [formula] represents a group represented by R ₁ is C ₁ -C ₄ alkyl; R ₂ is C ₁ -C ₄ alkyl or C ₃ -C ₆ cycloalkyl, and R ₁ and R ₂ taken together Sometimes they can also represent _C3 - _C6 cycloalkyl optionally substituted by methyl; _R3 is hydrogen; di-lower alkylimino; optionally the following groups: _C1 - _C3 alkoxy, halogen , hydroxyl, C ₃ - C ₆ cycloalkyl, benzyloxy, furyl, phenyl, halophenyl, lower alkyl phenyl, lower alkoxy phenyl, nitrophenyl, carboxyl, lower alkoxycarbonyl, cyano or tri-lower alkyl ammonium: optionally one of _{the following groups: C1-C3 alkoxy , phenyl} , halogen or lower alkoxycarbonyl, or two C1 _{- C3} alkoxy groups or two May be substituted with halogen groups
_C3 - _C12 alkenyl; C3 _{- C6} cycloalkyl optionally substituted with one or two _C1 - _C3 alkyl groups; optionally one or two C1 _{- C3 C3} - _C10 alkynyl optionally substituted with an alkyl group; or a cation; _R6 is hydrogen, hydroxyl, _C3 -alkenyl,
C ₃ -alkynyl or optionally substituted with one hydroxyl or one chlorine group
C ₁ -C ₄ alkyl; B is H, COR ₄ or SO ₂ R ₅ , provided that when B is COR ₄ or SO ₂ R ₅ , A is
COOR ₃ (where R ₃ is H or other than a salt-forming cation), CH ₃ or CN, W is O, and Y and Z are not alkylamino, hydroxyl or hydroxy-lower alkyl; R ₄ is _C1 - _C11 alkyl, chloromethyl or phenyl optionally substituted with one chloro, one nitro or one methoxy group; _R5 is _C1 - _C4 alkyl or phenyl optionally substituted with one methyl group; W is O or S; _R8 is _C1 - _C4 alkyl or phenyl; X is hydrogen, halogen, hydroxyl or methyl; Yes, provided that when Y and Z are taken together to form a ring and YZ is represented by the structural formula -(CH ₂ )n- (where n is 3 or 4), X is hydrogen. and Y and Z are hydrogen, halogen, C ₁ ~
C ₆ alkyl, hydroxy-lower alkyl, C ₁ ~
_C6 alkoxy, _C1 - _C4 alkylthio, phenoxy, _C1 - _C4 -haloalkyl, nitro, cyano,
_C1 - _C4 alkylamino, di-lower alkylamino or _C1 - _C4 alkylsulfonyl group, or optionally substituted with one _C1 - _C4 alkyl, _C1 - _C4 alkoxy or halogen represents a member selected from the group consisting of phenyl, and Y and Z can form a ring and YZ has the structure -( _CH2 )n-, where is an integer) or [Formula], where L, M, Q and R ₇ are hydrogen, halogen,
_C1 - _C4 alkyl, _C1 - _C4 alkoxy, _C1 - _C4 −
Alkylthio, _C1 - _{C4alkylsulfonyl} , _C1
~ _C4 haloalkyl, _NO2 , CN, phenyl, phenoxy, amino, _C1 - _C4 alkylamino, di-lower alkylamino, chlorophenyl, methylphenyl or substituted with one Cl, _CF3 , _NO2 or _CH3 group represents a member selected from the group consisting of phenoxy, with the proviso that L, M, Q or
Only one of R ₇ is hydrogen, halogen, C ₁ to C ₄
can represent substituents other than alkyl or _C1 - _C4 -alkoxy, and W is O and A is CN, _CH3 or
COOR ₃ , with the proviso that R ₃ cannot be an unsaturated alkyl, and Y and Z cannot be alkylamino, dialkylamino or alkylthio] , their N-oxides, and their optical isomers when R ₁ and R ₂ are not the same, and their acid addition salts except when R ₃ is a salt-forming cation. 8 20-45% by weight of finely divided solid inert carrier, 45
Claim 7, comprising ~80% by weight of the herbicidally active ingredient represented by the above structural formula, about 2-5% by weight of a dispersant, and about 2-5% by weight of a surfactant. solid herbicide composition. 9. Claims consisting of 5 to 25% by weight of the herbicidally active ingredient represented by the above structural formula, about 65 to 90% by weight of an inert organic solvent, and about 5 to 10% by weight of a surfactant. 8. The liquid herbicide composition according to item 7. 10. Claim 7, comprising about 80-97% by weight of an inert granular carrier and about 3-20% by weight of a herbicidally active ingredient represented by the above structural formula.
The granular herbicide composition described in . 11 Structural formula [wherein R ₁ is C ₁ -C ₄ alkyl; R ₂ is C ₁ -C ₄ alkyl or C ₃ -C ₆ cycloalkyl, and when R ₁ and R ₂ are taken together they are _C3 - _C6 optionally substituted with methyl
It can also represent cycloalkyl; A is COOR ₃ or CONHR ₆ and R ₃ optionally represents the following groups: C ₁ -C ₃ alkoxy, halogen, hydroxyl, C ₃ -C ₆ cycloalkyl,
Benzyloxy, furyl, phenyl, halophenyl, lower alkyl phenyl, lower alkoxyphenyl, nitrophenyl, carboxyl, lower alkoxycarbonyl, cyano or tri-lower alkylammonium: C ₁ -C ₁₂ alkyl optionally substituted with one of the following: C optionally substituted with one of the following groups: _C1 - _C3 alkoxy, phenyl, halogen or lower alkoxycarbonyl or with two _C1 - _C3 alkoxy groups or two halogen groups; ₃
~ _C12 alkenyl; _C3 - _C6 cycloalkyl optionally substituted with one or two _C1 - _C3 alkyl groups; optionally one or two _C1 - _C3 alkyl groups _C3 - _C10 alkynyl optionally substituted with; or a cation; _R6 is hydrogen, hydroxyl, _C3 -alkenyl,
C ₃ -alkynyl or optionally substituted with one hydroxyl or one chlorine group
_C1 - _C4 alkyl; B is H, W is O, and X is hydrogen, halogen, hydroxyl or methyl, provided that Y and Z taken together form a ring and YZ is represented by the structural formula -( _CH2 )n-, where n is 3 or 4, then X is hydrogen; Y and Z are each hydrogen, halogen, _C1-
C ₆ alkyl, hydroxy-lower alkyl, C ₁ ~
_C6 alkoxy, _C1 - _C4 alkylthio, phenoxy, _C1 - _C4 -haloalkyl, nitro, cyano,
_C1 - _C4 alkylamino, di-lower alkylamino or _C1 - _C4 alkylsulfonyl group, or optionally substituted with one _C1 - _C4 alkyl, _C1 - _C4 alkoxy or halogen represents a member selected from the group consisting of phenyl, and Y and Z can be taken together to form a ring;
If X is hydrogen, YZ has the structural formula -(CH ₂ )n-
(where n is an integer selected from 3 and 4) or [Formula], where L, M, Q and R ₇ are hydrogen, halogen,
_C1 - _C4 alkyl, _C1 - _C4 alkoxy, _C1 - _C4 −
Alkylthio, _C1 - _{C4alkylsulfonyl} , _C1
~ _C4 haloalkyl, _NO2 , CN, phenyl, phenoxy, amino, _C1 - _C4 alkylamino, di-lower alkylamino, chlorophenyl, methylphenyl or substituted with one Cl, _CF3 , _NO2 or _CH3 group represents a member selected from the group consisting of phenoxy, with the proviso that L, M, Q or
Only one of R ₇ is hydrogen, halogen, C ₁ to C ₄
can represent a substituent other than alkyl or C ₁ -C ₄ -alkoxy] A method for producing a compound having the structural formula [wherein R ₁ , R ₂ , X, Y and Z are as above]
alcohols and alkali metal alkoxides R ₃ O ⁻ M ⁺ represented by R ₃ OH, where R ₃ is as above and M ⁺ is an alkali metal;
reacted alone or in the presence of an aprotic solvent at a temperature between about 20° C. and 50° C., whereby A is COOR ₃ and R ₃ , R ₁ , R ₂ ,
or (b) at least one equivalent of structural formula
R ₆ NH ₂ , where R ₆ is as defined above, by itself or in the presence of an aprotic solvent, at a temperature between about 80° C. and 125° C.; A process characterized in that A is CONHR ₆ and R ₆ , R ₁ , R ₂ , X, Y and Z are as defined above. 12 Structural formula [wherein R ₁ is C ₁ -C ₄ alkyl; R ₂ is C ₁ -C ₄ alkyl or C ₃ -C ₆ cycloalkyl, and when R ₁ and R ₂ are taken together they are A can also represent _C3 - _C6 cycloalkyl optionally substituted by methyl; A is _COOR3 , _CONHR6 , _CH2OH , _COCH3 ,
COC ₆ H ₅ , or [Formula], where R ₃ is di-lower alkylimino, optionally the following groups: C ₁ -C ₃ alkoxy, halogen, hydroxyl, C ₃ -C ₆ cycloalkyl, benzyloxy, furyl , phenyl, halophenyl, lower alkylphenyl, lower alkoxyphenyl, nitrophenyl, carboxyl, lower alkoxycarbonyl, cyano or tri-lower alkylammonium.
_C1 - _C12 alkyl; optionally from the following groups _C1 - _C3 alkoxy, phenyl,
1 of halogen or lower alkoxycarbonyl
species or 2 C ₁ -C ₃ alkoxy groups or 2
C ₃ to C ₁₂ optionally substituted with halogen groups
Alkenyl; _{C3 - C6} cycloalkyl optionally substituted with one or two C1- _C3 alkyl groups; optionally substituted with one or two _C1 - _C3 alkyl groups _C3 - _C10 alkynyl optionally; or cation; _R6 is hydrogen, hydroxyl, _C3 -alkenyl,
C ₃ -alkynyl or optionally substituted with one hydroxyl or one chlorine atom
_C1 - _C4 alkyl; B is H, W is O, and X is hydrogen, halogen, hydroxyl or methyl, provided that Y and Z taken together form a ring and YZ is represented by the structural formula -( _CH2 )n-, where n is 3 or 4, then X is hydrogen; Y and Z are each hydrogen, halogen, _C1-
C ₆ alkyl, hydroxy-lower alkyl, C ₁ ~
_C6 alkoxy, _C1 - _C4 alkylthio, phenoxy, _C1 - _C4 -haloalkyl, nitro, cyano,
_C1 - _C4 alkylamino, di-lower alkylamino or _C1 - _C4 alkylsulfonyl group, or optionally substituted with one _C1 - _C4 alkyl, _C1 - _C4 alkoxy or halogen represents a member selected from the group consisting of phenyl, and Y and Z can be taken together to form a ring, and YZ has the structure -(CH ₂ ) n-, where n is 3 and 4, if X is hydrogen; ) or [Formula], where L, M, Q and R ₇ are hydrogen, halogen,
_C1 - _C4 alkyl, _C1 - _C4 alkoxy, _C1 - _C4 −
Alkylthio, _C1 - _{C4alkylsulfonyl} , _C1
~ _C4 haloalkyl, _NO2 , CN, phenyl, phenoxy, amino, _C1 - _C4 alkylamino, di-lower alkylamino, chlorophenyl, methylphenyl or substituted with one Cl, _CF3 , _NO2 or _CH3 group represents a member selected from the group consisting of phenoxy, with the proviso that L, M, Q or
Only one of R ₇ is hydrogen, halogen, C ₁ to C ₄
can represent a substituent other than alkyl or C ₁ -C ₄ -alkoxy] A method for producing a compound having the structural formula [wherein R ₁ , R ₂ , X, Y and Z are as above]
Alcohols and alkali metal alkoxides R ₃ O M represented by R ₃ OH, where R ₃ is as above and M is an alkali metal.
and, alone or in the presence of an aprotic solvent, at a temperature between about 20°C and 50°C;
Thereby A is COOR ₃ and R ₃ , R ₁ ,
obtain the desired product in which R ₂ , X, Y, and Z are as described above, or (b) at least one equivalent of the product represented by the structure R ₆ NH ₂ , where R ₆ is as described above. 80°C to 125°C in the presence of a lower alkyl alcohol or an aprotic solvent.
reaction at a temperature between, whereby A becomes
or (c ₎ at least one _{equivalent of} magnesium _methyl bromide and an aprotic In the presence of solvent, −50℃ to −
reacted under an inert gas atmosphere at a temperature between 80°C, whereby A is _COCH3 and
to obtain the desired product in which R ₁ , R ₂ , X, Y and Z are as above, or (d) at -50° C. in the presence of at least one equivalent of phenyllithium and an aprotic solvent. The reaction is carried out under an inert gas atmosphere at a temperature between ~-80°C, whereby A is
to obtain the desired product in which COC ₆ H ₅ and R ₁ , R ₂ , X, Y and Z are as above, or
(e) in the presence of at least one equivalent of trimethylphosphonoacetate and an aprotic solvent from −50°C to
react at -80° C. under an inert gas atmosphere, thereby obtaining the desired product in which A is and R ₁ , R ₂ , X, Y and Z are as above; or (f) a process characterized in that it is reacted with at least one equivalent of sodium borohydride in ethanol at -10°C to +20°C, thereby obtaining the desired product in which A is CH ₂ OH. . 13 Structural formula [wherein R ₁ is C ₁ -C ₄ alkyl; R ₂ is C ₁ -C ₄ alkyl or C ₃ -C ₆ cycloalkyl, and when R ₁ and R ₂ are taken together they are It may also represent _C3 - _C6 cycloalkyl optionally substituted by methyl; X is hydrogen, halogen, hydroxyl or methyl, provided that Y and Z together form a ring. and when YZ is represented by the structural formula -( _CH2 )n- (where n is 3 or 4), X is hydrogen; Y and Z are hydrogen, halogen, _C1-
C ₆ alkyl, hydroxy-lower alkyl, C ₁ ~
_C6 alkoxy, _C1 - _C4 alkylthio, phenoxy, _C1 - _C4 -haloalkyl, nitro, cyano,
_C1 - _C4 alkylamino, di-lower alkylamino or _C1 - _C4 alkylsulfonyl group, or optionally substituted with one _C1 - _C4 alkyl, _C1 - _C4 alkoxy or halogen represents a member selected from the group consisting of phenyl, and Y and Z can be taken together to form a ring, and YZ has the structure -(CH ₂ ) n-, where n is 3 and 4, if X is hydrogen; is an integer selected from ) or [Formula], where L, M, Q and R ₇ are hydrogen, halogen,
_C1 - _C4 alkyl, _C1 - _C4 alkoxy, _C1 - _C4 −
Alkylthio, _C1 - _{C4alkylsulfonyl} , _C1
~ _C4 haloalkyl, _NO2 , CN, phenyl, phenoxy, amino, _C1 - _C4 alkylamino, di-lower alkylamino, chlorophenyl, methylphenyl or substituted with one Cl, _CF3 , _NO2 or _CH3 group represents a member selected from the group consisting of phenoxy, provided that L, M, Q or
Only one of R ₇ is hydrogen, halogen, C ₁ to C ₄
can represent a substituent other than alkyl or C ₁ -C ₄ -alkoxy] A method for producing a compound having the formula [wherein _R3 is di-lower alkylimino, optionally the following groups: _C1 - _C3 alkoxy, halogen, hydroxyl, _C3 - _C6 cycloalkyl, benzyloxy, furyl, phenyl, halofenyl, lower alkyl] may be substituted with one of the following: enyl, lower alkoxyphenyl, nitrophenyl, carboxyl, lower alkoxycarbonyl, cyano, or tri-lower alkylammonium
_C1 - _C12 alkyl; optionally substituted with one of the following groups: _C1 - _C3 alkoxy, phenyl, halogen or lower alkoxycarbonyl or with two _C1 - _C3 alkoxy groups or two halogen groups C ₃
~ _C12 alkenyl; _C3 - _C6 cycloalkyl optionally substituted with one or two _C1 - _C3 alkyl groups; optionally one or two _C1 - _C3 alkyl groups _{C3 - C10} alkynyl optionally substituted _with characterized by reacting in an aqueous solution and heating the mixture between 20°C and 50°C; cooling the mixture and adjusting its PH between 6.5 and 7.5 by adding a strong mineral acid to it; How to do it. 14 The following formula [where A ¹ is H or COOR ₃ and R ₃ is hydrogen, di-lower alkylimino, or optionally the following groups: C ₁ -C ₃ alkoxy, halogen, hydroxyl, C ₃ -C ₆ cyclo Alkyl, benzyloxy, furyl, phenyl, halophenyl, lower alkylphenyl, lower alkoxyphenyl, nitrophenyl, carboxyl, lower alkoxycarbonyl, cyano or tri-lower alkylammonium: C ₁ -C optionally substituted with one of the following: ₁₂ alkyl; optionally substituted with one of the following groups: C1 _{- C3} alkoxy, phenyl, halogen or lower alkoxycarbonyl or with two _C1 - _C3 alkoxy groups or two halogen groups; Moyoi C ₃
~ _C12 alkenyl; _C3 - _C6 cycloalkyl optionally substituted with one or two _C1 - _C3 alkyl groups; optionally one or two _C1 - _C3 alkyl groups _C3 - _C10 alkynyl optionally substituted with; or is a cation; _R1 is _C1 - _C4 alkyl; _R2 is _C1 - _C4 alkyl or _C3 - _C6 cycloalkyl; , and when R ₁ and R ₂ are taken together they are C ₃ -C ₆ optionally substituted by methyl
It can also represent cycloalkyl; Y and Z are hydrogen, halogen, C ₁ -
C ₆ alkyl, hydroxy-lower alkyl, C ₁ ~
_C6 alkoxy, _C1 - _C4 alkylthio, phenoxy, _C1 - _C4 -haloalkyl, nitro, cyano,
_C1 - _C4 alkylamino, di-lower alkylamino or _C1 - _C4 alkylsulfonyl group, or optionally substituted with one _C1 - _C4 alkyl, _C1 - _C4 alkoxy or halogen represents a member selected from the group consisting of phenyl, and Y and Z can be taken together to form a ring;
YZ has the structural formula -(CH ₂ )n- (where n is 3 or 4
or is represented by [Formula], where L, M, Q and R ₇ are hydrogen, halogen,
_C1 - _C4 alkyl, _C1 - _C4 alkoxy, _C1 - _C4 −
Alkylthio, _C1 - _{C4alkylsulfonyl} , _C1
~ _C4 haloalkyl, _NO2 , CN, phenyl, phenoxy, amino, _C1 - _C4 alkylamino, di-lower alkylamino, chlorophenyl, methylphenyl, or one Cl, _CF3 , _NO2 or
represents a member selected from the group consisting of phenoxy substituted with CH ₃ group, with the proviso that L,
Only one of M, Q or R ₇ can represent a substituent other than hydrogen, halogen, C ₁ -C ₄ alkyl or C ₁ -C ₄ -alkoxy. , the following formula [Here, the definitions of A ¹ , R ¹ , R ² , W, X, Y and Z are the same as above] Cyclizing a compound represented by (this compound may be formed in situ) A method characterized by: 15. The method of claim 14, wherein the cyclization is carried out in an anhydrous alkaline medium.