NZ206857A

NZ206857A - Pyridine derivatives and herbicidal compositions

Info

Publication number: NZ206857A
Application number: NZ206857A
Authority: NZ
Inventors: M Los
Original assignee: American Cyanamid Co
Priority date: 1980-06-02
Filing date: 1981-05-29
Publication date: 1985-11-08

Description

<div class="application article clearfix" id="description"> New Zealand Paient Spedficaiion for Paient Number £06857 2068S7 NO y 1 IBS Priority Date(s) «? -k-s' Filed: ?.^:f.'.. ftp] W A-3. J ft o)< fto Complete Specification Class: . £<?;T£ '/ £ ft /£ i fr&lPZ '.4^'J Publication Date P.O. Journal, No 68 NOV 1985 " "(277. "Under the provisions of Reg lation 23 (I) the ! . . Specification has been ante-dot to __ .<£j-....jr)..ery. I9£_ ,v * NEW ZEALAND PATENTS ACT, 1953 No.: Date: COMPLETE SPECIFICATION PYRROLOPYRIDINE AND QUINOLINE NITRILES AND ACETAMIDES AND CARBAMOYLNICOTINIC AND 3-QUINOLINE CARBOXYLIC ACIDS AND DERIVATIVES THEREOF I/We, AMERICAN CYANAMID COMPANY, a corporation organized and existing under the laws of the State of Maine, United States of America, and having its executive offices at Wayne, New Jersey, United States of America hereby declare the invention for which we pray that a patent may be granted to eqe/us, and the method by which it is to be performed, to be particularly described in and by the following statement: - - 1 - (followed by la) 2068&1 - la - PYRROLOPYRIDINE AND QUINOLINE NITRILES AND ACETAMIDES AND CARBAMOYLNICOTINIC AND 3-QUINOLINE CARBOXYLIC ACIDS AND DERIVATIVES THEREOF The present invention relates to novel pyrrolo-pyridine (and quinoline) nitriles pyrrolopyridine (and quinoline) acetamides and carbamoylnicotinic and 3-quinolinecarboxy1ic acids of the following formulae: V\J fl I L>— /V' I 2 s (XI) \A..« t1 ■ H-C-CCSt /"V j (XII) „ ? -COOK, \ / 3 • • i n _ 2y'S/'\ j1 CONH—C—CONH^ (XV) // V o.w I'Y r; ^26MJGW5r wherein R^ is C^-C^ alkyl; R^ is C^-C^ alkyl or C^-C^ cycloalkyl; and when R^ and R^ are taken together with the carbon to which they are attached they may represent C^-Cg cycloalkyl optionally substituted with methyl; R^ is hydrogen, di(C^-C^ alkyl)methylideneamino, C^-C^2 alkyl optionally substituted with one of the following groups: C^-C^ alkoxy, halogen, hydroxy, C--C,. cycloalkyl, benzyloxy, furyl, J D phenyl, halophenyl, (C1-C3 alkyl)phenyl, (C^-C^ alkoxy)phenyl, nitrophenyl, carboxyl, (C^-C^ alkoxy)carbonyl, cyano or tri(C^-C^ alkyl)ammonium; C^-C^2 alkenyl optionally substituted with one of the following groups: C^-C^ alkoxy, phenyl, halogen or (C^-C alkoxy)carbonyl or with two C^-C^ alkoxy groups or two halogen groups: C-.-C- cycloalkyl optionally substituted with one O D or two C^-C^ alkyl groups; C3-C10 alkynyl optionally substituted with one or two C^-C^ alkyl groups; or, a cation; X is hydrogen, halogen, hydroxyl or methyl, with the proviso that when Y and Z are taken together to form a ring and YZ is -(CH„) -, where n is 3 or 4, X is ^ n hydrogen; Y and Z are each hydrogen, halogen, C..-C,. alkyl, i D hydroxy-C^-C^ alkyl, C^-C^ alkoxy, alkylthio, phenoxy, C^-C^ haloalkyl, nitro, cyano, alkyl- amino, difC^-C^ alkyl)amino or alkylsulfonyl group, or phenyl optionally substituted with one C^-C^ alkyl, C^-C^ alkoxy or halogen; and, when taken together, Y and Z may form a ring in which Y and Z are "(CI^) -, w^ere n an integer of 3 or 206857 3 that X is hydrogen; or L M Q R7 I I I I -C=C-C=C-, where L, M, Q and R7 are each hydrogen halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkyl-thio, C1-C4 alkylsulfonyl, C1-C4 haloalkyl, NO2> CN, phenyl, phenoxy, amino, (4-C4 alkyl-amino, di(C -C^ alkyl)amino, chlorophenyl, methyl-phenyl, or phenoxy substituted with one CI, CF3, NO2 or CH3 group, with the proviso that only one of L, M, Q or R7, may represent a sub-stituent other than hydrogen, halogen, C1-C4 alkyl or C1-C4 alkoxy, and when and R2 are not the same, the optical isomers thereof. One group of the above novel formula XI, XII and XV compounds have the formulae o n o o R 2 wherein Y is hydrogen, alkyl, C1~C4 alkoxy, cyano, nitro or halogen; ^ is C1-C/} alkyl; R2 is c^-<-4 alkyl or cycloalkyl; and when and - 4 - %068$y are taken together with the carbon to which they are attached, they can represent C^-C^ cycloalkyl optionally substituted with methyl; and when and R2 are not the same, the optical isomers thereof. are intermediates for the preparation of herbicidal Formula (I) 2-(2-imidazolin-2-yl)pyridine and quinoline compounds disclosed in our New Zealand Patent Specification No. 197247 and herbicidal formula (III) and (VII) imidazopyrrolopyridine (and quinoline) diones disclosed in our New Zealand Patent Specification No. 206856 filed concurrently with the instant application. The above novel formula XI, XII and XV compounds (I) (III) 2.06% One general method for the preparation of the formula (I) compounds involves the reaction of a quino-linic anhydride of formula (XVI) hereinbelow, with an appropriately substituted a-aminocarbonitrile of formula (XVII), hereinbelow, to yield a mixture of the monoamides of nicotinic or quinolinic acid of formula (IX) and formula (X). This reaction is carried out at a temperature between about 20°C and 70° and preferably between about 35°C and 40°C in an inert solvent, such as tetrahydro-furan, methylene chloride, ether, chloroform, toluene or the like. The thus-formed acids are then cyclized to the corresponding pyrrolopyridine or quinoline aceto-nitrile, depicted by formula (XI), by heating the reaction mixture with an excess of acetic anhydride in the presence of a catalytic amount of sodium acetate or potassium acetate. In general, the above reaction is carried out by treating the reaction mixture with acetic anhydride, acetyl chloride, thionyl chloride or the like and heating said mixture to a temperature between about 20°C arid 100°C. Hydration of the thus-formed pyrrolopyridine acetonitrile formula (XI) is carried out by treating said acetonitrile with a strong acid such as sulfuric acid. This reaction yields the formula (XII) pyrrolo-pyridine acetamide. Although the addition of a non-miscible solvent such as methylene chloride, chloroform or the like is not essential to the conduct of the above described reaction, addition of such a solvent to the reaction mixture is generally preferred. Said reaction is usually carried out at a temperature between about 10°C to 70°C. 1 FLOW DIAGRAM I 10 15 20 25 T V\J iN L> r-V J (XVI) \X /°°h nh2-C-cn (XVII) 1 (IX) ^conh^-CK T ii r2 ^ V\ V (CH3C0)20 COOH (X) 30 v\j h • •• " ,-CN (XI) /V I r2 35 V°4 \1/ f vA. f S x !i i -CONH. % ' /V I *2 (XII) 1 0&&57 Another general method for the preparation of the formula (I) pyridine derivatives involves the reaction of a quinolinic anhydride of formula (XVI), with an appropriately substituted a-aminocarboxylic acid such as o-methylvaline represented by formula (XIX), preferably in a ketonic solvent such as acetone under a blanket of nitrogen to yield an isomeric mixture of the formula (XX) and formula (XXI) acids. The mixture is then treated with acetic anhydride and a catalytic amount of sodium acetate at an elevated temperature to give the dihydrodioxopyrrolopyridine acid formula (XXII). Reaction of the thus-formed acid with a thionyl halide, such as thionyl chloride or thionyl bromide, in the presence of an organic solvent such as toluene, xylene, benzene or the like, at an elevated temperature, i.e., 80°C to 150°C, gives the formula (XXIII) acid halide corresponding to the formula (XXII) acid. Treatment of this acid halide with excess ammonia then yields the formula (IV) dihydrodioxopyrrolopyridine acetamide. The reaction is preferably carried out in the presence of an aprotic solvent. % 2 OGS57 1 -X- FLOW DIAGRAM II 10 IS V\_S (XVI) w COOH ^V\0Ji -COOH A. (XIX) « Y V ^ N z/V •-CONH-(j:-COOH •-COOH R2 20 (XX) (XXI) (CH3C0)20 25 \.X i? •v • ^ v a -COOH 30 (XXII) 35 I FLOW DIAGRAM IT (CONTINUED) 1 063 57 * SOCl. V'N—U1 V' ft ■ A. l-COCl 10 (XXIII) 15 20 NH. h f' V ft *2 ^N-J-CONH, (IV) 25 30 - 10 - 206#57 Several routes are employed to prepare pyrroloquinoline acetamides represented by formula (XXXVIII). Preferably hydration of the pyrroloquinoline acetonitrile of formula (XXXX) is accomplished by treatment with a strong acid such as sulfuric acid. This reaction yields the formula (XXXVIII) pyrroloquinoline acetamide. Although the addition of a non-miscible solvent such as methylene chloride/ chloroform or the like is not essential to the conduct of the above described reaction, addition of such a solvent to the reaction mixture may be preferred. Said reaction is usually carried out at a temperature between 10°C to 70°C. Alternatively, the pyrroloquinoline acetamide of formula (XXXVIII) may be obtained by the Diels-Alder cycloaddition reaction between substituted antnranils of formula (XXXXI) and the dioxopyrroline acetamide of formula (XXXXII). These reactions are carried out in a wide temperature range: below 130°C significant amounts of the intermediate aldehyde of formula (XXXXIII) are obtained, but at 130°C - 200°C the pyrroloquinoline acetamide of formula (XXXVIII) is formed. Alternatively, the intermediate aldehyde of formula (XXXXIII) may be isolated and cyclized in refluxing xylene in the presence of an acid catalst, such as £-toluene sulfonic acid. This reaction yields the desired formula (XXXVIII) pyrroloquinoline acetamide. These reactions may be graphically illustrated as shown below on Flow Diagram V. 206857 - 11 -FLOW DIAGRAM V \ sm ym Vs- Q— f ^N—C—CHN Yv I K Cxxxx) V°4 M—•' /\A f ?! I | | yi-CO-SHj Q-i. J I I y v j K 7 (XXXVIII) - 12 - FLOW DIAGRAM V (CONTINUED) 206957 "1 i=CHv Q—• V w I -CO-NH. (XXXXI) (XXXXII) i ^cH° 5 ft ll >4- A, Nk" I A. -CONH. (XXXXIII) CR3-N >"S03H V I ^ \ ^ \ II R. n ! i >f :-CO-NH. ^yV; j 2 (XXXVIII) 206857 13 A variety of routes may also be employed to obtain the formula (XXXX) pyrroloquinoline acetonitriles depending on the nature of the L, M, Q and substituents. The formula (XXXX) pyrroloquinoline acetonitriles may be prepared by reacting the appropriately substituted anhydride (XXXXIV) with an appropriately substituted a-aminocarbonitrile of formula (XVII), to yield a mixture of the monoamides of the formula (XXXXVa) and formula (XXXXV b) acids. This reaction is carried out at a temperature between 20°C and 70°C and preferably between about 35°C and 40°C in an inert solvent, such as tetrahydrofuran, methylene chloride, ether, chloroform, toluene or the like. The thus-formed acids are then cyclized to the corresponding pyrroloquinoline acetonitrile, depicted by formula (XXXX). This is accomplished by heating the reaction mixture to a temperature between about 75°C and 150°C with an excess of acetic anhydride in the presence of a catalytic amount of sodium acetate or potassium acetate. In general, the above reaction is carried out by treating the reaction mixture with acetic anhydride, acetyl chloride, thionyl chloride or the like, and heating said mixture to a temperature between about 20°C and 100°C. The above reactions are illustrated graphically on Flow Diagram VI below, wherein , R2, X, L, M, Q and R7, are as defined above. 20S857 - 14 - FLOW DIAGRAM VI 10 V } s* f V v i > V | Cxxxxiv) nh. (xvii) 15 \ ? .cooh A/s/ M—• • • ^Yv^--L X (XXXXVa) 3 Q— 5" f conh—c—cn / W i V V\ j cooh (XXXXVb) 20 25 30 (ch3co)2o V f h->V*s V If Q * vv | (XXXX) :-cn 35 / -*\\ 2 6 AUGJ98S ^ P p. 1 M o m/ b - X - A preferred route to pyrroloquinoline acetonitrile of formula (XXXX) is the Diels-Alder thermal cycloaddition reaction of an appropriately substituted maleimide of formula (XXXXVI) with an appropriately substituted anthranil. In this route X must be hydrogen. The outcome of this reaction is dependent upon the reaction temperature. Intermediate of formula (XXXXVII) is obtained at -S5°C. As the reaction mixture is heated further, to temperatures between 55°C and 130°C, the intermediate of formula (XXXXIII) aldehyde is obtained. If the reaction is conducted in the presence of an aprotic solvent such as o-dichlorobenzene, and the reaction mixture heated to between 140°C and 200°C, the reaction yields the pyrroloquinoline acetonitrile of formula (XXXX). The reaction is illustrated on Flow Diagram VII below. % lb - X - flow diagram vii 10 IS 5 ^ \ <j-L J V R -=t/ 7 (xxxxi) M—• * ; /fs ;:v i? 9 qH (xxxxvi) :-cn ;-cn. a 4 20 25 30 (xxxxvii) * s\ m-? s—cho • (XXXXIII) ff —cn 35 % s. n., . , - " V.J c. / I ■' if"';': <■">) SI 'K - FLOW DIAGRAM VII (CONTINUED) i , V s. *■% /% 10 K <? V- 6 -CN 2 (XXXX) 15 The above route is particularly effective when L, M, Q and R7 groups are electronegative, e.g., 20 halogens, nitro, CF3, S02CH3, CN. 25 \« - X - A variation of this procedure involves the reaction of an o-aminoacetal of formula (xxxxviii) with an appropriately substituted formula (xxxxx) maleimide or dioxopyrroline acetamide, in the presence of an aprotic solvent such as xylene or toluene at a temperature between about 50°C and 130°C. These reactions are graphically illustrated below. M-! * chr—or' or ii in (xxxxviii) t fl ">4 :-cn _ ir I A> (xxxxx) l- \ 2.h+ ^ * /™ \ *Vv i k, h ie. (xxxxxi) II M-r L pV< 'v f > 1 1-conh. 1. A 2. HH I M-"' Q—■ v xcho - fl \ 4 V v r7 h A I -CONH. (xxxxviii) (XXXXIII) I i'' V /> , - 11 X- Yet a further variation, useful for synthesis from anilines bearing electron donor substitution in the L, M, Q and R^, positions or one halogen or CF^ function, is the interaction of o-alkyl or arylthiomethylanilines formula (XXXXIX) with a bromomaleimide of formula (XXXXX) 5 to give the maleimide of formula (XXXXXI) which is oxidized to the maleimide of formula (XXXXXII). The maleimide of formula (XXXXXII) is then cyclized in an acid catalyzed reaction to yield the pyrroloquinoline acetonitrile of formula (XXXX). The reactions are graphically illustrated 10 below. R^, R^f L, M, Q and R7 are as defined above. 15 20 25 Aryl or M-f *-CH2Sali£yl f —KH; A. (xxxxix) Bi (xxxxx) ic. * ,CH2Salkyl or Aryl Q— i7 h (xxxxxi) f? ^N-CH-CN VV 8 -2 Oxidation 30 y* /* M—• V S '"VV *7 h V r-u L-alkyl or Aryl „y\/ J (? ,M * i \ ll ( Y a (xxxx) (xxxxxii) 35 2 0 6* Compounds of formula (XXXX) bearing electron donor substitution on the L, M, Q and positions, such as alkyl, alkoxy, alkylthio, dialkylamino, hydroxy and a single halogen may be prepared by reaction of an appropriately substituted o-aminobenzyl alcohol of formula (XXXXXIII) or anthranilic acid of formula (XXXXXXV) with a bromo(or chloro)maleimide of formula (XXXXX). This reaction is conducted in the presence of a protic solvent, such as isopropyl or t-butylalcohol at 0°C to 30°C to yield respectively, the hydroxy-methylanilinomaleimide of formula (XXXXXV) or dioxo-pyrrolinyl anthranilic acid of formula (XXXXXVI). A variety of base acceptors can be employed in the above reactions, e.g., alkaline earth metal hydroxides, such as Ba(0H)2, BaO or sodium acetate. However, the reactions in many instances proceed satisfactorily without the aid of the base acceptor. Oxidation of the formula (XXXXXV) alcohol to the formula (XXXXIII) aldehyde may be accomplished using a wide variety of oxidizing agents exemplified by pyridinium— chlorochromate in methylene chloride or activated manganese dioxide in t-butanol. Cyclization of the aldehyde of formula (XXXXIII) to the pyrroloquinoline acetonitrile of formula (XXXX) is achieved by one of the methods described above, such as heating said aldehyde to between 140°C and 200°C in the presence of an aprotic solvent. Cyclization of the o-anilinocarboxylic acid of formula (XXXXXVI) to the acetoxyquinoline of formula (XXXXXVII) is accomplished with acetic anhydride, triethylamine and 4-dimethylaminopyridine at ambient temperatures. Mild reductive elimination gives the pyrroloquinoline acetonitrile of formula (XXXX). Hydrolysis in warm aqueous acetic acid gives formula (XXXX) where X » OH, further reaction with phosphorus oxychloride and pyridine, affords compounds where X is chlorine. These reactions are illustrated in Flow Diagram VIII below. •—cooh (xxxxxiii) (xxxxxiv) 0 (xxxxx) (xxxxx) o t - - flow diagram vtti ccontinued) 2 06 g 57 * _s\ M-r •—chjoh f 10 K 1 :-cn «-% j .cooh A / (\/ 1 -CN 15 20 (XXXXXV) Oxidation "f /H0 9 a A./ —v I1 ax i-iT x\/ (XXXXXVI) L OAC J .i ^*N j? M—? • ^/V"! A. 1 -cn 25 30 35 (XXXXIII) Reduction V 1*V'V\ t? *Vv & 7 (With X=H) (XXXX) 1 -cn (XXXXXVH) v \ * »y Ys- A 11. V/ v i V (XXXX) ^N-C-CN *3 - Another route to the 2^- (2-imidazol in-2-yl)quino line compounds of formula (II), particularly useful in synthesizing analogs in which the A group is varied, employs the 2-(2-imidazolin-2-yl)quinoline of formula (XXXXXIX). This intermediate is prepared from quinoline-carboxylic acid of formula (XXXXXVIII) which is converted to the acid chloride or anhydride and then reacted with either an appropriately substituted a-aminocarbonitrile of formula (XVII) to give the formula (XXXXXX)nitrile, or with the aminoamide of formula (XXXXXXI) to give the carboxamidoamide of formula (XXXXXXII). Cyclization of said carboxamidoamide is accomplished by the previously discussed procedures, although cyclization with sodium hydride in the presence of xylene is preferred. The above-described reactions are graphically illustrated on Flow Diagram IX below. FLOW DIAGRAM IX The above-described reactions are graphically illustrated on Flow Diagram IX below. (xxxxxviii) (xvii) (xxxxxx) \.. ? (XXXXXXII) - 24 - 206857 The formula (I) and formula (II) 2-(2-imidazolin-2-yl)pyridines and 2-(2-imidazolin-2-yl)quinolines and the formula (III) and formula (VII) imidazopyrrolopyridine-diones and imidazopyrroloquinolinediones and also the formula (IV) dioxopyrrolopyridine and dioxopyrroloquinoline acetamides of the present invention are exceedingly effective herbicidal agents useful for the control of an exceptionally wide variety of herbaceous and woody annual and perennial • monocotyledonous and dicotyledonous plants. Moreover, these compounds are herbicidally effective for controlling weeds indigenous to both dry land and wet land areas. They are also useful as aquatic herbicides and " are unique in their effectiveness in controlling the above-said plants when applied to the foliage thereof or to soil or water containing seeds or other propagating organs of said plants such as tubers, rhizomes or stolons at rates of from substantially 0.016 to 4.0 kg/ha, and preferably at rates from about 0.032 to 2.0 kg/ha. It is, of course, obvious that rates of application above the 4.0 kg/ha level can also be used to effectively kill undesirable plant species; however, rates of applica tion of toxicant above the level necessary to kill the undesirable plants should be avoided since application of excessive amounts of toxicant is costly and serves no useful function in the environment. - 25 - 206857 Among the plants which may be controlled with the compounds of this invention are: Elatine triandra, Sagittaria pygmaea, Scirpus hotarui, Cyperus serotinus, Eclipta alba, Cyperus difformis, Rotala indica, Lindernia pyridoria, Echinochloa crus-galli, Digitaria sanguinalis, Setaria viridis, Cyperus rotundus, Convolvulus arvensis, Agropyron repens, Datura stramonium, Alopecurus myosuroides, Ipomoea spp. , Sida sponosa, Ambrosia artemisiifoliat Eichhornia crassipes, Xanthium pensylvanicum, Sesbania exaltata, Avena fatua, Abutilon theophrasti, Bromus tectorum, Sorghum halepense, Lolium spp., Panicum dichotomiflorum, Matricaria spp., Amaranthus retroflexus, Cirsium arvense, and Rumex japonicus. At rates of application not exceeding about 0.01 kg per hectare, it has also been found that certain of the formula (I) and formula (II) pyridines and quinolines are effective for increasing branching of leguminous crops and affecting early maturation of grains. The formula (XI) pyrrolopyridine acetonitriles, formula (xii) pyrrolopyr idine acetamides, formula (XXXX) pyrroloquinoline acetonitriles and formula (XXXVIII) . pyrroloquinoline acetamides are useful as intermediates for the preparation of the above-mentioned herbicidal formula (I) and formula (II) 2-(2-imidazolin-2-yl) pyridines and quinolines and the herbicidal formula (III) and formula (xxxvii) imidazopyrrolopyridinediones and imidazopyrroloquinolinediones. The following examples illustrate the invention. - 10 EXAMPLE 1 Preparation of 5 ,7-Dihydro-qL-isopropyl-<3.-methyl-■5 , 7-dioxo-6Ei-pyrrolo[ 3 ,4-k3pyridine-6-acetonitrile To a stirred solution containing 212 g quinolinic anhydride in 950 ml methylene chloride is added at a moderate rate 167 g of 2-amino-2,3-dimethylbutyronitrile. The mixture had reached the boiling point of the solution after about one quarter of the aminonitrile had been added and the rate of addition is adjusted to maintain this temperature. After the addition the solution is heated under reflux for a further 4 hours. The solution is cooled, filtered and concentrated to a thick oil. This oil is dissolved in 950 ml acetic anhydride, 6 g anhydrous sodium acetate added and the mixture distilled until the vapor temperature reached 118°C when the heating was continued under reflux for 3 hours. The mixture is concentrated in vacuo the residue dissolved in 500 ml toluene and again concentrated- This is repeated. The residue is slurried with a mixture of ether and hexane and the.crude product which crystallizes collected (3^9 g). This is dissolved in 700 ml _ methylene chloride and filtered through a column ^^ containing 700 g silica gel and the product eluted 25 with methylene chloride. Concentration of the eluant gave 258 g of the desired product. An analytically pure sample with mp 95-96°C can be obtained by the recrystallization of the product --v from ether-methylene chloride. Using the appropriate amino nitrile and quinolinic anhydride in the above procedure, the following pyrrolopyridines are prepared: 30 35 - 27 - 206857 li Ez x y z no°c ch3 ch3 h h h 119 - 123 ch3 c2h5 h h h 95 - 97 ch3 h h h 69 - 73 ch3 ch2ch(ch3)2 h h h oil -(ch2)5- h h h 85 - 87 c2h5 c2h5 h h h 71 - 72.5 ch3 ch(ch3)2 ch3 h h 129.5 - 131.3 ch3 ch(ch3)2 h H • OCH3 108-110 ch3 ch(ch3)2 H H ci 94 - 96 2 06S EXAMPLE 2 Preparation of 5 , 7-Dihydro-9s.-isopropyl-3.-tnethyl-5 ,7 , dioxo-6H-pyrrolo[3,4-b1pyridine-6-acetamide added portion wise with thorough stirring 298 g finely divided nitrile so that the temperature did not go about 72°C. After the addition the temperature is.adjusted to 60-65°C and maintained there for 1 1/2 hours. The mixture is cooled, quenched with ice and finally diluted to approximately 4 liters. After adding 454 g sodium acetate and cooling at 0°C for 2 hours the mixture is filtered, the solids collected and washed twice with 500 ml water containing sodium acetate followed by water to remove all the sulfuric acid. The solid is dried to give 289 g of product, mp 176-178°C. Material made in a similar way and analytically pure had mp 188-190°C. acetonitrile in the above procedure, the following pyrrolopyridineacetamides are prepared. To 330 ml concentrated sulfuric acid is Employing the appropriate pyrrolopyridine- & - - 11 «2 x y z mD°c ch3 ch3 . h h h 203 - 5 ch3 • c2h5 h h h *— VO 1 CO in ch3 -A h h h 195 - 198 15 20 25 30 35 EXAMPLE 3 Preparation of Methyl 2-C(carbamoyl-!,2-dimethyl-propyl)carbamoylInicotinate in mineral oil) is reacted with 500 ml dry methanol under nitrogen. • To this is added 51.4 g of the amide of Example 2 and the mixture stirred at room temperature overnight. The mixture is concentrated, the residue dissolved in methylene chloride and the solution washed first with 150 ml water followed by 150 ml brine. After drying (Na2S02j), the organic phase is concentrated and the residue crystallized from ether to give 47.85 g of product which is analytically pure mp 108-145°C with decomposition. Sodium hydride (0.47 g of a 50? suspension ^ r.-j« ■ , x // ■ - • 'v7 ^ // 31 ^Sv- EXAMPLE 4 Preparation of 5 ,7-Dihydro-a3-isopropyl-<3.-methyl-5 ,7-dioxo-6iL-pyrroloC3 , 4-.k.]pyr id ine-6-acet amide f y>pooH ^ i^VvT3 %Jh Lch > >W- *V 7 CH(CH ) . . " 0 ~ff £H(CHJ 3 2 /\J fa j || ^N—C—CONH. nh3 10 %^-J CH(CH3) 2 To a mixture containing 32 g of (-)-acid in 375 ml of toluene is added 2 ml of dimethyl-formamide followed- by 13 ml of thionyl chloride. 15 After heating at reflux for 1.25 hours, the mixture is concentrated ijn vacuo. The residue is dissolved in 350 ml of tetrahydrofuran, cooled to 0°C and a slight excess of gaseous ammonia bubbled through the mixture. The solvent is removed in vacuo to 20 leave a solid which is washed with water and air-dried. A portion of this solid is crystallized twice from ethyl acetate (with charcoal treatment) to give the desired product as a white crystalline solid, mp 188-189°C U3q5 = + 3.59 (c = 0.0791, DMS0) 25 By essentially the same procedure and using the appropriate acid, the following amides are prepared. 30 35 206857 - 32 - X J\j vf -CONH. Rl R< mp°C CH3 CH(CH3)2 H CH3 CH2CH(CH3)2 H -CHCH2CH2CH2CH2- H CH3 Trans (CH3 to C0NH2) H H 189.5 - 192 25 CCX]D = -3.02 (c = 0.0744,DMSO) H H 176 178 H H 186 188 .r J y\ ^ V--V- 'i 2 6 AUG S985 SI '':~y ' y J* EXAMPLE 5 Preparation of 5-Butyl-N-(1-carbamoyl-1,2-dimethyl propyl)picolinamide ~'H9 \ X * —* n^CUoJ*-io«« tt cooh ch(ch )„ W I 2 32 r 4h(ch3) To a suspension of 20 g of acid in 200 ml of dry tetrahydrofuran is added with stirring 10.7 ml of ethyl chlorformate. The mixture is cooled to -10°C and and 17.1.ml of triethylamine added dropwise so that the temperature does not exceed 0°C. After 10 minutes, a solution containing 14.3 g of the amino amide in 150 ml of dry tetrahydrofuran is added dropwise at 0°C with stirring. The mixture is allowed to reach room temperature and after 2 hours, enough water added to dissolve the solid. The tetrahydrofuran is removed in vacuo. The aqueous residue is extracted with ethyl acetate, and after saturating with salt, extracted again. The organic phases are combined, washed with brine > dried and concentrated. The residual oil crystallized. A portion was crystallized first from methylene chloride-hexane followed by ether-hexane to give analytically pure product mp 83-86°C. Using essentially the same procedures described above the following picolinic acids are prepared. 206857 - 34 - * f3 z—• •-conh—c—c0nh2 Ch(ch3)2 Y Z mp°C CH3 H 126 - 127.5° H CH3 C6H5 H N02 H 158 - 160 EXAMPLE ft Preparation of l,3-Dihydro-a-isopropyl-ci-methyl-l,3-dioxo- 2-H-pyrrolo~ [3,4-h.l quinoline-2-acetonitrile Procedure A ,AA '"vT3 /yV!\j"= i T ;o ♦ ii V-c-cn i T ii >-£-cn nj/ta( ch3 )2 V V nj/ch( ch3 )2 Anthranil (59.6 g, 0.5 mol) is added dropwise under nitrogen, with stirring, over a 45 minute period, to a refluxing solution of a-isopropyl-a-methyl-2,5-dioxo- 3-pyrroline-l-acetonitrile in o-dichlorobenzene (450 ml). After 13 hours the reaction mixture is cooled and methylene chloride added. This solution is passed through a 3 inch silica gel column, by eluting vith. methylene chloride. The ^luate is concentrated to 500 ml and hexane added. A precipitate forms and is filtered off and air dried, to yield the product 110.6 g, (75%) as a light brown solid. Crystallization from ethyl acetate-hexane gives pale yellow crystals, mp 195-196°C. Anal, calcd. for cX7H15N3°2: C' 69.61! H, 5.15; N, 14.33. Found: C, 69.37; H, 5.15; N, 14.43. Employing similar conditions the compounds of Table I are prepared. 10 20 - >& - Procedure B Cyclization of o-formylanilino-maleimides VCH° /yV\f' T II II >-i-CN —> T T || V-C-CN V' NNH/ Nj» CH(CH ) V' NJJ CH(CH3)2 o o A solution of N-(1-cyano-l,2-dimethylpropyl)-2-(o-fformylanilino) maleimide (7.19 g, 0.023 mol) in xylene (300 ml) containing £-toluenesulfonic acid (0.3 g, 0.0016 mol) is heated at reflux for 4 hours using a Dean-Stark trap to collect the eliminated water. The 15 reaction is cooled, evaporated under reduced pressure and dissolved in hot ethyl acetate which is passed through a 3 inch silica gel column. The ethyl acetate fractions eluted are combined to give a solid, mp 195-195.5°C, 5.51 g, (81%) of l,3-dihydro-a-isopropyl-a-methyl-l,3-dioxo-2-H-pyrrolo [3,4-b] quinoline-2-acetonitrile. Other compounds prepared by this procedure are listed in Table I. 25 30 15 20 v-> ( •: j7 EXAMPLE 7 Procedure C Preparation of l,3-Dihydro-a-isopropyl-a-raethyl-l,3-dioxo-2-H-pyrrolol3,4-b] 4-acetoxyquinoline-2-acetonitrile PAcfl I # # # :-CN (CH3}2 V V Y 25 A solution of N-[1-(1-cyano-l,2-dimethylpropyl) 2,5-dioxo-3-pytrolin-3-yl anthranilic]acid (3.27 g, 0.01 mol) in acetic anhydride (20 ml) is treated all at once with triethylamine (10 ml) and dimethylaminopyridine (0.122 g, 0.001 mol). After stirring under nitrogen for 1 hour at 25° the reaction is poured into ice-water. A solid forms and is filtered off. Purification is achieved by re-suspension in ether, filtering and drying. Yield 2.54 g (72%) of product, mp 145-151°C, m+la 352. 30 35 o Table I V If ft M-/W\ T1 " I t n >-*-< q"VvV I. 8 R2 X L M Q R7 Procedure CII3 CH(CH3 2 H H no2 H H a CH3 CH(CH3 2 H II H no2 H « a. cir3 CH(CH3 2 H z o to II H 11 cir3 CH(CH3 2 II II H H NO2 a (2113 CH(C113 2 11 Br 11 h 11 a ch3 ch(ch3 2 II ci H H H a,£ ch3 C!1(CH3 2 H II cf3 II 11 D ch3 CII(CII3 2 h II ii ci II d mp°C 230-232 260-261 P & 161-167 139.5-142 188 Table I cont'd R2 CH(CH3 CH(CH3 CH(CH3 CH(CH3 CH(CH3 CH(CH3 CH(CII3 CH(CH3 CH(CII3 CH(CH3 CH(CH3 C3,:7 C2»5 2 2 2 2 2 2 2 2 2 2 2 X H H M H H II II II II II Cll II II Cll-ll CI II CI II II H 3 II Cll II H 3 H H CH- H OCIlj H II II II Cll. II II II CI H II II II II H Cll3 Cll II CH H CH CI CH II CH H CH II OCH II II Procedure B B B B B B B B B B B ^ A A mp°C 186-190 241-217 244 £ 147-149 v y- Table I cont'd r r2 X l M 0 r ch h II h II H ch £-c4h9 H H 11 H H ch i-C4H9 H II h II h ch t-c4H9 II II H H H ch cyclopropyl H II II H 11 ch ch2cii=ch2 II H II H h ch cyclohexyl H II ii 11 11 (ch 2)5 II II 11 II II ch Cll (Cll3 2 ci II 11 H H ch ch(cii3 2 ch3 h II 11 11 ch cii(cii3 2 f II II II II ch ch (cll3 2 och3 II II II II ch CH(CH3 2 oh II II II 11 Procedure mp°C A A A A A 182-185 A, A A b 161-168 / Table I cont'd R1 R2 X L M 0 R" ch3 ch(ch3)2 h ii ci ii Procedure mp°C 202.5-203.5 N> C* QQ Ot | (T>. "~r ^5 c) 10 >V- EXAMPLE 8 Preparation of 1,3-Dihydro-q-isopropyl-a-methyl-l,3-dioxo-2-B-pyrrolo [3,4-inquinoline-2-acetamide fl _ . . ? /VV'VP3 T ii T >-£-cn » T i ii V-C-CL.... vvylH(cH3)2 vvy iH(cH3)2 l,3-Dihydro-a-isopropyl-a-methyl-l,3-dioxo-2-S-pyrrolo [3,4-lj, ]quinoline-2-acetoni tr ile (0.44 g, 0.0015 mol) is dissolved in conc. sulfuric acid (5 ml) at room temperature and stirred overnight. The reaction <15 mixture is poured onto crushed ice (50 ml) and a white precipitate forms and is filtered off, washed with water, aqueous sodium bicarbonate and water and then vacuum dried. This gives 0.34 g (74%) of product, mp 237-239°C (dec.). Anal, calcd. for C17Hi7N303: C, 65.58; H, 5.50; 20 N, 13.50. Pound: C, 65.03; H, 5.63; N, 13.19. The following compounds are prepared in the same manner as described above. 25 30 3 V m Ob -Xk- Table II * * A . Y Y \4- Yv» -CONH2 z Rl R2 - X L M Q R? mp°C I n w 1 u CH(CH3 }2 H B no 2 B B 225-227(c 10 ch3 CH(CH3 }2 H B B no2 B 2^7-238 ch3 CH(CH3 ]2 H no2 B B B cn3 CH(CH3 }2 a Br B B B 197-198 ch3 CH(CH3 }2 h B CI B B 216-217 15 ch3 CH(CB3 ' 2 h B cf3 B B ■ ch3 CH(CH3 }2 • h B B C?3 B ch3 ch(ch3 }2 h B B CI B 232-234 20 ch3 ch(ch3 }2 b B B B CI 207.5-208.5 cs3 ch(ch3 ]2 h B CH3 B B 226-227 ch3 ch(ch3 ]2 h B B cb3 B 256-260 ch3 ch(ch3 *2 B B B B ch3 25 cs3 ch(ch3 ] 2 B B ocb3 B B 225-280 ch3 ch(ch3 ]2 B B B cb3 ch3 ch3 ch(ch3 >2 B B CH3 B CH3 208-214 ™ 30 15 20 25 AH- Table II (cont'd) 10 CH, C,H«; H H H H H 222-224 ri R2 x l m q r 7 ch3 ch(ch3)2 h ch3 h a ch3 ch3 ch(ch3)2 h h h cl c83 ch3 ch(ch3)2 h ci h a ch3 ch3 ch(ch3)2 h h ci a ca3 ch3 ch(ch3)2 h ci h a och ch3 C3H7 h h a a a ch3 c2H5 h h h a a ch3 c4h9 h h a a h ch3 —"C4H9 h h H a a ch3 i~C4H9 h h a a a ch3 —"C4H9 h h a h H ch3 h h a a h ch3 ch2ch»ch2 h H a a a ch3 • • \ / h h a a h (ch2)5 h h a a a ch3 ch(ch3)2 ci h H h a ch3 ch(ch3)2 ch3 h h a a ch3 ch(ch3)2 p h H a a ch3 ch(ch3)2 och3 h a a h <■ / -S mp°C 195-197 202-205 30 206857 - 45 - Table II cont'd R2 XL M Q R7 mp°C CH3 CH(CH3)2 OH H H H H CH3 CH(CH3)2 OAc H H H H CH3 CH(CH3)2 H CI H H H 198-199 (dec.) 2068 EXAMPLE 9 Preparation of N-(1-cyano-l,2-dimethylpropyl-2-( o-formylanilino)maleimide Procedure A (V> * OH?" )H^h , ^ ^ / \ / L.,^ x *V .v !? CH(CH ) 10 n- n« j CH(CH3)2 • V\ho Ii 3 2 15 20 25 A solution of anthranil (3.55 g, 0.0298 mol) and a-isopropyl-a-methyl-2,5-dioxo-3-pyrroline-1-acetonitrile (5.73 g, 0.0298 mol) in xylene (20 ml) is heated at reflux for 39 hours under nitrogen. On cooling a yellow precipitate forms and is filtered off to give 2.78 g of mp 19l7l92°C product. Anal, calcd. for C17H17N3° 2: C, 65.58 ; H, 5.50; N, 13.50. Found: C, 65.33; H, 5.44; N, 13.36. 30 V /- - 10 15 20 3 2 25 EXAMPLE 10 Procedure B Preparation of N-(1-cyano-l,2-dimethylpropyl)-2-(2-formyl-5-chloroanilino)maleimide .. T ii f 3 * < > Vvi >f« Cr0. /vra0 ff CH J istcH ) ^ HCl -* f 5 / \ j 3 & V Nra-!! M-® j CH(C?„) 0 Pyridinium chlorochromate (4.4 g, 0.0204 mol) in methylene dichloride (20 ml) is added rapidly to a methylene chloride (20 ml) solution of N-(l-cyano-l,2-dimethylpropyl)-2-(5-chloro-2-hydroxymethylanilino)maleimide (4.75 g, 0.0136 mol). After 2 hours the dark reaction mixture is diluted with ether (20 ml) and a yellow precipitate is formed and is filtered off. This solid is redissolved in ethyl acetate:methylene chloride (1:1) and is passed through a silica gel column to give a yellow solid 4.31 g, (92%) with mp 80°C (dec.). The following aldehydes are prepared according to Procedures A or B as shown in Table VII. 30 7 A ^ ^ r* Table VII \j\ J <^1 > • \ V ¥-C-CN R2 1 l • a M 2 Q _jr Example Method mp°C ch(ch3 2 ci h h h ch(ch3 2 h ci h h 5CT ch(ch3 2 h h ci h 49A 80 ch(ch3 2 h h h ci ch(ch3 2 ch3 ' h h h 206-225 ch(ch3 2 h ch3 h 5 50B. 234-238 ch(ch3 2 h h ch3 h 5 OB 210-215 ch(ch3 2 h h h n UJ UJ ch(ch3 2 h h h och3 ch(ch3 2 h h ci ch3 ch(ch3 2 ci h h ch3 ch(ch3 2 h ci h ch3 ch(ch3 2 ci h h och3 ch(ch3 2 ch3 h h ch3 ch(ch3 2 h ch3 h ch3 206857 - 49 - Table VII cont'd *1 *2 l m Q r ch3 ch(ch3 h h h ch3 ch. ch3 ch(ch3 ^ 2 h cf3 e h ch3 ch(ch3 }2 h h cf3 h -(ch-)c h h h h Example Method 20 'vof° ->9*- EXample 11 :-cn Preparation of N-(1-cyano-l,2-dimethylpropyl)-2-(2-hydroxy-methylanilino)maleimide 5 AjH* a/vb ?h T « +11 V-C-CN > I n / V T 2 br'n{j ch(ch ) ^ nh—• /l" 2 Ii 32 Y ch( ch ) 10 o To o-aminobenzyl alcohol, (2 g, 0.0125 mol) and 3-bromo- -isopropyl- -methyl-2,5-dioxo-3-pyrroline-l-acetonitrile (2.7 g, 0.01 mol) is added absolute ethanol ^5 (100 ml) containing 3 g of 5 A pulveriz-ed sieves. The mixture is stirred for 20 hours at room temperature. The solvent is removed and the residue is purified through a silica gel dry column, eluant ether-hexane (2:1). Starting broraomaleimide is first recovered, followed by a bright yellow solid 1.89 g (60%), mp 39-45°C. Anal, calcd. for ci7Hi9N3°3: c' 65.16; H, 6.11; N, 13.41. Found: C, 65.94; H, 6.21; N, 12.87. Other compounds are prepared by the above procedure with variously substituted o-aminobenzyl-alcohols, 25 Employing j^-propanol or _t-butanol for ethanol generally improves the product yield and bases as acid acceptors may also be employed. 30 Table viii \ X /CVH 9 0 1 " /#v f1 /"-j"™ « J R1 R2 L M Q R mp°C CH3 ch(ch3 2 h h h ch3 <=*3 ch(ch3 2 h h ch3 h gum CH3 ch(ch3 2 h ch3 h h gum ch3 ch(ch3 2 ch3 h h h gum ch3 ch(ch3 2 h h h ci ch3 ch(ch3 2 h h ci h 98-100 ch3 ch(ch3 2 h ci h h ch3 ch(ch3 2 ci h h h CH3 ch(ch3 2 h h h och3 CH3 ch(ch3 2 h h ci ch3- ch3 ch(ch3 2 h ci h ch3 ch3 ch(ch3 2 ci h h och3 CH3 ch(ch3 2 ch3 h h ch3 ch3 ch(ch3 2 h ch3 h ch3 oil CH3 ch(ch3 2 h h ch3 CH3 ) R2 ch(ch3)2 ch(ch3)2 (CH2) 5* Table VIII cont'd l m q r h h cf3 h h cf3 h h h h h h 0.04 2s"7 2os? 10 15 20 25 EXAMPLE 1 ? Preparation of 3-Bromo-q-isopropyl-a-methyl-2,5-dioxo« 3-pyrroline-l-acetoni trile 8 ™ 9 *3 -cn /\ j 3 A f H )n-C-CN + Br2 > B V-j Y "(CH3'2 ^8 ®tCVj To a solution of a-isopropyl-a-methyl-2,5-dioxo-3-pyrroline-l-acetonitrile (50 g, 0.25 mol) in acetic acid (500 ml) heated at 75°C is added bromine (40.76 g, 0.255 mol) in acetic acid (80 ml) dropwise with stirring. The reaction is maintained at 85° overnight and evaporated to a syrup, which is dissolved in methylene chloride (300 ml), is cooled to 5°C to which triethylamine (34.78. ml) is added. After stirring for 2 hours the brown methylene chloride solution is diluted with ether and a white precipitate is formed. This is extracted with water (400 ml) and the organic layer is dried over anhydrous magnesium sulfate, then passed through a 2 inch bed of silica gel with methylene chloride to elute. The eluate is obtained as a dark brown oil. Anal, calcd. for C1QH10N2O2Br: C, 44.29; H, 4.09; N, 10.33. Found: C, 43.37; H, 4.05; N, 10.07. 30 ? n:f A -ptv - o 3 9* X- Other bromomaleiinides are prepared in a similar manner. fl _ ✓\J' II V-C-CN Br' ^ 2 10 15 20 *1 r2 ch3 c2h5 ch3 C4H9 ch3 C4H9-iS£ ch3 C4H9-sec ch3 C^H^-tert ch3 •— • / \ N V KCH2>5-ch2ce ch3 ch3 ch2ch=ch2 25 30 10 15 20 EXAMPLE 13 Preparation of q-isopropyl-a-methyl-2,5-dioxo-3-pyrroline-1-acetoni trile /Nf5- I! fa3 > Ii SC0NH-i-CH Y Ah(CH3)2 CH(CH3)2 A solution of N-(1-cyano-l,2-dimethylpropyl)-maleamic acid (595 g, 2.83 mol) in acetic anhydride (3.96 liters) containing sodium acetate (13.72 g, 0.167 mol) is heated under reflux for one hour, cooled and the solvent removed in vacuo. The product is distilled* at 120-130°C/0.1 nnn to give 337 g (63%) of product. *The pot temperature should not excede 200°. Anal, calcd. for C10H12N2°2: C,' 62.49? H, 6.29; N-, 14.57. Found: C, 62.32; H, 6.36; N, 14.59. 25 30 * 206f57 - 56 - In a similar manner the following compounds are prepared. 10 15 20 CH- CH- CH- CH- CH- CH- CH. CH- tf _ Oj1 8 k -CN 2 CH(CH3)2 C2H5 C3H7 c4H9 C^g-iso C^Hg-sec C4HD-tert / \ • ( \ / mp°C oil 25 CH- / \ •{ch2)5- CH 3- ch2ch=ch2 oil oil 30 r* Qs>\ 2 6 AUGS85 j. . ^ /' / ft* ,-/y .si -X- EXAMPLE 14 Preparation of N-[1-(1-cyano-l,2-dimethylpropyl)-2,5-dioxo-3-pyrrolin-3-yl1 anthranilic acid A /c°2r r \\ V Nh. h(ch3)2 A/C02H » T ii /• • v t • V ^ra-S A mixture of anthranilic acid, (13.7 g, 0.1 mol), 3-brOmo-a-isopropyl-a-methyl-2,5-dioxo-3-pyrroline-1-acetonitrile (27 g, 0.1 mol), isopropanol (200 ml) and sodium acetate (8.2 g) is stirred at room temperature 3 days and then is heated at reflux 1 hour. On cooling, and with the addition of ether, a yellow solid 31.6 g, (97.7%) is obtained, mp 262-266°C after crystallizing from acetic acid. Anal, calcd. for C]_7Hi7I?3°4; c' 62.37; H, 5.24; N, 12.84. Found: C, 62.24; H, 5.19; N, 12.70. to 1.7 »s^ ,v v. Vy r , /,■' In a similar manner other maleimides may be prepared. \ A /°*H 9 . * ii /*\ ?i /V\h-J Xf™ 5 2 15 r1 r2 l m q r7 gh3 ch(ch3)2 h ci h h ch3 ch(ch3)2 h h ci h ch3 ch(ch3)2 h ch3 h h ch3 ch(ch3)2 h h ch3 h 20 25 30 \ example 15 Preparation of N-(1-carbamoyl-l,2-dimethylpropyl)-quinaldamide /Y\ fa ;-conh2 s(cs3)2 To a solution of quinaldic acid (20 g, 0-116 mol) in tetrahydrofuran (500 ml) cooled to -9°C is added methyl chloroformate (8.92 ml, 0.116 mol) followed by triethylamine (18.4 ml, 0.139 mol). After 20 minutes a-isopropyl-a-methyl-3-pyrroline-l-acetamide (15.1 g, 0.116 mol) is added and the mixture stirred overnight at room temperature. Water is added and the solution A is reduced to 200 ml on a rotorvap. A white solid separates and is filtered off, water washed and dried. Recrystallization from absolute ethanol gives the product mp 179-180°C, 26.86 g (87%). Anal, calcd. for C16H19N3°2: C' 67-34' H' 6.73; N,14.72. Found: C, 67.14; H, 6.17; N, 14.72. 206SS7 - 60 - In a similar manner other quinolinecarboxamides may be prepared. M ^ ? 1W\ i Ii I I' ^•yv "i"0"™1 H, 2 R^ R2 X L M Q R7 mp°C CH3 ch(ch3)2 0CH3 h h h h 167-169 CH3 ch(ch3)2 CH3 h h h h CH3 ch(ch3)2 ci h h h h 188-195 ch3 ch(ch3)2 h h h h ci 223-224 ch3 ch(ch3)2 . H h ■h ' h no 2 CH3 c2h5 • h h h h h ch3 cijhg-sec h h h h h (ch2)5 h h h h h CH3 ch(ch3)2 h h h h Br EXAMPLE 16 Preparation of a-Isopropyl-3-methyl-2,5-dioxo-3-pyrroline-1-acetamide 3-pyrroline-l-acetonitrile (2.0 g, 0.104 mol) in methylene chloride (30 ml) is added in a fine stream to concentrated sulfuric acid at room temperature. After stirring overnight at room temperature for 16 hours the mixture is poured onto ice, containing sodium chloride and ethyl acetate. The organic layer is washed with aqueous sodium • * »* • bicarbonate, brine-and dried. Evaporation after washing with ether-pentane gives a solid (72%), mp 138.5-140°C. Anal, calcd. for C, 57.13; H, 6.71; N, 13.33. Found: C, 56.89; H, 6.64; N, 13.16. 5 10 A solution of a-isopropyl-a-methyl-2,5-dioxo- 25 30 - a ZOi<ZSl Ih a similar manner other imideamides are prepared. (CH2>! 25 5 9 o fl s y f—c—CONH • \ / \ K 10 ri r2 ch3 c2b5 • ch3 c3h7 15 ch3 c4h9-n ch3 C4H9-iso ch3 C^hg-sec ch3 . c4hg-tert 20 • , ch3 /\| ch3 ch2ch=ch2 ch3 \ \ / 30 fp**. ii ' ■ EXAMPLE 22 Post-Emergence Herbicidal Evaluation of Test Compounds The postemergence herbicidal activity of the compounds of the present invention is demonstrated by the _5 following tests, wherein a variety of monocotyledonous and dicotyledonous plants are treated with test compounds dispersed in acueous acetone mixtures. In the tests, seedling plants are grown in jiffy flats for about two weeks. The test compounds are dispersed in 50/50 acetone/ water mixture 10 containing 0.5% TWEEN3 20, a polyoxyethylene sorbitan mono-laurate surfactant of Atlas Chemical Industries, in sufficient quantity to provide the equivalent of about .016 kg of 10 kg per hectare of active compound when, applied to the plants through a spray nozzle operating at 4 0 psi 'for a pre-15 determined time,. After spraying, the plants are placed on greenhouse benches and are cared for in the usual manner, commensurate .with conventional greenhouse practices. From 4 to 5 weeks after treatment,-the seedling plants, are examined and rated according to the rating system provided below 20 The data obtained are recorded in Table XI below. Ratine System % Difference in Growth ■from the Check* 0 - No effect 0 1 - Possible effect 1-10 25 2 - Slight effect 11-25 3 - Moderate effect 2 6-4 0 5 - Definite injury 41-60 6 - Herbicidal effect 61-75 7 - Good Herbicidal effect 76-90 3q 8 - Approaching complete kill 91-99 9 - Complete kill 100 4 - Abnormal growth, that is, a definite physiological malformation but with an over-all effect less than a 5 on the rating scale * 35 In most cases the data are for a single test, but in several stances, they are average values obtained from more than cr.e test. 10 15 _ Barnyardgrass Green foxtail Purple Nutsedge Wild Oats Quackgrass Field Bindweed Cocklebur Morningglory Ragweed Velvetleaf 3arley Corn Rice Soybean Sunflower Wheat 2os ?5 7 >K- Plant Soecies Used (Zchinochloa crusgalli) (Setaria viridis) (Cyperus rotundus L.) (Avena Fatua) (Agropyron resens) (Convolvulus arvensis L.) (Xanthium per.svlvanicum) (Ipomoea purpurea) (Ambrosia artemisiifolia) (Abutilon Theophrasti) (Hordeum vulgare) (2ea mays) (Oryza Sativa) * (Glycine max) (Helianthus annus) (Triticum aestivum) 20 25 30 35 n Table XI POST-EHERGEHCE TESTS — RATES IH KG/HA RATE BARIJV AROGR GREEN rox P HUT SEOOE Willi OATS QUACK GRASS FLO B imin hRIIGL RY 5P RAGWE EO VELVE TLEAF 8 BAR LY LA CORH FIELD COTTO N RICE, IIATO SOYBE AN AO Compound <3l-Cyclopropyl-5 ,7-dihydro-<L-methyl-5 ,7-dioxo-6n-pyrrolo[3»1-b]- pyrldlne-6-aoetamlde 5.000 1.000 9.0 9 0 8.0 9.0 9 0 .500 9.0 9 A A n . o n 9 a 9 0 9 0 9 0 9.0 9 0 9.0 .0 9 0 9 0 1 .250 9.0 9 0 0.0 9.0 a 0 9 0 9 0 . 9 0 9.0 9 0 9.0 .• 9 0 f 0 .ICS 9.0 9 0 0.0 9.0 0 0 9 0 9 0 J 0 0.0 9 0 6.0 .0 0 0 0 0 UI .065 7.0 9 0 2.0 7.0 1 0 9 0 7 0 2 0 0.0 9 • 4.0 .0 0 0 0 0 i .0)2 2.0 7 0 1.0 1.0 6 0 9 0 7 0 1 0 0.0 9 0 3.0 .0 J 0 7 0 1 N> o $ *4 ' . • ' ") r-:p *~rp } / a - >8s- ' EXAMPLE 23 Preemercence Herbicidal Evaluation of Test Compounds The preemergence herbicidal activity of the compounds of the present invention is exemplified by the 5 following tests in which the seeds of a variety of monocotyle-donous and dicotyledonous plants are separately mixed with ^ potting soil and planted on top of approximately one inch of soil in separate pint cups. After planting, the cups are sprayed with the selected aqueous acetone solution containing 10 test compound in sufficient quantity to provide the equivalent of about 0.016 to 10 Jcg per hectare of test compound per cup. The treated cups are then placed on greenhouse benches, watered and cared for in accordance with conventional greenhouse procedures. From 4 to 5 weeks after treatment, 15 the tests are terminated and each cup is examined and rated according to the rating system-set forth above. The herbicidal proficiency of the active ingredients of the present invention is evident from the test results which are recorded • in Table XII below. Where more than one test is involved for a 20 given compound, the data are averaged. 25 30 35 </div>

Claims

<div class="application article clearfix printTableText" id="claims"> n' Table XII ptte-ellfrccltce tes13 -- rates ih kg/ha Compound 4,-Cyclopropyl -5,7-d i hydro-ol-me thy 1 -5,7-dloxo-6U-pyrrolo[ 3, 'J-b]-pyrldine-6-acetamide bariiy greek p hut who quack fir b wltgl rague veive 3 bar corii cotto rice, soybe rate ai100r fox seuge oats grass iiigco ry 5p eo t leaf iy la field ii iiato am ao .500 9.0 9.0 9.0 9.0 0.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0 1 .250 6.0 9.0 9.0 9.0 0.0 9.0 9.0 6.0 9.0 9.0 9.0 9.0 9.0 9.0 cl . 12s 1.0 6.0 6.0 7.0 9.0 e.o 0.0 2.0 9.0 9.0 9.0 7.0 9.0 7.0 .061 1.0 1.0 6.0 • 3.0 •• .0 9.0 4.0 0.0 7.8 7.0 4.0 4.0 1.0 1 - 68 - 206957 WHAT WE CLAIM IS: V-' 1. A compound of the following formula: f o „ ] o T j •cooa ✓\ t . VJ h • Vs-/ 3 j r>4^ • I L>H / V\0HJl /V j i3 r'V | """-j .C0NH-<-C0NH2 wherein is alkyl; is C^-C alkyl or C^-Cg cycloalkyl; and when R^ and R^ are taken together with the carbon to which they are attached they may represent C -C, cycloalkyl optionally substituted with 3 b methyl; R^ is hydrogen, difC^-C^ alkyl)methylideneamino, C^-C^2 alkyl optionally substituted with one of the following groups: C^-C^ alkoxy, halogen, hydroxy1, C^-C^ cycloalkyl, benzyloxy, furyl, phenyl, halophenyl, (Cj-C3 alkyl)phenyl, nitrophenyl, carboxyl, (C^-C^ alkoxy) carbonyl, cyano or tritC^-C^ alkyl)ammonium; C3~C12 al^enyl optionally substituted with one of the following groups: Ci-C3 alkoxy, phenyl, halogen or (C-^-C^ alkoxy) carbonyl or with two C^-C^ alkoxy groups or two halogen groups; C^-C, cycloalkyl optionally substituted with one O D or two C^-C^ alkyl groups; C3~C10 alkyny1 optionally substituted with one or two C^-C^ groups; or, a cation; - 69 - 206957 X is hydrogen, halogen, hydroxyl or methyl, with the proviso that when Y and Z are taken together to form a ring and YZ is -(CH2)n~> where n is 3 or 4, X is hydrogen; Y and Z are each hydrogen, halogen, C^-Cg alkyl, hydroxy-C -C4 alkyl, Ci-Cfc alkoxy, C1-C4 alkyl-thio, phenoxy, C1-C4 haloalkyl, nitro, cyano, C1-C4 alkylamino, ditC^-C^ alkyl)amino or C1-C4 alkylsulfonyl group, or phenyl optionally substituted with one C1-C4 alkyl, C1-C4 alkoxy or halogen; and, when taken together, Y and Z may form a ring in which YZ is: -(CH2)n~j where n is an integer of 3 or 4, provided that X is hydrogen; or L M Q R7 , where L, M, Q and R7 are each hydrogen, halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkylsulfonyl, C4-C4 haloalkyl, NO2, CN, phenyl, phenoxy, amino, C1-C4 alkylamino, difCj-C^ .alkyl) amino, chloro-phenyl, methylphenyl, or phenoxy substituted with one CI, CF3, NO2 or CH3 group, with the proviso that only one of L, M, Q or R7 may represent a substituent other than hydrogen, halogen, C1-C4 alkyl or C1-C4 alkoxy; and when Rl and R2 are not the same, the optical isomers thereof. 2. A compound according to Claim 1 of the following formula: .wherein R^, R2, X, Y and Z are as described therein. - 70 - 206SS7 3. A compound according to Claim 1 of the following formula: V » vt /V" 6 -conh, wherein Ri, R2, X, Y and Z are as described therein, 4. A compound according to Claim 1 having the structure: \ A /coos> I II • . m v\_ f 1 CONH—C—CONH X 2 wherein , R2, R3, X, Y and Z are as described therein. 5. A compound according to Claim 1 of the follow ing formula: r N-C-CONH-, o*- wherein Y is hydrogen, alkyl, C1~C4 alkoxy, cyano, nitro or halogen; R;[ is alkyl; R2 is C^^ alkyl or cycloalkyl; and when R^ and are taken together with the carbon to which they are attached, they represent C3~C6 cycloalkyl optionally substituted with methyl;and when and R2 are not the same' an optical isomer thereof. (i - 71 - 2.06857 6. A compound according to Claim 1 of the following formula: .1 ONH-C-CONH-

1 2 *2 wherein Y is hydrogen, C^-C^ alkyl, alkoxy, cyano, nitro or halogen; is C^-C^ alkyl; R2 is C^-C^ alkyl or C~Cc cycloalkyl; and when R.. and R are taken together 3 6 1 2 with the carbon to which they are attached, they can represent C--C., cycloalkyl optionally substituted with 3 b methyl; and when R^ and R2 are not the same, an optical isomer thereof. 7. A compound according to Claim 2, wherein the compound is 5 , 7-dihydro-a-isopropyl-a-methyl-5,7-dioxo-6H-pyrrolo [ 3 , 4-b] pyridine-6-acetonitrile, a-cyclo-propyl-5 , 7-dihydro-a-methyl-5 , 7-dioxo-6H-pyrrolo [ 3, 4-b] -pyridine-6-acetonitrile, 5 ,7-dihydro-a-isopropyl-2-methoxy-a-methyl-5 , 7-dioxo-6H-pyrrolo [ 3 , 4-b] pyridine-6-acetonitrile, 1, 3-dihydro-a-isopropyl-a-methyl-l, 3-dioxo-2H-pyrrolo- [ 3 , 4-b] quinoline-2-acetonitrile , or 2-chloro-5 , 7-dihydro-a-isopropyl-a-methy 1-5 , 7-dioxo-6H-pyrrolo [ 3 ,4-b] pyridine-6-acetonitrile. 8. A compound according to Claim 3,. wherein the compound is 1, 3-dihydro-a-isopropyl-a-methyl-l, 3-dioxo-2H-pyrrolo [ 3 , 4-b] quinoline-2-acetamide or 2-chloro-5,7-dihydro-a-isopropyl-a-methyl-5 , 7-dioxo-6H-pyrrolo [ 3 ,4-b] pyridine-6-acetamide. 9. A compound according to Claim 3, wherein the compound is 5 , 7-dihydro-a-isopropyl-a-methyl-5 ,7-dioxo-6H-pyrrolo[3,4-b]pyridine-6-acetamide. 206957 - 72 - 10. A compound according to Claim 4, wherein the compound is methyl

2-[(1-carbamoyl-l,2-dimethylpropyl) carbamoyl]-nicotinate 11. A method for the control of monocotyledonous and dicotyledonous annual, perennial and aquatic plant species comprising: applying to the foliage of said plants or to soil or water containing seeds or other propagating organs thereof, a herbicidally effective amount of a compound of the following formula: f * h n./ \(-i-cotra2 A/"""* i. wherein R^ , R^, X, Y and Z are as defined in Claim 1. 12. A method according to Claim 11, wherein said compound is applied to the foliage of said plants or to soil or water containing seeds or other propagating organs of said plants at a rate between substantially 0.16 to 4.0 kg/ha. 13. A herbicidal composition comprising an inert solid or liquid diluent and a herbicidally effective amount of a compound having the formula: X, Y and Z are as defined in Claim 1. WAT£D THISDAY OF A. J. PARK & SON per j -s ■ ^ AGENTS FOR THE APPLICANTS </div>