IE46511B1 - Herbidical compositions - Google Patents

Abstract

New compounds of the formula: in which R1, R2, R4 and X have the meanings given in Claim 1 can be used for the pre-emergence or post-emergence control of monocotyledon and dicotyledon plant species and for inhibiting the enzyme phosphodiesterase in humans and other mammals. Some of the compounds of the formula I are prepared from new compounds of the formula: in which R, R1, R2 and X have the meanings given in Claim 6 by heating in a nonpolar solvent followed optionally by chlorination or bromination. The compounds of the formula II in which R, R1, R2 have the meanings given in Claim 8 and X represents oxygen or sulphur are obtained by condensation of a 4-imidazolecarboxaldehyde of the formula: with a compound of the formula: H2N-NH-CX2R.h

Description

This invention relates to novel imidazo triazines which show activity both as therapeutic agents and also as herbicides.

More specifically, this invention is concerned with substituted imidazo /T,5qd/ -as - triazin - 4 (3ff) - ones and -thiones which may be represented by the following structural formula J Λ »-»3 »1 R4 wherein X is a divalent oxygen or divalent sulfur; R^ is hydrogen, alkyl (C-t-Cg), bromo, chloro, iodo, or halo alkyl (C-j-C3); R2 is hydrogen, alkyl /cycloalkyl (Cg-Cg), methoxymethyl, benzyl, naphthyl or phenyl optionally mono-substituted with halogen, alkyl C^-C^, alkoxy C-j-C^, haloalkyl C-j-Cg, amino, dialkylamino and nitro, R3 is hydrogen, alkyl C^-Cg .alkenyl (Cg-C^) or alkynyl (fcg-C^); and R^ is hydrogen or alkyl (C-|-C4).

A preferred embodiment of the present invention may he represented by the above structural formula (I) wherein X is divalent oxygen; Rj is methyl, bromo or chloro; R2 is cycloalkyl (Cg-Cg), phenyl or m-tolyl; and Rg and R^ are both hydrogen.

The novel compounds of the present invention are generally obtainable as white to yellow crystalline materials having characteristic melting points and absorption spectra and which may be purified by recrystallization from common organic solvents such as methanol, ethanol, dimethylformamide, chloroform, and the like. They are appreciably soluble in non-polar organic solvents such as diphenyl ether and carbon tetrachloride but are relatively insoluble in water.

The compounds(I) of the present invention wherein Rg and R^ are both hydrogen may be readily prepared in accordance with the following reaction scheme: - 2 1 4β#ΐ1 (Vl) (VII) wherein R is alkyl C^-Cj, and 1(^ and lb, areas hereinabove defined. In accordance with the above reaction scneme, an appropriately substituted 4-imidazolemethanol (II) is oxidized with concentrated nitric acid to provide the corresponding 4-imidazolecarboxaldehyde (III). This oxidation is best carried out by suspending or dissolving each gram of starting material (II) in from about one ml. to about seven ml. of concentrated nitric acid and heating the reaction mixture at steam bath temperature for 2-3 hours. Alternatively, the reaction mixture may first be allowed to stand at room temperature for 8-16 hours and then heated for a short time (15-30 minutes) on the steam bath. The resulting reaction solution is preferably first diluted with water and then neutralized 511 soda with any convenient base such as caustic/, soda ash, or concentrated aqueous ammonia. The precipitated product (III) is removed, washed with water, and purified by recrystallization from common organic solvents such as ethyl acetate, ethanol, and the like. Alternatively, the 4-imidazolemethanol (II) may be oxidized with activated manganese dioxide in chloroform or tetrahydrofuran from room tempeature to reflux temperatures for a period of 4-6 hours to provide the 4-imidazolecarboxalJehyde >(111).

The 4-imidazolecarboxaldehyde (III) may be readily converted to the 3-(4-imidazolylmethylene)dithiocarbazic acid ester (IV) or the 3-(4-imidazolylmethylene)carbazic acid ester (V) by treatment with methyl or ethyl dithiocarbazinate or with methyl or ethyl carbazate, respectively. This condensation is conveniently carried out in a (C-j-C^) alkanol solvent containing a few drops of glacial acetic acid at a temperature of 25°-75°C. whereupon the product (IV) or (V) forms almost immediately and is removed by filtration. Cyclization of the 3-(4-imidazolylmethylene)dithiocarbazic acid ester (IV) and the 3-(4-imidazolylmethylene)carbazic acid ester (V) is readily accomplished by heating in a non-polar high boiling organic a period o^ time, usually solvent such as diphenyl ecner at 175°-275°C. for/15-30 min,for a substantial degree of ring closure to occur utes,'whereby the corresponding imidazo[l,5-d]-as-triazin -4(3H)-thiones (VI) and imidazo[1,5-d]-as-triazin-4(3H)-ones (VII) are obtained.

The compounds (VII) wnerein R^ is chloro or bromo may be prepared by the chlorination or bromination, respectively, of the corresponding compounds (VII) wnerein R^ is hydrogen. This halogenation is accomplished by treating the starting materials with chlorine or bromine in an inert solvent such as chloroform or carbon tetrachloride at steam bath temperature. The oxo compounds (VII) can be converted to the thio compounds (VI) by treating witn phosphorus pentasulfide in an inert solvent such as pyridine at tne reflux temperature. This is a particularly convenient metnod when Rj is halogen.

The compounds (VII) wherein R^ is iodo may be prepared as follows: Tho aldehyde (III) wherein Rj is hydrogen is converted to the dimethyl acetal in methanol/HCl. The dimetnyl acetal is iodinated, and then hydrolyzed to yield the corresponding iodoaldehyde (Ilia): R2 z\ N NH (Ilia) CH0 The thus-obtained iodoaldehyde (Ilia) is then Converted by following the above-described route to the desired compound (VII) wherein Rj is iodo.

Introduction of a R^ substituent into the imidazoas-triazinone ring may be accomplished by treatment of aldehyde (III) with alkyl (C-^-Cj) magnesium bromide followed by a Jones oxidation. The latter method is described by Jones et al in J.C.S. 1946, 39 and in J.C.S. 1953, 457, 2548 and 3019. During oxidation of the secondary alcohol, a ketone (VIII) is obtained. These reactions are illustrated hereinbelow as follows: -CHOH I ALKYL(Cj-Cg) alkyl(Cj-Cg) 10 (VIII) The remaining synthetic steps to the formula (I) product, wherein X is hydrogen and Rg is hydrogen, are accomplisned by the above-described procedures via cyclization of the carbazic acid ester derivative of formula (VIII) ketone in either diphenyl ether or, preferably, o-dichlorobenzene.

Alkylation of formula (I) imidazo-as-triazonone compounds (Rg is hydrogen) at the 3-N-position is accomplished using conventional alkylating agents.

Another superior procedure for the 3-N-methylation of a specific imidazo-aa-triazinone, namely, 8-methyl-6phenylimidazo[1,5-d]-as-triazinin-4(3H)-one is the reaction of the latter triazinone with dimethyl formamide dimethyl acetal in an inert solvent, such as benzene or toluene, at a temper25 ature of about 80-90°C.

Compounds of the present invention are .also active as broad spectrum herbicides and'in inhibiting the enzyme cyclic -AMP phosphodiesterase which is responsible for the metabolism of cyclic AMP. As such, they are useful in the treatment of psoriasis, a disease in which the epidermal cyclic AMP levels are reported to be decreased. Also as such they are useful in the treatment of asthma, since elevated levels of cyclic AMP in most cells are reported to inhibit the release of histamine and other mediators and since elevated levels of cyclic AMP in bronchial smootn muscle are reported to cause bronchodilatlon See Ann. Reports in Medicinal Chem., Vol. 10, 197 (1975).

The inhibition of phosphodiesterase is determined by the mouse skin and monkey lung phosphodiesterase (PDE) inhibition tests as follows: (A) Mouse Skin Inhibition Preparation of Mouse Skin PDE Hairless mice (Jackson Laboratories), 3-4 months old are killed by cervical dislocation and their skins removed. Epidermal slices are taken at a tnickness of 0.2 mm. The slices are weighed and homogenized at 100 mg./ml. in ice-cold tris-HCl buffer (0.04M, pH 8, containing 0.005M MgCl2). Homogenates are centrifuged at 17,000 x gravity for 30 minutes. The supernatants are divided into aliquots wnich are stored at -20°C. Dilutions of the PDE are made with tris-HCl buffer just prior to use.

Anion Exchange Resin AG1-X2, 200-400 mesh (a polystyrene anionic exchange resin 8% cross linked from Bio-Rad Lab.) is washed with 0.5N HCl, 0.5N NaOH, 0.5N HCl and repeatedly with double distilled water to pH 5. The resin is allowed to settle and 2 volumes of water .are added to one volume of settled resin.

Purification of H Cyclic AMP ^Η-Cyclic AMP (21 c/m mole, Schwarz-Mann inc.) is purified by addition of 0.1 to 0.2 ml. of stock (in 50% eth7 anol) to 5 ml. of anion exchange resin and 0.4 ml. of tris-HC1 buffer. The mixture is vortexed, centrifuged at 1200 x gravity for 5 minutes and the supernatant is discarded. The resin is washed in the same manner eight more times with two 3 volumes of tris-HCl buffer. Resin bound H-cyclic AMP is eluted by two successive washings with 4 ml. of 0.025N HCl (resin pH = 2.0). After centrifugation, the pooled acid washes containing H-cyclic AMP are aliquoted and lyophilized. The material is stored dry at -20°C. and reconstituted with tris-HCl buffer just prior to use with a volume sufficient to give approximately 200,000 CPM/0,1 ml.

PDE Assay PDE activity 4s measured by the method of W. J.

Thompson and Ν. N. Appleman, Biochemistry 10, 311 (1971).

Assays are conducted in 12 x 75 mm. polypropylene test tubes.

The reaction mixture consists of H-cyclic AMP (200,000 CPM) unlabeled cyclic AMP, PDE (100 ug. protein) and test compound which are prepared by dissolving the compounds in methanol at a concentration of 10 mg./ml and then dilution in tris-HCl buffer. Pinal concentration of the test compounds in the incubation mixture is 10 ug./ml. The total volume of tne incubation mixture is increased to 0.4 ml. with tris-HCl buffer containing 3.75 millimoles of 2-mercaptoethanol. The enzyme is incubated for 10 minutes at room temperature in the presence of the test compounds or buffer prior to the addition of the mixture of H-cyclic AMP and unlabeled cyclic AMP. Reactions are run at 30°C. for 15 minutes and then terminated by immersing in acetone-dry ice until frozen, followed by boiling for 3 minutes. Tubes are cooled to room temperature. H-5' AMP, formed in the reaction is converted to ll-adenosine by the addition of 0.1 ml. of a solution of 5'-nucleotidase [16 ug,/ml. in double distilled water Crotalus venom (Sigina Chemicals)] to the tubes which are incubated for 20 minutes at room temperature. This reaction is ended by the addition of one ml. of ice cold, stirred resin slurry wnich binds charged nucleotides (including 3H~cyclic AMP) but not ^H-adenosine. Tubes are vortexed and immersed in an ice bath for 15 minutes and then centrifuged at 1200 x gravity for 5 minutes. A 0.5 ml, portion is taken from each, placed in liquid scintillation vials with 10 ml. of Ready-Solv VI (Beckman Ind.) and counted for radio activity. Assay blanks, determined with assay buffer substituted for PDE are less than 1% of total H-cyclic AMP added when H-cyclic AMP is purified as indicated.

(B) Monkey Lung Inhibition Preparation of Monkey Lung Cyclic AMP Phosphodiesterase Lung paraenchyma of African green monkeys is homogenized in a Waring blender and centrifuged at 40,000 x gravity for 20 minutes. The supernatant is brought to 70% saturation of ammonium sulfate, centrifuged and the pellet redissolved and dialysed, before aliquoting and storage at -20°C.

Assay of Monkey Lung Phosphodiesterase Phosphodiesterase is assayed by the method of Thompml son and Appleman, ibid. An assay tube contains a 0.4/solution of the following: 45 mM tris-HCl buffer, pH 7,4, 6,25 MgCl2, 0.1 mM dithioerythritol, 10“6 M cyclic AMP, 0.1 uCi [^h]-cyclic AMP, and test compound at the desired concentration (usually 1 mM or 0.1 mM). Compounds not readily soluble in water are dissolved at 40 times the desired concentration in methanol, and diluted 20 times with water. If tne compound is not dissolved at this time, it is suspended by sonication 6 811 before being diluted 1:2 into the assay tube. In tnis case the activity of the enzyme in the presence of the compound is compared to a solvent control (2.5% methanol), although the solvent alone has negligible effect. The reaction is initiated by additon of enzyme and proceeds at 25 °C. for 20 minutes. It is terminated by incubation at 100°C. for 2 minutes. The tubes are cooled to 25°C., 0.8 ug of 5’-nucleotidase (Crotolus adamantus toxin) is added to each and the tubes incubated at 25°C. for 30 minutes. A one milliliter suspension of Bio-Rad Labs. AGIXI (about 0.5 ml. of settled resin) is added, the tubes centrifuged at 900 x gravity for 10 minutes and an aliquot of supernatant removed for scintillation counting.

The inhibition by the test compound is calculated as: % of control = 'compound1 - 1 blank1 'control' - 'blank' where 'compound' is the cpm in the presence of compound, 'control' is the cpm in the absence of compound, and 'blank* is the cpm in the absence of enzyme. Since this assay requires sequential hydrolysis of cyclic AMP to AMP (by phosphodiesterase) followed by hydrolysis of AMP to adenosine (by 5'-nucleotidase) , a compound which profoundly inhibited nucleotidase would appear to inhibit phosphodiesterase. For tnis reason, 3 control tubes which contained [ H]-AMP instead of [ H]-cyclic AMP are run in parallel. A correction of the apparent phosphodiesterase activity is made for the rare compound which inhibited the hydrolysis of AMP.

Criterion for Activity as Inhibitor of Skin Phosphodiesterase A compound is considered active if it inhibits more than theophylline, that is, to 50% of control at 1 mM con- 10 46811 centration of compound, or to 80% of control of 0.05 mM concentration of compound.

The results with typical compounds of the present invention on inhibition of phosphodiesterase are recorded in Table I below.

TABLE 4β«ΐι TABLE I - (Continued) [ Mouse Skin Phosphodiesterase (A) φ φ φ φ φ φ >>>>>> •rt »rt υ υ υ υ υ υ <<<<<< 5 « O' « C M fi v ►4 +·» n Φ Φ « -rt a *σ « 0 λ ti § a e 0 u Φ fi φ 0 c 1 0 OS 0 43 β <*> fi 4J ο ~ 0 1 •rt ~ 43 1 0 -* 0 K TJ C C K C Π 1 «rt ο Μ 0 *— — N 1 ~ 1 «tf ffi rt ~ — 1 N 44 rt *0 rt 1, rt ι , •rt ι -rt w » 0 ’rt 0 -rt rt fi N g N g rt o rt ή rt ή Ό 43 *0 1 Ό 1 •rt Λ -rt rrt «rt rrt e 5 ε * e >, •rt X ·Η 4J *rt J* ι 0 t a ι x) rrt Qt rrt £Q rrt φ >i 0 >i 1 , 0 Λ Μ N 4J ,c ·Η 4J ti fi H -P Q 0 1 φ φ φ | X 01 0 4J| £ O 1 1 1 1 1 CO K0 KO KO 00 KO . 46311 Some of the novel compounds of the present invention possess anti-hypertensive activity at non-toxic doses and as such are useful as hypotensive agents. These compounds have been tested pharmacologically and found to have sucn pro5 perties with a desirable wide spread between doses producing lowered blood pressure and toxic symptoms. In determining this effect of these compounds on hypertension, adult male, 16-20 week old, spontaneous hypertensive rats from Taconic Farms, Germantown, New York, weighing about 300 grams are used: The rats are dosed by gavage with the test compounds at the indicated dose. All doses of drug were suspended in 2% starch (2 ml./kg.). A second identical dose of tne test compound is given at the 24th hour. The mean arterial blood pressure (MAP) of the conscious rats is measured directly oy femoral artery puncture at the 28th hour. The results of this test on these compounds appear in Table II below. 46S11 TABLE II Compound Dose mg/kg RAP (mm Hq) 28th hour Imidazo[i,5-d J-aa-triatin-4(3H)-thione 100 123 3-Methyl-imidazo[1,5-d] -aa-triazin -4(3H)-tEione 25 130 5-Propyl-imidazo[1,5-d]-aa-triazin -4(3H)-tEione 100 136 B-Methyl-6-phenyl-imidazo [ 1, 5-d] -aa-triazin .-4(3H)-thione 100 128 6-Phenyl-imidazo(1,5-d]-aa-triazin-4(3H)-one 100 117 8-Methy1-6-phenyl-imidazo [1 , 5-d]-as-triazin-4(3H)-one 100 133 6,8-Dimethyl-imidazot1,5-d)-aa-triazin-4(3H)-one 50 70 6-tart-Butyl-imidazo[1,5-d]-aa-triazin-4(3HJ-one 100 135 6-Methyl-iraidazo[1,5-d]-as-trlazin-4(3H)-one 100 120 8-Methyl-iraidazo(1,5-d]-aa-trlazin-4(3H)-one 100 91 6-tert-Butyl-8-methyl-imidazo(1,5-d]-as-triazin-4(3H)-one 100 133 6,8-Dimethyl-imidazo[l,5-d]-ae-triazin -4(3H)-tETone 100 93 8-Methyl-6-propyl-imidazo[l,5-d]-aa-triazin-4(3H)-one 50 127 6-Methoxymethyl-itnidazo[l,5-d)-aa-triazin -4 (3H)-tETone 100 100 Controls vehicle 166 The novel 'compounds of the present invention have tnus oeen found to be highly useful for meliorating astnma and for inhibiting the enzyme phosphodiesterase in mammals wnen administered in amounts ranging from about 1.0 mg to about 100.0 mg. per kilogram of body weight per day. A preferred dosage regimen for optimum results would be from about 5.0 mg. to about 50.0 mg. per kilogram of body weight per day, and such dosage units are employed that a total of from about 0.35 gram to about 3.5 gram of active compound for a subject of about 70 kg. of body weight are administered in a 24 hour period. The dosage regimen may be adjusted to provide the optimum therapeutic response. For example, Several divided doses may be administered' daily or the dose may be proportionally reduced as indicated by the exigencies of the therapeutic situation. A decided practical advantage of this invention is that the active compounds may be administered in any convenient manner such as by the oral, intravenous, intramuscular, or subcutaneous routes, and also by inhalation therapy including aerosol sprays.

Compositions according to the present invention having the desired clarity, stability and adaptability for parenteral use are obtained by dissolving from 0.10% to 10.0% by weight of active compound in a vehicle consisting of a polyhydric aliphatic alcohol or mixtures thereof. Especially satisfactory are glycerin, propylene glycol, and polyethylene glycols. The polyethylene glycols consist of a mixture of non-volatile, normally liguid, polyethylene glycols whicn are soluble in both water and organic liquids and which nave molecular weights of from about 200 to 1500. Although the amount of active compound dissolved in the above venicle may vary »«oii from 0.10 to 10.0¾ by weight, it is preferred that tho amount of active compound employed be from about 3.0 to about 9.0% by weight. Although various mixtures of the aforementioned non-volatile polyethylene glycols may be employed, it is preferred to use a mixture having an average molecular weignt of from about 200 to about 400.

In addition to the active compound, tne parenteral solutions may also contain various preservatives which may be used to prevent bacterial and fungal contamination. The preservatives which may be used for these purposes are, for example, myristyl-gamma-picolinium chloride, benzal kyl ammonium chloride, phenethyl alcohol, £>-chlorophenyl-a-glycerol ether, methyl and propyl parabens, and thimerosal. As a practical matter, it is also convenient to employ antioxidants. Suitable antioxidants include, for example, sodium bisulfite, sodium metabisulfite, and sodium formaldehyde sulfoxylate. Generally, from about 0.05 to about 0.2% concentrations of antioxidant are employed.

For intramuscular injection, the preferred concentration of active compound is 0.25 to 0.50 mg./ml. of the finished compositions. The novel compounds of the present invention are equally adapted to intravenous administration when diluted with water or diluents employed in intravenous therapy such as isotonic glucose in appropriate quantities.

For intravenous use, initial concentrations down to about 0.05 to 0.25 mg,/ml. of active ingredient are satisfactory.

The active compounds of the present invention may be orally administered, for example, with an inert diluent or with an assimilable edible carrier, or tney may be enclosed in hard or soft shell gelatin capsules, or tney may be com17 pressed into tablets, or tney may be incorporated directly with the food of the diet. For oral therapeutic administration, the active compounds may be incorporated with excipients and used in the form of tablets, troches, capsules, elixirs, suspensions, syrups, wafers, and the like. Such compositions and preparations should contain at least 0.1% of active compound. The percentage of the compositions and preparations may, of course, be varied and may conveniently be between about 2% to about 60% of the weight of the unit. The amount of active compound in such therapeutically useful compositions is such that a suitable dosage will be obtained. Preferred compositions or preparations according to the present invention are prepared so that an oral dosage unit form contains between .about 250 and 500 milligrams of active compound.

The tablets, troches, pills, capsules and the like may also contain the following: a hinder such as gum tragacanth, acacia, corn starch or gelatin; excipients such as dicalcium phosphate; a disintegrating agent such as corn starch, potato starch, alginic acid and the like; a lubricant such as magnesium stearate; and a sweetening agent such as sucrose, lactose or saccharin may be added or a flavoring agent such as peppermint, oil of wintergreen, or cherry flavoring. When the dosage unit form is a capsule, it may contain, in addition to materials of the above type, a liquid carrier such as a fatty oil. Various other materials may be present as coatings or to otherwise modify the physical form of the dosage unit. For instance, tablets, pills, or capsules may be coated with shellac, sugar or both. A syrup or elixir may contain the active compound, sucrose as a sweetening agent, methyl and propylparabens as preservatives, a dye and flavoring such as cherry or orange flavor. Of course, any material used in preparing any dosage unit form snould be pharmaceutically pure and substantially non-toxic in the amounts employed .

As indicated above, compounds represented by formula (I) are useful herbicidal agents for the control of both monocotyledonous and dicotyledonous plants. They are effective for the preemergence control of said undesirable .preferably plants,and are' applied at a rate of from 0.07 kg per hectare to 11.2 kg per hectare to soil containing seeds, seedlings or propagating organs of said broadleaf weeds, or grass plants.

The compounds of formula (I) are also effective_for the postemergence control of said undesirable plant species ,are preferably and ' applied at the rate of from 3.28 kg per hectare to 11.2 kg per hectare to the foliage of said plants.

Since the imidazo-ajs-triazinones and imidazo-asfor use as herbicfcles -triazinethiones exhibit limited solubility in water,'they are generally formulated as wettable powders, emulsifiable concentrates, or flowable (thixotropic) concentrates which are usually dispersed in water or other inexpensive liquid diluent for application as a liquid spray. The above compounds may also be prepared as granular formulations containing, generally about 10% to 15% by weight of toxicant.

Typically, a wettabie powder can be prepared by grinding together about 25% to 80% by weight of a formula (I) compound, about 2% to 5% by weight of a surfactant sucn as eodium N-methyl-N-oleoyl taurate, alkyl pneoxy polyoxyetnylene ethanol, or sodium alkyl naphthalene sulfonate, 5% to 10% by weight of a dispersing agent such as a highly purified sodium lignosulfonate and 25% to 63% by weight of a finely divided carrier such as kaolin, attapulgite, diatomaceous earth, or the like.

A typical formulation prepared in accordance with the above description is as follows: 50% by weight of 8-methyl-6-phenyl-imidazo[1,5-d]as-triazin-4 (3H) -one, 3% by weight of sodium i'I-metnyl-N-oleoyl taurate, 10% by weight of sodium lignosulfonate, and 37% by weight of kaolin.

Flowable (thixotropic) concentrates can be prepared by grinding together about 40% to 60% by weight of tne sodium salt of condensed naphthalene sulfonic acid, 2% to 3%. by weight of a gelling clay, 2% by weight of propylene glycol, and from 54% to 32% by weight of water.

A typical granular formulation can be prepared by dissolving or dispersing the active compound in a solvent and applying the toxicant to a sorptive or nonsorptive carrier such as attapulgite, corn cob grits, pumice, talc or the like.

The invention is illustrated by the following specific examples.

Example 1 -Methyl-2-phenyl-4-imidazolemethanol A 100 gm. portion of benzamidine hydrochloride is 46311 dissolved in a minimum of water (350 ml.) at room temperature. A 67 gm. portion of freshly distilled 2,3-butanedione is added giving a yellow solution. Adjusting the pH to 6-7 with 2N NaOH gives a solid which is allowed to stand at 0°C. for 2 hours, collected, pressed dry and then wasned with 100 ml. of acetone. This material is heated with stirring on a steam bath with 855 ml. of concentrated HCl and 2437 ml. of water for 4 hours giving a solution. Cooling to room temperature overnight and then to 0°C. produces a solid which is collected and air dried. This solid is dissolved in 350 ml. of ethanol, filtered and cooled producing a gel, which is taken up in 250 ml. of 50°-60°C. water, adjusted to pH 5.5 with concentrated NaOH and then to pH 7-8 with solid KHCO-j. The mixture is cooled to 0°C. and the product is collected, wasned with water, and air dried. This product is recrystallized from one liter of methanol giving the final product, m.p. 197°199°C.

Alternatively, this product may be prepared by the method of Imbach et al., Bull. Soc, Chim. France, 1971, 1052.

Example 2 2-Phenyl-4-imidazolemethanol This product is prepared by the methods of Dziuron and Sohunack, Arch. Pharm., 306, 347 (1973) and 307, 46 (1974). Example 3 2-n-Propyl-4-imj.dazolumethanol A mixture of 180 gm. of 1,3-dihydroxyacetone dimer, 245 gm. of butyramidine hydrochloride and one liter of liquid ammonia are warmed to 60°C. for 5 hours in a bomb. The mixture is evaporated to dryness and the residue is stirred with 600 ml. of 2-propanol. The mixture is filtered and the fil21 trate is concentrated in vacuo . A 600 ml. portion of 50% saturated aqueous sodium carbonate is added and tne mixture is extracted with three 150 ml. portions of tetrahydrofuran. The combined organic layers are washed with 330 ml. of saturated aqueous sodium carbonate. The organic layer is dried over anhydrous sodium sulfate and evaporated to dryness. The residue is twice recrystallized from acetone giving the product, m.p. 95°-101°C.

Example 4 2,5-Dimethyl-4-imidazolemethanol hydrochloride This product is prepared by the method of Imbach et al., Bull. Soc. Chim. France, 1971, 1052.

Example 5 2-Methyl-4-imidazolemethanol A 189 gm. portion of acetamidine hydrochloride and 180 gm. of 1,3-dihydroxyacetone are combined with one liter of liquid ammonia as described in Example 3, giving the desired product, m.p. 115°-117.5°C.

Example 6 4,5-Dimethyl-2-n-propyl-2-imidazoline-4,5-diol hydrochloride A 112.7 gm. portion of butyramidine hydrochloride is dissolved in 200 ml. of water. A 107 gm. portion of freshly distilled diacetyl is added and the mixture is stirred. The pH is adjusted to 6.5-7.0 with 2N NaOH and the solution is chilled. The desired product is collected as a solid, m.p. 104°-107°C.

Example 7 -Methyl-2-n-propyl-4-imidazolemethanol The product from Example 6 is dissolved in 900 ml. of water and 350 ml. of concentrated hydrochloric acid, heated on a steam bath for 5 hours and then chilled. The solution is concentrated in vacuo and a mixture of 100 ml. of acetone and 100 ml. of ethanol is added. The mixture is filtered.

The filtrate is evaporated and the residue is dissolved in 50 ml. of water and neutralized with a concentrated solution of K2CO3, until bubbling ceases. The top layer is separated and combined with 5 ml. of methanol. On standing, a precipitate forms. The solid is collected and the filtrate is diluted with acetone to give a second precipitate wnich is also collected. The solids are combined and recrystallized from hot acetone giving the desired product, m.p. 134°-136°C.

Example 8 -Methyl-4-imidazolemetnanol This product is prepared by the method of Ewins, J. Chem. Soc. 9j), 2052' (1911) .

Example 9 2-(o-Propoxyphenyl)-4-imidazolemethanol A 130 gm. portion of salicylamide in 500 ml. of ethanol is reacted with 52.4 gm. of sodium metnoxide and 164.9 gm. of 1-iodopropane by heating at reflux. The mixture is cooled, precipitated in 1500 ml. of water and tne solid is recrystallized from hot ethanol giving o-propoxybenzamide.

A 109 gm. portion of the above compound in 500 ml. of chloroform is reacted with 49.4 ml. of methyl fluorosulfonate by refluxing for 3 hours. After cooling, the mixture is concentrated to an oil. Ether is added forming crystals whicn are recovered, giving o-propoxy benzimidic acid methyl ester fluorosulfate.

A 180 gm. portion of this latter product and 55,0 gm. of 1,3-dihydroxyacetone in one liter of liquid ammonia are reacted as in Example 3, giving the desired product, m.p. 90°-92°C.

Example 10 2-Ben.zyl-4-imidazolemethanol A 352 gm. portion of benzyl cyanide, 750 ml. of diethyl ether and 300 ml. of dry ethanol are placed in a two liter, three-necked flask with a magnetic stirrer, drying tube and quick-disconnect gas inlet. The mixture is stirred in an ice bath while hydrogenchloride gas is bubbled in for one hour.

The mixture is placed in a chill room overnight. One liter of ether is added and the mixture is cooled. The precipitate is collected and washed with ether giving ethyliminophenylacetate hydrochloride.

A 272 gm. portion of the above compound and 12ό gm. of 1,3-dihydroxyacetone in one liter of liquid ammonia are reacted as in Example 3 giving the desired product, m.p. 134°-135°C.

Example 11 2-Methoxymethyl-4-imidazolemethanol A 307.2 gm. portion of ethyl 2-methoxyacetimidate hydrochloride [ Rule. J. Chem. Soc. 113, 9 {1918)] and 180 gm. of 1,3-dihydroxyacetone in one liter of liquid ammonia are reacted as described in Example 3 giving the desired product as an oil. A crystalline picrate salt (m.p. 175°-178°C.) is obtained by heating the oily product and picric acid in water. Example 12 2-tert-Butyl~4-imidazolemethanol A mixture of 326 gm. of pivalimidic acid methyl ester hydrochloride and 193.5 gm. of 1,3-dihydroxyacetone in 2 liters of liquid ammonia are reacted as described in Exam24 pie 3, giving the desired product, m.p. 212°-221°C.

Example 13 2-tert-Butyl-5-methyl-4-imidazolemethanol In a two liter, three-necked flask, equipped with a magnetic stirrer, drying tube and gas inlet tube, is put 200 gm. of trimethylacetonitrile, 250 ml. of methanol and 500 ml. of diethyl ether. Hydrogenchloride gas is bubbled in for 2 hours with stirring. The mixture is transferred to a beaker, ether is added and the beaker is covered and stored in a cold room overnight. Λ 500 ml, portion of ether ia added and the solid is filtered and washed with ether, giving white crystals of pivalimidic acid methyl ester hydrochloride.

A 75 gm. portion of the above material is converted to 2,2- dimethylpropionamidine hydrochloride by the method of Brown and Evans, J. Chem. Soc. 1962, 4039.

A 61 gm. portion of this latter product is dissolved in 50 ml. of water with warming and then cooled to room temperature. A 38.3 gm. portion of freshly distilled diacetyl is added and the reaction is continued as described in Exam20 pies 6 and 7 giving tne desired product as white crystals, m.p. 195.5--196,5°C.

Example 14 2-Benzyl-5-methyl-4-imidazolemethanol To a solution of 109.6 gm. of a-phenylacetamidine hydrochloride [Luckenbach, Chem. Ber. 17, 1423 (1884)] in 50 ml. of water is added 55.4 gm. of freshly distilled diacetyl. The mixture is stirred, the precipitate is collected, triturated in portions with 200 ml. of acetone and air dried, giving 2-benzyl-4,5-dimethyl-4,5-dihydroxyimidazolidine.

A mixture of 106 gm. of this latter product, 170 ml. of concentrated hydrochloric acid and 170 ml. of water is reacted as described in Example 7 giving the desired product, m.p. 134°-138°C.

Example 15 2-Phenyl-4-imidazolecarboxaldehyde A 17.4 gm. portion of 2-phenyl-4-imidazolemethanol and 13.4 ml. of concentrated HN03 are heated on a steam bath for 2 1/2 hours. Three drops of fuming HNO3 are added to start the reaction. The pH is adjusted to 8 witn concentrated aqueous Na2CO3 and the mixture is cooled to θ'-C. overnight.

The solid is recovered, washed with water and recrystallized from a mixture of 70 ml. of ethyl acetate and 20 ml. of petroleum ether giving a yellow solid. Treatment of tne mother liquor with petroleum ether gives an additional tacky substance which is triturated with isopropanol giving a second solid. These two solids are taken up in hot isopropanol and recrystallized as a yellow solid. This solid is recrystallized from ethanol:water (1:1) giving yellow crystals, m.p. lb9°-171.5°C.

Example 16 2-n-Propyl-4-imidazolecarboxaldehyde A solution Of 108.6 gm. of 2-n-propyI-4-imidazolemethanol in 107 ml. of concentrated HNO3 is reacted as in Example 15, giving the desired product, m.p. 103.5°-105.5°C.

Example 17 2-n-Buty1-4-imidazolecarboxaldehyde Following the general procedure of Example 15, 2-n-butyl-4-imidazolemethanol is converted to 2-n-butyl-4imidazolecarboxaldehyde.

Example 18 -Methyl-2-phenyl-4-imidazolecarboxaldehyde A 102.1 gm. portion of 5-methyl-2-phenyl-4-imiJazole~ methanol is dissolved in 765 ml. of concentrated HNO-j. Tne solution is cooled in an ice bath and allowed to stand for ib hours. The solution is heated on a steam bath for 30 minutes, diluted with 2.3 liters of water and neutralized with 50% NaOH while cooling in an ice bath. The solid is collected, dried, recrystallized from 200 ml. of ethanol and then from one liter of 1:2 ethanoliwater giving the desired product, m.p. 102°115°C.

Alternatively, this product may be prepared by the method of Diels and Schleich, Chem. Ber. 49, 1711 (1916).

Example 19 -Ethyl-2-phenyl~4-imidazolecarboxaIdehyde The procedure of Example 18 is repeated substituting an equimolecular amount of 5-ethyl-2-phenyl-4-imidazolemecnanol for the 5-methyl-2-phenyl-4-imidazolemethanol employed in that example. There is thus obtained the title compound in equally good yield.

Example 20 2,5-Dimethyl-4-imidazolecarboxaldehyde A 42.2 gm. portion of 2,5-dimethyl-4-imidazolemethanol and 44.8 ml. of concentrated nitric acid are mixed.

When the initial reaction subsides, the solution is heated on a steam bath for one hour. The reaction mixture is neutralized with concentrated aqueous sodium carbonate, then concentrated under vacuum. After leaching the residue with 150 ml. of hot ethanol several times, the combined organic solutions are concentrated under vacuum. Chromatographing the residual oil on silica gel gives a solid which is recrystallized from isopropanol-ethyl acetate to give the desired proauct, m.p. 164,5°-166°C.

Example 21 -Methyl-4-iinidazolecarboxaldehyde This product is prepared by the method of Hubball and Pyman, J. Chem. Soc. 1928, 21.

Example 22 2-o-Propoxyphenyl-4-imidazolecarboxaldehyde A 44 gm. portion of 2-(o-propoxyphenyl)-4-imidazolemethanol is placed in a 2 liter round bottom flask together with 500 ml. of chloroform and 100 gm. of manganese dioxide. The mixture is stirred and refluxed for 5 1/2 hours. The reaction mixture is filtered while hot. The manganese dioxide is triturated with 500 ml. of hot chloroform and filtered.

The two filtrates are combined and evaporated. The solid residue is recrystallized from 200 ml. of hot ethyl acetate and charcoal giving the desired product, m.p. 104°-105°C.

Example 23 2-Methyl-4-imidazolecarboxaldehyde A 143.0 ml. portion of concentrated HNO3 is added in two portions to 119.2 gm. of 2-methyl-4-imidazolemethanol, with cooling after the first portion, and reacted as described in Example 15, giving the desired product, m.p. 170°-176°C.

Alternatively, this product may be made by the methods of Streith et al., Bull. Soc. Chim. France, 4159 (1971) and also Afaushanab et al., J. Org. Chem. 40, 3376 (1975).

Example 24 2-Benzyl-4-imidazolecarboxaldehyde A 125 gm. portion of 2-benzyl-4-imidazolemethanol and 500 g. of manganese dioxide in 2 liters of chloroform are reacted as described in Example 22 giving the desired product, m.p. 130°-136°C.

Example 25 2-(Methoxymethyl)-4-imidazolecarboxaldehyde A 145.9 gm. portion of 2-methoxymethyl-4-imidazolemethanol and 137 ml. of concentrated HHO3 are reacted as described in Example 15. After adjusting the pH to 7.0 with concentrated aqueous Νβ2<303, the solution is concentrated under vacuum. Extraction of the residue three times with hot ethanol gives, after combining and concentrating the extracts, a yellow gum. This gum is chromatographed on silica gel. Fractions 7-15 are combined and recrystailized from 120 ml. of isopropanol, treated with charcoal and the desired product is recovered, m.p. 100°-103°C.

Example 26 2-Ben zyl-5-methy1-4-imidazolecarboxaldehyde A mixture of 8.79 gm. of 2-benzyl-5-methyl-4-imidazolemethanol and 55.7 ml. of concentrated HWO3 is left at room temperature overnight. The solution is heated for 45 minutes on a steam bath, cooled, the basified with aqueous sodium carbonate. After heating the resulting mixture on a steam bath, it is cooled and the solid collected. Two recrystallizations from ethanol give the desired product, m.p. 171°-173°C.

Example 27 2-Benzyl-5~n-propyl-4-imidazolecarboxaldehyde The general procedure of Example 26 is repeated but replacing the 2-benzyl-5-methyl-4-imidazolemethanol employed in that example with 2-benzyl-5-n-propyl-4-imidazolemethanol.

Example 28 -Methyl-2-n-propyl-4-imidazolecarboxaldehyde An 80 gm. portion of 5-inethyl-2-.n-propy 1—1-imiilnzolemethanol is oxidized with 67.3 ml. of concentrated HNOj.

A second portion of 101.4 gm. of the above compound is oxidized with 77 ml. of the acid. The reaction mixtures are combined, neutralized and worked up as in Example 25, giving the desired product, m.p. 126°-129°C.

Example 29 2-tert-Butyl-4-imidazolecarboxaldehyde A 7.7 gm. portion of 2-tert-butyl-4-imidazolemethanol is added to 100 ml. of chloroform and 100 ml. of tetrahydrofuran and heated gently. A 25 gm. portion of manganese dioxide is added and the mixture is reacted as described in Example 22 giving the desired product as white crystals, m.p. 194°-195°C.

Example 30 * 2-tert-Butyl-5-methyl-4-imidazolecarboxaldehyde A 19.76 gm. portion of 2-tert-butyl-5-methyl-4-imidazolemethanol and 16,5 ml. of concentrated HNOg are reacted as described in Example 25 giving the desired product, m.p. 196°-198°C.

Example 31 2-Isobutyl-5-isopropyl-4-imidazolecarboxaldehyde The procedure of Example 30 is repeated substituting an equimolecular amount of 2-isobutyl-5-isopropyl-4-imidazolemethanol for the 2-tert-butyl-5-methyl-4-imidazolemechanol employed in that example. There is thus obtained Die title compound in equally good yield.

Example 32 3-(4-rmidazolylmethylene)dithiocarbazic acid methyl ester A 17.78 gm. portion of imidazole-4-carboxaldehyde (Pyman, J. Chem. Soc. 1916, 186) is dissolved in 200 ml. of hot ethanol. A hot solution of 24.4 gm. of methyl dithiocarbazinate [Audrieth et al., J. Org. Chem. 19, 733 (1954)] in 50 ml. of ethanol is added. A precipitate forms immediately and the mixture is heated and stirred for about 10 minutes. The mixture is cooled to 0°C. The precipitate is collected giving yellow crystals, m.p. 259°-261°C.

Example 33 3-(2-Phenyl-4-imidazolylmethylene)dithiocarbazic acid methyl ester A 35 gm. portion of 2-phenyl-4-imidazolecarboxaldehyde is taken up in 250 ml. of hot ethanol. A solution of 22.8 gm. of methyl dithiocarbazinate in 40 ml. of hot ethanol is added and the procedure of Example 32 is followed giving the desired product, m.p. 166°-170°C.

Example 34 3-[(5-Methyl-2-pheny1-4-imidazolyl) methylene]dithiocarbazic acid methyl ester A 60 gm. portion of 5-methyl-2-phenyl-4-imidazolecarboxaldehyde and 36.8 gm. of methyl dithiocarbazinate are reacted as described in Example 32 giving the desired product m.p. 180°-185°C.

Example 35 3-[(5-Ethyl-2-phenyl-4-imidazolyl)methylene]dithiocarbazic acid methyl ester Following the general procedure of Example 34, 5-ethyl-2-phenyl-4-imidazolecarboxaldehyde is conversed to 3-[(5-ethyl-2-phenyl-4-imidazolyl)methylene]dithiocarbazic acid methyl ester.

Example 36 3-(2-n-Propyl-4-imidazolylmethylene)dithiocarbazic acid methyl ester A 60 gm. portion of 2-n-propyl-4-imidazolecarboxal5 dehyde and 53.7 gm. of methyl dithiocarbazinate are reacted as described in Example 32 giving the desired product, m.p. 95°-104°C, Example 37 3-(2-Methyl-4-imidazolyl-methylene)dithiocarbazic acid methyl ester A 33 gm. portion of 2-methyl-4-imidazolecarboxaldehyde and 40,3 gm. Of methyl dithiocarbazinate are reacted as described in Example 32 giving the desired product, m.p. 274°-279°C.

Example 38 3-(5-Methyl-4-imidazolylmethylene)dithiocarbazic acid methyl ester A 16 gm. portion of 5-methy1-4-imidazolecarboxaldehyde and 19.5 gm. of methyl dithiocarbazinate are reacted as described in Example 32 giving the desired product, m.p. 180°C.(dec.) resolidifies 230°-260°C.

Example 39 3-[(2,5-Dimethy1-4-imidazolyl)methylene]dithiocarbazic acid methyl ester A 20 gm. portion of 2,5-dimethyl-4-imidazolecarboxaldehyde and 20.8 gm. of methyl dithiocarbazinate are reacted as described in Example 32 giving the desired product, m.p. 279°-281°C.

Example 40 3-£[2-(Methoxymethyl)-4-imidazolyl]methylenejdithiocarbazic - acid methyl ester A 40 gm. portion of 2-(methoxymethyl)-4-imidazolecarboxaldehyde and 38.4 gm. of methyl dithiocarbazinate are reacted as described in Example 32 giving the desired product, m.p. 150°-154’C.

Example 41 3-f(5-Methyl-2-n-propyl-4-imidazolyl)methylene]dithiocarbazic acid methyl ester A 20 gm. portion of 5-methyl-2-n-propyl-4-imidazolecarboxaldehyde and 17.7 gm. of methyl dithiocaroazinate are reacted as described in Example 32 giving the desired product, m.p. 175°-179°C.

Example 42 The general procedure of Example 41 is repeated but replacing the 5-methyl-2-n-propyl-4-imidazolecarboxaldehyde employed in that example with 2-benzyl-5~n-propyl-4-imida zolecarboxaldehyde.

Example 43 3-[ (2,5-iJiniethyl-4-imj.dazolyl)muthylene]carbazie acid ethyl ester A 6.2 gm. portion of 2,5-dimetnyl-4-imidazolecarboxaldehyde and 6.24 gm. of ethyl carbazate are reacted as described in Example 32 giving the desired product, m.p. 207.5°210°C. (resolidifies 248°-252“C.).

Example 44 3-(2-n-Propyl-4-imidazolylmethylene)carbazic acid ethyl ester A 7.8 gm. portion of 2-n-propyl-4-irnidazolecarboxaldehyde and 6.24 gm. of ethyl carbazate is reacted as described in Example 32 giving the desired product, m.p. 180°182°C. 46811 Example 45 3-(2-Phenyl-4-imidazolylmethylene)carbazic acid ethyl ester A mixture of 8.16 gm. of 2-phenyl-4-imidazdlecarboxaldehyde and 5.52 gm. of ethyl carbazate are reacted as described in Example 32 giving the desired product, m.p. 196°200°C.

Example 46 3-[(5-Methyl-2-phenyl-4-imidazolyl)methylene]carbazic acid ethyl ester A mixture of 10.25 gm. of 5-metnyl-2-phenyl-4-imidazolecarboxaldehyde and 5.72 gm. of ethyl carbazate in 30 ml. of ethanol containing one drop :of acetic acid is boiled for 30 minutes. The mixture is cooled to 0°C. and concentrated under an air stream on a steam bath. A 50 ml. portion of carbon tetrachloride is added and the mixture is cooled to 0°C. overnight. The solid is collected giving the desired product, m.p. 209°~211°C.

Example 47 3-[(2-o-Propoxyphenyl-4-imidazolyl)methylene]carbazic acid &hhyl ester A 4.3 gm. portion of 2-o-propoxyphenyl-4-imidazolecarboxaIdehyde and 1.98 gm. of ethyl carbazate are reacted as described in Example 32 giving tne desired product, m.p.. 129°—132°C.

Example 48 3-[(2-Benzyl-4-imidazolyl)methylene]carbazic acid ethyl ester To a 37.2 gm. portion of 2-benzyl-4-imidazolecarboxaldehyde in 200 ml. of ethanol is added 20.8 gm. of ethyl carbazate and a few drops of concentrated acetic acid. The mixture is reacted as described in Example 32 giving tne desired product m.p. 184°-185°C.

Example 49 3- (2-tert-Butyl-4-imidazolylmethylene)carbazic acid ethyl eater A 7.6 gm. portion of 2-tert-butyl-4-imidazolecarboxaldehyde and 5.2 gm. of ethyl carbazate in 100 ml. of etnanol are reacted as described in Example 32 giving tne desired product, m.p. 194°-197°C.

Example 50 3-(2-n-Butyl-4-imidazolylmethylene)carbazic acid ethyl ester The procedure of Example 49 is repeated substituting an equimolecular amount of 2-n-butyl-4-imidazolecarboxaldehyde for the 2-tert-butyl-4-imidazolecarboxaldehyde employed in that example. There is thus obtained the title compound in equally good yield.

Example 51 3-(2-Methyl-4~imidazolylniethylene)carbazic acid ethyl ester A solution of 16.68 gm. of ethyl carbazate in 50 ml. of hot ethanol is added to a solution of 16.50 gm. of 2-methyl-4-imidazolecarboxaldehyde in 100 ml. of hot ethanol containing 2 drops of acetic acid. The reaction is carrieu out as described in Example 32 giving the desired product, m.p. 210.5°-211.5°C.

Example 52 3-(5-Methyl-4-imidazolylmethylene)carbazic acid ethyl ester A mixture of 7.0 gm. of 5-methyl-4-imidazolecarboxaldehyde and 7.3 gm. of ethyl carbazate are reacted as described in Example 32 giving the desired product, m.p. 195°203eC.

Example 53 3-[2-(Methoxvmethyl)-4-imidazolyl]methylene carbazic acid i— ί ethyl ester 46S11 A 19.60 gm. portion of 2-(methoxymethyl)-4-imidazolecarboxaldehyde and 16.02 gm. of ethyl carbazate are reacted as described in Example 32 giving the desired product, m.p. 186°-190°C.

Example 54 3-[(2-Benzyl-5-methyl-4-imidazolyl)methy?ene]carbazic acid ethyl ester A 4.08 gm. portion of 2-benzyl-5-methyl-4-imidazole carboxaldehyde and 2.29 gm. of ethyl carbazate are reacted as described in Example 32 giving tne desired product, m.p. 190° -191.5°C.

Example 55 (2-tert-Butyl-5-methyl-4-imidazolyl)methylene]carbazic acid ethyl ester A 6.17 gm. portion of 2-tert-butyl-5-methyl-4-imidazolecarboxaldehyde and 4.20 gm. of ethyl carbazate are reacted as described in Example 32 giving the desired product, m.p. 226°-228.5°C.

Example 56 3-[(2-Isobutyl-5-iso-propyl-4-imidazolyl)methylene]carbazic acid ethyl ester Following the general procedure of Example 55, 2-isobutyl-5-lsopropyl-4-imidazolecarboxaldehyde is converted to the title compound in equally good yield.

Example 57 3-[(5-Methyl-2-n-propyl-4-imidazolyl)methylene]carbazic acid ethyl ester A 12 gm. portion of 5-methyl-2-n-propyl-4-imidazole carboxaldehyde and 9.06 gm. of ethyl carbazate are reacted as described in Example 32 giving the desired product, m.p. 184°-188°C.

Example 58 Imidazo[1,5-dj-as-triazin -4(3H)-thione A suspension of 164,5 gm. of 3-(4-imidazolylmethyl5 ene)dithiocarbazic acid methyl ester in 1.2 liters of diphenyl ether is heated and stirred at 175°C. until tne methylmercaptan evolution subsides (20 minutes). The precipitate obtained on cooling to room temperature is collected and washed with petroleum ether, then acetone. The precipitate is then slur10 ried with 1.2 liters of boiling methanol and filtered while hot to give the desired product, m.p. 271°-273°C.

Example 59 8-Methyl-imidazo[1,5-d]-as-triazin -4(3H)-thione A suspension of 14.39 gm. of 3-(5-methyl-4-imida15 zolylmethylene)dithiocarbazic acid methyl ester in 100 ml. of diphenyl ether is reacted as described in Example 58 giving the desired product as yellow crystals, m.p. 262°-268°C.

Example 60 6-Phenyl-imidazo[1,5-d]-as-triazin -4(3H)-thione A suspension of 7.05 gm. of 3-(2-phenyl-4-imidazolylmethylene)dithiocarbazic acid methyl ester in 100 ml. of diphenyl ether is reacted as described in Example 58 giving the desired product, m.p. 210°C.

Example 61 6-n-Propyl-imidazo[1,5-d]-as-triazin. -4(3H)-thione A 102.2 gm. portion of 3-(2-n-propyl-4-imidazolylmethylene)dithiocarbazic acid methyl ester in 500 ml. of diphenyl ether is reacted as described in Example 58 giving tne desired product as a white solid, m.p. 201.5o-203.5°C.

Example 62 8-Metnyl-6-pnenyl-imidazo[1,5-d]-as-triazin. .-4(3H)-thione A mixture of 73.4 gm. of 3-[(5-methyl-2-phenyl-4-imidazolyl)methylene]dithiocarbazic acid methyl ester and 500 ml. of diphenyl ether is reacted as described in Example 58 giving the desired product as purple crystals, m.p. 237.5°-239°C.

Example 63 8-Ethyl-6-phenyl-imidazo[l,5-d]-as-triazin --4(3H)-thione - — .·.- ----.------- - ....... ..... .....

The general, procedure of Example 62 is repeated but replacing the 3-[(5-methyl-2-phenyl-4-imidazolyl)methylene]dithiocarbazic acid methyl ester employed in that example with 3- L{5-ethyl-i2-phenyl-4-imidazolyl)methylene]dithiocarbazic acid methyl ester.

Example 64 6,8-Dimethyl-imidazo[1,5-d]-as-triazin -4(3H)-thione A mixture of 30.26 gm. of 3-[(2,5-dimethyl-4-imidazolyl)methylene]dithiocarbazic acid methyl ester and 125 ml. of diphenyl ether is reacted as described in Example 58 giving a solid which is the desired product, m.p. 287.5e-290°C. Example 65 6-Benzyl-8-methyl-imidazo[1,5-d]-as-triazin -4(3H)-thione A 2.04 gm. portion of 2-benzyl-5-methyl-4-imidazolecarboxaldehyde is dissolved in 20 ml. of ethanol containing 2 drops of acetic acid. A 1.34 gm. portion of methyldithiocarbazinate is added, the mixture is boiled for 30 minutes and then cooled to 0°C. overnight. The mixture is evaporated giving 3-[(2-benzyl-5-methylinndazo1y]) methylene]dithiocarbazic acid methyl ester as an oil.

A 3 .40 gm. portion of the above product is dissolved in 30 ml. of diphenyl ether and heated for 9 minutes at 194°-207°C. The mixture is cooled to room temperature and diluted with hexane. The solid is recrystallized from 150 ml. of methanol and treated with charcoal giving the desired product, m.p. 207°-209.5°C.

Example 66 6-Benzyl-8-n-propyl-imidazo[1,5-d]-as-triazin -4(3H)-thione The procedure of Example 65 is repeated substituting an equimolecular amount of 3-[(2-benzyl-5-n-propylimidazolyl)10 methylene]dithiocarbazic acid methyl ester for the 3-[(2-benzyl-5-methylimidazolyl)methylene]dithiocarbazic acid methyl ester employed in that example. There is thus obtained the title compound in equally good yield.

Example 67 8-Methyl-6-n-propyl-imidazo[l,5-d]-a£-triazin -4(3H)-thione Λ mixture of 32.12 gm. of 3-[(5-methyl-2-n-propyl-4-imidazoiyl)methylene]dithiocarbazic acid methyl ester and 200 ml. of diphenyl ether is reacted as described in Example 58 giving the desired product, m.p. 183°-186°C.

Example 68 6-Methyl-imidazo[1, 5-d]-as—triazin -4(3H)-thione A mixture of 53.9 gm. of 3-(2-methyl-4-imidazolylmethylene)dithiocarbazic acid methyl ester and 200 ml. of diphenyl ether is reacted as described in Example S8 giving the desired product, m.p. 280.5°-284°C.

Example 69 6-Metnoxymethyl-imidazo[1,5-d]-as-triazin -4(3H)-thione A mixture of 62.4 gm. of 3- [2-(methoxymethyl)-4-imidazolyl]methylene dithiocarbazic acid methyl ester and 3Q 250 ml. of diphenyl ether is reacted as described in Example ... · 4 6 811 58 giving the desired product, m.p. 219.5°-223°C.

Example 70 6-o-Propoxyphenyl-imidazo[1,5-d]-as-uriazin-4(3H)-one A 10.5 gm. portion of 3-[(2-o-propoxyphenyl-4-imida5 zolyl)methylene]carbazic acid ethyl ester in 100 ml. of diphenyl ether is heated on an oil bath with stirring at 255°265°C. until effervesence subsides. The mixture is cooled to room temperature. The addition of petroleum ether produces a solid which is recrystallized from methanol with the aid of charcoal giving the desired product as a bright yellow solid, m.p. 197°-200°C.

Example 71 6-Benzyl-imidazo[1,5-d]-as-triazin-4(3H)-one A 7.0 gm. portion of 3-[(2-benzyl-4-imidazolyl)meth15 ylene]carbazic acid ethyl ester in 50 ml. of diphenyl ether is reacted as described in Example 70 giving tne desired product as white crystals, m.p. 215°-217°C.

Example 72 6-Phenylrimidazo[l,5-d]-as-triazin-4(3H)-one A 7.76 gm. portion of 3-(2-phenyl-4-imidazolylmethyl ene)carbazic acid ethyl ester in 50 ml. of diphenyl ether is reacted as described in Example 70 giving the desired product, m.p. 245°-248°C.

Example 73 8-Methyl-6-phenyl-imidazo[l,5-d]-as-triazin-4(3H)-one An 8.33 gm. portion of 3-[(5-methyl-2-phenyl-4-imidazolyl)methylene]carbazic acid ethyl ester in 60 ml. of diphenyl ether is heated in an oil bath at 215°-230°C. for 20 minutes. The reaction mixture is diluted to 400 ml. with petroleum ether. The precipitate is collected and recrystal40 48511 lized from 350 ml. of benzene giving the desired product, m.p. 182°-184.5°C.

Example 74 6-n-Propyl-imidazo[l,5-d]-as-triazin-4(3H)-one An 8.75 gm. portion of 3-(2-n-propyl-4-imidazolylmethylene)carbazic acid ethyl ester in 50 ml. of diphenyl ether is reacted as described in Example 70 giving the desired product, m.p. 159°-162.5°C.

Example 75 6,8-Dimethyl-imidazo[1,5-d]-as-triazin-4(3H)-one A mixture of 7.37 gm. of 3-[(2,5-dimethyl-4-imidazolyl)methylene]carbazic acid ethyl ester and 50 ml. of diphenyl ether is reacted as described in Example 70 giving the desired product, m.p. 263°-263.5°C.Example 76 6-tert-Butyl-imidazo[1,5-d]-as-triazin-4(3H)-one A 6.15 gm. portion of 3-(2-tert-butyl-4-imidazolylmethyl ene)carbazic acid ethyl ester in 40 ml. of diphenyl ether is reacted as described in Example 70 giving the desired product, m.p. 186°-188°C.

Example 77 b-n-Butyl-imida zo[l,5-d]-as-triazin-4(3H)-one Following the general procedure of Example 76, 3-(2-n-butyl-4-imidazolylmethylene)carbazic acid ethyl ester is converted to the title compound.

Example 78 6-Methyl-imidazo[l,5-d]-as -triazin-4(3H)-one A 27.2 gm. portion of 3-(2-methyl-4-imidazolylmethylene)carbazic acid ethyl ester in 200 ml. of diphenyl ether is reacted as described in Example 70 giving the desired prod41 uct, m.p. 303°-305.5°C.

Example 79 8-Methyl-imidazo[1,5-d)-as-triazin-4(3H)-one A mixture of 10.26 gm. of 3-(5-methyl-4-imidazolyl 5 methylene)carbazic acid ethyl ester and 100 ml. of diphenyl ether is reacted as described in Example 70 giving tiie desired product, m.p. 276°-282°C.

Example 80 6-Benzyl-8-methyl-imidazo[1,5-d]-as-triazin-4(3H)-one 10 A mixture of 4.89 gm. of 3-[(2-benzyl-5-methyl-4-imidazolyl)methylene]carbazic acid ethyl ester and 50 ml. of diphenyl ether is reacted as described in Example 70 giving the desired product, m.p. 244°-247°C.

Example 81 6-tert-Butyl-8-methyl-imidazo[1,5-d]-as-triazin-4(3H)-one A mixture of 5.11 gm. of 3-[(2-tert-butyl-5-methyl -4-imidazolyl)methylene]carbazic acid ethyl ester and 50 ml. of diphenyl ether is reacted as described in Example 70 giving the desired product, m.p, 198°-200°C.

Example 82 6-lsobutyi-8-isopropyl-imidazo[1,5-d]-as-triazin-4(3H)-one The general procedure of Example 81 is repeated but replacing the 3-[(2-tert-butyl-5-methyl-4-imidazolyl)methylene]carbazic acid ethyl ester employed in that example with 3-[(2-isobutyl-5-isopropyi-4-imidazolyl)methylene]carbazic acid ethyl ester.

Example 83 8-Methyl-6-n-propyl-imidazo[l,5-d]-as-triazin-4(3H)-one A 14.50 gm. portion of 3-[(5-methyl-2-n-propyl-430 -imidazolyl)methylene]carbazic acid ethyl ester and 100 ml. of diphenyl ether are reacted as described in Example 7u giving the desired product, m.p. 129.5°-131.5°C.

Example 84 6-Methoxymethyl-imidazo[1,5-d]-as-triazin-4(3H)-one A mixture of 25.9 gm. of 3-t2-(methoxymethyl)-4-imidazolyljmethylene carbazic acid ethyl ester and 125 ml. of diphenyl ether is reacted as described in Example 70 giving the desired product, m.p. 200°-205°C.

Example 35 8-Bromo-6~phenyl-imidazo[1,5-d]-as-triazin-4 (3H)-one A 3.0 gm. portion of 6-phenyl-imidazo[1,5-d]-as-triazin-4(3H)-one is stirred with 100 ml. of chloroform.

The mixture is heated slightly and a solution of one ml. of bromine in 10 ml. of chloroform is slowly dripped into the reaction mixture. The mixture is refluxed for one hour, cooled to room temperature, and filtered. To the solid is added aqueous Nt^CO^ and chloroform and the mixture is shaken in a separatory funnel. The remaining solid and the organic phase are combined and evaporated on a steam bath. Methanol and 2-propanol are added and the mixture is treated twice with charcoal. Cooling gives the desired product as a solid, m.p. 192°-194°C.

Example 86 8-Bromo-6-n-butyl-imidazo[1,5-d]-as-triazin-4(3H)-one The procedure of Example 85 is repeated substituting an equimolar amount of 6-n-butyl-imidazo[1,5-d]-as-triazin-4(3H)-one for the 6-phenyl-imidazo[1,5-d]-as-triazin-4(3H)-one employed in that example. There is thus obtained the title compound in equally good yield.

Example 87 8-Chloro-6-phenyl-imidazo[1,5-d]-as-triazin-4(3H)-one A 5.0 gm. portion of 6-pnenyl-imidazo[l,5-d]-as-triazin-4(3H)-one is mixed with 100 ml. of chloroform on a steam bath while chlorine gas is bubbled through the mixture. A 25 ml. portion of methanol is added. Chlorine is again bubbled through for 10-15 minutes. The mixture is cooled to room temperature, transferred to a separating · funnel, washed with aqueous Na2CO2, aqueous NaHSO^ and finally with water.

The mixture is evaporated to 75 ml. on a steam bath, cooled and filtered. The filtrate is evaporated overnight giving a solid. This solid is dissolved in 30 ml. of hot chloroform and filtered. The filtrate is treated with charcoal and 2-propanol is added giving the desired product as a solid, m.p. 201°-203°C.

Example 88 8-Chloro-6-benzyl-imidazo[1,5-d]-as-triazin-4(3H)-one Following the general procedure of Example 87, 6-benzyl-imidazo[1,5-d]-as-triazin-4(3H)-one is chlorinated to give the title compound.

Example 89 8-Methyl-6-phenyl-imidazo[l,5-d]-as-triazin --4(3H)-thione To a solution of 4.5 gm. of 8-methyl-6-phenyl-imidazo-[1,5-d]-as-triazin-4(3H)-one in 100 ml. of pyridine is added 5 gm. of phosphorus pentasulfide. The reaction mixture is heated at 100°C. for 8 hours, filtered, and poured into dilute hydrochloric acid. The precipitated product is isolated by filtration, washed with water, and dried.

Example 90 8-Bromo-6-pheny1-imidazo[1,S-d]-as-triazin -4(3H)-thione The procedure of Example 89 is repeated but substituting an equimolar amount of 8-bromo~6-phenyl-imidazo (1,5-d]-as-triazln-4(3ll)-one for the 8-methyl-b-phenyl-imidazo[1,5-dJ-as-triazir 4(3H)-one employed in that example.

Example 91 8-Chloro-6-phenyl-imidazo[1,5-d]-as-triazin-4(3H)-One The use of 5-ohloro-2-phenyl-4-imidazolecarboxaldehyde and ethyl carbazate in the procedure of Example 46 affords 3-[(5-chloro-2-phenyl-4-imidazolyl)methylene]-carbazic acid etnyl ester, wnich is converted to the title compound by heating in diphenyl ether as in Example 70.

Example 92 -Methyl-2-m-tolyl-4-imidazolemethanol A mixture of cis and trans-4,5-dimethyl-2-m-tolyl-2-imidazoline-4,5-diol hydrochloride (9.0 g, 0.035 mole) and 3N hydrochloric acid (135 ml) is stirred and heated on a steam bath for 2.5 hours and then stirred at 0-5° for 0.75 hours. The reaction mixture is filtered to yield 7.4 g. (0.031 mole) of a white solid. The solid is treated with base to afford the title compound, m.p. 190-192°C (d).

Analysis calculated for ci2Hi4K2°' c ?1·26; H 6.98; N 13.85; Found: C 70.94; H 7.07; N 13.92.

Additional imidazolemethanol compounds prepared by the above procedure are listed in Table III below.

Table III N-n—CH2OH R2%JL·, r2 m η ίΓ°\ Analysis calculated Found02n-^Q>- 215-216((3) C 56.65 H 4.75 N 18.02 C 56.64 H 4.73 N 17.74 >150(d) C 71.26 H 6.98 N 13.85 C 70.86 H 6.97 N 13.60 CH3-HCl 111-114CH3°-O 205-207 C 66.04 H 6.47 N 12.83 C 65.75 H 6.88 N 12.90 CH3-^~^—. -HCl 132-134(d) «Ο -¾° 205-207(d) C 59.33 H 4.98 N 12.58 C 59.73 H 5.22 N 12.44C1_<cz^ HC1 >170(d) C 59.33 H 5.09 N 10.11 C 59.73 H 5.18 N 9.86 Q- ^ch3 175-177 OCr 188-190 (d) CO·-01 >120(d) C4H9- syrupC6H13 syrup t> 104-106(d) TABLE III (cont.) R2 m.p.(Ce) Analysis Calculated Found E> 115-120(d) O 182-183(d) c 68.00 H 9.34 N 14.42 C 67.73 H 9.55 N 13.87 Example 93 Preparation of 2-substituted 5-methyl-4-imida2olecarboxa)de· Method A -Methyl-2 - mtolyl-4-imidazolecarboxaldehyde A mixture of 5-methyl-2-nitolyl-4-imidazolemethanol (13.0 g, 0.064 mole), activated manganese dioxide (65g) and methylene chloride (200 ml) is stirred at room temperature for 20 hours. The reaction mixture is then filtered, the solvent removed vacua to afford 9.1 g(0.045 mole) of peach-colored solid.

Method B -methy1-2-(p-nitrophenyl)-4-imidazolecarboxaldehyde A mixture of 5-methyl-2-(p-nitrophenyl)-4-imidazole15 methanol (2.9 g, 0.012 mole) and 70% nitric acid (20 ml) is stirred at 50°C for 3 hours, followed by dilution with water and neutralization with base. The precipitated yellow solid is collected by filtration to yield 2.4 g (0.011 mole) of title product, dec >270°C.

Analysis calculated for C-^^HgNgO^: C 57.14; H.3.92; N 18.17; Found: C 56.69; H 3.96; N 18.08.

Method C Preparation of 2-alkyl(cycloalkyl)-5-methylimidazole-4-carboxaldehydes.

A mixture of 2-alkyl(cycloalkyl)-5-methyl-4-imidazolemetnanol (0.1 mole), activated manganese dioxide (0.5 mole) and chloroform (500 ml) is stirred and refluxed for two hours, then stirred overnight (appx. 15-16 hours) at room temperature. The mixture is filtered througn a bed of filter-aid, the solution evaporated to dryness and the residue 46811 recrystallized from the appropriate solvent.

By one or the other methods of preparation, a number of 2-substituted 5-methyl-4-imidazolecarboxaldehydes are made. The compounds, their method of preparation, melt5 ing points and analytical data are given in Table IV below. 46311 Table IV CHO ch3 R2 Method* Analysis m.p.(C°) Calculated FoundcH3 O A 142-194(d) N 13.99 N 14.28 CH3O-^ A 161-163(d) C 66.6S H 5.89 N 12.95 C 66.52 H 5.86 N 13.08CIO A 237-239(d) C 59.88 H 4.11 N 12.70 C 59.30 H 4.17 N 12.61 q-„3 A 140-143(d) C 7T79§ H 6.04 N 13.99 C 71.61 H 6.37 N 13.87 00- A » 197-199(d) C 76.25 H 5.12 N 11.86 C 76.15 H 5.25 N 11.81 C4Hg A 83- 84 C 65.03 H 8.49 N 16.85 C 64.85 H 7.96 N 17.04 C6H15 A syrup C 65.00 H 9.42 N 13.79 C 65.72 H 9.15 N 13.64 > A 104-109 o A 114-130 A 159-162 C 68.72 H 8.39 N 14.57 C 69.06 H 8.44 N 14.43 * Preferred solvent is chloroform. g-dioxane and tert-butanol are also used.

Example 94 ot.-Methyl-2-phenyl-4-imidazolemethanol Methyl magnesium to bromide (15.3 ml, 2.5 molar in ether) is added dropwise to a solution of 2-phenyl-4imidazolecarboxaldehyde (3.0 g, 0.017 mole) in dry tetrahydrofuran (45 ml; dried over a molecular sieve) while the temperature of the reaction mixture is maintained with cooling at 25°C. The mixture is stirred for 2 hours and then decomposed by adding a large volume of water dropwise. The mixture is extracted with ether (3 x 75 ml), the ethereal extract is partially evaporated to yield a white precipitate, the crystalline alcohol, m.p. 197-198°C.

Analysis calculated for εχχΗχ2Ν2Ο: C 70-19* H 6.43; N 14.88; Found; C 70.10; H 6.68; N 14.90.

Example 95 g,5-dinjethy1-2-phenyl-4-imidazolemethanol a,5-Dimethyl-2-phenyl-4-imidazolemethanol is prepared from 5-methyl-2-phenyl-4-imidazolecarboxaldehyde (37.0 g, 0,199 mole) by the method of Example 94. The product (38.4 g, 95.5%) is obtained as a white crystalline solid, m.p. 189-190“C.

Example 96 Preparation of methyl 2-phenyl-4-imidazolyl ketone Jones reagent [5 ml; a solution of chromium trioxide (10.3 g) in a mixture of sulfuric acid (8.7 ml) and water (30 ml)] is added at 0-5°C over 1 hour to a solution of methyl-2-phenyl-4-imidazolemethanol (3.0 g, 0.016 mole) in acetone (25 ml). Tne temperature is allowed to rise to 120°C for 30 minutes then water (150 ml) is added. Tne mixture is stirred for 1 hour and the precipitated solid col51 lected by filtration. The solid is treated with 2N hydrochloric acid (15 ml), stirred 5 minutes, and is tnen neutralized with 10% sodium hydroxide. The aqueous mixture is extracted with methylene chloride (3 x 75 ml). Removal of the methylene chloride yields the ketone as a white crystalline solid (1.73 g), m.p. 158-158.5°C.

Analysis calculated for cnHx2N20: C ^θ·95; H 5.41; N 15.04 Found: C 70.34; H 5.52; N 15.08.

Example 97 Preparation of methyl-5-methyl-2-phenyl-4-imidazolyl ketone By the method of Example 96, methyl-5-methyl-2phenyl-4-imidazolyl ketone is prepared from a,5-dimethyl-2phenyl-4-imidazolemethanol (12.Og, 0.059 mole). The product is obtained as a pale yellow crystalline solid (6.88 g, 58.3%), m.p. 188-190°C.

Analysis calculated for C 71.98; H 6,04; N 13.99; Found: C 71.30; H 6.29; N 13.40.

Example 98 Preparation of 2-phenyl-5-imidazolecarboxaldehyde dimethyl acetal A solution of 2-phenyl-5-imidazolecarboxaldehyde (6,10 g, 0.035 mole) in methanol (200 ml) is cooled in an ice bath and then saturated with hydrogen chloride. The reaction mixture is stirred overnight (appx. 15-16 hrs.) and added slowly to cold 6N sodium hydroxide (200 ml). The • O solution is neutralized with concentrated hydrochloric acid and the precipitated solid collected by filtration (7.56 g; 0.035 mole). Recrystallization from chloroform yields white needles, m.p. 158-160°C.

Analysis calculated for ci2H14N2°2: c 66·03? H 6·48; N 12,83 Found: C 65.38; H 7.01; N 12.63.

Example 99 Preparation of 4-iodo-2-phenyl-5-·imidazolecarboxaldehyde dimethyl acetal, and 4-iodo-2-phenyl-5-imid;izolecarboxaldehyde A solution of iodine (10.25 g, 0.0404 mole) in methanol (200 ml) is added with stirring to a solution of 2-phenyl-5-imidazolecarboxaldehyde dimethyl acetal (7.56 g, 0.035 mole) is methanol (200 ml), water (20 ml) and 6N sodium hydroxide (13 ml). The reaction mixture is stirred for 5 hours, and then concentrated in vacuo to about 75 ml volume. Water (200 ml) is added and the precipitated 4-iodo-2-phenyl-5-imidazolecarboxaldehyde dimethyl acetal (2.82 g, 0.0082 mole) is collected by filtration, m.p. 144-148.5°C(d).

The aqueous filtrate is acidified with concentrated hydrochloric acid and the precipitated 4-iodo-2-phenyl-5inndazolecarboxaldehyde (5.51 g, 0.018 mole) is collected by filtration, m.p. 208-210°0(d).

Recrystallization of 4-iodo-2-phenyl-5-imidazolecarboxaldehyde dimethyl acetal from methyl cyclohexane yields white crystals, m.p. 152-153.5°C.

Analysis calculated for C^H^NjOI: C 41.88; H 3.82; N 8.14; Found: C 41.82; H 4.19; N 8.34.

Recrystallization of 4-iodo-2-phenyl-5-imidazolecarboxaldehyde from ethyl acetate yields a white solid, m.p. 211.5-212.5°C.

Analysis calculated for C 40.29; II 2.37; N 9.39; Found: C 40.19; H 2.37; N 9.34.

Example 100 Method for the preparation of 3-[(2-substituted-5-mechyl4-imidazolyl)methylene]carbazic acid methyl escer Λ. 3-[(5-methyl-2-w-tolyl-4-imidazolyl)methylene]-earbazic acid, methyl ester.

A mixture of 5-methyl-2-ot-tolyl-4-imidazolecarboxaldehyde (6.9 g, 0.034 mole), methyl carbazate (3.1 g, 0.034 mole),, methylene chloride (70 ml) and acetic acid (1 drop) is refluxed for 1 hour. The precipitated white solid is collected by filtration to yield 7.1 g (0.026 mole), mp. 162164°C.

By the above procedure, several 2-aryl analogs of the above compound are prepared. These compounds, their melting points and analyses are listed in Table V oelow.

B. Preparation of 3-[(2-alkyl or cycloalkyl-5-methyl-4imidazolyl)methylene]earbazic acid, methyl esters.

A mixture of 2-aIkyl(cycloalkyl)-5-methylimidazole4-carboxaldehyde (0.1 mole), methyl carbazate (0.1 mole), toluene (60 ml) and acetic acid (0.5 ml) is refluxed for 2 hours. The reaction mixture is then cooled down, tne solids are collected by filtration, and are recrystallized from the appropriate solvent.

The 2-alkyl and cycloalkyl compounds prepared by the above procedure are listed in Table V below.

Table V ch=n-nh-co2ch3R1 <Ί R2R1 m.p.(°C) Analysis Calculated Found ojN-^y CH3- 264-265(d) C 51.49 H 4.32 N 23.09 0 50.96 H 4.33 N 23.21 ch3-0- ch3-‘ 226-227(d) ch3o-Q- ch3- 176-178(d) C 58.32 H 5.59 N 19.43 C 58.01 H 5.60 N 19.23 Cl-0- ch3- 234-235(d) C 53734- H 4.48 N 19.14 C 52.95 H 4.42 N 18.99 ch3 ch3- 160-162(d) CCr ch3- >170(d) C4H9- ch3- 189.5- 190.5(d) C 55.44 H 7.61 N 23.52 C 55.09 H 7.71 N 23.54 C6r13- ch3- 164-165(d) C 58.62 H 8.33 N 21.04 C 58.34 H 7.78 N 20.83 ch3- 184-186(d) C 54.04 H 6.35 N 25.21 C 54.25 H 6.49 N 25.33 0 ch3- 196-197(d) 0- CH3- 193-194(d) C 59.07 H 7.63 N 21.20 C 58.62 H 7.61 N 20.80 Cl-θ-.h2o Cl 147-148 C 43.5 H 3.63 N 16.9 C 45.04 H 3.05 N 16.09 Example 101 Preparation of 3-[1-(5-iodo-2-phenyl-4-imidazolyl)ethylidene]carbazic acid, methyl ester A solution of 4-iodo-2-phenyl-5-imidazolecarboxaldehyde (5.21 g, 0.017 mole) in a mixture of methanol (50 ml), toluene (250 ml), acetic acid (1 ml) and methyl carbazate (1.73 g, 0.019 mole) is refluxed for 24.5 hours. Tne solution is then heated for an additional hour, allowing solvent (100 ml) to distill off. The remaining solvent is then removed in vacuo. The solids are extracted with methylene chloride (300 ml), and the extract washed with water (3 x 200 ml). At this point the product crystallizes and is collected by filtration (2.16 g, 0.0056 mole). Evaporation of the filtrate yields additional product (3.44 g, 0.0093 mole). Recrystallization from methanol-methylene chloride yields white crystals, m.p. 145-147°C(d).

Example 102 Preparation of 3-[5-methyl-2-phenyl-4-imidazolyl)ethylidene]carbazate acid, methyl ester.

Methyl 5-methyl-2-phenyl-4-imidazolyl ketone (4.5 g, 0.023 mole) is refluxed with methyl carbazate (2.4 g, 0.023 mole) in toluene (112 ml) for 5 hours. The toluene is removed., and the solid washed with water (3 χ 50 ml). The solid is recrystailized from methanol to yield the product (1.28 g, 20,9%), m.p. 199-201°C.

Analysis calculated for C 61.75; H 5.92; N 20.57; Found: C 60.05; H 6.25; N 19.96.

Example 103 Preparation of 3-[1-(2-phenyl-4-ima.dazolyl)ethylidene]carbazic acid, methyl ester. - 56 — By the method of Example 102, tne title product is prepared from methyl 2-phenyl-4-imidazolyl ketone and methyl carbazate. The product is obtained in 91% yield, m.p. 22b.5227°C.

Analysis calculated for ; C 60.46; H 5.46; d 21.69; Found: C 60.59; H 5.60; N 21.89.

Example 104 Preparation of 6-(aryl)-8-methyl-imidazo[1,5-d]-js-triazin4 (3jt)-ones.

Method A Methyl-6-m-tolyl-imidazo[l,5-dj -AS.-triazin&^-4 (3H)-one.

A mixture of 3-[(5-methyl-2-ra-tolyl-4-imidazolyl)methylene]carbazic acid, methyl ester (5.1 g, 0.019 mole) and £-dichlorobenzene (75 ml) is heated slowly (45 minutes) to reflux, refluxed for 1.5 hours, then stirred at room temperature over night (appr. 15-16 hours). The reaction mixture is filtered to afford 3.9 g (0.016 mole) title product. Recrystallization from o-dichlorobenzene yields partially solvated product, m.p. 188-198°C.

By substituting 3^[5-methyl-2-(α,α,α-trifluoro-’mtolyl)-4-imidazolyl]methyleneJf'Carbazic acid, methyl ester for 3-[(5-methyl-2-m-tolyl-4-imidazolyl)methylene]carbazic acid, methyl ester in the above reaction, 8-methyl-6-(α,α,α-trifluoro-m-tolyl)-imidazo(l,5-d]-as- triazine-4 (3H ,-one can be obtained.

Method B 8-Methyl-6- (p-nitrophenyl) -imidazo [1,5-g] -qg-triazin -4 (3jj) one, monohydrate. 3-[ 2- (£-nitrophenyl)-5-methyl-4-imidazolyl]methyleneicarbazic acid, methyl ester (2.5 g, 0.0082 mole) is immersed in diphenyl ether (25 ml) at 240°C for 20 minutes, then stirred in an ice bath for 1 hour. The reaction mixture is diluted with ether and filtered to afford 2.2 g (0.008 mole) title product. The product is purified via an acetone soxhlet extraction to give a yellow solid, m.p. 295-297°C.

Analysis calculated for ci2HHN5°4: C 49.83; H 3.83; N 24,21; Found: C 49.69; H 3.71; N 23.88.

Method C Preparation of 6-alkyl(cycloalkyl)-8-methylimidazo-[1,5-d]as -triazin-4(3H)-ones.

The above compounds are prepared by Method A excepting that the mixture of 6-alkyl(cycloalkyl)-5-methylimidazole-4-carboxalolehyde methyl carbazone and o-dichloroben15 zene is heated until a boiling point of 180°C is obtained.

The solvent is removed by evaporation and the residue recrystallized from the appropriate solvents.

The compounds prepared by Method A, B and C, their melting points and analyses are listed in Table VI below.

TABLE VI ι «4 Rlr2 r4 Method m.p.(°C)CalcfraW8Found ch3- “Ό H A 169-171.5 ch3- ch3o-0- H A 216-217(a) C 60.93 C 60.52 H 4.72 H 4.80 N 21.86 N 21.70 ch3-ciO H A >240(a) ch3- Q- ch3 H A 185-191 co- H A 247-251(a) Cl- O H B 245-246(a) C 47.00 C 47.72 H 2.15 H 2.41 N 19.93 N 19.57 H 0- CH,· A 281-281.8 CH, σ CH,· A 207-212 ch3 c4h9- H C 118-120 C 58.23 C 58.16 H 6.84 H 6.84 N 27.17 N 27.14 ch3 C6H13- H C 118-119 C 61.51 C 61.28 H 7.74 H 7.61 N 23.91 N 23.68 CH3 0 H C 210.5-211.5 C 56.83 C 56.65 H 5.30 H 5.64 N 29.46 N 29.43 ch3 ........... H C 179-181 ch3 σ H C 145-147 C 64.94 C 63.38 H 7.78 H 8.10 N 21.15 N 20.41 Example 105 Preparation of 6-Phenyl-8-iodo-imidazo[1,5-d]-gs-triazin4(3H)-one. 3-[1-(5-Iodo-2-phenyl-4-imidazolyl)alkylidene]carbazic acid methyl ester (1.01 g, 0.0027 mole) is dissolved in a mixture of o-dichlorobenzene (150 ml) and methanol (15 ml). The solution is heated to the boiling point and boiled for 20 minutes allowing solvent to distill off partially.

The reaction mixture is chromatographed over a silica gel column and eluted with a hexane-etnyl acetate (2:1) mixture to yield the title product (0.63 g, 0.0019 mole). Recrystallization from ethyl acetate-hexane yields the product as yellow needles, m.p. 170-189°C.

Example 106 Preparation of 6- Xp-aminopheny] )-S-methy]-inridazo|j ,5-<ΐ1-αΞtriazin -4 (3g)-one. t Catalytic reduction of 8-methyl-6-(p-nitrophenyl)imidazo(1,5-d]-as-triazin-4(3/f)-one, monohydrate (1.3g, 0.0048 mole) in dimethylformamide (50 ml) with hydrogen in the presence of 10% Pd/C catalyst and at atmospheric pressure, followed by solvent removal in vacuo affords the product (1.0 g, 0.0043 mole). Crystallization from dimetnylformamidewater yields a mustard-yellow solid, m.p. 252-254°C (dec.).

Example 107 Preparation of 8-Bromo-6-(nrann'nopheny] )imidazo . Q ,5-dJ-as triazin-4 (3 fl) -one.

A mixture of S-bromo-e-fe-nitrophenyDimidazo[1,5-d]-as-triazin-4(3H)-one (2.0 g, 0.00595 mole) and catalyst (Ru/C, 5%, 700 mg) are blanketed with nitrogen at atmospheric pressure and dimethylformamide (45 ml) is added.

The flask containing the above mixture is vigorously shaken while hydrogen is introduced and absorbed (399 ml, 0.01785 mole). The catalyst is then filtered and washed with dimethylformamide. The filtrate is evaporated in vacuo. . The product is recrystallized from diethyl ether, m.p. 205°C (dec.).

Example 108 Preparation of 8-Bromo-6-(ni-dimethylaminophenyl)-imidazo[1,5-d]-as-triazin-4 (3 H>-one.

Sodium cyanoborohydride (1.2 g, 0.019 mole) is added to a stirred solution of 8-bromo-6-(m-aminophenyl)imidazo- [1,5-d]-as -triazir. -4(3]i)-one, aqueous formaldehyde (5 ml, 37%) in acetonitrile (110 ml). The reaction mixture is stirred for 15 minutes then acetic acid is added to adjust the pH of the reaction mixture to 7. The reaction mixture is stirred for 45 minutes while the pH of the mixture is maintained at 7 with acetic acid being added as needed.

The solvent is then evaporated in vacuo the residual oil is added to 2N potassium hydroxide (150 ml), and crystallized, The product is washed with water, and recrystallized from acetone-water, m.p. 206°c (dec.).

Example 109 Preparation of 6- /m-NitrophenyT/imidazo[1,5-d]-as -triazin............ -.......- < . ------- — ------- ... ... . (3H ) -one.

A mixture of 90% fuming nitric acid (0.4 ml; d'=1.5, 0.0086 mole) and sulfuric acid (10 ml) is added slowly at 5°C to a solution of 6-phenyl-imidazo[l,5-d]- as triazin-4(3hH-one (2.12g, 0.01 mole) in sulfuric acid (50 ml). The mixture is stirred overnight (appr. 15-16 hours) at room temperature, and then poured over ice. The mixture is made slightly aklaline, stirred with· ethyl acetate and is filtered.

The isolated solid is recrystailized from aqueous dimethylformamide to yield 0.83 g of a buff-colored, fluffy solid (32%), m.p. 294-296°C(with violent decomposition).

Analysis calculated for C 51.36; H 2.74; 15 27.23; Found; C 51.28; H 2.85; M 27.17.

Example 110 Preparation of 8-Bromo-6-( m-nitrophenyl)imidazo[1,3-d]-a<. triazin-4(3H)-one, compound with dimethylformamide.

A mixture of 90% fuming nitric acid (1.87 ml, d,= 1.5, 0.04 mole) and sulfuric acid (10 ml) is added slowly at 5 °C to a solution of 8-bromo-6-phenyl imidazo[1,5-d]-as triazin -4(3z;)-one (5.82 g, 0.02 mole) in sulfuric acid.

The reaction mixture is stirred for 1 hour, poured over ice, the precipitated solid is isolated by filtration and dried.

A dark brown solid (6.58 g, 98%) is obtained, m.p. 244-246°C (rise.). Recrystallization from aqueous dimethyl formamide yields the title compound, a buff colored solid, m.p. 246-248°C (dec.) Analysis calculated for C11H5BrN5O3, C3H7NO: C 41.09; H 3.20; N 20.54; Br 19.53; Found C 40.99; H 3.15; N 20.34, Br 20.50.

Example 111 Preparation of 8-Bromo-imidazo [1,5-d] - g3-triazin-4 ( 3;/- -one.

A solution of bromine (8.Og, 0.05 mole) in acetic acid (10 ml) is added to a mixture of imidazo[1,5-d]-us 25 triazin -4 (3//)-one (6.8 g, 0.05 mole) and acetic acid (500 ml). The reaction mixture is stirred for 1 hour, poured into water and extracted with chloroform. The aqueous layer is separated, made slightly alkaline and extracted witn ether. Evaporation of the chloroform and the ether layers yields .0 g of a solid (46.3%). This solid is recrystailized to - 62 46511 afford the title product, a cream colored solid, m.p. 244245°C (dec.).

Analysis calculated for C5H3BrN4O: C 27.80; H 1.40; N 25.94; Br 37.00; Found: C 28.99; H 1.36; W 26.46; Br 35.91.

Example 112. preparation of 8-bromomethyl-6-phenyl~imidazo[1,5-d]triazin-4(3// )-one.

A mixture of 8-methyl-6-phenylimidazo[l,5-dJ-triazin -4(3//)-one (4.52 g, 0.02 mole), N-bromosuccinimide 1θ (3.92 g, 0.044 mole), benzoyl peroxide (0.24 g, 0.002 mole) and carbon tetrachloride (200 ml) is refluxed for 8 hours.

The reaction mixture is cooled and filtered. The isolated product is washed with water and with methylene chloride.

The product (2.1 g, 34.4%) is recrysLallized from nitromethane to yield pale yellow crystals, m.p. 254-256eC(u).

Analysis calculated for C^^HgBrN^O: C 47.24; H 2.97; N 18.48; Br 26.20; Found: C 47.50; H 3.21,- N 18.48; Br 25.78.

Evaporation of the filtrates and washings followed - bJ w 4βδϋ by recrystallization of the residue from nitromethane yields a second crop (14.8%) of the product.

Example 113 Preparation of 3-alkyl-8-methyl-0-phenylimidazo-a5-[l,5-d]5 triazin-4(3H)-ones.

Method A Sodium methoxide (0.81 g, 0.015 mole) is added to a solution of 8-methyl-6-phenylimidazo-as-[l,a-d]-triazin4(3H)-one (3.39 g, 0.015 mole), followed by the addition of the appropriate alkylating agent (i.e. methyl iodide, allyl bromide, propargyl bromide, benzyl chloride, dipropyl sulfate, and the like). The reaction mixture is then stirred at 20°C for 16 hours, heated at 40°C for 45 minutes, cooled and poured on a mixture of ice and dilute hydrochloric acid. The product is extracted from the above aqueous mixture with chloroform and isolated by evaporation of the chloroform layer.

Purification is affected by crystallization (cyclohexane or cyclohane-benzene), or by silica gel dry column chromatography in chloroform.

Method B 3,8-Dimethyl-6-phenylimidazo[1,5-d]-as-triazin-4(3H)-one.

Dimethylformamide dimethyl acetal (0.73 ml; d= 0.897, 0.005 mole) is added slowly to a slurry of 3-methyl6-phenylimidazo[1,5-d]-as-triazin-4(3H)-one (1.13 g, 0.005 mole in benzene (25 ml). The reaction mixture is stirred, refluxed for 24 hours, cooled and filtered. The filtrate is evaporated to yield 1.4 g (100%) product. Recrystallization from methyl cyclohexane yields yellow crystals, found to be identical (ir: nmr) to the product obtained by Metnod A.

Compounds prepared by the above procedures are listed in Table VII below. *3 Method m.p.(°C) Analysis Calculated Found c 64.98 C 65.09 ch3- A or B 144-146 H 5.03 H 5.11 N 23.32 N 23.45 ϋΊΤ.ίδ C 67.70 CH2=CH-CH2- A 134-134.5 H 5.30 H 5.25 N 21.04 N 21.21 C 68.11 C 66'. 24' ch=c-ch2- A 192.5- H 4.58 H 4.56 193.5 N 21.20 N 21.17 C''67'.14— C 67.IS C3H7- A 144.5-145 H 6.01 H 6.19 N 20.88 N 20.96 Example 114 Preparation of 3,8-Dimethyl-6-phenyl-imidazo[l,5-d]-aa-triazin4 (3)/) -thione. 8-Methyl-6-phenyl-imidazo [ 1,5-d] -ga-tr iazin-4 (3//)thione (3.76 g, 0.014 mole) is dissolved in aqueous sodium bicarbonate (125 ml, 6.7%). Dimethyl sulfate (1.85 g, 0.0147 mole) is added at room temperature and the reaction mixture stirred overnight (appr. 15-16 hours). The precipitated solid is collected by filtration and washed thoroughly with water.

The dried solid (3.84 g) is extracted with benzene. The benzene solution is evaporated to dryness, and the residual red solid obtained is extracted with hexane. Evaporation of the hexane solution yields a tan solid (0.25 g). Recrystallization of this tan solid from methanol yields pale yellow crystals, m.p. 194-195°C.

Analysis calculated for ci3Hx2N4S: C 60.92; H 4.72; N 21.86; Found: C 60.31; H 4.90; N 21.34.

Example 115 Preparation of 50 mg. Tablets Per Tablet Per 10,000 Tablets 0.050 gm. 0.080 gm. 0.010 gm. 0,008 gm. 0.148 gm, 0.002 gm. 0.130 gm. 6-phenyl-8-isopropyl-imidazo[1,5-d]-as-triazine-4(3H)- -ΈΗίοηβ 500 gm. Lactose (for mix) 800 gm. Corn Starch 100 gm. Corn Starch (for paste) 75 gm. - 1473 gm. Magnesium Stearate (1%) 15 gm. TW gm.

The 6-phenyl-8-isopropyl-Imidazo[1,5-d]-as-triazine-4(3H)-thione, lactose and corn starch (for mix) are blended together. The corn starch (for paste) is suspended in 600 ml. of water and heated with stirring to form a paste. This paste is then used to granulate the mixed powders. Additional water is used if necessary. The wet granules are passed through a No. 8 hand screen and dried at 120°F. Tne dry granules are then passed through a No. 16 screen. The mixture is lubricated with 1% magnesium stearate and compressed into tablets in a suitable tableting machine.

Example 116 Preparation of Oral Suspension Ingredient Amount 6-benzyl-8-ethyl-imidazo[1,5-d]- -as-triazin-4(3H)-one 500 mg. sSrhitol solution (70% N.F.) 40 ml. Sodium benzoate 150 mg. Saccharin 10 mg. Red dye 10 mg. Cherry flavor 50 mg. Distilled water qs to 100 ml.

The sorbitol solution is added to 40 ml. of distilled water and the 6-benzyl-8-ethyl-imidazo[1,5-d]-as-triazin-4(3H)-one is suspended therein. The saccharin, sodium benzoate, flavor and dye are added and dissolved. The volume is adjusted to 100 ml. with distilled water. Each ml. of syrup contains 5 mg. of 6-benzyl-8-ethyl-imidazo[1,5-d]-astriazin-4(3H)-one.

Example 117 Preparation of Parenteral Solution Tn a solution of 700 ml. of propylene glycol and 200 ml. of water for injection is suspended 20.0 grams of 6-isobutyl-8-n-propyl-imidazo[1,5-d]-as-triazin-4(3H)-one with stirring. After suspension is complete, the pH is adjusted to 5.5 with hydrochloric acid and the volume is made up to 1000 ml. with water for injection. The formulation is sterilized, filled into 5.0 ml. ampoules each containing 2.0 ml. (representing 40 mg. of drug) and sealed under nitrogen. Example 118 Preparation of Aerosol Spray A suspension is prepared of: 8-chloro-6-isopropyl-imidazo[1,5-d]-as-triazine-4(3H)-thione; micro- nized (0.5-5.0 microns) 400 mg. Dichlorodifluoromethane 100 ml. Sorbitan trioleate 6.9 mg.

The active ingredient and sorbitan trioleate are placed in a beaker and the dichlorodifluoromethane is added at -40°C. whereupon a suspension is formed. The mixture is sonified, that is, treated with a Sonifier, manufactured by the Branson Sonic Power Co. of Danbury, Connecticut, as model LS-75 at a current input of 9 amperes for 2 minutes. Additional cold dichlorodifluoromethane is added as necessary to keep the volume at 100 ml. The mixture is uniformly dispersed, and has increased stability resulting from the Bonification. Each of six 19 ml. stainless steel containers are filled with 15 ml. of the cold mixture, then valves are inserted and sealed in place. On warming, after storage, the 8-chloro-6-isoprQpyl-imidazo[1,5-d]-as-triazin -4(3H)-thione remains dispersed and, after merely casual shaking gives uniform doses of finely divided drug.

Example 119 Preparation of Amidines The amidines prepared by known procedures and used as starting materials for the preparation of imidazo-as-triazinones are listed in Table VIII below, characterized as hydrochlorides unless otherwise noted. Known literature references are also given.

TABLE VIII (continued) 00 lo σι H »—» σι γ*·~ «0 I r-i '-, u ω 0 0) n| in u 0 • 0 c 00 n Φ u m © )4 O CM Φ ί I IO CM Φ o m © « Hl CM <—% H rtl H . w m ω -Pl RJ © nJ ol H ~ C •9 S’ Η φ .P > © > UJ -rl © H k Oi cm tr> +J C · « · H ft cn Qi Φ · υ · is g ό ε ω Ό Ό Ο Ό υ *-* H •X** •rt 0 «tf © M4 O tf © ft cm in Η »H f*T CM 00 in Ο fl ·· σι • CM Η Ό CM CM H m □ Η ΦΗ 1 1 Η | I I 1 W Η Η 1 • H ©Hr- CM 00 •tf 0 0 fl) Η g in © 0 CM © in q to Μ σι CM H W CM CM H © OH Φ ΪΗ -rt M β η, //\\ | CM Lx U \‘ - / tf f* \z / \ Γ 1 O 1 m *© Κ iT m U—> H κ L U ffi ”tf 10 ο ffi U U TABLE VIII (continued) in fi in 4-) > rrt O' rrt tn nj in rt *· w * w •tf •tf in j-i m u •tf CQ •tf 0 -ffi OJ n m ϋ Ui M fi fi rt •U rt OJ fi fl k 0) Π3 G> Ό 0) fi φ •P OJ M-t « Λ rt £5 OJ ti Ή ti -H K b υ • ϋ in m cn cn OJ • 0) t3 Ό □ Ό 0 u •rt 0 TT a 04 0 Ό « irt O-rt 0. 1 04 « H 0 0 e OJ m cn rt cn 5h Λ Oj Λ Δ ό Example 12Q Cis and trans-4,5-Dimethyl-2-m-tolyl-2-imidazoline-4,5-diol hydrochloride 2,3-Butanedione (7.3 ml., 0.084 mole) is added 5 dropwise to a cold slurry of m-toluamidine hydrochloride (13.6 gm ., 0.0797 mole) in water (35 ml.) and stirred at room temperature for 15 minutes. The precipitated product is collected by filtration and washed with acetone to give 12.2 gm., m.p. 135-137°C.

Analysis calculated for Cj^H^yNjC^Cl s C 56.14; H 6.67; N 10.91; Cl 13.81. Found: C 55.92; H 6.66; N 10.94; Cl 14.09 Additional 2-substituted cis and trans -4,5dimethyl-imidazoline 4,5-diol hydrochlorides prepared by the above procedure, their melting points, and deviations from the above procedure, are listed in Table IX below. 46811 « TABLE IX • 46S11 Example 121 Preemergence Herbicidal Activity The preemergence nerbicidal activity of the compounds of the present invention is exemplified by the following tests in which the seeds or propagating organs of a variety of monocotyledonous and dicotyledonous plants are separately mixed with potting soil and planted on top of approximately 2.5 cm. of soil in separate cups. After planting, the cups are sprayed with the selected aqueous acetone solution contain10 ing test compound in sufficient quantity to provide the equivalent of about 0.07 kg to 11.2 kg 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. Three to five weeks afeer treatment, the tests are terminated and each cup is examined and rated according to the rating system provided below. The data obtained are reported in Table X below. 46311 Rating System: % Difference in Growth from the Check* - No effect θ - Possible effect 1-10 - Slight effect 11-25 3 - Moderate effect 26-40 - Definite injury 41-60 - Herbicidal effect 61-75 - Good herbicidal effect 76-90 - Approaching complete kill 91-99 9 - Complete kill 100 - Abnormal growth; that is, a definite physiological malformation but with an over-all effect less than a 5 on the rating scale.

*Based on visual determination of stand, size, vigor, chlorosis, growth malformation and over-all plant appearance.

Plant Abbreviations SE - Sesbania (Sesbania exaltata) LA - Lambsquarters (Chenopodium album) MU - Mustard (Brasslca kaber) PI - Pigweed (Amaranthus retroflexus) RW - Ragweed (Ambrosia artemisiifolia) MG - Morningglory (Ipomoea purpurea) BA - Barnyardgrass (Echinochloa crusgalli) CR - Crabgrass (Digltaria sanguinalis) FO - Green Foxtail (Setaria viridis) WO - Wild Oats (Avena fatua) TW - Teaweed (Sida spinosa) VL - Velvetleaf (Abutilon theophrasti) JW - Jimsonweed (Datura stramonium L.) Evaluation of the preemergence herbicidal activity of imidazo-as—triazinones and triazinethiones for the control « Ό QJ Φ ω □ c lo >1 •P o ϋ •H Tf £ ό β Μη X η oo rt rt O ο :< ο CJ rrt O' vp VP rt Q e ffl o o o —'-* -------- — — — ---- ------ ο Cm > ησ Γ» rt O oo rt o O' O' r- rt o O' ρ- ο ο o & υ VO Ρ- Ο P- VO O VO CN O σι σ' vo in o O' p* CN Ο O Γ* ιη ο in rt o CN rt o σ» O' p- vo rt oo rt © © © £ cn θ' ο O' o o © o © O' O' CN © © o' o' tn © © TW σ* © cn rt o rt ο o O' m ο o © σ' σι co r*· o MG <Ν rt ο o o o rt· ο o O' co o © o cn O' © oo in & mmoo o κ Γ- ο ο co r* o o o O' O' oo © Η o' cn O' f oo θ' 00 ο O' rt O O' CN O O' O' co rt © □ Ε σ> οο ο O' O' © 00 rt O O' os o' co in cn LA co co © o W W σ' ιη ο eo rt rt ο in o O' O' O' Γ* o O' .· © 00 CN 00 CN 00 CN co CN VO oo cn vo CO αι χ: •υ \ nJ tn (Ν *ί· Η CN *3· rt CN rt* rt CN -ττ rt ιη CN CN CN rt m CN rt Η rt rt· rt rt rt rt r-i 24· rt 6 6 rt CN rt ο O « λ: rrt rt rt rt rt r~J ΌI( tn 0 oil k« Ν Φ 1 nJ rt nJ C w . W I_1 Ό 0 njl nil r-i 0 ri 1 1 Tfl Ν φ S —7, r-i 1—1 nJ c •h ml Ol Ol in Ό 0 l rt 1 QJ * Φ •rt ’rt rt *“* in φ in β rt β Ε Λ >1^ * G · 0 u-J o •rt 4J C 1 Ό rt 0 rt ·Η 0 -rt 1 1 tt) c β i-j-rt ·- ’Λ N XJ rt —* Xj Ή α 0 JZ 0 4J « 4J >iKl 0. N 0 Ν -P N | Ό 1 β rt ι nJ α nJ I nJ — QJ *- VO *rt Fi XJ —>. Ό iJ3| e ml Χί ·* 1 M 0 H cq 1 Ή rt •rt rt Οι 1 1 rt -P υ ε e 1 *1. •rt *-* •rt rt· rt rt U3 (3 XJ V) 1 1 1 >i 1 1 -rt p nil rt | rt & rt N Φ r >1 >i β 0 β >. nJ ε ·i. Χί - e ή k| rt XJ -rt -) tJ 4J £ Φ N 0. N -P P Q 1 J! N Λ nJ I nJ <1> 4-> I m 04 ’rt CH E 1 . co »· 1 »1— 1 M 1 rt ι w| * rt 00 i_ i£> 4J VO 4J oo nJ 1 rt i—j 4-) ί ο 5 σ m r- t- o σ © CN © co r-i © ρ- © ο o cn cn o Γχ 00 ο VO fx o Ο Εη cn m o σ m cn © σ in © σ cn ο σ in o CR cn in «Η σ\ co ex o σ σ ο σ in cn σ co to EQ cono r- co cn o vo cn ο com ο Γ* V0 © g CN Ο © CO cn o o CD Ο Ο σ © ο σ © o g cn cn cn σ σ σ σ σ ο © σ ο ο σ ο o 0 eg © o © σ σ ο ο π· ο ο σ σ ο σ σ o . RW ο ο o ο cn σ ο © cn ο co Η © Γχ CN © H σ σ © EM cn cn cn σ σ σ σ co σ m 00 CN ο § co σ ρ- σ σ 5 co © CO CN © σ ο ω cn σ σ SE cn σ ο σ σ ·· nJ *ϋ· CN ςρ CN VO CN •cP <Ν CN <11 XJ CN CN H CN CN rH ιη CN CN .-ί CN CN Η CN <Ν «—1 4J \ β 0 β 0 0 0 0 • t » • · 0 • · β nJ σ r-l CN H Η CN «-4 Ο Η CN Η ι—1 ΓΝ Η Η CNH £ 44 r-l r-| r-i ι—1 r-i 1 0 0 •rl d) •Η d) Ν Ν ε α ε ο rt rt •rl 0 •Η 0 Ό 0 Ό 1 1 1 •Η Μ •rl Η rx ε ο rt α> ε φ >K| >ιεΰΙ •Η 0 Ό C •η α 0>π ΰ μ 0 •Η 0 1 0 0 φ Χ-* (-< 1 β ι **· 1 p Λ >ί— •Η —. r-i . 0< 1 Eh 1 0 ΚΙ 1 ΚΙ >ιΚ| ,fi 1 Εί 0) m Η cn ¢5 η cH © Ή Χ!'- >1 — φ χ·* N 1 Ν ΟιΊ C Μ· χ: ν n <0 r-4 (0 1 0) 1 a ι τ3 •H >1-rl ιο q xj c ο c d «Η P fi ρ •rl 0(·Η Μ ·Ρ 3 >1«P R+> Η Ν Μ Ρ Ν 0 fi 1 . Q. 1 , >1 rt 10 nJ ••Ί Π) cu rt ω{ ο ω χ: ·η •Η EJ-H 6 xi ml 1-( nil -Ρ Μ Η μ 1 Ρ 0 Eh 1 0. 1 ΰί χ) >4J ει-ρ □ m 1 n A 1 fi I *-* ι . T3I n Til ch| P W| ι ιο| 1 1 1 03 Π)| rt rtl vo rtl h tn r-| in I 5 1 1 1 >t * >t * r-Ι ΓΊ 0 «n ο *—· •C -1 J3H >ι*ϋ| ε όι ε όΙ 4J i—i JJ l__J 44 1 0 1 0 I rt o rt 0 Η ιη P in Μ ιη e n £ N ni * Λ ·» ® * 1 rt ι rt 1 H 1 Η CO r0 © TJ m ι—j CD «—1 © 1—1 7b TABLE X - continued ίξ * * * * 00 VO xt M* * * . · · · 01 01 00 CO 00 M* © * * * * c * * · · · · * a > cochchChCooor^cOO vo VO * * * * ch h r> co c * * · · · · * b a\ σι vo η σ chchChaicocokOfMO oo in o © * * * * * * · · · * u chttr·' no 0)00'00'Xr>’3'H r* io cm o VO * * r- r> * * * · · * * oq cn r- vo CM r-| OTChOChChCOr^LOf—i > in cm o Γ* * * * in oo p- iJ * * * · · · * > ch ch Ch co vo ο o m * * r- 3: * * * · · * * H σ» σ» ch m o cnchcnchChcoM'OO r- r- ο o in S2 * * i-h m * * * * · · * s cn σι oo η H chchch r· vo © o r* * * * vo oo in a * * * · · · * & O') Ch oiooOioiOTX’ro r- co © o rH * * * Ch VO CO w * * * . . . * & !DO\COOO OitJOOiOiXr-NO oo co © o 00 ***** s 0) O' Ο) 0) H cn σι ch oo ch f* o Γ- * * r- cm 5 * * * * · · σ\ ch Ch σ\ vo τ? o * in w * * * * · w Ch oo ο ο ο ο η o o Γ* ·. re m CO CM vO CO OOxtCMvOCOxtr^CH CO CM vo CM rr Η ιΛ CM CMxtCM·—imCMrHO© CM H m CM μ \ • fl? 0> Η Μ* Η Ο 0 rWNHOOOOO rH « J4 rH rH rH rH ti •H 1 N r-i nJ Ol 1 . ‘H 1 w M in 1 nil 1 •P (fl 1 . rH nil I r~i i__l φ Ol I ml 0 G π r-ι ¢) N 0 *G| I in nJ 1 Ol a t3 —, m 1 0 •d al κ 1_1 in ι ε n ι—1 0 •rl 1__1 N T5 i-t Xl I <* 0 nJ β i.._j m rH 1 Ν φ Φ P 0 >1 fi fi fi •Η β 0 N M· β ·Η Ό 0 ε ο £ fO Φ N •rl 1 •Η ε T3 A nJ ε — 1 0 •H QrH •h al H Bl CJ 6 1 Ll 1 <*> >>ι*ι •H VO 4J 1—I ’ 43 1 1 1 , >1^ Β μ· r-H rH (fl JX 1 φ ι >t 10 0 c ε α c si M -H •Η ·ιΗ Φ 4J 0) N Ο Ν X! Φ 1 10 1 Φ (X ε GH 00 -Η VO 1 1 Lc * Μ 00 VO 4J νο 4-> _ ----- e< ξ Ο Σ5 ID © © © © SO © © © © > © oo r* in Ο fa con o © © © © © © © © © © SO CN © © © ro o Pi o r* o © © © © © © © © © © © CN CN O © © tn ro ffl r- cn Η © © © © © © © © © © > CN © © © so in g VD CN © © © © © © © © © © © CN © © © tn o © g ω cn © © © © © ro © © © © 09 CN © O © © cm o s r* in m © © © in © © © © CO © © O O © © CN o g 05 SO CN O © © © © © © © © © CO SO O © oo © to H H fa co ro cn © © © © © © © © © © Γ* 00 © © © in cn g © Π r-f © © © © © © © © © © to ro © CO © Γ* CN H ω co in ro 00 © © © © © © © © © > CN o 00 © 00 CN «ο rd CO CM cm so oo sr CM SO co «Ν’ 00 CN OO CN SO on (Ν rH SD H in CM r-| CN H tn CN pH CN Ν’ pH cn Ν' H in •P'S 3 *? pH «Μ* rH tn H © © © r-i pH Ο © O i-H Ν’ pH pH N* pH © « J4 rH pH rH H 1 I Γ-1 1 r-i XJ| ι—1 Ol 1 Ol 1 in 1 tn .1, | tn s i-4 wj H 1 LJ dl pH l_J Wl 0 1 l—l 0 fi N 1—1 0 N 1 d T3l N d <—J 1 d XJ xj| •H if) XJ •H 1 £ κ •Η 0) ε o m •H QJ Xi (-i Ε β •rl C s 1 fi s LJ •Η O 1 0 H H 0 3 0 φ 1 1 r-i I i_j Q) >i 1 0 ΰ S H >1~ 0 fi J3 — a It) o >|M| fi Ml Ν O 4J Ml ε XJ I fi ro qj ro d ι φ ro 0 •H . QJ xs Ό g *-χ u ε mi Χί N* faTj· •H Ml i N* Ή ro fa 1 I 1 gm 00 1 ί 1 fi so fi •ri *-* 1 fi Η ID Ή 1 -H 1 N· Η Ή > 1 1 N 0 N H | >1 CM P c o d u id >1 fi p d a *h S ·Η OH ►fi -H 3 *rl XJ N 0 M rH M Ρ N -Q P I ,d M P XJ P 0 id 1 p +»H Λ L> 1 , SH P| 1 , 1 M 1 01 1 (Ω 1 L ι «1 SO P oo id I oo ·Η| 00 p io id 1 46311 TABLE X_- continued ζ ffl (κ O o to ffl o wo co^^mo so to cn © © tn o to © H o o h to to to r* © to to cn ο to © ο o r* © to co co m (ύ υ σ\ to © [k cj oo to co © to co in © r* to to co © m to to co r**o r^tovo© to in cn o o to co r· r* g to to r-ί o o to to CN o to oo © © ffl CN to to CN © g to to o © © CM CO ο o to © CN © co © to co © o J? to to ro © o mnoo to © © © © o to © CN © & to to to to o to to CN o to ©© © o o to to f*. cn H A to to to © to to o © to to to co to co to oo ro o g to to to m o to to © © to to to 5 to co © © to in cn ω ω to to oo Η o oo in ο o to © to .. ιβ 00 CN © ffl © CN © CN © co Mf Mf CN © +J\ OIM-Hincs CN * r-l in CN H to CM CN CN CN CN H to <1 O' • » · · · » · · · • · · · • · • · · · « M H*f HOO rt ·» rt O Η H © © H CN H CN H © H H H H H 1 Φ 1 •Η φ •d rt B rt Β o rt 0 V •Η I 1 1 1 ι ci 10 S 0 0 — Ml tdS N Q Ν I H to I χ: π itf Ϊ id >1^ ttl 3 — Ό—·. Ό Si β xr Π) φ «φ •ksI •H CO Φ 1 1 S 1 Brt S'— β G r-t ι rt •H ** •Η M· ftrt 7' ffl ·Η 1 Mf 1 1 0 N 1 N l“i 1 r4 H ιβ to f-h <0 *9 s fi >ι β 0 ·Η * Girt girt rt M Η Φ >< h 50 ΰ 0 N X! -P ι—ί cs fi 4J 3 Μ 10 M 10 0 1 0 0 Φ 1 1 Λ Ή 1.Η Dirt l,M Gj<«l N | io Λ ttl & B el-fj rtl-U — < Ό Si >i 1 0 • ι. 1 1 . 1 r-i •H to X r-i o © tt ι «ι © tt 1 (0 UJ ΌΙ e~ •Η 0 TJ| •fi 1 Η 1 rt 1 0 to 1 1 ΰ to ί*’-1. >,(—1 M M ο a 57’ jjm 57' J{ m 0 H H i__i β 0 Brt 0 N H ιβ S H &lo 55 * ¥ - U N Α ·Η w N 1 Η 1 rH 1 ιβ 1 M 1 >0 ffluu CO ι—i » ό ffl P © Ό ,. 46511 Μ Em ξ tn σ οκ in o ok ok ok ok tn OK 03 Ο © ο fc fc js ο ο ο< cn σκ m m ok ok ok ok co m ο» ok m oj oj ο ϋ fc oa οι ο οκ σκ o* m σκ σκ σκ σκ m o co in ο o © ti υ Γ* 03 Ο fc σ· σκ r- m 0K 0K OK 0K K0 Ol ok in © © © «< fc fc Ο Ο Ο οκ σκ r*· m OK OK OK OK 00 OJ οκ σκ m 03 © g fc m κο fc OK Ot 03 o Ok ok Ok Ok © © σκ ok in © © 8 fc tn mo fc OK © © o σκ ©κ co oj © o σκ σκ © © o ο fc c-t Μ σκ ο ο ok ok ο o OK OK OK KO o o ok ok ok m o fc . fc Bi' ο ο ο OK OK 03 O OK OK OK GO in o ok ok m rt o Η & fc Λ cn to ο OK OK OJ o ο» ok ο» m © o ok ok in oj © Β *d* fc <ο fc Ok Ok OK 05 Ο ΟΚΟ» © ok ok ok 0* m ok in m © Η fc fc 0} σ OK OK OK ·· rt ΟΙ 19 •tf 03 t© -tf OJ KO 00 *tf τ* oa o oo βΐϋ οιη <η 03 05 rt in OJ OJ rt in O! rt oj oj rt in oi •w \ β β 0 β β β β • 0 « · · · • · · · « rt rt rt Ο rtWrt ο rt OJ rt o o o rt oa rt © © rt rt rt rt - Φ 1 § 0 ·Η ι ω 1 0 0 s ν a> rt (ϋ& Μ 0 as e ί fi Ό 1 rt -ο >0 0 0 0 rt s·** Ό rt 1 Ν 1 § ai •rf SI s-~. rt i*··. rt m s m •3 tel Ί3 SI *-* •Η '*·* 1 m •H m rt t? I. <3· rt ·** B — >, ! *“*» ί >lV rt*tf fi d fi G 1 1 Ό ® a 3 fi rt rt rt C X!d rt M >«•3 3 n o rt a n Λ N 0 4Jrt I rt 5 uj KO rt l,N ©rt rt rt - 0 1 M el-w I H a m 0 rt fi Ξ?, rt £ 1 4J υ & 1. 1 rt Ν I , 00 I , £3 W K9 rt X wi 1 « •3 ta| 1 I 0Ϊ nJ| d (81 W 1 γΜι-ί •fi B >i 1 Bn, ><Ό{ o r—J Xi—ι •4 O( d T) 0 Ό Ό 1 -yin υ 8 £J 1 8 in rt » I .m co *» art ?4 © fi * *rt 8 1 d l^L-J C3t_J I—J KO UJ TABLE X_- continued © © © © © o rt ©©(***© OH © © © © © rt © rt © CM © © r* o FO © © © © © o © o O O © co in rt Bi O © © © © © rt r* © 00 o © © in rn 3 © © © © © CM r* o © © © © in rt ί © © © © CM © ω © © CM © a in © g © © © © CM O co o r* o © © rt rt £ © © © © © O © o CM O © rt © © £ © © © © © m © © © CM © © © r* H ft © © © © © © r- o © O © © © © s © © CM 3 © © © © r* © CM © © © rt « ω © © rt ··' (Q M· CM © © tf tf CM CM © © tf V fi CM CM rt tf) CM rt CM CM CM rt rt tn CM rt 4J X ·»···· • * • · • · · « IB Oi rt CM rt Ο Ο O rt CM rt rt rt © o o Bi 44 rt rt rt 1 1 r-i tfl in 1 ι—l fll 0 Φ 0 V fe n a n a rt in <0 0 ro o UJ fe fl 1 tf 1 0 rt i Ml •rt **·, s B N (0 1_1 0 •H rt •rt rt tf N 1 1 (fl ·—. tf ^fetf g Φ fl 0 rt | rt 1 rt <3 Η β S.5 rt rt 1 0 rt 1 S 0 rt f tf 0 N 0 N >1—. 1 ***. c d nJ jj m a «1 fl Bl 3 iiS 1 ,rt φ rt Sfl 0 0 M Χί c — ft '-'•υ OfV Φ tf B1 . 1 1 , 1 I X! 1 0 io OJ © to © β a. a υ ι iel ι ibi 1 fl t rt rt 1 rt I rt N © N >1^. >11-1. >1 nJ 1 IB 5?' © Φ in SV 5’2 0-H fl M Φ in jj 44 0 4J B - s - Β 1 , rt I , 1 rt I rt 1 u 1 w CO i_i © l—J fl IB © tfl w 0) +> O •H rt a φ M φ M I Ή O V tn IS M V - S3 4 0 511 Example 12 2 Postemergence Herbicidal Activity The postemergence herbicidal activity of the compounds of the present invention is demonstrated by the following tests, wherein a variety of monocotyledonous, and dicotyledonous plants are treated with test compounds dispersed in aqueous acetone mixtures. In the tests, seedling plants are grown in separate cups for about 2 weeks. The test compounds are dispersed in 50/50 acetone/water mixtures containing 0.5% of a polyoxyethylene sorbitan mono,sold under the Trade Mark TWEEN 20 by laurate surfactant' Atlas Chemical Industries, in sufficient quantity to provide the equivalent of about 0.07 kg to 11.2 kg per hectare of active compound when applied to the 2 plants through a spray nozzle operating at 2.81 kg/cm pressure for a predetermined time. After spraying, the plants are placed on greenhouse benches and are cared for in the usual manner, commensurate with conventional greennouse practices. Two weeks after treatment, the seedling plants are examined and rated according to the rating system set forth in Example 122. The data obtained are reported in Table XI below. « ιη © βο # * ιη ιη * <# · · to to <η ιη η * * ιη ιη * * · · to σι <*> m γΝ ο * * * to to <*)(*> Η Η m cn * ♦ ** »* to to co γ* cn © * * * r> cn ι** • < ·* * to to © < Η H © * * * CN © CN * * · ♦* to to r* cn ο ο o * * Mf © • * · -H * to to co © © © * * * m © © • · * * to to r* cn © © © « to to co η Η * ιη * * · to to © to r« in * * · to to r· © © n* * # © *k * · φ to to © η» © Mf * * © © * * · · to to to to co r* * © « # # · to to to to to r* * * © cn * * * · · to to to co jk Mf cn * * * r* r* © © to to © © cn © © 4c 4t 4t 4t to to to to p- mp cn * * * * Γ* Γ*· Γ*· Ϊ*· to to CO CO © rH © * * CN © * * · · * to to to to co Is· to to to to to to * * * r* co m * « · · *K to co © cn cn to to to cn cn to, ·· Ιβ φ χ; Ο © cn © co CN Mf CN H © CN H^CSHOO h mp cn h © © © TO I I © tOI ι © I r-i TOl © >iWl fi n Φ *—* •ST 7.5 rt N > Q ?i, oo fll N fl TO •H •5 8 I 0 Η I rtWI Φ co X3 Oi< © fi I ·Η Η N >fl X3 Ή •Ρ M Φ 43 B I , ι to eo fl| o N fl »0 Φ ? H — >l«l I c ©•H I N 8-5 Ο P Μ -P Λ 1 . I tt CO fl o N fl TO a s I 0 Η I >1«—» Sal m It ι n co cel g co co p* ο s P* OQ CM rrf © © © CM © © © © CM rrf ra cn © o ο ft r* © ro cm Ό © CD ro fM © © © © © © CN © © a o p* in ro H in © f- © © © © rrf O © © © © dj ffl in in ro cm r* r* © ο o ra © © «rf © © © o o g P- H © © © © © CM © © rrf CN rrf © © CN © © g © ro ro rrf os © in in o © ro tn cn © © © © © g in © © a © © © © ro ra © © © rrf © Ρ» © © s © ro cm © © © © ro o © © © © © © o o © w Ch © © © © © © © © © © © © © 00 rrf © p* ro § © © © © © © © © © © © © © © © ro ro © ffl w ω © CM H © © © © o © © © © ro © eo fi © CM IO © cm ©ra ra cm © ra N* CM © e><2 CM in CMrrf m CN CM N* rrf ro CM CM CM rrf ΙΑ M\ ο α β o β ο σ · p • BIBO Β Β Β B fl Φ H^HO rrf Ν’ rrf © © ΗΜΉΟΟ H CM rrf O »44 •rf rrf rrf rrf( r~i 1 r-i nil nil Oi 1 1 I 0 8 m ro •rf fi tn «* te S 0 *. rrf •rf 1 rrf L-J UJ L_J 0 0 **. Kl 0 N N ΗΠ M fi fi CS *© Ό Φ e* Ό •rf •H « 0 8 •rf s g 0 43 fl s ‘rf ·Η·Η ftM ‘rf 0 8 fi 8 0 A fi 8S H 0 >,0 >ι 1 0 ’rf >11 ft f ft— rrf rf Pc. o nl Λ -P 4> Kl y tni rf ro U 1 g « ftm Ql^ 1 w| g w 8 t? el's· 1 ,N· fit fafi *-* 1 ra I i 8 r 1 fro h-5 T-S T-S TT1 >|H Η M rrf N 0 ro *P fi >i ra >1 fi rf * 3 τ’ Λ·Η 43-H 0 rrf Xl rf Z> rf u H rrf I—J 1.,+1 0 4J 0 •fi 0 •Jl ι, g ι. £ 1. θ N 1 w.| 8 at 1 w 1 fi io fil ra fi| aa ral ra Ό 'BJ5.

TABLE XI - continued ζ o © cn cn σι cm © © © © © s Γ CM 00 σι 10 01 CM © © cn cm © s cn c © ρ in © © σι in © © © cn ο ο o Oi o in o *0 09 β Ο Ο © in © © © in cm © o rf « n· © © Ch νο ρ* νο ο σι σι in cm © p* cm © © moo VO σι σι in m σι σι in © © cn cn o © £ oo o o © ρ* cn ο ο σι σι ο © ©OOOO o • X © CM 00 © © © © σι © © cn © © © © © £ in » o σι σι σι ο ο © © cn Η © © © © cn H b ο in o © 00 ο © ο σι © in cm © © © © © S 00 ch σι © © 5 on o ch CM <Μ © in cn © © © P* « cn ch ch © © «1 flj V CM Μ* CM VO M* CM VO m* cm co co CM CM H CM CM CM η m CM CM rH m CM CM rH in CM • · · • • · · · • · 4 • · a · · 4 fci rH CM H rH Η CM rH O rH CM rH O rH CM rH © O «X rH H rH rH rd 1 m d 4> Ol ε κ 1 •K 0 1 m 1 f 1 0 1 rH »**. ο ω Ν φ 0 Φ inssl n a fi fi l_J n a Xj M « 0 Ό 0 0 (0 0 4J ·**· Ό 1 •h r N Ό 1 Π »iH #-» .ss1 ή wi 1 cn Φ _2 '3 al •h cn Ό 00 >H 1 *** H >- n 1 fi 1 N •Η Φ 3 >-w Φ rH I •G < ι a Η 1 & Η Ή S G Η Ή is it te 5 fi μ 5! 1. S3 b Sal S« X W 1 ·Η CO Ή m cn 1 Ή CX φ| α μ 1 M S~ Bid >ι 1 — μ d μ 1 M- S'jj 2$'Λ < ι. S ι. 09 I f t. 0 Ό| νο η 5? H 1 G io w| 5 ιί> ι fil V fil rH ·ιΗ 1 fil Η 1 A l ΪΧ M H 1 On X Φ >^r-i ξΜ, I UH 5 Τ' 7JT' φ ·<Η A M 5?' ao ω ιη >1V1 1 A* Φ m *-* N S * 0 * fil ι, s - 1 Λ 1 Η 1 rd 1 w 1 H m Ό 00ι_Π 10 UH vo « 00 UH TABLE XI - continued © •is in 45 £ 4ί β σ © ρ- ρ- in in o & £ · o lL> in in r* in co H o o o o # * * in m in o fe 0 * 0 fo in © 10 in CN rd © © ο o £ ft <: in m m & •fe « · · © © © © u in © Ρ» *3» CN r-i •is * in in <4 it <5 «0 © P- © p. 10 CM H o o o o •fe tn μ ·« a 9-is co co σ © in r-i © © © © •fe -fe -fe ·» 6- m o σ σ in © © © © © o «fe -κa CN © 611? CO H CN © © © £ in *r» •fe £ £ « s CN © ο eip’? POOO H £ £ £ £ fo σ co σ σ σ © σ σ σ cm s in rtl £ £ £ £ 3 CN σ σ σ v© © © © © w w cn •β (ΰ «0» CM 10 © «5? •^ CN V0 © 0 CM CM Η in CN r-l CM I-l tn CN -P \ 0 β ο 0 o · 0 0 0 0 rt r4 CM H © © © CM r-i ©O fo a: H 1 0 N fi rt r~j T3 | o rt 1 ε rt n a in •H fi rd 0 u 1 0 Ό 1 H «—» 9 •ri xx l—J S El 0 >tSl •H (*) N β n fi *** rt rt*- « «5? Ό 0> X3 V r4 0 •d d a i >i 3 § 0 o « Η Ή fi-H Ό fi 0 M r ~ •Η N fi rt -) El s rt 3 ί ·Η >|(Π fQ Ή 0 0 Μ fi - ί,Η χ-*ψ, rt Sl-M s a: i 0 15 0)f o, a ί ω| u 1 (3 fi -rl vo rt © N 1 I i rt pro 57' o-ri p gifll 0 1 ϋ in o +> ρ m a - •rt 1 , JQ “ fi H 9 W fi H CO i~J co ra| ©L-J or more replicates

Claims (17)

1. A compound of the formula: wherein X is divalent oxygen or divalent sulfur; R^ is selected from hydrogen, alkyl (C-j-Cg), chloro, bromo, iodo and haloalkyl (C.|-C 3 ); 5 R 2 is selected from hydrogen, alkyl (Cj-CgX cycloalkyl (C 3 -C g ), methoxymethyl, benzyl, naphthyl, phenyl and mono-substituted phenyl wherein said substituent is selected from halo, alkyl (C^C^), alkoxy , haloalkyl (C^-C 3 ), amino, dialkylamino and nitro; R 3 is selected from hydrogen, alkyl (C-j-Cg), alkenyl (Cg-C 4 ) and alkynyl (Cg-C^); R^ is 10 selected from hydrogen and alkyl (C-j-C^).

2. , A compound according to Claim 1, wherein X is oxygen; R-| is methyl, bromo or chloro; R 2 is cycloalkyl (C 3 -C g ), phenyl or m-tolyl; and R 3 and R^ are both hydrogen,

3. The compound according to Claim 1 which is selected from: 8 15 methyl - 6 - phenyl - imidazo/T,5 -#7 - aa - triazin - 4(377) - one, 8bromo 6 - phenyl - imidazo/T,5 - / - as- triazin - 4( 37/) - one, 8 chloro - 6 - phenyl - imidazo/T,5 -d7 -as- triazin-4(3#) - one, 6 cyclohexyl - 8 - methyl - imidazo/1,5-4) -as - triazin - 4(3#) - one, 8 - methyl - 6 - m - tolyl - imidazo/1>5-d7 - as - triazin - 4(3#) - one, 20 6 - phenyl - imidazo2T,5 -J/' -as - triazin - 4(3#) - one, 8 - iodo - 6 phenyl - imidazo /T,5 -/- aa- triazin - 4(3«) - one, 8 - methyl - 6 n - propyl - imidazo/T,5 -J/' -as - triazin - 4(3#) - one, 8 - methyl 6 - n - propyl - imidazo/T,5 -Jf - as - triazin - 4(3#) - thione, 6,8 dimethyl - imidazo/T,5 - as - triazin - 4(3#) - one, 8 - methyl 25 imidazo/T,5 -JT - as - triazin - 4(3#) - one, 6 - tsvt - butyl - 8 methyl - imidazo/T,5 -/ - ao - triazin - 4(3#) - one, 8 - methyl - 6 - 89 n- propyl - imidazo/T,5 -jj - aa - triazin - 4(3//) - one, 8 - bromo - nitrophenyl - imidazo /T, 5 -dl - as - triazin - 4(3#) - one, 3,8 dimethyl - 6 - phenyl/T,5 -dl - as - triazin - 4(3#) - one, 6 - p 5 chlorophenyl - 8 - methylimidazo/T,5-^7 - as- triazin - 4 (3#) - one, 6 - n- butyl - 8 - methylinndazo/T,5 - dJ - as- triazin- 4 (3#) - one, 6 - cyclopropylimidazo/T,5 -dl - as - triazin - 4(3#) · one, 8 - methyl - 6 phenyl - 3(2-propynyl)inridazo/T,5 - dl - as - triazin - 4(3?) - one and 10 8 - methyl - 6 - phenyl - 3 - n - propylimidazo/T, 5 -dJ - as- triazin - 4(3?) - one.

4. A compound according to Claim 1, wherein R-j is hydrogen, chloro, bromo or alkyl(C^-C 3 ); Rg is hydrogen, alkyl (C-j-C^), phenyl, benzyl, methoxymethyl, or o-propoxyphenyl; and R 3 and R^ are both hydrogen. 15

5. A therapeutic composition, comprising a compound as claimed in any preceding claim, in association with a pharmaceutical carrier.

6. A therapuetic composition according to Claim 5 in dosage unit form.

7. A process of preparing a compound of the formula: Ν' NH 20 wherein X, R·] and Rg are defined in Claim 1, which comprises heating a compound of the formula: Ν' NH R. . I - I— CH= N NH — C — X —R X ‘1 - 90 46511 wherein R is methyl or ethyl and X, and Rg are as hereinabove defined in a non-polar high boiling organic solvent at a temperature of 175°-275 c C.

8. A process for preparing a compound of the formula wherein Rg is as defined in Claim 1 and R^ is chloro or bromo; which comprises treating a compound of the formula: wherein Rg is as hereinabove defined with chlorine or bromine in an 10 inert solvent at steam bath temperature.

9. A process of preparing a compound of the formula: wherein R^ and Rg are as defined in Claim 1, which comprises treating a compound of the formula: wherein and Rg are as hereinbefore defined with phosphorous pentasulfide in an inert solvent at reflux temperature.

10. A method for the pre- or post-emergence control of monocotyledonous 5 and dicotyledonous plant species, comprising applying to the foliage of said plants or to soil in which said seeds or other propagating organs of said plants are present a herbicidally effective amount of a compound according to any one of Claims 1-4.

11. A method according to Claim 10, wherein said compound is applied at 10 the rate of from 0.07 to 11.2 kg per hectare.

12. A herbicidal composition for the control of monocotyledonous or dicotyledonous plant species, comprising a compound according to any preceding claim and a solid or liquid carrier or diluent therefor.

13. A compound according to Claim 1 and substantially as described in any 15 one of Examples 58-91, 104-118 , 121 or 122 herein.

14. A process for preparing a compound according to Claim 1, substantially as described in any one of Examples 58-91 or 104-114 herein.

15. A compound according to Claim 1, whenever prepared by a process according to any one of Claims 7-9 or Claim 14. 20

16. A therapeutic composition according to Claim 5 and substantially as described in any one of Examples Π5-Π8 herein.

17. A method for the pre- or post-emergence control of monocotyledonous or dicotyledonous plant species, according to Claim 10 and substantially as described in either of Examples 121 and 122 herein.