CA1058187A - 2-(1,3,4-thiodiazol-2-yl)benzoic acids - Google Patents

Abstract

ABSTRACT OF THE DISCLOSURE
Plant growth regulant effects, such as dwarf-ing, cessation of terminal growth, increased flower set, increased fruit and pot set, fruiting body abor-tion, twisting and epinastic responses, etc., may be accomplished on crops such as soybeans, cotton, etc., by application of certain 2-(1,3,4-oxadiazol-2-yl) or 2-(2-oxazolyl) or 2-(1,3,4-thiadiazol-2-yl)benroic acids, salts and esters, having the formula

Description

1058~87 This invention relates to a method of regulat-ing plant growth and to plant growth regulant composi-tions as well as to new 2-(1,3,4-thiadiazol-2-yl)ben~
20iC acids, salts and esters.
Copending Canadian application Serial No. 142,574 of Brouwer, MacPherson, Ames and ~eidermyer, filed May lg, 1972, discloses herbicidal action o~ certain 2-(1,3,4-oxadiazol-2-yl) and 2-(2-oxazolyl)benzoic acids, salts and esters. The present invention is directed to i 10 the use of said compounds, as well as certain new 2-(1,3,4-thiadiazol-2-yl)benzoic acids, salts and esters, as plant growth regulants.
The compounds employed in the present in~ention as plant growth regulants are benzoic acids (or salts or esters thereof) of the for~ula wherein:
: X is nitrogen or C-R't (R" being hydrogen or methyl);
Z is oxygen or sulfur when X is nitrogen, Z
is oxygen when X is C-RIl;
R is a heterocyclic group or the group Y~
Y~\Yl ~051~187 and the Y's are the same or dif~erent and are selected from the group consisting of hydrogen, halo-gen, nitrog lower alkyl, and lower alkoxy.
The compounds in wh$ch Z is sul~ur, that is, the 2-(1,3,4-thiadiazole-2-yl)benzoic acids, salts and esters, are new chemicals.
One preferred sub-class o~ chemicals e~ployed as plant g~owth regulants in the invention is that repre-sented by the benzoic acids (or salts or esters thereo~) of formula X --- N
I ~ ~ COOH

R ~

where X and Z have the values previously stated and R
is phenyl, lower alkylphenyl (e.g., o-methylphenyl), lower alkoxyphenyl (e.g., 2-methoxyphenyl),halophenyl, nltrophenyl, heterocyclic (e.g., pyridyl, ~uryl) or substituted heterocyclic (e.g., trimethylfuryl).
In more detail, plant growth regulant compounds employed in the invention may be represented by the for-mula X -- - N
~ ~ COOR
/ \
R ~

where X, Z and R are as previously defined and R' is hydrogen or a salt-forming or ester-forming moiety.
When R' i~ hydrogen this formula of course represents the benzoic acids themselves. In the salts R' is ~V 5 ~ ~7 typically an alkali metal (preferably sodium orpo-tassium although llthium or other metal may also be used a~ the salt-~orming molety including polyvalent metals such as copper, zinc, calcium, barium, magnes-ium, ~ron [~errlc or ferrous] aluminum, and the like), ammonium, alkylammonium having up to 12 carbon atoms (e.g., methylammonium, ethylammonium, diethylammonium, hexylammonium, dodecylammonlum), alkanolammonium hav-ing up to 12 carbon atoms (e.g., ethanolammonium, di-ethanolammonium, hexanolPmmonium, dodecanolammonium), choline, and the like. In the esters, R' is commonly represented by aliphatic or cycloaliphatic hydrocarbyl moleties havlng up to 12 carbon atoms, notably alkyl (e.g., methyl, ethyl, n-propyl, isopropyl? n-butyl, iso-butyl, sec.-butyl, tert.-butyl, etc.), alkenyl (e.g., allyl, methallyl, etc.)~ alkynyl (e.g., 2_pro-pynyl, 2-butynyl, etc.), and the like, or by epoxy-alkyl (e.g., 2,3-epoxypropyl, 2,3-epoxybutyl, 3,4_ epoxybutyl, etc.). In addition to the acids them-selves (R' is hydrogen) preferred bodies are the al-kali metal salts (R' is alkali metal) and the alkyl esters (Rl is alkyl).
Also particularly advantageous in certain respects are chemicals in which the 5-substituent (R) on the oxazole, oxadiazole or thiadiazole ring is phenyl, that is, Yl, Y2, Y3, Y4 and Y5 are all hydrogen, or a mono-substituted phenyl, that is, all but one of Yl, Y2, Y3, Y4 and Y5 are hydrogen (although di-, tri-, tetra- and p~nta- substituted phenyl as defined herein may also be used).

~oS~}~87 Examples o~ oxadiazoles, oxazoles and thia-diazoles useful in plant growth regulation in accor-dance with the in~ention are 2-(5-phenyl-1,3,4-oxa_ diazole-2-yl)benzoic acid, the methyl ester o~ same, the eth~l ester of same, the butyl ester of same, (or similar alkyl esters in whlch the alkyl group is normal or iso, primary, secondary or tertiary, ~traight.chain or branched), 2-~5-(2-tolyl)-1,3,4-oxadiazole-2_yl]ben_ zoic acid (also the m-methylphenyl and p-methylphenyl analogs of same), ethyl 2-[5-(2,3-dimethylphenyl)-1,3, 4-oxadiazol-2-yl]benzoate, amyl 2-[5-(2,3,4-trimethyl-phenyl)-1,3,4-oxadiazol-2-yl~benzoate, 2-~5-(4-chloro-phenyl)-1,3,4-oxadlazol-2-yl]benzoic acid, methyl 2-[5-(2,3,4-tribromophenyl)-1,3,4-oxadiazol-2-yl]benzo-ate, 2-~5_(3-nitrophenyl)-1~3,4-oxadiazol_2-yl]ben_ zoic acid, isopropyl 2-[5-(2-chloro-3-nitro-4-methoxy-phenyl)-1,3,4-oxadiazol-2-yl]benzoate, methyl 2-[5-(2,3,4-trimethoxyphenyl)-1,3,4-oxadiazol-2-yl]benzoate, butyl 2-(5-phenyl-2-oxazolyl)benzoate, 2-[5 ~ -nitro-phenyl)-2-oxazolyl]benæoic acid, 2-[5-(2,3,4-trichloro-phenyl)-2-oxazolyl]benzoic acid, sodium 2-[5-(2,3~4_ trichlorophenyl)-2-oxazolyl]benzoate, ethyl 2-[5-(2, 3,4,5-tetrachlorophenyl)-1,3,4-oxadiazol-2-yl]benzoate, ethyl 2-[5_(2,3,4,5,6-pentachlorophenyl)-1,3,4-oxadia_ zole-2-yl]benzoate, potassium 2-(5-phenyl_2-oxazolyl) .
benzoate, ammonium 2-[5-phenyl-1,3,4-oxadiazol-2-yl]
benzoate, 2-[5-(5-chloro-3-pyridyl)-1,3,4-oxadiazol-2_yl~benzolc acld, n-butyl 2-(5-phenyl-2-oxazolyl) benzoate, allyl 2-[5-(4-nitrophenyl)-1,3,4-oxadiazol_ 2_yl~benzoate, methallyl 2-(4-methyl-5-phenyl-2-oxazolyl) ~os~

benzoate, propyl 2-[5_(2-chlorophenyl3-1,3,4-oxadia-zol_2_yl~benzoate, butyl 2-(4-methyl-5_phenyl_2_ oxazolyl)benzoate, 2,3-epoxypropyl 2-(5-phenyl-1,3,4-oxadiazol-2-yl)benzoate, ~erric tri[2-(5-phenyl-1,3,4-oxadiazol-2-yl)benzoate], manganese di~2-(5-phenyl-2-oxazolyl)benzoate], 2-[5-(3,4~5-trimetho~yphenyl)-1, 3,4-oxadiazol-2-yl]benzoic acid, n-butyl Z-(1,3,4-oxadiazol-2-yl)benzoatej 2-[5-(2,4,5_trimethyl-3_ furyl)-1,3,4-oxadiazol-2-yl]benzoic acid, 2-~5-(2-fury1)-1,3,4-oxadiazol-2-yl]benzoic acid, 2-[5-(2,5-dimethyl-3-furyl)-1,3,4-oxadiazol-2-yl]benzoic acid, 2_~5-(2-methyl-3-furyl)-1,3,4-oxadiazol-2-yl]benzoic acid, 2-[5-(3-furyl)-1,3,4-oxadiazol-2-yl]benzoic acid,

2-[5-(3-pyridyl)-1,3,4-oxadiazol-2-yl]benzoic acid, and the like.
Pre~erred plant growth regulating chemicals employed in the invention are those selected from the group consisting of 2-(5-phenyl-1,3,4_oxadiazole_2_ yl)benzoic acid, 2-[~-(2-tolyl)-1,3,4-oxadiazole_2-yl~
benzoic acid, 2-[5-(4-chlorophenyl)-1,3,4_oxadiazole_ 2-yl]benzoic acid, 2-[5-(2-chlorophenyl)-1,3,4-oxa-diazole-2-yl]benzoic acid, 2-[5_(3-chlorophenyl)-1,3,4-oxadiazole-2-yl~benzoic acid, 2-[5-(3-pyridyl)-1,3,4-oxadiazole-2-yl]benzoic acid, 2 (5-phenyl-2-oxazolyl)benzoic acid, 2-[5-(2-methoxyphenyl)-1,3,4-oxadiazole-2-yl]benzoic acld, propargyl 2-(5-phenyl-1,3,4 oxadiazole-2-yl)be~zoate, 2-(4-methyl-5-phenyl-2_oxazolyl)benzoic acid, butyl 2_(5-phenyl_1,3,4_oxa-diazole-2-yl)benzoate, 2-[5-(3-nitrophenyl)-1,3,4-oxa-diazole-2-ylJbenzoic acid, 2-[5-(2,4,5-trimethyl-2-~058~7 fuxyl)-1,3,4-oxadiazole-2-yl)benzoic acid, methyl 2-(5-phenyl-1,3,4-oxadiazole-2-yl)benzoate, methyl 2-(5-phenyl-2-oxazolyl)benzoate, and 2-(5-phenyl-1,3,4-thiadiazol-2-yl) benzoic acid.
In one aspect of this invention there is provided a 2-(1,3,4-thiadiazol-2-yl)benzoic acid, salt or ester of the formula .
N N

R

where R is:
-phenyl which may be substituted with up to three substituents selected from:
-halogen -nitro, -alkyl having 1 to 4 carbon atoms, and -alkoxy having 1 to 4 carbon atoms;
-2,4,5-trimethyl-2-furyl;
-4-met.hyl-2-(3-pyridyl)-5-thiazolyl: or -pyridyl;
R' is selected from the group consisting of:
-hydrogen . .
-alkali metal -ammonium; and - a moiety having up to 12 carbon atoms selected from:
-alkyl, -alkynyl; and -epoxyalkyl.

~ - 6 -~05~}i87 In another aspect of this invention there is provided a method of regulating the growth of plants. The method comprises applying to plants, in an amount effective to regulate the growth of the plan~s, a 2-(1,3,4-thiadiazol-2-yl)benzoic acid, salt or ester as defined in the immediately preceding paragraph.
The 2-(1,3,4~oxadiazol-2-yl)benzoic acid plant growth regulant chemicals employed in the invention may be prepared as disclosed in Canadian Patent 966,490 referred to above. One method, herein below referred to as Method Ia, involves the preparation of 2-(1,3,4-oxadiazole-2-yl)benzoic acids of the formula N - N

~ O ~

wherein Ra is selected from the group consisting of phenyl, 2-chlorophenyl, 4-chlorophenyl, 2-methylphenyl, 3-methylphenyl and 4-methylphenyl. According to this method, a hydrazide of the formula NH - NH
R IO CO

: COOH

(wherein Ra is as previously defined) is mixed with sulfur tri-oxide in dimethylformamide medium at a temperature of from -10 to 20C, and thereafter the 2-(1,3,4-oxadiazole-2-yl)benzoic acid of the stated formula is recovered from the mixture. In the course of the reaction the elements of water are removed from the precursor. In this method the selection of the start-ing hydrazide chemical is critical, since some otherwise similar ~ - 6(a) -.. ..

1058~6~7 chemicals, in which the value of Ra is other than the values above states, are inoperative. Also critical is the use of s~lfur trioxide-dimethylformamide complex as the cyclizing agent, since numerous .

. .

- 6(b) -. ., ~

- lOS8~

other common cyclizing agents are inoperative. Thus, such cyclizing agents as phosphorus oxychloride, thionyl chloride, polyphosphoric acid, etc., fail to accomplish cyclization.
Also critical is the temperature at which the reaction is carried out, since at higher temperatures than those stated, very poor yi~lds are obtained. The proportions of hydrazide starting chemical, sulfur trioxide and dimethylformamide are not critical and may vary widely. For example, for each mole of hydrazide starting chemical employed, there may be used 10 from l mole to 3 moles or more of sulfur trioxide and from 10 moles to 15 moles or more of dimethylformamide.
In accordance with another method hereinbelow referred to as Method Ic, 2-(1,3,4-oxadiazole-2-yl)benzoic acid itself is prepared according to a similar procedure, but employing fuming sulfuric acid as the agent to remove the elements of water and bring about cyclization. In this method the hydrazide chemical, namely, l-benzoyl-2-(2-carboxy-benzoyl)hydrazine NH NH
~ IO IO

- - - COO~
is mixed with fuming sulfuric acid at a temperature of from -10 to 20, and thereafter the 2-(1,3,4-oxadiazoyl-2-yl) benzoic acid ~ ~ COOH
~~
is recovered from the mixture. Cooling is necessary to main-tain the temperature within the stated range during the cyclo-dehydration. In this method the selection of the specific cycling agent, fuming sulfuric acid, is critical, as is the use of relatively 1~5l }18~
low reaction temperature. The proportions of the starting hy-drazide chemical and fuming sulfuric acid are not critical and may vary widely. For example, for each 100 parts by weight of starting hydrazide there may be employed from 200 parts to 800 parts by weight or more of fuming sulfuric acid (or 100 parts to 400 parts by volume). The concentration of sulfur trioxide in the fuming sulfuric acid is conventional and usually ranges from 15 to 30% by weight.
It will be noted that in the foregoing methods the carboxylic acid group is present throughout. Other methods useful for ma~ing chemicals employed in the invention, to be described below, include syntheses which involve a group such as methyl, chloromethyl~ dichloromethyl, trichloromethyl, formyl, acetyl, ester, etc., which can be chemically converted i to the carboxylic acid group when required.
The following are appropriate methods of synthesis:
Method Ia Formula description:

CONHNH
~ ~ NH -NH

R O ~ O C

(I) O (II) (III) ) ~ N-NHCO ~ + ~ COOH

(IV) Rl (V) A derivative of benzhydrazide (I) is heated with phthalic anhydride (II) in an inert solvent to give a ~05~3187 quantitative yield of the hydrazide (IIIj where Rl is hydrogen or certain substituents. This hydrazide (III) can be cyclized by dimethylformamide-sulfur trioxide complex to two products, a phthalimido derivative (IV) or a 2-(1,3,4-oxadiazole-2-yl) benzoic acid (V). The respective yields of these two products vary depending upon the Rl substituent. In some cases the yield of the 1,3,4-oxadiazol~ (i.e. compound V) is zero. Pyrolysis of a 2-(1,3,4-oxadiazole-2-yl) benzoic acid results in the formation of the phthalimido derivative (i.e. IV). The phthalimido derivative (IV) can be converted to hydrazide (III) on treatment with aqueous base followed by neutralization with aqueous acid, and the hydrazide (III) can be recyclized to (IV) and (V). When Rl is hydrogen (preferred) or is a substituent selected from 2-chloro, 4-chloro, 2-methyl, 3-methyl or 4-methyl, the specific cyclizing agent ~dimethylformamide-sulfur trioxide complex) produces the desired product (V), as indicated previously.
Method Ib Formula description:

NO

tVI) NO2 (VII) This method involves the nitration of 2-(5-phenyl-1,3,4-oxadiazole-2-yl) benzoic acid (VI) which was prepared by Method la. Nitration occurs exclusively in the 5-phenyl ring.
30 The nitro derivatives produced can be separated by crystal-lization.

i~S~lt37 Method Ic This method is similar to that of Method Ia except that fuming sulfuric acid is used to cyclize the hydrazide (III) [specifically, Rl is hydrogen, i.e. 1-(2-carboxybenzyol)-2-benzoylhydrazine~ to 2-(5-phenyl-1,3,4-oxadiazole-2-yl) benzoic acid.
Method Id This method involves synthesis of esters. A
2-(1,3,4-oxadizaole-2-yl) benzoic acid derivative in chloroform in the presence of an excess of thionyl chloride is refluxed till the evolution of hydrogen chloride and sulfur dioxide ceases. After the removal of chloroform and excess thionyl chloride the residue (the acid chloride of the oxadiazole acid) is dissolved in toluene or benzene and added to a solution of appropriate alcohol in toluene or benzene along with an organic base to act as hydrogen chloride acceptor. The mixture is washed with water, dilute acid, dilute biCarbonate, dried and the solvent removed. The esters so produced are usually viscous oils.
Esterification can also be brought about by diazoalkane treatment or by the reaction of the sodium or potassium salt of an oxadiazole acid with an alkyl halide.
Method II
-Formula description:

CONHNR2 ~ COCl NH - NH

~H ~ CO CO
(I) (VIII)3 Rl (IX) ~ ~ ~ H3 Rl (X) Rl(V) ~058~8~

Benzhydrazide derivative (I) is reacted with o-toluoyl chloride (VIII) to produce l-aroyl-2-o-toluoyl hydrazine (IX) which can be cyclized to a 2-aryl-5-_-tolyl-l,3,4-oxadiazole (X) by any o the standard cyclizing agents reported in the literature. The methyl group (CH3) on the diphenyloxadiazole (X) can be converted by permanganate oxidation to form a 2-(5-phenyl-l,3,4-oxadiazole-2-yl) benzoic acid (V).
Method IIIa Formula description:

~ C00~1 NH4 100 ' ~ z ~ ) COORl (A) (B) O ~

(C) In this method a 2-cyanobenzoic acid or ester (A) can be converted to a tetrazolyl derivative (B) by heating with excess sodium azide/ammonium chloride in dimethylformamide (D.M.F.). When this tetrazole is treated with an acid chloride in pyridine and subsequently heated, it rearranges with the loss of hydrogen chloride and nitrogen to the oxadiazole (C).
The method is especially appropriate for preparation of pro-ducts in which the benzoic acid nucleus is variously sub-stituted, although it is also applicable to products having no substituents on the benzoic acid nucleus.

Method IIIB
This method involves the hydrolysis of esters to 1~5t~1~37 their corresponding acids. The ester is hydrolyzed in methanolic sodium hydroxide at room temperature. The hydrolysis is usually complete in 2 hours. Room temperature reaction conditions avoid difficulty from decomposition of 2-(1,3,4-oxadiazole-2-yl) benzoic acids or benzoates at elevated temperature.
Method IV
This method involves the chlorination of 2-(5-phenyl-1,3,4-oxadiazole-2-yl) benzoic acid (VI) to 2-(5-chlorophenyl-1,3,4-oxadiazole-2-yl) benzoic acid.
Method Va This method describes the oxazole synthesis.

~JCOCH2R2 ~ COCHR2 Rl N B.S. 1 (E) (D) O

~ ~ N-K

COOH R3 (F) ~ O C ~ ~2) HCl ~ N-C,HCO

Rl (H) 3 ~ ~ (G) Rl (J) An acetophenone (D) is brominated to the corres-ponding bromide (E) which in D.M.F. is treated with an analog of potassium phthalimide (F) to give the corresponding * N-Bromosuccinimide ~ ~ 8~ ~
phthalimide (G). Subse~uent ring opening with dilute base fo~lowed by acidi~ication affords a phthalamlc acid (~). Ring closure wit~. co~centrated sulfuric acid at room temperature will gi~e a 2-(2-oxa201yl) benæoic acid tJ) ~ethod Vb Th~ synthesis of the esters of oxazole herbicides may follow standard literature procedures for aromatic ester preparation. The sxazole acid may be refluxed in an excess ¦ of ~ppropriate alcohol in the presence of an acid catalyst._ _ _ . . _ .. . . . .
1~ The new 2-(1,3,4-thiadiazole-2-yl)benzoic acid plant growth regulant chemicals o~ the in~ention may be prepared by the aqueous permanganate oxidation of 2-methylphenyl-5-phenyl-1,3,4-thiadiazoles.
.~ In accordance with the lnvention, a 2-(1,3,4-oxadlazol-2-yl) or 2-(2_oxazolyl) or 2-(1,3,4_thiadi_ azol-2-yl)benzoic acid chemical of the kind described ls applied to plants in an amount effectiYe to regulate the growth of the plants. Regulation of the growth of plants is frequently desirable for a number of reasons.
Thus, useful plant growth regulant effects contemplated by the invention include:
a. Dwarfing;
b. Cessation of terminal growth;
c. Increased flower set;
d. Frult and pod set;
e. Fruitlng body abortion; and f. Twisting and epinastic responses.
Other useful effects include forced axillary growth when the chemical ls applied to retard vegètative - growth. Also, the flowerlng characteristics of certain .~ .
. .,. _ .

,. . .

specie~ can be altered such as in monocot3 to ~acili-tate sterility. In sugar producing species (e.g., sugar cane, sugar beets), a positive increase in per-c~nt sugar can be obtained.
Control of lodging is an important plant growth regulant effect of the present chemlcals. For example when soybeans are harvested, many bushels of plants per acre are frequently lost due to lodged plants. A com-mon soybean combine is not capable o~ harvesting lodged plants. By application o~ the present chemlcals, dwarf-ing may be accomplished and lodging prevented.
In all cotton producing areas there are times when climatic conditions increase the vegetative growth o~ the cotton; the result is called "rank cotton". The chemicals described herein stop this rank growth by preventing terminal vegetat$ve growth, thus forcing the plant to contlnue its reproductive activity.
In areas where a second crop of cotton is plant-ed and har~ested the same year, many times the cotton matures too late. Thls 810w8 down the planting o~ sub-sequent crops and in some cases may completely eliminate - the planting of that crop. The chemicals herein described, when applied to cotton that is in the 80% boll ~et stage, will abort any subsequent flowers. This hastens the ma-- 25 turlty of the existing cotton bolls and hence allows early harvesting. This phenomenon may also be called a "cut off spray".
Further plants on which the present growth regu-lant chemicals are useful include peanuts and small grainsO such as rye and the various cereal grain type ~058~

plants, e.g., wheat, barley, oats, and the li~e.
While it ls not deslred to limit the invention to any particular theory of operation, it can be postu-lated from the results obtained with the present plant growth regulating chemicals that the chemieals effect a basic metabolic change in the plant that increases the sugar level directly or prevents the breakdown of sugars.
In one aspect, the in~ention is directed to plant growth retardat~on. Various plant growth regu-lant effects noted above are directly or indirectly related to retardation in many cases, that ls, certain desirable ef~ects including control o~ lodging, preven-tion of termlnal vegetative growth, and other effectæ, may be regarded as manifestations of, or ~ide e~fects o~ retardation in one form or another. Thus, when the chemical is applied to retard vegetative growth, forced axial growth may occur; application of the chemical to accomplish dwarfing m~y prevent lodging; etc. The ef-~ects with which the invention is conce m ed are of course non-herbicidal effects, that is, the present chemicals are employed in amount insufficient to injure the plants to whtch they are applied.
To use the present chemicals as plant growth regulants, the chemical ls applied to a locus where such control is to be effected in an amount sufficient to regulate the growth of the plant in the manner de-sired. The amount employed follows conventional prac-tice for plant growth regulants, and is frequently in the range of from 0002 to 10 pounds per acre, depending 10~8187 on the plant species being treated. The chemical is suitably ~pplled as a formulation in accordance with conventional agricultural chemical practice.
Thus, the chemical may be impregnated on ~lne-ly-divided or granular inorganic or organic carrlers such as attapulgite clay, sand, vermiculite, corn cobs, activated carbon or other granular carriers know~ to the art. The impregnated granules m2y then be spread on the soil. Furthermore, the chemical may be formu-lated, for example, as a wettable powder by ~mpregnat-ing it on to an inactive powdered carrier to which a surface active d~spersing agent has been added. Typi-cal powdered solid carriers are the various mineral silicates, e.g., mica, talc, pyrophyllite and clays.
The wettable powder may then be dispersed in water and sprayed on plants, or the soil sur~ace, or plants to be o 16 -105~18'7 prepared for harvesting. Similarly, an emulsifiable con-centrate may be prepared by dissolving the chemical in a suitable solvent to which a surface active dispersing agent has been added. The emulsifiable concentrate may then be dispersed in water and applied by spraying. A soluble con-centrate may be prepared by reacting the chemical with a stoichiometric quantity of base to which a surface active wetting agent has been added. This formulation may also be applied to foliage by spraying. Suitable surface ac~ive agents are well known to those skilled in the art and refer-ence may be had to McCutcheon's Detergents and Emulsifiers, 1970, Allured Publishing Corp., Ridgewood, New Jersey, or Hoffman et al., Canadian patent 507,164 issued November 9, 1954 or Sundholm Canadian patent 512,908 issued May 17, 1955, for examples of appropriate surface active agents.
The concentration of active chemical in the for-mulation may vary widely, e.g. from 10 to 95%. The concen-tration of active chemical in a dilution applied to the soil or foliage is almost invariably from 0.001% to 75%. The chemical scope includes compounds that are active at very low dosages and therefore the plant growth regulation properties should not be confused with the herbicidal properties which were roundwhen the chemical was applied at higher rates.
The following examples will serve to illustrate the practice of the invention in more detail.
Example 1. Method Ia Step 1. 1-Benzoyl-2-(2-carboxybenzoyl) hydrazine At a temperature of about 18, powdered benzhydra-zide (126 g, 1 mole) was suspended in stirred benzene (1.6 1), and 24-mesh phthalic anhydride (148 g, 1 mole) was added portion-wise over 15 to 20 minutes. After the addition the 10~ 8~
reaction mixture was stirred for a further hour. The product, l-benzoyl-2-(2-carboxybenzoyl)-hydrazine (III) (Rl=H) was collected on a filter, pressed free of benzene and air dried, 276 g, 98%, M.P., 205-208.
Step 2. 2-(5-Phenyl-1,3,4-oxadiazGle-2-yl) benzoic acid.
Dry dimethylformamide (D.M.F.) (300 ml) was cooled in an ice-bath and with stirring treated dropwise with sulfur trioxide (SO3) (100 ml) such that the temperature did not exceed 5. With continued ice-bath cooling the D.M.F./SO3 complex was treated dropwise with a solution of 1-benzoyl-2-(2-carboxybenzoyl) hydrazine (148.5 g, 0.52 mole) dissolved in dry D.M.F. (200 ml). After the addition, the reaction was stirred for a further 1/2 hour at 0 and then for several hours with the ice-bath removed. The reaction mixture was poured into water (2 1) and allowed to stand until the paste which separated became hard. The crude product was collected on a filter, washed well with water, then air dried, wt. 143 g.
This crude product was stirred into a solution of sodium bicarbonate (150 g) in water (1.4 1) till all effervescence had ceased. Undissolved material was collected on a filter, washed with water and air dried, 26 g (18~). Recrystallization from methanol gave white crystals of N-phthalimidobenzamide, (IV) (Rl=H), M.P. 215-218.
Acidification of the bicarbonate extract gave a precipitate which was collected on a filter, washed with water and air dried, 116 g (82%). A portion was recrystallized from acetone to give 2-(5-phenyl-1,3,4-oxadiazole-2-yl) benzoic acid (V) (Rl=H), M.P. 172.6. Analysis gave C, 67.55; H,

3.75; N, 10-26. C15Hl~N2O3 requires C, 67.66; H, 3.79; N, 10.52.

1058~87 Step 3. Conversion of N-phthalimidobenzamide to l-benzoyl-2-(2-carboxybenzoyl) hydrazine N-Phthalimidobenzamide (353 g, 1.32 mole) was dissolved in a slight excess of 2N sodium hydroxide solution.
After filtering, the reaction mixture was poured into 2N
hydrochloric acid. The precipitate, l-benzoyl-2-(2-carboxy-benzoyl) hydrazine was filtered, washed with water and air dried, wt. 368 g.
Example 2. Method II
Step l. l-(2-Chlorobenzoyl)-2-(2-toluoyl) hydrazine o-Chlorobenzhydrazide (80 g, 0.47 molè) was suspended in benzene (1 1) to which was added pyridine (38.2 ml).
With vigorous stirring, the suspension was treated dropwise with o-toluoyl chloride (74.5jg, 0.48 mole) and on completion the reaction was heated to reflux over 2 hours. After cooling, the product was filtered and washed with water. Recrystalliza-tion from 75% ethanol gave 1-(2-chlorobenzoyl)-2-(2-toluoyl) hydrazine (IX) (Rl=o-Cl) 107.5 g, 79%, M.P. 206-208. (Found: -C, 62.94, 62.97; H, 4.73, 4.74; N, 9.57, 9.54. C15H13ClN2O2 requires C, 62.39; H, 4.54; N, 9.90).
Step 2. 2-(2-Chlorophenyl)-5-(2-tolyl)-1,3,4-oxadizaole Dry D.M.F. (160 ml) was cooled in an ice bath and with stirring treated dropwise with SO3 (55 ml) such that the temperature did not exceed 5. On completion the D.M.F.-SO3 complex was treated with a solution of l-(2-chlorobenzoyl)-2-(2-toluoyl) hydrazine (IX) (Rl=_-Cl) (87.5 g, 0.3 mole) dis-solved in dry D.M.F. (170 ml). The reaction mixture was stirred in the ice-bath for 1 l/2 hours, then heated on the steam bath till it was homogeneous. The reaction mixture was poured into ice-water and the solid which precipitated was collected on a filter, washed with water and air dried. Recrystallization ~05~8~
from ethanol gave 2-(2-chlorophenyl)-5-(2-tolyl)-1,3,4-oxadiazole (x) (Rl=o-Cl), 48.5 g, 59~, M.P. 102-4. Found, C, 65.96, 65.92; H, 4.10, 4.Q5; N, 10.07, 10.00. C15HllClN2O
requires C, 66.55; H, 4.10; N, 10.35.
Step 3. 2-[5-(2-Chlorophenyl)-1,3,4-oxadiazole-2-~1]
benzoic acid ..~ __ A
2-(2-Chlorophenyl)-5-(2-tolyl)-1,3,4-oxadizaole (X) (Rl=o-Cl) (27 g, 0.1 mole) was added to a stirred solution of potassium permanganate (38 g, 0.24 mole) in water t500 ml).

The mixture was heated to reflux. Refluxing was continued till the color of the permanganate had discharged. The reaction mixture was filtered hot and the manganese dioxide on the filter was washed with hot water tlO0 ml), then extracted with cold acetone. Removal of the acetone yielded starting material (13 g after recrystallization).
The combined aqueous filtrate was acidified, ex-tracted with ether and the ether extract washed with water and dried. Evaporation of the ether left an oil which slowly solidified, 1.5 g, 9.6% (based on amount of (X) (Rl=o-Cl) consumed). Recrystallization from acetone gave 2-[5-t2-chlorophenyl)-1,3,4-oxadiazole-2-yl] benzoic acid tV) tR1=O-C1), M.P. 142-4. (Found, C, 59.77, 59.68; H, 3.28, 3.10; N, 9.17, 8.84. C15HgClN2O3 requires C, 59.91; H, 3-02; N, 9.32.) Example 3. Method Ib 2-[5-(2-Nitrophenyl)-1,3,4-oxadiazole-2-yl]
benzoic acid and 2-[5-(3-nitrophenyl)-1,3,4-oxadiazole-2-yl] benzoic acid.
Finely-powdered 2-~5-phenyl-1,3,4-oxadiazole-2-yl) benzoic acid (VI) (133 g. 0.5 mole) was added portionwise to stirred concentrated sulfuric acid (200 ml) kept cool in an ice-bath. On completion, the mixture was treated dropwise while stirring with a solution of concentrated sulfuric `~

~05~ 37 acid (42 ml) in nitric acid (42 ml, S.G. 1.42) such that the temperature did not exceed 5. After the addition, the reaction mixture was stirred for a further 2 hours in the ice-bath and then poured into cold water (4 1). The yellow solid which precipitated was filtered, washed well with water, and air dried, 143 g.
A 10 g portion of crude product was stirred in cold methanol (100 ml) for 1 1/2 hours. Undissolved material was collected and dried, 6.5 g. The mother liquor was con-centrated to 50 ml to give a second crop of 1 g. Two types of crystals separated when the mother liquor was concentrated to 25 ml. The amber-coloured crystals were hand picked to yield 0.8 g of material which was recrystallized from methanol to give 2-[5-(2-nitrophenyl)-1,3,4-oxadiazole-2-yl] benzoic acid (VII) (Rl=_-NO2), M.P. 182-7. Yield estimated at about 10-15%. (Found: C, 57.96, 57.42; H, 2.97, 3.07; N, 13.51, 13.52. C15HgN3O5 requires C, 57.88; H, 2.91; H, 13.50.) The remaining light yellow crystals were combined with the other two crops and recrystallized from acetone to give 2-[5-(3-nitrophenyl)-1,3,4-oxadiazole-2-yl] benzoic acid (VII) (Rl=(m-NO2), M.P. 222-6. Yield estimated at 85-90%.
(Found: C, 57.94, 58.06; H, 2.96, 3.00; N, 13.64, 13.49.
C15HgN3O5 requires C, 57.88; H, 2.S1; N, 13.50.) Example 4 Method Ic 2-(5-Phenyl-1,3,4-oxadiazole-2-yl) benzoic acid Fuming sulfuric acid (100 ml) (20%) was cooled in an ice/salt bath, then with vigorous stirring treated portionwise with powdered l-(2-carboxybenzoyl)-2-benzoyl-hydrazine (113.6 g, 0.4 mole) such that the temperature did not exceed 0 (time of addition, 15-20 mins.). On completion of the addition, the reaction mixture was stirred for a further ~0~8~87 3/4 hour, then poured into ice water. The precipitated solid was filtered, washed with water and digested with aqueous sodium bicarbonate. The undissolved material was collected, washed with water and dried, to give N-phthalimidobenzamide, M.P. 210-4, 13 g.
Acidification of the aq. bicarbonate solution gave 2-(5-phenyl-1,3,4-oxadiazole-2-yl) benzoic acid, which was filtered, washed with water and dried, M.P. 163-170, 84 g, 79~.
Example 5 Method IIIa.
Step 1. Phthalamic acid With vigorous stirring, concentrated ammonia solution (900 ml, S.G. 0.9) was treated portionwise with phthalic anhydride (600 g, 4.0 moles) over a period of 1 1/2 hrs.
After the reaction mixture had cooled to room temperature, the precipitated ammonium phthalamate was filtered, then dissolved in the minimum of water. When this solution was acidified to pH 2, phthalamic acid began to crystallize, M.P. 132-6.
Acidification of the ammoniacal mother liquor gave a 2nd crop. Total weight of product, 551 g, 78~.
Step 2. Methyl 2-cyanobenzoate Phthalamic acid (240 g, 1.37 moles) in methylene-chloride (1.7 1) was stirred and cooled to ~ 5 in an ice bath. Triethylamine ~244 ml, 176 g, 1.74 moles) was added and a clear solution was obtained. Methyl chloroformate (200 g, 163 ml, 2.1 moles) was added at such a rate that the temperature did not exceed 5. As the addition continued, triethylamine hydrochloride precipitated and carbon dioxide was evolved. On completion of the addition, the ice bath was removed and stirring was continued for 12-20 hrs. at room temperature. Triethylamine hydrochloride was removed by ~058~7 filtration and the methylene chloride evaporated. The residue was dissolved in ether (2 1), and this ether solution washed with water, dried over anhydrous sodium sulfate and evaporated.
Distillation under reduced pressure gave methyl 2-cyano-benzoate, b.p. 125 at 2.5 mm, 215 g (97%), a solid at room temperature, M.P. 45-6.
Step 3. ~lethyl 2-(5-2H-tetrazolyl) benzoate Methyl 2-cyanobenzoate (54 g, 0.33 mole) in D.M.F.
(165 ml) was treated with sodium azide (23.4 g, 0.36-mole) and ammonium chloride (19.3 g, 0.36 mole). After the reaction mixture had been stirred on the steam bath for 20 hrs, the D.M.F. was removed under reduced pressure and the residue ; dissolved in water (200 ml). The solution was filtered, cooled in ice and acidified to give a white precipitate which was filtered, washed with water and dried. This gave methyl 2-(5-2H-tetrazolyl) benzoate, M.P. 132-5, 19 g (28%). (Found:
C, 53.79, 52.59, 52.33; H, 4.25, 4.17, 4.07; N, 26.7g, 26.84, 27.25. CgH8N4O2 requires C, 52.94; H, 3.95; N, 27.44.) Step 4. Methyl 2-[5-(4-nitrophenyl)-1,3,4-oxadiazole-2-yl]
benzoate Methyl 2-(5-2H-tetrazolyl) benzoate (2 g, 0.01 mole) in pyridine (30 ml) was treated with _-nitrobenzoyl chloride (3.6 g, 0.02 mole). Heat was emitted and a white precipitate appeared. Heating on the steam bath produced a homogeneous reaction mixture and effervescence occurred.
After 1/2 hour, gassing ceased, the reaction mixture was cooled, treated with a few drops of water and allowed to stand for 15 mins. Addition of water (500 ml) gave a light yellow precipitate which was collected, washed with water and dried.
Recrystallization from acetone gave yellow crystals of methyl 2-[5-(4-nitrophenyl)-1,3,4-oxadiazole-2-yl] benzoate, M.P.
170-2, 2.2 g, 70%. (Found: C, 59.08; H, 3.50; N, 12.76.

105~187 C16HllN3O5 requires C, 59.08; H, 3.41; N, 12.92.) Example 6 Method V
. . .
Step l. N-alpha-Methylphenacylphthalimide To a stirred solution of 2-bromopropiophenone (21.3 g, 0.1 mole) in D.M.F. (80 ml) was added portionwise over 10 mins. potassium phthalimide (20 g, 0.12 mole). The tempera-ture rose slightly and after stirring for 3 hours the reaction mixture was poured into water (600 ml). The yellow precipitate was collected, washed with water and dried. Recrystallization from ethanol gave N-alpha-methylphenacylphthalimide, M.P.
82-4, 21.5 g, (77%).
Step 2. N-alpha-Methylphenacylphthalamic acid N-alpha-Methylphenacylphthalimide (27.9 g, 0.1 mole) was added to 1 N sodium hydroxide (110 ml) and stirred for 24 hrs. The resulting solution was filtered and poured into stirred N/2 hydrochloric acid (240 ml). N-alpha-Methylphenacyl-phthalamic acid was collected, washed with water and dried, M.P. 132-6, 20.3 g, (68%).
Step 3. 2-(4-Methyl-5-phenyl-2-oxazolyl) benzoic acid N-alpha-Methylphenacylphthalamic acid (20.3 g, 0.068 mole) was added portionwise to conc. sulfuric acid (50 ml) over 15 mins. during which time the temperature rose to 40.
The reaction mixture was stirred for 24 hrs. then poured into ; ice water (500 ml). The resulting precipitate was filtered, washed with water and digested with aqueous sodium bicarbonate.
Acidification of the aqueous bicarbonate solution and crystal-lization from water/ethanol (1:1) gave 2-(4-methyl-5-phenyl-2-oxazolyl) benzoic acid, M.P. 188-190, 12 g, (63%). (Found:
C, 72.07, 72.11; H, 4.83, 4.77; N, 4.99, 4.98. C17H13NO3 required C, 73.3; H, 4.66; N, 4.06) ~OS~ 7 Example 7 Method IIIb 2-~5-Phenyl-1,3,4-oxadiazole-2-yl) benzoic acid Benzoyl chloride (2.8 g, 0.2 mole) was added dropwise to a solution of methyl 2-(5-2H-tetrazolyl) benzoate (2 g, 0.01 mole) in pyridine (30 ml). Heat was emitted and a pre-cipitate of pyridine hydrochloride appeared. Heating on the steam bath caused the evolution of nitrogen. After 1/2 hour, all effervescence had ceased, the reaction mixture was cooled, a few drops of water added and the reaction allowed to stand 15 mins. An oil was obtained when the reaction mixture was added to cold water (500 ml). This oil was dissolved in ether.
The ether extract was washed with dilute acid, dilute bicar-bonate solution and water then dried over anhydrous sodium sulfate and evaporated.
The crude oil so obtained was dissolved in methanol ~0 ml) and added to a solution of sodium hydroxide (0.5 g) in methanol (20 ml). After this solution had been stirred at room temperature for 1 hour, the methanol was removed, the residue dissolved in water, washed with ether and acidified. The solid which precipitated was filtered, washed with water and dried.
1.5 g (56%) of crude product was obtained. Recrystallization from ethanol gave 2-(5-phenyl-1,3,4-oxadiazole-2-yl) benzoic acid, M.P. 175-7. The infrared spectrum was identical to that of 2-(5-phenyl-1,3,4-oxadiazole-2-yl) benzoic acid, made by methods Ia, Ic and II.
Example 8 Method II
2-(5-Phenyl-1,3,4-oxadiazole-2-yl) benzoic acid 2-Phenyl-5-(2-tolyl)-1,3,4-oxadiazole (47.2 g, 0.2 mole) was added to a solution of potassium permanganate (75 g, 0.47 mole) in water (875 ml) and refluxed till the color of permanganate had discharged. The reaction mixture was filtered lOS~87 hot and the manganese dioxide collected on the filter was washed with hot water (100 ml). After cooling, the combined filtrates were acidified and extracted with ether. ~he ether extract was washed with water, dried over anhydrous sodium sulfate and evaporated to leave a white solid. Recrystallization from methanol gave 2-(5-phenyl-1,3,4-oxadiazole-2-yl) benzoic acid, M.P. 173-5, 3.8 g (7.1%). The infrared spectrum was identical to that of 2-(5-phenyl-1,3,4-oxadiazole-2-yl) benzoic acid prepared by Method Ia.
Example 9 Method lIIb 2-[5-(4-Anisyl)-1,3,4-oxadiazole-2-yl] benzoic acid The same procedure is used as that for the preparation of 2-(5-phenyl-1,3,4-oxadiazole-2-yl) benzoic acid, Example 7, Method IIIB. The quantities of reagents used differ and ~-anisoyl chloride was used in place of benzoyl chloride.
Pyridine (60 ml) p-Anisoyl chloride (6.9 g, 0.04 mole) Methyl 2-(5-2H-tetrazolyl) benzoate (4 g, 0.02 mole) Sodium hydroxide (2 g) in methanol (100 ml) 2-~5-(4-Anisyl)-1,3,4-oxadiazole-2-yl] benzoic acid, M.P. 213-4 (50% aq. methanol), wt., 3 g (51%) Example 10 Method IIIb 2-[5-(3,5-Dimethylphenyl)-1,3,4-oxadiazole-2-yl]
benzoic acid c.f. Example 7, Method IIIB
Methyl 2-(5-2H-tetrazolyl) benzoate (4 g, 0.02 mole) Pyridine (60 ml) Sodium hydroxide (2 g) in methanol (100 ml) 3,5-Dimethylbenzoyl chloride (6.5 g, 0.04 mole) 2-~5-(3,5-Dimethylphenyl)-1,3,4-oxadiazole-2-yl]
benzoic acid, M.P. 162-4 (benzene), wt., 2.8 g (48%).

~ - 26 -1051~187 Example 11 Method IIIa Methyl 2-[5-(3,5-dichloro-4-ani syl ) -1,3,4-oxadiazole-2-yl] benzoate c.f. Example 5 Methyl 2-(5-2H-tetrazolyl) benzoate (3.75 g, 0.018 mole) Pyridine (60 ml)~
3,5-Dichloro-4-anisoyl chloride (9 g, 0.036 mole) Methyl 2-[5-(3,5-dichloro-4-anisyl)-1,3,4-oxadiazole-2-yll benzoate, M.P. 153-7 (ethanol), wt., 5 g (57~).
Example 12 Method IIIa Methyl 2-[5=~4-methyl-2-(3-pyridyl)-5-thiazolyl-]

- 26a -lt~S~18'~
1,3,4-oxadiazole-2-yl] benzoate c.f. Example 5. Step 4 The precipitated crude product was washed with water and aqueous bicarbonate solution.
~ethyl 2-(5-2H~tetrazolyl)benzoate (4 g, 0.02 mole) Pyridine (60 ml)

4-Methyl-2-(3-pyridyl~-5-thiazolylcarbonyl chloride hydrochloride (9.7 g, 0.04 mole) Methyl 2-[5-~4-methyl-2-(3-pyridyl)-5-thiazolyl3-1,3,4-oxadiazole-2-yl] benzoate, M.P. 152-3 (ethanol), wt., 1.8 g (24%).
Example 13 Method III~
; 2-[5-(2,4-Dichlorophenyl)-1,3,4-oxadiazole-2-yl benzoic acid c.f. Example 7, Method IIIb Methyl 2-(5-2H-tetrazolyl) benzoate (10.5 g, 0.051 mole) Pyridine (150 ml) 2,4-Dichlorobenzoyl chloride (21.0 g, 0.1 mole) Sodium hydroxide (3 g) in methanol (200 ml) 2-[5-(2,4-Dichlorophenyl)-1,3,4-oxadiazole-2-yl] benzoic acid, M.P. 168-171, wt., 5.5 g (31%) Example 14 Method IIIa Methyl 2-(5-methyl-1,3,4-oxadiazole-2-yl) benzoate Methyl 2-(5-2H-tetrazolyl) benzoate (16.5 g, 0.08 mole) and acetyl chloride were refluxed for 4 hours on a steam bath. Excess acetyl chloride was removed and the residue heated on the steam bath till effervescence had ceased. Dis-tillation of the residue under reduced pressure gave methyl 2-(5-methyl-1,3,4-oxadiazole-2-yl) benzoate, b.p. 165-9/lmm, 8.5 g (48~). a solid at room temperature, M.P. 67-8. (Found, C, 30 60.72, 60.66; H, 4.06, 4.57; N, 12.72, 12.75. CllHloN2O3 requires C, 60.54; H, 4.62; N,12.84.) Example 15 Method II
2-~5-(3-Chlorophenyl)-1,3,4-oxadiazole-2-yl]

-1~58187 benzoic acid c.f. Example 2 2-(3-Chlorophenyl)-5-(2-tolyl)-1,3,4-oxadiazole (54 g, 0.2 mole) Potassium permanganate (75 g, 0.47 mole) in water (1 1) Reco~ered starting material ~27 g) 2-[5-(3-Chlorophenyl)-1,3,4-oxadiazole-2-yl] benzoic acid, M.P. 184-8, wt. 1.0 g (3.3~).
Example 16 Method Ia 2-[5-(4-Chlorophenyl-1,3,4-oxadiazole-2-yl]
benzoic acid c.f. Example 1, Method Ia Sulfur trioxide (50 g, 35 ml) in D.M.F. (100 ml).
1-(4-Chlorobenzoyl)-2-(2-carboxybenzoyl) hydrazine (45 g, 0.15 mole) in D.M.F. (75 ml) 2-[5-(4-Chlorophenyl)-1,3,4-oxadiazole-2-yl] benzoic acid, M.P. 206-9 (acetone), wt., 9 g (21%). (Found: C, 59.09, 58.88; H, 3.03, 2.97; N, 8.16j 8.16; Cl, 11.48, 10.94, 11.32, 11.51 C15HgClN2O3 requires, C, 59.91; H, 3.02; N, 9.32;
Cl 11.79).
Example 17 Method Ia 2-[5-(2-Tolyl)-1,3,4-oxadiazole-2-yl] benzoic acid c.f. Example 1, Method Ia Sulfur trioxide (250 g, 175 ml) in D.M.F. (500 ml) 1-(2-Carboxybenzoyl)-2-(2-toluoyl) hydrazine (250 g, 0.9 mole) in D.M.F. (200 ml).
2-[5-(2-Tolyl)-1,3,4-oxadizaole-2-yl]benzoic acid, M.P. 154-5 (acetone/30-65 ligroin), wt., 33.5 g (14~).
(Found: C, 67.72, 67.78; H, 4.72, 4.31; N, 8.71, 8.67.
C16H12N2O3 requires C, 68.56; H, 4.32; N, 10.00) Example 18 Method II
2-[5-(2~Anisyl)-1,3,4-oxadiazole-2-yl] benzoic acid c.f. Example 2 1~5~8t7 2-Anisyl-5-(2-tolyl)-1,3,4-oxadiazole (26 g, 0.1 mole) Potassium permanganate (37.5 g, 0.24 mole) in water (450 ml) Recovered starting material (18 g) 2-~5-(2-Anisyl)-1,3,4-oxadiazole-2-yl] benzoic acid, M.P. 157-160 (henzene/ethanol) wt., 1,7 g (17.9%) (Found: C, 66.22, 65.42; H, 4.46, 4.46; N, 9.6~, 9.97.
C16H12N2O4 requires C, 64.-86; H, 4.08; N, 9.'46.) Example 19 Method II
2-[5-(3-Pyridyl)-1,3,4-oxadiazole-2-yl] benzoic acid c.f. Example 2 2-(3-Pyridyl)-5-(2-tolyl)-1,3,4-oxadiazole (20 g, 0.09 mole) Potassium permanganate (3 g, 0.02 mole) in water (375 ml) Recovered starting material ~8.5 g) 2-[5-(3-Pyridyl)-1,3,4-oxadiazole-2-yl] benzoic aaid, M.P.
213-5 (ethanol) wt., 5 g (36%). (Found: C, 62.83, 62.71;
H, 3.64, 3.47; N, 16.17, 16.05. C14HgN3O3 requires, C, 62.92;
H, 3.39; N, 15.73.) Example _0 Method Id Ethyl ?- ( 5-phenyl-1,3,4-oxadiazole-2-yl) benzoate 2-(5-Phenyl-1,3,4-oxadiazole-2-yl) benzoic acid (26.6 g. 0.1 mole) in chloroform (100 ml) and thionyl chloride (20 ml) were refluxed for 1 hour. The e~cess thionyl chloride and chloroform were removed under reduced pressure to leave a colorless oil which slowly solidified. Benzene (100 ml) was added. The resulting solution was added dropwise to a stirred solution of ethanol (6 ml. 0.11 mole) and pyridine (10 ml) in benzene (200 ml). After 12 hours, an equal volume of ether was added. The solution was washed with water (500 ml) N/50 HCl (500 ml), 5% aq. bicarbonate (500 ml) and again with water (500 ml). Evaporation of the ether left a light yellow viscous oil which could not be distilled 23 g (78%).

105~

Example 21 Methyl 2-(5-phenyl-1,3,4-oxadiazole-2-yl) benzoate 2-(5-Phenyl 1,3,4-oxadiazole-2-yl) benzoic acid (15 g, 0.056 mole) in dry ether (700 ml) was treated with ethereal diazomethane till the color of the ethereal diazo-methane persisted. Subsequent filtration and evaporation of the ether left a light yellow oil which could not be distilled.
After prolonged refrigeration, a solid was obtained from toluene/
ligroin. This gave methyl 2-(5-phenyl-1,3,4-oxadiazole-2-yl) benzoate, M.P. 40-41, wt. 8.5 g (54%). (Found: C, 69.39, 69.28; H, 4.47, 4.40; N, 9.33, 9.35. C16H12N2O3 requires C, 68.56; H, 4.32; N, 10.00.) Example 22 Propargyl 2-(5-phenyl-1,3,4-oxadiazole-2-yl) benzoate 2-(5-Phenyl-1,3,4-oxadiazole-2-yl) benzoic acid (26.6 g, 0.1 mole) was added to a solution of potassium hydroxide (6 g, 0.11 mole) in methanol (250 ml). When all the acid had dissolved, propargyl bromide (20 ml) was added and the reaction mixture refluxed for 2 1/2 hours. The solvent was removed, the residue was dissolved in ether which was subsequently washed with water, aqueous bicarbonate, again with water and dried. Removal of the ether gave a light brown solid which was recrystallised from ether. This gave propargyl 2-~5-phenyl-1,3,4-oxadiazole-2-yl) benzoate as tan-colored crystals, M.P.
99-101, 11.5 g (38%). (Found: C, 71.43; H, 4.04; N, 9.27.
C18H12N2O3 requires, C, 71.04; H, 3.98; N, 9.21.) Example 23 Methyl 2-[5-(3-nitrophenyl)-1,3,4-oxadiazole-2-yl]
benzoate c.f. Example 22 2-[5-(3-Nitrophenyl)-1,3,4-oxadiazole-2-yl] benzoic acid (31.1 g, 0.1 mole) 105~87 Potassium hydroxide (5.6 g, 0.1 mole) in methanol (600 ml) Methyl iodide (17 ml) Methyl 2-[5-(3-nitrophenyl)-1,3,4-oxadiazole-2-yl)]
benzoate, M.P. 132-4 (methanol), wt. 33.5 g (97%). (Found:
C, 59.39, 58.72; H, 3.52, 3.34; N, 13.15, 12.91. C16HllN3O5 requires C, 57.51; H, 3.54; N, 13.42.) Example 24 2,3-Epoxypropyl 2-(5-phenyl-1,3,4-oxadiazole-2-yl) benzoate c.f. Example 22, same quantities, epibromohydrin (15 ml) as alkylating agent. The product, 2,3-epoxypropyl 2-(5-phenyl-1,3,4-oxadiazole-2-yl) benzoate was a viscous oil which could not be distilled, wt. 12 g (37%).
Example 25 Buty_2-(5-phenyl-1,3,4-oxadiazole-2-yl) benzoate c.f.Example 20, same molar quantities, n-butanol (7.4 g, 9.2 ml, 0.1 mole) used. The product, butyl 2-(5-phenyl-1,3,4-oxadiazole-2-yl) benzoate was a viscous oil, wt. 25 g (83%).
Example 26 Octyl 2-(5-phenyl-1,3,4-oxadiazole-2-yl) benzoate c.f. Example 20, n-octanol (12.5 g, 0.1 mole) used. The pro-duct, n-octyl 2-(5-phenyl-1,3,4-oxadiazole-2-yl) benzoate was a viscous oil, wt. 28 g (74%).
Example 27 Dodecyl 2-(5-phenyl-1!3,4-oxadiazole-2-yl) benzoate c.f. Example 20 Dodecyl alcohol (18.6 g, 0.1 mole) Dodecyl 2-(5-phenyl-1,3,4-oxadiazole-2-yl) benzoate, a viscous oil, wt. 35 g (81%).
Example 28 3-Butynyl 2-(5-phenyl-1,3,4-oxadiazole-2-yl) benzoate 1~5~
c.f. Example 20 3-sutyne-1-ol (7 g, 0.1 mole) 3-Butynyl 2-(5-phenyl-1,3,4-oxadiazole-2-yl) benzoate, a viscous oil, wt. 12 g (38~).
Example 29 Method Vb Methyl 2-(5-phenyl-2-oxazolyl) benzoate 2-(5-Phenyl-2-oxazolyl) benzoic acid (5 g, 0.02 mole) in methanol (50 ml) and conc. sulfuric acid (0.5 ml) was refluxed 16 hours. The methanol was removed and the residue dissolved in chloroform. The chloroform solution was washed with dilute bicarbonate solution, water, then dried and evapor-ated. Recrystallization of the residue from ethanol gave methyl 2-(5-phenyl-2-oxazolyl) benzoate, M.P. 77-9, wt. 3 g (57%).
(Found: C, 73.16, 73.40; H, 4.77, 4.72; N, 4.95, 5.00.
C17H13NO3 requires C, 73.11; H, 4.69; N, 5.02.) Example 30 Ethyl 2-(5-phenyl-2-oxazolyl) benzoate c.f. Example 29 2-(Phenyl-2-oxazolyl) benzoic acid (10 g, 0.04 mole) Ethanol (100 ml) conc. sulfuric acid (10 ml) reflux time - 20 hours Ethyl 2-(5-phenyl-2-oxazolyl) benzoate, M.P. 49-50 (ligroin) wt. 8 g (72%). (Found: C, 73.86, 73.99; H, 5.27, 5.20; N, 4.70, 4.85; requires C, 73.80; H, 5.12; N, 4.78.) Example 31 n-Butyl 2-(5-phenyl-2-oxazolyl) benzoate c.f. Example 29 2-(5-Phenyl-2-oxazolyl) benzoic acid (10 g, 0.04 mole) n-Butanol (100 ml), conc. sulfuric acid (0.5 ml) Heated on steam bath 20 hrsO
n-Butyl 2-(5-phenyl-2-oxazolyl) benzoate, a viscous light yellow l~Sb~:~L87 oil, wt. 10.5 g (90%).
Example 32 Propargyl 2-[5-t3-nitrophenyl)-1,3,4-oxadiazole-2-yl] benzoate c.f. Example 22 2-[5-(3-Nitrophenyl)-1,3,4-oxadiazole-2-yl] benzoic acid (31.1 g, 0.1 mole) Potassium hydroxide (6 g, 0.11 mole) in methanol (250 ml) Freshly distilled propargyl bromide (20g) Propargyl 2-[5-(3-nitrophenyl)-1,3,4-oxadiazole-2-yl)]
benzoate, M~P~ 124-6, wt. 12 g (34~). (Found: C, 61.87/ 61.75;
H, 3.43, 3.33; N, 12.64, 12.31; C18HllN3O5 requires C, 61.90;
H, 3.16; N, 12.00.) Example 33 Methyl 2-[5-(2-nitrophenyl)-1,3,4-oxadiazole-2-yl]
benzoate.
2-[5-(2-Nitrophenyl)-1,3,4-oxadiazole-2-yl]
benzoic acid (31 g, 0.1 mole) in acetone (1 1) was treated with dimethyl sulfate (10 ml) and anhydrous potassium carbonate (15 g). The reaction mixture was refluxed and stirred for 20 hours. After the removal of the solvent, the residue was treated with water, and the undissolved material filtered, washed with water and dried. Recrystallization from acetone gave methyl 2-[5-(2-nitrophenyl)-1,3,4-oxadiazole-2-yl] benzoate, M~Po 165-9, 5g.
Example 34 2-[5-(4-Nitrophenyl)-1,3,4-oxadiazole-2-yl]
benzoic acid Crude reaction product from a repeat run of Example 5 was dissolved in methanol (25 ml) and stirred for 2 hrs. in a solution of sodium hydroxide (0.75 g) in methanol (50 ml). Methanol was then removed and the residue was dissolved in 11U~i~187 water, extracted with ether to remove unreacted ester and acidified. The precipitate was filtered, washed with water and dried. This gave 2-[5-(4-nitrophenyl)-1,3,4-oxadiazole-2-yl] benzoic acid, M.P. 215-7, 0.8 g. 1.6 G of methyl ester was obtained from the ether extract.
Example 35 2~(5-Phenyl-1,3,4-thiadiazol-2-yl)benzoic acid was prepared by the following method.
2-o-Methylphenyl-5-phenyl-1,3,4-thiadiazole (25 g.) was suspended in a solution of potassium permanganate (40 g.) in water (475 ml.). The reaction mixture was stirred and refluxed until the color of permanganate had discharged, then filtered and cooled. Unreacted 2-o-methylphenyl-5-phenyl-1,3,4-thiadiazole which separated was removed by filtration.
When this filtrate was acidified, 2-(5-phenyl-1,3,4-thiadiazol-2-yl)benzoic acid was obtained and recrystallized from ethanol to give white crystals, M.P. 178-180. Analysis gave C, 63.37;
H, 3.74; N, 9.74. C15HloN2O2S requires C, 63.83; H, 3.51;
N, 9.93.
Example 36 This example illustrates the growth regulating properties of the chemicals on four crops; Pinto Beans -Phaseolus vulgasis; Cotton - Gossypium hirsutum; Pea-nuts - Arachis hypogaea and Oats - Avena sativa. Six hundred mg of chemical are dissolved in 10 ml acetone and 30 mg of Triton Xl00 (trademark; isooctyl phenyl poly ethoxy ethanol). This mixture was diluted to a 100 ml volume with distilled water.

1051~ 7 ~, Respectlve concentrations of 2000 and 1000 ppm are made ~rom the 6000 ppm stock. The appTspriate mlx-ture was sprayed to runoff on the four species afore-mentioned. m e plants were sprayed witha DeVilbiss atomizing sprayer at the following ~tages of growth -Pinto Beans - very early l~t tri~oliate Cotton - Fully expanded primary lea~ stage Peanuts - 2_4 leaf stage Oats - 2-4 leaf stage 1 0 .... .. ...... , .. ~. . . . .. ,. . ._.
SubJective plant growth regulant ob~ervations were made from five days a~ter spraying through three weeks. The~e observations included retardation, for-mat~ve effects and phytotoxicity. m ese data aee pre-sented in TABLE I, wherein the chemicals employed are identlfied by the letters A through P as follows:
A. 2-(5-Phenyl-1,3,4-oxadiazole-2-yl)benzoic i acid.
! B, 2-[5-(2-Tolyl)-1,3,4-oxadiazole-2-yl]ben_ zoic acld.
C. Z-[5-(4-Chlorophenyl)-1,3,4-oxadlazole-2_yl~benzo~c acid.
D~ 2-[5-(2-Chlorophenyl)_1,3,4-oxadlazole_2_ yl]benzoic acid.
E. 2-[5-(3-Chlorophenyl)-1,3,4-oxadiazole-2-yl]benzoic acld.
F. 2-~5-(3-Byridyl)-1,3,4-oxadiazole-2-yl3 benzoic acid.
G. 2-(5-Phenyl-2-oxazolyl)benzoic acid.
H. 2-~5-(2-~ethoxyphenyl)-1,3,4-oxadiazole-2-yl]benzoic acld.
I. Propargyl 2-(5-phenyl_1,3,4-oxadiazole_2_ yl)benzoate.
J. 2-(4-Methyl-5-phenyl-2 oxazolyl)benzoic acid.

-``` 1()5~1~7 -- `

K. Butyl 2-(5-phenyl-1,3,4-ox diazole-2-yl~
benzoate.
L. 2-{5-(3-Witrophenyl)-1,3,4-oxadiazole-2-yl]benzoic acid.
M. 2-[5-(2,4,5-~rimethyl-2-furyl)-1,3,4-oxa-diazole-2-yl~benzoic acld.

I N. Methyl 2-(5-phenyl-1,3,4-oxadiazole-2-yl) b~..oate.
O. Methyl 2_(5-phenyl-2-oxazolyl)benzoate.
P. 2-(5-Phenyl-1,3,4-thiadiazol-2-yl)benzoic acid.
TABL$ I
Plant Growth Regulation .
Rate Plant Growth Regulating Chemical PPM . Crop Response A 2000 Pinto Bean Severe epinasty and re-tarding and twisting B 2000 Pinto Bean Severe retardation and tri~ol~ates inhibited B 6000 Peanuts 80~ retarded and severe epinasty C 2000 Pinto Bean Trifoliates inhibi~ed +
severe epinasty C 6000 Cotton 80% retarded Peanuts 80% retarded D 2000 Pinto Bean 80-100% retardation;
moderate epinasty D 6000 Peanuts Moderate epinasty E 1000 Pinto Bean Moderate epina3ty, 80-100% retardation Cotton Severe eplnasty Peanut 50-60~ retardation;
moderate epinasty F . 2000 Pinto Bean 80-100% retardation;
terminals killed F 6000 Cotton Moderate epinasty Peanut Moderate epinasty G 1000 Pinto Bean 80~ retardation; ter-minais inhlbited G 6000 Cotton 20~ retardation G 6000 Peanut 60% retardation G 6000 Oat 20% retardatlon ~OS8187 TABLE I ~Cont'd.) Rate Plant Growth Regulating Chemical PPM Crop ResPonse ~ . .
H 1000 Pinto Bean 80% retardation H 6000 Peanut 20% retardation H 6000 Oat 20% retardation I 1000 Pinto Bean Severe epinasty 100% retardation Cotton 20% retardation Peanuts 20% retardation Oats 20% retardation J 6000 Cotton New Growth twisted + 30% ret'd.
Peanut 50~ retarded Oat 80~ retarded K 6000 Cotton Trifoliates 80~ retarded & deformed Peanut Slight twisting; 30% retarded Oat 80% retarded L 6000 Cotton Leaves stunted Peanut Moderately retarded M 1000 Pinto Bean Trifoliates retarded, forced axillary growth 6000 Peanuts Twisted N 1000 Tomato Severely epinasty Pinto Bean 100% retarded 6000 Cotton 30% retarded O 1000 Pinto Bean 80% retarded O 6000 Peanut Moderate epinasty P 2000 Pinto Bean 100% retarded, terminals killed ~20 P 6000 Peanut 50% retardation Example 37 This Example illustrates the growth retarding effects of the present chemicals on soybeans, Glycine max. Twelve mg of chemical are dissolved in 10 ml acetone and 30 mg Triton Xl00 (isooctyl phenyl poly ethoxyethanol). This mixture was diluted to a 100 ml volume with distilled water, making it a 120 ppm solution. Respective concentrations of 60 and 30 ppm are made from the 120 ppm stock solution. Three pots containing two soybean plants at the fully expanded first trifoliate leaf stage are sprayed to run-off with a DeVilbiss atomizing spr~yer. The plants are placed in ~OS~ 7 the greenhouse. The plants are measured at spraying time and when the control plants begin to po~ or ap-proximately ~our wee~s after spraying. The actual measurement used for e~aluation is the difference in growth ~rom first measurement to the last measurement.
A percent growth flgure is obtained by using the fol-lowing formula:
Growth o~ control ln cm - Growth of Treated in Cm X 100 ~ % retardation Growth of Control in cm The results are shown in TABLE II, wherein the letters represent various chemicals identified in Exam-ple 36.

_ 38 _ 10~8~87 TABLE II
__ RateRetardation o~ Soybeans ~hemical PPM % Retardation , A ~0 78 B ~0 42 C ~0 89 G ~0 83 J 12~ 7~

Example 38 ~his Example ~urther illustrates practice of the lnvention on cotton.
one hundred mg o~ chemical formulated in a three pound acti~e gallon (see Example 40-i for Composition) were dissolved in 400 ml o~ water. This solution has a concentration of 1000 ppm. Respective concentra-tions of 500 and 250 ppm were made by dllutlng the stock solution oflO00 ppm. Four cotton seeds, Goseypium :

1~5~8~

hirsutum, varlety Stoneville 213g were planted in six-inch pots. The pots were eventually thinned to one plant per pot. The spray appli~ation was made when the plant~ had developed twa bolls one inch in diame-ter. Three plants were used ~or each chemical treat-I me~t which was applied to run-off wlth a DeVilbiss I atomizing sprayer. The last terminal boll that was one-half inch in diameter was marked with a "twistem".
The cotton was allowed to mature seven weeks beyond spray application before data were taken. The data consisted of measuring the growth in cm from the marked boll to the terminal growing point and also the number of bolls that developed beyond the marked boll were counted. The percent decrease in height and number of bolls was calculated by using the following formula, Height in cm of check -Height in cm of treated X 100 = ~ retardation Helght in cm of Check The data are given in Table II, illustrating the dra_ matic reduction in height and boll number due to the chemical application.

TABLE I~
Growth Regulation on Cotton Rate % Decrease in 25 Chemical PPM~ Retardation Boll Number 11~5~8~

Example 39 To illustrate ~urther the growth regulating properties of the chemicals on the metabolic activity of plants, 10.5 ml of formulation (~srmulated as a three pound active gallon - see Example 40-ii for com-position) were brought up to a 1892 ml volume with ~:-water. This solution was applied at 0.5 lbs. active per acre in 30 gallons of water to sugarbeets, Beta vul~aris, six weeks be~ore harvest.
The yield data were determined by hand harvest-ing each of three treatment replicates which consisted ; o~ one row fi~teen ~eet long. The sugar content was ; determined by measuring the sucrose content o~ beets that were randomly selected ~rom each plot.
The data are given in TABLE IV, lllustrating the increase in sugar content due to the chemical ap-plication.

TABLE IV
Increase_in Sugar Rate Lbs./
Chemical Acre ~ Sugar _ A 1/4 15.48 A 1/2 15.76 A 1 15.18 Control 14.85 ~ ased on an average yield of 40,000 pounds of beets per acre, the 0.91~ increase over the control would bring the farmer 364 extra pounds o~ sugar per acre.

11)58~7 Example 40 Listed below are non-llmiting examples a~ ~or~
mulationS which can be prepared for use in the invention.
g i. 32.7~ act~ve by volume (3 lb/
gallon soluble liquid)_ a. 2-(5-Phenyl-1,3,4-oxadiazol-2-yl)benzoic acid 36.o b. ~H40H (58.6%) 17.0 c. Water 57.o - 100.O
ii. 32.96% active by volume (3 lb/
gallon soluble liquid) a. 2-(5-Phenyl-1,3,4-oxadiazol-2-yl)benzoic acid 36.o b. NH40H (58.6%) 22.0 c. Dow~ac (trademark) 2Al (solution) sodium dodecyldiphenyl ether dl-sul~onate 2.25 d. Water 59.75 iii. 22~ active by volume (2 lb/
gallon soluble liquid) a. 2-(5-Phenyl-1,3,4-oxadiazol-2-yl)benzoic acid 24.0 b. KOH (95.5%) 6.o c. Water 78.8 iv. 10~ active granule a. 2-(5-Phenyl-1~3,4-oxadiazol-2-yl)benzoic acid 30.0 b. NH40H (58-6%) 13.2 c. Water 31.8 d. 25/50 mesh RVM Attaclay (trade-mar~) attapulgite clay 270.0

Claims (2)

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

1. 2-(5-Pheng1-1,3,4-thiadiazol-2-yl)benzoic acid.

2. A method of regulating the growth of plants comprising applying to plants, in an amount effective to regulate the growth of the plants, 2-(5-phenyl-1,3,4-thiad1azol-2-yl)benzoic acid.