WO1987000840A1 - Nouveaux derives d'uree, procedes de production et herbicide - Google Patents

Description

' DESCRIPTION

NOVEL UREA DERIVATIVES , PROCESSES FOR PRODUCTION THEREOF AND HERBICIDE

Technological field

This invention relates to novel urea derivatives having herbicidal activity and being useful as a herbicide, processes for production thereof and a herbicide comprising such a urea derivative.

Background technology

Wheat, corn, r ice and soybean are important crops , and many herbicides have been used to increase the harvest of these crops . Conventional herbicides , however , have not proved to be entirely satisfactory in regard to herbicidal activity or safety on crops , and it has been desired to develop herbicides which kill hazardous weeds in low dosages and do not cause phytotoxicity to crops .

It is an obj ect of this invention to provide herbicidally active urea derivatives which are not descr ibed in the prior literature and can meet the afore - said desire , processes for production thereof , a herbicide comprising such a urea derivative as an active ingredient , and a method of controlling weeds .

Disclosure of the invention

The present inventors have made investigations in order to develop a herbicidally active compound which is not likely to cause unnegligible phytotoxicity to useful crops and can control hazardous weeds in low dosages . These investigations have led to the successful synthesis of urea der ivatives represented by the follow - ing formula 【1 ] not descr ibed in the prior literature , and also to the discovery that the compounds of formula [ I ] are useful for controlling hazardous weeds at reduced dosages , have low phytotoxicity on useful crops , and are very superior compounds in herbicide applications .

wherein

A represents the bond -N= or -C= in which

Y

X is a hydrogen atom, a chlorine atom, a nitro group or a trif luoromethyl group;

B represents a hydrogen atom, a methyl group or a methoxy group ; and

Ar represents one member selected f rom the group consisting of

in which R to R _f independently from each other , represent a hydrogen atom, a lower alkyl group or a lower alkoxy group; may further represent a hydroxy 1

2 2 δ 7

group; a prior of R and R _f a pair of R and R and

9 io

a pair of R and R each , taken together , may represent an alkylene linkage and may form a 5 - or 6-membered ring together with the two adj acent carbon atoms to which

11 12

they are ' bonaed; R and R , taken together , may form

li 15 an ethylenedioxy linkage - 0- (CH₂) ₂ - 0 - , or R and R , taken together , may form an alkylene linkage and form a

5 - or 6-membered ring together with the carbon atoms to which they are bonded , or R and , taken together , may represent a methylene linkage and form a 5 - or 6-merabered ring together with one carbon atom to which they are

14 is

bonded _r or R and R , taken together _f may form a di - chloromethylene linkage .

1 38

When in general formula 【1】 , R to R represent a lower alkyl group or a lower alkoxy group, they usually contain 1 to 4 carbon atoms , preferably 1 to 3 carbon atoms . Specific examples include methyl , ethyl , n - propyl , isopropyl , n - butyl , isobutyl , sec - butyl , tert- butyl , methoxy_f ethoxy n-propoxy _r isopropoxy n-butoxy, isobutoxy and sec-butoxy groups .

2 3

When R and R are bonded to each other to form an alkylene group, the total number of carbon atoms of the alkylene group is usually 3 or 4 · Examples of the alkylene group are «fCH and +(：1^ ₄，

When and are bonded to each other to form an alkylene group, the total number of carbon atoms of the alkylene group are usually 3 to 5 · Examples include -

CH₃

2 3 2 4 2 3

CH₃

- CH_n^-CH-CH₂- . When R⁹ and R¹⁰ are bonded to each other to form an alkylene group, the total number of carbon atoms of the alkylene group is usually 4 or 5 . Examples include - CH- . and +CHつ ·

² 11 2 5 ₁₅

When R and R are bonded to each other to form an alkylene group, the total number of carbon atoms of the alkylene group is usually 2 or 3 . Examples include CH₂>₂ and -fCH

When R¹⁵ and R are bonded to each other to form an alkylene group, the total number of carbon atoms is usually 4 or 5 2 . Examples include - CH₂^₄ and H₂ 6 .

Examples of the Ar group are listed below .

一 S 一 £00/98df/lDd o o 8 O u

一 9 一

e00/98df/l3d 0t¾00/ム 8 OM

£00/98cir/丄：) d 0t¾00/.8 OM 86ε l〕d oio卜/ 8 O

し.

H^DO ³H³DO "HDO

HD 'HD HD

Among these urea der ivatives of this invention, preferred specif ic examples are shown in Tables 1 to 11. Table

一 to be continued 一 Table 1 (continued)

― to be continued一 Table 1 (continued)

一 to be continued 一 Table 1 (continued)

一 to be continued 一 Table 1 (continued)

一 to be continued ― Table 1 (continued)

Compound No. R¹ R² R³ R⁴ B

52

^CH3 H ^C2^H5 CH^

^CF3

53 CH₃ H CH₃

^C2^H5 ^0CH3

54 H CH₃ CH₃ H

^C2^H5

55 H CH^

^C2^H5 CH₃ CH₃

56 C₂H₅ H CH^ CH₃

^0CH3.

57 H _(CH₂)₄- CH₃

^CH3

58 H - (CH₂)₄- CH₃ 0CH₃

1

Table 2

一 to be continued 一 Table 2 (continued)

一 to be continued 一 Table 2 (continued)

- to be continued 一 Table 2 (continued)

一 to be continued 一 Table 2 (continued)

Table ：

一 to be continued 一 Table 3 (continued)

一 to be continued 一 Table 3 (continued) q

Compound No. R¹⁰ B

151 C₂H₅ ^C2^H5 OCH₃

152 -（CH .H

2)4- .

153 -(CH

2)4-

154 -（CH

2)4- ^0CH3

Table 4

一 to be continued 一 Table 4 (Continued)

一 to be continued 一 Table 4 (Continued)

一 to be continued 一 Table 4 (Continued)

一 to be continued 一 Table 4 (Continued)

一 to be continued一 Table 4 (Continued)

一 to be continued 一 Table 4 (Continued)

to be continued 一 Table 4 (Continued)

一 to be continued 一 Table 4 (Continued)

― to be continued 一 Table 4 (Continued)

一 to be continued 一 Table 4 (Continoed)

― to be continued 一 Table 4 (Continued)

一 to be continued - Table 4 (Continued)

Table S

一 to be continued ― Table 5 ( continued)

Compound No. R¹⁷ R¹⁸ R¹⁹ R²⁰ B

, 331 CH， OCH₃ H H H

332 CH₃ OCH₃ H H CH-5

333 OCH₃ H H OCH₃

^CH3

Table 6

22

ComDound No. R²¹ B

334 H H

335 H

336 、Η₇ H OCH^

337 ' 、H₉ H CH^

338 ₉ H OCH,

339 H CH₃

^C2^H5

340 H OCH^

^C2^H5

n

341 H H

^C3^H7

n

342 H CH₃

^C3^H7

n

343 H 0CH₃

^C3^H7

344 H 、Η₇ CH^

345 H 、Η₇ OCH^ Table '

0CH₃ oen

Table 8

Compound No. R^{3 0} R³¹ B

355 CH₃ CH₃ H

356 CH₃

^CH3 ^CH3

357 CH₃ CH₃ OCH₃ Table 10

Compound No. R³² R³³ R³⁴ B

358 CH₃ CH₃ CH₃ H

359 CH₃ CH₃ CH₃ CH₃

360 CH₃ CH₃ CH₃ 0CH₃

361· CH₃ CH₃ H

^C2^H5

362 CH₃ CH₃ CH₃

^C2^H5

363 CH₃ CH₃ OCH₃

^C2^H5

Table 11

Compound No . R^{3 5} R³⁶ R³⁷ R³⁸ B

ん

364 H H CH₃ CH₃ CH^

365 H H CH- CH^ OCH,

3 3 3

36ζ H Ή OCH₃ CH₃ H

367 H H OCH₃ CH₃ CH^

368 H H CH₃ OCH₃

^0CH3

369 H CH₃ OCH₃ CH₃ H

370 H CH₃ CH₃ CH^

^0CH3

371 H CH₃ OCH₃ CH₃ OCH,

' he compound of formula (I) provided by this invention can be produced/ for example, by reacting an aminopyridine or an aniline derivative represented by the following formula (II)

Ar»0-^^V- H₂ [II] wherein Ar and A are as defined with regard to formula [ェ] ,

with methyl isocyanate, N N-dimethylcarbamoyl chlo ide or N-methoxy-N-methylcarbamoyl chloride.

The compound of formula [11】 used in the above reaction can be produced by a synthesis route consisting of the following reactions (1) and (2) .

In performing the reaction (1) , known reaction means of forming an aromatic ether compound by reaction of a phenolic hydroxy 1 group with an aryl chloride may be applied. Specifically, it can be cafr ied out by stirring the reaction mixture at a temperature of 20 to 150°C_f for 0.5 to 10 hours in an aromatic hydrocarbon (e.g. _f benzene, toluene _f xylene), in an aprotic polar solvent (e.g. , N N-dimethylf ormamide_f l-methyl-2-pyrrolidone) or in their mixture in the presence of a base such as sodium hydroxide potassium hydroxide, sodium carbonate and potassium carbonate. After the reaction, the compound [V] can be isolated by a known means such as column chromatography.

On the other hand, known means of producing an aromatic amine by reducing an aromatic nitro compound with hydrogen may be applied to the practice of the reaction (2) . Specifically, the reduction with hydrogen can be carried out at a temperature of 20 to 100°C

2

under normal pressure to 20 kg/ cm of hydrogen in an inert solvent such as benzene, toluene, xylene, methanol, ethanol or ethyl acetate in the presence of an ordinary reducing catalyst such as Raney nickel or palladium - carbon. After the reaction, the compound [11】 can be isolated by operations including removal of the catalyst, removal of the solvent, and as required, recrystalliza - tion.

Referential Examples 39 and 41 given hereinbelow illustrate the synthesis of compound [V〗 by the reaction (1) , Synthesis of compound [11〗 by the reaction (2) is illustrated in Referential Examples 40, 42, 45, 47 and 48 given hereinbelow.

• Among the compounds of general formula [V〗 , ' compounds of the following general formula [V-ll

in which R1 is a lower alkoxy group or a hydroxy 1 group,

can also be produced by a synthesis route consisting of the following reactions (3) and (4) .

.. (3)

After the reaction (3) , the compound [VI] can be isolated by the same operations as in the case of obtaining the compound [V】 by the above reaction (1) ·

The reaction (4) proceeds by heating the reaction mixture at 40 to 120°C in the absence of solvent or in an inert solvent such as acetone, dioxane, benzene or toluene in the presence of an acid catalyst such as hydrochloric acid_f sulfuric acid and Amberlyst- After the reaction, the compound [V-l] can be isolated by recrystallization_f column chromatog etc. after optionally removing the catalyst and the solvent.

Synthesis of the compound [VI] by the reaction (3) is shown in Referential Example 43, and synthesis of the compound 【V - 1〗 by the reaction (4) , in Referential Examples 44 and 46.

Among the compounds of general formula 【V】 , compounds of general formula [V-2】

may also be synthesized from the compound [VI] in accordance with the following reaction (5) · - -

【VI〗 【V 】

Known procedures of reacting a cyclohexene ring with dichlorocarbene to introduce a dichloromethylene group into the double bond portion of the cyclohexene ring may be applied to the practice of the reaction (5) . Specifically, the reaction (5) proceeds by stirring the compound [VI], chloroform and sodium or potassium

hydroxide in the absence of solvent or in water as a solvent in the presence of a quaternary ammonium salt such as ben2yltrimethylammonium chloride*

Referential Ex'ample 48 illustrates the production of a compound of general formula [V - 2〗 by the reaction (5) .

Use of a base in the reaction of the compound of formula [II] with the carbamoyl chloride can increase the yield of the product. Examples of the base are pyridines such as pyridine _f picoline, lutidine and colli- dine, tertiary amines such as triethylamine, 1 _r 8-diaza- bicyclo [5 _f 4 ,0 ] undecene-7 and N_f -dimethylaniline_r and inorganic bases such as sodium bicarbonate, potassium bicarbonate, sodium carbonate, potassium carbonate, sodium hydroxide and potassium hydroxide. The amount of the base used is from 0,5 to 20, preferably from 1 to 10, as the molar ratio to the carbamoyl chloride.

The reaction of the compound [11〗 with methyl isocyanate proceeds in the absence of a catalyst, but as required, may be car ied out in the presence of 0.1 to 5 mole , based on the compound [II], of a tertiary amine such as triethylamine. The use of a reaction solvent is not necessary , but there may be used a solvent inert to the reaction, for example an aromatic hydrocarbon such as benzene , toluene and xylene, a halogenated hydrocarbon such as 5 chloroform, dichloromethane , carbon tetrachloride,

dichloroethane, trichloroethane, tetrachloroethane, chlorobenzene or dichlorobenzene , tetrahydrof uran, ethyl acetate or dimethylf orinamide , either alone or in combination.

10 The reaction is carried out by mixing 1 mole of the aminopyridine derivative or aniline derivative [ II ] and 0.8 to 3 moles , preferably 1 to 2 moles, of methyl isocyanate or the carbamoyl chloride with or without the base in the absence of solvent or in the aforesaid

15 solvent, and stirring the mixture at a temperature of 一 20 to 100°C , 'preferably 0 to 80°C, for 0 .3 to 30 hours .

After the reaction, the f inal desired product can be obtained by various separation methods shown in Examples given hereinbelow.

i (\ According to another embodiment of producing the compound of formula [ 1〗 , the compound of formula [ I ] can be produced by reacting an isocyanate derivative - represented by the following formula [ III ]

25 wherein Ar and A are as def ined with regard to formula [ I ] ,

with' an amine compound represented by the following formula 【IV】

30 wherein B is as def ined with regard to formula

[ I ]， The isocyanate derivative [ III ] may be obtained by subj ecting the compound [ 11】 to a known means of reacting an aniline with phosgene to synthesize a

phenyl isocyanate . Referential Example 49 given herein - below illustrate synthesis of one example of the compound of formula [ III ] .

Known means of reacting an isocyanate ester with an amine to form a urea may be applied to the practice of the reaction of the isocyanate derivative [ II I ] with the amine 【IV〗 . he reaction may be carried out without a reaction solvent. If desired, however , there may be used a solvent inert to the reaction, for example an aromatic hydrocarbon such as benzene , toluene or xylene , a halogenated hydrocarbon such as chloroform, dichloromethane, carbon tetrachloride , dichloroethane , trichloroethane , tetrachloroethane, chlorobenzene or dichlorobenzene , tetrahydrofuran, dioxane , ethyl acetate and dimethylf ormamide. '

The reaction is carried out by "mixing 1 mole of the isocyanate derivative and 0 .8 to 5 moles , preferably 1 to 2 moles , of the amine in the absence of a solvent or in the aforesaid solvent, and stirring the mixture at a temperature of - 20 to 100°C , preferably 0 to 50°C , for 0 .5 to 30 hours .

After the reaction, the desired product may be isolated bv a conventional procedure such as the one shown in Example 3 given hereinbelow.

Guidelines for the synthesis of the compounds of the general formula Ar - OH used in the synthesis of the compounds [V】 by the reaction ( 1) are shown in the reaction schemes given in the column of Synthesis Method in Table 12 . Precursor Nos . 1 to 38 in Table 12 correspond respectively to Referential Examples 1 to 38 given hereinbelow. For example , the precursor for which a synthesis method is described in Referential Example 1 is one example of compounds which belong to the precursor No . 1. Table 12 also describes literature references which are closely related to the reaction schemes of the synthesis methods .

It is believed that one skilled in the art can easily understand the method of synthesis of Ar-OH when he refers to Table 12 and Referential Examples 1 to 38 ·

Japanese Patent Application No. 279 , 193/1985 cited as reference for the precursor No. 2 was filed on the basis of an invention made by two of the inventors of the present application and has not yet been published. Precursor No. 2 may be synthesized in accordance with this method by reacting 1 mole of 1 , 3-dihydroxybenzene and about 0 .5 to 5 moles of a ketone in the presence or absence of a solvent using an acid catalyst such as hydrochloric acid, sulfuric acid or a cation exchange resin at room temperature to 12 o C for 2 to 30 hours .

In the reaction scheme for precursor No. 5 , the aforesaid reaction technique can be applied to the- f irst reaction, and the subsequent hydrogenation reaction is well known per se.

There has been no prior example in which the prescursor No. 24 shown in Table 12 was synthesized by the synthesis route shown in the reaction scheme in Table 12 . In the reaction scheme, the reaction of a ketone with ethylene glycol to form a 5-merabered ring comprising an ethylenedioxy group is well known per se, and the reaction of forming the phenolic hydroxyl group by the reaction of hydrogen on phenylbenzyl ether is ' also well known. Hence , the precursor 24 can be easily sysnthe- sized by following this reaction scheme and Ref errential Example 24 ,

The reaction for producing precursor No. 26 is neither known heretofore, ahd was discovered for the

irst time by the inventors of the present application. This reaction proceeds by reacting the two reactants under ice cooling in the presence of an alcohol of the formula R^-H using an acid catalyst such as sulfur ic acid , toluenesulf onic acid or a cation exchange resin.

In Table 12 , Bz in Table 12 stands for the benzyl group.

The method of synthesizing the starting material of the following formula

used in the reaction (3 ) above is described, for example , in ϋ . S . Patent 4 ,323 ,505 .

Referential Examples 1 to 38 given hereinbelow illustrate synthesis of typical compounds of general formula Ar-OH .

Referential Examples 39 and 41 show synthesis of intermediates coming within the compounds 【V〗 in accordance with the reaction ( 1) . Referential Examples 40 , 42 , 45 and 47 show synthesis of intermediates coming within the compounds [ 11】 in accordance with the reaction ( 2 ) . Referential Example 43 shows synthesis of an intermediate coming within the compounds [VI ] in accordance with the reaction (3 ) . Referential Example 48 shows synthesis of an intermediate falling with the compound [V-2 ] in accordance with the reaction 5 and subsequent sysnthesis of an intermediate coming within the compound [ 11〗 by the reaction 2 . Referential Example 49 shows synthesis of an intermediate falling within the compound [ II I ] .

In these Referential Examples , column chromatography was carr ied out using a sil ica gel column and hexane-ethyl acetate mixture as an eluent . Table 12

to be continued -

Table 12 (continued)

— to be continued一

Table.12 (continued)

- to be continued一

6 I Table 12 (continued)

- to be cont nued一

Table 12 (continued)

oo

to be continued一

Table 12 (continued)

I

Table 12 (continued) o

Table 12 (continued)

I Table 12 (continued)

2 I Table 12 (continued)

to be continued一

Table 12 (continued)

to be continued 一

Table 12 (continued)

to be continued -

I Table 12 (continued)

- to be continued -

I Table 12 (continued)

to be continued

Table 12 (continued)

to be continued -

8 I Table 12 (continued)

I

to be continued -

Table 12 (continued)

The compounds of formula 【I〗 provided by this invention have low phytotoxicity to useful crops arid are useful for controlling or eradicating undesired vegetation at low dosasges . Thus , according to this in - vention, there can be provided a herbicidal composition comprising a herbicidally effective amount of at least one compound of formula [I ] and an agr iculturally acceptable diluent or carrier .

The herbicidal composition may be in various formulations such as emulsif iable concentrates , wettable powders , dusts , or granules . Suitable agriculturally acceptable diluents or carriers include , for example , solid diluents or carriers such as clay, talc ,

bentonite , kaolin, diatomaceous earth , white carbon, vermiculite , slaked lime , and silica sand, and liquid diluents or carriers including solvents and surfactants , such as alkylbenzenesulf ate esters , alkylbenzenesulf onate salts , polyoxyethylene glycol ether , polyoxyethylene alkyl aryl ethers , polyoxyethylene sorbitan monoalkyl - ates , sodium alkylsulf ates , sodium alkylnaphthalene- sulfonates , and sodium ligninsulfonate .

The herbicidal composition of the invention may contain the compound of formula 【I〗 in a herbicidally ef fec、..iv'e amount which, for example , is about 0 .5 to about 70% by weight , based on the weight of the composition, and is usually f rom 0 .5 to 20% by weight for granules or dusts , and f rom 5 to 70% by weight for emulsif iable concentrates or wettable powders , based on the weight of the composition .

According to this invention there may also be provided a method of controlling the growth of undesired vegetation which compr ises applying a herbicidally effective amount of at least one compound represented by formula 【I〗 to the weeds or the locus of such weeds .

The compound of formula 【1〗 , either as such or as the aforesaid composition or as a dilution or suspen- sion of it in water , etc. , can be applied to the locus where undesired vegetation is growing or is likely to grow. In the method of controlling the growth of

undesired vegetation, the rate of application of the com - pound of formula [1〗 may be varied depending upon the formulation, the crop to be applied, the weed to be applied, climatic conditions , etc . For example , it is about 50 g to about 3 kg/hectare .

The herbicide of this invention exhibits a high herbicidal efficacy by soil treatment or foliar treatment against various weeds , particularly various weeds in upland farms , for example important weeds such as barnyard grass (Echinochloa crus-qalli ) , f ingergrass (Digi - taria sanquinalis ) , dent foxtail (Alopecurus aequalis ) , cocklebur (Xanthium strumarium) , blackj ack ( Bidens pilosa) and velvet leaf (Abutilan theophrasti )' and also weeds of Compositae_r Rubiaceae, Scrophulariaceae , Solanaceae,

Umbellif erae , Vidlaceae , Oxalidaceae , Euphorbiaceae ,

Brassicaceae _f Caryophyllaceae , Amaranthaceae , Chenopudi - aceae , and Polygonaceae. Particularly, in foliar treatment, it can be used safely on important crops , for example gramineous crops such as wheat , corn and rice and leguminous crops such as soybean and peanut , and can kill a wide range of weeds at low dosages .

The herbicide of this invention may also be applied to lawns , orchards , pastures and non-agricultural lands .

As desired, the herbicide of this invention may be used as a mixture with , or jointly with , other agri- cultural chemicals such as another herbicide , a fungicide or an insecticide , or a fertilizer . Examples of the other agricultural chemicals include methyl 2 -【4一（2 , 4 - dichlorophenoxy) henoxy 1 ropionate , isobutyl 2 -【4一（4一 chlorophenoxy ) henoxy ] ropionate , 2 - [ 4— ( 3 , 5 - dichloiro - 2 - pyridyloxy) henoxy ] ropionic acid , butyl 2 -【4一（5 - tri一 f luoromethyl-2-pyridyloxy) phenoxy] propionate , dimethyl tetrachloroterephthalate , isopropyl-N-phenylcarbamate , 4-chloro-2-butynyl-N- ( 3-chlorophenyl) carbamate/ methyl N-(3 _f4-dichlorophenyl) carbamate, S - ethyl N_f N-diisobuthyl- thiocarbamate, S -（2,3 ,3-trichloro - 2 - propenyl) N, -diiso- pr ODylthiocarbamate , 2-chloro-N-isopropylacetanilide, 2-chloro-2 · ,6¹ -diethyl-N-raethoxymeth lacetanilide

2-chloro-N-ethoxymethyl-2 ' -ethyl-6 '-methylacetanilide, 2 - chloro-2 '一 ethyl - N - ( 2-methoxy-l-methylethyl)一 6， -methyl - acetanilide, 3 ' ,4 '-dichloropropionanilide, ethyl 2 -【N - benzoyl-N-(3 , 4-dichloro henyl) amino] ropionate, 3 -（4一 chlorophenyl) -1-methoxy-l-methylurea, 3 -（3 ,4 - dichloro - phenyl) -1-raethoxy-l-raethylurea, 2-(3 , 5-dichlorophenyl)ー2 - (2 ,2 _f 2-trichloroethyl) oxirane, 3-amino-2 5-dichlorobenzoic acid, 3 ,6-dichloro-2-methoxybenzoic acid, 2 ,6 - dinitro— N,N - dipropyl-4-trif luororaethylaniline, 1 ,2 - dimethyl - 3 ,5 - di - phenyl-lH-pyrazolium methyl sulfate, S-2 ,3-dichloroallyl- Ν,Ν-diisopropyl thiolcarbamate, and ethyl N - benzoyl - N -（3 - chloro-4-f luorophenyl) -2-aminopropionate.

Best node for practicing the invention

The best mode of practicing the invention will be shown below by examples of producing the synthesis intermediates of the compounds of this invention, examples of producing the compounds of this invention, examples of the herbicidal composition of this invention and examples of herbicidal tests.

REFERENTIAL EXAMPLE 1

2 , 3-Dihydro-3-ethyl-6-hydroxybenzof uran (a precursor of compound No. 13)：-

A mixture of 5,0 g of 2 ' _f 4 '-dihydroxypropio- phenone, 5.4 g of benzyl bromide, 6.2 g of potassium carbonate and 50 ml of acetone was ref luxed for 7 hours. After cooling, the solid was separated by filtration.

The filtrate was concentrated, and the residue was separated by column chromatography to give 4.7 g of

4¹ -benzyloxy-2¹ -hydroxypropiophenone as a white solid (yield 61% , melting point 111.5 - 112.5°C) . Then, a mixture of 4 .5 g of this solid , 3 .5 g of ethyl bromo - acetate , 6 .1 g of potassium carbonate and 45 ml of acetone was ref luxed for 7 .5 hours . After cooling, the solid was separated by filtration. The filtrate was concentrated, and the residue was purified by column chromatography to give 5 .8 g of ethyl 3-benzyloxy-6-propionylphenoxyacetate as white crystals (yield 97% , melting point 81.5 to

82 .0°C) . This ester (5 * 5 g) was dissolved in a solution composed of 1.3 g of potassium hydroxide and 55 ml of methanol , and the solution was stirred at room temperature for 2 hours to hydrolyze the ester . The hydrolysis product was worked up in a customary manner to give 3 .9 g ( yield 77% ) of 3-benzyloxy-6-propionylphenoxyacetic acid as a pale yellowish orange solid . Then, 9 .3 g of sodium acetate and 39 ml of acetic anhydride were added to this solid , and the mixture was heated at 155°C for 30

minutes . The solvent was evaporated, and the residue was purified by column chromatography to give 2 .8 g (yield 95% , melting point 69 .5 - 70 .5°C) of 6-benzyloxy-3- ethylbenzofuran as a white solid . Palladium (5% ) -carbon ( 0 .27 g) and 27 ml of acetic acid were added to 2 .7 g of the resulting benzof uran, and the mixture was stirred at room temperature for 3 hours in an atmosphere of nitrogen. The catalyst was separated by f iltration, and the filtrate was concentrated and then purif ied by column chromatography to give 1.7 g (yield 90% ) of the desired product as a pale orange liquid .

REFERENTIAL EXAMPLE 2

2 ,3-Dihydro-6-hydroxy-2 , 2 , 3-trimethylbenzof uran ( a precursor of compound No. 6 )：-

A 100 ml three-necked flask equipped with a condenser and a thermometer was charged with 11 g ( 0 .1 mole) of resorcinol , 8 .6 g ( 0 .1 mole) of isopropyl methyl ketone and 1.3 g ( 12% by weight based on resorcinol) of a cation exchange resin (Amberlyst-15 ) as a catalyst . The mixture was sti rred at 100°C in a nitrogen atmosphere for 10 hours . After cooling , the catalyst was separated by filtration, and the residue was purified by column chromatography to give 11.8 g (yield 66%) of the desired productg as colorless needle-like crystals.

Melting point: 67.5"C.

REFERENTIAL EXAMPLE 3

2 ,3-Dihydro-6-hydroxybenzof uran (a precursor of compound No. 11):一

A mixture of 18 g of resorcinol, 12 g of chlocoacetonitrile, 12 g of zinc chloride and 100 ml of diethyl ether was bubbled with HCl gas at room temperature with stirring. The white crystals that precipitated were collected by filtration, and suspended in 200 ml of water . The suspension was ref luxed for 0.5 hour. After cooling, the white crystals were collected by filtration and ref luxed together with 16 g of potassium acetate and 100 ml of ethanol for 0.5 hour. After cooling, 300 ml of water was added and 2N-HC1 was added until the solution became acidic. -As a result 20 g of 2 , 3-d i hydro - 7 - hydroxy-3-oxobenzof uran was obtained as brown crystals.. The compound was acetylated in a customary manner . The resultig acetylated product (3.0 g) was stirred together with 0.3 g of 10% palladium-carbon and 50 ml of ethanol at 60°C for 4 hours in an atmosphere of hydrogen to give 2.0 g of white ccystals. The crystals were hydrolyzed in a customary manner to give 1.0 g ( total yield 41%) of the desired product as a brown liquid.

REFERENTIAL EXAMPLE 4

2 ,3-Dihydro-2-sec-butyl-6-hydroxybenzof uran (a precursor of compound No. 29)：-

A mixture of 9,0 g of potassium hydroxide, 150 ml of ethanol and 10 g of 2 ,3 - dihydro - 6 - hydroxy - 3 - oxo - benzof uran was stirred at room temperature for 0.5 hour , and then 9.7 g of ethyl methyl ketone was added. The mixture was stirred at room temperature for 16 hours.

2N-HC1 was added until the aqueous layer became acidic . The mixture was then extracted with ethyl acetate. The extract was dried over magnesium sulfate, and ethyl acetate was evaporated. The resulting crude crystals were recrystallized from hexane-ethyl acetate to give 7.4 g of brown crystals. Sodium borohydr ide (4.0 g) was gradually added to a mixture of 2.3 g of these crystals, 1.5 g of sodium hydroxide and 100 ml of water, and then the

mixture was stirred at 100 "C for 2 hours. The mixture was acidified with 2N-HC1 and extracted with ethyl

acetate. After evaporating ethyl acetate, 0.1 g of 10% palladium-carbon and 30 ml of ethanol were added to the residue, and the mixture was stirred at room temperature for 3 hours in an atmosphere of hydrogen. The palladium- carbon was separated by filtration, and the filtrate was concentrated. The residue was purified by column chromatography to give 2.0 g (yield 36%) of the desired product as a colorless liquid.

REFERENTIAL EXAMPLE 5

2 _f 3-Dihydro-2 _f 3-dimethyl~6-hydroxybenzof uran - (a precursor of compound No. 17)：-

A mixture of 1.9 g of resorcinol, 1.8 g of

3-methoxy-2-butanone, 0,2 g of Amberlyst-15 and 2 ml of toluene was stirred at 90 'C for 10 hours. After cooling, the catalyst was separated, and the filtrate was concentrated. The residue was purified by column chromatography to give 1.7 g of 2 ,3 - dimethyl - 6 - hydroxybenzof uran as pale yellow crystals. The crystals were dissolved in 20 ml of acetic acid, and 0.2 g of 5% palladium-carbon was added. The mixture was stirred at room temperature for 12 hours in an atmosphere of hydrogen. The crude product was purified by column chromatography to give 1.5 g (yield 54%) of the desired product as a brown liquid.

REFERENTAIL EXAMPLE 6

2 , 3-Dihydro-2 2-dimethyl-6-hydroxybenzof uran ( a precursor of compound No. 32)： -

3-Benzyloxyphenol (5.0 g) , 2.0 g of isobutyr- aldehyde, 0,1 g of methanesulf onic acid and 50 ml of toluene were put into a flask equipped with the Dean- Stark condenser, and stirred under reflux for 4 hours. Low-boiling compounds were evaporated under reduced pressure. The residue was purified by column chromatography to give 3.8 g of 6-benzyloxy - 2 ,3 - dihydro—2 ,2- dimethylbenzof uran as a brown liquid. This product was dissolved in ethanol, and 0.4 g of 5% palladium-carbon was added. The mixture was stirred at room temperature for 8 hours in an atmosphere of hydrogen. The catalyst was separated by filtration, and the filtrate was concentrated. The residue was purified by column chromatography to give 2.0 g (yield 50%) of the desired product as a pale yellow liquid.

REFERENTIAL EXAMPLE 7

2 ,3-Dihydro-5-hydroxy-2-methylbenzofuran

(a precursor of compound No. 60)：-

A mixture of 4.6 g of hydroquinone, 7.5 g of hydroquinone diacetate, 13.8 g of potassium carbonate, 12.1 g of allyl bromide and 60 ml of acetone was ref luxed for 4 hours. After cooling, the solid was separated by nitration, and the filtrate was concentrated. The residue was purified by column chromatography to give 丄 3·6 g (yield 85%) of 4-acetoxyphenyl allyl ether as a pale orange liquid. Then, 4.0 g of this liquid was dissolved in N_f -dimethylaniline, and the solution was heated at 210^QC for 6 hours. The crude product was purified by column chromatography to give 3.5 g (yield 88% ) of 4-acetoxy-2-allylphenol . This phenol was dissolved in a methanol solution of potassium hydroxide and hydrolyzed. The hydrolyzed product was worked up in a customary manner, and purified by column chromatography to give 2.2 g (yield 82%) of 2-allylhydroquinone as a pale orange solid. To 1.7 g of this solid were added 8.5 ml of acetic acid and 3.4 ml of 47% hydrobromic acid, and the mixture was heated at 75°C for 16 hours. The reaction mixture was neutralized with aqueous sodium carbonate and extracted with ethyl acetate . The extract was dried over magnesium sulfate, and concentrated. The residue was purif ied by column chromatography to give 1.4g (yield 82%) of the desired product as a reddish brown liquid .

REFERENTIAL EXAMPLE 8

2 3-Dihydro-3 , 3-dimethyl-5-hydroxybenzof uran ( a precursor of compound No. 88 )：-

A solution composed of 46 ml of isobutyr- aldehyde and 1 ml of triethylamine was refluxed, and a mixture of 5 .0 g of p-quinone and 46 ml of isobutyraldehyde was added . The mixture was refluxed for 15 minutes . Low-boiling compounds were evaporated under reduced pressure. The residue was purified by column chromatography to give 2 -（ 1-f ormyl - 1 - methylethyl) hydro- quinone as a deep orange liquid . This liquid was reduced with 0 .87 g of sodium borohydride in 83 ml of ethanol, and then refluxed for 1.5 hours in 85 ml of toluene together with a catalytic amount of p-toluenesulf onic acid . The crude product .was purif ied by column chromatography to give 4 .8 g of the desired product having a reddish orange color .

REFERENTIAL EXAMPLE 9

2 , 3 - Dihydr o - 3 , 3-dimethyl-5-hydroxy-2-raethoxy- benzof uran ( a precursor of compound No. 95 )：-

A mixture of 46 ml of isobutyraldehyde and 1.0 ml of triethylamine was refluxed, and a mixture of 5 .0 g of p-quinone and 46 ml of isobutyraldehyde was gradually added dropwise to the mixture. The reaction mixture was distilled under reduced pressure, and the residue was refluxed for 1.5 hours together with 50 ml of methanol and 0 .5 g of p-toluenesulf onic acid . The reaction mixture was extracted with ethyl cetate . The extract was concentrated , and the residue was purif ied by column chromato - graphy to give 7 .0 g ( yield 79% ) of the desired product as a brown liquid . REFERENTIAL EXAMPLE 10

2 ,3 - Dihydro - 2 - ethoxy - 3 - ethyl - 5 - hydroxybenzo - f uran (a precursor of compound No. 107)：- o a solution of 20 g of p-quinone in 200 ml of toluene was added 39 g of 1-niorpholino-l-butene at room temperature^ and the mixture was stirred for 6 hours.

Toluene was evaporated, and the residue was dissolved in ethanol . he solution was added dropwise to 150 ml of 4N-HC1/ and the mixture was stirred at room temperature, and extracted with ethyl acetate. The extract was concentrated, and the residue was purified by column chromatography to qive 18.6 g (yield 48%) of the desired product as a brown liquid.

REFERENTIAL EXAMPLE 11

2 _f 3-Dihydro-3-ethyl-5-hydroxybenzof uran

(a precursor of compound No. 65)：-

The adduct of p-quinone and enamine shown in Referential Example 10 (5.0 g) was stirred together with 150 ml of 4N-HC1 at room temperature for 16 hours. The crude product was purified by column chromatography to give 1.6 g (yield 49%) of 3 -ethy 1-5 -hydroxybenzof uran. This product was hydrogenated in isopropanol at room temperature for 7 hours in the presence of a catalytic amount of Raney nickel to give 1.5 g (yield 99% ) of the desired product as a brown liquid.

REFERENTIAL EXAMPLE 12

2 ,3 - Dihydro - 5 - hydroxy - 2 - sec - butylbenzof uran (a precursor of compound No. 73)：-

Ref erential Example 11 was repeated except that 4一 methyl - 2 - raorpholino - 1一 pentene was used as the enamine. The desired compound was obtained as a brown liquid in a yield of 41% .

REFERENTIAL EXAMPLE 13

1,2,3 4 ,4a, 9b-hexahydro-8-hydroxydibenzof uran (a precursor of compound No. 117)： -

Referential Example 11 was repeated except that 1- morpholino-l-cyclohexene was used as the enamine. The desired compound was obtained as a brown liquid in a yield of 63%.

REFERENTIAL EXAMPLE 14

2 - Ethyl - 5 - hydroxy - 2 - methyl - 1 ,3-dioxolane

(a precursor of compound No. 129)：-

Catechol (20 g) , 55 ml of methyl ethyl ketone, 10 mg of p-toluenesulf onic acid and 100 ml of toluene were put into a flask equipped with the Dean-Stark condenser _r and ref luxed for 36 hours to give 23.6 g of 2 - ethyl -

2- methyl-l ,3-dioxolane as a colorless liquid. The liquid was stirred in acetic acid together with 127 g of Pb(OAc) ^ at 140°C for 9.5 hours. The crude product was purified by column chromatography to give 7.2 g of the acetoxylated product as a brown liquid. This liquid was hydrolyzed using potassium hydroxide, methanol and water to give 5,8g (yield 18%) of the desired product as a brown liquid.

REFERENTIAL EXAMPLE 15

2-Ethoxy-5-hydroxy,-2-methyl-l,3-dioxolane

(a precursor of compound No. 138)：-

A solution composed of 5.0 g of 1,2/4-tri- ydroxybenzene , 9.7 g of triethyl orthoacetate and 50 ml of toluene-carbon tetrachlo ide (1:1) was ref luxed for 1.5 hours. The solvent was evaporated, and the residue was purified by column chromatography to give 6.7 g

(yield 86%) of the desired product as pale brown crystals having a melting point of 86 to 87 'C.

REFERENTIAL EXAMPLE 16

2 , 3-Dihydro-7-hydroxy-4H-l-benzopyran (a precursor of compound No. 155)：-

5.0 g of 7-hydroxycoumarin was hydrogenated using 0.5 g of 5% palladium-carbon as a catalyst at

80°C for 9 hours in 13 ml of acetic acid and 25 ml of ethyl acetate. The reaction residue was recrystallized from hexane-ethyl acetate to give 4.9 g of white crystals (m.p. 135 一 137 C) . The crystals were dissolved in 15 ml of tetrahydrof uran, and the solution was added dropwise at room temperature to a mixture of 0 .9 g of lithium aluminum hydride and 10 ml of tetrahydrof uran, and the mixture was then ref luxed for 3 hours . The reaction mixture was worked up in a customary manner , and the product was dissolved in 30 ml of toluene without purif ication. A catalytic amount of p-toluenesulf onic acid was added _f and the mixture was heated at 120°C for 6 hours . The reaction mixture was worked up in a customary manner . The residue after concentration was purif ied by column chromatography to give 1.6 g (yield 36% ) of the desired product as pink crystals .

REFERENTIAL EXAMPLE 17

2 ,3 - Dihydro - 3 ,4 - dimethyl - 7 - hydroxy - 4H—1 - benzopyran ( a precursor of compound No . 227 )

Resorcinol ( 5 .5 g) and 7 .2 g of ethyl 2 - methyl - acetoacetate were stirred at 10 °C for 3 hours in the presence of a catalytic amount concentrated sulfuric acid to give 7 .8 g (yield 83% ) of 3 , 4 - dimethyl - 7 - hydroxy - coumarin . -The product was hydrogenated and dehydrated as in Referential Example 16 to give 5 .7 g ( 78% ) of the desired product as a pale brown liquid .

REFERENTIAL EXAMPLE 18

2 , 3 - Dihydro - 4 , 4一 diraethyl-7 - hydroxy— 4H - 1一 benzopyran ( a precursor of compound No. 166 ) ：-

A mixture of 103 g of resorcinol and 4 .6 g of cone , sulfuric acid was heated at 130°C with sti r ring , and 58 g of methyl 3 , 3-dimethylacrylate was added. The mixture was heated at 130°C for 3 hours with stirring . The reaction mixture was worked up in a customary manner , and the residue after concentration was purif ied by column chromatography to give 24 g ( yield 27% ) of 4 ,4- dimethyl-7-hydroxycoumarin (melting point 84 - 85°C) .

The product was worked up in the same way as in

Referential Example 16 to give 16 .8 g (yield 75% ) of the desired product as colorless crystals (melting point 88-88 .5°C) .

REFERENTIAL EXAMPLE 19

2 ,3-Dihydro-7-hydroxy-2-methyl-4H-l-benzopyran ( a precursor of compound No. 164 )：-

Ά 100 ml autoclave was charged with 20 g of resorcinol , 12 g of butadiene, 4 ml of H₃P0₄ and 60 ml of toluene _f and purged with nitrogen. The mixture was then heated at 100°C for 3 .5 hours . The crude product was purified by column chromatography to give 24 .1 g ( yield 82% ) of the desired product as a brown liquid .

REFERENTIAL EXAMPLE 20

2.3- Dihydro-7-hydroxy-2 , 4 ,4-trimethyl-4H-l- benzopyran ( a precursor of compound No. 180 )：-

A 100 ml autoclave was charged with 6.0 g of 7-hydroxy-2 ,4 _f 4-trimethyl-4H-l-benzopyran synthesized bv the method of Japanese Laid-Open Patent Publication No. 5475/1981 , 1.0 g of 5% palladium-carbon and 20 ml of ethanol , and hydrogenatibn was carried out at 85 C .

The resulting product was recrystallized f rom n-hexane - toluene to give 5 .2 g ( 86% ) of the desired product as colorless crystals (melting point 97 - 98°C) .

REFERENTIAL EXAMPLE 21

3 .4 - Dihydro - 7 - hydroxy - 2 , 2 , 4 - trimethyl - 2H - 1一 benzopyran ( a precursor of compound No . 184 )：-

7-Hydroxy-2 ,2 , 4-trimethyl-2H-l-benzopyran synthesized by the method of Japanese Laid-Open Patent Publication No. 109779/1982 was hydrogenated as in

Referential Example 20 . The product was purif ied by column chromatography to give the desired product as colorless liquid in a yield of 83% .

REFERENTIAL EXAMPLE 22

2 , 3 - Dihydro - 7—hydroxy—2 - isopropyl - 4H - 1一

benzopyran ( a precursor of compound No. 216 )：ー

Pyrrolidine ( 14 .2 g) was added dropwise at room temperature to a mixture of 15 g of 4-acetylresorcinol , 14 .4 g of isobutyr aldehyde and 100 ml of toluene , and thfe mixture was stirred at room temperature for 6 hour/ and thereafter ref luxed for 8 hours. The crude product was purified by column chromatography to give 11.4 g of pale yellow crystals. The hydroxyl group of the resulting compound was benzylated with benzyl bromide, and then the product was reduced with sodium borohydride in methanol and further dehydrated with p-toluenesulf onic acid in toluene. Then, the product was hydrogenated at room temperature for 13 hours in ethanol, in the presence of 5% palladium- carbon. The solvent was evaporated, and the residue was purified by column chromatography to give 6.5 g (yield 34%) of the desired product as a pale yellow liquid.

REFERENTIAL EXAMPLE 23

2 _f 3-Dihydro-2 _f 2-dimethyl-7-hydroxy-4-methoxy-4H-

1-benzopyran (a precursor of compound No, 187)： -

7 - Benzyloxy - 2 ,3—dihydiro - 2 ,2 - dimethyl - 4一 oxo - benzopyran synthesized as in Referential Example 22 was dissolved in 60 ml of methanol, and reduced with 1.0 g of sodium borohydride at room temperature. The product was dissolved in 10 ml of tetrahydrof uran, and the solution was added dropwise to a mixture of 1.0 g of 60% sodium hydride and 5 ml of tetrahydrof uran. After generation of hydrogen ceased, 4.3 g of methyl iodide was added drop - wise, and the mixture was further stirred for 2.5 hours at room temperature. The reaction mixture was extracted with ethyl acetate. The extract was concentrated, and the residue was dissolved in 30 ml of ethanol and hydrogenated at room temperature for 8 hours in the presence of 5% palladium-carbon catalyst. The crude product was purified by column chromatography to give 2.2 g (yield 58% ) of the desired product as a pale brown liquid.

REFERENTIAL EXAMPLE 24

2 ,3 - Di hydro - 4 ,4-eth lenedioxy-7-hvdroxy-2- methyl - 4H-1 - benzopyran (a precursor of compound No.

289)：- A mixture of 2 .2 g of 7-benzyloxy-2 ,3-dihydro- 2-methyl-4-oxobenzop tan_f 4 .5 g of ethylene glycol , 1 .8 g of triethyl orthof ormate , 80 mg of p-toluenesulfonic acid and 20 ml of toluene was ref luxed for 5 .5 hours . The reaction product was purified fay column chromatography to give 2.6 g of the acetal . The acetal was hydrogenated at room temperature for 9 .5 hours in ethanol with 5%

palladium-carbon. The hydrogenated product was purif ied by column chromatography to give 1.4 g (yield 76% ) of the desired product as pale pink crystals .

REFERENTIAL EXAMPLE 25

2 /3-Dihydro-7-hydroxy-2-methoxy-2-methyl-4H-l- benzopyran (a precursor of compound No. 258 )：-

Methyl vinyl ketone (7 .7 g ) was added dropwise under ice cooling to a solution composed of 11 g of resorcinol , 11.7 g of trimethyl orthof ormate and 0.1 ml of cone, sulfuric acid. After the addition, the mixture was stirred at room temperature for 2 hours . The reaction mixture was neutralized with a saturated aqueous solution of sodium bicarbonate _f and then extracted with ethyl acetate . The residue left after evaporation of the solvent as purified by column chromatography to give 12.5 g (yield 70% ) of the desired product as colorless crystals (melting point 107-108°C) .

REFERENTIAL EXAMPLE 26

2 , 3-Dihydro-2-ethoxy-7-hydroxy-4H-l-benzopyran ( a precursor of compound No. 221 ) : -

A solution of 1.6 g of acrolein diethylacetal in 4 ml of ethanol was added dropwise under cooling to a solution composed of 1.1 g of resorcinol , 0 .05 g of cone, sulfuric acid and 6 ml of ethanol . While maintaining the temperature at less than 10°C _f the mixture was sti rred for 2 hours . The reaction mixture was neutralized with an aqueous solution of sodium carbonate and extracted with ethyl aceate . The solvent was evaporated , and the residue was purif ied by column chromatography to give 1.2 g (yield 63%) of the desired product as a colorless liquid.

REFERENTIAL EXAMPLE 27

2 ,3 - Dihydro - 2 ,3-<3imethyl - 7 - hydroxy - 4H— l-benzo - pyran (a precursor of compound No. 239)：-

Resorcinol (11 g) and 20 g of tiglic acid were heated together with 15 g of zinc chloride at 180°C for 30 minutes with stirring. After cooling, the reaction mixture was extracted with ethyl acetate. The extract was concentrated to give 13 g of crystals. The crystals were benzylated with benzyl bromide in acetone in the presence of potassium carbonate, dissolved in a mixture of ethanol and tetrahydrof uran, and reduced with sodium borohydride. The reaction product was dehydrated in toluene with a catalytic amount of p-toluenesulf onic acid. The dehydrated product was purified by column chromatography to give the benzyl ether (colorless

liquid) . The liquid was hydrogenated in ethanol at room temperature for 15 hours using a 5% palladium-carbon catalyst. The crude product was purified by column chromatography to give 10.5 g (yield 59%) of the desired product as a pale yellow liquid.

REFERENTIAL EXAMPLE 28

2 ,3 - Dihydro-2 ,4-dimethyl - 7 - hydroxy - 4H - 1一 benzo - pyran (a precursor of compound No. 230 )： -

Resorcinol (11 g) and 17.2 g of crotonic acid were heated at 180— C for 30 minutes together with 15 g of zinc chloride with stirring. The reaction mixture was extracted with ethyl acetate, and purified by column chromatography to give 7.3 g of 2 ,3 - dihydro-7 - hydroxy - 2 - methyl-4-oxobenzoDvran. The OH group of the compound was benzylated in a customary manner, and then the product was reacted with CH^MgBr in tet ahydrof uran. The product was then hydrogenated in ethanol at room temperature for 13 hours in the presence of 5% palladium-carbon. The hydrogenated product was purified by column chromatography to give 4 .2 g ( yield 24% ) of the desired product as a brown liquid.

REFERENTIAL EXAMPLE 29

2 , 3 - Dihydr o - 7 - hydr oxy - 2 , 2 , 3-tr iraethyl - 4H - 1一 benzopyran (a precursor of compound No. 275 )：-

A mixture of 5 .0 g of 2 , 3 - dihydro - 2 ,2 - dimethyl - 7-hydroxy-4-oxobenzopyran, 3 .8 g of 37% aqueous formaldehyde , 10 .5 g of potassium hydroxide and 50 ml of ethanol was heated at 50 "C for 3 hours with stirring . The

" reaction mixture was acidified with 2N-HC1 and extracted with ethyl acetate . The extract was purified by column chromatography to give 1.8 g of the enone. In a customary maime the enone was hydrogenated, and then reacted with ben-zyl bromide to give 7 - benzyloxy - 2 ,3 - dihydro - 4一 oxo- " 2 , 2., 3-trimethylbenzopyran. The product was reduced with 2.0 g of sodium borohydride in methanol-tetrahydrof uran, and then dehydrated in toluene using 0 .1 g of p - toluene— sulfonic acid . This compound was hydrogenated in a customary manner to give 1.4 g (yield 27% ) of the desired product as a pale brown liquid .

REFERENTIAL EXAMPLE 30

2 ,.3 - Dihydro - 7 - hydroxy - 4一 methoxy - 4H - 1一 benzopyran ( a precursor of compound No . 211)：-

Under ice cooling , A1CI₃ ( 3 molar equivalent) was added little by little to a solution composed of 11 g of resorcinol , 12 .7 g of 2 -chloropropionyl chloride and 120 ml of nitrobenzene . After the addition, the mixture was heated at 40 to 50°C for 4 hours with stirring .

The reaction mixture was worked up and purif ied in a customary manner to give 4 .1 g of 2 ,3 - dihydro— 7 - hydroxy - 4一 oxobenzopyran . The resulting compound was benzylated , reduced with sodium borohydride in methanol , and then methylated with methyl iodide in tetrahydrof uran in the presence of sodium hydride . In a customary manner , the methylated product was hydrogenated to give 1.7 g ( yield 9 .4% ) of the desired product as a colorless liquid . REFERENTIAL EXAMPLE 31

2 _r3-Dihydro-6-hydroxy-2-methyl-4H-l-ben20Dyran (a precursor of compound No. 320)： -

Referential Example 19 was repeated except that hydroquinone was used instead of resorcinol. There was obtained the desired product as a colorless liquid (yield 65%; b. p. 160-162°C/12 mm) .

REFERENTIAL EXAMPLE 32

2 ,3· - Dihydro - 6 - hydroxy - 2 - methoxy - 2 - methyl - 4H - 1一 benzopyran (a precursor of compound No. 332)：-

Ref erential Example 25 was repeated except that hydroquinone was used instead of resorcinol. Pale brown crystals were obtained in a yield of 36% .

REFERENTIAL EXAMPLE 33

2 _f 3-Dihydro-4 ,4一 dimethyl - 6 - hydroxy - 4H - 1一 benzo - p ran (a precursor of compound No. 329)：-

A mixture of 8.8 g of hydroquinone, 5 g of methyl 3 _f 3-dimethylacrylate and 0.4 g of cone, sulfuric acid was heated at 130°C for 4 hours. The reaction mixture was cooled, and then 15 ml of toluene was added. The crystals that precipitated were separated by filtration. The filtrate was concentrated and then distilled under reduced pressure to give 4.6 g (yield 70%) of 3,4- α二 hydro - 4 ,4一 dimethyl - 6 - hydrroxycoumarin as pale pink crystals (melting point 95 - 96°C) . The crystals (3.0 g) were dissolved in 10 ml of tetrahydrof uran, and the solution was added dropwise at room temperature to a mixture of 0,9 g of lithium aluminum hydride and 20 ml of tetra- hydrof uran. The mixture was then ref luxed for 4 hours . The reaction mixture was worked up in a customary manner _f and the crude product, without purification, was dissolved in 30 ml of toluene. A catalytic amount of p-toluenesulf onic acid was added to the solution, and the o

mixture was heated at 120 C for 1.5 hours . In a customary manner , the reaction mixture was worked up, and the residue after concentration was isolated and purified by column chromatography to give 2.4 g (yield 85%) of the desired product as a yellow orange liquid.

REFERENTIAL EXAMPLE 34

5-Hydroxy-2-isopropylbenzof uran (a precursor of compound No. 334)：-

In accordance with Referential Example 10 , 5.0 g of an adduct was synthesized from p-quinone and 3-methyl-2-raorpholino-l-butene, and stirred together with 150 ml of 4N-HC1 at room temperature for 16 hours. The reaction mixture was worked up in a customary manner, and purified by column chromatography to give 1.6 g

(yield 49%) of the desired product as a yellowish orange liquid.

REFERENTIAL EXAMPLE 35

3 - Ethyl - 5 - hydroxybenzof uran (a precursor of compound No. 339): -

The captioned compound was synthesized by the method of Referential Ex'ample 11.

' REFERENTIAL EXAMPLE 36

2,3~Dihydro-7-hydroxy-2-methylben20f uran (a precursor of compound No. 346)：-

A mixture of 10.7 g of catechol , 17.3 g of catechol diacetate, 34.5 g of potassium carbonate , 30.3 g of allyl bromide and 200 ml of acetone was ref luxed for 5 hours. The reaction mixture was filtered, and the filtrate was concentrated and purified by column chromatography to give 26.5 g (yield 71%) of 2-acetoxyphenyl allyl ether as a pale yellow liquid. Ten grams of this liquid was heated at 220 to 230°C for 1.5 hours. After cooling, the reaction mixture was purified by column chromatography to give 6.5 g (yield 65%) of 2-acetoxy-6- allylphenol as a pale yellow liquid. Then, 3.0 g of this liquid and 12 ml of an acetic acid solution of 25% hydro - bromic acid were reacted at 70°C for 6 hours . The reaction mixture was poured into ice water, neutralized with an aqueous solution of sodium bicarbonate , and exracted with ethyl acetate. The concentrate was hydrolyzed with potassium hydroxide and aqueous ethanol, and worked up in a customary manner. The product was then purified by column chroamtography to give 0.7 g (yield 31%) of the desired product as a pale yellow liquid.

REFERENTIAL EXAMPLE 37

2 ,3 - Dihydro - 2 ,2 - dimethyl - 8 - hydroxy - 4H - 1— benzo - pyran (a precursor of compound No. 353)：- While a mixture of 10 g of catechol, 50 ml of p - xylene, 25 ml of hexane, 1 ml of phosphoric acid and 0.3 ml of water was heated at 100°C, 7.3 g of isoprene was added dropwise over 10 minutes, and the reaction was further carried out for 7 hours. After cooling, the resulting precipitate was separated by filtration. The filtrate was concentrated, and purified by column chromatography to give 1.7 g (yield 11%) of the product as a pale pink liquid.

REFERENTIAL EXAMPLE 38

2 , 2-Dimethyl-4-hydroxybenzodioxolane (a precursor of compound No. 355)：-

A mixture of 9.0 g of pyrogallol, 7.5 g of 2 ,2-diraethoxypropane and 100 ml of toluene was ref luxed for 4.5 hours . After cooling, the reaction mixture was worked up in a customary manner and purified by column chromatography to give 2.0 g (yield 17%) of the desired product as a pale yellow solid.

REFERENTIAL EXAMPLE 39

2 ,3-Dihydro-2 ,2-dimethyl-7-(4-nitrophenoxy)一 4H-l-benzopyran (an intermediate of compound No. 172)：- 2,3-Dihydro-2 _f 2-dimethyl-7-hydroxy-4H-l-benzo- pyran (2.0 g) synthesized as in Referential Example 19, 1.8 g of p - chloronitrobenzene, 0,9 g of potassium hydroxide, 20 ml of Ν,Ν-dimethylf orraamide and 10 ml of toluene were put into a flask equipped with the Dean- Stark condense , and were heated to 110°C. While remo ing evaporated water as an azeotrope with toluene , the reaction was carried out for 1 hour . After cooling , the reaction mixture was poured into water / and extracted with ethyl acetate. The extract was dried over magnesium sulfate, and the solvents were evapo ated. The residue was purified by column chromatography to give 2.8 g

( yield 84% ) of the desired product as a brown liquid .

REFERENTIAL EXAMPLE 40

4一（2',3-Dihydro - 2 , 2-dimethyl - 4H - 1一 benzopyran - 7- yl) oxyaniline ( an intermediate of compound No. 172)

To 2 .7 g of the nitrobenzene derivative obtained in Referential Example 39 were added 0 .3 g of 5%

palladium-carbon and 20 ml of ethanol , and the mixture was stirred at 40 to 50°C for 5 hours in an atmosphere of hydrogen. The catalyst was separated by filtration, and the filtrate was concentrated to give 1.8 g (yield 72% ) of the desired product as a gray powde .

, REFERENTIAL EXAMPLE 41

2- ( 2 ,3-Dihydro-2 ,2-dimethyl-4H-l-benzopyran-7- yl) oxy-5-nitropyridine ( an intermediate of compound No. 169 ) : -

Five milliliters of an Ν,Ν-dimethylf ormamide solution of 1.5 g of 2 , 3 - dihydro - 2 , 2 - dimethyl - 7 - hydroxy - H-l-benzopyran synthesized by the method of Referential Example 19 was added dropwise to a mixture of 0 .35 g of sodium hydride and 4 ml of Ν,Ν-dimethylf ormamide. '

The mixture was stirred at room temperature for 0 .5 hour , and 6 ml of an Ν,Ν-dimethylf ormamide solution of 2 - chloro - 5-nitropyridine . ( 1.3g) was added to the resulting reddish orange solution , and the mixture was stirred at room temperature for 5 hours . The reactio"n mixture was poured into 100 ml of water , and extracted with 100 ml of ethyl acetate . The extract was dr ied over magnesium sulfate , and concentrated . The residue was pur if ied by column chromatography to give 2 .1 g (yield 84% ) of the desi red product as a yellow liquid . REFERENTIAL EXAMPLE 42

5 - Amino - 2 -（2,3 - dihydro - 2 ,2 - dimethyl - 4H - 1-benzo - pyran-7-yl) oxypyridine (an intermediate of compound No. 169)：- The nitro compound obtained in Referential

Example 41 (2.1 g) was dissolved in 11 ml of ethyl

acetate _r and 0,11 g of 5% palladium-carbon was added .

Hydrogenation was carried out in accordance with the method of Referential Example 40, The filtrate was concentrated to give 1.9 g (yield 100%) of the desired product as a pale pink solid (melting point 93-94°C) .

REFERENTIAL EXAMPLE 43

7-(4-Nitrophenoxy) -2,4 ,4一 trimethyl - 4H - 1一 benzo - pyran (an intermediate of compound No. 194)：ー

One hundred grams of 7_hydroxy - 2 ,4 ,4 - trimethyl - 4H-l-benzopyran ( synthesized by the method of Japanese Laid-Open Patent Publication No. 5475/1981) , 79 g of p— chloronitrobenzene, 42 g of potassium hydroxide, 500 ml of Ν,Ν-dimethylf ormamide and 500 ml of toluene were introduced into a flask equipped with the Dean-Stark condenser, and heated at 110 to 116°C. While removing the distilled water as an azeotrope with toluene the mixture was stirred for 2 hours. The reaction mixture was cooled to room temperature, and 1 liter of water , 500 ml of ethyl acetate and 120 ml of 2N-HC1 were added. The insoluble materials were separated by filtration. The filtrate was subjected to oil-water separation. The oil layer was washed with 500 ml of brine, and dried over magnesium sulfate. The solvent was evaporated. Methanol (650 ml) was added to the residue, and crystals that precipitated were collected, washed with 650 ml of hexane, and dried to give 106 g (yield 67%) of the desired product as a brown powder (melting point 80— C) .

REFERENTIAL EXAMPLE 44

2 ,3-Dihydro-2-methoxy-7-(4-nitrophenoxy) -2,4 ,4- trimethyl-4H-l-benzopyran (an intermediate of compound No. 194) A mixture of the 7- (4-nitrophenoxy) -2/4 ,4-tri- methyl-4H-l-benzopyran obtained in Referential Example 43, 66 ml of methanol, 0.7 g of Ani erlyst-15 and 6 ml of toluene was stirred for 4.5 hours, and Amberlyst-15 was separated by filtration. The filtrate was concentrated, and 30 ml of methanol was added. Crystals that precipitated were collected by filtration, washed with 50 ml of methanol, and dried to give 6.7 g (90%) of the desired product as a white powder (melting point 125°C) .

REFERENTIAL EXAMPLE 45

7- ( 4-Aminophenoxy ) -2 , 3 - dihydro - 2 - methoxy - 2 ,4,4— trimethyl-4H-l-benzopyran (an intermediate of compound No, 194)： -

A mixture of 6.7 g of the 2 ,3 - dihydro - 2 - methoxy - 7 -（4-nitrophenoxy) - 2, 4, 4 - trimethyl - 4H-1 - benzopyran obtained in Referential Example 44, 0.7 g of 5% palladium- carbon/ and 67 ml of ethyl acetate was stirred a.t room temperature for 5.5 hours in an atmosphere of hydrogen. Palladium-carbon was separated by filtration, and the filtrate was concentrated to give 6.0 g (yield 98 %) of the desired product as a yellow liquid.

REFERENTIAL EXAMPLE 46

2 _r3-Dihydro-2-hydroxy-7-(4-nitrophenoxy)-2,4 _r4- trimethyl-4H-l- benzopyran (an intermediate of compound No. 319)：-

A mixture of 6.5 g of the 7- (4-nitrophenoxy ) - 2 ,4 ,4 - trimethyl - 4H - 1一 benzopyran, 26 ml of water, 13 ml of cone, hydrochloric acid and 65 ml of acetone was ref luxed for 2 hours. An 10% aqueous solution of sodium hydroxide was added to the reaction mixture to neutralize it, and then 100 ml of water and 200 ml of ethyl acetate were added, and the mixture was subjected to oil-water separation. The oil layer was washed with 50 ml of brine, dried over magnesium sulfate and concentrated. Toluene (5 ml) and 45 ml of hexane was added to the residue, and the precipitated crystals were collected by filtration, washed with 50 ml of hexane and dried to give 5.1 g (yield 70%) of a pale brown powder (mp. 159 - 160^QC, recrystallized from ethanol) .

REFERENTIAL EXAMPLE 47

7- ( 4-Aminophenoxy )一 2 ,3 - dihydro - 2-hydroxy - 2 ,4 ,4- trimethyl-4H-l-benzopyran (an intermediate of compound No. 319)：-

A mixture of 5,0 g of 7- (4-nitrophenoxy) -2,4,4- trimethyl - 4H - 1一 benzopyran, 0.5 g of 5% palladium - carbon and 50 ml of ethyl acetate was stirred at room temperature for 5.5 hours in an atmosphere of hydrogen. The palladium-carbon was separated by filtration, and the filtrate was concentrated. The residue was recrystallized from ethyl acetate-hexane to give 4.3 g (yield 93%) of the desired product as a white powder.

REFERENTIAL EXAMPLE 48

7 - ( 4-Aminophenoxy)一 2 , 3 - dichloromethano - 2 , 3-di - hydro-2 ,4 ,4-trimethyl-4H-l-benzopyran (an intermediate of compound No. 309): - '

A solution of 0.02 g of benzyltrimethylaminonium chloride in 5 ml of chloroform was added dropwise to a mixture of 1.6 g of 7- (4-nitrophenoxy) -2 4 ,4-tr imethyl- 4H - 1一 benzopyran, 20 ml of chloroform and 0.7 g of sodium hydroxide with stirring at 5°C. The mixture was stirred at room temperature for 2 hours, poured into ice ater containing dilute hydrochloric acid, and extracted with dichloromethane. The extract was washed with brine, dried over sodium sulfate, and concentrated. Ethyl acetate (30 ml) and 5% palladium-carbon were added to the residue, and the mixture was stirred at 60°C for 5 hours in an atmosphere of hydrogen. The palladium-carbon was removed by filtration, and the filtrate was concentrated. The residue was purified by column chromatography and recrystallization (dichloromethane-hexane) to give 0.74 g (yield 40%) of the desired product as colorless crystals (melting point 46 to 147°C) .

REFERENTIAL EXAMPLE 49

4-(2 ,3-Dihydro-2 ,2-dimethyl-4H-l-benzopyran-7- yl) oxyphenyl isocyanate (an intermediate of compound No. 172) :-

A solution of 8.1 g (0.03 mole) of the aniline derivative obtained by the method of Referential Example 40 was added dropwise at 0°C to 60 ml of ethyl acetate into which 0.12 mole of phosgene had been blown, and the mixture was stirred for 0.5 hour . Thereafter, the mixture was ref luxed fo 1 hour, and the excess of phosgene was replaced by nitrogen gas . The ethyl acetate was evaporated under reduce pressure to give 8.7 g (yield 98%) of the desired product as a yellow orange liquid ( IR: 2260 cm ) .

The following Example illustrates the synthesis of typical examples of the compounds of formula [1〗 and their properties.

Compound No. 1: 1, 1-dimethyl - 3 - [2 -（3-methyl - 2,3-dihydro-6-benzof uryloxy) yridin-5-yl] urea

2 -（3 - Methyl - 2 ,3-dihydro-6-benzof urylo-xy) -5- aminopyridine (0.5 g) was dissolved in 2.5 ml of pyridine, and a solution of composed 0.27 g of dimethylcarba - moyl chloride and 2.5 ml of toluene was added. A solution composed of 0.27 g of diethylcarbamoyl chloride and 2.5 ml of toluene was added, and the mixture was stirred at room temperature for 9 hours . Water and ethyl acetate were added to the reaction mixture, and the organic layer was separated. The organic layer was washed with a saturated aqueous solution of sodium chloride, and dried over anhydrqus magnesium sulfate. Ethyl acetate was evaporated under reduce'd pressure, and the precipitated crystals were washed with n-hexane to give 0.63 g (yield 96%) of the desired product as pale brown crystals.

Melting point: 153-154°C

Mass spectrum: m/Z' 313 (molecular ion peak)

IR spectrum ( Br disk； cm )

3260, 3050, 2958, 1637, 1602, 1357,

1274, 1237, 113.3, 979, 850, 842, 760. •H-NMR spectrum (CDC1₃ solution; ppm)

(a) 1.31 (3H_fd_rJ=7.2Hz)

(b) 3.00 (6H,s)

(c) 3.28 (lH_rm

(d) 4.09 (1H, t, J=

(e) 4.71 (lH,t_r

(f) 6.51 (lH d J=2.7Hz

(g) 6.57 (lH,dd,J=2.7 7,2Hz)

(h) 6.70 (lH,brs)

(i) 6.92 (lH d,J=9.0Hz)

(j) 7.08 (lH d, J=7.2Hz)

(k) 7.91 * (lH,dd_r J=2.7, 9.0Hz)

( ） 8.02 (lH,d_f J=2.7Hz)

Compound No. 331 : 1一 methyl - 3 - [4一（2 - methoxy - 2 - raethyl-2 , 3-dihydro-6-benzopyranyloxy) phenyl] urea

Methyl isocyanate (0.16 g) was added at room temperature to a solution composed of 0.4 g of 4一（2 - methoxy-2~methyl-2 3-dihydro-6-benzopyranyloxy) aniline and 3.0 ml of toluene , and the mixture was stirred for 6 hours . Addition of n-hexane to the mixture yielded crystals which were collected by filtration to give the desired product as white crystals (yield not less than 97%) .

Melting point: 140-140.5°C

Mass spectrum: m/Z 342 (molecular ion peak)

IR spectrum (KBr disk； cm" )

3330, 2950, 1642, 1605, 1586, 1505, I486, 1212, 1092, 1058, 918, 872.

H-NHR spectrum (CDC1 solution; ppm)

(a) 1.54 (3H, s)

(b) 1.68-2.24 (2H, ra)

(c) 2.32-3.28 (2H, m)

(d) 2.75 (3H, d, J=5.4)

(e) 3.28 (3H_r s)

(f ) 5.43 (1H, d, J=5.4)

(g) 6.60-7.40 (8H, m)

Compound No. 172: 1,1 - Dimethyl-3 -【4 -（2,2 - di - methyl-2 ,3 -dihydro-7-benzopyr any loxy) henyl] urea

A solution of 0.5 g of 4一（2 ,2 - dimethyl - 2 ,3 - di - hydro-6-benzopyranyloxy) henyl isocyanate in 2.5 ml of toluene was added dropwise at 0°C to a solution of 0.2 g of dimethylamine in 3 ml of toluene, and the mixture was then stirred _aat room temperature for 2 hours. Toluene was evaporated under reduced pressure, and the precipitated crystals were washed with n-hexane to give 0.62 g (yield 97%)' of the desired product as white crystals.

Melting point: 137 - 138°C

Mass spectrum: m/Z 340 (molecular ion peak) .

IR spectrum (KBr disk cm~^)

3310, 3040, 2940, 1640, 1602,

1370, 1210, 1147, 996, 838, 813.

H-NMR spectrum (CDC1 solution; ppm)

(a) (a)

(a) 1.30 (6H s)

(b) 1.77 (2H t_f J=7.2 Hz)

(c) 2.72 (2H, t, J=7.2 Hz)

(d) 3.02 (6H, s)

(e) 6.33 (lH brs

(f ) ' 6.39 (1H, d, J=2.7 Hz)

(g) 6.47 (1H, dd, J=2.7_f 7.2 Hz)

(h) 6.96 (2H, d, J=9.0 Hz)

(i) 6.97 (1H, ά, J=7.2 Hz)

(j) 7.34 (2H, d, J=9.0 Hz)

Other compounds of formula [1】 shown in Tables 1 to 11 were synthesized in accordance with the method used to produce compound No. 1 or No. 331, and the re - suits are shown in Table 13. The NMR spectra were measured in CDC1- . he IR spectra of solid compounds were measured using KBr disks , and those of liquid compounds were measured at neat.

00

to be continued一

Table 13 (continued)

to be continued

O 一

o Table 13 (continued)

to be continued 一

Table 13 (continued)

to be continued 一

10 I Table 13 (continued)

to be continued

10 I Table 13 (continued)

一 to be continued

10 I Table 13 (continued)

- to be continued

Table 13 (continued)

Table 13 (continued)

I Table 13 (continued)

一 to be continued一

Table 13 (continued)

Compound Yield Melting point

Spectral data

No. (%) (°C) not less IR: 3305 (v_MU) , 1660 (v ) .

62 128-129 NH c=o

than 97

63 82 120-122

NMR: 1.29 (3H,d,J=6,9) , 3.19 (3H,s) , 3.32-3.72 (lH,m) ,

O Qn U_fl O Λ 3,76 (3H,s) , 4.09 (lH_rt, J=9.0) , 4.70 (lH_ft_f J=9.0) ,

6.68-7.52 (7H,m) , 7.73 (lH,brs) .

00

IR: 3325 (\)_MU) , 1645 (v ) .

NH c=0 I

65 95 liquid NMR >·: 0.92 (3H_rt,J=7.2) , 1.66 (2H,q, J=7 ,2) , 3.00 (6H,s) ,

cr H 3.32 (lH,m) , 4.21 (lH,dd, J=7.2 , 9.0) , 4.63 (lH,t, J= H l C¹O9.0) , 6.36 (lH,brs) , 6.60-7.40 (7H,m) ·

IR: 3325 (V ) , 1675 ( ) .

NH、、 C=0

66 85 liquid NMR: 0.96 (3H,t,J=7.2) , 1.68 (2H,q J=7.2) , 3.20 (3H,s) ,

3.26 (lH,ro) ,i it i • 3.78 (3H,s) , 4.21 (lH_rdd,J=7.2 9.0) , 4.65 (lH_rt,J= vo9.0) , 6.68-7.32 (7H,m) , 7.63 (lH,brs) . t 、

J。一^ 一 to be continued 一

H" li

on

o一 EC •

、 Table 13 (continued) o

一 to be continued -

Table 13 (continued)

to be continued一

Table 13 (continued)

一 to be continued

Table 13 (continued)

Compound Yield Melting point

o ¹ \ Spectral data

NO . \ し J not less

95-96.5 IR: 3370 lo / ( _e— _Q》 ·

86

than 97 not less IR: 3350 ( V_MU) 90 (v )

87 191.5-193 Nn , 32

Nn ₉ 1636 (v ) ·

C=0

than 97

88 75 115-116 IR: 3260 (v而）, 1635 (v_c=Q) .

89 83 99.5-101 IR: 3360 ( _N'_H) _# 1664 ( _c=Q) .

90 95 97-99 IR: 3290 ( _NH) , 1640 ( _C=Q) . '

··

OH CO i V

卜 in

not less o o ·

91 liquid 1 o 1

than 97

NMR: 1.27 H,s) oO ΓΟ C, 1.29 (3H,s), 3.05 (6H,s) , 3.56 (3H,

92 81 17.5-178 s), 5.14 UH,s), 6.34 (lH,brs) , 6.70-6.93 (3H,ra),

7.85-8.08 (3H,m). O · to be continued一 で ^

*

^ It

o m•

cs一

卜H i

O G

2 I Table 13 (continued)

to be continued一

Table 13 (continued)

to be continued一

Table 13 (continued)

to be continued

Table 13 ( continued)

i♦ 一 to be continued i

曰D I

^

33 · Table 13 ( continued)

I

- to be continued i 一

I

•

Γ

n i 卜 Table 13 (continued)

to be continued

8 I Table 13 (continued)

一 to be continued一

Table 13 (continued)

- to be continued 一

Table 13 (continued)

Compound Yield Melting point

Spectral data

No. (%) (°C) not less

139 liquid IR: 3320 (v_NH), 1675 ( _C=Q) .

than 97

140 92 liquid

NMR: 1.21 (3H,t_# J=7.2) , 1.27 (3H, t , J=7 ,2) , 2.07 (2H,q, not less 1 nil Ί \ J=7.2) , 3.19 (3H,s), 3.62 (2H,q, J=7 ,2) , 3.77 (3H, *ft

than 97 s) , 6.32-6.88 (3H,m) , 6·93 (2H_fd_r J=9.0) , 7.40 (2H, d,J=9.0) , 7.66 (lH brs) .

142 83 103-104 IR: 3300 1635 not less

143 liquid IR: 3390 ( _NH) ₉ 3300 1668

than 97

144 80 113-114 IR: 3275 ( _NH) 1633 ( v_c==Q) . not less

145 liquid IR: 3390 3300 _NH) 1668 ( _C=Q) .

than 97 to be continued

• o. Table 13 (continued)

- to be continued

Table 13 (continued)

一 to be continued

Table 13 (continued)

to be continued一

Table 13 (continued)

一 to be continued一

12 I Table 13 (continued)

to be continued一

I Table 13 (continued)

to be continued

Table 13 (continued)

Compound Yield Melting point

Spectral data

o . (¾ J ( ^UC)

187 69 129-130

NMR: 1.33 (3H,s>, 1.42 (3H,s), 1.99 (lH,d, 7 ·2) ,

2.04 (lH d_r J=7.2) , 3.19 (3H,s) , 3.46 (3H,s) ,

188 92 96.5-97.5 3.77 (3H,s) , 6.37 (lH,d,J=2.7) , 6.55 (lH,dd, J=2 ,7 ,

9.0) , 6.99 (2H,d_r J=9.0) , 7.31 (li!,d, J=9 ,0) ,

7.42 (2H_/d J=9.0) 7.67 (lH,brs) . not less

189 179-182

than 97 I : 3320 (v_NH), 1638 (v_c=0) .

o m m σ»

not less

190 97-98

than 97

で Jで WJ

not less

191 70-71

than 97

― to be continued 一 でで

で^ ^

m IIH

で^！ as · Table 13 (continued)

to be continued ―

Table 13 (continued)

Compound Yield Melting point

Spectral data

No. (% ) (°C)

IR: 3350 ( _NH) , 3280 ( ） , 1644 (v_c=Q) ,

198 72 210-212

152。 （ 。2 1346 (ν_Νθ2) . ―

199 63 163-164

IR: 3260 ( _NH) , 1650 (v_c=Q) ,

200 86 142-144

¹⁵²⁵ (リ _No₂)' ¹³⁴⁰

o not less ·· I

201 201-202

than 97 m

o

not less

202 174-175

than 97 not less

203 145-147

than 97

o o一

to be continued > -

II

o Table 13 (continued)

Compound Yield Melting point

Spectral data

No. (%) (°C)

NMR: 1.00 (3H_ft,J=7.2) , 1.45 (3H,s) , 1.50 (3H,s) ,

1.80 (lH,d,J=14,0) , 2.04 ( lH,d , J=14 ,0) ,

3.03 (6H,s) , 3.55 (2H_rq,J=7.2) , 6.30 (lH,brs)

204 69 186-188

6.43 (lH,d,J=2.7) , 6.58 (lH_rdd, J=2.7 , 9.0) ,

6.98 (2H,d,J=9.0) , 7.21 ( 1H ,d , J=9 ·0 ) ,

7.34 (2H,d, J=9.0) . not less

205 liquid IR: 3325 (v

than 97 NH ) , 1675 (v_c=0) .

206 82 153.5-154.5

NMR: 0.72 (3H,t, J=7.2) , 1.20-1.60 (2H,m) , 1.28 (3H,s) , 1.46 (3H,s) , 1.52 (3H,s), 1.82 ( lH,d, J-13.5) , not less 206 (lH,d, J=13 ,5) , 3.20 (3H,s) , 3.47 (3H,t,J=7.2)

207 liquid

than 97 3.69 (3H,s) , 6.44 (lH_fd,J=2.7) , 6.60 (lH,dd, J=

2.7, 9.0) , 6.99 (2H,d_rJ=9.0) , 7.23 (lH,d, J=9.0) , 7.43 (2H,d,J=9.0) , 7.67 (lH,brs) · not less

208 173-174

than 97

209 81 62-63 IR: 3320 ( _MU) , 1653 (v )

UU c=o

一 to be continued -

Table 13 (continued)

Compound Yield Melting point

Spectral data

No. (%) (。C) not less

210 liquid IR: 3320 (v_Mt-) , 1673 (v ) .

than 97 H C=0

211 61 liquid

t

212 69 liquid

213 58 143-145

NMR: 1.00 (3H,t, J=7.2) , 1.40-2.16 (4H,m) , 2.50-3.00 not less

214 liquid (2H,m) , 3.18 (3H,s) , 3.70-4.04 (lH,m) ,

than 97 3.76 (3H,s) , 6.32-7.56 (7H,m) , 7.67 (lH,brs

215 80 146-148

i、

、、

216 90 151-153

00 to be continued一 H) CO» w w * 3：

o、O C

K、 Table 13 (continued)

to be continued

Table 13 (continued)

to be continued

ψ

Table 13 (continued)

I

to be continued 一

Table 13 (continued)

一 to be continued

Table 13 (continued)

- to be continued -

Table 13 (continued)

一 to be continued

Table 13 (continued)

to be continued

Table 13 (continued)

Compound Yield Melting point

Spectral data

No. (%) (°C) not less

260 liquid

than 97 IR: 3310 ( _NH), 1670 ( _C=Q) · '

261 85 liquid

NMR; 0.84 (3H,d,J=7.2) _# 1.13 (3H,d, J=7 ·2) , 1.54 (3H,s) , 1.64-2.18 (2H,m), 2.30-3.00 (2H,m) , 3.15 (3H,s),

262 91 liquid

3,73 (3H,s), 4.20 (lH_rm) , 6.36-6.58 (2H,m),

6.84-7,04 (3H,m) .

o not less

263 147-148

than 97

264 90 141-143 IR: 3290 ( ）, 1636 (^>_C=Q ·

to be continued一 、、

、 Table 13 (continued)

i V to be continued - C

マ w - Όn i * ·

O

一

^ ^ Table 13 (continued)

Compound Yield Melting point

Spectral data

No. (%) (°C)

270 77 167 - 168

271 84 liquid

NMR: 1.07 (3H,d,J=7,2) , 1.38 (3H,d, J=7.2) , 1.60-2.00

T / y u 1 iju o (lH,m), 3,02 (6H,s), 3.31 (3H,s), 3.80-4.36 (2H, m) , 6.20-7.44 (8H,m) .

！

273 87 liquid σν 3：

n ro CM *

CO、

not less o

274 163-164

than 97 一 、 *■

― to be continued一

一

1 Table 13 (continued)

一 to be continued

Table 13 (continued)

一 to be continued一

Table 13 (continued)

一 to be continued -

Table 13 (continued)

一 to be continued一

Table 13 (continued)

to be continued

Table 13 (continued)

to be continued ―

Table 13 (continued)

一 to be continued

Table 13 (continued)

o

I

to be continued一

Table 13 (continued)

to be continued 一

Table 13 (continued)

Compound Yield Melting point

Spectral data

No. (%) (°C)

NMR: 1.38 (3H,d,J=7.2) , 1.64-2.00 (2H,m) , 2.60-2.92

320 72 128.5-130 (2H,m) , 3.00 (6H,s) , 4.00-4.36 (lH,m) , 6,63 (1H,

brs) , 6.70-7.00 (4H,m) , 7.90 ( lH,dd, J=2 ·7 , 9.0) , 8.01 (lH,d J=2.7) .

NMR: 1.39 (3H,d,J=7.2) , 1.64-2.00 (2H,m) , 2.68-3.00

321 91 93-94 (2H,m) , 3.20 (3H,s) , 3.78 (3H,s) , 3.92-4.40

(lH,m) , 6.72-7.00 (4H,m) , 7.69 (lH,brs) ,

8.01 (lH,dd J=2.7, 9.0) , 8.14 (lH_#d_f J=2.7) . nut. e ϋ

322 180-182

than 97

323 95 154-155 IR: 3335 (v_MU) , 1642 (v^ .

NH C-O not less

324 108-109 IR: 3310 (v_MU) , 1665 ( _Λ ) .

than 97 NH C not less

325 100-102 II

than 97 o 一 to be continued ω

as

2 I Table 13 (continued)

to be continued一

Table 13 (continued)

to be continued

Table 13 (continued)

一 to be continued一

Table 13 (continued)

一 to be continued

Table 13 (continued)

to be continued

Table 13 (continued)

- to be continued -

Table 13 (continued)

Compound Yield Melting point

Spectral data

No. (%) (°C)

NMR: 1.28 (6H,s) , 1.78 (2H,t, J=7 ,1) , 2.16 (3H,s) , 2.56 (2H,t,J=7.1) , 3.16 (3H,s) , 3.72 (3H,s) ,

365 80 liquid 6.28 (lH,d, J=2.7) , 6.40 (lH,d_f J=2.7) , 6.97 (2H, d,J=9,0) , 7.42 (2H,d_r J=9.0) , 7,76 (lH,brs) . not less

366 164-165

than 97

86

367 181-182 - not less

368 109-111

than 97 not less

369 176-177

than 97

370 92 179-180.5

371 88 liquid

The following Formulation Examples are given for the herbicide of this invention. All percentages in these examples are by weight.

FORMULATION EXAMPLE 1

Wettable powder

The compound [1〗 of this invention (10%), 3% of a sodium salt of a higher alcohol sulfate ester and 87% of kaolin were uniformly mixed and pulverized to form a wettable powder .

FORMULATION EXAMPLE 2

Emulsif iable concentrate : -

The compound [I] of this invention (20%) , 10% of polyoxyethylene alkylaryl ether, 30% of cyclohexanone and 40% of dimethylf ormamide were uniformly dissolved to form an emulsif iable concentrate.

FORMULATION EXAMPLE 3

Granules :-

The compound [1】 of this - invention (5%), 40% of benzonite, 50% of clay and 5% of sodium ligninsulf onate were uniformly mixed and pulverized. The mixture was kneaded with water, granulated and dried' to form granules.

FORMULATION EXAMPLE 4

Dust :-

The compound [1】 of this invention (3%) and 97% of clay were uniformly mixed and pulverized to form a dust.

The following Test Examples specifically illustrate the herbicide of this invention.

TEST EXAMPLE 1

Herbicidal test in upland foliage treatment： - Porcelain pots (12 cm in inside diameter ) were filled with sieved upland farm soil, and seeds of cockle- bur _f blackjack , velvet leaf, jirasonweed, soybean, wheat, corn and rice were sown and covered with the soil (1 cm) . They were grown in a greenhouse until the first leaf of soybean developed. A predetermined amount of each of the test compounds , formulated into a wettable powder in accordance with Formulation Example 1 , was dispersed in 15 liters (per are ) of water containing 500 ppra of Neo - esterin as a sticker ) . The dispersion was sprayed to the leaves and stalks of the plants from the top of the plants by a small atomizer . After the treatment , the plants were grown further in the greenhouse for 20 days , Herbicidal effects and phytotoxicity on these plants were examined , and evaluated in accordance with the standards shown in Table 14 · The results are shown in Table 15 ,

Table 14一

Index Herbicidal effect and phytotoxicity

5 more than 99 % to 100 % (withered)

4 .5 90 % to 99 %

4 80 % to 89' %

3 .5 70 % to 79 %

3 60 % to 69 %

2 .5 50 % to 59 %

. 2 40 % to 49 %

1.5 30 % to 39 %

1 20 % to 29 %

0 .5 1 % to 19 %

0 less than 1 % ( no herbicidal ef fect , or no phytotoxicity)

Table 15

― to be continued 一 Table 15 (continued)

一 to be continued 一 Table 15 (continued)

一 to be continued 一 Table 15 (continued)

to be continued ― Table 15 (continued)

― to be continued 一 Table 15 (continued)

一 to be continued 一 Table 15 (continued)

一 to be continued 一 Table 15 (continued)

一 to be continued 一 Table 15 (continued)

一 to be continued 一 Table 15 (continued)

一 to be continued 一 Table 15 (continued)

一 to be continued 一 Table 15 (continued)

一 to be continued 一 Table 15 (continued)

一 to be continued 一 Table 15 (continued)

一 to be continued 一 Table 15 (continued)

一 to be continued 一 Table 15 (continued)

to be continued Table 15 (continued)

一 to be continued 一 Table 15 (continued)

- to be continued Table 15 (continued)

Comparative

Compound (1)

(the compound described in Jap.

Laid-Open Pat. Publn. No. 111542/77)

Comparative

Compound (2)

(the compound described in Jap.

Laid-Open Pat. Publn. No. 36456/81)

(chloroxuron) In Table 15 above and Table 16 given below, the names of the plants are indicated by letters A to J as follows： -

A cocklebur (Xanthium canadense )

B blackjack (Bidens oilosa)

C velvet leaf (Abutilon theophrasti ) D j imsonweed (Datura stramonium)

E wheat (Triticum aestivum)

F corn ( Zea mays )

G r ice (Oryza sativa )

H soybean (Glycine max)

barnyard grass (Echinochloa crus-galli)

J Pigweed (Amaranthus retrof lexus )

TEST EXAMPLE 2

Herbicidal test by soil treatment：-

Porcelain pots (9 cm in diameter ) were filled with sieved upland farm 'soil , and seeds of the plants . indicated in Table 16 were sown and covered with the soil ( 1 cm) . Immediately then, a predetermined amount of a wettable powder of each of the test compounds , prepared as in Formulation Example 1 , was diluted with 1.5 ml of water , and the dispersion was uniformly sprayed onto the surface of the soil y a small atomizer . The plants were grown in a green house for 20 days after the soil treat - ment , and the herbicidal effect of each of the test compounds was examined and evaluated in accordance with the standards shown in Table 14 · The results are shown in Table 16 .

Table 16

一 to be continued 一 Table 16 (continued)

Herbicidal effect

Test Rate

compound kg/ha

I J B C

5 1 5 5 5

151

2.5 0 5 5 4.5

5 5 5 5 5

169

2.5 5 3 5 4

5 4 5 5 5

190

2.5 2 5 5 5

5 4.5 5 5 5

.191

2.5 3 5 5 5

*

5 2 5 5 5

194

2.5 0 5 5 5

5 0 5 5 5

310

2.5 0 5 4.5 4.5

5 3.5 5 5 5

319

2.5 0 5 5 4.5

5 1 5 5 5

365

2.5 0 2 5 5 Industrial utilizability

The compounds of formula 【1 ] of this invention are useful for controlling undesired vegetation in low dosages without substantial phytotoxicity on useful crops .

Claims

1. A urea derivative represented by the following formula 【1 ] til

wherein

A represents the bond -N= or -C= in which is a hydrogen atom, a chlorine atom, a nitro group or a trif luororaethyl group;

B represents a hydrogen atom, a methyl group or a methoxy group; and

Ar represents one member selected f rom the group consisting of

1 38 一

in which R to R , independently from each other , represent a hydrogen atom, a lower alkyl group or lower alkoxy group; may further represent a hydroxy 1 group ; a pair of and R a pai of R and R and a pair of R and R¹⁰ each, taken together _f may represent an alkylene linkage and may form a 5 - or 6 - membered ring together with the two adj acent carbon atoms to which they are

11 12

bonded ; R and R , taken together , may form an

11 1 5

ethylenedioxy linkage - 0 - CH -0-, or R and R taken together , may form an alkylene linkage and form a 5 - or 6 -membered ring together with the carbon atoms to which they are bonded, or R and R ⁰ , taken together , may represent a methylene linkage and form a 5 - or 6 -membered ring together with one carbon atom to which they are

14 15

bonded , or R and R , taken togethe , may form a di - ' chloromethylene l inkage .

2 . A process for producing a urea de ivative represented by formula [ 1 in claim- 1 , which comprises reacting an aminopy.ridine or aniline .derivative of the following formula 11 ]

wherein Ar and A are as def ined with regard to formula 1 ] in claim 1 ,

with methyl isocyanate, N N-dimethylcarbamoyl chloride or N-methoxy-N-methylcarbaraoyl chloride .

3 , A process for producing a urea derivative represented by formula [I ] in claim 1 which comprises reacting an isocyanate ester derivative represented by the following f ormula [ III ]

wherein Ar and A are as def ined with regard to formula [ II ] ,

with an amine compound represented by the following formula [ IV] Η [IV]

wherein B is as defined with regard to formula 【1】，

4 · A herbicidal composition comprising a herbicidally effective amount of at least one compound of formula [1】 according to claim 1 and an agriculturally acceptable diluent or carrier.

5. The herbicidal composition of claim 4 wherein the amount of the compound of formula [I] is about 0.5 to about 70% by weight based on the weight of

the composition.

6. The herbicidal composition of claim 4 which is in the form of granules or a dust and in which the amount of the compound of formula [I] is 0.5 to 20% by weight based on the weight of the composition.

7. The herbicidal composition of claim 4 which is in the form of an emulsif iable concentrate or wettable powder and in which the amount of the compound of formula [1〗 is 5 to 70% by weight based on the weight of the composition.

8. Use of the compound of formula 【I〗 according o claim 1 as a herbicide.

9. A method for controlling the growth of weeds, which comprises applying a herbicidally effective amount of at least one compound of formula [I] according to claim 1 to the weeds or the locus of such weeds.