CA1076600A - Process for producing 2-substituted-benzanilide - Google Patents

Abstract

ABSTRACT OF THE DISCLOSURE
A 2-Substituted-benzanilide is produced by reacting an alkyl 2-substituted-benzoate having the formula wherein X represents halogen, or lower alkyl group and R re-presents a lower alkyl group with an aniline having the formula

Description

The present invention relates to a process for produc-ing a 2-substituted-benzanilide which is useful as an agricultural germicide. In particular the present invention relates to an improved industrial process for producing a 2-substituted-benzani-lide having high purity by reacting an alkyl 2-substituted-benzoate with aniline or an aniline derivative.
The 2-substituted-benzanilides have a high germicidal effect and a broad anti-microbial spectrum and are effective in preventing plant diseases, such as rice sheath blight, bacterial leaf blight, tomato late blight, cucumber anthracnose, haricot stem rot, alternaria leaf spot, powdery apple mildew, orange phoma rot, wheat bund, rusting of wheat, barley turf, coffee, ornamental plants, vegetables, cereals and grasses, smut and Rhizoctonia and Fusarium soil diseases. They are also effective as disinfectants for seeds.
It is known to produce benzanilides having an un-sub-stituted benzene nucleus of benzoyl group by reacting an alkyl benzoate unsubstituted on benzene nucleus with an aniline compound in the presence of an alcoholate e.g~ sodium methylate in an organic solvent and a by-product alcohol in an azeotropic condition. For example, in Richard J. De Feo et al., Journal of Organic Chemistry Vol 28, P 2915 (1963) and USP No. 3,462,486, benzanilides are produced by reacting ethyl benzoate with an aniline compound in benzene and by-product ethyl alcohol in an azeotropic condition in the presence of solid sodium methylate as shown in the following equation:-O

C -- C2H5 + H2N

be~e~e ~ C - NH ~ 2 5 -- 1 -- ~,,~4j -10766VC~

In order that the condensation reaction of an alkyl carboxylate pr~ ~e~/s s~ O 0~ /y with an aniline compound~ it is necessa~y to readily remove by-product alcohol from the reaction system. Accordingly, it has been considered that the optimum condition is to use an organic solvent which is azeotropically distilled with the by-product alcohol. Benzene has been used as the organic solvent. However, it has been difficult to produce a 2-substituted-benzanilide having a high germicidal effect and a broad antimicrobial spectrum in high yield by the conventional processes. In particular it has been difficult to produce a 2-substituted-benzanilide in high yield by reacting alkyl 2-substituted-benzoates which have a substituent at ortho position to the alkoxy carbonyl group with an aniline compound.
In the aforesaid processes, N-alkyl benzanilides have been readily produced as by-product, and it has been difficult to substantially completely inhibit the formation of the by-product. ~hen the 2-substituted-benzanilide is contaminated with the by-product, the germicidal effect of 2-substituted-benzanilide may be adversely affected. The present invention improves the conventional processes to inhibit the formation of the by-product of N-alkylbenzanilide so as to produce in high yield 2-substituted-benzanilides which have a high germicidal effect and a broad antimicrobial spectrum. It has been found that the optimum condition is to react an alkyl 2-substituted-benzoate with an aniline compound in an organic solvent which is difficultly azeotropically distilled with the by-product alcohol. It has also been found that the reactivity is different depending upon carbon atoms of the alkyl group of alkoxy carbonyl group of the alkyl 2-substituted-benzoate. It has further been found that 2-substituted-benzaniliaes can be produced in high yield essentially without the formation of the by-product N-alkylbenzanilide by reacting an alkyl 2-substituted-benzoate having the alkoxy carbonyl group having specific carbon atoms with an aniline compound in the presence of specific alcoholate in an organic solvent which is difficultly azeotropically dis-tilled with the by-product alcohol.
The present invention provides a process for producing a 2-substituted-benzanilide in high yield without significant formation of a by-prodcut of N-alkylbenzanilide.
According to the present invention there is provided a process for producing a 2-substituted-benzanilide having the formula O y ~ C - NH ~ .............................. [III]

wherein X represents halogen, or lower alkyl group and Y repres-ents hydrogen atom or an alkyl alkoxy, alkenyloxy, alkynyloxy, benzyloxy, or halobenzyloxy group, which comprises reacting an alkyl 2-substituted-benzoate having the formula X ol ....................... ...[I]

~ C - OR

wherein R represents a C2 4 alkyl group and X is as above with an aniline having the formula

2 ~ ................................. ...[II]

whereinY is as above in the presence of an alcoholate in an organic solvent which is difficultly azeotropically distilled with by-product alcohol.

. . . ,, .. :.. ~.:

1~7~6~o The reactant alkyl-2-substituted-benzoates have the ~ormula [I] wherein X is halogen group, such as chlorine, bromine or iodine, a nitro radical or lower alkyl group such as methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, iso-butyl or tert-butyl group; and R is a C2 4 alkyl group such as ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl or tert-butyl, and preferably a C2 3 alkyl group. When R is methyl group, N-methyl-benzanilide is formed as a by-product. When R is an alkyl group having more than 5 carbon atoms or a phenyl group, the yield of 2-substituted-benzanilide is relatively low.
The anilines have the formula [II] wherein Y is hydrogen atom, an alkyl group such as methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, iso-pentyl, sec-pentyl, tert-pentyl, an alkoxy group such as methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, sec-butoxy, iso-butoxy, tert-butoxy, pentyloxy, iso-pentyloxy, hexyloxy, octyloxy, or dodecyloxy group; and an alkeny-loxy group such as vinyloxy, allyloxy or l-methylallyloxy group and an alkynyloxy group such as acetyleneoxy, propargyloxy, l-propylpropargyloxy group and benzyloxy group or halobenzyloxy group such as chlorobenzyloxy group. The alcoholates used in the process of the invention are alkali metal alcoholates and alkaline earth metal alcoholates such as potassium methylate, sodium ethylate, sodium n-propylate, sodium-iso-propylate, pot-assium ethylate, potassium n-propylate, potassium-iso-propylate and the like.
When methylate is used, N-methylbenzanilides are produced as the by-product. When methylate and a compound having the formula [I] wherein R is methyl group is used a large amount of N-methylbenzanilide is produced.
The solvent which is quite important in the process of the invention is preferably a compound having the formula Rl ~07~ )0

3 ~ R2 ................................... [IV]

wherein Rl represents a lower alkyl yroup or chlorine atom;
R2 represents hydrogen atom, a lower alkyl group or chlorine atom, and R3 represents hydrogen atom, a lower alkyl group or chlorine atom, or a compound naving the formula . R4 - O - R5 -----..[V]
wherein R4 and R5 respectively represent alkyl groups having more than 5 carbon atoms. Suitable solvents include the com-pounds having the formula [IV] wherein ~ Rl is methyl, R2 is a Cl 4 alkyl group or CQ and R3 is H or CQ or Rl is CQ, R2 is H or CQ and R3 is H or ~ Rl is a C2 5 alkyl group and R2 and R3 are H, and the compounds having the formula [V] wherein R4 and R5 are C5 6 alkyl groups.
Typical solvents include o-, m- and p-xylene, o-, m- and p-ethyl-toluene; o-, m- and p-propyltoluene; o-, m- and p-cymene; o-, m-2Q and p-chlorotoluene; 2,4-, 2,5- and 2,6-dichlorotoluene; 3,4-dichlorotoluene, chlorobenzene, o-dichlorobenzene, m-dichloro-benzene, ethylbenzene, n-propylbenzene, cumene, n-butylbenzene, iso-butylbenzene, sec-butylbenzene, tert-butylbenzene, n-amylben-zene, iso-amylbenzene, tert-amylbenzene, mesitylene, diethyl-benzene, n- or iso-dibutyl ether, n-amyl ether and iso-amyl ether.
When the solvent o-, m-, or p-xylene, or chlorobenzene is used in the case that R in the compound [I] is n-propyl group; or the solvent o-, m-, or p-xylene, ethylbenzene or chlorobenzene is used in the case that R of the compound ~I] is n-butyl group or the solvent of o-xylene, ethylbenzene or chlorobenzene is used in the case that R of the compound [I] is iso-butyl group, an azeo-tropic distillation is caused with the by-product alcohol formed iO7~600 by the reaction in some degree. The other solvents have dis-advantage as follows. When benzene or toluene is used, an azeo-tropic distillation is caused with the by-product alcohol formed in the reaction, whereby it is hard to produce 2-subs~ituted-benzanilide in high yield. When dimethylformamide is used, it reacts with the aniline compound to produce the by-products of formamidines. When alcohols and lower alkyl ethers are used, the reaction is not smooth or the yield of the product is not satisfactorily high. When chlorohydrocarbon, such as chloroform, is used, side reactions occur.
The reaction of the process of the invention is usually carried out by reacting the alkyl 2-substituted-benzoate ~I] with the aniline compound ~II] under atmospheric pressure in the pre-sence of the specific alcoholate in the specific solvent with stirring under heating. For example, the alkyl 2-substituted-benzoate ~I] is added to a mixture of the specific alcoholate and the aniline [II] in the specific solvent with stirring under heating or the specific alcoholate is added to a mixture of the alkyl 2-substituted-benzoate [I] and the aniline compound [II]
in the specific solvent. The amount of the alkyl 2-substituted-benzoate [I] is usually in a range of 0.9 to 1.5 mole preferably l to 1.3 mole per l mole of the aniline compound [II]. The amount of the specific alcoholate is usually in a range of 0.9 to 2.0 mole preferably 1 to 1.5 mole per 1 mole of the aniline compound [II]. The reaction temperature is in a ran~e of lO0 to 200C pxeferably 120 to 150C. The reaction time is in a range of 1 to 20 hours preferably 2 to 6 hours.
After the reaction, the product of 2-substituted-ben-zanilides are produced in the form of alkali metal or alkaline earth metal salts. It is usual to add a mineral acid for hydrol-ysis of metal salts of benzanilides. However, in accordance with the process of the invention, it is possible to hydrolyze the 107~600 metal salts of 2-substituted-benzanilides by adding water to the reaction mixture, whereby 2-substituted-benzanilides [III] can be separated in high yield.
The following are the characteristics and advantages of the invention. Firstly, 2-substituted-benzanilides which are useful as germicides and had previously been hard to be produced in high yield can be produced in high yield. Secondly, 2-sub-stituted-benzanilides can be produced in high yield while inhib-iting the formation of by-product of N-alkylbenzanilides. As N-alkylbenzanilide is not included in the product, the product of 2-substituted-benzanilides can be used as a germicide with a stable and high germicidal effect.
The invention will be further illustrated by certain examples and comparative references in detail.
EXAMPLE 1:

Preparation of 3'-iso-propoxy-2-methylbenzanilide:
In a 200 mQ four necked flask equipped with a stirrer, a thermometer, a condenser and a dropping funnel, were charged 50 mQ of p-xylene, 15.1 g (0.1 mol) of m-iso-propoxyaniline and 37.4 g of 20% ethyl alcohol solution of sodium ethyl alcoholate (0.11 mol as NaOC2H5). The mixture was heated at 80 to 90C
to distill ethyl alcohol.
The mixture was heated to 130C and 19.6 g (0.11 mol) of isopropyl 2-methylbenzoate was added dropwise to the mixture at 130C during 30 minutes with stirring and the reaction was further continued for 5 hours. The by-product of isopropyl alcohol formed by the adaition of isopropyl 2-methylbenzoate was distilled off during the reaction.

After the reaction, the reaction mixture was cooled and 50 mQ of water was added to the reaction mixture and 50 mQ
of n-hexane was added and the precipitated crystals were filtered to obtain 25.6 y (yield 95.2~) of white crystals of 3'-isopropoxy-~0'-7~
2-methylbenzanilide (m.p. 91 to 92C). According to gas chroma-tography analysis, it was confirmed tha~ a by-product of N-alkyl-3-isopropoxy-2-methylbenzanilide was not formed. The purity of the product was 99.8~.
EXAMPLE 2:
In accordance with the process of ~xample 1, the reactions of various alkyl 2-methylbenzoates with m-isopropoxy-aniline were carried out in various solvents of p-xylene, ethyl-benzene and chlorobenzene. As the results, when methyl 2-methyl-benzoate was used, N-methyl-3'-isopropoxy-2-methylbenzanilide was produced as by-product in all solvents. The yields of 3'-isopropoxy-2-methylbenzanilides in the reactions are as follows.
Table 1 CH3 O-C H -iso C - OR + H2N ~ CH3 3 7 2 5 > ~ C - NH
solvent 10'76~;00 Experi- Organ ic solvent (yield %) ment R p-xylene ethyl chloro No. benzene benzene 2-1 -CH3 73.6 72.3 74.9 2-2 -CH2CH3 93.1 92.1 91.2 2-3 -CH2CH2CH3 80.1 93.7 79.9 2-4 -CH(CH3)2 95.2 94.0 94.6 2-5 -(CH2)3CH3 79.1 78.3 72.7 -CHCH2CH3 93.5 9~.~

2-7 -CH2CH(CH3)2 93.8 7~ ~ 74,4 2-a -C(CH3)3 97.3 95.9 96.7 2-9 (CH2)4CH3 64.1 65.1 66.4 2-10 -(CH2)2CH(cH3~2 66.5 67.3 57.0 .
65.9 ~ ] ~3 As shown in Example 2, when p-xylene was used as the solvent and R is n-propyl or n-butyl group, the yield was low.
When ethylbenzene was used as the solvent and R is n-propyl or n-butyl group, the yield was low. When chlorobenzene was used and R is n-propyl, n-butyl or iso-butyl group; the yield was low.
Thus, in accordance with the process of Example 2, the reactions were carried out by using p-cymene, cumene or mesitylene.
As the results, the yields were not decreased, and 3'-isopropoxy-2-methylbenzanilide could be obtained in high yield of 10~i600 more than 90% except when R is methyl, n-amyl or isoamyl group.
EXA~LE 3:

Preparation of 4'-methoxy-2-methyl-benzanilide:
In the flask of Example 1, were charged 50 mQ of cumene, 13.7 g (0.1 mol) of p-ethoxyaniline and 37.4 g of 20~ of ethyl alcohol solution of sodium ethylate (0.11 mol as NaOC2H5). The mixture was heated at 80 to 90C to distill off ethyl alcohol and 18.1 g (0.11 mol) of ethyl-2-methylbenzoate was added dropwise to the mixture at 130C during 30 minutes with stirring, and the reaction was further continued for 5 hours. The by-product ethyl alcohol formed by the addition of ethyl 2-methylbenzoate was distilled off in the reaction.
After the reaction, the reaction mixture was treated in accordance with the process of Example 1 to obtain 25.0 g (yield 92.9~? of white needles of 4-methoxy-2-methylbenzanilide (m.p. 149 to 149.5C).
EXAMPLE 4:
By the same procedure as in the process of Example 3, the reactions were carried out using various alkyl 2-methyl benzoates and m-iso-propylaniline in the presence of various alcoholates and various solvents to obtain the corresponding 3'-iso-propyl-2-methylbenzanilides. The results obtained are shown in Table 2.
Table 2 3 ~_~ C3 7-(i) ~ COOR + NH2 ~

alcoholate ~ CH3 C3H7-iso solvent ~ CONH ~

1(3'7~VO

No. alcoholate solvent Yield (%) _ _

4-1 C2H5 3 7-n n-propyl benzene 93.4 4-2 C3H7-nNaOC2H5 p-cymene 95.2 4~3 C8 7 isoNaOC2H5 ethyl toluene 97.4 4-4 C4Hg-nNaOC2H5 mesitylene 96.3 4-5 C4Hg-sec.NaOC2H5 di-n-butyl ether 95.0 4-6 C4Hg-isoNaOC2H5 p-cymene 93.2 4-7 C4H9-tertNaOC2H5 di-n-amyl ether 94.6 4-8 C4Hg-tert3 7 i 2,3-dichloro toluene 97.0 4-101 CH3NaOCH3 benzene 39.3 4-102 C2H5NaOC2H5 benzene 31.4 4-103 C2H5NaOC2H5 toluene 38.6 4-104 C2H5NaOC2H5 DMF 10.2 4-105 C2H5NaOC2H5 DMSO 24.3 4-106 C2H5NaOC2H5 _ 58.2 . . . ... ...
, Note:

1. In experiment No. 4-101 and 102, the reaction was car-ried out by azeotropically distilling off the alcohol formed during the course of the reaction with the solvent, benzene, under reflux.
2. In experiment No. 4-101, N-methyl-3'-iso-propyl-2-methylbenzanilide was produced in an amount of about 30 ~ as by-product.
3. In experiment No. 4-102, no by-product is produced.
4. In experiment No. 4-103, the reaction was carried out by azeotropically distilling off the ethyl alcohol formed during the course of the reaction with the solvent, toluene, under reflux.

5. In experiment No. 4-104, and 105, the reaction was 10~00 carried out at 130C and formamidin was produced as by-product.

6. In experiment No. 4-106, the reaction was carried out at 170C without using any solvent. A small amount of polymer was produced as by-product.
EXAMPLE 5:
By the same process as Example 1, the reactions were carried out using various alkyl 2-substituted-benzoates and various aniline compounds in the presence of various alcoholates and various solvents to produce the corresponding 2-substituted-benzanilides. The results obtained are shown in Table 3.
Table 3 O y C-OR + H2N

(I) (II) alcoholate ¦ ¦ ¦ ~ Y
~ ~/ \~ C - NH
solvent \==J
(III) Conditions of Reactions:
.
Experi- Benzoate Aniline Alaoholate Solvent Reaction e~ (I) _ (amount) temp .

5-1 X = CH3 Y = H NaOC2H5 2 5 (20~)p-xylene 130 18.1 g 9.3 g 37.4 g (0.11 1) (0.1 mol) (0.11 mol) 5-2 2 5 Y = H NaOC2H5 R = C4Hg-(iso (20~) p-cymene 150 22.7 g 9.3 g 37.4 g (0.11 mol) (0.1 mol) (0.11 mol) 10'76601~

Table 3 (continued) _..~
Experi- Benzoate ~niline ¦Alcoholate ¦Solvent Reaction ment No. (I) I (II) ¦(amount) temp.
.... _ i ( C) 5-3 C3 7 (iso) Y = H ¦NaOC2H5 R = C4Hg-(tert) 1(20%) p-xylene 130 24.2 g !9.3 g 137.4 g (0.11 mol) ~.1 mol) (0.11 mol) 5-4 X = CH3 Y - OCH3 NaOC3H7 R = n-C3H7 at meta (20%) 0-cymene 150 19.6 g 12.3 g 45.1 g (0.11 mol) (0.1 mol) (0.11 mol) 5-5 X = CH3 Y = OC3H7 NaOC2H5 R = C4Hg-(sec.) at para (20%) p-xylene 130 21.1 g 15.1 g 37.4 g (0.11 mol) (0.1 mol) (0.11 mol) .
5-6 X = CH3 4 9 NaOi-C H
R = C3H7-(iso) (sec.) at meta (10%) p-xymene 150 22.7 g 16.5 g 90.3 g (0.11 mol) (0.1 mol) (0.11 mol) . _ _ . . _ 5-7 X = CH3 4 9 NaOC2H5 (n) (20%) chloro- 125 2 5 at meta benzene 18.1 g 16.5 g 37.4 g (0.11 mol) (0.1 mol) (0.11 mol) 5-8 X= CH3 5 11 NaOC2H5 R = C2H5 (sec.) ethyl 130 at meta (20%) benzene 18.1 g 17.9 g 37.4 g (0.11 mol~ (0.1 mol) (0.11 mol) ....... .. ' '.. _ ' ._ 5-9 X = CH3 Y=OCH2.Ph NaOC2H5 R - C2H5 at meta (20%) mesity- 150 18.1 g 19.9 g 37.4 g lene -(0.11 mol) (0.1 mol3 (0.11 mol) _ ... _._ 5-10 X = CH Y = NaOC2H
3 OCH2PhCQ- 5 chloro 125 R C2H5 (o) (2~%) benzene 18.1 g at meta 37.4 g (0.11 mol1 23.3 g (0.11 mol) (0.1 mol.) .. ~ _ Table 3 (continued) Experi- I Benzoate Aniline Alcoholate Solvent Reaction ment No. I (I) (II)(amount) temp.
I (C) s-ll ¦ X = CQ 3 7NaOC2H5 2 5 (iso)(20%) p-xylene 130 at meta 20.3 g 15.1 g37.4 g ~_ (O.ll mol) (0.1 mol) (0.11 mol) 5-12 X - Br Y - OC2H5 NaOC2H5 R = n-C H at meta (20%) p-xylene 130 31.9 g 13.7 g 37.4 g ~ (0.11 mol) (0.1 mol) (O.ll mo11 _ 5-13 X = I C3 7 NaOC2H5 (iso) (20%) p-xylene 130 R C2 5 at meta `
30.4 g 13.5 g 37.4 g (0.11 mol) (0.1 mol) (0.11 mol) ... . _ .
5-14 X = I Y OC4 9 NaOC2H5 2 5 (sec. ) (20%) at meta p-xylene 130 30.4 g 16.5 g 37.4 g (0.11 mol) (0.1 mol) (0.11 mol) -: ::
5-15 X = I Y = H NaOC2H5 (20%) cumene 140 3 7 ( ) 31.9 g 9.3 g 37.4 g ~0.11 mol) (0.1 mol) (0.11 mol) 5-16 X = CH3 Y = CH3 NaOC2H5 2 5 at meta (20%) p-xylene 130 18.1 g 10.7 g 37.4 g (0.11-mol) (0.1 mol) (0.11 mol) 5-17 X = CH3 C3H7 NaOC3H7- ethyl 130 3 7 (iso) (iso) benzene (iso) at meta (10%) 19.6 g 13.5 g 90.3 g (0.11 mol) (0.1 mol) (0.11 mol) 107~600 Table 3 (continued) Products (III) .

Experi- Product Amount Yield Melting Crystals ment point No. (g) (%) (C) 5-1 X = CH3 19.5 92.4 125-126 white Y = H powder X = C2H5 _ 5-2 Y = H 20.4 90.7 141-142 5-3 X = C3H7-(iso) Y = H 20.3 84.9 135-136 ,.
_ X = CH
5-4 Y = OC~3 22.3 92.1 74-75 white at meta prism X = CH3 5-5 Y = OC3H7 25.7 95.5 151-152 white at para powder X = CH3 5-6 Y = C4Hg-(sec.) 26.3 92.9 75-77 Wnehedtele 2q 5-7 Y = OC4Hg-(n) 27.4 96.8 87 needle at meta _ __ X = CH3 5-8 C5 11 (sec.) 27.793.3 70-73 brown at meta X = CH3 5-9 Y = OCH2 ~ 28.3 89.3 114-115 whidle at meta nee e X = CH3 CQ
5-10 Y = OCH ~ 31.0 88.1 115-116 at meta _ 5-11 X=CQ 26.9 92.8 b.p. ~ pale OC3~7 (iso) 173-175C)I yellow at meta /0.007 J oil mmHg 10~7~6V0 Table 3 (continued) Products (III) Experi- Product Amount ¦Yield iMelting Crystals ment point No. (g) (~) (C) 5-12 X=Br 29.2 91.3 114-115 white Y=OC2H5 needle at meta 5-13 X=I 35.2 96.5 112-113 pale 3 7 ( ) brown at meta l solid . _ _ __ 5-14 X=I 36.0 91.1 86-87 white Y=OC4H9-(sec) needle at meta I

5-15 IX-I ,~
- 29.1 90.1 144-145 white needle l i~ .
5-16 ¦X=CH3 20.9 92.9 138 white Y=CH3 at meta _ needle 5-17 X=CH3 23.9 94.5 70- 71 white C3H7 (iso) l needle Typical compounds prepared by the above processes are listed below. The compound numbers appearing below will be re-ferred to later in the text.
Compound No. 1 2'-methoxy-2-methylbenzanilide white prisms m.p. 74 - 75C
Compound No. 2 3'-methoxy-2-methylbenzanilide fine white prisms m.p~ 142 - 143C

10766~)0 Compound No. 3 4'-methoxy-2-methylbenzanilide white needles m.p. 136 - 137C
Compound No. 4 2'-ethoxy-2-methylbenzanilide clear pinkish oil b.p. 148C/0.04 mm Hg Compound No. 5 3'-ethoxy-2-methylbenzanilide white needles m.p. 115 - 116C
Compound No. 6 4'-ethoxy-2-methylbenzanilide white needles m.p. 149 - 149.5C
Compound No. ?
2'-iso-propoxy-2-methylbenzanilide clear reddish brown oil b.p. 143 - 145C~0.01 mm Hg Compound No. 8 3l-iso-propoxy-2-methylbenzanilide white prisms m.p. 92C
Compound No. 9 4l-n-propoxy-2-methylbenzanilide powdery white crystals m.p. 151 - 152C
Compound No. 10 3'-n-pentyloxy-2-methylbenzanilide white needles m.p. ~0C

Compound No. 11 3'-octyloxy-2-methylbenzanilide white needles m.p. 95C
Compound No. 12 3'-n-dodecyloxy-2-methylbenzanilide powdery white crystals ~I.p. 65 - 66C
Compound No. 13 2'-allyloxy-2-methylbenzanilide -pale reddish brown oil m.p. 151C/0.025 mm Hg Compound No 14 3l-allyloxy-2-methylbenzanilide powdery white crystals m.p. 85- 89C
Compound No. 15 3'-propargyloxy-2-methylbenzanilide fine white powder m.p. 93 - 95C
Compound No. 16 3'-benzyloxy-2-methylbenzanilide white needles m.p. 114 - 115C
Compound No. 17 3'-2-chlorobenzyloxy-2-methylbenzanilide fine white needles m.p. 116C
Compound No. 18 3'-n-propoxy-2-methylbenzanilide white prisms m.p. 92 - 93C

-107f~ )0 Compound No. 19 2'-sec-butoxy-2-methylbenzanilide white needles m.p. 75 - 77C
Compound No. 20 3'-n-butoxy-2-methylbenzanilide greyish needles m.p. 87C
Compound No `21 .
3'-methyl-2-chlorobenzanilide white needles m.p. 124C
Compound No. 22 3l-methoxy-2-chlorobenzanilide white needles m.p. 143 - 144C
Compound No. 23 3'-ethoxy-2-chlorobenzanilide needle m.p. 105 - 106C
Compound No. 24 3'-n-propoxy-2-chlorobenzanilide pale yellow oil b.p. 172 - 175C/0.02 mm Hg Compound No 25 -3l-isopropoxy-2-chlorobenzanilide pale yellow oil b.p. 173 - 175C/0.007 mm Hg Compound No. 26 _ . _ _ _ _ _ _ _ _ 3'-methoxy-2-bromobenzanilide white needles m.p. 162 - 164C

107~;00 Compound No. 27 3'ethoxy-2-bromobenzanilide white needle m.p. 114 - 115C
Compound No. 28 3'-isopropoxy-2-bromobenzanilide white prism m.p. 89 - 91C
Compound No. 29 3'-isopropyl-2-bromobenzanilide white needle m.p. 79 - 80C
Compound No. 30 _ _ _ _ 3'-methyl-2-iodobenzanilide white needle m.p. 164 - 165.5C
Compound No. 31 3'-ethyl-2-iodobenzanilide white crystals m.p. 153 - 155C
Compound No. 32 3l-isopropyl-2-iodobenzanilide pale brown needles m.p. 112 - 113C
Compound No. 33 3l-methoxy-2-iodobenzanilide white needles m.p. 154 - 155.5C
Compound No 34 .
3'-ethoxy-2-iodobenzanilide white needles m.p. 126 - 128C

107f~00 Compound No. 35 3'-n-propoxy-2-iodobenzanilide white needles m.p. 114 - 115C
Compound No. 36 3'-isopropoxy-2-iodobenzanilide white prism m.p. 94 - 96C
Compound No. 37 3'-n-butoxy-2-iodobenzanilide white needles m.p. lQ2 - 105C
Compound No. 38 3'-isobutoxy-2-iodobenzanilide white needles m.p. 13~.5 - 141.5C
Compound No. 39 _ _ 3l-sec-butoxy-2-iodobenzanilide white needles m.p. 86 - 87C
Compound No. 40 3l-n-pentyloxy-2-iodobenzanilide white crystal m.p. 115-118QC
Compound No. 41 3l-n-hexyloxy-2-iodobenzanilide white crystal m.p. 112.5 - 113.5C
Compound No. 42 3'-methyl-2-nitrobenzanilide pale brown prism m.p. 145 - 147C

1C~'7~6V0 Compound No. 43 3'-methoxy-2-nitrobenzanilide pale yellow needle m.p. 155 - 157C
Compound No. 44 3'-methyl-2-methylbenzanilide white needle m.p. 138C
Compound No. 45 3l-ethyl-2-methylbenzanilide white needle m.p. 114 - 117C
Compound No 46 3l-isopropyl-2-methylbenzanilide white needle m.p. 70 - 71C
Compound No.'47 3'-tert-butyl-2-methylbenzanilide yellow oil b.p. 181 - 186C/0.04 - 0.06 mm Hg ~Compound No. 48 3'-tert-pentyl-2-methylbenzanilide white crystal m.p. 68 - 71C
The agricultural effects of the compounds of the invention are shown in the Test Example below.
Test Exa'mple .. . .
Preventive e'ffect'on 'r'ice' sheath ~light:
Porcelain pots of a diameter of g cm were filled with soil from a rice paddy field, and water was added to the pot to simulate the condition in a rice field. 9 stal~s, in groups of 3 stalks each, of rich plant seedlings (Oryza sativa L. var ~o766 Kinmaze) were planted and cultivated in each pot. When said seedlings reached the booting stage, a wettable powder * diluted with water to a given concentration was sprayed in an amount of 15 mQ per pot. Rice sheath blight (Pellicuralia Sasakii) culti-vated on potato sucrose agar medium was inoculated on the leaf sheath.
After the inoculation the rice plants were placed in a high humidity chamber (25 - 30C), and the length of lesions formed in the leaf sheath part was measured after 10 days. The following table shows the results for 3 pots for each test.

Total length of lesions in Protection - 1 tre.ate.d plants value (%) ~ x 100 Total length of lesions in non-treated plants Note:
* Preparation of wettable powder One of the numbered compounds (50%), diatomaceous earth (45%), sodi~m dinaphthylmethane sulfonate (2~) and sodium lignin sulfonate (3%) were mixed and uniformly crushed to give a wettable powder.
Table 4 .
Germicidal ~oncentration Total Protection (Chemical ingredient (ppm) length of value (%) injury) . . (cm) . phytotoxicity . _ Compound No. 1500 14.2 95.5 I None No. 2ll 4.5 98.6 ., No. 3ll 32.5 89.6 No. 4ll 4.3 98~6 . ll No. 5 l 0 100 n No. 6 ll 42.5 86.4 ll No. 7 ll 1.4 99.6 ll : .
No. 8 .. 0 100 No. 9 ll 24.5 92.1 No. 10 ll 4.5 98.6 No. 11 ll 14.3 95.5 No. 12 .- 42.5 86.4 No. 1 ll 3.2 99.0 No. 14 ll 0 100 No. 15 ll 0 100 ll No. 16¦ _ 100 _ _ 10~600 Table 4_(continued) ¦ Germicidal ¦Concentration Total IProtection ~Chemlcal ingredient (ppm) length of ¦value (~) injury) l lesions phytotox-_ (cm) icity Compound No. 17500 12.5 1 96.0 ¦ None No. 18 .. 0 100 ~ "
No. 19 .. 0 100 1 "
No. 20 .. 4.3 ~ 98.6 1 "
No. 21100 127.9 72.3 1 "
No. 22., 138.1 1 70.1 ~ "
No. 23 .. 72.5 ,l 84.3 ..
No. 24 .. 17.5 1 96.2 ..
No. 25 .. 0 1 100 ..
No. 26 .. 76.2 83.5 ..
No. 27 ll 45.7 90.1 I~
No. 28 ., 0 100 ..
No. 29 ll 0 100 ..
No. 30 .- 62.3 86.5 ..
No. 31 .- 26.3 94.3 ..
No. 32 .. 0 100 . ., No. 33 .. 86.8 81.2 ll No. 34 .. 40.6 91.2 ..
No. 35 .. 0 100 ..
No. 36 .. 0 100 ..
No. 37 .- 0 100 ..
No. 38 - 0 100 ..
No. 39 .. 0 100 ,.
No. 40 .. 0 100 ..
No. 41 .. 0 100 ..
No. 42 ll 109.4 76.3 ..
No. 43 .. 136.7 70.4 _ 107~i6V0 Table 4 (continued) ¦ Germicidal IConcentration Total Protectionj(Chemical ingredient ~ (ppm) length of value (~) injury) lesions phytotox-(cm) icity Compound No. 44 100 92.3 80.0 None ll 49.9 89.2 46 ll 0 100 47 ll 0 100 ll 48 ., 0 100 ..
*Neo-Asozine 32.5 38.8 91.6 ..
solution Non-treated 461.7 Note: * Neo-Asozin (Trademark) solution: Ferric ammonium salt of methane arsonic acid, effective concentration 6.5%.

. . . . .

Claims (13)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. A process for producing a 2-substituted-benzanilide having the formula ..... [III]
wherein X represents a halogen atom or lower alkyl group and Y
represents hydrogen atom, an alkyl, alkoxy, alkenyloxy, alkynyloxy, benzyloxy or halobenzyloxy group which comprises reacting an alkyl 2-alkylbenzoate having the formula ......[I]
wherein R represents a C2-4 alkyl group with an aniline compound having the formula ......[II]
in the presence of an alkali metal or alkaline earth metal alcoholate having 2 to 4 carbon atoms in an organic solvent which is difficultly azeotropically distilled with by-product alcohol and is a compound having the formula or wherein R1 represents a lower alkyl group or a halogen; R2 and R3 respectively represent hydrogen or halogen atom or a lower alkyl group; R4 and R5 respectively represent alkyl group having more than 5 carbon atoms.

2. The process according to claim 1, wherein the alcoholate is sodium or potassium ethylate, sodium or potassium n- or iso-propylate, or sodium or potassium n-, iso, sec, or tert- butylate.

3. A process as claimed in claim 2 in which the solvent is o-, m-, or p-xylene, ethylbenzene, propylbenzen, isopropylbenzene, o-, m-, or p-cymene, trimethylbenzen, n- or iso-butylbenzene, amylbenzene, o-, m-, or p-chlorotoluene, 2,4-, 2,5-, 2,6- or 3,4-dichlorotoluene, chlorobenzene, o-, m-, or p-dichlorobenzene, n- or iso-dibutyl ether or n- or iso-amyl ether.

4. The process according to Claim 1, wherein the solvent is not azeotropically distilled with an alcohol formed in the reaction.

5. The process according to Claim 1, 2 or 3, wherein the reaction is carried out at 100 to 200°C.

6. A process according to Claim 1, 2 or 3, wherein the reaction is carried out at 120 to 150°C.

7. The process according to Claim 1, 2 or 3, wherein a molar ratio of the alkyl 2-alkylbenzoate [I] to the aniline [II]
is in a range of 0.9 to 1.5.

8. The process according to Claim 1, 2 or 3, wherein a molar ratio of the alcoholate to the aniline [II] is in a range of 0.9 to 2Ø

9. The process according to Claim 1, wherein a 2-substituted-benzanilide having the formula wherein X represents iodine or methyl; Y represents an alkyl or alkoxy group is produced.

10. The process according to Claim 9, wherein Y re-presents a branched alkyl or alkoxy group.

11. The process according to Claim 10, wherein Y re-presents iso-propyl, sec-butyl, iso-propoxy, iso-butoxy, sec-butoxy, tert-butoxy, iso-pentyloxy or sec-pentyloxy group.

12. A process as claimed in Claim 1 in which in the reactants X is chlorine, bromine, iodine, a nitro group, methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, iso-butyl, or tert-butyl; R is ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl or tert-butyl and Y is hydrogen, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, iso-pentyl, sec-pentyl, tert-pentyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, iso-butoxy, tert-butoxy, pentyloxy, iso-pentyloxy, hexyloxy, octyloxy, dodecyloxy, vinyloxy, allyloxy, 1-methyalyloxy, acetyleneoxy, propargyloxy, 1-propylpargyloxy, benzyloxy or chlorobenzyloxy.

13. A process as claimed in Claim 12, in which Y is in the meta position in the benzene ring.