NZ209827A - Process for the preparation of 2,3-dihydro-2,2-dimethylbenzofuran-7-yl n-(n,n-disubstituted aminosulphenyl)-n-methyl carbamate derivatives - Google Patents

Description

New Zealand Paient Spedficaiion for Paient Number £09827 '"7/' rv ' ^ /•:, Wnder the provisions of RegO4^ latlon 23 (I) the | j Specification has been ante-doted] to ISkdf^sL 7r$m Patents Form No. 5 Jfi7C;?fice NEW ZEALAND PATENTS ACT 1953 j ^ ■ £~IV£D COMPLETE SPECIFICATION "PROCESS FOR PREPARING CARBAMATE DERIVATIVES USEFUL AS INSECTICIDAL, MITICIDAL OR NEMATOCIDAL COMPOUNDS" WE, OTSUKA CHEMICAL CO., LTD a Japanese company, of No 10, Bungo-machi, Higashi-ku, Osaka-shi, Osaka, Japan, hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which is. is to be performed, to be particularly described in and by the following statement (followed by page 1A) This invention relates to a novel carbamate derivative having an insecticidal, miticidal or nematocidal activity. The invention further relates to a process for preparing the carbamate derivative using as a starting material an amincsulfehyl derivative. in the present specification, the term "insecticidal" includes "miticidal" and "nematocidal" in addition to "insecticidal", and the term "insect(s)" includes "mite(s)" and "nematode(s)" in addition to "insect(s)", respectively, unless otherwise indicated.

An arninosulf enyl. ch&oride derivative according to this invention is expressed by the formula (I): R1 ^VTyj_c_f N-S-Ci (I) 2/ 1 2 wherexn R and R , which may be the same or different, 3 each represents (1) -X-COOR , in which X represents an 3 alkylene group having 1 to 6 carbon atoms, and R repre- - 1A - 2 >r- & A sents an alkyl group having 1 to 8 carbon atoms or a cycloalkyl group having 3 to 6 carbon atoms; or (2) -Y-CN, in which Y represents an alkylene group having 1 to 6 2 carbon atoms; and R further represents an alkyl group 5 having 1 to 8 carbon atoms; a cycloalkyl group having 3 to 6 carbon atoms; a benzyl group which may be substituted with a halogen atom, an alkyl group having 1 to 3 carbon atoms or an alkoxy group having 1 to 3 carbon atoms; a phenyl group which may be substituted with a halogen atom, an alkyl group having 1 to 3 carbon atoms 4 or an alkoxy group having 1 to 3 carbon atoms; or -Z-R , in which Z represents a carbonyl gTo.up or a sulfonyl 4 group, and R represents an alkyl group having 1 to 6 carbon atoms, a phenyl group which may be substituted 15 with an alkyl group having 1 to 3 carbon atoms or a halogen atoms, an alkoxy group having 1 to 3 carbon atoms or a phenoxy group, which has not been disclosed in any literature and which has been discovered by the present inventors for the 20 first time.

In the definition for the formula (I) above, the alkyl moiety in the alkyl group, alkylene group and alkoxy group may be straight chain or branched chain.

The compound of the formula (I) is highly 25 reactive and can easily react with a group such as an -NH2 group, an -SH group, an -OH group, etc., and there- & fore, it is useful as an intermediate for various reactions. For example, the compound of the formula (I) can be reacted with 2,3-dihydro-2,2-dimethylbenzofuran-7-yl N-methyl-carbamate (hereinafter referred to as "carbo-furan", as generally called) represented by the formula CII): CII) to introduce into a 2,3-dihydro-2,2-dimethylbenzofuran-7-yl N-(N,N-disubstituted aminosulfenyl)-N-methyl-10 carbamate represented by the formula CHI) : 0 II /CH3 j OCNC ✓ R s-n; 'R2 (III) 1 2 wherein R and R are the same defined above, which is useful as an insecticide.

Carbofuran per se is known to have the highest 15 insecticidal activity heretofore known in the known carbamate compounds, but it causes problems in practical X 09 17 use due to high toxicity to warm-blooded animals. On the other hand, the compound of the formula (III) is comparable to carbofuran in insecticidal activity or controlling effect on agricultural and forestry noxious S insects and household noxious insects, with the toxicity to warm-blooded animals being as low as about 1/5 to about 1/100 the toxicity of carbofuran. Accordingly, the compound of the formula (I) is quite useful as an intermediate in the preparation of insecticides. 10 The compound of the formula (I) can be prepared by various methods, and above all, the following Methods 1 and 2 are preferred.

Method 1 The compound of the formula (I) is easily 15 obtainable by the reaction of an amine derivative represented by the formula (IV): R1 2/NH (IV) R 1 2 wherein R and R are the same as defined above, with sulfur monochloride or sulfur dichloride as illustrated 20 in the following reaction (1) or (2) .

R1 2^NH + S2C£2 > 2/N"S_CA + S * HC£ R R 2 098 R R 2^NH + SC*2 > 2^N-S-C£ + HC£ (2) R R 1 2 In the above reactions (1) and (2) , R and R are the same as defined above.

In any of the reaction (1) wherein sulfur monochloride is used and the reaction (2) wherein sulfur dichloride is used, the reaction can proceed within a short period of time, but in the reaction (1), sulfur is liberated. The reaction in both the reactions (1) and (2) proceeds under the same condition, and may be conducted in the presence or absence of a solvent. Examples of the solvent which can be used include halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, trichloroethylene, methylchloroform, etc.; ethers such as diethyl ether, dipropyl ether, dibutyl ether, tetra-hydrofuran, dioxane, etc.; hydrocarbons such as n-pentane, n-hexane, n-heptane, cyclohexane, etc.; and aromatic hydrocarbons such as benzene, toluene, xylene, chlorobenzene, etc. The proportion of the compound of the formula CIV) and sulfur monochloride or sulfur dichloride is not particularly limited but is widely variable suitably. Usually 1 to 2 moles, preferably 1 to 1.2 moles, of the latter is used per mole of the former. Preferably, the reaction is carried out in the presence of a basic compound. Examples of the basic compound which can be used include tertiary amines such as triethylamine, tributylamine, dimethylaniline, 5 diethylaniline, ethylmorpholine, etc.; and pyridines such as pyridine, picoline, lutidine, etc. The basic compound can be used in an amount sufficient to capture the hydrogen chloride to be produced by the reaction as a by-product. Usually, about 1 to about 2 moles, prefer-10 ably 1 to 1.5 moles, of the basic compound is used per mole of the compound of the formula (IV). The reaction, which proceeds with cooling, at rolSnLjtemperature- or with heating, is carried out usually at about -20 to about 50°C, preferably -10 to 30°C. The reaction time varies 15 depending upon the basic compound used, but usually is about 1 to about 2 hours.

Method 2 The compound of the formula (I) is easily obtainable by reacting the compound of the formula (IV) 20 and sulfur monochloride to form a bisaminodisulfide derivative represented by the formula (V): R 2/ N-S-S-N • R 'R (V) 2 098 2 7 1 2 wherein R and R are the same as defined above, and then chlorinating it as illustrated in the following reactions (3) and (4). r! 2 r2>H ♦ S2C<t2 > >-S-S-<;r2 ♦ 2HCi. (3) R0^.N-S-S-N^R0 Chlorxnation 2R.^N-S-CJl (4) R R > R The reaction in the reaction (3) may be conducted in the presence or absence of a solvent, or by a two-phase reaction of a solvent and water. Examples of the solvent which can be used include halogenated 10 hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, trichloroethylene, methylchloroform, etc.; ethers such as diethyl ether, dipropyl ether, dibutyl ether, tetrahydrofuran, dioxane, etc.; hydrocarbons such as n-pentane, n-hexane, n-15 heptane, cyclohexane, etc.; and aromatic hydrocarbons such as benzene, toluene, xylene, chlorobenzene, etc. In the reaction C3), the proportion of the compound of the formula (IV) and sulfur monochloride is not particularly limited but is widely variable suitably. Usually, 20 about 0.5 mole of the latter is used per mole of the former. Preferably, the reaction in the reaction (3) is carried out in the presence of a basic compound. The amine compound used as a starting material in the reaction (3) can be used as the basic compound. Other examples of the basic compound include tertiary amines such as triethylamine, tributylamine, dimethylaniline, diethylaniline, ethylmorpholine, etc.; and pyridines such as pyridine, picoline, lutidine, etc. On the other hand, when the reaction is carried out by the two-phase reaction of a solvent and water, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, etc., can be used as the_basic compound. The basic compound can be used in an amount sufficient to capture the hydrogen chloride to be produced by the reaction as a by-product. Usually, about 1 to about 10 moles, preferably 1 to 5 moles, of the basic compound is used per mole of the compound of the formula (IV). The reaction, which proceeds with cooling, at room temperature or with heating, is carried out usually at about -20 to about 50°C, preferably -10 to 30°C. The reaction time varies depending upon the basic compound used, but usually is about 1 to about 2 hours. The thus pbtained bisaminodisulfide derivative of the formula (V) can be purified and then used, or the reaction solution can be washed with water, dried and then used in the sequent reaction as it is. 2098 2 7 The reaction in the reaction (4) may be conducted in the presence or absence of a solvent. Any of the solvents which are useful in the reaction (3) can be used. Examples of a chlorinating agent which 5 can be used include chlorine, sulfuryl chloride, etc. The proportion of the compound of the formula (V) and the chlorinating agent is not particularly limited but is widely variable suitably. Usually, about 0.5 to about 5 moles, preferably 0.5 to 1.5 moles, of the latter is 10 used per mole of the former. The reaction, which proceeds with cooling, at room temperature or with heating, is carried out usually at about_-20 to about 50°C, preferably -10 to 30°C. The reaction completes within about one to about 2 hours.

The amine compounds of the formula CIV) are known compounds.

Examples of useful amine compounds of the formula CIV) are those secondary amines represented by the formulae CVI) to 00 : .X-COOR3 HN^ (VI) NR /Y-CN HN CVII) R .X-COOR3 HN (VIII) ^X"-COOR ^X-COOR3 HN CIX) ^Y-CN /Y-CN HN (X) Y"-CN In the formulae CVI) to QO, X, Y and R3 are as defined above; R represents an alkyl group having 1 to 8 carbon atoms; a cycloalkyl group having H to 6 carbon atoms; a benzyl group which may be substituted with a halogen atom, an alkyl group having 1 to 3 carbon atoms or an alkoxy group having 1 to 3 carbon atoms; a phenyl group which may be substituted with a halogen atom, an alkyl group having 1 to 3 carbon atoms or an alkoxy group 4' having 1 to 3 carbon atoms; or Z'-R , in which Z1 represents a carbonyl group or a sulfonyl group, and 4' R represents an alkyl group having 1 to 6 carbon atoms, a phenyl group, a benzyl group, an alkoxy group having 1 to 6 carbon atoms or a phenoxy group (in which the alkyl group and alkoxy gToup may be straight or 3" 3 branched chain) ; R has the same meaning as in R ; X" has the same meaning as in X; and Y" has the same meaning as in Y.

Representative examples of the amine compound of the formula (VI) are N-methylglycine methyl ester, N-methylglycine ethyl ester, N-methylglycine butyl esterj N-ethylglycine ethyl ester, N-n-propylglycine ethyl ester, N-isopropylglycine ethyl ester, N-n-butylglycine ethyl ester, N-isobutylglycine ethyl ester, N-sec-butyl-glycine ethyl ester, N-n-octylglycine ethyl ester, N-cyclohexylglycine ethyl ester, N-benzylglycine ethyl ester, N-(4-methylbenzyl)glycine ethyl ester, N-(4-chlorobenzyl)glycine ethyl ester, N-phenylglycine ethyl ester, N-(3-methylphenyl)glycine ethyl ester, N-(4-methoxyphenyl)glycine ethyl ester, N-methoxycarbonyl-glycine ethyl ester, N-ethoxycarbonylglycine methyl ester, N-ethoxycarbonylglycine ethyl ester, N-ethoxy-carbonylglycine phenyl ester, N-phenoxycarbonylglycine ethyl fester, ethyl N-methylaminopropionate, ethyl N-n-propylaminopropionate, methyl N-isopropylaminopropionate ethyl N-isopropylaminopropionate, butyl N-isopropylaminopropionate, 2-ethylhexyl N-isopropylaminopropionate methyl N-n-butylaminopropionate, ethyl N-n-butylamino-propionate, ethyl N-isobutylaminopropionate, ethyl N-sec-butylaminopropionate, ethyl N-t-butylaminopropionate ethyl N-n-amylaminopropionate, ethyl N-isoamylamino-propionate, ethyl N-n-hexylaminopropionate, ethyl N- cyclohexylaminopropionate, ethyl N-ethoxycarbonylamino-propionate, N-acetylglycine ethyl ester, N-chloro-acetylglycine ethyl ester, N-propionylglycine ethyl ester, N-benzoylglycine ethyl ester, N-(4-chlorobenzoyl) glycine ethyl ester, N-tosylglycine ethyl ester, etc.

Representative examples of the amine compound of the formula CVII) are N-methylaminoacetonitrile, N-ethylaminoacetonitrile, N-n-propylaminoacetonitrile, N-isopropylaminoacetonitrile, N-n-butylaminoacetonitrile, N-isobutylaminoacetonitrile, N-benzylaminoacetonitrile, N-phenylaminoacetonitrile, N- C4-methylphenyl)amino-acetonitrile, N-methylaminopropionitrile, N-n-propyl-aminopropionitrile, N-isopropylaminopropionitrile, N-n-butylaminopropionitrile, N-isobutylaminopropionitrile, N-sec-butylaminopropionitrile, N-ocylaminopropionitrile, N-cyclohexylaminopropionitrile, methyl N-cyanomethyl-carbamate, ethyl N-cyanomethylcarbamate, ethyl N-cyano-ethylcarbamate, etc.

Representative examples of the amine compound of the formula CVIII) are methyl iminodiacetate, ethyl iminodiacetate, isopropyl iminodiacetate, butyl iminodiacetate, pentyl iminodiacetate, hexyl iminodiacetate, cyclopropyl iminodiacetate, cyclopentyl iminodiacetate, cyclohexyl iminodiacetate, methyl iminodipropionate, 2098 2 7 ethyl iminodipropionate, ethyl N-ethoxycaTbonylmethyl-aminopropionate, ethyl 4-(ethoxycarbonylmethylamino)-butyrate, ethyl-2-(pthoxycarbonylmethylamino)butyrate, etc.

Representative examples of the amine compound of the formula (IX) are N-cyanomethylglycine ethyl ester, N-cyanoethylglycine ethyl ester, ethyl N-cyano-methylaminopropionate, ethyl N-cyanoethylaminopropionate, etc.

Representative examples of the amine compound of the formula (X) are iminodiacetonitrile, iminodi-propionitTile, iminodibutyronitrile, etc.

The aminosulfenyl chloride derivative of the formula (I) can be prepared in any of the above-described Methods 1 and 2. However, its preparation may be selected by the kind of the amine compound of the formula (IV) .

For example, when the amine compound is represented by 4' the formula (VI) or (VII) wherein R represents Z'-R , Method 2 is preferable. With respect to other amine compounds, there is no substantial difference between Method 1 and Method 2.

Typical of the compounds of the formula (I) are those as described in Examples 1 to 34 set forth hereinafter.

The reaction between the compound of the formula (I) and the compound of the formula CH) may be conducted in the presence or absence of a solvent. Examples of the solvent which can be used include halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, trichloroethylene, methyl-chloroform, etc.; and ethers such as diethyl ether, dipropyl ether, dibutyl ether, tetrahydrofuran, dioxane, etc. The proportion of the compound of the formula CH) and the compound of the formula CI) is not particularly limited but is widely variable suitably. Usually, about 1 to about 2 moles, preferably 1 to _1_.2 moles, of the latter is used per mole of the former. Preferably, the reaction is carried out in the presence of a basic compound. Examples of the basic compound which can be used include tertiary amines such as triethylamine, tributylamine, dimethylaniline, diethylaniline, ethyl-morpholine, etc.; and pyridines such as pyridine, picoline, lutidine, etc. The basic compound can be used in an amount sufficient to capture the hydrogen chloride to be produced by the reaction as a by-product. Usually, about 1 to about 10 moles, preferably 1 to 5 moles, of the basic compound is used per mole of the compound of the formula CII)• The reaction, which proceeds with cooling, at room temperature or with heating, is carried 209827 out usually at about -20 to about 50°C, preferably 0 to 40°C. The reaction time varies depending upon the kind and amount of the basic compound used, etc., but usually is about 1 to about 20 hours.

The compound of the formula CHI) thus-obtained can be easily isolated and purified by a usual method of separation, such as solvent extraction, recrystallization or column chromatography.

Typical of the compounds of the formula CHI) 10 are those as described in Examples 35 to 42 set forth hereinafter.

The compounds of the fofHiuLa CHI) have outstanding insecticidal activity or controlling effect on agricultural and forestry noxious insects and house-15 hold noxious insects and are comparable in such effect to carbofuran which has the highest insecticidal activity heretofore known. These compounds are effective on a wide variety of noxious insects, mites and nematodes which are harmful to vegetables, trees, other plants and 20 man, such as Hemiptera, Lepidoptera, Coleoptera, Diptera, Thysanoptera, Orthoptera, Isopoda, Acarina, Tylenchida, etc.

The toxicity of the compounds of the formula CHI) to warm-blooded animals is as low as about 1/5 to 25 about 1/100 the toxicity of carbofuran. These compounds 09S ? exhibit insecticidal activity or controlling effect on the above-mentioned organisms in any stage or a specific stage of their growth and are therefore effectively usable for controlling them in the fields of agriculture, forestry and sanitation.

In practical uses, the compounds of the formula CIII) are formulated into various forms, such as an emulsion, wettable powder, suspension, concentrated suspension, granule, fine particle, pellet, dust, coating composition, foam spray, aerosol, microcapsule composition, impregnant to be applied to a natural or synthetic material, fumigant, concentrated preparation to-be applied in a small amount, etc.

The following Examples 1 to 34 will explain in greater detail the preparation of the compound of the formula CI) • EXAMPLE 1 Preparation of BisCethoxycarbonylmethyl)aminosulfenyl Chloride 2.1 g CO.02 mole) of sulfur dichloride was dissolved in 35 m£ of carbon tetrachloride, and 1.6 g CO.02 mole) of pyridine was dropwise added to the resulting solution at 0 to 5°C. After completion of the dropwise addition, 3.8 g (0-02 mole) of ethyl iminodiacetate was further dropwise added thereto at 10 to 209 °C, and the resulting mixture was stirred for one hour at the same temperature. After completion of the reaction, crystals were filtered off, and the mother liquor was concentrated under reduced pressure to obtain an oily product. Yield: 5.0 g (98$).

The NMR in CDCi^ of this oily product is as follows: 6 1.28 ppm (t, 6H), 6 4.18 ppm (q, 4H), 6 4.28 ppm (s, 4H) The IR absorption spectrum showed absorption 0 -1 H p. -1 peaks at 1750. cm for -C- and 76^ cm for -S-C£, respectively.

Thus, the product was confirmed to have the following formula: 0 II Hr C~0CCH7 ^ 3 L L .N-S-C£ HcC_OCCH~ . 5 2 II 2 0 EXAMPLE 2 Preparation of Bis(ethoxycarbonylmethyl)aminosulfenyl Chloride 2.7 g (0.02 mole) of sulfur monochloride was dissolved in 35 m£ of methylene chloride, and 1.6 g (0-02 mole) of pyridine was dropwise added to the result- ■A T< "i) =5? - (j ing-solution at 0 to 5°C. After completion of the dropwise addition, 3.8 g CO.02 mole) of ethyl iminodiacetate was further dropwise added thereto at 10 to 20°C, and the resulting mixture was stirred for one hour at the same temperature. After completion of the reaction, crystals were filtered off, and the mother liquor was concentrated under reduced pressure to obtain an oily product. Yield: 4.9 g (96%).

This oily product was the same as that obtained in Example 1.

EXAMPLE 3 Preparation of BisCisopropoxycarbenylmethyl)aminosulfenyl Chloride 2.1 g CO.02 mole) of sulfur dichloride was dissolved in 35 mJl of carbon tetrachloride, and 1.6 g CO.02 mole) of pyridine was dropwise added to the resulting solution at 0 to 5°C. After completion of the dropwise addition, 4.3 g CO-02 mole) of isopropyl iminodiacetate was further dropwise added thereto at 10 to 20°C, and the resulting mixture was stirred for one hour at the same temperature. After completion of the reaction, crystals were filtered off, and the mother liquor was concentrated under reduced pressure to obtain an oily product. Yield: 5.5 g C97%).

The NMR in CDCfc^ of this oily product is as follows: 709327 ' 6 1.26 ppm (d, 12H), 6 4.20 ppm (s, 4H), 6 5.09 ppm (m, 2H) The IR absorption spectrum showed absorption 0 -i « -i peaks at 1745 cm for -C- and 770 cm for -S-C£, respec- tively.

Thus, the product was confirmed to have the following formula: 0 H-C^ || ° .HCOC H,C * "N-S-CA HsC>coc/' H,C II 0 0 EXAMPLE 4 Preparation of Bis(methoxycarbonylmethyl)aminosulfenyl Chloride The same procedure as in Example 1 was repeated except that methyl iminodiacetate was used in place of ethyl iminodiacetate. Thus, the titled compound in an 15 oily state was obtained.

The NMR in CDCH^ of this compound is as follows 6 3.78 ppm Cs, 6H), 6 4.29 ppm (s• 4H) 2-09 2 EXAMPLE 5 Preparation of Bis(cyclohexyloxycarbonylmethyl)amino-sulfenyl Chloride The same procedure as in Example 1 was repeated except that cyclohexyl iminodiacetate was used in place of ethyl iminodiacetate. Thus, the titled compound in an oily state was obtained.

The NMR in CDCi^ of this compound is as follows 6 1.0-2.2 ppm Cm, 20H), 6 4.25 ppm (s, 4H), 6 4.6-5.2 ppm G&, 2H) EXAMPLE 6 Preparation of N - Ace ty l-N-ethoxycdTbojiylme thy 1 amino -sulfenyl Chloride 2.7 g ((K02 mole) of sulfur monochloride was dissolved in 50 mfi, of carbon tetrachloride, and 2.9 g CO.02 mole) of N-acetylglycine ethyl ester was dropwise added to the resulting solution at 0 to 5°C. After completion of the dropwise addition, 2.4 g (0.024 mole) of triethylamine was further dropwise added thereto at the same temperature, and the resulting mixture was stirred for one hour at the same temperature. After completion of the reaction, crystals were filtered off, and the mother liquor was concentrated under reduced pressure to obtain an oily product. Yield: 3.8 g (90.5%) The NMR in CDCs,^ of this oily product is as follows: 209327 6 1.24 ppm (t, 3H) , 6 4.14 ppm (q, 4H), 6 2.52 ppm (s, 3H), 6 4.38 ppm (s, 2H) Thus, this oily product was confirmed to have the following formula: /CH7C00C7H,.

CJ>-S-N^ L L * COCHj EXAMPLE 7 Preparation of N-Methoxycarbonyl-N-ethoxycarbonylmethyl-aminosulfenyl Chloride 2.1 g (0.02 mole) of sulfur dichloride was dissolved in 50 mJt of carbon tetrachloride, and 1.6 g (0.02 mole) of pyridine was dropwise added to the resulting solution at 0 to 5°C. After completion of the drop-wise addition, 3.2 g (0.02 mole) of N- glycine ethyl ester was further dropwise added thereto at 10 to 20°C, and the resulting mixture was stirred for one hour at the same temperature. After completion of the reaction, crystals were filtered off, and the mother liquor was concentrated under reduced pressure to obtain an oily product. Yield: 4.2 g (93.3%).

The NMR in CDCJlj of this oily product is as follows: X09P7J * 6 1.27 ppm Ct, 3H), 6 3.79 ppm O, 3H) , 6 4.16 ppm Cq» 2H) , 6 4.35 ppm (s, 2H) The NMR analysis showed that the oily product contained small amounts of the starting materials and 5 bisaminosulfide, but confirmed it to have the following formula: ^CH COOC-H,.

C£-S-N Z 1 5 ^cooch3 EXAMPLE 8 Preparation of N-n-Butyl-N-ethoxycarbonylethylamino-10 sulfenyl Chloride 1.4 g CO-01 mole) of sulfur monochloride was dissolved in 50 m£ of carbon tetrachloride, and to the resulting solution were dropwise added successively 3.5 g CO.02 mole) of ethyl N-butylaminopropionate and 2 g 15 CO.02 mole) of triethy1amine at 0 to 5°C. After completion of the dropwise addition, the resulting mixture was stirred for one hour, and the reaction solution was washed with 50 mJl of water three times. The carbon tetrachloride layer was dried over sodium sulfate and 20 subjected to filtration, and the carbon tetrachloride solution was again cooled to 0°C with stirring. After the cooling, 1.4 g (0.01 mole) of sulfuryl chloride was 20982 dropwise added thereto under cooling and stirred for one hour at the same temperature. The reaction solution was concentrated under reduced pressure to obtain an oily product. Yield: 4.5 g (93.8%).

The NMR in CDC£j of this oily product is as follows: 6 0.7-2.0 ppm (m, 7H) , 6 1.26 ppm (t, 3H), 6 2.70 ppm (t, 2H) , 6 3.25 ppm (t, 2H), 6 3.43 ppm (t, 2H) , 6 4.08 ppm (q, 2H) The NMR analysis showed that this ouly product contained a small amount of bisaminodisulfide, but confirmed it to have the following formula: /CH?CH7C00C7H, Cfc-S-N L L L * CH -CH-.CH-CH, EXAMPLE 9 Preparation of N-Isopropyl-N-ethoxycarbonylethylamino-sulfenyl Chloride 3.2 g CO.02 mole) of ethyl N-isopropylaminopropionate was dissolved in 30 mH of n-hexane, and 50 mi. of a 5% sodium hydroxide aqueous solution was added 20 thereto. After cooling the mixture to 5°C, a solution of 1.4 g (0.01 mole) of sulfur monochloride dissolved in 50 mil of n-hexane was dropwise added thereto, and the n) v £ resulting solution was stirred for one hour at the same temperature. After completion of the reaction, the n-hexane layer was separated, washed with water, and then dried. The n-hexane layer was again stirred under cooling, and 1.4 g CO-01 mole) of sulfuryl chloride was drop-wise added thereto, followed by stirring for one hour. The n-hexane was concentrated under reduced pressure to obtain an oily product. Yield: 4.1 g C91%) • The NMR in CDCfc^ of this oily product is as follows: 6 1.23 ppm Ct, 3H) , 6 1.26 ppm Cd, 6H) , 6 2 .77 ppm Ct, 2H) , 6 3t0;3.8 ppm (m,-3H), 6 4.06 ppm Cq> 2H) .

The NMR analysis showed that this oily product contained a small amount of bisaminodisulfide, but confirmed it to have the following formula: ^ch2CH2COOC2H5 cs,-s-n^ rh . / 3 ch 5 •ch3 EXAMPLES 10 TO 34 The compounds shown in Table 1 below were prepared in the same manner as in Examples 6 to 9. The NMR data Cin CDC£j) of these compounds are also shown in Table 1.

TABLE 1 Example No.

Structure NMR (In CDC&3) ppm ca-s-n ,ch2cooc2h5 'ch2ch2ch2ch3 6 0.7-2.0 Cm, 7H), 6 1.29 (t, 3H), 6 3.31 (t, 2H), 6 4.05 (s, 2H), 6 4.16 (q, 2H) 11 ca-s-n ,ch2cooc2h5 CH. 6 1.26 (t, 3H), 6 2.34 (s, 3H), 6 4.13 (q, 2H), 6 4.59 (s, 2H), 6 6.9-7.5 (m, 4H) 12 CH2COOC2H^ ca-s-n N^>OCH3 6 1.18 Ct, 3H), 6 3.67 (s, 3H), 6 4.08 (q, 2H), 6 4.46 (s, 2H), 6 6.9-7.5 (m, 4H) 13 ca-s-n ,ch2cooc2h5 'c0ch2ch3 6 1.-1-9 (t, 3H), 6 1.29 Ct, 3H), 6 2.96 (t, 2H), 6 4.23 (q, 2H), 6 4.39 (s, 2H) 14 ca-s-n ^CH2cooc2H5 \oh^3 6 1.29 (t, 3H), 6 4.19 (q, 2H), 6 4.53 (s, 2H), 6 7.1-7.8 (m, 5H) cjl-s-n ^,CH2cooc2H5 so, 6 1.26 (t, 3H), 5 2.45 (s, 3H), 6 4.16 (q, 2H), 6 4.38 (s, 2H), 6 7.2-8.0 (m, 4H) 16 ci-s-n .ch2cooc2h5 *cooch_ 6 1.28 (t, 3H), 6 3.81 (s, 3H), 6 4.17 (q, 2H), 6 4.36 (s, 2H) 17 ca-s-n ,CH2cooc2H5 kCOOC2H5 6 1.27 (t, 3H), 6 1.33 (t, 3H), 6 4.16 (q, 2H), 6 4.25 (q, 2H), 6 4.39 (s, 2H) (cont'd) - 9Z ~ (P.^uoo) EH:)\ 7 (HV *m) 9'£-S6*Z 9 r HO HO (HZ 9 '(HZ '3) *£*Z 9 HOT \ '(HI '*) 3-3-9*1 9 N-S-70 S3 (He '3) VE'T 9 '(H9 'P) £8'0 9 H 3000 HO HO (HE 's) 85*E 9 '(HZ *5) 9£*£ 9 EHOZHOZHOZHO (HZ *5) ii*e 9 '(HZ '3) Z9*Z 9 ^N-S-*0 *Z '(HZ 'm) O'Z-Z'O 9 HOOOO HO HO £h3\ (HZ *b) 90't7 9 f HO ' (HE '*) g-e-O'E 9 bH3^ \ '(HZ 'a) U'Z 9 C 7 7 7 /"S 73 " (H9 *P) 9Z'T 9 '(HE '3) EZ'T 9 H 0000 HO HO (H3 'b) 90* V 9 ' (H3 *3) IY £ 9 (HZ '3) OZ'E 9 * (HZ *3) 89*Z 9 H06H0CH0^ '(HZ '®) Z'Z-VT 9 c N-S-70 ZZ (he *3) <7z*t 9 '(he '3) £6*0 9 ^0000 ho^ho^ E Z Z Z _ HO HO HO HO (HZ *s) S0*V 9 '(HZ *3) ZZ'E 9 ^N-S-70 TZ *(H£ 'm) O'Z-Z'O 9 NO£HO E (HZ *s) Z£** 9 HO \ '(HI '*) 6*£-£*£ 9 _ > '(H9 'P) EE'T 9 NO HO (HZ 'b) 9Z*^ 9 NO^HO^HO^ (HZ 's) OZ'V 9 '(HZ *3) S9*£ 9 c ? N-S-70 61 (HZ '3) 68*Z 9 '(HE '3) OE'T 9 H 0000 HO (HZ *s) 89 llu^oz N-S-70 OZ (HS •-») rt-fi 9 W \.s.„ 8I <^j)-ooo.

(HZ 'b) ST** 9 '(HE *3) OE'T 9 H 0000 HO mdd (E?300 UI) HHN ilruonUg ' roS aXdiuBX-j - LZ - (hs '*) s*z-o**9 (hz *b) 4 (hz *5) s£*£j (hz '}) ZL'Z 9 ' (h£ '}) *z*i9 (H* '®) 8*£-0*£9 '(HZ 'b) n'*l 9 (HZ 's) T0*«7 9 '(HZ '^) ££*£ 9 (HZ '}) *£-Z 9 ' (H£ 'l) <7Z*I 9 O-n SHZDOODZHDZHD^ N-S-?3 73"C^~< hd \ sHzOOOD3hdzHD''' n-s-'jd *lZ ££ (HS '°0 S*£-6*9 9 4 (HZ 'b) 9r* 9 (HZ 's) <76*£ 9 ' (HZ *5) S£"£ 9 (HZ '5) S£*Z 9 '(H£ *3) 9Z*I 9 hd. \ gH3DOODZHDZHD/' k-s--5d z£ (HV '5) 89*£ 9 *(HV *3) <76'Z 9 NDZHD3HD^ ndzhdzhdx' n-s-7d IE (HZ *1) £S*E 9 (HZ *5) S8*Z 9 *(H6 's) S£*I 9 e(CHD)3> nd3hd3hd' n-s-tfd oe (HZ '5) 6£*£ 9 '(H* 'ra) Z*£-S"Z 9 '(HI *m) S"Z-£"I 9 '(H9 'P) 16*0 9 HD\ Z hd hd* hd \ n-s-id NDZHD3H3^ 6Z (HZ 'b) 90*V 9 '(H£ '«0 S*£-8*Z 9 (HZ *3) S9"Z 9 ' (H£ '*) *Z*I 9 '(HOI '®) Z*Z-8*0 9 <zx SHZDOODZHDZHDy/' N-S^JTD 8z (HZ «b) ZO'V 9 '(HZ *3) 6£"£ 9 (HZ '}) 6I*£ 9 '(HZ '3) Z9*Z 9 '(HOT '*) 0"Z~9*0 9 £h3zh33hd3h3zhdzhd> 5hzdoodzhdzhd^ m-s-tfd LZ (hz 'b) vi* ^ 9 (hz '*) £s*£ 9 '(hz '!) 9i*z 9 (H6 's) 6£*I 9 '(H£ '*) 9Z*I 9 g(ehd)d, 5hzdoodzhdz:hd/ n-s-7d 9Z mdd (E-JOaD Uf) HHM axn^otu^S •on axdnrexa LZSbQZ The following Examples 35 to 42 will explain in greater detail the preparation of the compound of the formula (III).

EXAMPLE 35 Preparation of 2,3-Dihydro-2,2-dimethylbenzofuran-7-yl N-[N,N-Bis (ethoxycarbonylmethyl) aminosulfenyl] -N-methyl-carbamate 4.4 g (0.02 mole) of 2,3-dihydro-2,2-dimethyl-benzofuran-7-yl N-methyl-carbamate, 5.1 g (0.02 mole) of bis(ethoxycarbonylmethyl)aminosulfenyl chloride obtained in Example 1 or 2, and 4.7 g (0.06 mole) of pyridine were dissolved in 35 mi, of methylene chloride, and the resulting solution was stirred for 30 hours at 30 to 35°C. After completion of the reaction, the reaction solution was washed successively with water, diluted hydrochloric acid and water. The methylene chloride layer was dried over sodium sulfate and concentrated under reduced pressure to obtain an oily product.

Yield: 7.5 g (85.2%).

For the identification of the product, a portion thereof was purified by silica gel column chromatography, using benzene/ethyl acetate (4:1) as the elution solvent, whereby an oily product was obtained. nmr in cdc£3: 6 1.24 ppm (t, 6H) , 6 1.48 ppm (s, 6H), 6 3.02 ppm (s, 2H) , 6 3.42 ppm (s, 3H), 6 4.20 ppm (q> 4H) , 6 4.28 ppm (s, 4H) , 6 6.6-7.2 ppm (m» 3H) Elemental Analysis: H N Found C%): 54.49 6.47 6.40 Calcd. for C2()H28N207S: 54.53 6.41 6.36 (molecular wt. 440.53) Thus, the product was confirmed to have the following formula: — 0 0 II /CH || OCN^ ^CH-COC-jH,.

S_N^ * * xh2coc2h5 0 example 36 Preparation of 2,3-Dihydro-2,2-dimethylbenzofuran-7-yl s.

N- [N,N-Bis (isopropoxycarbonylmethyl)aminosulfenyl] -N-methyl-carbamate 4.4 g CO.02 mole) of 2,3-dihydro-2,2-dimethyl-benzofuran-7-yl N-methyl-carbamate, 5.7 g CO.02 mole) of bis Cisopropoxycarbonylmethyl)aminosulfenyl chloride obtained in Example 3, and 4.7 g (0.06 mole) of pyridine vere dissolved in 30 mJl of chloroform, and the resulting solution was stirred for 30 hours at 30°C. After completion of the reaction, the reaction solution was washed successively with water, diluted hydrochloric acid and water. The chloroform layer was dried over sodium sulfate and concentrated under reduced pressure to obtain an oily product which was almost entirely composed of the desired product although containing small amounts of the starting materials and impurities. Yield: 7.9 g C84.0%). portion thereof was purified by silica gel column chromatography, using benzene/ethyl acetate (4:1) as the elution solvent, whereby an oily product was obtained. NMR in CDCJl3: For the identification trf_ the product-, a 6 1.23 ppm (d, 6H) , 6 1.46 ppm (s, 6H), 6 3.03 ppm (s, 2H) , 3.42 ppm (s, 3H), 6 4.26 ppm (s, 4H) , 6 5.08 ppm (m, 1H), <5 6.6-7.2 ppm (m, 3H) Elemental Analysis: C H N Found (%) 56.35 6.91 5.86 Calcd. for C^H^N^S: 56.40 6.89 5.98 (molecular wt. 468.49) Thus, the product was confirmed to have the following formula: II OCN 0 3 3 3 3 0 EXAMPLE 37 Preparation of 2 ,3-Dihydro-2,2-dimethylbenzofuran-7-yl N- [N,N-Bis(methoxycarbonylmethyl)aminosulfenyl] -N-methyl-carbamate repeated except that bis(methoxycarbonylmethyl)aminosulfenyl chloride as obtained in Example 4 was used in place of bis(ethoxycarbonylmethyl)aminosulfenyl chloride. Thus, an oily product was obtained.

NMR in CDCJl^: The same procedure as in Example 35 was 6 1.47 ppm (s, 6H) 6 3.41 ppm Cs, 3H) 6 4.30 ppm Cs, 4H) 6 3.02 ppm Cs, 2H) 6 3.73 ppm Cs, 6H), 6 6.7-7.2 ppm (m, 3H) A 209827 Elemental Analysis: H n Found (!): Calcd. for : 52.11 5.91 6.63 52.42 5.87 6.79 (molecular wt. 412.47) Thus, the product was confirmed to have the following formula: 0 II ch2coch3 ch-coch, II 3 _ 0 EXAMPLE 38 Preparation of 2,3-Dihydro-2,2-dimethylbenzofuran-7-yl N- [N,N-Bis Ccyclohexyloxycarbonylmethyl)aminosulfenyl] -N-methyl-carbamate The same procedure as in Example 35 was repeated except that bis(cyclohexyloxycarbonylmethyl)-15 aminosulfenyl chloride as obtained in Example 5 was used in place of bis(ethoxycarbonylmethyl)aminosulfenyl chloride. Thus, an oily product was obtained.

NMR in CDCfc3: 6 1.0-2.2 ppm (m, 20H), 6 1.48 ppm (s, 6H), 20 6 3.02 ppm (s, 2H), ; 6 3.43 ppm (s, 3H), 6 4.28 ppm Cs, 4H), 6 4.5-5.1 ppm Cm, 2H) , 6 6.7-7.2 ppm Cm, 3H) Elemental Analysis: h n Found C%): 61.32 7.39 4.95 Calcd. for C2gH4()N207S: 61.29 7.35 5.11 Cmolecular wt. 548.71) Thus, the product was confirmed to have the following formula: 0 h3c h,c EXAMPLE 39 Preparation of 2,3-Dihydro-2,2-dimethylbenzofuran-7-yl N - [N,N-Bis Ccyanoethyl) aminosulfenyl] -N-methyl - carbamate 4.4 g CO.02 mole) of 2,3-dihydro-2,2-dimethyl-benzofuran-7-yl N-methyl-carbamate, 3.8 g (0.02 mole) of bisCcyanoethyl)aminosulfenyl chloride obtained in Example 31, and 4.7 g CO.06 mole) of pyridine were dissolved in 35 mj, of methylene chloride, and the resulting solution vas stirred for 20 hours at 25 to 30°C. After completion "•'x (o) c'~'. of the reaction, the reaction solution was washed successively with water, diluted hydrochloric acid and water. The methylene chloride layer was dried over sodium sulfate and concentrated under reduced pressure 5 to obtain an oily product which was almost entirely composed of the desired product although containing small amounts of the starting materials and impurities. Yield: 6.2 g (82.7%).

For the identification of the product, a 10 portion thereof was purified by silica gel column chromatography, using benzene/ethyl acetate (4:1) as the elution solvent, whereby an oxlyproduct was obtained.

NMR in CDC*3: 6 1.43 ppm (s, 6H), 6 2.73 ppm (t, 4H), 6 2.97 ppm (s, 2H), 6 3.37 ppm (s, 3H), 6 3.43 ppm Qt, 4H), 6 6.5-7.2 ppm (m, 3H) Elemental Analysis: C H N Found (%): 57.84 5.81 15.06 Calcd. for C18H22N4°3S: 57-73 5-92 14.96 (molecular wt. 374.472) Thus, the product was confirmed to have the following formula: 2098 27 o 1 ,/CH3 OCN^ - .CH-CH-CN S-N^ 1 L xh2CH2CN */ EXAMPLE 40 Preparation of 2,3-Dihydro-2,2-dimethylbenzofuran-7-yl N- CN-n-Butyl-N-ethoxycarbonylethylaminosulfenyl) -N-5 methyl-carbamate 2.2 g (0.01 mole) of 2,3-dihydro-2,2-dimethyl-benzofuran-7-yl N-methyl-carbamate and 2.4 g (0.01 mole) of N-n-butyl-N-ethoxycarbonylethylanrrnosulfenyl chloride as obtained in Example 8 were dissolved in 30 m£ of 10 methylene chloride, and the solution was cooled to 0°C. 1.2 g (0.012 mole) of triethylamine was dropwise added thereto with stirring, and allowed to react for 2 hours at the same temperature. After completion of the reaction, the reaction solution was washed successively 15 with water, diluted hydrochloric acid and water. The methylene chloride layer was dried and concentrated undeT reduced pressure to obtain an oily product which was almost entirely composed of the desired product although containing small amounts of the starting materials and 20 impurities. 7 ?) ^ i/., ^ // For the identification of the product, a portion thereof was purified by silica gel column chromatography, using benzene/ethyl acetate (10:1) as the elution solvent, whereby an oily product was 5 obtained.

NMR in CDCJl^: 6 0.7-1.8 ppm (m, 10H), 6 1.41 ppm (s, 6H), 6 2.4-2.8 ppm (m, 2H), 6 2.95 ppm (s, 2H), 6 3.33 ppm (s, 3H), 6 3.1-3.4 ppm (m, 4H), 6 3.97 ppm (q, 2H), 6 6.6-7.2 ppm (m, 3H) Elemental Analysis: C~ __ H N- Found (%): 59.01 7.38 6.79 Calcd. for C2]H32N205S: 59.42 7.60 6.60 (molecular wt. 424.569) Thus, the product was confirmed to have the following formula: O h3c CH2CH2COOC2H5 CH2CH2CH2CH3 2 7 EXAMPLE 41 Preparation of 2,3-Dihydro-2 ,2-dimethylbenzofuran-7-yl N- (N-1 sopropyl-N-cyanoe thyl aminosulfenyl) -N-me thyl -carbamate 2.2 g (0.01 mole) of 2,3-dihydro-2,2-dimethyl-benzofuran-7-yl N-methyl-carbamate and 1.8 g (0.01 mole) of N-isopropyl-N-cyanoethylaminosulfenyl chloride were dissolved in 30 m£ of methylene chloride, and the solution was cooled to 0°C. 1.2 g (0.012 mole) of triethylamine was dropwise added thereto with stirring, and allowed to react for 2 hours at the same temperature. After completion of the reaction, the reaction solution was washed successively with water, diluted hydrochloric acid and water. The methylene chloride layer was dried and concentrated under reduced pressure to obtain an oily product which was almost entirely composed of the desired product although containing small amounts of the starting materials and impurities.

For the identification of the product, a portion thereof was purified by silica gel column chromatography, using benzene/ethyl acetate (10:1) as the elution solvent, whereby an oily product was obtained.

NMR in CDC£3: 6 1.21 ppm (d, 6H), 6 1.43 ppm (s, 6H), 6 2.72 ppm (t, 2H), 6 3.00 ppm (s, 2H), 2 09 6 3.0-3.8 ppm (m, 3H) , 6 3.32 ppm (s, 3H), 6 6.6-7.2 ppm (m, 3H) Elemental Analysis: C H N Found (%): 59.55 6.74 11.84 Calcd. for C18H25N303S: 59.49 6.93 11.56 (molecular wt. 363.488) Thus, the product was confirmed to have the following formula: Preparation of 2,3-Dihydro-2,2-dimethylbenzofuran-7-yl N-(N-Ethoxycarbonyl-N-ethoxycarbonylmethylaminosulfenyl)-N-methyl-carbamate benzofuran-7-yl N-methyl-carbamate, 2.4 g (0.01 mole) of N-ethoxycarbonyl -N-ethoxycarbonylmethylaminosulfenyl chloride obtained in Example 17, and 3.2 £ (0.04 mole) of pyridine were dissolved in 30 mj, of chloroform, and the resulting solution was stirred for 24 hours at 20 to 0 EXAMPLE 4 2 2.2 g (0.01 mole) of 2,3-dihydro-2,2-dimethyl- 2 °C. After completion of the reaction, the reaction solution was washed successively with water, diluted hydrochloric acid and water. The chloroform layer was dried and concentrated under reduced pressure to obtain an oily product which was almost entirely composed of the desired product although containing small amounts of the starting materials and impurities.

For the identification of the product, a portion thereof was purified by silica gel column chromatography, using benzene/ethyl acetate (4:1) as the elution solvent, whereby an oily product was obtained. — NMR in iCDCA^-ic-r^-c 6 1.17 ppm Ct, 6H) , 6 1.44 ppm (s, 6H), 6 2.94 ppm Cs, 2H) , 6 3.41 ppm Cs, 3H) , 6 4.05 ppm C<1» 2H) , 6 4.15 ppm Cq» 2H) , 6 4.41 ppm Cs, 2H) , 6 6.5-7.0 ppm (m, 3H) Elemental Analysis: H N Found (%): 53.46 6.31 6.39 Calcd. for C19H26N2O7S: 53.51 6.14 6.57 (molecular wt. 426.499) Thus, the product was confirmed to have the following formula: Z 09g 0 II /CH 3/ch2cooc2h ocn ^COOC2H5 While the invention has been described in detail and with reference to specific embodiments thereof, it will be apparent to one skilled in the art 5 that various changes and modifications can be made therein without departing from the spirit and scope thereof. 209827

Claims (7)

WHAT WE CLAIM IS:

1. A process for preparing a 2,3-dihydro-2,2-dimethylbenzofuran-7-yl N-(N,N-disubstituted aminosulfenyl ) -N-methyl-carbamate represented by the formula (iii): o (III) 1 2 wherein R and R , which may be the same or different, 3 each represent (1) -X-COOR , in which X represents an 3 alkylene group having 1 to 6 carbon atoms, and R represents an alkyl group having 1 to 8 carbon atoms or a cycloalkyl group having 3 to 6 carbon atoms; or (2) -Y-CN, in which Y represents an alkylene group having 1 to 6

2 carbon atoms;-and R further represents an alkyl group having 1 to 8 carbon atoms; a cycloalkyl group having 3 to 6 carbon atoms; a benzyl group which may be substituted with a halogen atom, an alkyl group having 1 to 3 carbon atoms or an alkoxy group having 1 to 3 carbon atoms; a phenyl group which may be substituted with a halogen atom, an alkyl group having 1 to 3 carbon atoms 4 or an alkoxy group having 1 to 3 carbon atoms; or -Z-R in which Z represents a carbonyl group or a sulfonyl 2Q9B27 10 15 4 group, and R represents an alkyl group having 1 to 6 carbon atoms, a phenyl group which may be substituted with an alkyl group having 1 to 3 carbon atoms or a halogen atom, an alkoxy group having 1 to 3 carbon atoms or a phenoxy group, which comprises reacting an aminosulfenyl chloride derivative represented by the formula (I): R1 :n-s-c f 1 2 wherein R and R are the same as defined above, with 2,3-dihydro-2,2-dimethylbenzofuran-7-yl N-methyl-carbamate represented by the formula (II): O (ii) 20 2. A process according to Claim 1, wherein the reaction is carried out in the presence of a solvent,

3. A process according to Claim 1, wherein the reaction is carried out in the presence of a basic 25 compound. - 42 - 203SZ7

4. A process according to Claim 1, wherein the reaction is carried out at a temperature of -20 to 50^C for 1 to 20 hours.

5. A process according to any one of Claims 1 to 4, wherein 1 to 2 moles of the aminosulfenyl chloride derivative of the formula (I) is used per mole of the compound of the formula (II).

6. A process for preparing a carbamate derivative of formula (III) as hereinbefore defined using an aminosulfenyl chloride of formula (I) as hereinbefore defined substantially as specifically described herein in any one of Examples 35 to 42.

7. A carbamate derivative of formula (III) as hereinbefore defined, when prepared by a process according to any one of claims 1 to 5. 43