JP2002220370A - Method for producing sulfene amide compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an industrially advantageous method for producing sulfene amide compound which is useful of a rubber vulcanizing agent and a physiological activity, in safety, in a good yield and without using any harmful reagent. SOLUTION: When sulfene amide compound represented by the general formula (I) is produced, S-[2-(3-oxo-1,2-benzoisothyazolinyl]-2-mercaptobenzoate ester compound represented by the general formula (II) (wherein, R1 is a 1-6C alkyl or cycloalkyl; R4 is a 1-8C alkyl or cycloalkyl, alkoxy, halogen, nitro radical and R4 may be the same or different when R4 is plural; and n is 0 or 1-4) is reacted with amines represented by the general formula: R2R3NH (wherein R2, R3 are each H or a 4-12C alky, cycloalkyl or aromatic radical; and R2 and R3 may couple each other and form a ring with N).

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a method for producing a sulfenamide compound. More specifically, the sulfenamide compound is converted to S- [2- (3-oxo-1,
2-benzoisothiazolinyl)] 2-mercaptobenzoic acid ester compound and an amine to produce an efficient method.

[0002]

2. Description of the Related Art Sulfenamide compounds have been reported to have various functions, for example, a vulcanizing agent for rubber (Japanese Patent Publication No. 64-48831; U.S. Pat. No. 2,866,777 (1955)), It is known to have an action such as a herbicide for pre-emergence treatment (JP-A-53-31643) and a fungicide (JP-A-55-51053). In the case of an N-monosubstituted-2-alkoxycarbonylphenylsulfenamide compound,
The following reaction formula (d)

Embedded image Cyclization in the presence of a base as shown in JP-A-46-5516; J. Org. Chem., 40 , 2
029 (1975)), 1,2-benzisothiazoline-3- which is known to have physiological activities such as antibacterial and antibacterial activities.
On compounds can be prepared.

Conventionally, sulfenamides have been prepared by reacting a compound having a mercapto group or a disulfide group with chlorine gas to react a sulfenyl chloride compound obtained with chlorine gas with an amine, or by reacting a chloramine compound with a mercapto compound. Although the method was used to produce starting materials, toxic chlorine gas must be used to produce the starting materials, and chlorine gas has the problem of corrosion of the production equipment. Is desired.

[0004]

DISCLOSURE OF THE INVENTION The present invention overcomes the drawback of using toxic chlorine gas, which is a conventional method, in producing a sulfenamide compound, and provides an industrial process for producing a sulfenamide compound. The purpose of the present invention is to provide an advantageous method.

[0005]

Means for Solving the Problems The present inventors have conducted intensive studies on a method for producing a sulfenamide compound, and as a result, have found that S- [2- (3-oxo-1,2-benzisothiazolinyl) ] It has been found that a sulfenamide compound can be safely and easily obtained by reacting a 2-mercaptobenzoic acid ester compound with an amine, and the present invention has been completed based on this finding.

That is, according to the present invention, the following general formula (A)

Embedded image(Where R¹Is an alkyl group having 1 to 6 carbon atoms or
Represents a loalkyl group. R ², R³Is hydrogen atom or charcoal
An alkyl or cycloalkyl group having a prime number of 4 to 12
Or an aromatic group;²And R³Are connected to each other
It may form a ring together with the elementary atoms. R⁴Is the carbon number
1-8 alkyl or cycloalkyl groups, alcohol
Represents a xyl group, a halogen atom or a nitro group;⁴Is multiple
If so, each R⁴Are the same but different
And n is 0 or an integer of 1 to 4)
In the method for producing a sulfenamide compound,
General formula (b)

Embedded image(Where R¹Is an alkyl group having 1 to 6 carbon atoms or
Represents a loalkyl group. R ⁴Is an alkyl having 1 to 8 carbon atoms
Group or cycloalkyl group, alkoxyl group, halogen
Represents a nitrogen atom or a nitro group;⁴When there are a plurality of
⁴May be the same or different from each other, and n is 0
Or an integer of 1-4) represented by S- [2- (3-O
Xo-1,2-benzisothiazolinyl)]-2-mercapto
A benzoic acid ester compound represented by the following general formula (c)

Embedded image (Wherein, R ² and R ³ represent a hydrogen atom or a C 4-12
Wherein R ² and R ³ may be linked to each other to form a ring together with a nitrogen atom). A method for producing a sulfenamide compound is provided.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION In the above general formula (A), which represents a sulfenamide compound which is a production target compound of the present invention,
R ¹ represents an alkyl group having 1 to 6 carbon atoms or a cycloalkyl group. Illustrative examples of the alkyl group or cycloalkyl group include a methyl group, an ethyl group, a propyl group,
Isopropyl group, pentyl group, butyl group, s-butyl group,
Examples include a t-butyl group, a hexyl group, a cyclohexyl group, an ethoxyethyl group, and a benzyl group. Also, R ² , R
³ represents a hydrogen atom, an alkyl group having 4 to 12 carbon atoms, a cycloalkyl group, or an aromatic group. These alkyl groups may have a substituent such as an alkoxyl group and a dialkylamino group. Specific examples of the alkyl group or the cycloalkyl group include a butyl group, an isobutyl group, a t-butyl group, a hexyl group, a cyclohexyl group, a cumyl group, and a benzyl group. Examples of the aromatic group include a phenyl group, a tolyl group, a xylyl group, a naphthyl group and a biphenyl group. These aromatic groups may have a substituent such as a halogen atom, an alkoxyl group, a dialkylamino group, an acyl group or an alkoxycarbonyl group. Examples of amines in which R ² and R ³ are linked to each other to form a ring together with a nitrogen atom include pyrrolidine, piperidine, and morpholine. Also, R
⁴ represents an alkyl group having 1 to 8 carbon atoms, a cycloalkyl group, an alkoxyl group, a halogen atom, or a nitro group.
Illustrative examples of the alkyl group include a methyl group, an ethyl group, a propyl group, an isopropyl group, a cyclopropyl group,
Examples include a pentyl group, a butyl group, an s-butyl group, a t-butyl group, a cyclobutyl group, a hexyl group, a cyclohexyl group, and a benzyl group. Specific examples of the alkoxyl group include a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, and a hexyloxy group. n shows 0 or the integer of 1-4.

The novel synthesis reaction of the present invention can be represented by the following reaction formula.

Embedded image

The production of the sulfenamide compound in the present invention is preferably carried out in the presence of a reaction solvent.
The reaction solvent in this case is methanol, ethanol, isopropanol, acetonitrile, benzene, toluene,
The reaction is performed in a solvent such as xylene, chlorobenzene, dichlorobenzene, or anisole. These solvents are used alone or in the form of a mixed solvent.

[0010] The temperature in the above-mentioned production method is 20 degrees to 15 degrees.
The reaction can be carried out at a temperature around 0 ° C. However, if the temperature is too low, the reaction time will be delayed, and if the temperature is too high, the decomposition reaction and side reactions will increase. Is preferred. The reaction time depends on the reaction temperature and cannot be determined unconditionally, but usually 2 to 8 hours is sufficient.

Representative examples of the sulfenamide compound obtained by the present invention are as follows. Methyl 2- (N-phenyl) sulfenamoylbenzoate, ethyl 2- [N- (4-methylphenyl)] sulfenamoylbenzoate, 2-
Methyl [N- (4-methoxyphenyl)] sulfenamoylbenzoate, methyl 2- (N-cumyl) sulfenamoylbenzoate, methyl 2- [N- (t-butyl)] sulfenamoylbenzoate, 2- (N, N- Diethyl) methyl sulfenamoyl benzoate and the like.

[0012]

Next, the present invention will be described in detail with reference to examples. It should be noted that the embodiments of the present invention are representative ones to facilitate understanding of the present invention, and the present invention is not limited to these. The sulfenamide compounds produced in the following examples were identified by comparing the melting point and various spectral data of known compounds, and various spectra of unknown compounds were used as main criteria.

Example 1 S- [2- (3-oxo) was placed in a glass container having an inner volume of 50 ml.
-1,2-Benzoisothiazolinyl)] methyl-2-mercaptobenzoate (127 mg, 0.4 mmol) and aniline (47 mg, 0.5 mmol) in methanol (10 m
1) and reacted under reflux for 3 hours. The methanol is distilled off under reduced pressure, and the crude product is purified by silica gel chromatography (elution solvent: methylene chloride).
Methyl 2- (N-phenyl) sulfenamoylbenzoate
Obtained in 7 mg yield. Yield: 94%; melting point: 152.5-154.0 ° C (literature: 154-155.
5 ° C) (recrystallization solvent: benzene-hexane); ¹ H-NMR (CD
Cl ₃ ) δ3.96 (3H, s), 5.08 (1H, br s), 6.87 (1H, t, J
= 7.3 Hz), 6.99 (2H, dd, J = 7.7, 1,1 Hz), 7.14-7.25
(3H, m), 7.41 (1H, td, J = 7.7, 1.3 Hz), 7.50 (1H, d
d, J = 8.2, 1.4 Hz), 8.05 (1H, dd, J = 8.1, 1.2 Hz); I
R (KBr) ν _max 3333, 1696, 1437, 1277, 1233, 855, 74
8 cm ^-1 .

Example 2 In Example 1, p-toluidine was used in place of aniline to obtain methyl 2- [N- (p-methylphenyl)] sulfenamoylbenzoate. Yield 90%; melting point 131.5-132.0 ° C (recrystallization solvent: methylene chloride-hexane); ¹ H-NMR (CDCl ₃ ) δ 2.25 (3H,
s), 3.95 (3H, s), 4.99 (1H, br s), 6.88 (2H, d, J =
8.5 Hz), 7.02 (2H, d, J = 8.5 Hz), 7.15 (1H, td, J =
7.5, 1.2 Hz), 7.40 (1H, td, J = 7.7, 1.4 Hz), 7.50
(1H, dd, J = 8.2, 1.4 Hz), 8.03 (1H, dd, J = 7.8, 1.4 H
z); IR (KBr) ν _max 3343, 1692, 1510, 1435, 1275, 12
38, 905, 812, 745 cm ^-1 . Elemental analysis value as C ₁₅ H ₁₅ NO ₂ S (%) Measurement value: C, 65.87, H, 5.46, N, 5.01 Calculated value: C, 65.91, H, 5.53, N, 5.12

Example 3 In Example 2, methyl 2- [N- (p-methylphenyl)] sulfenamoylbenzoate was obtained in 83% yield by stirring at room temperature for 7.5 hours.

Example 4 In Example 1, reflux was carried out for 1.5 hours using p-anisidine instead of aniline to obtain methyl 2- [N- (p-methoxyphenyl)] sulfenamoylbenzoate. Yield: 97%; melting point 106.5-108.0 ° C (literature 106-10
7 ° C) (recrystallization solvent: methylene chloride-methanol); ¹ HN
MR (CDCl ₃ ) δ 3.75 (3H, s), 3.95 (3H, s), 4.90 (1H,
br s), 6.79 (2H, d, J = 9.1 Hz), 6.92 (2H, d, J = 9.1 Hz)
Hz), 7.16 (1H, td, J = 7.4, 1.4 Hz), 7.42 (1H, td, J
= 7.3, 1.4 Hz), 7.52 (1H, dd, J = 8.2,1.4 Hz), 8.04
(1H, dd, J = 8.1, 1.2 Hz); IR (KBr) ν _max 3347, 1692,
1508,1273,1242,820,741 cm- ¹ .

Example 5 S- [2- (3-oxo) was placed in a glass container having an inner volume of 50 ml.
-1,2-Benzoisothiazolinyl)] ethyl 2-mercaptobenzoate (0.4 mmol) and p-toluidine (0.5 m
mol) was dissolved in methanol (10 ml) and reacted under reflux for 3 hours. The methanol was distilled off under reduced pressure, and the crude product was purified by silica gel chromatography (elution solvent: methylene chloride) to obtain ethyl 2- [N- (p-methylphenyl)] sulfenamoylbenzoate. Yield 99%; melting point 101.0-102.5 ° C (recrystallization solvent: methylene chloride-hexane); ¹ H-NMR (CDCl ₃ ) δ 1.43 (3H,
t, J = 7.1 Hz), 2.26 (3H, s), 4.42 (2H, q, J = 7.1 H
z), 4.98 (1H, br s), 6.89 (2H, d, J = 8.5 Hz), 7.02
(2H, d, J = 8.5 Hz), 7.16 (1H, td, J = 7.5, 1.2 Hz), 7.
40 (1H, td, J = 7.7, 1.3 Hz), 7.50 (1H, dd, J = 8.2,
1.1 Hz), 8.06 (1H, dd, J = 7.7, 1.4 Hz); IR (KBr) ν
_max 3356, 1690, 1512, 1269, 1248, 1098, 810, 745 c
m ^-1 . Elemental analysis for C ₁₆ H ₁₇ NO ₂ S (%) Found: C, 66.73, H, 5.86, N, 4.71 Calculated: C, 66.87, H, 5.96, N, 4.87

Example 6 Methyl 2- (N-cumyl) sulfenamoylbenzoate was obtained in the same manner as in Example 1 except that cumylamine was used instead of aniline. Yield 73%; Melting point 138.5-140 ° C (recrystallization solvent: benzene-hexane); ¹ H-NMR (CDCl ₃ ) 1.58 (6H, s), 3.07
(1H, br s), 3.89 (3H, s), 7.12 (1H, td, J = 7.1, 1.
1 Hz), 7.23-7.28 (1H, m), 7.34-7.39 (2H, m), 7.51-
7.57 (3H, m), 7.98 (1H, dd, J = 7.7, 1.4 Hz), 8.26
(1H, dd, J = 8.2, 0.8 Hz); IR (KBr) 3304,1692,1435,
1273, 1101, 750, 698 cm ^-1 . C ₁₇ H ₁₉ NO ₂ Elementary analysis as S (%) Found: C, 67.57, H, 6.31 , N, 4.57 Calculated: C, 67.74, H, 6.35 , N, 4.65

Example 7 In Example 1, 2- [N- (t-butyl)] sulfenamoyl benzoate was prepared by using t-butylamine instead of aniline and heating and stirring at 80 ° C. using a sealed tube. Methyl acid was obtained. Yield 43%; melting point 89.0-89.7 ° C (recrystallization solvent: methylene chloride-hexane); ¹ H-NMR (CDCl ₃ ) δ 1.22 (9H, s),
2.55 (1H, br s), 3.92 (3H, s), 7.10 (1H, td, J = 7.
8, 1.2 Hz), 7.50 (1H, td, J = 7.8, 1.4 Hz), 7.98 (1
H, dd, J = 7.8, 1.5Hz), 8.16 (1H, dd, J = 8.4, 1.0 H
z); IR (KBr) ν _max 3291, 2961, 1701, 1433, 1269, 74
8 cm ^-1 . Elemental analysis for C ₁₂ H ₁₇ NO ₂ S (%) Obtained: C, 60.33, H, 7.18, N, 5.76 Calculated: C, 60.22, H, 7.16, N, 5.85

Example 8 In Example 1, methyl 2- (N, N-diethyl) sulfenamoylbenzoate was obtained by using diethylamine in place of aniline and heating and stirring at 80 ° C. using a sealed tube. Was. Yield 47%; ¹ H-NMR (CDCl ₃ ) δ 1.16 (6H, t, J = 7.1 H
z), 3.07 (4H, q, J = 7.1 Hz), 3.91 (3H, s), 7.11 (1
H, td, J = 7.4, 1.1 Hz), 7.49 (1H, td, J = 7.4,1.4 H
z), 7.94 (1H, dd, J = 7.4, 1.4 Hz), 8.00 (1H, dd, J =
7.4, 1.1 Hz); IR (liquid film) ν _max 1711, 1458, 1435, 126
9, 745 cm ^-1 ; high resolution MS, C ₁₂ H ₁₇ NO ₂ S: calculated 239.0980; found 239.1005.

Example 9 Methyl 2- (N, N-dibenzyl) sulfenamoylbenzoate was obtained in the same manner as in Example 1 except that dibenzylamine was used instead of aniline. Yield 89%; ¹ H-NMR (CDCl ₃ ) δ 3.87 (3H, s), 4.17
(4H, s), 7.10 (1H, td, J = 7.4, 1.1 Hz), 7.2-7.35 (1
0H, m), 7.47 (1H, td, J = 7.4, 1.1 Hz), 7.90 (1H, d,
J = 8.0 Hz), 7.97 (1H, dd, J = 8.2, 1.4 Hz); IR (KBr)
ν _max 1707, 1456, 1435, 1271, 745, 698 cm ^-1 .

Example 10 In Example 1, morpholine was used in place of aniline to obtain methyl S- (1-morpholino) -2-mercaptobenzoate. Yield 97%; ¹ H-NMR (CDCl ₃ ) δ 3.08 (4H, t, J = 4.7 H
z), 3.82 (4H, t, J = 4.7 Hz), 3.91 (3H, s), 7.17 (1
H, td, J = 6.6, 1.1 Hz), 7.55 (1H, td, J = 7.1,1.1 H
z), 8.01-8.05 (2H, m); IR (KBr) ν _max 1709, 1458, 1
432, 1269, 745 cm ^-1 .

Example 11 Methyl S- (1-pyrrolidino) -2-mercaptobenzoate was obtained in the same manner as in Example 1 except that pyrrolidine was used instead of aniline. Yield 47%; ¹ H-NMR (CDCl ₃ ) δ 1.93-1.97 (4H, m),
3.18-3.22 (4H, m), 3.91 (3H, s), 7.12 (1H, dd, J =
7.1, 1.1 Hz), 7.50 (1H, td, J = 7.1, 1.4 Hz), 7.71 (1
H, dd, J = 7.7, 1.1 Hz), 8.01 (1H, dd, J = 7.1, 1.4 H
z); IR (KBr) ν ma x 1709, 1458, 1439, 1269, 745 c
m ^-1 .

[0024]

According to the present invention, S- [2- (3-oxo-1,2-
Benzoisothiazolinyl)]-2-mercaptobenzoic acid ester compound and an amine can produce a sulfenamide compound in good yield. Moreover, because it can be safely manufactured without using toxic chlorine gas,
It is optimal as an industrial method for synthesizing sulfenamide compounds.

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Yasuo Kama 1-1-1, Higashi, Tsukuba, Ibaraki Pref., Ministry of Economy, Trade and Industry, National Institute of Advanced Industrial Science and Technology (MHI) (72) Inventor, Motonari Shibagami, Higashi 1, Tsukuba, Ibaraki 1st-chome, Ministry of Economy, Trade and Industry, National Institute of Advanced Industrial Science and Technology (72) Inventor, Toshiyuki Takagi 1-1-1, Higashi, Tsukuba-shi, Ibaraki F-term (Reference) 4H006 AA02 AC60

Claims (1)

[Claims] 1. A compound represented by the following general formula (a):(Where R¹Is an alkyl group having 1 to 6 carbon atoms or
Represents a loalkyl group. R ², R³Is hydrogen atom or charcoal
An alkyl or cycloalkyl group having a prime number of 4 to 12
Or an aromatic group;²And R³Are connected to each other
It may form a ring together with the elementary atoms. R⁴Is the carbon number
1-8 alkyl or cycloalkyl groups, alcohol
Represents a xyl group, a halogen atom or a nitro group;⁴Is multiple
If so, each R⁴Are the same but different
And n is 0 or an integer of 1 to 4)
In the method for producing a sulfenamide compound,
The general formula (b)(Where R¹Is an alkyl group having 1 to 6 carbon atoms or
Represents a loalkyl group. R ⁴Is an alkyl having 1 to 8 carbon atoms
Group or cycloalkyl group, alkoxyl group, halogen
Represents a nitrogen atom or a nitro group;⁴When there are a plurality of
⁴May be the same or different from each other, and n is 0
Or an integer of 1-4) represented by S- [2- (3-O
Xo-1,2-benzisothiazolinyl)]-2-mercapto
A benzoic acid ester compound represented by the following general formula (c):(Where R², R³Represents a hydrogen atom or a carbon number of 4 to 12
Alkyl or cycloalkyl group or aromatic
A group represented by R²And R³Are linked together with a nitrogen atom
(Which may form a ring)
For producing sulfenamide compounds characterized by the following:
Law.