JPH0552824B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial Application Field) The present invention relates to a method for producing sulfenamide derivatives, more specifically, treating an amide type compound with sodium hydride and iodine and then reacting it with a dithiocarbamate. In particular, the present invention relates to a method for producing sulfenamide derivatives simply, rapidly, and in good yields.

(Prior Art) Conventionally, methods for producing N-aroyl-S-disubstituted thiocarbamoylsulfenamide (represented by general formula () below), its analogs, N-acyl-S-thioaroylsulfenamide, etc. As such, an aroylation or acylation reaction of the corresponding N-unsubstituted sulfenamide has been used (Japanese Patent Publication No. 41712/1982, Japanese Patent Application No. 219738/1983).

However, the raw material N-unsubstituted sulfenamide has a stability problem, and the acyl group or aroyl group (substituent R ¹ in general formula () below) of the sulfenamide derivative that can be synthesized by this method
The types were limited.

(Problems to be Solved by the Invention) An object of the present invention is to provide a method for producing a wide variety of sulfenamide derivatives using a dithiocarbamate simply, rapidly, and in good yields, which overcomes the drawbacks of the conventional methods described above. With the goal.

(Means for Solving the Problems) The above object of the present invention is to solve the general formula (In the formula, R ¹ represents an aryl group, a heterocyclic group, an alkyl group, a dialkylamino group, or an alkoxy group.) After treating the amide type compound represented by the formula with sodium hydride and iodine, (In the formula, R ² and R ³ represent lower alkyl groups, R ² ,
R ³ may be combined to form a ring, and M ⁺ represents a metal cation. ) The general formula is characterized by reacting with a dithiocarbamate represented by (In the formula, R ¹ , R ² and R ³ have the same meanings as above.) This was achieved by a method for producing a sulfenamide derivative represented by the following formula.

In the method of the present invention, R ¹ in the above general formula ()
Specific examples include phenyl group, p-anisyl group, p-tolyl group, p-chlorophenyl group, 2-
thienyl group, 3-pyridyl group, 2-furyl group, t
-butyl group, n-butyl group, methyl group, dimethylamino group, diethylamino group, diisopropylamino group, methoxy group, ethoxy group, isopropoxy group and the like. This R ¹ may have a substituent that is inactive in the reaction. General formula ()
Examples of the R ² R ³ N group in parentheses include a dimethylamino group, a diethylamino group, a diisopropylamino group, a morpholino group, and a piperidino group. M ⁺ in general formula () is Na ⁺ , K ⁺ ,
Examples include Ag ⁺ .

In the method of the present invention, the reaction solvent is preferably an anhydrous ether type, such as tetrahydrofuran,
Dioxane etc. are suitable. Moreover, sodium hydride can be either anhydrous or oil suspension (50 to 60%).

In the method of the present invention, the reaction first begins with the general formula ()
The amide type compound represented by is dissolved in a suitable solvent, preferably 1 to 0.75 equivalents, more preferably
Add 0.75 equivalents of sodium hydride and stir at room temperature. After the generation of hydrogen gas has stopped, preferably 0.75 to 0.5 equivalent, more preferably 0.5 equivalent, of iodine is added to the amide type compound, and the mixture is further stirred.
Finally, the dithiocarbamate represented by the general formula () is preferably used in an amount of 1 to 1.2 equivalents relative to iodine,
More preferably, 1.2 equivalents are added and stirred for about 1 to 2 hours. The completion of the reaction can be determined by the discoloration of the reaction solution. The reaction temperature is usually room temperature, but the reaction can be accelerated if necessary by heating. For post-treatment after the reaction is complete, first pour into water, extract with methylene chloride, column chromatography,
Separation and purification can be performed by recrystallization.

The reaction in the method of the present invention can be expressed by the scheme below.

Structural confirmation of the obtained sulfenamide derivatives is performed by comparing known compounds with standard products, and for new compounds by infrared absorption spectra,
This can be carried out using nuclear magnetic resonance spectroscopy, mass spectrometry, and elemental analysis.

(Effects of the Invention) According to the method of the present invention, the reaction proceeds rapidly under relatively mild conditions, and sulfenamide derivatives can be obtained in good yields. The raw materials and reaction reagents used are both inexpensive and easy to handle, and in post-treatment, inorganic components and unreacted raw materials can be effectively removed by extraction. In addition, by appropriately selecting an amide type compound represented by the general formula (),
Various substituents R ¹ can be introduced into the sulfenamide derivative.

The sulfenamide derivative produced by the method of the present invention and the 1,4,2-dithiazolium salt obtained by cyclodehydration thereof are both used as fog suppressants for silver halide photography (patent application No. 63-53073, patent application No. 1-94149
issue). In addition, 1,4,2-dithiazolium salt is an intermediate raw material for various sulfur-containing, nitrogen-containing heterocyclic compounds, and is a useful compound in organic synthesis.

Furthermore, this reaction is not limited to amide-type compounds, but can also be applied to primary or secondary amines, and thiolates can be used instead of dithiocarbamates, and various general synthesis methods for sulfenamides can be used. Applicable to compound synthesis.

(Examples) Next, the present invention will be described in more detail based on Examples.

Example 1 225 mg (3 mmol) of methyl carbamate was dissolved in 12 ml of anhydrous tetrahydrofuran, and 108 mg of sodium hydride (50% oil suspension) was dissolved in 12 ml of anhydrous tetrahydrofuran.
(2.25 mmol) was added, and after hydrogen generation had stopped, the mixture was further stirred for 5 minutes. Iodine 381mg (1.5mmol)
was added and stirred for 5 minutes, then 461 mg (1.8 mmol) of silver diethyldithiocarbamate was added and stirred for 30 minutes.
Add water and extract with methylene chloride. At that time, insoluble matter was filtered off. After distilling off the solvent, it was treated with silica gel column chromatography and recrystallized from pentane-ether to give 291 mg of N-methoxycarbonyl-S-diethylthiocarbamoylsulfenamide (yield: 87%) as white crystals with a melting point of 66-67°C. I got it.

¹ H-NMR (CDCl ₃ , TMS) δ = 1.29 (6H, t,
J=7.5Hz), 3.79 (3H, s), 3.4−4.2 (4H, br.),
6.35 (br.s) IR (KBr, cm ^-1 ) 3228 (NH), 1735 (C=O) Elemental analysis (%) Measured value C; 37.82 H; 6.27 N; 12.50 S; 28.73 Calculated value C; 37.82 H ; 6.35 N; 12.60 S; 28.85 Example 2 2.04 g (27.2 mmol) of methyl carbamate was dissolved in 35 ml of anhydrous tetrahydrofuran, and 0.98 g of sodium hydride (50%) was added in the same manner as in Example 1.
(20.4 mmol), iodine 3.45 g (13.6 mmol), morpholine-N-dithiocarboxylic acid sodium 3.02 g
(16.3 mmol) were added one after another and stirred for 2 hours. After the post-treatment in the same manner as in Example 1, white crystals of N-
Methoxycarbonyl-S-(morpholine-N-thiocarbonyl)sulfenamide 2.50g (78%)
I got it.

^1H -NMR ( _CDCl3 , TMS) δ = 3.7-3.8 (4H,
m), 3.9−4.1 (4H, m), 3.80 (3H, s), 6.22 (br.s) ¹³ C-NMR (CDCl ₃ , TMS) δ = 50.37, 53.56,
65.67, 156.87, 198.51 Example 3 Benzamide 121 instead of methyl carbamate
Sodium hydride (0.75 mmol), iodine (0.5 mmol),
Silver diethyldithiocarbamate (0.5 mmol) was sequentially added and stirred for 1 hour. The following post-treatment was carried out in the same manner as in Example 1, and 71 mg of N-benzoyl-S-diethylthiocarbamoylsulfenamide was obtained as white crystals.
(53%).

Identification was made by comparison with a standard specimen (Bull.Chem.Soc.Jpn.59, 2017 (1986)).

Example 4 122mg of nicotinamide instead of benzamide
The reaction and post-treatment were carried out in the same manner as in Example 3, except that N-(3 mmol) was dissolved in 4 ml of anhydrous tetrahydrofuran. -pyridylcarbonyl)-S-diethylthiocarbamoylsulfenamide 50 mg (37%) was obtained.

¹ H-NMR (CDCl ₃ , TMS) δ = 3.31 (6H, t,
J = 7.5Hz), 3.5-4.2 (4H, br.), 7.3-7.5 (1H,
m), 8.2-8.4 (1H, m), 8.7-8.8 (1H, m), 9.2
−9.3 (1H, m) MS (m/z) 269 (M ⁺ ), 116 (Et ₂ NCS ⁺ ) Example 5 N,N-dimethylurea 88 instead of benzamide
The reaction and post-treatment were carried out in the same manner as in Example 3, except that 1 mmol of N-dimethylthiocarbamoyl-S-diethylthiocarbamoylsulfenamide was dissolved in 4 ml of anhydrous tetrahydrofuran. (16%).

¹ H-NMR (CDCl ₃ , TMS) δ = 1.30 (6H, t,
J=7.5Hz, 3.09 (6H, s), 3.5−4.2 (4H, br.),
6.10 (br.s) IR (KBr, cm ^-1 ) 3228 (NH), 1651 (C=O) MS (m/z) 235 (M ⁺ ), 116 (Et ₂ NCS ⁺ ) Example 6 Substitute for benzamide pivalic acid amide 101mg
(1 mmol) was dissolved in 4 ml of anhydrous tetrahydrofuran, and the reaction and post-treatment were carried out in the same manner as in Example 3. Thiocarbamoyl sulfenamide 51 mg (41%)
I got it.

^1H -NMR ( _CDCl3 , TMS) δ = 1.3 (6H, t), 1.33 (9H, s), 3.5-4.2 (4H, br.), 7.1 (br.s) MS (m/z) 249 ( M ⁺ ), 116 ( _Et2 NCS ⁺ )

Claims (1)

[Claims] 1. General formula (In the formula, R ¹ represents an aryl group, a heterocyclic group, an alkyl group, a dialkylamino group, or an alkoxy group.) After treating the amide type compound represented by the formula with sodium hydride and iodine, (In the formula, R ² and R ³ represent lower alkyl groups, R ² ,
R ³ may be combined to form a ring, and M ⁺ represents a metal cation. ) The general formula is characterized by reacting with a dithiocarbamate represented by (In the formula, R ¹ , R ² and R ³ have the same meanings as above.) A method for producing a sulfenamide derivative represented by the following.