CS234041B2 - Method of 2,3-dihydro-1,4-dithion making - Google Patents

Abstract

The present invention relates to a process for the preparation of 2,3-dihydro-1,4-dithiin derivatives. One of the prior art methods (Method I) for the synthesis of said compounds described in US No. 3,920,438, includes the reaction of the β-haloketones with 1,2-dithiols. This reaction can be represented by the reaction scheme: where X is halogen. In another method (Method II) of the same US patent, the ketone is reacted with dithiol to form 1,3-dithiolane which is then converted to 1,4-dithiine by halogen; this reaction can be represented by the reaction scheme: where X is halogen. 234041

Description

The present invention relates to a process for the preparation of 2,3-dihydro-1,4-dithine derivatives.

One prior art method (Method I) for the synthesis of said compounds, described in U.S. Patent No. 3,920,438, involves the reaction of ω-haloketones with 1,2-dithiols. This reaction can be illustrated by the following reaction scheme:

R ^{* 2} + ¹ COCHXR HSCHR ³ CHR ⁴ SH

H ₂ O + HX where

X is halogen.

In another method (Method II) of the same US patent, a ketone is reacted with dithiol to form 1,3-dithiolane, which is then converted to 1,4-dithiine by halogen treatment; this reaction can be illustrated by the reaction scheme:

where

X is halogen. 234041

These prior art methods have some drawbacks; include the use of toxic, corrosive and costly halogenating agents such as chlorine, bromine or sulfuryl chloride, requiring the use of expensive enamelled equipment and complicated protective measures for the operator. They also produce two molar equivalents of hydrogen halide, which must be disposed of in an environmentally acceptable manner, which entails considerable costs. Furthermore, the prior art methods are limited in their applicability to synthesis; since unsymmetrical ketones can be specifically halogenated in one position (J, Chem. Soc. wherein R and R are the same alkyl group (other than methyl) available by the methods described.

Halogenation of symmetrical ketones to produce a single uniform haloketone product yields only unsymmetrically substituted dithiins; R ¹ cannot have the same meaning o as R 1. A similar disadvantage is characterized by the method II described above, in which the use of 12 dithiolenes with different meanings R and R inevitably leads to the formation of product mixtures which cannot be separated.

SUMMARY OF THE INVENTION It is an object of the present invention to provide a novel process for the preparation of 2,3-dihydro-1,4-dithiin derivatives which does not suffer from the above disadvantages.

The present invention provides a process for the preparation of 2,3-dihydro-1,4-dithiins of the general formula I _R 4 R ¹

A ² (I), where i 2

R and R are both hydrogen or the same or different C 1 -C 6 alkyl groups, or together are a ring of 3 or 4 methylene groups; and

R ³ and R ⁴ are both hydrogen or the same or different C 1 -C 10 alkyl groups, the alkyl groups themselves being optionally substituted by 1 or 2 C 1 -C 3 alkoxy groups consisting of 1,2-dithiol of formula III

HSCHR ³ CHR ⁴ SH (III), where

R ³ and R 6 are as defined above, reacted with a t-hydroxyketone of formula II

R ¹ CHOHCOR ² (II) wherein

2

R and R are as defined above, in the presence of an acid catalyst to form the dihydrodithiin of formula (1) and reaction water.

As a rule, the process according to the invention is carried out in the presence of an organic solvent, such as benzene, toluene or xylene. As mentioned above, water is formed in the reaction. The presence of an acid catalyst (e.g. p-toluenesulfonic acid, methanesulfonic acid, naphthalenesulfonic acid, polyphosphoric acid) promotes the elimination of water. Although the process of the invention may be carried out at room temperature or even below room temperature (e.g., 0 ° C), the reaction is typically carried out by heating the reaction mixture to an elevated temperature (e.g., up to 180 ° C). . often the reaction mixture is heated to the boiling point of the reaction mixture. The resulting water is preferably removed, especially at the end of the reaction, in order to complete the reaction completely. Suitably, the reaction water is removed azeotropically, the solvent forming the second component of the azeotropic mixture. Upon practical completion of the reaction (usually, for example, 1/2 to 10 hours), the 2,3-dihydro-1,4-dithiine of formula (I) formed can be isolated from the reaction mixture by conventional means.

Thus, the process of the invention does not involve the use of any halogenating agents and only two molar equivalents of water according to the reaction scheme hschr ³ chr ⁴ sh + r ¹ cochohe ² -

where

R ^1, R ^2, R and ^R4 are as defined above.

For this reason, equipment costs and costs associated with preventing environmental pollution are substantially lower.

Another advantage of the invention is that the symmetrically substituted Dithiine are easily prepared, because it can easily be prepared starting symmetrically-substituted hydroxyketones of type r'cochohr ^2, where 1?

R and R are the same lower alkyl groups by different synthetic procedures. However, the process of the invention is equally easy to use for the synthesis of unsymmetrically substituted dithiins.

The 2,3-dihydro-1,4-dithiins which can be prepared by the process of the present invention include 2,3-dihydro-5-methyl-1,4-dithiine, 2,3-dihydro-2,5-dimethyl- 1,4-dithiine, 2,3-dihydro-2,6-dimethyl-1,4-dithiine, 2-ethyl-2,3-dihydro-5-methyl-1,4-dithiine, 2-ethyl-2, 3-dihydro-6-methyl-1,4-dithiine, 2,3-dihydro-5,6-dimethyl-1,4-dithiine, 2,3-dihydro-2,5,6-trimethyl-1,4- dithiine, 2,3-dihydro-2,3,5,6-tetremethyl-1,4-dithiine, 2-ethyl-2,3-dihydro-5,6-dimethyl-1,4-dithiine, 2,3- diethyl-5,6-dihydro-1,4-dithiine, 5,6-diethyl-2,3-dihydro-2-methyl-1,4-dithiine, 2,5,6-triethyl-2,3-dihydro- 1,4-dithiine, 2,3-dihydro-5,6-dipropyl-1,4-dithiine,

2,3-dihydro-2-methyl-5,6-dipropyl-1,4-dithiine, 2-ethyl-2,3-dihydro-5,6-dipropyl-1,4-dithiine,

2,3-dibutyl-5,6-dihydro-1,4-dithiine, 5,6-dibutyl-2,3-dihydro-2-methyl-1,4-dithiine, 5,6-dibutyl-2-ethyl-2, 3-dihydro-1,4-dithiine, 2,3-dihydro-5,6-dipentyl-1,4-dithiine, 2,3-dihydro-2-methyl-5,6-dipentyl-1,4-dithiine, 2-ethyl-2,3-dihydro-5,6-dipentyl-1,4-dithiine, 2,3-dihexyl-5,6-dihydro-1,4-dithiine, 5,6-dihexyl-2,3- dihydro-2-methyl-1,4-dithiine, 2-ethyl-5,6-dihexyl-2,3-dihydro-1,4-dithiine, 2,3-dihydro-5,6-di (2-methylpropyl) -1,4-dithiin,

2,3-dihydro-2-methyl-5,6-di (2-methylpropyl) -1,4-dithiine, 2-ethyl-2,3-dihydro-5,6-di (2-methylpropyl) -4- dithiin, 2,3-dihydro-2-propoxymethyl-5,6-dimethyl-1,4-dithiin, 2,3234041

-dihydro-5,6-dimethyl-2 - [(1-methylethoxy) -methyl] -1,4-dithiine, 2-decyl-5,6-diethyl-2,3-dihydro-1,4-dithiine, J , 6,7,8-tetrahydro-1,4-benzodithian, 5,6,7, Q-tetrehydro-2-methyl-1,4-benzodithian and 2-ethyl-5,6,7,8-tetrahydro-1 , 4-benzoditian.

The product obtainable by the process according to the invention is particularly suitable for oxidation not appropriate

2,3-dihydro-1,4-dithiine-1,1,4,4-tetreoxides carried out in a conventional manner. These oxides are important plant growth regulators (see U.S. Pat. No. 3,920,438). Surprisingly, the product produced by the process of the invention can be oxidized without distillation, while the product produced by the prior art, when subjected to the same conditions, provides a much lower yield of the product, which is moreover unacceptably contaminated.

The following examples illustrate the invention.

Example 1

44 g of acetoin, 47.1 g of 1,2-ethanedithiol and 4.9 g of 70% methanesulfonic acid are dissolved in 170.8 of toluene and the resulting solution is heated at 60-75 ° C for 1 hour. 18.3 g (calculated 18.0 g) of water are formed

2,3-dihydro-5,6-dimethyl-1,4-dithiine in 91.1% yield,

NMR spectrum (CDCl 3): 1.86 S (singlet), 3.12 S (singlet).

This result is unexpected in particular β given the fact that an attempt to perform the synthesis below in a similar manner does not achieve the desired result;

/ SH _x Sx _n / ^C « ^H 23

If Γ + jf ^ _SH-CL1 H HO ₂₃

Therefore, the method of the present invention is not predictable, nor is it easy to read from the treatises of Marehall and Stevenaon, published in J. Chem. Soc., 1959, p. 2,360, which states that the yield obtained in the synthesis below was low:

(see also U8 Patent No. 3,947,264). The difficulty of predicting how a particular hydroxyketone will react with dithiol is emphasized by the fact that when attempting to carry out the reaction below, the reactants being subjected to conditions giving good yields in Example 1, only a negligible yield is obtained:

and p-toluenesulfonic acid toluene

4- 2 H ₂ O

This can be done as follows:

To 200 ml of toluene is first added 30 g of benzoin and then 0.5 g of p-toluenesulfonic acid hydrate and 13.3 g of etendithiol. The resulting solution was heated to reflux for 80 minutes with a Dean-Stark trap. After this time, it was found that only a small amount of water (about 0.2 ml) was collected, most of which were the catalyst hydration water and the water contained in etendithiol.

Upon cooling, a solid with a melting point of 105 DEG -126 DEG C. begins to crystallize; the melting point of the mixture and the benzpiper is 105 to 128 (i.e. essentially unchanged benzoin). The filtrate has a characteristic unpleasant odor of unchanged ethanediol. (See these results with Example 1 above and Example 2 below.)

Example 2

43.5 g of acetoin, 46.6 g of 1,2-ethanedithiol and 3.8 g of p-toluenesulfonic acid are dissolved in benzene and the solution is maintained at a temperature in the range of 70-78 ° C for 1 hour. 18.0 g (calculated 18.0 g) of water are obtained. Removal of the solvent gives 2,3-dihydro-5,6-dimethyl-1,4-dithiine in a yield of 94.7%. The NMR spectrum is the same as in Example 1,

Example)

10 g of butyroin, 6.7 g of 1,2-ethanedithiol and 0.5 g of p-toluenesulfonic acid are dissolved in 50 g of toluene, and the resulting solution is heated under reflux with a Dean-Starter cap. Gradually, 1.1 g (calculated 1.28 g) of water was collected. The resulting solution was cooled, washed with dilute aqueous sodium bicarbonate solution and dried.

After removal of the solvent, the oily residue was distilled under reduced pressure. The fraction having a temperature in the range of 80 to 104 ° C under a pressure of 4 Pe is 2,3-dihydro-5,6-dipropyl-1,4-dithiine, which is obtained in a yield of 5.5 g (38%).

NMR Spectrum (CDCl3); 0.93 6 (triplet), 1.23-1.85 µ (multiplet), 2.11-2.38 S (complex quartet), 3.14 5 (singlet).

Example 4

12.2 g of butyroin, 14.4 g of butane-1,2-dithiol and 0.5 g of p-toluenesulfonic acid are dissolved in 50 g of toluene and the resulting solution is heated to reflux with a Dean-Stark trap. Further work-up is carried out as described in Example 3 to give 8.5 g (yield 44% of theory) of 2-ethyl-2,3-dihydro-5,6-dipropyl-1,4-dithiine as a clear greenish liquid with an o distillation range 92 to 105 ° C / 3.33 Pa.

NMR Spectrum (CDCl3): 0.78-1.14 δ (overlapping triplets), 1.21-1.80 δ (multiplet), 2.07-2.37 δ (complex quartet), 2.6- 3.4 S (multiplet).

Example 5

The procedure is as in Example 4, except that 12 g of butyroin, 9 g of propa-1,2-dithiol and 0.5 g of p-toluenesulfonic acid are used. 7.5 g (yield 35% of theory) of 2,3-dihydro-2-methyl-5,6-dipropyl-1,4-dithiine are obtained in the form of a greenish liquid with a distillation range of 76 to 85 ^° C / 7.33 Pa. .

NMR Spectrum (CDCl3): 0.92 δ (triplet), 1.25-2.4 δ (complex overlapping doublet, triplet and quartet), 2.6-3.6 δ (complex multiplet).

Example 6

The procedure is as in Example 4, except that 17.2 g of valeroin is used,

9.4 g of ethane-1,2-dithiol and 0.5 g of p-toluenesulfonic acid. Yield: 66.3%

2,3-dibutyl-5,6-dihydro-1,4-dithiin in the form of a greenish oily liquid with a distillation range of 95 to 110 ° C / 5.33 Pa.

NMR Spectrum (CDCl3): 3.12? (Singlet), 0.7 to 2.4? (Complex series of multiplets in 3 groups).

Example 7

The procedure is as in Example 4, except that 22.8 g of 7-hydroxy-tetra-adadan-8-one, 9.4 g of ethanedithiol and 0.5 g of p-toluenesulfonic acid are used. 2.3 g of dihexyl-5,6-dihydro-1,4-dithiine are obtained in a yield of 67.8% as a greenish oily liquid with a distillation range of 145-155 [deg.] C./12 mbar.

Nuclear Magnetic Resonance Spectrum (CDCl3): 3.13 S (singlet), 0.7 to 2.4 δ (complex series of multiplets).

Example

The procedure is as in Example 4, except that 22.8 g of 7-hydroxytetradecan-8-one, 10.8 g of propane-1,2-dithiol and 0.5 g of p-toluenesulfonic acid are used. In a yield of 63%, 2,3-dihexyl-5,6-dihydro-5-methyl-1,4-dithiine is obtained as a greenish oil liquid with a distillation range of 148-155 ° C / 1 mm Hg.

NMR Spectrum: 0.7 to 1.8 δ (multiplets), 2.05 to 2.35 δ (wide triplet), 2.45 to 3.6 δ (multiplets), 2.95 δ (doublet).

Example 9

The procedure is as in Example 4, except that 10 g of 2-hydroxy-cyclohexanone, 8.3 g of ethanedithiol and 0.5 g of p-toluenesulfonic acid are used. In a yield of 75.1%, 5,6,7,8-tetrahydro-1,4-benzodithiane was obtained as a brownish oil (in the undistilled state).

NMR Spectrum (CDCl 3): 3.14 δ, 1.5 to 2.3 δ (two overlapping complex multiplets).

Example 10

The procedure is as in Example 4 except that 47 g of acetol, 37 g of ethanedithiol and 0.5 g of p-toluenesulfonic acid are used. In a yield of 63.4%, 2,3-dihydro-5-methyl-1,4-dithiine is obtained as a greenish oily liquid with a distillation range of 93-120 ° C / 50 mm Hg.

Nuclear Magnetic Resonance Spectrum (CDCl 3): 5.83 δ (quartet), 3.14 δ (narrow multiplet), 1.92 δ (doublet).

They did

The procedure was as in Example 4 except that 11.6 g of propionic acid (4-hydroxy-3-hexanone) and 16.6 g of 3- (1-methylethoxy) propane-1,2-dithiol were used. 5.6% of diethyl-2,3-dihydro-2- (1-methylethoxy) methyl-1,4-dithiine was obtained in 23% yield as a greenish oil liquid with a distillation range of 80-100 [deg.] G / mmHg.

NMR Spectrum (CDCl3): 0.98 to 1.22 δ (overlapping doublet and triplet), 2.18 δ (triplet), 2.98 to 3.71 δ (overlapping multiplets).

Example 12

The procedure is as in Example 4 except that 25 g of isovaleroin is used,

13.7 g of ethanedithiol and 0.5 g of p-toluenesulfonic acid. In a yield of 61%, 2,3-dihydro-5,6-di- (2-methylpropyl) -1,4-dithiine is obtained as a greenish oily liquid with a distillation range of 96-112 ° C / 24 Pa.

NMR Spectrum: 3.13 δ (singlet), 1.6 to 2.3 δ (multiplets), 0.95 δ (doublet).

Example 1 a d 13

The procedure was as in Example 4 except that 11.6 g of propion (4-hydroxy-3-hexanone) and 16.6 g of 3-propoxypropane-1,2-dithiol were used. In a yield of 42%, 5,6-diethyl-2,3-dihydro-2-propoxymethyl-1,4-dithiine is obtained as a greenish oil liquid with a distillation range of 1 rozmezí to 11 1.5 ° C / 26.7 Pa.

NMR spectrum (CDCl 3): 0.8 to 1.25 δ (triplets), 1.6 to 1.95 δ (complex overlapping signals), 2.75 to 3.65 δ (complex overlapping signals).

Example 14

The procedure is as in Example 4 except that 8.2 g of propioin (4-hydroxy-3-hexanone) and 15.1 g of dodecane-1,2-dithiol are used. 2-Decyl-5,6-diethyl-2,3-dihydro-1,4-dithiine was obtained as a non-distillate oil in 58% yield.

NMR Spectrum (CDCl-j): 0.8 to 1.28 δ (overlapping triplets), 1.38 δ (extended singlet), 2.05 to 2.41 δ (quartet), 2.7 to 3.88 δ (multiplet).

Claims (7)

A process for the preparation of 2,3-dihydro-1,4-dithiins of the general formula I wherein I 2 R and R are both hydrogen or the same or different C 1 -C 6 alkyl groups or together are a ring of 3 or 4 methylene groups with R ⁴ and R ⁴ are both hydrogen or the same or different C 1 -C 10 alkyl groups, the alkyl groups themselves being optionally substituted by 1 or 2 C 1 -C 3 alkoxy groups, characterized in that 1,2- dithiol of formula III HSCHR ³ CHR ⁴ SH (III), where R ⁴ and R ⁴ are as defined above, reacted with an α-hydroxyketone of the general formula II r'chohgor ² (II), where 1 2 R and R are as defined above, in the presence of an acid catalyst to form the dihydrothiin of formula I and reaction water 2. The process of claim 1 wherein the catalyst is p-toluenesulfonic acid or methanesulfonic acid. 3. Process according to claim 1, characterized in that the water produced in the reaction is removed azeotropically. 4. The process of claim 2 wherein the reaction is carried out in the presence of a solvent selected from the group consisting of benzene, toluene or xylene. 5. A process according to claim 1, wherein the starting compounds are used 1 and 2 -dihydroxyketonu formula II wherein R and R are methyl groups, and 1,2-dithiol of the formula III, wherein R and R ⁴ represent hydrogen atoms. 6. A process according to claim 1, wherein the starting compounds are used 1 2 a-hydroxyketone of formula II wherein R and R are methyl groups, and 1,2-dithiol of the formula III wherein R is methyl and R ⁴ is hydrogen. 7. A method according to claim 1, characterized in that the starting compounds used and dihydroxyketonu-formula IX, wherein R ¹ and R ² are methyl groups, and 1,2-dithiol of the formula III wherein R represents an ethyl group and R ⁴ represents a hydrogen atom.