CN85103016B - Preperation of domidin and its usage - Google Patents

Abstract

A germicide called as 'Duomeijing' (chemical name: 4-isothiazolin-3-ketone, namely 3-hydroxyl isothiazole) (I) has the structural formula of *** (disclosed in the specification). The present invention relates to a method for preparing the compound, which comprises the steps that chlorine gas is introduced into the acetic acid solution of 3, 3'-dithio-dipropionamide (II), and the 4-isothiazolin-3-ketone is obtained after alkali treatment, wherein the intermediate (II) of the germicide is obtained by the method that acrylamide and sodium polysulfide react in water solution in the existence of sodium bicarbonate, and then the product of the reaction is treated by the water solution of sodium sulfite. By using the method for synthesizing (I), hydrogen sulfide gas with high toxicity does not need to be used, and raw materials with low price and easy obtainment are adopted; the present invention has the advantages of convenient operation, high yield and easy industrial production. The 'Duomeijing' can be used for commercial sterilization and mildew prevention. 233:61)(C07D403/04:95, 249:08).

Description

Many mould clean preparations and application

The invention belongs to the sterilant class.

Synthetic 4-isothiazoline-3-ketone (I), i.e. " how mould clean ", if according to literature method (1), its intermediate 3,3 '-dithio dipropyl acidamide (II) is 1: 3.5 with the mole ratio of chlorine reaction, yield is 75%.The synthetic method of intermediate (II), at patent U.S.3,769,315(1973) in, by acrylamide and sulphur, hydrogen sulfide and ammonium sulfide or sodium tetrasulfide reaction and prepare.All toxic bigger hydrogen sulfide is participated in the reaction process, and yield is up to 72%.

The objective of the invention is to improve operational path, reduce toxicity, improve yield, be convenient to suitability for industrialized production.

Method with the present invention's preparation (I) is as follows:

(1) intermediate (II) is synthetic:

At first, under agitation be heated to and boil with sodium sulphite and sulphur (mole ratio is 1: 2.5), up to producing the transparent sodium polysulphide liquid of reddish-brown.Put and treat coldly usefulness.

Then, (1: 1) ， of mole ratio And adds an amount of water, fully stirs the frozen water cooling to add acrylamide and sodium bicarbonate in four-hole bottle.Slowly drip the sodium polysulfide solution for preparing above simultaneously.Continue to stir 3-5 hour, filter, obtain many sulphur of solid thing.Many sulphur of solid thing of hygrometric state is handled with the sodium sulfite aqueous solution of 1 molconcentration of capacity.Filtration, drying promptly obtain intermediate (II) then.

The mole ratio of above-mentioned each raw material is: CH ₂=CHCONH ₂: Na ₂Sx: NaHCO ₃: Na ₂SO ₃=2: 1: 2: 1.2

(2) (II) that aforesaid method is made and chlorine reaction preparation (I).Wherein (II) is 1: 3.05 with the mole ratio of chlorine.The solvent ethyl acetate sectional reclaims, and recycles.

With the present invention's preparation (I), product yield brings up to 83%.The solvent ethyl acetate rate of recovery is more than 90%, and recycles and do not influence product yield and content.Needn't use deleterious hydrogen sulfide during preparation intermediate (II), yield brings up to 83%.Simultaneously, raw material is cheap and easy to get.And (I) has activity antimycotic, bacterium, can be as industrial biocide mildewcide.During application, at first will how mouldly be dissolved in only in water or ethanol, ethyl acetate, the acetone and other organic solvent, joining then needs in the industrial goods of the fungus and mildew resistance material, is made into minimal effective concentration and gets final product.

Example 1

3,3 '-preparation of dithio dipropyl acidamide

Take by weighing 62.4 grams (0.26 mol) and contain the sodium sulphite of 9 crystal water and the sulphur of 20.8 grams (0.65 mol), the beaker of packing into is heated with stirring to and boils, and the transparent liquid of reddish-brown that generate this moment is sodium polysulfide solution, puts cold standby.

In 500 milliliters of four-hole bottles, add 35.5 gram (0.5 mol) acrylamides (also available industrial acrylamide solution), 42 gram (0.5 mol) sodium bicarbonate and 320 ml waters, fully stir, the frozen water cooling slowly drips the sodium polysulfide solution for preparing above, continue to stir 5 hours, filter the gained solid and be many sulphur thing, take advantage of and wet the step to handle.

Many sulphur of gained thing to be handled with the sodium sulfite aqueous solution of about 300 milliliter of 1 molconcentration, filtration drying promptly get 3,3 '-dithio dipropyl acidamide 44.5 restrains.Fusing point 176-180 ℃, content 97%, pure yield 83%.

(product content is through high pressure liquid chromatographic analysis)

Crude product is through the ethanol/water recrystallization.Fusing point 176-178 ℃

Ultimate analysis: analytical value S% 30.42 H% 13.36

30.47 13.56

Calculated value 30.77 13.46

Raman spectrum (acetone soln) ν _S-S510cm ^-1ν _C-S658cm ^-1

Example 2

The preparation of 4-isothiazoline-3-ketone (promptly how mould clean)

Adding content is (II) 44.1 gram (0.2 mol) and 200 milliliters of exsiccant ethyl acetate of 94% in 500 milliliters of four-hole bottles, heat is to 40 ℃, feed chlorine, temperature of reaction remains on 45-50 ℃, reaction later stage hydrogen chloride gas is emitted rapidly, after reacting completely, forms uniform cream-colored suspension, commonly go into chlorine 43.2 grams (0.61 mol), be chilled to room temperature, filter.Again with solid suspension in 150 milliliters of ethyl acetate, being neutralized to ph value of aqueous phase with 20% aqueous sodium hydroxide solution is about 4.5 down in cooling, tell organic layer, drying, desolventizing promptly get product, weigh 34.1 grams, content 98.3%(through high pressure liquid chromatography, thin layer scanning or gc analysis all can), yield 83%, the sherwood oil recrystallization gets white needle-like crystals, fusing point 72.5-73 ℃

Ultimate analysis: analytical value S% 31.39 N% 13.66

31.56 13.58

Calculated value 31.68 13.86

δ12.80ppm（1H.S.OH）

　　　　δ8.44，8.52ppm（1H d Hb）

　　　　δ6.60，6.68ppm（1H d Ha）

Example 3

The recycling use method of solvent ethyl acetate

The ethyl acetate that logical one step of chlorine is filtered the acid gas-containing of back gained is heavily steamed, be used further to logical one step of chlorine.The ethyl acetate of final product desolventizing gained is directly used in one step of alkaline purification.

Example 4

Many mould clean biological activitys to various industrial moulds, bacterium

How mould clean employing contain mould medium method and measure " " relative inhibition percentage to various common industrial moulds; Adopt " turbidimetry " to measure how mould clean minimal effective concentration and the results are shown in table one, table two various common industrial bacteriums.

How mould clean table one " " suppress percentage relatively to various industrial moulds

Mould title 250 100 50(PPM)

Aspergillus niger 100 87.5 85.0

Penicillium citrinum " 88.3 86.6

Wood mould " 81.6 55.0

Chaetomium globosum " 85.0 68.0

Cladosporium herbarum " 81.0 74.8

Paecilomyces varioti " 100 80.5

How mould clean table two " " to various industrial bacteriums

Minimum inhibitory concentration

Bacteria name minimum inhibitory concentration PPM

Bacillus megaterium 6.25

Bacillus subtilus 6.25

Intestinal bacteria 50

Light pseudomonas 6.25

Streptococcus aureus 25

Example 5

How mould clean " " renderd a service the acrylic latex coating mildew-resistant

(5 * 5cm) is clean with solvent scouring with aluminium sheet, the acrylic latex coating that contains the finite concentration mould inhibitor is smeared on top, after paint film is done, lie in the incubator that contains the PDA substratum, with evenly spraying industrial mould spores suspension on the equal model of the mould device of spray, the ware lid is placed in the tube of preserving moisture in the lid then, relative humidity is more than 95%, temperature remains in 26 ℃ the thermostat container, and month " Invest, Then Investigate " model degree that mildews the results are shown in Table three.

Grade scale

0 grade of mildew not

The local fragmentary little mildew of I level

II level mildew area is no more than 1/4

III level mildew area accounts for whole area about 1/2

The whole surface of IV level is covered with mould class

How mould table three is renders a service the acrylic latex coating mildew-resistant only

Medicament title concentration

0.2% 0.1% 0.05%

Many mould clean 00 I

N-54-D 0 Ⅰ Ⅱ

Contrast IV IV IV (level)

Example 6

How mould clean " " prevent the corrupt effectiveness of acrylic latex coating

Preparation contains the acrylic latex coating of finite concentration mould inhibitor, does contrast with not dosing.Add in the lacquer 1% cause the putrid various bacterium mixed solutions of emulsion paint.Be placed in 37 ℃ of thermostat containers and keep relative humidity more than 95%.With bacterium viable count colony counting method, counting is respectively handled the viable count that every gram emulsion paint contains after one month.The results are shown in Table four

How mould clean table four " " prevent the corrupt effect of acrylic latex coating

The viable count of the every gram emulsion paint of medicament title concentration

Many mould clean 0.1% 3 * 10 ⁴

N-54-D 0.1% 5.5×10 ^４

Contrast-7.8 * 10 ⁴

Annotate: (1) N-54-D is clean for the mildew-resistant that the U.S. big auspicious Mei Hua company limited provides.Chemical name: daconil M trade(brand)name: Nopcoide-N-54-D.

(2) used bacterial classification is respectively table one, the listed bacterial classification of table two.

Reference

〔1〕S.N.Lewis et al J.Heter hem 1971 8（4）P571-80

Claims (18)

1, a kind of with 3,3 '-dithio dipropyl acidamide (II) is a raw material with chlorine, with the ethyl acetate be solvent preparation " how mould clean " (

, (I)) method, when it is characterized in that synthetic intermediate (II), adopt following route:

During with (II) preparation (I), (II) is 1: 3.05 with the mole ratio of chlorine.

2, how mould clean according to the method for the said manufacturing of claim 1 " " (I), when it is characterized in that synthesizing (II), the mole ratio of each raw material is:

CH _２＝CHCONH _２∶Na _２Sx∶NaHCO _３∶Na _２SO _２＝2∶1∶2∶1.2

3,, it is characterized in that the solvent for use ethyl acetate is recyclable to recycle according to the method for claim 1 or 2 said preparations (I).

4, a kind of use how mould only as the method for industrial fungus and mildew resistance, when it is characterized in that using, at first with how mould being dissolved in only in water or the common organic solvents (as ethanol, ethyl acetate, acetone), and then join (as producing employed gelatin solution, machine tool coolant, paste, recirculated water, electrophoretic coating liquid and various paint etc. such as film and opticinstrument element) in the Industrial materials that need fungus and mildew resistance, be made into minimal effective concentration and get final product, how mould clean quenchable industrial mould, bacterium and minimal effective concentration thereof be as follows:

The how mould clean minimal effective concentration 50(PPM of aspergillus niger)

Penicillium citrinum " 50(PPM)

Wood is mould " 100(PPM)

Chaetomium globosum " 100(PPM)

Cladosporium herbarum " 100(PPM)

Paecilomyces varioti " 50(PPM)

Bacillus megaterium " 6.25(PPM)

Bacillus subtilus " 6.25(PPM)

Intestinal bacteria " 50(PPM)

The fluorescent pseudomonas " 6.25(PPM)

Streptococcus aureus " 25(PPM)