CN102977050B - Method for synthesizing 2-benzothiazolyl dimethylacetal and 2-benzothiazol formaldehyde - Google Patents
Method for synthesizing 2-benzothiazolyl dimethylacetal and 2-benzothiazol formaldehyde Download PDFInfo
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Abstract
The invention discloses a method for synthesizing 2-benzothiazolyl dimethylacetal and 2-benzothiazol formaldehyde. According to the method, benzothiazole shown in a formula III and methanol shown in a formula IV are taken as raw materials, and reaction is carried out under the action of an oxidant so as to produce the 2-benzothiazolyl dimethylacetal shown in a formula I; and in an organic solvent, the 2-benzothiazolyl dimethylacetal shown in the formula I is subjected to reaction under the action of an acid catalyst so as to produce the 2-benzothiazol formaldehyde shown in a formula II. The method disclosed by the invention has the advantages of low price and easy acquisition of raw materials, simple process, simplicity and convenience in operation, environmental friendliness and high atom economy.
Description
(1) technical field
The present invention relates to the synthetic method of 2-[4-morpholinodithio dimethylacetal and 2-[4-morpholinodithio formaldehyde.
(2) background technology
Benzothiazole is the extremely important heterogeneous ring compound of a class, at medicine (Curr. Med. Chem., 2009,16 (19): 2430-2440), agricultural chemicals (Agriculture of Anhui science, 2005,33 (7): 1254-1257), there is purposes widely in the field such as material engineering (Organic Electronics, 2010,11 (1): 1-9).Such as, pharmaceutically, benzothiazole compound can as sterilant, fungicides etc., can also be used for parasiticide, antituberculosis, wind resistance diseases caused by dampness and anticancer etc.; Agriculturally, benzothiazole compound has anti-agricultural fungi, desinsection, weeding, plant growth regulating isoreactivity; In material engineering field, benzothiazole compound can be used as uv-absorbing agent, liquid crystal display material, electroluminescent material and fluorescence probe material etc. in thiofide, dyeing of plastics agent, makeup and sun glasses.2-[4-morpholinodithio dimethylacetal and 2-[4-morpholinodithio formaldehyde are owing to having the very high dimethylacetal base of reactive behavior and formyl radical; can number of chemical transformationreation be carried out, thus become the numerous important intermediate of benzothiazole analog derivative that there is potential physiology or pharmacologically active or there is multiple material functional attributes of synthesis.Such as, Ullapu etc. report 2-[4-morpholinodithio formaldehyde in document (Bull. Korean Chem. Soc., 2011,32 (8): 3063-3073) is the key intermediate synthesizing a kind of T-type ockers; It is a kind of important intermediate for the treatment of the heterocyclic drug of nervus centralis and metabolism class disease of synthesis that Campbell etc. report 2-[4-morpholinodithio formaldehyde in patent documentation (WO 2011150156 A2, Dec.01,2011); The report 2-[4-morpholinodithio formaldehyde in patent documentation (WO 2010108059 A1, Sep. 23,2010) such as Zhou is the important intermediate of synthesizing a kind of histamine H 4 receptor antagonist; It is the synthesis precursor preparing a kind of novel brominated photosensitizers that Gao etc. then report 2-[4-morpholinodithio formaldehyde in patent documentation (CN 101973958A, Feb.16,2011).
Although 2-[4-morpholinodithio formaldehyde has purposes widely, but until today, its synthetic method is still very limited.
Ullapu etc. are at document (Bull. Korean Chem. Soc., 2011,32 (8): 3063-3073) report in and under-78 ° of C, first react obtained benzothiazole lithium reagent with butyllithium by 2-bromo benzothiazole, benzothiazole lithium reagent reacts to prepare 2-[4-morpholinodithio formaldehyde with DMF again; Campbell etc. are at patent documentation (WO 2011150156A2, Dec.01,2011) report in and directly under-78 ° of C, react obtained benzothiazole lithium reagent by benzothiazole and butyllithium, then react to prepare 2-[4-morpholinodithio formaldehyde with DMF.These two kinds of methods all will use the butyllithium reagent to water and air sensitivity, and reaction needed is carried out at low temperatures, and reagent is expensive, operation inconvenience.2008; Belda etc. are at patent documentation (WO 2008107365 A1; Sep. 12; 2008) a kind of synthetic method of synthesizing 2-[4-morpholinodithio formaldehyde is reported in; namely first 2-ethoxycarbonyl benzothiazole is reacted to obtain, then at reductive agent AlH (Bu-i) by o-amino thiophenol and oxalic acid diethyl ester
2effect under 2-[4-morpholinodithio formaldehyde.The defect of this method is AlH (Bu-i)
2price comparison is expensive, and need use cold condition (-50 ° of C) equally, and operation inconvenience, is unfavorable for scale operation.Finn etc. are at patent documentation (WO 2004076386A2, Sep. 10,2004) report in tin anhydride be oxidizing 2-methylbenzothiazole to prepare 2-[4-morpholinodithio formaldehyde, this method need use poisonous tin anhydride for oxygenant, easily cause side reaction, productive rate is lower.
In view of above Problems existing, design that raw material is cheap and easy to get, easy and simple to handle, the route of environmental protection ground synthesis 2-[4-morpholinodithio formaldehyde seems and is extremely necessary.
(3) summary of the invention
The technical problem to be solved in the present invention is to provide that a kind of raw material is cheap and easy to get, technique is simple, easy and simple to handle, the method for synthesizing to environmental friendliness, atom economy 2-[4-morpholinodithio formaldehyde.
For solving the problems of the technologies described above, the present invention adopts following technical scheme:
A synthetic method for 2-[4-morpholinodithio dimethylacetal shown in formula I, described method for: with the methyl alcohol shown in the benzothiazole shown in formula III and formula IV for raw material, the obtained 2-[4-morpholinodithio dimethylacetal shown in formula I of reaction under the effect of oxygenant; Described oxygenant is selected from one of following: iron trichloride, cupric oxide, potassium bichromate, permanganic acid acid potassium, perbenzoic acid acid anhydride, tertbutanol peroxide, potassium hydrogen persulfate composite salts (being called for short Oxone), Potassium Persulphate, Sodium Persulfate, ammonium persulphate, ceric ammonium nitrate (being called for short CAN), benzoquinones, 2,3-bis-chloro-5,6-dicyan-Isosorbide-5-Nitrae-benzoquinones (being called for short DDQ), ditertiary butyl peroxide or hydrogen peroxide;
。
The reaction formula of described reaction is as follows:
The raw material benzothiazole III that the present invention uses and methyl alcohol are commercial reagents, about raw material benzothiazole III, those skilled in the art also can prepare according to method disclosed in existing document voluntarily, such as document [Chinese Journal of Chemistry, 2009,27:379-383].
Further, preferred the method for the invention for: by the benzothiazole shown in formula III, oxygenant, methyl alcohol in closed reaction vessel, be heated to 80 DEG C ~ 150 DEG C stirring reactions 0.5 ~ 30 hour, gained reaction solution a obtains the 2-[4-morpholinodithio dimethylacetal shown in formula I through separation and purification.
In the present invention, the volumetric usage of described methyl alcohol counts 1 ~ 150 mL/mmol with the amount of substance of the quinoxaline shown in formula III, preferably 30 ~ 100 mL/mmol.
Oxygenant of the present invention is preferably Potassium Persulphate, Sodium Persulfate, ammonium persulphate or ceric ammonium nitrate.Most preferably Potassium Persulphate, is characterized in that productive rate is high, regioselectivity is high and oxygenant is nontoxic.
The ratio of the amount of substance of benzothiazole of the present invention, oxygenant is 1:1 ~ 8, preferred 1:3 ~ 5.
Described reaction is carried out under the temperature condition of 80 DEG C ~ 150 DEG C, and preferable reaction temperature is 110 DEG C.The described reaction times is 0.5 ~ 30 hour, preferably 15 hours.
Described reaction solution a separation purification method is preferably: gained reaction solution a filters, after filtrate washed with dichloromethane, concentrated except desolventizing, the thick product of gained is through column chromatography for separation, stationary phase is 200 – 300 object neutral aluminas, the mixing solutions being 6:1 with sherwood oil, ethyl acetate volume ratio is for eluent, and gained elutriant steams and desolventizes the 2-[4-morpholinodithio dimethylacetal obtained shown in formula I.
After obtaining 2-[4-morpholinodithio base dimethylacetal by synthetic method of the present invention, 2-[4-morpholinodithio formaldehyde can be converted into easily in acid condition.
Concrete; the present invention also provide shown in a kind of formula II the synthetic method of 2-[4-morpholinodithio formaldehyde; described method for: with the methyl alcohol shown in the benzothiazole shown in formula III and formula IV for raw material, the obtained 2-[4-morpholinodithio dimethylacetal shown in formula I of reaction under the effect of oxygenant; 2-[4-morpholinodithio dimethylacetal shown in formula I in organic solvent, under the effect of acid catalyst shown in the obtained formula II of reaction 2-[4-morpholinodithio formaldehyde; Described oxygenant is selected from one of following: the acid of iron trichloride, cupric oxide, potassium bichromate, permanganic acid potassium, perbenzoic acid acid anhydride, tertbutanol peroxide, potassium hydrogen persulfate composite salts, Potassium Persulphate, Sodium Persulfate, ammonium persulphate, ceric ammonium nitrate, benzoquinones, 2,3-bis-chloro-5,6-dicyan-Isosorbide-5-Nitrae-benzoquinones, ditertiary butyl peroxide or hydrogen peroxide;
。
Further, shown in described formula II the synthetic method of 2-[4-morpholinodithio formaldehyde preferably carry out according to the following steps: (1) by the benzothiazole shown in formula III, oxygenant, methyl alcohol in closed reaction vessel, be heated to 80 DEG C ~ 150 DEG C stirring reactions 0.5 ~ 30 hour, gained reaction solution a obtains the 2-[4-morpholinodithio dimethylacetal shown in formula I through separation and purification; (2) the 2-[4-morpholinodithio dimethylacetal shown in formula I adds in organic solvent, and under the effect of acid catalyst, react 1 ~ 20 hour under the temperature condition of 20 ~ 120 DEG C, gained reaction solution b aftertreatment obtains the 2-[4-morpholinodithio formaldehyde shown in formula II.
The reaction formula of described reaction is as follows:
Described acid catalyst is selected from following a kind of or two or more arbitrarily combination: sulfuric acid, nitric acid, phosphoric acid, hydrochloric acid, acetic acid, formic acid, ammonium chloride, potassium primary phosphate, sal enixum, boric acid, preferred hydrochloric acid, nitric acid or phosphoric acid, most preferably hydrochloric acid.Described hydrochloric acid is generally the hydrochloric acid of 1mol/L.
Described acid catalyst is 1 ~ 15:1 with the ratio of the amount of substance of the 2-[4-morpholinodithio dimethylacetal shown in formula I, preferred 15:1.Described acid catalyst adds fashionable in form of an aqueous solutions, and the amount of substance of acid catalyst refers to the amount of substance of the acid wherein contained, and such as, for hydrochloric acid, in fact refers to the amount of substance of the HCl wherein contained.Those skilled in the art can understand the physical meaning of the amount of substance of acid catalyst.
Described organic solvent is following a kind of or two or more arbitrarily combination: methylene dichloride, acetonitrile, ether, Nitromethane 99Min., tetrahydrofuran (THF), methyl alcohol, toluene, 1,2-ethylene dichloride, trichloromethane, 1,4-dioxane, methyl-sulphoxide, N, dinethylformamide, preferably 1,2-ethylene dichloride, Isosorbide-5-Nitrae-dioxane, ether or tetrahydrofuran (THF), most preferably Isosorbide-5-Nitrae-dioxane.
The reaction being prepared 2-[4-morpholinodithio formaldehyde by 2-[4-morpholinodithio base dimethylacetal of the present invention, preferably carry out under the temperature condition of 20 ~ 120 DEG C, the reaction times is preferably 1 ~ 20 hour.
Described reaction solution b post-treating method is: gained reaction solution b is concentrated except after desolventizing, the thick product of gained is separated through silica gel column chromatography, the mixing solutions being 6:1 with sherwood oil, ethyl acetate volume ratio is for eluent, and gained elutriant steams and desolventizes the 2-[4-morpholinodithio formaldehyde obtained shown in formula II.
More specifically, the present invention recommends the synthetic method of the 2-[4-morpholinodithio dimethylacetal shown in described formula I and the 2-[4-morpholinodithio formaldehyde shown in formula II to carry out as follows:
(1) by the benzothiazole shown in formula III, oxygenant, methyl alcohol in closed reaction vessel, be heated to 80 DEG C ~ 150 DEG C stirring reactions 0.5 ~ 30 hour, gained reaction solution a filters, after filtrate washed with dichloromethane, concentrated except desolventizing, the thick product of gained is through column chromatography for separation, and stationary phase is 200 – 300 object neutral aluminas, the mixing solutions being 6:1 with sherwood oil, ethyl acetate volume ratio is for eluent, and gained elutriant steams and desolventizes the 2-[4-morpholinodithio dimethylacetal obtained shown in formula I; The volumetric usage of described methyl alcohol counts 1 ~ 150mL/mmol with the amount of substance of the benzothiazole shown in formula III; Described oxygenant is selected from one of following: iron trichloride, cupric oxide, potassium bichromate, permanganic acid acid potassium, perbenzoic acid acid anhydride, tertbutanol peroxide, potassium hydrogen persulfate composite salts (being called for short Oxone), Potassium Persulphate, Sodium Persulfate, ammonium persulphate, ceric ammonium nitrate (being called for short CAN), benzoquinones, 2,3-bis-chloro-5,6-dicyan-Isosorbide-5-Nitrae-benzoquinones (being called for short DDQ), ditertiary butyl peroxide or hydrogen peroxide; The ratio of the amount of substance of described benzothiazole, oxygenant is 1:1 ~ 8;
(2) the 2-[4-morpholinodithio dimethylacetal shown in formula I adds in organic solvent, under the effect of acid catalyst, react 1 ~ 20 hour under the temperature condition of 20 ~ 120 DEG C, gained reaction solution b is concentrated except after desolventizing, the thick product of gained is separated through silica gel column chromatography, the mixing solutions being 6:1 with sherwood oil, ethyl acetate volume ratio is for eluent, and gained elutriant steams and desolventizes the 2-[4-morpholinodithio formaldehyde obtained shown in formula II; Described acid catalyst is selected from following a kind of or two or more arbitrarily combination: sulfuric acid, nitric acid, phosphoric acid, hydrochloric acid, acetic acid, formic acid, ammonium chloride, potassium primary phosphate, sal enixum, boric acid; Described acid catalyst is 1 ~ 15:1 with the ratio of the amount of substance of the 2-[4-morpholinodithio dimethylacetal shown in formula I; Described organic solvent is following a kind of or two or more arbitrarily combination: methylene dichloride, acetonitrile, ether, Nitromethane 99Min., tetrahydrofuran (THF), methyl alcohol, toluene, 1,2-ethylene dichloride, trichloromethane, 1,4-dioxane, methyl-sulphoxide, DMF.
Compared with prior art, the present invention by benzothiazole and methyl alcohol oxygenant effect next step obtain 2-[4-morpholinodithio base dimethylacetal, then 2-[4-morpholinodithio base dimethylacetal in acid condition deprotection can obtain 2-[4-morpholinodithio formaldehyde.The beneficial effect of the method is: raw material is cheap and easy to get, technique is simple, easy and simple to handle, oxygenant is nontoxic, environmental friendliness and Atom economy high.
(4) embodiment
Below in conjunction with specific embodiment, the present invention is described in further detail, but protection scope of the present invention is not limited thereto:
Embodiment 1
By benzothiazole III (27.0 mg, 0.2 mmol), Potassium Persulphate (0.27 g, 1.0 mmol), and dry methyl alcohol (6 mL) adds in withstand voltage reaction tubes, reacts 15 h at 110 DEG C.Be cooled to room temperature, cross and filter salt, by 3 × 10 mL washed with dichloromethane three times.After filtrate precipitation is concentrated, thick product column chromatography (chromatography neutral alumina; 200 – 300 orders; Eluent is V (sherwood oil)/V (ethyl acetate)=6/1) separating-purifying, gained elutriant steams to desolventize and obtains yellow oily liquid 2-[4-morpholinodithio base dimethylacetal (I) 26.8 mg, yield 64%.
Characterization data: R
f=0.40; IR (neat): v=3032,2926,2866,1598,1509,1448,1371 cm
-1;
1h NMR (CDCl
3, 500MHz): δ 8.10 (d, J=8.2 Hz; 1H), 7.92 (d, J=8.3 Hz; 1H), 7.52-7.49 (m, 1H); 7.44-7.40 (m; 1H), 5.71 (s, 1H); 3.51 (s, 6H);
13c NMR (CDCl
3, 125 MHz): δ 168.7,153.1,135.2,126.1,125.5,123.7,121.8,100.7,53.7; GC-MS (EI, 70eV): m/z (%)=209 (14) [M
+]; HRMS (EI) for C
10h
11nO
2s [M
+]: calcd. 209.0511, found 209.0505.
By 2-[4-morpholinodithio base dimethylacetal (I) (41.9 mg prepared according to the method described above, 0.2 mmol) be dissolved in 5 mL 1, in 4-dioxane, add 3 mL hydrochloric acid solns (1 mol/L) again, 6 h are reacted at 70 DEG C, after reaction solution precipitation is concentrated, thick product column chromatography (chromatography GF254 silica gel; 100 – 200 orders; Eluent is V (sherwood oil)/V (ethyl acetate)=6/1) separating-purifying, gained elutriant steams to desolventize and obtains yellow solid 2-[4-morpholinodithio formaldehyde (II) 29.7 mg, yield 91%.
Characterization data: mp 74-75 oC (lit. mp 74 oC); R
f=0.42;
1h NMR (CDCl
3, 500 MHz): δ 10.19 (s, 1H), 8.26 (d, J=8.5 Hz, 1H), 8.03 (d, J=8.5 Hz, 1H), 7.64-7.59 (m, 2H);
13c NMR (CDCl
3, 125 MHz): δ 185.4,165.4,153.6,136.4,128.4,127.4,125.8,122.6;
gC-MS (EI, 70eV): m/z (%)=163 (100) [M
+].
Embodiment 2
By benzothiazole III (27.0 mg, 0.2 mmol), Potassium Persulphate (0.43 g, 1.6 mmol), and dry methyl alcohol (6 mL) adds in withstand voltage reaction tubes, reacts 0.5 h at 150 DEG C.Be cooled to room temperature, cross and filter salt, filtrate is by 3 × 10 mL washed with dichloromethane three times.After filtrate precipitation is concentrated, thick product column chromatography (chromatography neutral alumina; 200 – 300 orders; Eluent is V (sherwood oil)/V (ethyl acetate)=6/1) separating-purifying, gained elutriant steams to desolventize and obtains yellow oily liquid 2-[4-morpholinodithio base dimethylacetal (I) 21.4 mg, yield 51%.
By 2-[4-morpholinodithio base dimethylacetal (I) (41.9 mg prepared according to the method described above, 0.2 mmol) be dissolved in 3 mL1, in 4-dioxane, add 3 mL hydrochloric acid solns (1 mol/L) again, 20 h are reacted at 70 DEG C, after reaction solution precipitation is concentrated, thick product column chromatography (chromatography GF254 silica gel; 100 – 200 orders; Eluent is V (sherwood oil)/V (ethyl acetate)=6/1) separating-purifying, gained elutriant steams to desolventize and obtains yellow solid 2-[4-morpholinodithio formaldehyde (II) 28.7 mg, yield 88%.
Embodiment 3
By benzothiazole III (27.0 mg, 0.2 mmol), Potassium Persulphate (0.16 g, 0.6 mmol), and dry methyl alcohol (6 mL) adds in withstand voltage reaction tubes, reacts 30 h at 80 DEG C.Be cooled to room temperature, cross and filter salt, filtrate is by 3 × 10 mL washed with dichloromethane three times.After filtrate precipitation is concentrated, thick product column chromatography (chromatography neutral alumina; 200 – 300 orders; Eluent is V (sherwood oil)/V (ethyl acetate)=6/1) separating-purifying, gained elutriant steams to desolventize and obtains yellow oily liquid 2-[4-morpholinodithio base dimethylacetal (I) 16.8 mg, yield 40%.
By 2-[4-morpholinodithio base dimethylacetal (I) (41.9 mg prepared according to the method described above, 0.2 mmol) be dissolved in 10 mL1, in 4-dioxane, add 3 mL hydrochloric acid solns (1 mol/L) again, 3 h are reacted at 70 DEG C, after reaction solution precipitation is concentrated, thick product column chromatography (chromatography GF254 silica gel; 100 – 200 orders; Eluent is V (sherwood oil)/V (ethyl acetate)=6/1) separating-purifying, gained elutriant steams to desolventize and obtains yellow solid 2-[4-morpholinodithio formaldehyde (II) 28.0 mg, yield 86%.
Embodiment 4
By benzothiazole III (27.0 mg, 0.2 mmol), Potassium Persulphate (0.27 g, 1.0 mmol), and dry methyl alcohol (6 mL) adds in withstand voltage reaction tubes, reacts 0.5 h at 110 DEG C.Be cooled to room temperature, cross and filter salt, filtrate is by 3 × 10 mL washed with dichloromethane three times.After filtrate precipitation is concentrated, thick product column chromatography (chromatography neutral alumina; 200 – 300 orders; Eluent is V (sherwood oil)/V (ethyl acetate)=6/1) separating-purifying, gained elutriant steams to desolventize and obtains yellow oily liquid 2-[4-morpholinodithio base dimethylacetal (I) 17.2 mg, yield 41%.
By 2-[4-morpholinodithio base dimethylacetal (I) (41.9 mg prepared according to the method described above, 0.2 mmol) be dissolved in 5 mL1, in 4-dioxane, add 3 mL hydrochloric acid solns (1 mol/L) again, 6 h are reacted at 20 DEG C, after reaction solution precipitation is concentrated, thick product column chromatography (chromatography GF254 silica gel; 100 – 200 orders; Eluent is V (sherwood oil)/V (ethyl acetate)=6/1) separating-purifying, gained elutriant steams to desolventize and obtains yellow solid 2-[4-morpholinodithio formaldehyde (II) 26.4 mg, yield 81%.
Embodiment 5
By benzothiazole III (27.0 mg, 0.2 mmol), Potassium Persulphate (0.27 g, 1.0 mmol), and dry methyl alcohol (1 mL) adds in withstand voltage reaction tubes, reacts 15 h at 110 DEG C.Be cooled to room temperature, cross and filter salt, filtrate is by 3 × 10 mL washed with dichloromethane three times.After filtrate precipitation is concentrated, thick product column chromatography (chromatography neutral alumina; 200 – 300 orders; Eluent is V (sherwood oil)/V (ethyl acetate)=6/1) separating-purifying, gained elutriant steams to desolventize and obtains yellow oily liquid 2-[4-morpholinodithio base dimethylacetal (I) 12.6 mg, yield 30%.
By 2-[4-morpholinodithio base dimethylacetal (I) (41.9 mg prepared according to the method described above, 0.2 mmol) be dissolved in 5 mL tetrahydrofuran (THF)s, add 3 mL hydrochloric acid solns (1mol/L) again, 6 h are reacted at 70 DEG C, after reaction solution precipitation is concentrated, thick product column chromatography (chromatography GF254 silica gel; 100 – 200 orders; Eluent is V (sherwood oil)/V (ethyl acetate)=6/1) separating-purifying, gained elutriant steams to desolventize and obtains yellow solid 2-[4-morpholinodithio formaldehyde (II) 27.4 mg, yield 84%.
Embodiment 6
By benzothiazole III (27.0 mg, 0.2 mmol), Potassium Persulphate (0.27 g, 1.0 mmol), and dry methyl alcohol (30 mL) adds in withstand voltage reaction tubes, reacts 15 h at 110 DEG C.Be cooled to room temperature, cross and filter salt, filtrate is by 3 × 10 mL washed with dichloromethane three times.After filtrate precipitation is concentrated, thick product column chromatography (chromatography neutral alumina; 200 – 300 orders; Eluent is V (sherwood oil)/V (ethyl acetate)=6/1) separating-purifying, gained elutriant steams to desolventize and obtains yellow oily liquid 2-[4-morpholinodithio base dimethylacetal (I) 26.5 mg, yield 63%.
By 2-[4-morpholinodithio base dimethylacetal (I) (41.9 mg prepared according to the method described above, 0.2 mmol) be dissolved in 5 mL1, in 4-dioxane, add 3 mL phosphoric acid solutions (1 mol/L) again, 6 h are reacted at 70 DEG C, after reaction solution precipitation is concentrated, thick product column chromatography (chromatography GF254 silica gel; 100 – 200 orders; Eluent is V (sherwood oil)/V (ethyl acetate)=6/1) separating-purifying, gained elutriant steams to desolventize and obtains yellow solid 2-[4-morpholinodithio formaldehyde (II) 28.4 mg, yield 87%.
Embodiment 7
By benzothiazole III (27.0 mg, 0.2 mmol), ammonium persulphate (0.23 g, 1.0 mmol), and dry methyl alcohol (6 mL) adds in withstand voltage reaction tubes, reacts 15 h at 110 DEG C.Be cooled to room temperature, cross and filter salt, filtrate is by 3 × 10 mL washed with dichloromethane three times.After filtrate precipitation is concentrated, thick product column chromatography (chromatography neutral alumina; 200 – 300 orders; Eluent is V (sherwood oil)/V (ethyl acetate)=6/1) separating-purifying, gained elutriant steams to desolventize and obtains yellow oily liquid 2-[4-morpholinodithio base dimethylacetal (I) 17.2 mg, yield 41%.
By 2-[4-morpholinodithio base dimethylacetal (I) (41.9 mg prepared according to the method described above, 0.2 mmol) be dissolved in 5 mL1, in 2-ethylene dichloride, add 3 mL salpeter solutions (1 mol/L) again, 6 h are reacted at 70 DEG C, after reaction solution precipitation is concentrated, thick product column chromatography (chromatography GF254 silica gel; 100 – 200 orders; Eluent is V (sherwood oil)/V (ethyl acetate)=6/1) separating-purifying, gained elutriant steams to desolventize and obtains yellow solid 2-[4-morpholinodithio formaldehyde (II) 27.7 mg, yield 85%.
Embodiment 8
By benzothiazole III (27.0 mg, 0.2 mmol), ceric ammonium nitrate (0.55 g, 1.0 mmol), and dry methyl alcohol (6 mL) adds in withstand voltage reaction tubes, reacts 15 h at 110 DEG C.Be cooled to room temperature, cross and filter salt, filtrate is by 3 × 10 mL washed with dichloromethane three times.After filtrate precipitation is concentrated, thick product column chromatography (chromatography neutral alumina; 200 – 300 orders; Eluent is V (sherwood oil)/V (ethyl acetate)=6/1) separating-purifying, gained elutriant steams to desolventize and obtains yellow oily liquid 2-[4-morpholinodithio base dimethylacetal (I) 16.8 mg, yield 40%.
By 2-[4-morpholinodithio base dimethylacetal (I) (41.9 mg prepared according to the method described above, 0.2 mmol) be dissolved in 5 mL ether, add 3 mL hydrochloric acid solns (1 mol/L) again, 20 h are reacted at 70 DEG C, after reaction solution precipitation is concentrated, thick product column chromatography (chromatography GF254 silica gel; 100 – 200 orders; Eluent is V (sherwood oil)/V (ethyl acetate)=6/1) separating-purifying, gained elutriant steams to desolventize and obtains yellow solid 2-[4-morpholinodithio formaldehyde (II) 28.0mg, yield 86%.
Embodiment 9
By benzothiazole III (27.0 mg, 0.2 mmol), Sodium Persulfate (0.24 g, 1.0 mmol), and dry methyl alcohol (6 mL) adds in withstand voltage reaction tubes, reacts 15 h at 110 DEG C.Be cooled to room temperature, cross and filter salt, filtrate is by 3 × 10 mL washed with dichloromethane three times.After filtrate precipitation is concentrated, thick product column chromatography (chromatography neutral alumina; 200 – 300 orders; Eluent is V (sherwood oil)/V (ethyl acetate)=6/1) separating-purifying, gained elutriant steams to desolventize and obtains yellow oily liquid 2-[4-morpholinodithio base dimethylacetal (I) 17.6mg, yield 42%.。
By 2-[4-morpholinodithio base dimethylacetal (I) (41.9 mg prepared according to the method described above, 0.2 mmol) be dissolved in 5 mL1, in 4-dioxane, add 3 mL hydrochloric acid solns (1 mol/L) again, 6 h are reacted at 120 DEG C, after reaction solution precipitation is concentrated, thick product column chromatography (chromatography GF254 silica gel; 100 – 200 orders; Eluent is V (sherwood oil)/V (ethyl acetate)=6/1) separating-purifying, gained elutriant steams to desolventize and obtains yellow solid 2-[4-morpholinodithio formaldehyde (II) 27.0mg, yield 83%.
Claims (6)
1. the synthetic method of the 2-[4-morpholinodithio dimethylacetal shown in a formula I, it is characterized in that described method for: by the benzothiazole shown in formula III, oxygenant, methyl alcohol in closed reaction vessel, be heated to 80 DEG C ~ 150 DEG C stirring reactions 0.5 ~ 30 hour, gained reaction solution a is selected from one of following through the separation and purification oxygenant obtained described in the 2-[4-morpholinodithio dimethylacetal shown in formula I: Potassium Persulphate, Sodium Persulfate, ammonium persulphate or ceric ammonium nitrate;
2. the method for claim 1, is characterized in that described oxygenant is Potassium Persulphate.
3. the method for claim 1, is characterized in that the ratio of the amount of substance of described benzothiazole, oxygenant is 1:1 ~ 8.
4. the method for claim 1, is characterized in that the volumetric usage of described methyl alcohol counts 1 ~ 150mL/mmol with the amount of substance of the benzothiazole shown in formula III.
5. shown in a formula II the synthetic method of 2-[4-morpholinodithio formaldehyde, it is characterized in that described method is carried out according to the following steps: (1) by the benzothiazole shown in formula III, oxygenant, methyl alcohol in closed reaction vessel, be heated to 80 DEG C ~ 150 DEG C stirring reactions 0.5 ~ 30 hour, gained reaction solution a obtains the 2-[4-morpholinodithio dimethylacetal shown in formula I through separation and purification; (2) the 2-[4-morpholinodithio dimethylacetal shown in formula I adds in organic solvent, and under the effect of acid catalyst, react 1 ~ 20 hour under the temperature condition of 20 ~ 120 DEG C, gained reaction solution b aftertreatment obtains the 2-[4-morpholinodithio formaldehyde shown in formula II; Described oxygenant is selected from one of following: Potassium Persulphate, Sodium Persulfate, ammonium persulphate or ceric ammonium nitrate; Described acid catalyst is hydrochloric acid, nitric acid or phosphoric acid; Described organic solvent is 1,2-ethylene dichloride, Isosorbide-5-Nitrae-dioxane, ether or tetrahydrofuran (THF);
6. method as claimed in claim 5, is characterized in that described acid catalyst is 1 ~ 15:1 with the ratio of the amount of substance of the 2-[4-morpholinodithio dimethylacetal shown in formula I.
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| CN105198835B (en) * | 2015-09-23 | 2017-09-29 | 上海泰坦科技股份有限公司 | The synthesis technique of the formic acid of benzothiazole 2 |
| CN105198833B (en) * | 2015-09-23 | 2017-09-29 | 上海泰坦科技股份有限公司 | The synthesis technique of the formaldehyde of benzothiazole 2 |
| CN109053625B (en) * | 2018-08-22 | 2020-08-11 | 浙江工业大学 | Preparation method of substituted benzothiazole C2 alkylated derivative |
| CN111909112B (en) * | 2020-08-24 | 2022-07-08 | 浙江工业大学 | Preparation method of C2 substituted 2H-benzothiazole acylated derivative |
| CN114605349B (en) * | 2022-04-07 | 2024-01-30 | 浙江工业大学 | Synthesis method of photocatalytic alkyl substituted benzothiazole derivative |
| CN115819371A (en) * | 2022-11-16 | 2023-03-21 | 新疆师范大学 | Preparation method of benzothiazole-2-formaldehyde and derivatives thereof |
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