CN109020918A - The synthetic method of 3- methyl-2-benzothiazolinone hydrazone hydrochloride and its hydrate - Google Patents
The synthetic method of 3- methyl-2-benzothiazolinone hydrazone hydrochloride and its hydrate Download PDFInfo
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- CN109020918A CN109020918A CN201810925158.8A CN201810925158A CN109020918A CN 109020918 A CN109020918 A CN 109020918A CN 201810925158 A CN201810925158 A CN 201810925158A CN 109020918 A CN109020918 A CN 109020918A
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- Prior art keywords
- methyl
- benzothiazolinone hydrazone
- hydrate
- hydrazone hydrochloride
- synthetic method
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- OEZPVSPULCMUQB-VRTOBVRTSA-N hydron;(e)-(3-methyl-1,3-benzothiazol-2-ylidene)hydrazine;chloride Chemical compound Cl.C1=CC=C2S\C(=N\N)N(C)C2=C1 OEZPVSPULCMUQB-VRTOBVRTSA-N 0.000 title claims abstract description 27
- 238000010189 synthetic method Methods 0.000 title claims abstract description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 32
- 238000006243 chemical reaction Methods 0.000 claims abstract description 26
- PHOLIFLKGONSGY-CSKARUKUSA-N (e)-(3-methyl-1,3-benzothiazol-2-ylidene)hydrazine Chemical compound C1=CC=C2S\C(=N\N)N(C)C2=C1 PHOLIFLKGONSGY-CSKARUKUSA-N 0.000 claims abstract description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 14
- PXDAXYDMZCYZNH-UHFFFAOYSA-N 3-methyl-2h-1,3-benzothiazole Chemical compound C1=CC=C2N(C)CSC2=C1 PXDAXYDMZCYZNH-UHFFFAOYSA-N 0.000 claims abstract description 9
- AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 claims abstract description 9
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 8
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 8
- XFOAZOPAGIZIHX-UHFFFAOYSA-N methyl(phenyl)carbamodithioic acid Chemical compound SC(=S)N(C)C1=CC=CC=C1 XFOAZOPAGIZIHX-UHFFFAOYSA-N 0.000 claims abstract description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 39
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 30
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 claims description 21
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 21
- 239000003960 organic solvent Substances 0.000 claims description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 9
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 9
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 claims description 8
- 238000010438 heat treatment Methods 0.000 claims description 8
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims description 8
- 235000019441 ethanol Nutrition 0.000 claims description 5
- 238000010992 reflux Methods 0.000 claims description 5
- SEBRPHZZSLCDRQ-UHFFFAOYSA-N 3-methyl-1-benzothiophene Chemical compound C1=CC=C2C(C)=CSC2=C1 SEBRPHZZSLCDRQ-UHFFFAOYSA-N 0.000 claims description 4
- 150000007857 hydrazones Chemical class 0.000 claims description 4
- 150000002576 ketones Chemical class 0.000 claims description 4
- 150000003851 azoles Chemical class 0.000 claims description 2
- DKVNPHBNOWQYFE-UHFFFAOYSA-N carbamodithioic acid Chemical compound NC(S)=S DKVNPHBNOWQYFE-UHFFFAOYSA-N 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 238000000034 method Methods 0.000 abstract description 16
- 230000036571 hydration Effects 0.000 abstract description 6
- 238000006703 hydration reaction Methods 0.000 abstract description 6
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 abstract description 4
- IYXXQOGEFHAQGU-GPWRMYTLSA-N [(z)-(3-methyl-1,3-benzothiazol-2-ylidene)amino]azanium;chloride;hydrate Chemical compound O.Cl.C1=CC=C2S\C(=N/N)N(C)C2=C1 IYXXQOGEFHAQGU-GPWRMYTLSA-N 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- QGJOPFRUJISHPQ-NJFSPNSNSA-N carbon disulfide-14c Chemical compound S=[14C]=S QGJOPFRUJISHPQ-NJFSPNSNSA-N 0.000 abstract 1
- 239000002994 raw material Substances 0.000 abstract 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 13
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 9
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 6
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 6
- 239000005457 ice water Substances 0.000 description 6
- -1 quinoline ketone Chemical class 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical class ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000012453 solvate Substances 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- HQZPQYUQNKTHRR-UHFFFAOYSA-N 1,3-benzothiazol-2-ylhydrazine;hydrochloride Chemical compound Cl.C1=CC=C2SC(=NN)NC2=C1 HQZPQYUQNKTHRR-UHFFFAOYSA-N 0.000 description 2
- DXYYSGDWQCSKKO-UHFFFAOYSA-N 2-methylbenzothiazole Chemical compound C1=CC=C2SC(C)=NC2=C1 DXYYSGDWQCSKKO-UHFFFAOYSA-N 0.000 description 2
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 150000002192 fatty aldehydes Chemical class 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- MSWZFWKMSRAUBD-UHFFFAOYSA-N 2-Amino-2-Deoxy-Hexose Chemical compound NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- UTBVIMLZIRIFFR-UHFFFAOYSA-N 2-methylthio-1,3-benzothiazole Chemical compound C1=CC=C2SC(SC)=NC2=C1 UTBVIMLZIRIFFR-UHFFFAOYSA-N 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 230000009935 nitrosation Effects 0.000 description 1
- 238000007034 nitrosation reaction Methods 0.000 description 1
- 238000005375 photometry Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 229910052711 selenium Inorganic materials 0.000 description 1
- 239000011669 selenium Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 125000005323 thioketone group Chemical group 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/68—Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D277/82—Nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Abstract
The present invention provides the synthetic methods of 3- methyl-2-benzothiazolinone hydrazone hydrochloride and its hydrate, belong to organic synthesis field.Methylphenylamine reacts to obtain N- Methyl-N-phenyl aminodithioformic acid with carbon disulfide, then it reacts to obtain 3- methylbenzothiazole -2- thioketones with bromine, then 3- methyl-2-benzothiazolinone hydrazone is generated with hydration hydrazine reaction, it then reacts to obtain 3- methyl-2-benzothiazolinone hydrazone hydrochloride with hydrochloric acid, 3- methyl-2-benzothiazolinone hydrazone hydrochloride hydrate is recrystallized to give in water.Raw materials used cheap and easy to get in the present invention, operating process is easy, and there is potential industry to amplify application prospect.
Description
Technical field
The invention belongs to chemosynthesis technical field more particularly to 3- methyl-2-benzothiazolinone hydrazone hydrochloride and its
The synthetic method of hydrate.
Technical background
3- methyl-2-benzothiazolinone hydrazone hydrochloride, CAS:149022-15-1, molecular formula: C8H10ClN3S, molecule
Amount: 215.7.3- methyl-2-benzothiazolinone hydrazone hydrochloride hydrate, CAS:38894-11-0, molecular formula:
C8H12ClN3OS, molecular weight: 233.7, structural formula difference is as follows:
3- methyl-2-benzothiazolinone hydrazone hydrochloride and its hydrate can be used for photometry measurement fatty aldehyde, measure mucopolysaccharide
In hexosamine, the Determination of Trace Selenium etc. in photometering environmental sample.Wherein for the measurement of fatty aldehyde, especially formaldehyde,
Have great importance.For example, newly-decorated house, finishing material used is easy to the formaldehyde that volatilizees, and one of harm of formaldehyde is just
It is easy leukemogenesis, especially initiation infant generates leukaemia, and endless pain is caused to many families.It is hidden to prevent
Suffer from, newly-decorated house should carry out the detection of content of formaldehyde.And phenol reagent has high sensitivity for aldehydes, answers extensively
For the detection of aldehyde, thus the synthetic methods of a variety of synthesis phenol reagents are found, is just very necessary and significant.
It prepares 3- methyl-2-benzothiazolinone hydrazone hydrochloride at present and its report of hydrate is few, conventional method is
N- Methyl-N-phenyl thiocarbamide is generated by methylphenylamine, regenerates intermediate 3- methyl -2- imino group benzothiazole.One
Method is, this intermediate through nitrosation, also original preparation 3- methyl-2-benzothiazolinone hydrazone, but there is also deficiencies for the method
Place, for example, yield it is low, have the shortcomings that side reaction, complex steps.Another method is this intermediate 3- methyl -2- imino group
Benzothiazole prepares 3- methyl-2-benzothiazolinone hydrazone with hydration hydrazine reaction, and the method reduces step etc. in yield
It is all substantially better than former approach, CN1634900A has been reported.In addition, passing through intermediate 2- methyl mercapto benzothiazole and hydrazine hydrate
The method for reacting to prepare MBTH, also there is document report.But there is also in place of the deficiencies of troublesome in poeration, expensive.
Summary of the invention
In view of the synthetic technology status of MBTH, the purpose of the present invention is to provide a kind of 3- methyl -2-[4-morpholinodithio quinoline ketone
The synthetic method of hydrazone hydrochloride and its hydrate, the present invention have the features such as easy to operate, high income, while also having briefly
Synthetic route, product have potential application foreground in industrialized production.
The present invention provides following synthetic technology scheme, a kind of 3- methyl-2-benzothiazolinone hydrazone hydrochloride and its hydration
The synthetic method of object, synthetic route of the present invention are as follows:
The following steps are included:
The first step, methylphenylamine, triethylamine and carbon disulfide mixing, reaction obtains N- Methyl-N-phenyl in organic solvent
Aminodithioformic acid；
Second step, N- Methyl-N-phenyl aminodithioformic acid and bromine, reaction obtains 3- methyl benzo thiophene in organic solvent
Azoles -2- thioketones；
Third step, 3- methylbenzothiazole -2- thioketones are dissolved in organic solvent, and hydrochloric acid and hydrazine hydrate, heating reflux reaction is added
Obtain 3- methyl-2-benzothiazolinone hydrazone；
4th step, 3- methyl-2-benzothiazolinone hydrazone are dissolved in organic solvent, and concentrated hydrochloric acid is added, 3- methyl-is obtained after filtering
2-[4-morpholinodithio quinoline ketone hydrazone hydrochloride；
5th step, 3- methyl-2-benzothiazolinone hydrazone hydrochloride are soluble in water, are recrystallized to give 3- methyl -2-[4-morpholinodithio
Quinoline ketone hydrazone hydrochloride hydrate.
Organic solvent is selected from methanol or ethyl alcohol in method of the present invention, the first step and third step；It is organic in second step
Solvent is selected from dichloromethane or chloroform；In 4th step, organic solvent is selected from methylene chloride, chloroform or ethyl acetate.
Method of the present invention, in the first step, the molar ratio of methylphenylamine, triethylamine and carbon disulfide is 1:1.1-
1.5:1-1.2.
Method of the present invention, in second step, reaction temperature is 0 DEG C to 25 DEG C.
Method of the present invention, in second step, N- Methyl-N-phenyl aminodithioformic acid and bromine molar ratio are 1:
1.0-1.2。
Method of the present invention, in third step, the molar ratio of 3- methylbenzothiazole -2- thioketones, hydrazine hydrate and hydrochloric acid
For 1:1.1-2:0.1-0.2.
Method of the present invention, in third step, the reaction time is 4-8 hour.
Method of the present invention, in the 4th step, the molar ratio of 3- methyl-2-benzothiazolinone hydrazone and concentrated hydrochloric acid is 1:
1.1-2。
Method of the present invention, in the 5th step, the mass ratio of 3- methyl-2-benzothiazolinone hydrazone hydrochloride and water is
1:1.5-2.
The beneficial effects of the present invention are: provide a kind of novel synthesis 3- methyl-2-benzothiazolinone hydrazone hydrochloride
And its method of hydrate, the advantage that this method has synthetic route brief, easy to operate, at low cost are suitble to industrialized production.
Specific embodiment
Be illustrated the present invention with specific embodiment below, these embodiments be for the present invention is specifically described,
Rather than limiting the invention.
Embodiment 1
(1) methylphenylamine (0.1mol, 10.7 grams), triethylamine (0.11mol, 11 grams), carbon disulfide (0.1mol, 7.6 grams)
It is dissolved in methanol 100mL, at 0 DEG C, is stirred to react two hours, then then at the reaction was continued at room temperature two hours, reaction
It finishes, methanol solvate is removed in rotation, and 100mL ethyl acetate is added, is washed twice with water, and anhydrous sodium sulfate is dry, and then acetic acid is removed in rotation
Ethyl ester is crystallized to obtain 15 grams of N- Methyl-N-phenyl aminodithioformic acid, yield 82% with methyl tertiary butyl ether(MTBE).HNMR
(DMSO-d6): δ ppm=7.29 (d, 2H), 7.17 (m, 3H), 3.66 (s, 3H)
(2) the resulting compound N-methy-N- phenyl aminodithioformic acid of step (1) (0.1mol, 18.3 grams) is dissolved in two
In chloromethanes 200mL, it is added dropwise to bromine (0.1mol, 16 grams) under ice-water bath and is reacted, about half an hour is added dropwise, then
It is stirred for reaction 2 hours, end of reaction is washed twice with water, and organic layer is dry with anhydrous sodium sulfate, and concentration obtains 3- methyl
16 grams of benzothiazole -2- thioketones, yield 88%.H NMR(CDCl3, 500MHz) and δ 7.47 (d, J=8.0Hz, 1H), 7.43-
7.40 (m, 1H), 7.32-7.29 (m 1H), 7.20 (d, J=8.5Hz, 1H), 3.85 (s, 3H)
(3) the resulting compound 3- methylbenzothiazole -2- thioketones of step (2) (0.1mol, 18.1 grams) is dissolved in methanol 200mL
In, concentrated hydrochloric acid 2mL is added, is added hydrazine hydrate (0.15mol, 7.5 grams), heating reflux reaction, after reacting 4 hours, screws out first
Alcoholic solvent is added methylene chloride dissolution, the washing of hydracid hydrogen sodium solution, then washes, and sodium sulphate is dry, and dichloromethane solvent is removed in rotation,
15 grams of 3- methyl-2-benzothiazolinone hydrazone are obtained, yield 84%.HNMR(DMSO-d6): δ ppm=7.49 (d, 1H), 7.22-
7.26(m,1H),7.05(d,1H),6.93-6.97(m,1H),5.04(s,2H),3.38(s,3H).
(4) the resulting compound 3- methyl-2-benzothiazolinone hydrazone of step (3) (0.1mol, 17.9 grams) is dissolved in dichloromethane
In alkane 100mL, concentrated hydrochloric acid (0.12mol, 12M, 10ml) is added under ice-water bath, there is solid generation, filters, obtain 3- methyl -2-
18 grams of benzothiazolinone hydrazone hydrochloride, yield 83%.HNMR(DMSO-d6): 10.20-10.24 (m, 2H), 7.83 (d, 1H),
7.43-7.44(d,2H),7.20-7.24(m,1H),3.56(s,3H).
(5) the resulting compound 3- methyl-2-benzothiazolinone hydrazone hydrochloride of step (4) (0.1mol, 21.6 grams) is dissolved in
It in water 40ml, dissolves by heating, crystallisation by cooling, filters, gained crystal is the hydration of 3- methyl-2-benzothiazolinone hydrazone hydrochloride
19 grams of object, yield 81%.HNMR(CD3OD): 7.81 (d, 1H), 7.52-7.56 (m, 2H), 7.35-7.39 (m, 1H), 3.72
(s,3H).
Embodiment 2
(1) methylphenylamine (0.1mol, 10.7 grams), triethylamine (0.12mol, 12 grams), carbon disulfide (0.1mol, 7.6 grams)
It is dissolved in ethyl alcohol 110mL, at 0 DEG C, is stirred to react two hours, then then at the reaction was continued at room temperature two hours, reaction
It finishes, alcohol solvent is removed in rotation, and 120mL ethyl acetate is added, is washed twice with water, and anhydrous sodium sulfate is dry, and then revolving removes
Ethyl acetate obtains crude product, then is crystallized to obtain 15.2 grams of N- Methyl-N-phenyl aminodithioformic acid with methyl tertiary butyl ether(MTBE),
Yield 83%.
(2) the resulting compound N-methy-N- phenyl aminodithioformic acid of step (1) (0.1mol, 18.3 grams) is dissolved in three
In chloromethanes 200mL, it being added dropwise to bromine (0.11mol, 17.6 grams) under ice-water bath and is reacted, about half an hour is added dropwise,
Then it is stirred for reaction 2 hours, end of reaction is washed twice with water, and organic layer is dry with anhydrous sodium sulfate, and concentration obtains 3-
16.2 grams of methylbenzothiazole -2- thioketones, yield 89%.
(3) the resulting compound 3- methylbenzothiazole -2- thioketones of step (2) (0.1mol, 18.1 grams) is dissolved in ethyl alcohol 200mL
In, concentrated hydrochloric acid 2mL is added, is added hydrazine hydrate (0.12mol, 6 grams), heating reflux reaction, after reacting 4 hours, screws out methanol
Solvent is added methylene chloride dissolution, the washing of hydracid hydrogen sodium solution, then washes, and sodium sulphate is dry, and dichloromethane solvent is removed in rotation, obtains
To 14.8 grams of 3- methyl-2-benzothiazolinone hydrazone, yield 83%.
(4) the resulting compound 3- methyl-2-benzothiazolinone hydrazone of step (3) (0.1mol, 17.9 grams) is dissolved in chloroform
In 100mL, concentrated hydrochloric acid (0.13mol, 12M, 11ml) is added under ice-water bath, there is solid generation, filters, obtain 3- methyl -2- benzene
And 18 grams of thiazolinone hydrazone hydrochloride, yield 83%.
(5) the resulting compound 3- methyl-2-benzothiazolinone hydrazone hydrochloride of step (4) (0.1mol, 21.6 grams) is dissolved in
It in water 35ml, dissolves by heating, crystallisation by cooling, filters, gained crystal is the hydration of 3- methyl-2-benzothiazolinone hydrazone hydrochloride
19.5 grams of object, yield 83%.
Embodiment 3
(1) methylphenylamine (0.1mol, 10.7 grams), triethylamine (0.13mol, 13 grams), carbon disulfide (0.11mol, 8.4 grams)
It is dissolved in methanol 120mL, at 0 DEG C, is stirred to react two hours, then then at the reaction was continued at room temperature two hours, reaction
It finishes, methanol solvate is removed in rotation, and the dissolution of 120mL ethyl acetate is added, is then washed twice with water, anhydrous sodium sulfate is dry, then revolves
Ethyl acetate is removed, crude product is obtained, is crystallized to obtain 15.5 grams of N- Methyl-N-phenyl aminodithioformic acid with methyl tertiary butyl ether(MTBE),
Yield 85%.
(2) the resulting compound N-methy-N- phenyl aminodithioformic acid of step (1) (0.1mol, 18.3 grams) is dissolved in two
In chloromethanes 220mL, it being added dropwise to bromine (0.12mol, 19.2 grams) under ice-water bath and is reacted, about half an hour is added dropwise,
Then it is stirred for reaction 2 hours, end of reaction is first washed with sodium bicarbonate solution, is washed with water and is washed primary, organic layer is with anhydrous
Sodium sulphate is dry, and revolving removes methylene chloride, obtains 16.2 grams of thioketones of 3- methylbenzothiazole -2-, yield 89%.
(3) the resulting compound 3- methylbenzothiazole -2- thioketones of step (2) (0.1mol, 18.1 grams) is dissolved in methanol 200mL
In, concentrated hydrochloric acid 1.5mL is added, is added hydrazine hydrate (0.18mol, 9.0 grams), heating reflux reaction, after reacting 4 hours, screws out
Methanol solvate is added methylene chloride dissolution, the washing of hydracid hydrogen sodium solution, then washes, and sodium sulphate is dry, and rotation goes methylene chloride molten
Agent obtains 15.5 grams of 3- methyl-2-benzothiazolinone hydrazone, yield 87%.
(4) the resulting compound 3- methyl-2-benzothiazolinone hydrazone of step (3) (0.1mol, 17.9 grams) is dissolved in dichloromethane
In alkane 120mL, concentrated hydrochloric acid (0.14mol, 12M, 12ml) is added under ice-water bath, there is solid generation, filters, obtain 3- methyl -2-
18.5 grams of benzothiazolinone hydrazone hydrochloride, yield 86%.
(5) the resulting compound 3- methyl-2-benzothiazolinone hydrazone hydrochloride of step (4) (0.1mol, 21.6 grams) is dissolved in
It in water 38ml, dissolves by heating, crystallisation by cooling, filters, gained crystal is the hydration of 3- methyl-2-benzothiazolinone hydrazone hydrochloride
20 grams of object, yield 85%.
Claims (9)
1. the synthetic method of a kind of 3- methyl-2-benzothiazolinone hydrazone hydrochloride and its hydrate, which is characterized in that reaction side
Formula is as follows:
2. the synthetic method of a kind of 3- methyl-2-benzothiazolinone hydrazone hydrochloride and its hydrate according to claim 1,
It is characterized by comprising the following steps:
The first step, methylphenylamine, triethylamine and carbon disulfide mixing, reaction obtains N- Methyl-N-phenyl in organic solvent
Aminodithioformic acid；
Second step, N- Methyl-N-phenyl aminodithioformic acid and bromine, reaction obtains 3- methyl benzo thiophene in organic solvent
Azoles -2- thioketones；
Third step, 3- methylbenzothiazole -2- thioketones are dissolved in organic solvent, and hydrochloric acid and hydrazine hydrate, heating reflux reaction is added
Obtain 3- methyl-2-benzothiazolinone hydrazone；
4th step, 3- methyl-2-benzothiazolinone hydrazone are dissolved in organic solvent, and concentrated hydrochloric acid is added, 3- methyl-is obtained after filtering
2-[4-morpholinodithio quinoline ketone hydrazone hydrochloride；
5th step, 3- methyl-2-benzothiazolinone hydrazone hydrochloride are soluble in water, are recrystallized to give 3- methyl -2-[4-morpholinodithio
Quinoline ketone hydrazone hydrochloride hydrate.
3. the synthetic method of 3- methyl-2-benzothiazolinone hydrazone hydrochloride according to claim 2 and its hydrate,
Be characterized in that: organic solvent is selected from methanol or ethyl alcohol in the first step and third step；In second step, organic solvent is selected from methylene chloride
Or chloroform；In 4th step, organic solvent is selected from methylene chloride, chloroform or ethyl acetate.
4. the synthetic method of 3- methyl-2-benzothiazolinone hydrazone hydrochloride according to claim 2 and its hydrate,
Be characterized in that: in the first step, methylphenylamine, triethylamine and carbon disulfide molar ratio are 1:1.1-1.5:1-1.2.
5. the synthetic method of 3- methyl-2-benzothiazolinone hydrazone hydrochloride according to claim 2 and its hydrate,
It is characterized in that, in second step, reaction temperature is selected from 0 DEG C to 25 DEG C.
6. the synthetic method of 3- methyl-2-benzothiazolinone hydrazone hydrochloride according to claim 2 and its hydrate,
Be characterized in that: in second step, N- Methyl-N-phenyl aminodithioformic acid and bromine molar ratio are 1:1.0-1.2.
7. the synthetic method of 3- methyl-2-benzothiazolinone hydrazone hydrochloride according to claim 2 and its hydrate,
Be characterized in that: in third step, 3- methylbenzothiazole -2- thioketones and hydrazine hydrate and hydrochloric acid molar ratio are 1:1.1-2:0.1-0.2.
8. the synthetic method of 3- methyl-2-benzothiazolinone hydrazone hydrochloride according to claim 2 and its hydrate,
Be characterized in that: in the 4th step, 3- methyl-2-benzothiazolinone hydrazone and concentrated hydrochloric acid molar ratio are 1:1.1-2.
9. the synthetic method of 3- methyl-2-benzothiazolinone hydrazone hydrochloride according to claim 2 and its hydrate,
Be characterized in that: in the 5th step, the mass ratio of 3- methyl-2-benzothiazolinone hydrazone hydrochloride and water is 1:1.5-2.
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| CN111892554A (en) * | 2020-08-10 | 2020-11-06 | 苏州亚科科技股份有限公司 | Preparation method of 2,2' -biazonitrogen-bis (3-alkylbenzothiazoline-6-sulfonic acid) salt |
| CN112500411A (en) * | 2020-12-14 | 2021-03-16 | 南京红太阳生物化学有限责任公司 | Preparation method of 1,1 '-ethylene-2, 2' -bipyridyl dichloride salt |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111892554A (en) * | 2020-08-10 | 2020-11-06 | 苏州亚科科技股份有限公司 | Preparation method of 2,2' -biazonitrogen-bis (3-alkylbenzothiazoline-6-sulfonic acid) salt |
| CN111892554B (en) * | 2020-08-10 | 2022-08-16 | 苏州亚科科技股份有限公司 | Preparation method of 2,2' -biazonitrogen-bis (3-alkylbenzothiazoline-6-sulfonic acid) salt |
| CN112500411A (en) * | 2020-12-14 | 2021-03-16 | 南京红太阳生物化学有限责任公司 | Preparation method of 1,1 '-ethylene-2, 2' -bipyridyl dichloride salt |
| CN112500411B (en) * | 2020-12-14 | 2023-03-14 | 南京红太阳生物化学有限责任公司 | Preparation method of 1,1 '-ethylene-2, 2' -bipyridyl dichloride salt |
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