CN101935284B - Preparation method of 2-nitro-5-substituent-1, 4-p-phenylenediamine - Google Patents
Preparation method of 2-nitro-5-substituent-1, 4-p-phenylenediamine Download PDFInfo
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- CN101935284B CN101935284B CN2010102300341A CN201010230034A CN101935284B CN 101935284 B CN101935284 B CN 101935284B CN 2010102300341 A CN2010102300341 A CN 2010102300341A CN 201010230034 A CN201010230034 A CN 201010230034A CN 101935284 B CN101935284 B CN 101935284B
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- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- 238000006243 chemical reaction Methods 0.000 claims abstract description 33
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims abstract description 16
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims abstract description 14
- 229910017604 nitric acid Inorganic materials 0.000 claims abstract description 10
- 239000003513 alkali Substances 0.000 claims description 11
- 239000002904 solvent Substances 0.000 claims description 11
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 9
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 claims description 9
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 238000001914 filtration Methods 0.000 claims description 6
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 claims description 5
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- 239000012065 filter cake Substances 0.000 claims description 5
- 238000000967 suction filtration Methods 0.000 claims description 5
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 4
- 239000003495 polar organic solvent Substances 0.000 claims description 4
- 235000017550 sodium carbonate Nutrition 0.000 claims description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 3
- STSCVKRWJPWALQ-UHFFFAOYSA-N TRIFLUOROACETIC ACID ETHYL ESTER Chemical compound CCOC(=O)C(F)(F)F STSCVKRWJPWALQ-UHFFFAOYSA-N 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 3
- 235000015320 potassium carbonate Nutrition 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- PNQBEPDZQUOCNY-UHFFFAOYSA-N trifluoroacetyl chloride Chemical compound FC(F)(F)C(Cl)=O PNQBEPDZQUOCNY-UHFFFAOYSA-N 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 2
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 2
- YHASWHZGWUONAO-UHFFFAOYSA-N butanoyl butanoate Chemical compound CCCC(=O)OC(=O)CCC YHASWHZGWUONAO-UHFFFAOYSA-N 0.000 claims description 2
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 claims description 2
- 235000019260 propionic acid Nutrition 0.000 claims description 2
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 claims description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 2
- 238000005406 washing Methods 0.000 claims description 2
- 238000000034 method Methods 0.000 abstract description 9
- 239000002253 acid Substances 0.000 abstract description 5
- CBCKQZAAMUWICA-UHFFFAOYSA-N 1,4-phenylenediamine Chemical compound NC1=CC=C(N)C=C1 CBCKQZAAMUWICA-UHFFFAOYSA-N 0.000 abstract 2
- 239000003999 initiator Substances 0.000 abstract 1
- 125000006239 protecting group Chemical group 0.000 abstract 1
- 239000002699 waste material Substances 0.000 abstract 1
- 239000003921 oil Substances 0.000 description 7
- 239000003643 water by type Substances 0.000 description 6
- 239000000118 hair dye Substances 0.000 description 5
- 238000001819 mass spectrum Methods 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 230000007613 environmental effect Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000006396 nitration reaction Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 0 *c(cc(cc1)N)c1N Chemical compound *c(cc(cc1)N)c1N 0.000 description 1
- 208000032467 Aplastic anaemia Diseases 0.000 description 1
- 206010065553 Bone marrow failure Diseases 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 230000006196 deacetylation Effects 0.000 description 1
- 238000003381 deacetylation reaction Methods 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 235000021463 dry cake Nutrition 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 208000014951 hematologic disease Diseases 0.000 description 1
- 208000018706 hematopoietic system disease Diseases 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000012567 medical material Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a preparation method of 2-nitro-5-substituent-1, 4-p-phenylenediamine,it uses 2-substituent-1, 4-p-phenylenediamine sulfate I as reaction initiator to obtain N by chemical reaction1，N4The -bis (trifluoroacetyl) -2-substituent p-phenylenediamine II, II is subjected to the action of concentrated nitric acid to obtain N1，N4And (3) bis (trifluoroacetyl) -2-nitro-5-substituent p-phenylenediamine III, and finally, removing a protecting group from the III under the action of weak base to obtain a target product 2-nitro-5-substituent-1, 4-p-phenylenediamine IV. The method for preparing the 2-nitro-5-substituent-1, 4-p-phenylenediamine saves the using amount of concentrated nitric acid, does not generate waste acid, is environment-friendly, has the yield of 50-60 percent, and can amplify the reaction.
Description
Technical field
The present invention relates to 2-nitro-5-substituting group-1, the preparation method of 4-Ursol D.
Background technology
2-nitro-5-substituting group-1,4-Ursol D and verivate thereof are one type of important kinds in the hair dye market, and such nitro hair dye kind is nontoxic, can obtain the ideal staining power when using these nitro hair dye hair dyeings.In addition, the nitro hair dye of this veriety can be united use with other hair dyes, can in the ammonia soln of hydrogen peroxide, keep enough stability.
Simultaneously, 2-nitro-5-substituting group-1,4-Ursol D and verivate thereof also are a kind of important medical materials.WO2006127458A2 utilizes 2-nitro-5-substituting group-1; 4-Ursol D and verivate thereof are raw material; The compound for preparing can be used for treatment and prevention red corpuscle disappearance and disease of hematopoietic system, because illnesss such as anemia that chronic diseases such as poor kidney or, HIV low such as autoimmunity, cancer cause and myelodysplastic syndrome, aplastic anemia disease, bone marrow depression, blood cell minimizings.
Though, 2-nitro-5-substituting group-1,4-Ursol D and verivate thereof of many uses seldom has pair report of its preparation method research.At present, only find one piece of relevant 2-nitro-5-substituting group-1, the patent documentation of 4-Ursol D and derivative preparation method thereof, CA935094A1.This patent is with N
1, N
4-diacetyl-2-substituting group-1,4-Ursol D are raw material, and it is dissolved in the vitriol oil, being no more than under 25 ℃ the condition, drip the mixture of the vitriol oil and concentrated nitric acid.Dropwise the back and continue reaction 1 hour in room temperature.Nitration reaction is poured into reaction system on the ice cube after finishing, and filters, and in the throw out that obtains, adds the vitriol oil, and reflux is poured into reaction system on the ice cube after reaction finishes, and the conditioned reaction system is alkalescence.Reaction system is filtered, dry cake obtains 2-nitro-5-substituting group-1,4-Ursol D again.Concrete reactions step is following:
Wherein, 1) be the vitriol oil, concentrated nitric acid; 2) be the vitriol oil, alkali.
Utilize CA935094A1 Synthetic 2-nitro-5-chloro-1, the shortcoming of 4-Ursol D is: 1) a large amount of vitriol oil and concentrated nitric acids of using in the reaction of nitration reaction and deacetylation produce a large amount of spent acid in aftertreatment.To prepare 1 mole of 2-nitro-5-chloro-1,4-Ursol D (187.5 gram) is an example, needs 3.47 kilograms of the vitriol oils, 0.24 kilogram of concentrated nitric acid.Handling the spent acid that produces has increased production cost and has been unfavorable for environmental protection; 2) this method productive rate is lower, has only about 40%; 3) this method can't be amplified, and only is fit to the reaction of 0.1 mole of charging capacity.
Summary of the invention
The purpose of this invention is to provide 2-nitro-5-substituting group-1, the preparation method of 4-Ursol D.
In order to realize the object of the invention, 2-nitro of the present invention-5-substituting group-1, the preparation method of 4-Ursol D, it comprises step:
1) with a mole 2-substituting group-1,4-p-phenylenediamine sulfate I, 2.2a mole reagent 1,3.2a mol alkali 1 and (0.5-1.0) a rise solvent 1, add in the reactor drum, stirred 1-3 hour under the room temperature, obtain b mole N after the filtration
1, N
4-two trifluoroacetyl groups-2-substituting group Ursol D II;
Wherein, described 2-substituting group-1, the structural formula of 4-p-phenylenediamine sulfate I is:
Wherein, R is C1-C6 alkyl, C1-C6 alkoxyl group, Wasserstoffatoms or halogen;
Described reagent 1 is analytically pure trifluoroacetic anhydride, trifluoroacetyl chloride, trifluoroacetic acid or Trifluoroacetic Acid Ethyl Ester;
Described alkali 1 is triethylamine, pyridine or DBU;
Described solvent 1 is analytically pure methyl alcohol, ethanol, methylene dichloride, THF or ether;
2) b mole II being joined (1.5-2.5) b rises in the solvent 2; Stir and form suspension-s; Drip (70-83) b milliliter analytical pure concentrated nitric acid in the room temperature downhill reaction system, dropwise continued and stirred 6-12 hour, filter; Each washing of filter cake water (800-1000) a milliliter and low polar organic solvent (800-1000) a milliliter once obtains c mole N after the drying
1, N
4-two trifluoroacetyl groups-2-nitro-5-substituting group Ursol D III;
Wherein, described solvent 2 is analytically pure acetate, diacetyl oxide, propionic acid, propionic anhydride, butyric acid, butyryl oxide, trifluoroacetic acid or trifluoroacetic anhydride;
Described low polar organic solvent is analytically pure acetone, ethyl formate, methyl acetate, ETHYLE ACETATE, MTBE, THF, dioxane or toluene;
3) c mole III, (3.0-5.0) c mol alkali 2 joined in the reactor drum with (2.0-4.0) c premium on currency, be heated to backflow 1-3 hour, obtain 2-nitro-5-substituting group-1 behind the suction filtration, 4-Ursol D IV;
Wherein, described alkali 2 is yellow soda ash or salt of wormwood.
Above-mentioned reactions step is:
Wherein, 1) be reagent 1, alkali 1, solvent 1; 2) be solvent 2, concentrated nitric acid; 3) be alkali 2, water.
Title product 2-nitro-5-substituting group-1 that the present invention obtains, the productive rate of 4-Ursol D is 50-60%.Gained compound process nmr spectrum (
1H NMR) and mass spectrum (MS) detect, structure is errorless.
The invention has the advantages that:
1) utilize method of the present invention to prepare 1 mole of 2-nitro-5-chloro-1,4-Ursol D (187.5 gram) is an example, needs concentrated nitric acid 0.10-0.12 kilogram, has reduced the nitric acid usage quantity of 50-58% than the method for CA935094A1;
2) do not produce spent acid in the preparation process, reaction system can be recycled after distillation through filtration, solvent, and this greatly reduces environmental protection pressure and has reduced production cost significantly;
3) the present invention uses weak base when obtaining final product removing the protection base, with respect to using concentrated acid to remove the method for protection base, greatly reduces environmental protection pressure;
4) productive rate is high, than the high 10-20% of compound method productive rate of CA935094A1;
5) utilize the inventive method to prepare 2-nitro-5-substituting group-1, the 4-Ursol D, reaction can be amplified and is not confined to the reaction of 0.1 mole of charging capacity.
Embodiment
Following examples are used to explain the present invention, but are not used for limiting scope of the present invention.
Embodiment 1
With 0.5 mole of (about 103.1 gram) 1,4-p-phenylenediamine sulfate I, 1.1 moles of (about 231 grams) analytical pure trifluoroacetic anhydrides, 1.6 moles of (about 162 grams) triethylamine and 250 milliliters of analytical pure methylene dichloride add in the reactor drum, fully stir 1 hour under the room temperature.Filter, obtain 142.5 gram N
1, N
4-two trifluoroacetyl groups-Ursol D II.
With N
1, N
4-two trifluoroacetyl groups-Ursol D II (60.3 grams, 0.2 mole) join in 300 milliliters of analytical pure diacetyl oxides, fully stir to form suspension-s.Drip 25 milliliters of analytical pure concentrated nitric acids in the room temperature downhill reaction system.Dropwising continued stirred 6 hours.With reacting liquid filtering, filter cake successively respectively washs once with 200 ml waters and 200 milliliters of analytical pure ETHYLE ACETATE then.Obtain 36.3 gram N after the thorough drying
1, N
4-two trifluoroacetyl groups-2-nitro-Ursol D III.
With 36.3 gram N
1, N
4-two trifluoroacetyl groups-2-nitro-Ursol D III, 53 gram yellow soda ash and 400 ml waters add in the reactor drum reflux 1 hour.Reaction is reduced to room temperature with reaction system after finishing.The reaction system suction filtration is obtained 16.1 gram 2-nitros-1,4-Ursol D.The three-step reaction overall yield is 50%; Product is the reddish black solid, and fusing point is 136-137 ℃.Proton nmr spectra: (
1H NMR, 300MHz, d-DMSO) δ 7.45 (s, 1H), 7.07 (s, 1H), 6.90 (s, 2H), 5.03 (s, 2H); Mass spectrum (EI): 153 (100), 107 (99).
Embodiment 2
With 1.0 moles of (about 236.2 grams) 2-methoxyl groups-1; 4-p-phenylenediamine sulfate I, 2.2 moles of (about 291.5 grams) analytical pure trifluoroacetyl chlorides, 3.2 moles of (about 253 grams) pyridine and 1000 milliliters of analytical pure THFs; Add in the reactor drum, fully stirred 3 hours under the room temperature.Filter, obtain 318.6 gram N
1, N
4-two trifluoroacetyl groups-2-methoxyl group Ursol D II.
With N
1, N
4-two trifluoroacetyl groups-2-methoxyl group Ursol D II (165.1 grams, 0.5 mole) join in 1000 milliliters of analytical pure acetate, fully stir to form suspension-s.5 milliliters of analytical pure concentrated nitric acids of Dropwise 5 in the room temperature downhill reaction system.Dropwising continued stirred 8 hours.With reacting liquid filtering, filter cake successively respectively washs once with 500 ml waters and 400 milliliters of analytical pure dioxane then.Obtain 116.7 gram N after the thorough drying
1, N
4-two trifluoroacetyl groups-2-nitro-5-methoxyl group Ursol D III.
With 116.7 gram N
1, N
4-two trifluoroacetyl groups-2-nitro-5-methoxyl group Ursol D III, 128 gram salt of wormwood and 1200 ml waters add in the reactor drum reflux 3 hours.Reaction is reduced to room temperature with reaction system after finishing.The reaction system suction filtration is obtained 57.0 gram 2-nitro-5-methoxyl groups-1,4-Ursol D.The three-step reaction overall yield is 60%; Product is the reddish black solid, and fusing point is 187-188 ℃.Proton nmr spectra (
1H NMR, 300MHz, d-DMSO) δ 7.45 (s, 1H), 7.07 (s, 1H), 6.90 (s, 2H), 5.03 (s, 2H); Mass spectrum (EI): 183 (100), 137 (99), 114 (35).
Embodiment 3
With 1.5 moles of (about 360.9 grams) 2-chloro-1,4-p-phenylenediamine sulfate I, 1.6 moles of (about 468.6 grams) analytical pure Trifluoroacetic Acid Ethyl Esters, 4.8 moles of DBU and 1000 milliliters of analytical pure methyl alcohol add in the reactor drum, fully stir 2 hours under the room temperature.Filter, obtain 484.3 gram N
1, N
4-two trifluoroacetyl groups-2-chloro-Ursol D II.
II (266.6 grams, 1.0 moles) is joined in 1800 milliliters of analytical pure trifluoroacetic acids, fully stir to form suspension-s.Drip 100 milliliters of analytical pure concentrated nitric acids in the room temperature downhill reaction system.Dropwising continued stirred 12 hours.With reacting liquid filtering, filter cake successively respectively washs once with 800 ml waters and 800 milliliters of analytical pure MTBEs then.Obtain 216.4 gram N after the thorough drying
1, N
4-two trifluoroacetyl groups-2-chloro-5-nitro-Ursol D III.
216.4 gram III, 241.7 gram yellow soda ash and 1140 ml waters are added in the reactor drum reflux 3 hours.Reaction is reduced to room temperature with reaction system after finishing.The reaction system suction filtration is obtained 106.8 gram 2-chloro-5-nitros-1,4-Ursol D.The three-step reaction overall yield is 55%; Product is the reddish black solid, and fusing point is 155-156 ℃.Proton nmr spectra: (
1H NMR, 300MHz, d-DMSO) δ 7.47 (s, 1H), 7.09 (s, 1H), 6.92 (s, 2H), 5.05 (s, 2H); Mass spectrum (EI): 189 (32), 187 (100), 143 (31), 141 (99).
Though, the present invention has been done detailed description in the preceding text with general explanation and specific embodiments, on basis of the present invention, can to some modifications of do or improvement, this will be apparent to those skilled in the art.Therefore, these modifications or the improvement on the basis of not departing from spirit of the present invention, made all belong to the scope that requirement of the present invention is protected.
Claims (1)
1.2-nitro-5-substituting group-1, the preparation method of 4-Ursol D is characterized in that, it comprises step:
1) with a mole 2-substituting group-1,4-p-phenylenediamine sulfate I, 2.2a mole reagent 1,3.2a mol alkali 1 and (0.5-1.0) a rise solvent 1, add in the reactor drum, stirred 1-3 hour under the room temperature, obtain b mole N after the filtration
1, N
4-two trifluoroacetyl groups-2-substituting group Ursol D II;
Wherein, described 2-substituting group-1, the structural formula of 4-p-phenylenediamine sulfate I is:
Wherein, R is C1-C6 alkyl, C1-C6 alkoxyl group, Wasserstoffatoms or halogen;
Described reagent 1 is analytically pure trifluoroacetic anhydride, trifluoroacetyl chloride, trifluoroacetic acid or Trifluoroacetic Acid Ethyl Ester;
Described alkali 1 is triethylamine, pyridine or DBU;
Described solvent 1 is analytically pure methyl alcohol, ethanol, methylene dichloride, THF or ether;
2) b mole II being joined (1.5-2.5) b rises in the solvent 2; Stir and form suspension-s; Drip (70-83) b milliliter analytical pure concentrated nitric acid in the room temperature downhill reaction system, dropwise continued and stirred 6-12 hour, filter; Each washing of filter cake water (800-1000) a milliliter and low polar organic solvent (800-1000) a milliliter once obtains c mole N after the drying
1, N
4-two trifluoroacetyl groups-2-nitro-5-substituting group Ursol D III;
Wherein, described solvent 2 is analytically pure acetate, diacetyl oxide, propionic acid, propionic anhydride, butyric acid, butyryl oxide, trifluoroacetic acid or trifluoroacetic anhydride;
Described low polar organic solvent is analytically pure acetone, ethyl formate, methyl acetate, ETHYLE ACETATE, MTBE, THF, dioxane or toluene;
3) c mole III, (3.0-5.0) c mol alkali 2 joined in the reactor drum with (2.0-4.0) c premium on currency, be heated to backflow 1-3 hour, obtain 2-nitro-5-substituting group-1 behind the suction filtration, 4-Ursol D IV;
Wherein, described alkali 2 is yellow soda ash or salt of wormwood; Said 2-nitro-5-substituting group-1, the structural formula of 4-Ursol D IV is shown below,
R is C1-C6 alkyl, C1-C6 alkoxyl group, Wasserstoffatoms or halogen.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010102300341A CN101935284B (en) | 2010-07-13 | 2010-07-13 | Preparation method of 2-nitro-5-substituent-1, 4-p-phenylenediamine |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA935094A (en) * | 1968-02-26 | 1973-10-09 | Halasz Alexander | Nuclear substituted nitroparaphenylenediamines as dyeing compositions |
| PL85584B1 (en) * | 1973-05-14 | 1976-04-30 | ||
| PL168990B1 (en) * | 1992-12-29 | 1996-05-31 | Inst Barwnikow I Produktow Org | Method of obtaining 2-nitro-1,4-phenyl diamine |
| CN1349974A (en) * | 2001-10-25 | 2002-05-22 | 武汉大学 | 2-methyl-5-chloro-1,4-diaminobenzene and its prepn and application |
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2010
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA935094A (en) * | 1968-02-26 | 1973-10-09 | Halasz Alexander | Nuclear substituted nitroparaphenylenediamines as dyeing compositions |
| PL85584B1 (en) * | 1973-05-14 | 1976-04-30 | ||
| PL168990B1 (en) * | 1992-12-29 | 1996-05-31 | Inst Barwnikow I Produktow Org | Method of obtaining 2-nitro-1,4-phenyl diamine |
| CN1349974A (en) * | 2001-10-25 | 2002-05-22 | 武汉大学 | 2-methyl-5-chloro-1,4-diaminobenzene and its prepn and application |
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Denomination of invention: Preparation method of 2-nitro-5-substituted-1,4-p-phenylenediamine Granted publication date: 20120425 Pledgee: Hefei Xingtai Technology Micro-loan Co.,Ltd. Pledgor: HEFEI HUANA BIOMEDICAL TECHNOLOGY Co.,Ltd. Registration number: Y2024980030202 |