CN104478852A - Novel diazo benzothiapyrone photosensitive protecting groups and synthesis method thereof - Google Patents
Novel diazo benzothiapyrone photosensitive protecting groups and synthesis method thereof Download PDFInfo
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- CN104478852A CN104478852A CN201410724607.4A CN201410724607A CN104478852A CN 104478852 A CN104478852 A CN 104478852A CN 201410724607 A CN201410724607 A CN 201410724607A CN 104478852 A CN104478852 A CN 104478852A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D335/00—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom
- C07D335/04—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D335/06—Benzothiopyrans; Hydrogenated benzothiopyrans
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- C—CHEMISTRY; METALLURGY
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- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having sulfur atoms, with or without selenium or tellurium atoms, as the only ring hetero atoms
- C07F9/655363—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having sulfur atoms, with or without selenium or tellurium atoms, as the only ring hetero atoms the sulfur atom being part of a six-membered ring
- C07F9/655372—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having sulfur atoms, with or without selenium or tellurium atoms, as the only ring hetero atoms the sulfur atom being part of a six-membered ring condensed with carbocyclic rings or carbocyclic ring systems
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Abstract
The invention discloses novel diazo benzothiapyrone photosensitive protecting groups and a synthesis method thereof. A compound disclosed by the invention can be used for protecting a phosphoric acid functional group compound. The novel benzothiapyrone photosensitive protecting groups disclosed by the invention are efficient and rapid in photo-dissociation reaction, have good relative stability under daily illumination conditions, and also have unique photosensitive structures which have response to light and can also be used for releasing potential fluorescent groups. According to the novel diazo benzothiapyrone photosensitive protecting groups disclosed by the invention, tracking and monitoring of a light control process can be facilitated, and the 'controllability' and 'visibility' of release can be achieved; and a novel research method for performing quantitative release and accumulation degree research under cell biological environments can be provided.
Description
Technical field
The invention belongs to new compound preparation method, be specifically related to a kind of novel diazo benzo thiapyran ketone photosensitive protective group and synthetic method.
Background technology
In order to optionally carry out a certain reaction in organic reaction process, need to use the intramolecular sensitive functional groups of specific radical protection or interference functional group, this kind of group is exactly protecting group.But this method implements exists shortcoming.Protecting group has its distinctive character; protect on carrying out and go must use specific reagent during protection; in multistep synthesis; this two-step reaction virtually increased; great inconvenience can be brought to experiment; and the productive rate of reaction can be made greatly to reduce, when especially having multiple site to need to protect in a molecule, the difficulty of experimental implementation will strengthen.
Photosensitive protective group is that the solution of the problems referred to above provides good scheme.Photosensitive protective group is the protecting group that a class contains photosensitive chromophoric group.In organic synthesis, be different from traditional protection base, deprotection only needs specific wavelength illumination, avoids strong acid, and basic conditions is on the impact of active group in molecule.Photosensitive protective group, especially for specific functional group the photosensitive protective group selected, when deprotection, photoresponse speed is fast and reaction is relatively single, and efficiency is higher.So compared with requiring relatively harsh general protecting group with reaction conditions, photosensitive protective group can protect complicated susceptibility molecule effectively.Along with the made rapid progress of life science, photosensitive protective group obtains very large development, is with a wide range of applications in biomedical science field.
Summary of the invention
The object of the invention is to overcome the deficiencies in the prior art part; a kind of novel diazo benzo thiapyran ketone photosensitive protective group and synthetic method are provided; the present invention take thiophenol as starting raw material, by synthesis above-claimed cpds such as condensation reaction, halogenating reaction, Suzuki reaction, redox reaction and esterifications.
The technical scheme that the present invention realizes object is as follows:
A kind of novel diazo benzo thiapyran ketone photosensitive protective group, its general structure is as follows:
Wherein R
1for: trifluoromethyl; Aryl; R
2for: to methoxyl group; Aryl.
And, described compound is 1,1-dioxo-2-tosylhydrazone-3-phenyl-4H-benzo thiapyran ketone or 1,1-dioxo-2-diazo-3-phenyl-4H-benzo thiapyran ketone or 1,1-dioxo-2-diazo-3-p-methoxyphenyl-4H-benzo thiapyran ketone or 1,1-dioxo-2-diazo-3-(3,5-bis-(trifluoromethyl)) phenyl-4H-benzo thiapyran ketone or 1,1-dioxo-2-diazo-3-(2-naphthyl)-4H-benzo thiapyran ketone or 1,1-dioxo-2-diazo-3-phenyl-4H-[f] aphthothiopyrans ketone.
Prepare the method for novel diazo benzo thiapyran ketone photosensitive protective group, step is as follows
(1), after catalyzer melting is dissolved, drip the mixed solution of thiophenol and methyl aceto acetate, after dropwising, react 3 hours, after completion of the reaction, reaction solution is poured in frozen water, extraction into ethyl acetate, organic layer NaOH solution washing, be adjusted to pH=9, after washing with water, organic over anhydrous MgSO
4drying, products therefrom ether condensing crystal, obtained yellow crystal 2-methyl-4H-benzo thiapyran ketone;
Step (1) described in catalyzer be phosphoric acid or Vanadium Pentoxide in FLAKES, the volume ratio of thiophenol and methyl aceto acetate is 1:1;
(2) by 2-methyl-4H-benzo thiapyran ketone, iodine, solvent and catalyzer temperature-elevating to 60 DEG C that step is (1) obtained, react 4 hours, be cooled to room temperature after completion of the reaction, with hypo solution cancellation, dichloromethane extraction, after mixing organic layer washs with saturated sodium-chloride, with anhydrous magnesium sulfate drying, steam solvent, column chromatography obtains the iodo-2-methyl of yellow crystal 3--4H-benzo thiapyran ketone;
Step (2) described in catalyzer be ceric ammonium nitrate, solvent is acetonitrile, and the mol ratio of 2-methyl-4H-benzo thiapyran ketone and iodine is 1:1.2;
(3) by the iodo-2-methyl of 3--4H-benzo thiapyran ketone, phenylo boric acid, solvent and catalyzer temperature-elevating to 80 DEG C that step is (2) obtained, react 4 hours, be cooled to room temperature after completion of the reaction, with saturated sodium-chloride and extraction into ethyl acetate, mixing organic layer is with anhydrous magnesium sulfate drying, screw out solvent, column chromatography obtains white crystal 2-methyl-3-phenyl-4H-benzo thiapyran ketone;
Step (3) described in catalyzer be two (triphenyl phosphorus) palladium chloride and salt of wormwood, solvent is DMF/water, and the mol ratio of the iodo-2-methyl of 3--4H-benzo thiapyran ketone and phenylo boric acid is 1:1.3;
(4) 2-methyl-3-phenyl-4H-benzo thiapyran ketone, tin anhydride, molecular sieve and solvent that step is (3) obtained are warming up to 150 DEG C, react 8 hours, after completion of the reaction, with saturated sodium bicarbonate solution cancellation, dichloromethane extraction, mixing organic layer is with anhydrous magnesium sulfate drying, and after screwing out methylene dichloride, column chromatography obtains yellow crystal 4-ketone group-3-phenyl-4H-benzo thiapyran-2-formaldehyde;
Step (4) described in solvent be orthodichlorobenzene, the mol ratio of 2-methyl-3-phenyl-4H-benzo thiapyran ketone and tin anhydride is 1:2.4;
(5) by (4) obtained for step 4-ketone group-3-phenyl-4H-benzo thiapyran-2-formaldehyde, metachloroperbenzoic acid and solvent normal-temperature reaction 24 hours, after completion of the reaction, with hypo solution and saturated sodium bicarbonate solution cancellation, dichloromethane extraction, mixing organic layer is with anhydrous magnesium sulfate drying, screw out solvent, column chromatography obtains yellow crystal 2-carboxaldehyde radicals-3-phenyl-4H-alkylsulfonyl benzo thiapyran ketone;
Step (5) described in solvent be methylene dichloride, the mol ratio of 4-ketone group-3-phenyl-4H-benzo thiapyran-2-formaldehyde and metachloroperbenzoic acid is 1:2.1;
(6) 2-carboxaldehyde radicals-3-phenyl-4H-alkylsulfonyl benzo thiapyran-4-ketone (5) obtained for step, p-toluene sulfonyl hydrazide are added drop-wise in EtOH, normal-temperature reaction 24 hours, after completion of the reaction, collected by filtration, yellow crystal 1,1-dioxo-2-tosylhydrazone-3-phenyl-4H-benzo thiapyran ketone is obtained by washing with alcohol;
(7) the 2-tosylhydrazone-3-phenyl-4H-alkylsulfonyl benzo thiapyran that step is (6) obtained is dissolved in solvent; after normal temperature drips sodium hydroxide solution; react 1 hour; after completion of the reaction, with dichloromethane extraction, after the washing of mixing organic layer; with anhydrous magnesium sulfate drying; screw out solvent, column chromatography obtains yellow liquid 1,1-dioxo-2-diazo-3-phenyl-4H-benzo thiapyran ketone.
The advantage that the present invention obtains and beneficial effect are:
The preparation method of novel diazo benzo thiapyran ketone photosensitive protective group provided by the invention; compound provided by the invention can to the protection of phosphonic functional groups's compound; novel benzo thiapyran ketone photosensitive protective group photodissociation reaction is rapidly efficient; and under daily illumination condition, there is good relative stability, and have and unique not only can discharge the photosensitive structure of potential fluorophor to photoresponse.Be convenient to carry out tracking monitor to light-operated process, reach ' controllability ', ' visuality ' of release.For quantitatively discharge under cell biological environment and degree of gathering research new research method is provided.
Accompanying drawing explanation
Fig. 1 is compound 2-methyl-4H-benzo thiapyran ketone hydrogen spectrogram;
Fig. 2 is compound 2-methyl-4H-benzo thiapyran ketone carbon spectrogram;
Fig. 3 is the iodo-2-methyl of compound 3--4H-benzo thiapyran ketone hydrogen spectrogram;
Fig. 4 is the iodo-2-methyl of compound 3--4H-benzo thiapyran ketone carbon spectrogram;
Fig. 5 is compound 2-methyl-3-phenyl-4H-benzo thiapyran ketone hydrogen spectrogram;
Fig. 6 is compound 2-methyl-3-phenyl-4H-benzo thiapyran ketone carbon spectrogram;
Fig. 7 is compound 4-ketone group-3-phenyl-4H-benzo thiapyran-2-formaldehyde hydrogen spectrogram;
Fig. 8 is compound 4-ketone group-3-phenyl-4H-benzo thiapyran-2-formaldehyde carbon spectrogram;
Fig. 9 is compound 1,1-dioxo-2-carboxaldehyde radicals-3-phenyl-4H-benzo thiapyran ketone hydrogen spectrogram;
Figure 10 is compound 1,1-dioxo 2-carboxaldehyde radicals-3-phenyl-4H-alkylsulfonyl benzo thiapyran ketone carbon spectrogram;
Figure 11 is compound 1,1-dioxo-2-tosylhydrazone-3-phenyl-4H-benzo thiapyran ketone hydrogen spectrogram;
Figure 12 is compound 1,1-dioxo-2-tosylhydrazone-3-phenyl-4H-benzo thiapyran ketone carbon spectrogram;
Figure 13 is compound 1,1-dioxo-2-diazo-3-phenyl-4H-benzo thiapyran ketone hydrogen spectrogram;
Figure 14 is compound 1,1-dioxo-2-diazo-3-phenyl-4H-benzo thiapyran ketone carbon spectrogram.
Embodiment
Below by specific embodiment, the invention will be further described, and following examples are descriptive, is not determinate, can not limit protection scope of the present invention with this.
A kind of novel diazo benzo thiapyran ketone photosensitive protective group, its basic structure is:
Preparation method is as follows:
(1), after catalyzer melting is dissolved, drip the mixed solution of thiophenol and methyl aceto acetate, after dropwising, react 3 hours, after completion of the reaction, reaction solution is poured in frozen water, extraction into ethyl acetate, organic layer NaOH solution washing, be adjusted to pH=9, after washing with water, organic over anhydrous MgSO
4drying, products therefrom ether condensing crystal, obtained yellow crystal 2-methyl-4H-benzo thiapyran ketone;
Step (1) described in catalyzer be phosphoric acid or Vanadium Pentoxide in FLAKES, the volume ratio of thiophenol and methyl aceto acetate is 1:1.
(2) by 2-methyl-4H-benzo thiapyran ketone, iodine, solvent and catalyzer temperature-elevating to 60 DEG C that step is (1) obtained, react 4 hours, be cooled to room temperature after completion of the reaction, with hypo solution cancellation, dichloromethane extraction, after mixing organic layer washs with saturated sodium-chloride, with anhydrous magnesium sulfate drying, steam solvent, column chromatography obtains the iodo-2-methyl of yellow crystal 3--4H-benzo thiapyran ketone;
Step (2) described in catalyzer be ceric ammonium nitrate, solvent is acetonitrile, and the mol ratio of 2-methyl-4H-benzo thiapyran ketone and iodine is 1:1.2.
(3) by the iodo-2-methyl of 3--4H-benzo thiapyran ketone, phenylo boric acid, solvent and catalyzer temperature-elevating to 80 DEG C that step is (2) obtained, react 4 hours, be cooled to room temperature after completion of the reaction, with saturated sodium-chloride and extraction into ethyl acetate, mixing organic layer is with anhydrous magnesium sulfate drying, screw out solvent, column chromatography obtains white crystal 2-methyl-3-phenyl-4H-benzo thiapyran ketone;
Step (3) described in catalyzer be two (triphenyl phosphorus) palladium chloride and salt of wormwood, solvent is DMF/water, and the mol ratio of the iodo-2-methyl of 3--4H-benzo thiapyran ketone and phenylo boric acid is 1:1.3;
(4) 2-methyl-3-phenyl-4H-benzo thiapyran ketone, tin anhydride, molecular sieve and solvent that step is (3) obtained are warming up to 150 DEG C, react 8 hours, after completion of the reaction, with saturated sodium bicarbonate solution cancellation, dichloromethane extraction, mixing organic layer is with anhydrous magnesium sulfate drying, and after screwing out methylene dichloride, column chromatography obtains yellow crystal 4-ketone group-3-phenyl-4H-benzo thiapyran-2-formaldehyde;
Step (4) described in solvent be orthodichlorobenzene, the mol ratio of 2-methyl-3-phenyl-4H-benzo thiapyran ketone and tin anhydride is 1:2.4.
(5) by (4) obtained for step 4-ketone group-3-phenyl-4H-benzo thiapyran-2-formaldehyde, metachloroperbenzoic acid and solvent normal-temperature reaction 24 hours, after completion of the reaction, with hypo solution and saturated sodium bicarbonate solution cancellation, dichloromethane extraction, mixing organic layer is with anhydrous magnesium sulfate drying, screw out solvent, column chromatography obtains yellow crystal 2-carboxaldehyde radicals-3-phenyl-4H-alkylsulfonyl benzo thiapyran ketone;
Step (5) described in solvent be methylene dichloride, the mol ratio of 4-ketone group-3-phenyl-4H-benzo thiapyran-2-formaldehyde and metachloroperbenzoic acid is 1:2.1.
(6) 2-carboxaldehyde radicals-3-phenyl-4H-alkylsulfonyl benzo thiapyran-4-ketone (5) obtained for step, p-toluene sulfonyl hydrazide are added drop-wise in EtOH, normal-temperature reaction 24 hours, after completion of the reaction, collected by filtration, yellow crystal 1,1-dioxo-2-tosylhydrazone-3-phenyl-4H-benzo thiapyran ketone is obtained by washing with alcohol;
(7) the 2-tosylhydrazone-3-phenyl-4H-alkylsulfonyl benzo thiapyran that step is (6) obtained is dissolved in solvent; after normal temperature drips sodium hydroxide solution; react 1 hour; after completion of the reaction, with dichloromethane extraction, after the washing of mixing organic layer; with anhydrous magnesium sulfate drying; screw out solvent, column chromatography obtains yellow liquid 1,1-dioxo-2-diazo-3-phenyl-4H-benzo thiapyran ketone.
The reaction scheme that the present invention relates to is as follows:
Embodiment 1
A kind of preparation of 1,1-dioxo-2-diazo-3-phenyl-4H-benzo thiapyran ketone, concrete steps are as follows:
(1) 2-methyl-4H-benzo thiapyran ketone
By 12.5g H
3pO
4, 18gP
2o
5stir at 70 DEG C, after dissolving, the mixed solution of 1.5mL thiophenol and 1.5mL methyl aceto acetate is dripped (15min) with constant pressure funnel, reacting poured in frozen water after 3 hours, extraction into ethyl acetate, the organic layer 10%NaOH aqueous solution (20mL × 3) washs, be adjusted to pH=9, after washing with water, organic over anhydrous MgSO
4drying, products therefrom ether condensing crystal obtains yellow crystal 1.6g, and yield is 77.4%.
1H-NMR(CDCl
3/TMS)δ:8.48(1H,J＝7.9Hz,d),7.56-7.52(2H,m),7.50(1H,J＝7.6,7.9Hz,dd),6.82(1H,s),2.44(3H,s).
13C-NMR(CDCl
3)δ:180.63,151.32,137.64,131.35,130.70,128.54,127.48, 125.98,124.89,23.31.
(2) the iodo-2-methyl of 3--4H-benzo thiapyran ketone
By 176mg2-methyl-4H-benzo thiapyran ketone (compound 2), 305mg I
2, the mixture of 603mg CAN in 4.0mL MeCN at N
2protect lower 60 DEG C of stirrings, react to raw material disappearance (monitoring of TLC point plate).Products therefrom pours cold Na into
2s
2o
3the aqueous solution, uses CH
2cl
2extraction, after organic layers with water is washed, uses anhydrous MgSO
4dry.Solvent steams, and products therefrom obtains yellow crystal 280mg by column chromatography, and yield is 93%.
1H-NMR(CDCl
3/TMS)δ:8.52(1H,J＝7.9Hz,d),7.60(1H,J＝7.6,7.9Hz,dd),7.55-7.51(2H,m),2.62(3H,s).
13C-NMR(CDCl
3)δ:175.46,151.12,136.32,131.59,129.77,128.12,126.90,124.86,103.70,32.44.
(3) 2-methyl-3-phenyl-4H-benzo thiapyran ketone
Weigh respectively in four-hole boiling flask and load 302mg3-iodo-2-methyl-4H-benzo thiapyran ketone (compound 3), 21mg Pd (PPh
3)
2cl
2, 159mg PhB (OH)
2with 552mg K
2cO
3, 3.2mL DMF and 0.8mLH
2o, stirring reaction 4 hours at 80 DEG C, aqueous layer with ethyl acetate extracts, and mixing organic layers with water and strong brine washing, then use anhydrous MgSO
4drying, solvent steams, and products therefrom obtains white crystals 244mg by column chromatography purification, and yield is 96%.
1H-NMR(CDCl
3/TMS)δ:8.51(1H,J＝8.6Hz,d),7.61-7.59(2H,m),7.53-7.4(1H,m),7.45(2H,J＝7.6,7.6Hz,dd),7.37(1H,J＝7.6,7.6Hz,dd),7.21(2H,J＝7.6Hz,d),2.26(3H,s).
13C-NMR(CDCl
3)δ:179.14,147.18,136.63,136.40,136.00,131.16,131.09,129.77,129.38,128.45,127.55,127.35,125.52,22.52.
(4) 4-ketone group-3-phenyl-4H-benzo thiapyran-2-formaldehyde
By 252mg2-methyl-3-phenyl-4H-benzo thiapyran ketone (compound 4), 266mg SeO
2, join in 10.0mL orthodichlorobenzene, be heated to 150 DEG C.Heated and stirred adds NaHCO after reacting 7 hours
3the aqueous solution, water layer CH
2cl
2extraction, mixing organic layers with water and strong brine washing, then use anhydrous MgSO
4dry.Solvent steams, and products therefrom obtains yellow crystal 163mg by column chromatography purification, and yield is 61%.
1H-NMR(500MHz,CDCl
3/TMS):δ＝9.73(1H,s),8.53(1H,d,J＝7.9Hz),7.74(2H,m),7.60(1H,dd,J＝6.7,6.7Hz),7.51(3H,m),7.39(2H,m).
13C-NMR(125MHz,CDCl
3/TMS):δ＝190.35,180.93,143.80,143.74,136.41,132.51,132.29,131.54,131.21,129.57,129.43,128.38,128.19,127.54.
(5) 2-carboxaldehyde radicals-3-phenyl-4H-alkylsulfonyl benzo thiapyran ketone
To containing 266mg4-ketone group-3-phenyl-4H-benzo thiapyran-2-formaldehyde (compound 5), in the flask of 515mg m-CPBA, add 5.0mL CH
2cl
2.Stirred at ambient temperature reacts 24 hours, adds 10.0mLNa after reaction
2s
2o
3the aqueous solution, water layer CH
2cl
2extraction, mixing organic layer NaHCO
3the aqueous solution and strong brine washing, then use anhydrous MgSO
4drying, solvent steams, and products therefrom obtains yellow crystal 268mg by column chromatography, and yield is 90%.
1H-NMR(500MHz,CDCl
3/TMS):δ＝9.54(1H,s),8.24(1H,d,J＝6.7Hz),8.15(1H,d,J＝7.9Hz),7.97(1H,dd,J＝7.9,7.9Hz),7.83(1H,dd,J＝6.7,7.9Hz),7.63(1H,dd,J＝7.3,7.9Hz),7.56(2H,dd,J＝7.9,7.3Hz),7.37(2H,d,J＝6.7Hz).
13C-NMR(125MHz,CDCl
3/TMS):δ＝185.3,179.5,148.7,141.8,141.2,135.7,133.4,131.5,131.1,129.0,128.7,128.5,128.1,123.4.HRMS(EI)m/z[M
+]calcdfor C
16H
10O
4S:298.0300；found:298.0298.
(6) 1,1-dioxo-2-tosylhydrazone-3-phenyl-4H-benzo thiapyran ketone
By 298mg2-carboxaldehyde radicals-3-phenyl-4H-alkylsulfonyl benzo thiapyran ketone (compound 6), 205mg p-toluene sulfonyl hydrazide slowly adds in 8mL EtOH, stirs energetically under normal temperature; after 24 hours; collected by filtration, obtains yellow crystal 386mg by washing with alcohol, and yield is 83%.
1H-NMR(500MHz,CDCl
3/TMS):δ＝8.20(3H,m),7.92(1H,dd,J＝7.9Hz),7.81(2H,d,J＝8.5Hz),7.78(1H,dd,J＝7.9Hz),7.50(3H,m),7.32(2H,d,J＝8.5Hz),7.19(2H,d,J＝7.0Hz),5.30(1H,s),2.42(3H,s).
13C-NMR(125MHz,CDCl
3/TMS):δ＝178.1,145.0,144.3,143.4,142.2,142.1,136.8,135.0,134.5,133.0,130.8,129.9,129.8,128.6,128.6,128.3,128.2,123.4,21.7.
(7) 1,1-dioxo-2-diazo-3-phenyl-4H-benzo thiapyran ketone
0.4mL 1%NaOH is dropwise joined under stirring at normal temperature, is dissolved in CH
2cl
2in 1,1-dioxo-2-tosylhydrazone-3-phenyl-4H-benzo thiapyran ketone (compound 7) of 47mg, stirred at ambient temperature reacts 1 hour, uses CH after reaction
2cl
2extraction, the CH of mixing
2cl
2anhydrous MgSO is used after solution washed with water
4dry.Steamed by solvent, obtain yellow liquid 27mg, yield is 86%.
1H-NMR(500MHz,CDCl
3/TMS):δ＝8.26(1H,d,J＝7.9Hz),8.06(1H,d,J＝7.9Hz),7.85(1H,dd,J＝7.9Hz),7.79(1H,dd,J＝7.9Hz),7.48(3H,m),7.27(2H,d,J＝7Hz),4.95(1H,s).
13C-NMR(125MHz,CDCl
3/TMS):δ＝175.0,139.6,133.5,133.5,132.5,129.8,129.6,129.1,128.9,128.8,128.7,127.4,122.7,47.5.
Embodiment 2
The synthesis of 1,1-dioxo-2-diazo-3-p-methoxyphenyl-4H-benzo thiapyran ketone, method with embodiment 1, yield 84%.
1H-NMR(CDCl3)δ：8.21(1H,d,J＝7.9Hz),8.09(1H,d,J＝7.9Hz),7.89(1H,dd,J＝7.9,7.9Hz),7.78(1H,dd,J＝7.9,7.9Hz),7.35(2H,d,J＝9.2Hz),7.00(2H,d,J＝9.2Hz),5.03(1H,s),3.86(3H,s).
13C-NMR(CDCl
3)δ:178.94,160.63,147.08,142.50,139.96,134.54,133.33,131.18,129.22,129.03,122.99,122.66,113.80,55.32,47.01.
Embodiment 3
The synthesis of 1,1-dioxo-2-diazo-3-(3,5-bis-(trifluoromethyl)) phenyl-4H-benzo thiapyran ketone, method with embodiment 1, yield 75%.
1H-NMR(CDCl
3)δ:8.25(1H,d,J＝7.9Hz),8.13(1H,d,J＝7.9Hz),8.02(1H,s),7.96(1H,dd,J＝7.9,7.9Hz),7.92(2H,s),7.85(1H,dd,J＝7.9,7.9Hz),5.05(1H,s).
13C-NMR(CDCl
3)δ:177.79,149.68,139.85,139.81,135.22,133.74,132.58,132.00,131.73,131.46,130.20,129.23,128.56,124.04,123.39,121.87,46.54.
Embodiment 4
The synthesis of 1,1-dioxo-2-diazo-3-(2-naphthyl)-4H-benzo thiapyran ketone, method with embodiment 1, yield 80%.
1H-NMR(CDCl
3)δ:8.23(1H,d,J＝7.9Hz),8.13(1H,d,J＝7.9Hz),7.95-7.89(5H,m),7.80(1H,dd,J＝7.9,7.9Hz),7.59-7.54(2H,m),7.43(1H,dd,J＝8.6,1.2Hz),5.05(1H,s).
13C-NMR(CDCl
3)δ:178.77,148.03,142.75,140.06,134.68,133.47,133.42,132.65,129.33,129.16,129.09,128.51,128.15,128.03,127.77,127.30,126.74,126.48,123.11,47.07.
Embodiment 5
The synthesis of 1,1-dioxo-2-diazo-3-phenyl-4H-[f] aphthothiopyrans ketone, method with embodiment 1, yield 76%.
1H-NMR(CDCl
3)δ:9.00(1H,d,J＝8.6Hz),8.34(1H,d,J＝8.6Hz),8.12(1H,d,J＝8.6Hz),7.98(1H,d,J＝8.6Hz),7.75-7.71(2H,m),7.52-7.47(5H,m),5.03(1H,s).
13C-NMR(CDCl
3)δ:182.30,145.07,145.02,140.20,136.02,135.43,131.12,130.85,129.72,129.55,129.48,129.24,129.02,128.50,127.42,126.90,118.52,117.68,46.98。
Claims (3)
1. a novel diazo benzo thiapyran ketone photosensitive protective group, is characterized in that: its general structure is as follows:
Wherein R
1for: trifluoromethyl; Aryl; R
2for: to methoxyl group; Aryl.
2. novel diazo benzo thiapyran ketone photosensitive protective group according to claim 1, it is characterized in that: described compound is 1, 1-dioxo-2-tosylhydrazone-3-phenyl-4H-benzo thiapyran ketone, or 1, 1-dioxo-2-diazo-3-phenyl-4H-benzo thiapyran ketone, or 1, 1-dioxo-2-diazo-3-p-methoxyphenyl-4H-benzo thiapyran ketone, or 1, 1-dioxo-2-diazo-3-(3, 5-bis-(trifluoromethyl)) phenyl-4H-benzo thiapyran ketone, or 1, 1-dioxo-2-diazo-3-(2-naphthyl)-4H-benzo thiapyran ketone, or 1, 1-dioxo-2-diazo-3-phenyl-4H-[f] aphthothiopyrans ketone.
3. prepare the method for novel diazo benzo thiapyran ketone photosensitive protective group according to claim 1, it is characterized in that: step is as follows
(1), after catalyzer melting is dissolved, drip the mixed solution of thiophenol and methyl aceto acetate, after dropwising, react 3 hours, after completion of the reaction, reaction solution is poured in frozen water, extraction into ethyl acetate, organic layer NaOH solution washing, be adjusted to pH=9, after washing with water, organic over anhydrous MgSO
4drying, products therefrom ether condensing crystal, obtained yellow crystal 2-methyl-4H-benzo thiapyran ketone;
Step (1) described in catalyzer be phosphoric acid or Vanadium Pentoxide in FLAKES, the volume ratio of thiophenol and methyl aceto acetate is 1:1;
(2) by 2-methyl-4H-benzo thiapyran ketone, iodine, solvent and catalyzer temperature-elevating to 60 DEG C that step is (1) obtained, react 4 hours, be cooled to room temperature after completion of the reaction, with hypo solution cancellation, dichloromethane extraction, after mixing organic layer washs with saturated sodium-chloride, with anhydrous magnesium sulfate drying, steam solvent, column chromatography obtains the iodo-2-methyl of yellow crystal 3--4H-benzo thiapyran ketone;
Step (2) described in catalyzer be ceric ammonium nitrate, solvent is acetonitrile, and the mol ratio of 2-methyl-4H-benzo thiapyran ketone and iodine is 1:1.2;
(3) by the iodo-2-methyl of 3--4H-benzo thiapyran ketone, phenylo boric acid, solvent and catalyzer temperature-elevating to 80 DEG C that step is (2) obtained, react 4 hours, be cooled to room temperature after completion of the reaction, with saturated sodium-chloride and extraction into ethyl acetate, mixing organic layer is with anhydrous magnesium sulfate drying, screw out solvent, column chromatography obtains white crystal 2-methyl-3-phenyl-4H-benzo thiapyran ketone;
Step (3) described in catalyzer be two (triphenyl phosphorus) palladium chloride and salt of wormwood, solvent is DMF/water, and the mol ratio of the iodo-2-methyl of 3--4H-benzo thiapyran ketone and phenylo boric acid is 1:1.3;
(4) 2-methyl-3-phenyl-4H-benzo thiapyran ketone, tin anhydride, molecular sieve and solvent that step is (3) obtained are warming up to 150 DEG C, react 8 hours, after completion of the reaction, with saturated sodium bicarbonate solution cancellation, dichloromethane extraction, mixing organic layer is with anhydrous magnesium sulfate drying, and after screwing out methylene dichloride, column chromatography obtains yellow crystal 4-ketone group-3-phenyl-4H-benzo thiapyran-2-formaldehyde;
Step (4) described in solvent be orthodichlorobenzene, the mol ratio of 2-methyl-3-phenyl-4H-benzo thiapyran ketone and tin anhydride is 1:2.4;
(5) by (4) obtained for step 4-ketone group-3-phenyl-4H-benzo thiapyran-2-formaldehyde, metachloroperbenzoic acid and solvent normal-temperature reaction 24 hours, after completion of the reaction, with hypo solution and saturated sodium bicarbonate solution cancellation, dichloromethane extraction, mixing organic layer is with anhydrous magnesium sulfate drying, screw out solvent, column chromatography obtains yellow crystal 2-carboxaldehyde radicals-3-phenyl-4H-alkylsulfonyl benzo thiapyran ketone;
Step (5) described in solvent be methylene dichloride, the mol ratio of 4-ketone group-3-phenyl-4H-benzo thiapyran-2-formaldehyde and metachloroperbenzoic acid is 1:2.1;
(6) 2-carboxaldehyde radicals-3-phenyl-4H-alkylsulfonyl benzo thiapyran-4-ketone (5) obtained for step, p-toluene sulfonyl hydrazide are added drop-wise in EtOH, normal-temperature reaction 24 hours, after completion of the reaction, collected by filtration, yellow crystal 1,1-dioxo-2-tosylhydrazone-3-phenyl-4H-benzo thiapyran ketone is obtained by washing with alcohol;
(7) the 2-tosylhydrazone-3-phenyl-4H-alkylsulfonyl benzo thiapyran that step is (6) obtained is dissolved in solvent; after normal temperature drips sodium hydroxide solution; react 1 hour; after completion of the reaction, with dichloromethane extraction, after the washing of mixing organic layer; with anhydrous magnesium sulfate drying; screw out solvent, column chromatography obtains yellow liquid 1,1-dioxo-2-diazo-3-phenyl-4H-benzo thiapyran ketone.
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|---|---|---|---|---|
| CN112300118A (en) * | 2020-09-23 | 2021-02-02 | 天津理工大学 | Novel benzothiopyranone compound and preparation method and application thereof |
| CN112592330A (en) * | 2020-12-14 | 2021-04-02 | 陕西师范大学 | Synthesis method of 2-aldehyde thiochromone compound |
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2014
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| Title |
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| YOULAI ZHANG: "Novel Photolabile Protecting Group for Phosphate Compounds", 《SYNLETT》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112300118A (en) * | 2020-09-23 | 2021-02-02 | 天津理工大学 | Novel benzothiopyranone compound and preparation method and application thereof |
| CN112300118B (en) * | 2020-09-23 | 2022-08-30 | 天津理工大学 | Benzothiopyranone compound and preparation method and application thereof |
| CN112592330A (en) * | 2020-12-14 | 2021-04-02 | 陕西师范大学 | Synthesis method of 2-aldehyde thiochromone compound |
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