CN110317198B - Phenothiazine compound and preparation method and application thereof - Google Patents
Phenothiazine compound and preparation method and application thereof Download PDFInfo
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- -1 Phenothiazine compound Chemical class 0.000 title claims abstract description 16
- 229950000688 phenothiazine Drugs 0.000 title claims abstract description 15
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 30
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims abstract description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract description 12
- DLYKFPHPBCTAKD-UHFFFAOYSA-N 2-methoxy-10H-phenothiazine Chemical compound C1=CC=C2NC3=CC(OC)=CC=C3SC2=C1 DLYKFPHPBCTAKD-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000007850 fluorescent dye Substances 0.000 claims abstract description 9
- 238000000034 method Methods 0.000 claims abstract description 9
- 239000000126 substance Substances 0.000 claims abstract description 9
- YYVYAPXYZVYDHN-UHFFFAOYSA-N 9,10-phenanthroquinone Chemical compound C1=CC=C2C(=O)C(=O)C3=CC=CC=C3C2=C1 YYVYAPXYZVYDHN-UHFFFAOYSA-N 0.000 claims abstract description 6
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000005695 Ammonium acetate Substances 0.000 claims abstract description 6
- 229960000583 acetic acid Drugs 0.000 claims abstract description 6
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims abstract description 6
- 229940043376 ammonium acetate Drugs 0.000 claims abstract description 6
- 235000019257 ammonium acetate Nutrition 0.000 claims abstract description 6
- 239000012362 glacial acetic acid Substances 0.000 claims abstract description 6
- 150000001335 aliphatic alkanes Chemical class 0.000 claims abstract description 5
- 125000003172 aldehyde group Chemical group 0.000 claims abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims description 11
- WRQHNSKKYGHTLO-UHFFFAOYSA-N 1h-phenanthro[9,10-d]imidazole Chemical compound C12=CC=CC=C2C2=CC=CC=C2C2=C1NC=N2 WRQHNSKKYGHTLO-UHFFFAOYSA-N 0.000 claims description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 10
- 230000008569 process Effects 0.000 claims description 4
- 238000005874 Vilsmeier-Haack formylation reaction Methods 0.000 claims description 2
- 238000010791 quenching Methods 0.000 claims description 2
- 150000001350 alkyl halides Chemical class 0.000 claims 1
- 229910052736 halogen Inorganic materials 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 14
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 abstract 2
- 150000002460 imidazoles Chemical class 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 230000005284 excitation Effects 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 2
- WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- RZNMTPYSJUIHID-UHFFFAOYSA-N 2-(2H-thiazin-3-yl)phenol Chemical group OC1=CC=CC=C1C1=CC=CSN1 RZNMTPYSJUIHID-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical group CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 241000282414 Homo sapiens Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 208000004852 Lung Injury Diseases 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- LFZAGIJXANFPFN-UHFFFAOYSA-N N-[3-[4-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)piperidin-1-yl]-1-thiophen-2-ylpropyl]acetamide Chemical compound C(C)(C)C1=NN=C(N1C1CCN(CC1)CCC(C=1SC=CC=1)NC(C)=O)C LFZAGIJXANFPFN-UHFFFAOYSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000004650 carbonic acid diesters Chemical class 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 239000002575 chemical warfare agent Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- ZWWWLCMDTZFSOO-UHFFFAOYSA-N diethoxyphosphorylformonitrile Chemical compound CCOP(=O)(C#N)OCC ZWWWLCMDTZFSOO-UHFFFAOYSA-N 0.000 description 1
- LGTLXDJOAJDFLR-UHFFFAOYSA-N diethyl chlorophosphate Chemical compound CCOP(Cl)(=O)OCC LGTLXDJOAJDFLR-UHFFFAOYSA-N 0.000 description 1
- VONWDASPFIQPDY-UHFFFAOYSA-N dimethyl methylphosphonate Chemical compound COP(C)(=O)OC VONWDASPFIQPDY-UHFFFAOYSA-N 0.000 description 1
- 238000001917 fluorescence detection Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000004896 high resolution mass spectrometry Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 231100000515 lung injury Toxicity 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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Abstract
The invention discloses a phenothiazine compound, a preparation method and application thereofThe phenothiazine compound is connected with phenanthro [9,10-d ] at the 3 position]Imidazole, the chemical structural formula of which is shown as formula I, wherein R is C1～C20Alkyl group of (1). The method comprises the steps of adding sodium hydroxide into a 2-methoxyphenothiazine solution and a halogenated alkane solution to prepare an intermediate 1, introducing aldehyde groups to obtain an intermediate 2, adding the intermediate 2 into an anhydrous dichloromethane solution of anhydrous aluminum trichloride to obtain an intermediate 3, dissolving the intermediate 3 and phenanthrenequinone in glacial acetic acid, and adding anhydrous ammonium acetate to react to obtain a target product. The compound can be used as a fluorescent probe for identifying phosgene. The compound of the invention is used as a fluorescent probe, has stable structure, is simple and easy to obtain, has higher preparation yield and has certain application value.
Description
Technical Field
The invention belongs to the technical field of functional compound synthesis, relates to a phenothiazine compound, a preparation method and application thereof, and particularly relates to a phenothiazine compound with phenanthro [9,10-d ] imidazole connected to the 3-position, and a preparation method and application thereof.
Background
Phosgene, also known as phosgene, has two reactive acid chloride functional groups in its structure that can react with nucleophilic groups such as hydroxyl and amino groups. Phosgene is colorless and highly toxic, and human beings can generate respiratory tract and lung injuries after being exposed to phosgene with the concentration of 20ppm for 20 minutes, and even die after being exposed for a long time, so that phosgene is used as a chemical weapon for war and terrorist activities. 80% of the number of people who become poisoned in world war ii are caused by phosgene. Phosgene production and use is strictly controlled and regulated in various countries. However, phosgene has a very important role in chemical synthesis due to its specific reactivity, for example, phosgene can be used for the construction of carbonic acid diesters and carbamates in pharmaceutical synthesis, and thus phosgene has wide application in laboratories and pharmaceutical companies. In order to effectively monitor the phosgene leakage in the experimental process or terrorist activities, thereby ensuring the social public safety, the development of an efficient phosgene detection means has important significance.
In the last two decades, due to its high sensitivity and selectivity, the fluorescence detection method has been widely used for the analytical detection of different substrates, and much attention has been paid to the development of phosgene fluorescent probes. However, these fluorescent probes still suffer from the problems of complicated synthesis, low yield, and insufficient selectivity to phosgene. Therefore, there is still a need to develop a phosgene fluorescent probe that is easy to synthesize and has high selectivity.
Disclosure of Invention
The invention aims to provide a phenothiazine compound with phenanthro [9,10-d ] imidazole connected to the 3-position, a preparation method and application thereof, wherein the phenothiazine has a larger conjugated system, and can be used for deriving a series of fluorescent dyes with better light stability and larger Stokes shift. The phenanthro [9,10-d ] imidazole contains active N-H, can act with phosgene, and the construction method of the phenanthro [9,10-d ] imidazole structure is mature and has high yield.
The invention is realized by the following technical scheme:
a phenothiazine compound with phenanthro [9,10-d ] imidazole connected to the 3-position has a chemical structural formula shown in a formula I:
wherein R is C1～C20Alkyl group of (1).
Preferably, R is C2～C12。
In another aspect of the present invention, there is provided a process for the preparation of said compounds, which comprises the following reaction scheme:
the method specifically comprises the following steps:
1) dissolving 2-methoxyphenothiazine and halogenated alkane R-X in dimethyl sulfoxide, adding sodium hydroxide, and reacting at 60-80 ℃ for 7-15 hours to prepare an intermediate 1;
2) introducing aldehyde group into 3-position of the intermediate 1 through Vilsmeier reaction to prepare an intermediate 2;
3) adding the intermediate 2 into an anhydrous dichloromethane solution of anhydrous aluminum trichloride, reacting for 10-14 hours at 20-30 ℃, and then adding a dilute hydrochloric acid solution to quench the reaction to prepare an intermediate 3;
4) dissolving the intermediate 3 and phenanthrenequinone in glacial acetic acid, adding excessive anhydrous ammonium acetate, and reacting at the temperature of 100-130 ℃ for 2-4 hours to prepare the phenothiazine compound with phenanthro [9,10-d ] imidazole connected to the 3-position.
Further, in the halogenated alkane R-X in the step (1), R is C1～C20Is alkyl of (A), X isHalogen, p-toluenesulfonate, methanesulfonate, and the like, which are easy to leave atoms or functional groups.
Furthermore, the dosage of the halogenated hydrocarbon and the 2-methoxyphenothiazine in the step (1) is 1.5-3.0: 1 based on the amount of the substance, and the dosage of 1mmol of 2-methoxyphenothiazine corresponding to dimethyl sulfoxide is 1.5-2.5 mL.
Furthermore, the dosage of the sodium hydroxide and the 2-methoxyphenothiazine in the step (1) is 1.2-2.2: 1 based on the amount of the substance.
Furthermore, the dosage of the anhydrous aluminum trichloride and the intermediate 2 in the step (3) is 2.0-3.0: 1 in terms of the amount of the substance, and the dosage of 1mmol of the intermediate 2 corresponding to anhydrous dichloromethane is 3-5 mL.
Further, the concentration of the dilute hydrochloric acid in the step (3) is 1-3 mol/L, and the HCl equivalent in the dilute hydrochloric acid is 2-3 times of that of the intermediate 3.
Further, the dosage of the phenanthrenequinone and the intermediate 3 in the step (4) is 1.1-1.3: 1 by mass, and the dosage of glacial acetic acid corresponding to 1mmol of the intermediate 3 is 10 mL.
Further, the amount of the anhydrous ammonium acetate and the intermediate 3 in the step (4) is 15-30: 1 in terms of the amount of the substances.
In another aspect of the present invention, there is provided the use of the above compound as a phosgene fluorescent probe.
Specifically, the phenothiazine compound with phenanthro [9,10-d ] imidazole connected to the 3-position is dissolved in chloroform to form a 10 mu M solution, triphosgene and triethylamine are added, and the change of a fluorescence signal can be detected by a fluorescence instrument.
The invention has the beneficial effects that:
according to the invention, a phenanthro [9,10-d ] imidazole structure is introduced into the 3-position of 2-hydroxyphenylthiazine, and double reaction sites of N-H and O-H are constructed, so that the reaction selectivity of the compound to phosgene is improved. The fluorescent probe has the advantages of stable structure, simplicity, easy obtaining, higher preparation yield and certain application value.
Drawings
Figure 1 hydrogen spectrum of compound 4.
Figure 2 carbon spectrum of compound 4.
FIG. 3 high resolution mass spectrum of Compound 4.
FIG. 4 selectivity test of compound 4 to phosgene in chloroform. Where the probe concentration is 2. mu.M, the test substrates are: acetyl chloride, benzoyl chloride, diethyl chlorophosphate, diethyl cyanophosphate, dimethyl methylphosphonate, oxalyl chloride, phosphorus oxychloride, thionyl chloride, p-toluenesulfonyl chloride and triphosgene/triethylamine. The concentration of each test substrate was 2. mu.M. The excitation wavelength was 388 nm.
FIG. 5 fluorescence titration of compound 4 against phosgene in chloroform. Wherein the probe concentration is 2 μ M, and the excitation wavelength is 388 nm.
Detailed Description
The technical solutions of the present invention will be described clearly and completely with reference to specific embodiments of the present invention, and it should be understood that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1 Synthesis of intermediate 1
Iodothane (3.9g,25mmol) and 2-methoxyphenolthiazine (2.29g,10mmol) were dissolved in 20mL of dimethyl sulfoxide, followed by addition of NaOH (0.8g, 20mmol) and warming to 65 ℃ for 15 hours. After completion of the reaction, the reaction mixture was cooled to room temperature, 300mL of water was added, extraction was performed with dichloromethane (50 mL. times.2), washing was performed with saturated brine (50 mL. times.2), drying was performed with anhydrous sodium sulfate, and then the solvent was removed under reduced pressure, and the resulting residue was separated with a 200-mesh 300-mesh silica gel column to obtain a white solid (2.3g, 89.5%).
1H NMR(600MHz,DMSO-d6)7.14(ddd,J＝8.4,7.2,1.4Hz,1H),7.08(dd,J＝7.6,1.7Hz,1H),7.02–6.94(m,2H),6.92–6.86(m,1H),6.51(d,J＝7.6Hz,2H),3.87(q,J＝6.9Hz,2H),3.70(s,3H),1.25(t,J＝6.9Hz,3H).
EXAMPLE 2 Synthesis of Compound 2
1.7mL of DMF was added dropwise to phosphorus oxychloride (1mL) under an ice bath under nitrogen, and after stirring for 15 minutes, a solution of intermediate 1(2.57g,10mmol) in DMF (7.5mL) was added dropwise to the reaction. After the dropwise addition, the temperature is raised to 60 ℃ for continuous reaction for 4 hours, then the reaction liquid is poured into ice water and stirred for a while, and saturated NaHCO is added3The solution was neutralized to neutral pH, followed by extraction with dichloromethane (50mL × 3), washing with saturated brine (50mL × 2), drying over anhydrous sodium sulfate, and then removing the solvent under reduced pressure, and the resulting residue was separated with a 200-mesh 300-mesh silica gel column to give a yellow solid (2.48g, 87%).
1H NMR(600MHz,Chloroform-d)10.19(s,1H),7.51(s,1H),7.13(t,J＝7.6Hz,1H),7.09(dd,J＝7.6,1.5Hz,1H),6.93(t,J＝7.3Hz,1H),6.87(d,J＝8.2Hz,1H),6.37(s,1H),4.08–3.92(m,2H),3.90(s,3H),1.45(t,J＝7.0Hz,3H).
Example 3 Synthesis of intermediate 3
Aluminum trichloride (1.98g, 10mmol) was added to anhydrous dichloromethane (15mL), and then a solution of intermediate 3(1.42g,5mmol) in anhydrous dichloromethane (5mL) was added dropwise thereto. After the addition was complete, the reaction was allowed to continue at 20 ℃ for 12 hours, and then quenched by the addition of hydrochloric acid solution (2M, 6 mL). Ethyl acetate (20 mL. times.3) was added for extraction, washed with saturated brine (30 mL. times.2), dried over anhydrous sodium sulfate, and then the solvent was removed under reduced pressure, and the resulting residue was separated with a 200-mesh 300-mesh silica gel column to give a yellow solid (1.26g, 92.6%).
1H NMR(600MHz,Chloroform-d)11.39(s,1H),9.60(d,J＝0.6Hz,1H),7.21–7.11(m,2H),7.10(dd,J＝7.7,1.7Hz,1H),6.97(td,J＝7.5,1.3Hz,1H),6.92(dd,J＝8.3,1.3Hz,1H),6.39(s,1H),3.95(q,J＝7.2Hz,2H),1.45(t,J＝7.1Hz,3H).
EXAMPLE 4 Synthesis of Compound 4
Intermediate 3(271mg, 1mmol) and phenanthrenequinone (250mg, 1.2mmol) were dissolved in glacial acetic acid (10mL), and anhydrous ammonium acetate (1.54g, 20mmol) was added. Heating the reaction system to 120 ℃ for further reaction for 2 hours, cooling to room temperature, adjusting the pH value to 5-6 by using a sodium hydroxide solution, adding dichloromethane (30mL multiplied by 3) for extraction, washing with saturated salt solution (30mL multiplied by 2), drying by using anhydrous sodium sulfate, removing the solvent under reduced pressure, and separating the obtained residue by using a 200-mesh 300-mesh silica gel column to obtain a yellow-green solid (400mg, 84.5%).
As shown in figure 1 of the drawings, in which,1H NMR(600MHz,DMSO-d6)8.90(dd,J＝18.7,8.3Hz,2H),8.53(d,J＝7.8Hz,1H),8.47(d,J＝7.8Hz,1H),8.01(s,1H),7.80(t,J＝7.4Hz,1H),7.76(t,J＝7.4Hz,1H),7.68(q,J＝8.4Hz,2H),7.26–7.20(m,2H),7.09(d,J＝8.2Hz,1H),6.99(td,J＝7.4,1.0Hz,1H),6.72(s,1H),4.01–3.97(m,2H),1.36(t,J＝6.9Hz,3H)。
as shown in figure 2 of the drawings, in which,13C NMR(150MHz,DMSO-d6)170.85,158.56,149.44,147.54,143.78,134.57,128.31,128.17,127.97,127.82,127.59,126.51,125.97,124.73,124.42,123.77,123.30,122.48,122.37,122.22,116.40,112.69,107.98,104.51,41.95,13.12。
as shown in FIG. 3, HR-MS (ESI) m/z theoretical value [ C29H21N3OS–H]–458.1333, respectively; actual value 458.1348.
As shown in FIG. 4, the selectivity of compound 4 to phosgene was tested and the excitation wavelength was 388 nm. As shown in FIG. 5, the fluorescence titration of compound 4 with phosgene gave an excitation wavelength of 388 nm.
Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.
Claims (9)
1. A phenothiazine compound, wherein the thiazine compound has phenanthro [9,10-d ] imidazole attached to the 3-position, and the structural formula of the thiazine compound is shown in formula i:
wherein R is C1～C20Alkyl group of (1).
2. A process for the preparation of a phenothiazine compound according to claim 1, comprising the steps of:
1) dissolving 2-methoxyphenothiazine and halogenated alkane R-X in dimethyl sulfoxide, adding sodium hydroxide, and reacting at 60-80 ℃ for 7-15 hours to prepare an intermediate 1;
2) introducing aldehyde group into 3-position of the intermediate 1 through Vilsmeier reaction to prepare an intermediate 2;
3) adding the intermediate 2 into an anhydrous dichloromethane solution of anhydrous aluminum trichloride, reacting for 10-14 hours at 20-30 ℃, and then adding a dilute hydrochloric acid solution to quench the reaction to prepare an intermediate 3;
4) dissolving the intermediate 3 and phenanthrenequinone in glacial acetic acid, adding excessive anhydrous ammonium acetate, and reacting at the temperature of 100-130 ℃ for 2-4 hours to prepare the phenothiazine compound with phenanthro [9,10-d ] imidazole connected to the 3-position.
3. The process according to claim 2, wherein R in the haloalkane of step (1) R-X is C1～C20X is halogen;
the dosage of the halogenated alkane R-X and the 2-methoxyphenothiazine is 1.5-3.0: 1 in terms of the amount of the substance, and the dosage of 1mmol 2-methoxyphenothiazine corresponding to dimethyl sulfoxide is 1.5-2.5 mL.
4. The preparation method according to claim 2, wherein the amount of the sodium hydroxide and the 2-methoxyphenothiazine used in step (1) is 1.2 to 2.2:1 based on the amount of the substance.
5. The method according to claim 2, wherein the amount of the anhydrous aluminum trichloride and the intermediate 2 used in the step (3) is 2.0-3.0: 1 based on the amount of the substance, and the amount of the anhydrous dichloromethane corresponding to 1mmol of the intermediate 2 is 3-5 mL.
6. The method according to claim 2, wherein the concentration of the dilute hydrochloric acid in the step (3) is 1 to 3mol/L, and the HCl equivalent in the dilute hydrochloric acid is 2 to 3 times of that of the intermediate 3.
7. The preparation method according to claim 2, wherein the amount of the phenanthrenequinone and the intermediate 3 in step (4) is 1.1-1.3: 1 by mass, and the amount of glacial acetic acid corresponding to 1mmol of the intermediate 3 is 10 mL.
8. The preparation method according to claim 2, wherein the amount of the anhydrous ammonium acetate and the intermediate 3 in the step (4) is 15-30: 1 by mass.
9. Use of a phenothiazine compound of claim 1 as a phosgene fluorescent probe.
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