JP2800845B2 - Anthracene derivative - Google Patents

Description

Description: FIELD OF THE INVENTION The present invention relates to anthracene derivatives. More specifically, the present invention relates to a novel anthracene derivative useful as a chemiluminescence sensitizer of a peroxalate chemiluminescence system.

(Prior art) In peroxalate chemiluminescence, an active intermediate formed from an oxalate and hydrogen peroxide forms a charge transfer complex with a fluorescent substance, and the fluorescent substance excited by the charge transfer returns to the ground state. Light emission that occurs sometimes.

As one using peroxalate chemiluminescence,
“Penlights” and “light emitting units” have been put to practical use. In addition, peroxalate chemiluminescence has recently attracted particular attention for its application to ultrasensitive analytical methods.

As a high-sensitivity analysis method, a fluorescence analysis method has already been put to practical use, and a detection limit of 10 ⁻¹⁵ mol (femtomole) has been achieved. Fluorescence analysis detects fluorescence generated when a fluorescent substance is irradiated with excitation light such as ultraviolet light. Therefore, by increasing the intensity of the excitation light, the generated fluorescence is increased, so that the detection limit should be able to be further expanded. However, larger the use of excitation light of high intensity, but the fluorescence intensity increases, the rise also stray and Raman light from the excitation light at the same time, as a result, the detection limit of 10 ^-15 mol (fmol) level or higher It is difficult to do.

On the other hand, chemiluminescence is light emission generated when a fluorescent substance is excited by a chemical reaction. Thus, chemiluminescence analysis, there is no interference by noise, such as stray light in a fluorescent assay, the detection limit of 10 ^-18 mol (attomole) level is achieved.

Examples of application of the chemiluminescence analysis method using peroxalate chemiluminescence include quantification of a trace amount of hydrogen peroxide or quantification of a trace amount of a substrate in an enzyme reaction system that generates hydrogen peroxide. To use chemiluminescence analysis effectively,
A fluorescent substance having excellent luminous efficiency as a chemiluminescence sensitizer is indispensable. At present, 9,10-diphenylanthracene is known as a typical fluorescent substance used as a chemiluminescent sensitizer. However, development of a chemiluminescent sensitizer having more excellent luminous efficiency has been demanded.

(Object of the Invention) It is an object of the present invention to provide a chemiluminescence sensitizer excellent in luminous efficiency of a peroxalate chemiluminescence system.

(Constitution of the Invention) The object of the present invention has been achieved by a novel anthracene derivative having a substituted or unsubstituted phenylethynyl group at the 9-position and the 10-position represented by the general formula [I].

(Wherein R ₁ and R ₂ are independently a lower (C ₁ -C ₂ ) alkyl group,
An amino group, a lower alkylamino group, a di-lower alkylamino group or a cyano group).

The chemiluminescence sensitizer is required to have excellent fluorescence intensity, fluorescence quantum yield, and chemiluminescence intensity.

The anthracene derivative represented by the general formula [I] of the present invention generates strong fluorescence when irradiated with excitation light such as ultraviolet light, and thus has excellent fluorescence intensity, and also generates strong chemiluminescence due to oxalate and hydrogen peroxide. It has excellent chemiluminescence intensity and is extremely useful as a chemiluminescence sensitizer for chemiluminescence analysis.

In order to exemplify that the anthracene derivative represented by the general formula [I] of the present invention is useful as a peroxalate-based chemiluminescence sensitizer, measurement results regarding the fluorescence intensity and the chemiluminescence intensity, which are indicators, are as follows: Table 1 shows the relative values when the known value of 9,10-diphenylanthracene was set to 1.00. In addition, the chemiluminescence intensity was calculated from the gradients of the calibration curves of the respective fluorescent substances by preparing a calibration curve for each fluorescent substance using a flow injection method.

From the results shown in Table 1, the anthracene derivative A of the present invention,
It is clear that B and C are superior to the known fluorescent substance D in performance as a chemiluminescence sensitizer.

The anthracene derivative represented by the general formula [I] of the present invention can be easily synthesized by the following novel synthesis method developed by the present inventors. The synthesis method developed by the present inventors is:
By treating an anthracene derivative having an ethylene group represented by the general formula [II] with potassium t-butoxide in dimethylformamide, a double bond is converted into a triple bond in a one-step reaction, and the corresponding acetylene group is obtained. To provide an anthracene derivative.

The anthracene derivative represented by the general formula [II] has R ₁
When R ₂ is the same, it can be synthesized, for example, by the method described in JP-A-51-98261. That is, 9,10-bis (chloromethyl)
Obtained by reacting anthracene with trimethyl phosphite 9,
Dimethyl 10-bis (anthrylmethyl) phosphonate
It only has to react with a substituted or unsubstituted benzaldehyde.

Further, R ₁ and if R ₂ is heterogeneous, the 9,10-di-formyl anthracene and p- nitrobenzyl triphenylphosphonium halide obtained by reacting 9-(p- nitrostyryl) -10-formyl-anthracene p Reacting with a substituted or unsubstituted benzyltriphenylphosphonium halide to synthesize 9- (p-nitrostyryl) -10- (p-substituted or unsubstituted styryl) anthracene, and converting the nitro group by various known methods. What is necessary is just to convert into another substituent.

(Example) An example is shown below, but the present invention is not limited to this example.

Example 1 Preparation of 9,10-bis (p-diethylaminophenylethynyl) anthracene 10.00 g (36.4 mmol) of 9,10-bis (chloromethyl) anthracene and 100 mL of trimethyl phosphite were mixed in xylene for 24 hours.
The mixture was stirred and refluxed for an hour. Then, xylene and excess trimethyl phosphite were distilled off and then cooled. The precipitate was collected and washed with hexane to obtain 15.17 g (99% yield) of dimethyl 9,10-bis (anthrylmethyl) phosphonate as yellow crystals.

2.00 g (4.74 mmol) of dimethyl 9,10-bis (anthrylmethyl) phosphonate was dissolved in dimethylformamide, and 6 mL (14 mmol) of 2.3 M sodium methoxysodium was added thereto, followed by stirring at room temperature for 1.67 g. (9.44 mmol) of p-diethylaminobenzaldehyde in dimethylformamide was added and stirred for 3 hours. The precipitated crystals were collected, dried and recrystallized from dichloromethane to give 1.04 g (4
9,10-Bis (p-diethylaminostyryl) anthracene was obtained as yellow crystals (mp284-285 ° C).

Then, 0.40 g (0.76 mmol) of 9,10-bis (p-diethylaminostyryl) anthracene was dissolved in 150 mL of dimethylformamide, and 2.56 g (22.9 mmol) of t was added thereto.
-Potassium butoxide was added and stirred at room temperature for 3 hours. The reaction was drained into water and extracted with dichloromethane.
After the extract was dried over anhydrous magnesium sulfate, the solvent was distilled off, and the residue was purified by alumina column chromatography.
g (28% yield) of 9,10-bis (p-diethylaminophenylethynyl) anthracene was converted to yellow-orange crystals (mp258-260).
° C).

The target compound was confirmed from the following analysis results.

MS (m / z): 520 (M +) IR (Nujol): 2200cm -1 (C≡C) Elemental analysis: C H N measurements 87.18 6.97 5.33 Calculated _{(C 38 H 36 N 2)} 87.65 6.97 5.38 embodiment Example 2 9,10-bis (p-methylphenylethynyl)
Preparation of anthracene 2.00 g (4.74 mmol) of the dimethyl 9,10-bis (anthrylmethyl) phosphonate obtained in Example 1 was dissolved in dimethylformamide, and 6 mL (14 mmol) of 2.3 M methoxysodium was added thereto. Then, 1.14 g (9.5mmo) with stirring at room temperature
l) A solution of p-methylbenzaldehyde in dimethylformamide was added and stirred for 3 hours. The precipitated crystals were collected, dried and recrystallized from dichloromethane to give 1.11.
g (57% yield) of 9,10-bis (p-methylstyryl) anthracene was obtained as yellow crystals (mp 281-283 ° C).

Then, 0.40 g (0.98 mmol) of 9,10-bis (p-methylstyryl) anthracene was dissolved in 150 mL of dimethylformamide, and 3.29 g (29.4 mmol) of potassium t-butoxide was added thereto. Stir for 3 hours. The reaction was drained into water and extracted with benzene. After the extract was dried over anhydrous magnesium sulfate, the solvent was distilled off, and the residue was purified by recrystallization from dichloromethane to obtain 0.12 g (30% yield) of 9,10-bis (p-methylphenylethynyl) anthracene. Was obtained as yellow-orange crystals (mp 257-258 ° C).

The target compound was confirmed from the following analysis results.

MS (m / z): 406 (M ⁺ ) IR (KBr): 2190 cm ^-1 (C≡C) Elemental analysis: CH measured 94.40 5.60 calculated (C ₃₂ H ₂₂ ) 94.55 5.45 Example 3 9,10 -Bis (p-cyanophenylethynyl)
Preparation of anthracene 2.00 g (4.74 mmol) of the dimethyl 9,10-bis (anthrylmethyl) phosphonate obtained in Example 1 was dissolved in dimethylformamide, and 6 mL (14 mmol) of 2.3 M methoxysodium was added thereto. Then, 1.24 g (9.47mmo) with stirring at room temperature
l) A solution of p-cyanobenzaldehyde in dimethylformamide was added and stirred for 3 hours. The precipitated crystals were collected, washed with methanol, dried and recrystallized from dichloromethane to give 1.38 g (67% yield) of 9,10-bis (p-cyanostyryl) anthracene as orange crystals (mp> 320 ° C.).
As obtained.

Then, 0.40 g (0.93 mmol) of 9,10-bis (p-cyanostyryl) anthracene was dissolved in 250 mL of dimethylformamide, and 2.07 g (18.5 mmol) of potassium t-butoxide was added thereto. Stirred for 10 minutes. The reaction solution was poured into water, and the precipitated crystals were dried, recrystallized from dichloromethane, and further purified by silica gel column chromatography to obtain 0.07 g (18% yield) of 9,10-bis (p-cyanophenyl). Ethynyl) anthracene is converted to an orange crystal (mp324-3
25 ° C).

The target compound was confirmed from the following analysis results.

MS (m / z): 428 (M +) IR (Nujol): 2210cm -1 (C≡C), 2240cm -1 (C≡
N) Elemental analysis: C H N measurements 89.01 4.02 6.42 Calculated _{(C 32 H 16 N 2)} 89.70 3.76 6.54 ( formula chemiluminescence sensitization anthracene derivative represented by [I] Effect) The present invention By using it as an agent, the detection limit of peroxalate-based chemiluminescence analysis can be expanded.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁶ Identification code FI C07C 255/50 C07C 255/50 255/51 255/51 G03G 5/09 101 G03G 5/09 101 (58) Fields surveyed (Int. .Cl. ⁶ , DB name) C07C 15/60, 25/24, 43/215, 43/225, 211/50, 255/50, 255/51 CA (STN)

Claims (4)

(57) [Claims] (1) 9,10-bis (p-) represented by the general formula [1]:
Substituted phenylethynyl) anthracene derivatives, (In the formula, R ₁ and R _{2 each} independently represent a lower (C ₁ -C ₂ ) alkyl group, an amino group, a lower alkylamino group, a di-lower alkylamino group or a cyano group). 2. The anthracene derivative according to claim 1, which is 9,10-bis (p-diethylaminophenylethynyl) anthracene. 3. The anthracene derivative according to claim 1, which is 9,10-bis (p-methylphenylethynyl) anthracene. 4. The anthracene derivative according to claim 1, which is 9,10-bis (p-cyanophenylethynyl) anthracene.