USE OF PENTA-SUBSTITUTED TETRAHYDROPYRIMIDINES IN PREPARATION OF THERMO-SENSITIVE FLUORESCENT MATERIALS

Abstract

The present invention provides use of penta-substituted tetrahydropyrimidines in preparation of thermo-sensitive fluorescent materials. Said penta-substituted tetrahydropyrimidine compounds have linear temperature dependence of red-edge excitation wavelength (LTDREEW). When different excitation wavelengths are chosen, such compounds present fluorescence color and/or fluorescence intensity on-off switching in different temperature ranges. Also their fluorescence intensity ratios or fluorescence intensities exhibit good linear relation or power function relation to temperature, which can be used as the thermo-sensitive fluorescent materials with high sensitivity and wide temperature range (0-450 K).

Claims

1. Use of penta-substituted tetrahydropyrimidines in preparation of a thermo-sensitive fluorescent material, said penta-substituted tetrahydropyrimidines have structures shown as formula (I): ##STR00014## wherein: R.sup.1 is selected from a group consisting of C.sub.1-8 linear or branched alkyls and substituted C.sub.1-8 alkyls; R.sup.2 and R.sup.4 are independently selected from a group consisting of C.sub.1-8 linear or branched alkyls, substituted C.sub.1-8 alkyls, C.sub.5-8 cycloalkyls, substituted C.sub.5-8 cycloalkyls, C.sub.5-6 aryls, substituted C.sub.5-6 aryls, C.sub.9-18 fused polycyclic aryls, substituted C.sub.9-18 fused polycyclic aryls, C.sub.5-6 heterocyclyls, substituted C.sub.5-6 heterocyclyls, C.sub.5-6 aromatic heterocyclyls and substituted C.sub.5-6 aromatic heterocyclyls; R.sup.3 is selected from a group of C.sub.5-6 aryls, substituted C.sub.5-6 aryls, C.sub.9-18 fused polycyclic aryls, substituted C.sub.9-18 fused polycyclic aryls, C.sub.5-6 aromatic heterocyclyls and substituted C.sub.5-6 aromatic heterocyclyls.

2. The use of claim 1, wherein the use of said penta-substituted tetrahydropyrimidine is in preparation of chemical and/or biological temperature fluorescent sensors or probes.

3. The use of claim 1, wherein R.sup.1 is C.sub.1-2 alkyls.

4. The use of claim 1, wherein R.sup.2 is selected from a group consisting of C.sub.1-5 linear or branched alkyls, substituted C.sub.1-5 alkyls, C.sub.5-8 cycloalkyls, C.sub.5-6 aryls and substituted C.sub.5-6 aryls.

5. The use of claim 1, wherein R.sup.3 is C.sub.5-6 aryls or substituted C.sub.5-6 aryls.

6. The use of claim 1, wherein R.sup.4 is selected from a group consisting of C.sub.1-5 linear or branched alkyls, substituted C.sub.1-5 alkyls, C.sub.5-8 cycloalkyls, C.sub.5-6 aryls and substituted C.sub.5-6 aryls.

7. The use of claim 1, wherein substituents are selected from a group consisting of halogens, C.sub.1-2 perhalogenated alkyls, C.sub.1-4 halogenated alkyls, hydroxyl, C.sub.1-6 linear or branched alkoxys, nitryl, cyano, amino, C.sub.1-6 monoalkyl aminos, C.sub.1-6 dialkyl aminos, C.sub.5-8 monocycloalkyl aminos, C.sub.5-6 monoheterocycloalkyl aminos, C.sub.5-6 monoaryl aminos, C.sub.1-6 alkyl acylaminos, C.sub.5-6 aryl acylaminos, amino carbonyls, C.sub.1-6 monoalkyl amino carbonyls, C.sub.1-6 dialkyl amino carbonyls, C.sub.1-6 alkyl acyls, C.sub.5-8 aryl acyls, amino sulfones, C.sub.1-6 monoalkyl amino sulfones, C.sub.1-6 dialkyl amino sulfones, C.sub.5-8 arylamino sulfones, C.sub.1-6 alkyl sulfonyl aminos, carboxyl, C.sub.1-6 monoalkyl sulfones, linear or branched alkyls, C.sub.5-8 cycloalkyls, substituted C.sub.5-8 cycloalkyls, C.sub.2-4 alkenyls, C.sub.2-4 alkynyls, aryl C.sub.1-3 alkyls, C.sub.5-6 aryls, substituted C.sub.5-6 aryls, C.sub.9-18 fused polycyclic aryls, C.sub.5-6 heterocyclyls, C.sub.5-6 aromatic heterocyclyls and C.sub.9-18 fused polycyclic aromatic heterocyclyls.

8. The use of claim 1, wherein, R.sup.1 is methyl or ethyl; R.sup.2 is selected from a group consisting of phenyl, methyl phenyl, chlorphenyl, bromophenyl, and trifluoromethyl phenyl, R.sup.3 is selected from a group consisting of phenyl, bromophenyl, phenyl substituted by methoxy hydroxyl, bromophenyl, trifluoromethyl phenyl, naphthyl, and thienyl; R.sup.4 is selected from a group consisting of phenyl, methyl phenyl, chlorphenyl, bromophenyl, and trifluoromethyl phenyl.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0028] FIG. 1 shows an example of prior macromolecule organic compound 1 with thermo-sensitive fluorescent material. a) Excitation spectrum and emission spectrum of compound 1 along with temperature variation. b) Relation graph of fluorescence intensity of compound 1 at the emission spectrum peak value (564 nm) to temperature;

[0029] FIG. 2 shows the molecular structure of reported small organic molecule compound 2 with thermo-sensitive fluorescent material and an example of linear relation graph of its emission wavelength in a polar solution to temperature;

[0030] FIG. 3 shows the molecular structures of reported small organic molecule compounds 3 and 4 with thermo-sensitive fluorescent material and an example of graph of solid fluorescence intensity or emission wavelength thereof reversibly varying with the temperature variation;

[0031] FIG. 4 shows the molecular structure of said penta-substituted tetrahydropyrimidine THP-1 according to the present invention and the photograph of its polymorph crystal THP-1g with green emitting (emission wavelength is 496 nm);

[0032] FIG. 5 shows, in 77-300K detective range, linear temperature dependence of red-edge excitation wavelength (LTDREEW) property of THP-1g, as well as property that fluorescence intensity thereof may presents on-off mutation in different temperature ranges when excited in different wavelengths and exhibits linear relation to temperature; a) excitation spectrum varying with temperature (emission wavelength is 496 nm, and dotted line basically coincident with line with symbols is excitation spectrum detected in circulate temperature); b) linear relation graph of red-edge excitation wavelength to temperature (straight line with black square symbols), linear relation graph of fluorescence intensity at 496 nm in 90-210K range, which is excited at 420 nm, to temperature (straight line with circle symbols), and linear relation graph of fluorescence intensity at 496 nm in 180-300K range, which is excited at 438 nm, to temperature (straight line with pentagram symbols); c) excited at 420 nm, emission spectrum in 77-300K range; and d) excited at 438 nm, emission spectrum in 150-300K range;

[0033] FIG. 6 shows temperature variation in different ranges precisely detected using the property that fluorescence intensity of THP-1g may presents sensitive on-off mutation in different temperature ranges when excited at different wavelengths. Wherein a) and b) respectively show when THP-1g was excited at 420 nm, emission spectrum in 80-120K range and the power function linear relation graph of emission peak fluorescence intensity to temperature; c) and d) respectively show when THP-1g was excited at 445 nm, emission spectrum in 210-300K range and the power function linear relation graph of emission peak fluorescence intensity to temperature;

[0034] FIG. 7 shows the molecular structure of said penta-substituted tetrahydropyrimidine THP-1 according to the present invention and the photograph of its polymorph crystal THP-1b with blue emitting (emission wavelength is 433 nm);

[0035] FIG. 8 shows, in 90-300K detective range, linear temperature dependence of red-edge excitation wavelength (LTDREEW) property of THP-1b, as well as property that fluorescence color and intensity thereof present mutation in different temperature range when excited in different wavelength and that fluorescence intensity exhibits linear relation to temperature. a) Excitation spectrums varying with temperature (lines with symbols are excitation spectrums where emission wavelength is 434 nm, while solid lines without symbols are excitation spectrums where emission wavelength is 510 nm, and the dotted lines basically coincident with the lines with symbols are excitation spectrums detected in circulate temperature); b) linear relation graph of red-edge excitation wavelengths at three different luminous intensity in FIG. 8a (three parallel lines in FIG. 8a) to temperature; c) excited at 365 nm, emission spectrum in 90-210K range; d) excited at 380 nm, emission spectrum in 90-300K range; and e) linear relation graph of fluorescence intensity at 433 nm in 90-210K range, which is excited at 365 nm, to temperature (straight line with square symbols), also linear relation graph of fluorescence intensity at 433 nm in 180-300K range, which is excited at 380 nm, to temperature (straight line with circle symbols);

[0036] FIG. 9 shows temperature variation in different ranges precisely detected using the property that its fluorescence color and intensity of THP-1b may present mutation in different temperature ranges when excited at different wavelengths. a) Emission spectrum in 80-120K range when THI-1b was excited at 365 nm; b) power function relation graph of ratio between fluorescence intensity at 433 nm and fluorescence intensity at 535 nm, to temperature;

[0037] FIG. 10 shows the emission spectrum of THP-1b in 4-298K range, which was excited at 360 nm excitation wavelength;

[0038] FIG. 11 shows, at 293K and 353K, the emission spectrums of THP-1˜12 which was emitted at maximum emission wavelength of each (with reference to Table 1) (THP-4b and THP-4g are polymorphs);

[0039] FIG. 12 shows, at 298K and 410K, the emission spectrum of THP-4p (polymorph of THP-4b and THP-4g) which was emitted at its maximum emission wavelength (425 nm);

[0040] FIG. 13 shows, at 293K and 353K, the emission spectrum of pyrene which was emitted at its maximum emission wavelength (496 nm).

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

[0041] The present invention is further described below in combination with specific embodiments which are not intended to limit the present invention in any manner. Unless otherwise specified, reagents and methods used in the embodiments are routinely used in this field of art.

[0042] Table 1 shows the molecular structures of compounds, maximum emission wavelength (λ.sub.em), ratio between fluorescence intensity at maximum emission wavelength at 80° C. and fluorescence intensity at maximum emission wavelength at 20° C. (I.sub.80/I.sub.20), and melting points of the compounds in embodiments. Some of the compounds in the embodiments have been already disclosed in CN201110129857.X, and those compounds which have not been disclosed in CN201110129857.X specifically will be provided with relevant structural characteristic data herein.

[0043] Table 1 the molecular structures of compounds, maximum emission wavelength (λ.sub.em), ratio between fluorescence intensity at maximum emission wavelength at 80° C. and fluorescence intensity at maximum emission wavelength at 20° C. (I.sub.80/I.sub.20), and melting points of compounds in embodiments

TABLE-US-00001 Compound Melting point/ number λ.sub.em.sup.a/nm I.sub.80/I.sub.20.sup.b ° C. Molecular structure THP-1b THP-1g 434 484   0.85 130.0-130.5 119.5-120.0 [00002] THP-2b 469 0.57 149.0-149.5 [00003] THP-3 448 0.52 121.4-121.6 [00004] THP-4b THP-4g THP-4p 445 468 425 0.43 0.60 136.5-137.0 144.5-145.0 153.0-153.5 [00005] THP-5 451 0.93 152.3-153.0 [00006] THP-6 473 0.48 158.8-159.1 [00007] THP-7 477 0.80 145.3-146.2 [00008] THP-8 480 0.58 153.1-153.9 [00009] THP-9 458 0.80 196.2-196.4 [00010] THP-10 479 0.44 164.1-164.6 [00011] THP-11 490 0.76 164.1-164.6 [00012] THP-12 480 0.57 112.9-113.9 [00013] .sup.aMaximum emission wavelength; .sup.bratio between fluorescence intensity at maximum emission wavelength at 80° C. and fluorescence intensity at maximum emission wavelength at 20° C.

[0044] Wherein, compounds THP-1, THP-2, THP-5˜8 and THP-10˜12 were disclosed in the above-mentioned patent; compounds THP-4g, THP-4b and THP-4p were polymorphs separated from the known compounds, they having same molecular structure and same structural characteristic parameters, but the melting points and optical properties being different (the melting point and maximum emission wavelength of each are shown in Table 1, excitation spectrums are shown in FIG. 11 and FIG. 12); and compounds THP-3 and THP-9 are new compounds of which synthetic methods may refer to the prior art with choosing relevant raw material, with properties as well as structural characteristic data thereof being as follows:

[0045] THP-3 Dimethyl 1,2,3,6-tetrahydro-1,3-diphenyl-2-(thiophen-2-yl)pyrimidine-4,5-dicarboxylate 35% yield, yellow solid, mp=121.4-121.6° C.; IR (KBr): v.sub.max=2949, 1742, 1702, 1593, 1495, 1241, 1110, 1064, 976, 843, 752, 696 cm.sup.−1; .sup.1H NMR (400 MHz, CDCl.sub.3) δ=7.47-7.02 (m, 13H), 6.30 (s, 1H), 4.33 (d, J=17.6 Hz, 1H), 3.88 (d, J=17.6 Hz, 1H), 3.72 (s, 3H), 3.66 (s, 3H) ppm; .sup.13C NMR (101 MHz, CDCl.sub.3) δ=165.71, 164.69, 148.49, 144.23, 143.91, 142.15, 129.32, 129.21, 127.08, 126.60, 126.46, 126.28, 124.18, 121.87, 119.06, 102.03, 52.52, 51.49, 42.65 ppm; MS (ESI): m/z 435 (M+H.sup.+, 27), 248 (100); Anal. Calcd for C.sub.24H.sub.22N.sub.2O.sub.4S: C, 66.34; H, 5.10; N, 6.45; Found: C, 66.53; H, 5.10; N, 6.61

[0046] THP-9 Dimethyl 1,3-bis(4-bromophenyl)-2-(4-(trifluoromethyl)phenyl)-1,2,3,6-tetrahydropyrimidine-4,5-dicarboxylate 24% yield, white solid, mp=196.2-196.4° C.; IR (KBr): vmax=2951, 2303, 1740, 1704, 1606, 1489, 1325, 1241, 1114, 893, 748 cm-1; 1H NMR (400 MHz, CDCl3) δ=7.76-6.73 (m, 12H), 6.04 (s, 1H), 4.24 (d, J=18.4 Hz, 1H), 3.72 (s, 3H), 3.69 (s, 3H), 3.53 (d, J=18.4 Hz, 1H) ppm; 13C NMR (101 MHz, CDCl3) δ=165.21, 164.33, 148.06, 143.06, 141.45, 132.55, 132.37, 127.28, 126.30, 125.05, 120.69, 119.75, 114.53, 103.19, 79.53, 52.83, 51.68, 42.66 ppm; MS (ESI): m/z 653 (M+H+, 27), 655 (M+H+, 53), 326 (100); Anal. Calcd for C27H21Br2F3N2O4: C, 49.57; H, 3.24; N, 4.28; Found: C, 49.58; H, 3.29; N, 4.17

Embodiment 1

[0047] (1) From 300 to 77K, excitation spectrum of penta-substituted tetrahydropyrimidine THP-1 green emitting polymorph (THP-1g, structure and crystal graph are shown in FIG. 4) was detected at maximum emission wavelength by a low-temperature luminoscope (seeing FIG. 5a), with two different red-edge excitation wavelengths being as emission spectrums (FIG. 5c and FIG. 5d). From FIG. 5a and FIG. 5b, it can be seen that red-edge excitation wavelength/fluorescence intensity exhibits good linear relation to temperature, i.e. with linear temperature dependence of red-edge excitation wavelength (LTDREEW) property. From FIGS. 5c, 5d and 5b, it can be seen that fluorescence intensity exhibits good linear relation to temperature in detective temperature range if suitable excitation wavelength is chosen.

[0048] (2) Temperature from 300 to 90K may be detected precisely by sensitive on-off fluorescence change of THP-1g by choosing suitable excitation wavelength using LTDREEW property.

[0049] Example 1, temperature from 80 to 120K was detected precisely at 420 nm excitation wavelength by the low-temperature luminoscope. As shown in FIG. 6a, when temperature varied 35K, fluorescence intensity of THP-1g varied as 10 times. At the same time, it can be seen from FIG. 6b that, fluorescence intensity exhibited good power function relation to temperature, and temperature from 80 to 120K can be detected precisely and sensitively.

[0050] Example 2, temperature from 300 to 210K was detected precisely at 445 nm excitation wavelength by the low-temperature luminoscope. As shown in FIG. 6c, when temperature varied 90K, fluorescence intensity of THP-1g varied as 14 times. At the same time, it can be seen from FIG. 6d that, fluorescence intensity exhibited good power function relation to temperature, and temperature from 300 to 210K can be detected precisely and sensitively.

Embodiment 2

[0051] (1) Every 30K from 300 to 90K, excitation spectrum of penta-substituted tetrahydropyrimidine THP-1 blue emitting polymorph (THP-1b) (crystal graph is shown in FIG. 7) was detected respectively at short wavelength and long wavelength for fluorescence component as maximum emission wavelength by a low-temperature luminoscope (seeing FIG. 8a), with two different red-edge excitation wavelengths being as emission spectrums (FIG. 8c and FIG. 8d). From FIG. 8a and FIG. 8b, it can be seen that red-edge excitation wavelength exhibits good linear relation to temperature, i.e. with linear temperature dependence of red-edge excitation wavelength (LTDREEW) property. From FIGS. 8c, 8d and 8e, it can be seen that good linear relation can be obtained in detective temperature range if suitable excitation wavelength was chosen.

[0052] (2) Temperature from 0K to melting point of THP-1b can be detected precisely by choosing suitable excitation wavelength using LTDREEW property and two-color fluorescence property of THP-1b.

[0053] Example 1, temperature from 120 to 80K can be detected precisely by the low-temperature luminoscope choosing 365 nm excitation wavelength. From FIG. 9a, it can be seen that when temperature varied 30K (from 110 to 80K), maximum emission wavelength varied 59 nm (from 433 to 492 nm). That is, fluorescence component transformed from basically short wavelength fluorescence component to basically long wavelength fluorescence component, and such fluorescence component transformation, i.e. fluorescence color change, can be observed directly by naked eyes. Meanwhile, as shown in. FIG. 9b, ratio of two fluorescent intensities of THP-1b exhibits great power function relation to temperature.

[0054] Example 2, temperature from 4 to 80K can be detected precisely by low-temperature luminoscope choosing 360 nm excitation wavelength. From FIG. 10, it can be seen that when temperature varied 56K (from 60 to 4K), maximum emission wavelength varied 66 nm (from 434 to 500 nm). That is, fluorescence component transformed from basically short wavelength fluorescence component to basically long wavelength fluorescence component, and such fluorescence component transformation, i.e. fluorescence color change, can be observed directly by naked eyes.

Embodiment 3

[0055] Excitation spectrums of twelve penta-substituted tetrahydropyrimidines THP-1˜12 and excitation spectrum of a general fluorescent probe pyrene for detecting critical micelle concentration of surface active agent were detected at 20° C. and 80° C. by a temperature regulating device using a general luminoscope (the molecular structures of compounds, maximum emission wavelength (λ.sub.em), ratio between fluorescence intensity at maximum emission wavelength at 80° C. and fluorescence intensity at maximum emission wavelength at 20° C. (I.sub.80/I.sub.20), and melting points of compounds are shown in Table 1), in order to determine whether the compound has LTDREEW property or not and to determine the sensitive level that the red-edge excitation wavelength shows to temperature. That is, based on the fact that red-edge excitation wavelength is influenced by temperature or not and the level of influence by temperature, it can determine whether the compound has LTDREEW property or not and to determine the sensitive level that the red-edge excitation wavelength shows to temperature. As shown in FIG. 11, red-edge excitation wavelengths of twelve penta-substituted tetrahydropyrimidines (THP-1˜12, wherein THP-4g and THP-4b are polymorphs) are all influenced by temperature, i.e. they all have LTDREEW property, but the red-edge excitation wavelengths were influenced by temperature on different levels. Some red-edge excitation wavelength difference value (Δλ) is 9 nm, while some red-edge excitation wavelength difference value (Δλ) is only 4 nm. Thus, all detective penta-substituted tetrahydropyrimidines can be used for fluorescent thermal detection or fluorescent thermal imaging analysis like THP-1.

Embodiment 4

[0056] Excitation spectrums of THP-4p (polymorph of THP-4g and THP-4g) (molecular structure of compound, maximum emission wavelength (λ.sub.em) and melting point of compound are shown in Table 1) were detected at 298K and 410 k by a low-temperature luminoscope. As shown in FIG. 12, when THP-4p is close to its melting point (153° C., i.e. 426K), the red-edge excitation wavelength of THP-4p still varied with temperature, i.e. it still had LTDREEW property, wherein the ratio between fluorescence intensity at maximum emission wavelength at 410K and fluorescence intensity at maximum emission wavelength at 298K was 0.68. This embodiment indicates that red-edge excitation wavelength of THPs from 0K to melting point thereof all have sensitive response to temperature, and they have relatively strong fluorescence intensity when close to the melting point.

Embodiment 5

[0057] Excitation spectrum of general fluorescent compound pyrene was detected at 20° C. and 80° C. by a temperature regulating device using a general luminoscope. As shown in FIG. 13, it can be seen that red-edge excitation wavelength of pyrene are not influenced by temperature, i.e. pyrene does not have LTDREEW property, and it indicates that not all fluorescent compounds have LTDREEW property.