Process and Apparatus for Locally Polymerizing a Starting Material by Dual Color Photopolymerization and Method for Volumetric Printing of a Shaped Body

Abstract

The present invention relates to a process, an apparatus and photoswitchable photoinitiators for locally polymerizing a starting material by dual color photopolymerization and a method for volumetric printing of a shaped body (xolography). In particular, photoinitiators are provided, which cause raring of photopolymerizable formulations upon irradiation with two different wavelengths and which maybe used for volumetric printing (xolocure initiators).

Claims

1. A process for locally polymerizing a starting material by dual color photopolymerization, comprising: providing a polymerizable starting material containing photoinitiator molecules which can be converted by sequential optical excitation into a reactive state in which the photoinitiator molecules locally trigger polymerization of the starting material; and photopolymerizing the starting material in a local volume by irradiating light of a first wavelength and light of a second wavelength, different from the first wavelength, into the local volume, whereby in the local volume the photoinitiator molecules are converted, due to the absorption of the light of the first wavelength, from an initial state in which the photoinitiator molecules substantially do not absorb the light of the second wavelength, into an intermediate state with changed optical properties compared to the initial state, such that the photoinitiator molecules in the intermediate state absorb the light of the second wavelength; and the photoinitiator molecules are transferred from the intermediate state to the reactive state due to the absorption of the light of the second wavelength, which triggers the polymerization locally.

2. A process according to claim 1, characterized in that the light of the first wavelength and the light of the second wavelength are simultaneously irradiated into the local volume.

3. A process according to claim 1, characterized in that the light of the second wavelength is irradiated into the local volume after the irradiation of the light of the first wavelength in the local volume has ended, the light of the second wavelength being irradiated before the end of a decay time of the intermediate state of the photoinitiator molecules.

4. A process according to claim 1, characterized in that the photoinitiator molecules in the intermediate state substantially do not absorb the light of the first wavelength.

5. A process according to claim 1, characterized in that the photoinitiator molecules are converted from the intermediate state to the initial state due to the absorption of light of a third wavelength in volumes where no polymerization is desired.

6. A process according to claim 1, characterized in that the photoinitiator molecules are converted into a reactive state due to the sequential absorption of light of the second wavelength which triggers a polymerization in the local volume.

7. A process according to claim 1, characterized in that the photoinitiator molecules are converted into a reactive state due to the absorption of the light of the second wavelength, which triggers a radical polymerization in the local volume.

8. A process according to claim 1, characterized in that the photoinitiator molecule is represented by the following formula (I) ##STR00128## wherein R.sup.a and R.sup.b are selected independently from unsubstituted or substituted aryl, unsubstituted or substituted alkyne or a linked to each other to form a unsubstituted or substituted ring structure, Y is selected from O, S, or N; where Y is N, the substituent contains the atoms necessary to complete a cyclic structure with R.sup.8 selected from the group consisting of benzimidazole, indoline, indole, dihydroquinoline, and tetrahydroquinoline; wherein Z is selected from N or CR.sup.4; wherein R.sup.3 to R.sup.8 are independently selected from the group consisting of H; D; halogen; NO.sub.2; CN; OH; SH; substituted or unsubstituted C.sub.1-C.sub.20-alkyl; substituted or unsubstituted C.sub.3-C.sub.20-cycloalkyl; substituted or unsubstituted C.sub.6-C.sub.48-aryl; substituted or unsubstituted C.sub.2-C.sub.42-heteroaryl; substituted or unsubstituted C.sub.2-C.sub.49-alkyl acyl; substituted or unsubstituted C.sub.2-C.sub.49-aryl acyl; substituted or unsubstituted C.sub.1-C.sub.20-alkoxy; substituted or unsubstituted C.sub.6-C.sub.48-aryloxy, and NH.sub.2; substituted or unsubstituted C.sub.1-C.sub.20-alkyl ester; substituted or unsubstituted C.sub.6-C.sub.48-aryl ester; substituted or unsubstituted C.sub.1-C.sub.20 alkyl amide; substituted or unsubstituted C.sub.6-C.sub.48-aryl amide; NR′.sub.2, SiR′.sub.3, —O—SiR′.sub.3 wherein R′ is independently selected from the group consisting of substituted or unsubstituted C.sub.1-C.sub.20-alkyl and substituted or unsubstituted C.sub.6-C.sub.48-aryl, two R′ may form a ring structure; substituted or unsubstituted carboxylic acids and salts thereof; substituted or unsubstituted sulfonic acids and salts thereof; substituted or unsubstituted sulfonic esters; substituted or unsubstituted sulfonic amides; formyl; ether, thioether; carbonate; carbonate ester; sulfates; boronic acids; boronic esters; phosphonic acids; phosphonic esters; phosphines; phosphates; peroxycarbonic acids; thiocarbonic acids; sulfinic acids; sulfinic esters; sulfonates; thiolesters, sulfoxides; sulfones; hydrazides; thio aldehydes; ketones; thioketones; oximes; hydrazines; nitroso; azo; diazo; diazonium; isocyanides; cyanate; isocyanate; thiocyanate; isothiocyanate; hydroperoxide; peroxide; acetals; ketal; orthoester; orthocarbonate esters; ammonium; imines; imides; azide; nitrate; isonitrile; nitrosoxy; substituted or unsubstituted carbamates; substituted or unsubstituted ethers; substituted or unsubstituted polyether carbamates; substituted or unsubstituted arylazo; substituted or unsubstituted C.sub.2-C.sub.20-alkynyl and substituted or unsubstituted C.sub.2-C.sub.20-alkenyl; wherein the one or more substituents, if present in one or more of R.sup.3-R.sup.8, are independently selected from the group consisting of D; halogen; NO.sub.2; CN, C.sub.2-C.sub.49-alkyl acyl; substituted or unsubstituted C.sub.1-C.sub.20-alkoxy; substituted or unsubstituted C.sub.6-C.sub.48-aryloxy; substituted or unsubstituted C.sub.2-C.sub.49-aryl acyl; (meth)acrylate; tosyl; NH.sub.2; and OH; and/or wherein two adjacent groups of R.sup.5-R.sup.8 may be linked to each other to form a fused ring structure; and wherein at least one of R.sup.3-R.sup.8, is selected from one of the following structures: ##STR00129## wherein R.sup.14 to R.sup.25 are independently selected from the group consisting of H; D; halogen; NO.sub.2; CN; OH; SH; substituted or unsubstituted C.sub.1-C.sub.20-alkyl; substituted or unsubstituted C.sub.3-C.sub.20-cycloalkyl; substituted or unsubstituted C.sub.6-C.sub.48-aryl; substituted or unsubstituted C.sub.2-C.sub.42-heteroaryl; substituted or unsubstituted C.sub.2-C.sub.49-alkyl acyl; substituted or unsubstituted C.sub.2-C.sub.49-aryl acyl; substituted or unsubstituted C.sub.1-C.sub.20-alkoxy; substituted or unsubstituted C.sub.6-C.sub.48-aryloxy, and NH.sub.2; substituted or unsubstituted C.sub.1-C.sub.20-alkyl ester; substituted or unsubstituted C.sub.6-C.sub.48-aryl ester; substituted or unsubstituted C.sub.1-C.sub.20 alkyl amide; substituted or unsubstituted C.sub.6-C.sub.48-aryl amide; NR′.sub.2, SiR′.sub.3, —O—SiR′.sub.3 wherein R′ is independently selected from the group consisting of substituted or unsubstituted C.sub.1-C.sub.20-alkyl and substituted or unsubstituted C.sub.6-C.sub.48-aryl, two R′ may form a ring structure; substituted or unsubstituted carboxylic acids and salts thereof; substituted or unsubstituted sulfonic acids and salts thereof; substituted or unsubstituted sulfonic esters; substituted or unsubstituted sulfonic amides; formyl; ether, thioether; carbonate; carbonate ester; sulfates; boronic acids; boronic esters; phosphonic acids; phosphonic esters; phosphines; phosphates; peroxycarbonic acids; thiocarbonic acids; sulfinic acids; sulfinic esters; sulfonates; thiolesters, sulfoxides; sulfones; hydrazides; thio aldehydes; ketones; thioketones; oximes; hydrazines; nitroso; azo; diazo; diazonium; isocyanides; cyanate; isocyanate; thiocyanate; isothiocyanate; hydroperoxide; peroxide; acetals; ketal; orthoester; orthocarbonate esters; ammonium; imines; imides; azide; nitrate; isonitrile; nitrosoxy; substituted or unsubstituted carbamates; substituted or unsubstituted ethers; substituted or unsubstituted polyether carbamates; substituted or unsubstituted arylazo; substituted or unsubstituted C.sub.2-C.sub.20-alkynyl and substituted or unsubstituted C.sub.2-C.sub.20-alkenyl; wherein the one or more substituents, if present in one or more of R.sup.14-R.sup.25, are independently selected from the group consisting of D; halogen; NO.sub.2; CN, C.sub.2-C.sub.49-alkyl acyl; substituted or unsubstituted C.sub.1-C.sub.20-alkoxy; substituted or unsubstituted C.sub.6-C.sub.48-aryloxy; substituted or unsubstituted C.sub.2-C.sub.49-aryl acyl; (meth)acrylate; tosyl; NH.sub.2; and OH; and R.sup.15 and R.sup.16 may be linked to each other to form a unsubstituted or substituted ring structure.

9. A process according to claim 1, characterized in that the photoinitiator molecule is represented by the following formula (II) ##STR00130## wherein X is selected from S, CR.sup.1R.sup.2, or NR.sup.1; Y is selected from O, S, or NW; when Y is N, the substituent W contains the atoms necessary to complete a cyclic structure with R.sup.8 selected from the group consisting of benzimidazole, indoline, indole, dihydroquinoline, and tetrahydroquinoline; Z is selected from N or CR.sup.4; and R.sup.1 to R.sup.13 are independently selected as defined in R.sup.3 to R.sup.8 regarding formula (I) above.

10. A process according to claim 8, characterized in that R.sup.14, R.sup.15, and R.sup.16 are independently selected from H, D, CN, halogen, substituted or unsubstituted C.sub.1-C.sub.10-alkyl; substituted or unsubstituted C.sub.3-C.sub.10-cycloalkyl; substituted or unsubstituted C.sub.6-C.sub.32-aryl; or substituted or unsubstituted C.sub.2-C.sub.28-heteroaryl.

11. A process according to claim 8, characterized in that R.sup.19 is selected from substituted or unsubstituted C.sub.1-C.sub.10-alkyl; substituted or unsubstituted C.sub.3-C.sub.10-cycloalkyl; substituted or unsubstituted C.sub.6-C.sub.32-aryl; substituted or unsubstituted C.sub.2-C.sub.28-heteroaryl, substituted or unsubstituted C.sub.2-C.sub.20-alkynyl and substituted or unsubstituted C.sub.2-C.sub.20-alkenyl, the substituent may contain the atoms necessary to complete a cyclic structure with one of R.sup.5-R.sup.8 or R.sup.10-R.sup.13 forming an anthracene, thioxanthone or fluorenone.

12. A process according to claim 8, characterized in that R.sup.14 is NR′.sub.2, wherein R′ is independently selected from the group consisting of H, D, substituted or unsubstituted C.sub.1-C.sub.10-alkyl and substituted or unsubstituted C.sub.6-C.sub.32-aryl, and two R′ may form a ring structure; or OR′, wherein R′ is selected from the group consisting of H, D, substituted or unsubstituted C.sub.1-C.sub.10-alkyl; substituted or unsubstituted C.sub.3-C.sub.10-cycloalkyl; substituted or unsubstituted C.sub.6-C.sub.32-aryl; substituted or unsubstituted C.sub.2-C.sub.28-heteroaryl, SiR″.sub.3, wherein R″ is independently selected from the group consisting of substituted or unsubstituted C.sub.1-C.sub.10-alkyl and substituted or unsubstituted C.sub.6-C.sub.32-aryl; and R.sup.15 and R.sup.16 are independently selected from H, D, CN, substituted or unsubstituted C.sub.1-C.sub.10-alkyl; substituted or unsubstituted C.sub.3-C.sub.10-cycloalkyl; substituted or unsubstituted C.sub.6-C.sub.32-aryl; substituted or unsubstituted C.sub.2-C.sub.28-heteroaryl.

13. A process according to claim 8, characterized in that R.sup.14 and R.sup.15 are OR′, wherein R′ is independently selected from the group consisting of H, D, substituted or unsubstituted C.sub.1-C.sub.10-alkyl; substituted or unsubstituted C.sub.3-C.sub.10-cycloalkyl; substituted or unsubstituted C.sub.6-C.sub.32-aryl; substituted or unsubstituted C.sub.2-C.sub.28-heteroaryl; and R.sup.16 is selected from H, D, CN, substituted or unsubstituted C.sub.1-C.sub.10-alkyl; substituted or unsubstituted C.sub.3-C.sub.10-cycloalkyl; substituted or unsubstituted C.sub.6-C.sub.32-aryl; substituted or unsubstituted C.sub.2-C.sub.28-heteroaryl.

14. A process according to claim 8, characterized in that R.sup.10-R.sup.13 are independently selected from the group consisting of H and electron withdrawing groups (EWG), and one of R.sup.5-R.sup.8 is selected from unsubstituted or substituted arylacyl; or unsubstituted or substituted alkylacyl; and/or at least one of R.sup.5-R.sup.8 is independently selected from the group consisting of electron donating groups (EDG), more preferably R.sup.8 is OH or methoxy and at least one of R.sup.5-R.sup.8, R.sup.10-R.sup.13 is selected from unsubstituted or substituted arylacyl; or unsubstituted or substituted alkylacyl; or at least one of R.sup.6, R.sup.7 and R.sup.12 is selected from the group consisting of CF.sub.3, SO.sub.2Me, SO.sub.2NH.sub.2, CN, F, NO.sub.2, C.sub.6-aryl, unsubstituted C.sub.6-arylacyl of the following formula ##STR00131## dimethoxy-substituted arylacyl of the formula ##STR00132## methoxy-substituted arylacyl of the formula ##STR00133## fluorine-substituted arylacyl of the following formula ##STR00134## alternatively of the formula ##STR00135## and C.sub.6-aryl.

15. A process according to claim 1, characterized in that the photoinitiator molecule used in the process according to the invention comprises one or more of the following compounds: ##STR00136## ##STR00137## ##STR00138## ##STR00139## ##STR00140## ##STR00141## ##STR00142## ##STR00143##

16. A process according to claim 1, characterized in that the polymerizable starting material further contains a co-initiator and/or a sensitizer.

17. A process according to claim 1, characterized in that the polymerizable starting material further contains an additive, an acid and/or a base.

18. A process according to claim 1, characterized in that a light beam of light of the first wavelength and a light beam of light of the second wavelength are irradiated at least partially overlapping in the local volume.

19. A process according to claim 1, characterized in that the starting material is polymerized in several local volumes by means of photopolymerization and thus a three-dimensional shaped body is produced in the starting material.

20. A process for 3D-printing a shaped body, wherein the shaped body is produced by means of a process according to claim 1.

21. Apparatus for locally polymerizing a starting material by dual color photopolymerization, comprising: an intake for a polymerizable starting material; light generating means arranged to generate light of a first wavelength and light of a second wavelength, the second wavelength being different from the first wavelength; and a light guide device arranged to irradiate the light of the first wavelength and the light of the second wavelength into a local volume; said device being adapted to perform the following procedure: taking up the polymerizable starting material by said intake, said starting material containing photoinitiator molecules which can be excited by sequential optical excitation into a reactive state in which the photoinitiator molecules locally initiate polymerization of the starting material; and photopolymerizing the starting material in a local volume by irradiating the light of the first wavelength and the light of the second wavelength into the local volume, whereby in the local volume the photoinitiator molecules, due to the absorption of the light of the first wavelength, are converted from an initial state in which the photoinitiator molecules substantially do not absorb the light of the second wavelength into an intermediate state with changed optical properties compared to the initial state, such that the photoinitiator molecules in the intermediate state absorb the light of the second wavelength; and the photoinitiator molecules are transferred from the intermediate state to the reactive state due to the absorption of the light of the second wavelength, which triggers the polymerization locally.

Description

BRIEF DESCRIPTION OF DRAWINGS

[0131] In the following, further design examples are explained with reference to figures in a drawing, wherein

[0132] FIG. 1 shows a schematic representation of an embodiment of the process according to the invention;

[0133] FIG. 2 shows a schematic representation of the process according to the invention; and

[0134] FIG. 3 shows a perspective view of the embodiment of the inventive step shown in FIG. 2.

[0135] FIG. 1 schematically shows an embodiment of the invention. By means of a first light source 10 a light with a first wavelength is generated and irradiated onto a structure comprising a curable composition 14. The assembly is a layered assembly comprising a light-blocking layer 11 and two transparent layers 12. The assembly further comprises a spacer 13. In the space formed by the two transparent layers 12 and the spacer 13, the curable composition 14 corresponding to the polymerizable starting material and containing one or more photoinitiator molecules according to the invention is introduced. The layered structure further comprises two light-blocking layers 11 arranged so that at least a portion of the curable composition 14 can be irradiated by both the light of the first wavelength generated by the first light source 10 and a light of a second wavelength generated by the second light source 15. The region of the curable composition 14 which can be irradiated both by light from the first light source 10 and by light from the second light source 15 is cured according to the mechanism described herein.

[0136] FIGS. 2 and 3 show a further embodiment of the invention in which a part of a curable composition 24, 34, is cured, which is simultaneously irradiated both by light from a first light source 20, 30 and light from a second light source 25, 35 through holes 23, 33 in light-blocking layers 21, 31 which partially shield the curable composition 24, 34 from the respective light sources 20, 30 and 25, 35, respectively. The curable composition 24, 34 is here arranged in a transparent container 22, 32. In this version it is provided that the light source 20, 30 is arranged orthogonally with respect to the second light source 25, 35. In principle, however, other angles are also provided here according to the invention.

[0137] In one embodiment, a process for local polymerization of a polymerizable starting material by means of dual color polymerization is provided. In dual color polymerization, photoinitiator molecules, which can also be designated as mediator molecules, absorb photons of light of different wavelengths in order to convert the photoinitiator molecules from the initial state via an intermediate state into a reactive state which is suitable for locally initiating or initiating a polymerization reaction in the polymerizable starting material so that the starting material is polymerized, up to hardening or curing, in particular in the case of plastics.

[0138] The mediator molecule, in the following also called photoinitiator molecule, and its necessary function can be produced in different ways. One example provides the following:

##STR00039##

[0139] The photoinitiator can exist in three different states, which are characterized as follows:

[0140] Initial State (A): [0141] Without light irradiation the photoinitiator molecules are present in this state.

[0142] Intermediate State (B): [0143] The B state is an electronic ground state. [0144] The intermediate state is created from the initial state A by absorption of light of wavelength λ.sub.1. [0145] The photoinitiator molecules have a new or more intense absorption band for light of wavelength λ.sub.2. [0146] Alternatively, the absorption band for λ.sub.1 disappears. The photoinitiator molecule returns to the initial state A spontaneously in the absence of light or by absorption of light of wavelength λ.sub.3.

[0147] Reactive State (C): [0148] The reactive state is generated from the intermediate state B by absorption of light of wavelength 4. [0149] The reactive state initiates a polymerization reaction in the immediate vicinity of the molecule. [0150] A back reaction to B is not intended.

EXAMPLES

[0151] Hereinafter, the action and effect of the invention will be described in detail through specific examples of the invention. However, the examples are provided only to illustrate the present invention, and the scope of the invention is not limited thereto.

Synthesis

[0152] Numbering Scheme for Spiropyrans

##STR00040##

[0153] General synthesis of spiropyrans, spirooxazines, spiroimidazoquinoline-indolines, benzothiazoles (Compounds 1-1, 13-21, 28, 29, 31-57, 62, 64, 70, 77, 78)

[0154] The indolene (1 mmol) or benzothiazole precursor (1 mmol) is dissolved in ethanol (5 mL). Where the indolenium salt or benzothiazolium salt is used, the salt (1 mmol) and piperidine (1.5 mmol) are dissolved in ethanol (5 mL) and stirred for 15 min. The salicylaldehyde (mmol) or the ortho-nitrosophenol (1 mmol), or the 1H-benzo[d]imidazole-4-carbaldehyde (1 mmol) is added and the mixture is heated to 70° C. until consumption of starting materials. After cooling to room temperature, the product precipitates or water is added to precipitate the product. The solid is filtered and washed with ethanol or water. Where the filtration procedure does not yield pure product, the aqueous mixture is extracted with dichloromethane. The combined organic layers are dried over anhydrous MgSO.sub.4 and the solvent is evaporated under reduced pressure. The solid residue is purified by recrystallization from ethanol or silica gel column chromatography using acetone/petroleum ether mixtures as eluent.

##STR00041##

[0155] .sup.1H NMR (500 MHz, Chloroform-d) δ 7 (dd, J=8.6, 1.0 Hz, 1H), 7.86-7.76 (m, 4H), 7.64 (d, J=2.1 Hz, 1H), 7.58 (dd, J=8.5, 2.2 Hz, 1H), 743 (ddd, J=8.5, 6.7, 1.4 Hz, 1H), 7.28-7.23 (m, 1H), 7.16 (t, J 8.6 Hz, 2H), 7.03-6.95 (m, 2H), 6.75-6.71 (m, 1H), 5.87 (d, J=10.3 Hz, 1H), 2.87 (s, 3H), 1.68 (s, 3H), 1.38 (s, 3H). ESI−MS [M+H]+m/z calculated for C.sub.30H.sub.25FNO.sub.2.sup.+: 450.186 measured: 450.197.

##STR00042##

[0156] .sup.1H NMR (500 MHz, Chloroform-d), δ 7.83-7.77 (m, 2H), 7.64-7.57 (s, 2H), 7.51 (dd, J=8.2, 1.7 Hz, 1H), 7.29 (d, J=1.7 Hz, 1H), 7.19-7.12 (m, 2H), 6.96 (d, J=10.3 Hz, 1H), 6.77 (d, J=8.4 Hz, 1H), 6.54 (d, J=8.2 Hz, 1H), 5-75 (d, J=10.3 Hz, 1H), 2.82 (s, 3H), 1.32 (s, 3H), 1.19 (s, 3H). ESI−MS [M+H]+m/z calculated for C.sub.27H.sub.22FN.sub.2O.sub.2.sup.+: 425.166 measured: 425.172.

##STR00043##

[0157] .sup.1H NMR (500 MHz, Chloroform-d) δ 7.80-7.74 (m, 2H), 7.74-7.68 (m, 2H), 7.58-7.52 (m, 1H), 7.50-7.44 (mu, 2H), 7.12 (ddd, J=8.1, 7.4, 1.7 Hz, 1H), 7.07 (dd, J=7.5, 1.7 Hz, 1H), 6.89 (dd, J=10.2, 0.7 Hz, 1H), 6.85 (td, J=7.4, 1.1 Hz, 1H), 6.73 (d, J=7.9 Hz, 1H), 6.50 (d, J=8.1 Hz, 1H), 5.67 (d, J=10.1 Hz, 1H), 2.83 (s, 3H), 1.5 (s, 3H), 1.20 (s, 3H). ESI−MS [M+H].sup.+ m/z calculated for C.sub.26H.sub.24NO.sub.2.sup.+: 382.180 measured: 382.190.

##STR00044##

[0158] .sup.1H NMR (500 MHz, Chloroform-d) δ 7.81-7.75 (m, 2H), 7.75-7.69 (m, 3H), 7.60 (dd, J=2.3, 0.7 Hz, 1H), 7.58-7.53 (m, 1H), 7.51-7.46 (m, 2H), 7.21 (d, J=8.3 Hz, 1H), 6.98 (dd, J=10.3, 0.8 Hz, 1H), 6.54 (d, J=8.6 Hz, 1H), 5.92 (d, J=10.3 Hz, 1H), 2.83 (s, 3H), 1.36 (s, 3H), 1.22 (s, 3H). ESI−MS [M+H].sup.+ m/z calculated for C.sub.26H.sub.22N.sub.2O.sub.4.sup.+: 427.165 measured: 427.173.

##STR00045##

[0159] .sup.1H NMR (500 MHz, Chloroform-d) δ 8.07-8.01 (m, 2H), 7.79-7.74 (m, 2H), 7.72 (d, J=7.1 Hz, 2H), 7.59-7.53 (m, 1H), 7.48 (dd, J=8.2, 6.8 Hz, 2H), 6.97 (d, J=10.3 Hz, 1H), 6.80 (d, J=8.7 Hz, 1H), 6.55 (d, J=8.8 Hz, 1H), 5.87 (d, J=10.3 Hz, 1H), 2.84 (s, 3H), 1.34 (s, 3H), 1.22 (s, 3H). ESI−MS [M+H].sup.+ m/z calculated for C.sub.2H.sub.23N.sub.2O.sub.4.sup.+: 427.165 measured: 427.172.

##STR00046##

[0160] .sup.1H NMR (500 MHz, Chloroform-d) δ 7.81-7.75 (m, 2H), 7.75-7.69 (m, 2H), 7.58-7.51 (m, 3H), 7.51-7.46 (s, 2H), 7.42 (dd, J=8.4, 7.1 Hz, 2H), 7.37 (dd, J=8.4, 2.3 Hz, 1H), 7.33-7.29 (m, 2H), 6.97 (dd, J=10.2, 0.7 Hz, 1H), 6.81 (d, J=8.4 Hz, 1H), 6.52 (d, J=8.1 Hz, 1H), 5.73 (d, J=10.1 Hz, 1H), 2.86 (s, 3H), 1.39 (s, 3H), 1.22 (s, 3H). ESI−MS [M+H].sup.+ m/z calculated for C.sub.32H.sub.28NO.sub.2.sup.+: 458.212 measured: 458.223.

##STR00047##

[0161] .sup.1H NMR (500 MHz, Methylene Chloride-d.sub.2) δ 7.81-7.76 (m, 2H), 7.61-7.56 (m, 2H), 7.21-7.14 (n 31), 7.08 (dd, J=7.3, 1.3, 0.5 Hz, 1H), 6.94 (dd, J=10.4, 0.7 Hz, 1H), 6.85 (td, J=7.4, 1. Hz, 1H), 6.77 (dt, J=8.3, 0.7 Hz, 1H), 6.54 (dt, J=7.8, 0.7 Hz, 1H), 5.80 (d, J=10.3 Hz, ill), 2.75 (s, 3H), 1.31 (s, 3), 118 (s, 3H).

[0162] ESI−MS [M+H].sup.+ m/z calculated for C.sub.26H.sub.23FNO.sub.2.sup.+: 400.171 measured: 400.175.

##STR00048##

[0163] .sup.1H NMR (500 MHz, Methylene Chloride-d.sub.2) δ 7.79-7.73 (m, 2H), 7.58 (dd, J=8.5, 2.2 Hz, 1H), 7.47 (d, J=2.2 Hz, 1H), 7.34-7.26 (m, 4H), 7.21-7.14 (m 4H), 7.09 (td, J=7.7, 1.3 Hz, 1H), 6.89 (td, J=7.4, 1. Hz, 1H), 6.83 (d, J=8.5, 0.7 Hz, 1H), 6.74 (dd, J=10.3, 0.7 Hz, 1H), 6.58 (dt, J=7.8, 0.7 Hz, 1H), 5.76 (d, J=10.3 Hz, 1H), 0.53 (s, 3H), 1.38 (s, 3H), 1.27 (s, 3H). ESI−MS [M+1].sup.+ m/z calculated for C.sub.31H.sub.25FNO.sub.2.sup.+: 462.186 measured: 462.190.

##STR00049##

[0164] .sup.1H NMR (500 MHz, Chloroform-d) δ 8.01 (d, J=2.1 Hz, 1H), 7.97 (dd, J=8.4, 2.1 Hz, 1H), 7.62-7.46 (m, 2H), 7.51-7.43 (m, 2H), 7.33-7.24 (m, 2H), 7.42 (dd, J=2.0, 1.0 Hz, 1H), 6.74 (d, J=8.4 Hz, 1H), 6.77 (d, J=8.3 Hz, 1H), 6.40 (dd, J=8.6, 1.0 Hz, 1H), 5-74 (d, J=8.6 Hz, 1H), 2.86 (s, 3H), 1.28 (s, 3H), 1.19 (s, 3H).

[0165] ESI−MS [M+H].sup.+ m/z calculated for C.sub.26H.sub.23N.sub.2O.sub.4.sup.+: 427.165 measured: 427.155.

##STR00050##

[0166] .sup.1H NMR (500 MHz, Methylene Chloride-d.sub.2) δ 7.74 (ddd, J=8.4, 3.1, 1.4 Hz, 4H), 7.70 (d, J=8.0 Hz, 2H), 7.66-7.60 (m, 2H), 7.60-7.55 (m, 2H), 7.49 (td, J=7.5, 7.0, 1.4 Hz, 4H), 6.98 (dd, J=10.4, 0.7 Hz, 1H), 6.80 (dd, J=8.2, 0.8 Hz, 1H), 6.57 (dd, J=8.0, 0.7 Hz, 1H), 5.80 (d, J=10.2 Hz, 1H), 2.86 (s, 3H), 1.37 (s, 3H), 1.22 (s, 3H).

[0167] ESI−MS [M+H].sup.+ m/z calculated for C.sub.33H.sub.28NO.sub.3+: 486.206 measured: 486.199.

##STR00051##

[0168] .sup.1H NMR (500 MHz, Methylene Chloride-d.sub.2) 87.59 (d, J=2.1 Hz, 1H), 7.54 (dd, J=8.5, 2.2 Hz, 1H), 7.50 (dd, =8.2, 1.7 Hz, 1H), 7.32-7.27 (m, 2H), 6.96 (dd, J=10.3, 0.7 Hz, 1H), 6.70 (dd, J=8.5, 0.6 Hz, 1H), 6.60-6.52 (m, 3H), 5.73 (d, J=10.3 Hz, 1H), 3.86 (s, 3H), 3.71 (8, 3H), 2.81 (s, 3H), 1.30 (s, 3H), 1.17 (s, 3H).

[0169] ESI−MS [M+H].sup.+ m/z calculated for C.sub.29H.sub.27N.sub.2O.sub.4.sup.+: 467.197 measured: 467.215.

##STR00052##

[0170] .sup.1H NMR (500 MHz, Methylene Chloride-d.sub.2) δ 7.86-7.76 (m, 2H), 7.64 (d, J=2.1 Hz, 1H), 7.58-7.47 (m, 2H), 7.47-7.35 (m, 5H), 7.17 (dd, J=8.4, 2.2 Hz, 1H), 6.88-6.85 (m, 2H), 6.48 (dd, J=8.6, 0.9 Hz, 1H), 6.38 (d, J=2.4 Hz, 1H), 5.84 (d, J=8.8 Hz, 1H), 3-85 (s, 3H), 3.71 (a, 3H), 2.87 (s, 3H), 1.43 (s, 3H), 1.14 (s, 3H).

[0171] ESI−MS [M+H].sup.+ m/z calculated for C.sub.35H.sub.32NO.sub.5.sup.+: 546.227 measured: 546.236.

##STR00053##

[0172] .sup.1H NMR (500 MHz, Toluene-d.sub.2) δ 7.51 (d, J=2.1 Hz, 1H), 7.48 (dd, J=8.8, 5.5 Hz, 2H), 7.35 (ddd, J=8.4, 5.0, 2.0 Hz, 2H), 7.31 (d, J=1.7 Hz, 1H), 6.66 (t, J=8.6 Hz, 2H), 6.45-6.40 (m, 2H), 6.33 (dd, J=10.3, 0.7 Hz, 1H), 5.95 (d, J=8.1 Hz, 1H), 5.26 (d, J=10.2 Hz, 1H), 2.43 (s, 3H), 1.10 (8, 3H), 0.87 (s, 3H).

[0173] ESI−MS [M+H].sup.+ m/z calculated for C.sub.26H.sub.22FINO.sub.2.sup.+: 526.369 measured: 526.354.

##STR00054##

[0174] .sup.1H NMR (500 MHz, Chloroform-d.sub.6) δ 7.69 (d, J=2.2 Hz, 1H), 7.61 (dd, J=8.8, 5.5 Hz, 2H), 7.51 (ddd, J=8.1, 1.9, 0.9 Hz, 1H), 7.47 (d, J=1.8 Hz, 1H), 7.44 (dd, J=8.4, 2.2 Hz, 1H), 6.76 (s, 1H), 6.55 (d, J=8.4 Hz, 1H), 6.39 (d, J=10.2 Hz, 1H), 6.22 (d, J=8.1 Hz, 1H), 5.30 (d, J=10.3 Hz, 1H), 2.52 (s, 3H), 1.23 (s, 3H), 0.95 (s, 3H).

[0175] ESI−MS [M+H].sup.+ m/z calculated for C.sub.27H.sub.22F.sub.4NO.sub.2.sup.+: 468.158 measured: 468.150.

##STR00055##

[0176] .sup.1H NMR (500 MHz, Chloroform-d) δ 7.75-7.70 (m, 2H), 7.61-7.55 (m, 2H), 7.54-7.49 (m, 1H), 7.42 (t, J=7.6 Hz, 2H), 7.25 (s, 3H), 7.22-7.16 (m, 1H), 7.08 (dd, J=7.3, 1.3 Hz, 1H), 7.06-6.98 (m, 2H), 6.85-6.78 (m, 2H), 6.74 (d, J=8.4 Hz, 1H), 6.28 (d, J=7.7 Hz, 1H), 5.79 (d, J=10.3 Hz, 1H), 4.55-4.46 (m, 1H), 4.16 (d, J=16.5 Hz, 1H), 1.33 (s, 3H), 1.26 (s, 3H).

[0177] ESI−MS [M+H].sup.+ m/z calculated for C.sub.32H.sub.28NO.sub.2.sup.+: 458.211 measured: 458.223.

##STR00056##

[0178] .sup.1H NMR (500 MHz, Chloroform-d) δ 7.70-7.64 (m, 3H), 7.61 (d, J=2.1 Hz, 1H), 7.54 (dd, J=8.4, 1.8 Hz, 1H), 7.27 (dd, J=1.9, 1.1 Hz, 1H), 7.18-7.05 (m, 2H), 6.85 (d, J=8.4 Hz, 1H), 6.71 (d, J=8.5 Hz, 1H), 6.43 dd, J=8.6, 1.0 Hz, 1H), 5.86 (d, J=8.5 Hz, 1H), 2.99 (s, 3H), 2.83 (s, 3H), 1.28 (s, 3H), 1.14 (s, 3H).

[0179] ESI−MS [M+H].sup.+ m/z calculated for C.sub.27H.sub.25FNO.sub.4S+: 478.148 measured: 478.122.

##STR00057##

[0180] .sup.1H NMR (400 MHz, Chloroform-d) δ 7.65-7.58 (m, 3H), 7.48 (dd, J=8-3, 2.1 Hz, 1H), 7.44 (dd, J-=8.3, 2.0 Hz, 1H), 7.32 (dd, J=0.8, 0.1 Hz, 1H), 7.15-7.09 (m, 2H), 6.78 (d, J=8-3 Hz, 1H), 6.65-6.50 (m, 2H), 6.31 (dd, J=8.5, 1.0 Hz, 1H), 6.28 (d, J=9.7 Hz, 1H), 5.89 (d, J=8.7 Hz, 1H), 2.96 (s, 3H), 1.26 (s, 3H), 1.8 (s, 3H).

[0181] ESI−MS [M+H].sup.+ m/z calculated for C.sub.26H.sub.24FN.sub.2O.sub.4S.sup.+: 479.144 measured: 479.163.

##STR00058##

[0182] .sup.1H NMR (400 MHz Methylene Chloride-d.sub.2) δ 9.40 (s, 1H), 7.73-7.66 (mu, 2H), 7.48-7.41 (m, 1H), 7.40-7.35 (m, 2H), 7.25-7.17 (m, 2H), 7.12-7.04 (m, 2H), 6.77 (td, J=7.8, 1.4 Hz, 1H), 6.62 (dd, J=7.7, 1.4 Hz, 1H), 6.38 (dd, J=8.7, 1.0 Hz, 1H), 5.82 (d, J=8.7 Hz, 1H), 2.90 (s, 3H), 1.31 (s, 3H), 1.09 (s, 3H).

[0183] ESI−MS [M+H].sup.+ m/z calculated for C.sub.26H.sub.24NO.sub.3.sup.+: 398.175 measured: 398.189.

##STR00059##

[0184] .sup.1H NMR (500 MHz, Methylene Chloride-d.sub.2) 8.99 (s, 1H), 7.70-7.63 (m, 2H), 7.52-7.44 (m, 1H), 7.40-7.32 (m, 2H), 7.23 (dd, J=8.0, 1.4 Hz, 1H), 7.05-6.97 (m, 1H), 6.72 (d, J=1.0 Hz, 1H), 6.65 (td, J=7.8, 1.5 Hz, 1H), 6.54 (dd, J=7.8, 1.5 Hz, 1H), 6.45 (dd, J=8.6, 1.0 Hz, 1H), 5.82 (d, J=8.6 Hz, 1H), 2.86 (s, 3H), 1.29 (s, 3H), 1.11 (s, 3H).

[0185] ESI−MS [M+H].sup.+ m/z calculated for C.sub.26H.sub.24NO.sub.4.sup.+: 414.170 measured: 414.161.

##STR00060##

[0186] .sup.1H NMR (500 MHz, Chloroform-d) δ 7.51 (dd, J=1.8, 1.0 Hz, 1H), 7.47-7.43 (m, 1H), 7.28 (d, J=2.2 Hz, 1H), 7.25-7.17 (m, 4H), 7.15 (dd, J=8.3, 2.2 Hz, 1H), 7.14-7.09 (m, 1H), 6.59 (dd, J=8.4, 6.7 Hz, 2H), 6.30 (dd, J=8.6, 1.0 Hz, 1H), 5.87 (d, J=8.9 Hz, 1H), 3.36 (s, 6H), 2.81 (s, 3H), 1.29 (s, 3H), 1.17 (s, 3H).

[0187] ESI−MS [M+H].sup.+ m/z calculated for C.sub.30H.sub.29F.sub.3NO.sub.4.sup.+: 524.204 measured: 524.216.

##STR00061##

[0188] .sup.1H NMR (400 MHz, Chloroform-d) δ 7.58 (dd, J=8.1, 1.8 Hz, 2H), 7.51 (dd, J=1.8, 1.1 Hz, 2H), 7.48-7.42 (m, 6H), 7.29-7.21 (m, 6H), 7.32-7.28 (m, 2H), 6.66 (dd, J=8.5, 3.4 Hz, 4H), 6.50 (dd, J=8.6, 1.0 Hz, 2H), 5.77 (d, J=8.5 Hz, 21), 5.61 (s, 1H), 3.28 (s, 3H), 2.77 (s, 3H), 1.29 (s, 3H), 1.08 (s, 3H).

[0189] ESI−MS [M+H].sup.+ m/z calculated for C.sub.29H.sub.27F.sub.3NO.sub.3.sup.−: 494.194 measured: 494.181.

##STR00062##

[0190] .sup.1H NMR (400 MHz, Chloroform-d) δ 7.48 (dd, J=8.3, 2.1 Hz, 1H), 7.41 (dd, J=2.0, 1.0 Hz, 1H), 7.35 (d, J=2.2 Hz, 1H), 7.17 (dd, J=8.4, 2.1 Hz, 1H), 6.75 (d, J=8.3 Hz, 1H), 6.65 (d, J=8.5 Hz, 1H), 6.41 (dd, J=8.7, 1.0 Hz, 1H), 5.79 (d, J=8.8 Hz, 1H), 3.79 (s, 3H), 2.79 (s, 3H), 1.21 (s, 3), 1.11 (s, 3H).

[0191] ESI−MS [M+H].sup.+ m/z calculated for C.sub.23H.sub.21F.sub.3NO.sub.4.sup.+: 432.142 measured: 432.151.

##STR00063##

[0192] .sup.1H NMR (500 MHz, Chloroform-d) δ 7.60-7.55 (m, 2H), 7.47-7.41 (m, 1H), 7.40-7.34 (m, 2H), 7.18-7.07 (m, 2H), 6.98 (dd, J=7.8, 1.1 Hz, 1H), 6.88 (td, J=7.5, 1.1 Hz, 1H), 6.75 (dd, J=7.5, 1.5 Hz, 1H), 6.64 (d, J=8.7 Hz, 1H), 6.52-6.43 (m, 2H), 5.81 (d, J=8.7 Hz, 1H), 2.81 (s, 3H), 1.27 (s, 3H), 1.19 (s, 3H).

[0193] ESI−MS [M+H].sup.+ m/z calculated for C.sub.16H.sub.24NO.sub.2.sup.+: 382.180 measured: 382.162.

##STR00064##

[0194] .sup.1H NMR (500 MHz, Chloroform-d) δ 7.75-7.64 (m, 2H), 7.49-7.41 (m, 1H), 7.39-7.31 (m, 2H), 7.21-7.10 (m, 2H), 7.08-7.00 (m, 2H), 6.88 (td, J=7.5, 1.2 Hz, 1H), 6.57-6.47 (m, 2H), 6.34 (dd, J=8.5, 1.0 Hz, 1H), 5.89 (d, J=8.7 Hz, 1H), 2.87 (s, 3H), 1.20 (s, 2H), 1.15 (s, 2H).

[0195] ESI−MS [M+H].sup.+ m/z calculated for C.sub.26H.sub.24NO.sub.2.sup.+: 382.180 measured: 382.184.

##STR00065##

[0196] .sup.1H NMR (500 MHz, Benzene-d.sub.6) δ 8.45 (dd J=2.3, 1.1 Hz, 1H), 7.96 (dd, J=8.4, 1.3 Hz, 2H), 7.89 (dd, J=8.6, 2.2 Hz, 1H), 7.28 (dd, J=7.6, 1.4 Hz, 1H), 7.25-7.22 (m, 1H), 7.09-7.01 (m, 2H), 6.98 (ddd, J=7.3, 3.6, 1.1 Hz, 2H), 6.94-6.89 (m, 2H), 6.67 (d, J=8.5 Hz, H), 6.60 (d, J=7.7 Hz, 1H), 6.41 (d, J=7.8 Hz, 1H), 2.68 (d, J=375 Hz, 3H), 1.53 (d, J=25.3 Hz, 3H), 1.38 (d, J=61.9 Hz, 3H).

[0197] ESI−MS [M+H].sup.+ m/z calculated for C.sub.27H.sub.24NO.sub.3.sup.+: 410.175 measured: 410.188.

##STR00066##

[0198] .sup.1H NMR (500 MHz, Chloroform-d) δ 7.79-7.74 (m, 2H), 7.72-7.65 (m, 3H), 7.57-7.52 (n, 1H), 747 (dd, J=8.2, 6.8 Hz, 2H), 7.29 (dd, J=7.5, 1.6 Hz, 1H), 6.96 (d, J=10.3 Hz, 1H), 6.91 (dd, J=8.3, 7.5 Hz, 1H), 6.51 (d, J=8.2 Hz, 1H), 5.85 (d, J=10.3 Hz, 1H), 2.83 (s, 3H), 1.40 (s, 3H), 1.22 (s, 3H).

[0199] ESI−MS [M+H].sup.+ m/z calculated for C.sub.26H.sub.23N.sub.2O.sub.4.sup.+: 427.165 measured: 427-154.

##STR00067##

[0200] .sup.1H NMR (400 MHz, Chloroform-d) δ 7.69-7.60 (m, 2H), 7.57-7.47 (m, 2H), 7.43-7.33 (m, 3H), 7.00 (dd, J=9.0, 1.0 Hz, 1H), 6.73 (d, J=8.5 Hz, 1H), 6.43 (dd, J=9.1, 2.4 Hz, 1H), 6.30 (dd, J=8.6, 1.0 Hz, 1H), 6.17 (d, J=2.4 Hz, 1H), 5.70 (d, J=8.5 Hz, 1H), 3.73 (s, 3H), 2.91 (s, 3H), 1.33 (s, 3H), 1.25 (s, 3H).

[0201] ESI−MS [M+H].sup.+ m/z calculated for C.sub.27H.sub.26NO.sub.3.sup.+: 412.191 measured: 412.184.

##STR00068##

[0202] .sup.1H NMR (500 MHz, Chloroform-d) δ 8.04 (d, J=8.5 Hz, 1H), 7.82-7.71 (m, 4H), 7.64 (dd, J=9.7, 5.0 Hz, 2H), 7.62-7.57 (m, 1H), 7.57-7.43 (m, 3H), 7.35 (ddd, J=8.0, 6.8, 1.1 Hz, 1H), 6.99 (d, J=8.8 Hz, 1H), 6.89 (d, J=8.1 Hz, 1H), 6.51 (d, J=8.2 Hz, 1H), 5.79 (d, J=10.4 Hz, 1H), 2.84 (s, 3H), 1.38 (8, 3H), 1.25 (s, 3H).

[0203] ESI−MS [M+H].sup.+ m/z calculated for C.sub.30H.sub.26NO.sub.2.sup.+: 432.196 measured: 432-201.

##STR00069##

[0204] .sup.1H NMR (500 MHz, Chloroform-d) δ 7.73-7.60 (m, 2H), 7.62-7.54 (m, 2H), 7.50-7.39 (m, 3H), 6.95 (d, J=8.5 Hz, 1H), 6.80-659 (m, 3H), 6.30 (dd, J=8.6, 0.9 Hz, 1H), 5.69 (d, J=8.6 Hz, 1H), 3.64 (s, 3H), 2.80 (s, 3H), 1.43 (s, 3H), 1.19 (s, 3H).

[0205] ESI−MS [M+H].sup.+ m/z calculated for C.sub.27H.sub.26NO.sub.3.sup.+: 412.191 measured: 412.184.

##STR00070##

[0206] .sup.1H NMR (50 MHz, Chloroform-d) δ7.97 (d, J=8.3 Hz, 2H), 7.77 (m, 2H), 7.76-7.72 (m, 3H), 7.41 (d, J=8.6 Hz, 2H), 7.38 (d, J=4.7 Hz, 2H), 7.20 (m, 2H), 7.06-6.98 (m, 1H), 6.51 (d, J=8.1 Hz, 1H), 5.71 (d, J=10.1 Hz, 1H), 2.82 (s, 3H), 1.37 (s, 3H), 1.26 (s, 3H).

[0207] ESI−MS [M+H].sup.+ m/z calculated for C.sub.30H.sub.26NO.sub.2.sup.+: 432.196 measured: 432.203.

##STR00071##

[0208] .sup.1H NMR (500 MHz, Methylene Chlorid d.sub.2) δ 7.75-7.71 (m, 2H), 7.70-7.65 (m, 2H), 7.60-7.54 (m, 1H), 7.51-7.45 (m, 2H), 7.42-7.36 (m, 2H), 6.85 (dd, J=10.3, 0.7 Hz, 1H), 6.52 (dd, J=8.2, 7.2 Hz, 2H), 5.74 (d, J=10.2 Hz, 1H), 2.82 (s, 3H), 1.32 (s, 3H), 1.19 (s, 3H).

[0209] ESI−MS [M+H].sup.+ m/z calculated for C.sub.26H.sub.23NO.sub.2.sup.+: 508.077 measured: 508.069.

##STR00072##

[0210] .sup.1H NMR (500 MHz, Methylene Chloride-d.sub.2) δ 7.86 (d, J=2.0 Hz, 1H), 7.76-7.67 (m, 4H), 7.59-7.54 (m, 1H), 7.51-7.45 (m, 2H), 7.39 (d, J=2.0 Hz, 1H), 6.78 (d, J=10.2 Hz, 1H), 0.60-6.53 (m, 1H), 5.76 (d, J=10.1 Hz, 1H), 2.79 (s, 3H), 1.34 (s, 3H), 1.21 (s, 3H).

[0211] ESI−MS [M+H].sup.+ m/z calculated for C.sub.26H.sub.22I.sub.2N.sub.2.sup.+: 633.973 measured: 633.971.

##STR00073##

[0212] .sup.1H NMR (500 MHz, Methylene Chloride-d.sub.2) δ 7.76 (dd, J=83, 1.7 Hz, 1H), 7.74-7.71 (m, 3H), 7.62 (d, J=1.7 Hz, 1H), 7.59-7.53 (m, 3H), 7.48 (dd, J=8.2, 6.8 Hz, 21), 7.42 (dt, J=75, 1.0 Hz, 1H), 7.33 (s, 1H), 7.27 (t, J=7.7 Hz, 1H), 6.66 (d, J=8.2 Hz, 1H), 2.89 (s, 3H), 1.42 (s, 3H), 0.72 (s, 3H).

[0213] ESI−MS [M+H].sup.+ m/z calculated for C.sub.27H.sub.24N.sub.3O.sup.+: 406.191 measured: 406.202.

##STR00074##

[0214] .sup.1H NMR (500 MHz, Chloroform-d) δ 8.09-8.02 (m, 1H), 7.78-7.70 (m, 4H), 7.64-7.57 (m, 3H), 7.54-7.45 (m, 5H), 7.20 (d, J=8.2 Hz, 1H), 6.97 (d, J=8.3 Hz, 1H), 2.80 (s, 3H), 1.26 (s, 3H), 1.12 (s, 3H).

[0215] ESI−MS [M+H].sup.+ m/z calculated for C.sub.29H.sub.25N.sub.2O.sub.2.sup.+: 433.191 measured: 433.196.

##STR00075##

[0216] .sup.1H NMR (500 MHz, Methylene Chloride-d.sub.2) δ 7.95 (s, 1H), 7.70-7.63 (m, 2H), 7.54-7.45 (m, 2H), 7.42-7.34 (m, 2H), 730 (d, J=1.7 Hz, 1H), 7.22 (dd, J=7.8, 1.6 Hz, 1H), 7.02 (td, J=7.4, 1.6 Hz, 1H), 6.91 (d, J=8.4 Hz, 1H), 6.85-6.73 (n 2H), 2.85 (3, 3H), 1.39 (s, 3H), 1.24 (s, 3H).

[0217] ESI−MS [M+H].sup.+ m/z calculated for C.sub.25H.sub.23N.sub.2O.sub.2.sup.+: 383.175 measured: 383.169.

##STR00076##

[0218] .sup.1H NMR (400 MHz, Chloroform-d) δ 8.95 (s, 1H), 7.75-7.68 (m, 3H), 7.51-7.44 (m, 2H), 7.37-7.31 (s, 3H), 7.14-7.06 (m, 2H), 6.97 (d, J=8.5 Hz, 1H), 2.86 (s, 3H), 1.31 (s, 3H), 1.14 (s, 3H).

[0219] ESI−MS [M+H].sup.+ m/z calculated for C.sub.27H.sub.23FN.sub.3O.sup.+: 424.182 measured: 424.199.

##STR00077##

[0220] .sup.1H NMR (500 MHz, Chloroform-d) δ 8.11-8.06 (s, 1H), 7.93-7.90 (s, 2H), 7.81-7.74 (m, 3H), 7.44-7.37 (m, 2H), 7.35-7.22 (m, 5H), 6.75 (d, J=8.3 Hz, 1H), 3.78 (s, 3H), 2.91 (s, 3H), 1.31 (s, 3H), 1.16 (s, 3H).

[0221] ESI−MS [M+H].sup.+ m/z calculated for C.sub.31H.sub.27N.sub.2O.sub.4.sup.+: 491.197 measured: 491.192.

##STR00078##

[0222] .sup.1H NMR (500 MHz, Chloroform-d) δ 7.75-7.71 (m, 2H), 7.51-7.37 (m, 5H), 6.92 (d, J=8.3 Hz, 1H), 6.47-6.39 (m, 2H), 6.40-6.31 (m, 2H), 5.86 (d, J=8.6 Hz, 1H), 3.60-3.32 (m, 4H), 2.87 (s, 3H), 1.30 (s, 3H), 1.24 (s, 3H), 1.21 (t, J=7.1 Hz, 6H).

[0223] ESI−MS [M+H].sup.+ m/z calculated for C.sub.30H.sub.33N.sub.2O.sub.2.sup.30 : 453.254 measured: 453.256.

##STR00079##

[0224] .sup.1H NMR (500 MHz, Chloroform-d) δ 8.07-7.99 (m, 1H), 7.76-7.68 (m, 2H), 7.60-7.55 (m, 1H), 7.49 (td, J=7.3, 1.9 Hz, 1H), 7.23 (dd, J=7.8, 2.4 Hz, 1H), 6.97 (d, J=10.4 Hz, 1H), 6.80 (d, J=8.8 Hz, 1H), 6.59 (t, J=8.6 Hz, 1H), 6.54 (d, J=8.0 Hz, 1H), 5.86 (d, J=10.3 Hz, 1H), 2.83 (s, 3H), 2.35 (s, 3H), 2.33 (s, 3H), 1.33 (s, 3H), 1.22 (s, 3H).

[0225] ESI−MS [M+H].sup.+ m/z calculated for C.sub.28H.sub.27N.sub.2O.sub.4.sup.+: 455.197 measured: 455.185.

##STR00080##

[0226] .sup.1H NMR (500 MHz, Chloroform-d) δ 7.69-7.59 (m, 2H), 7.55 (d, J=1.7 Hz, 1H), 7.49 (dd, J=8.3, 1.8 Hz, 1H), 7.15 (t, J=8.2 Hz, 2H), 7.06-6.99 (m, 2H), 6.80 (d, J=8.5 Hz, 1H), 6.61-6.52 (m, 1H), 6.47 (dd, J=8.6, 1.0 Hz, 1H), 5.80 (d, J=8.6 Hz, 1H), 2.90 (s, 3H), 1.31 (s, 3H), 1.18 (s, 3H), 1.11 (s, 9H).

[0227] ESI−MS [M+H].sup.+ m/z calculated for C.sub.30H.sub.31FNO.sub.2.sup.+: 456.233 measured: 456.240

##STR00081##

[0228] .sup.1H NMR (50 MHz, Benzene-d.sub.6) δ 7.94 (d, J=1.7 Hz, 1H), 7.66 (dd, J=8.1, 1.8 Hz, 1H), 7.61 (dd, J=8.7, 5.6 Hz, 2H), 6.85 (td, J=7.8, 1.7 Hz, 1H), 6.79 (dd, J=7.7, 1.7 Hz, 1H), 6.71 (t, J=8.7 Hz, 2H), 6.69-6.64 (m, 2H), 6.42 (d, J=10.2 Hz, 1H), 6.19 (d, J=8.1 Hz, 1H), 5.27 (d, J=10.2 Hz, 1H), 2.51 (s, 3H), 1.24 (s, 3H), 0.96 (s, 3H).

[0229] ESI−MS [M+H].sup.+ m/z calculated for C.sub.26H.sub.23FNO.sub.2.sup.+: 400.171 measured: 400.175.

##STR00082##

[0230] .sup.1H NMR (500 MHz, Toluene-d.sub.8) δ 10.40 (s, 1H), 7.93 (dd, J=15.6, 2.1 Hz, 2H), 7.75 (d, J=6.8 Hz, 1H), 7.68 (dd, J=8.1, 1.7 Hz, 1H), 7.19-7.15 (m, 1H), 7.13 (dd, J=6.0, 1.4 Hz, 2H), 7.11 (m, 1H), 7.08 (d, J=2.5 Hz, 1H), 6.40 (d, J=10.3 Hz, 1H), 6.13 (d, J=8.1 Hz, 1H), 5.29 (d, J=10.3 Hz, 1H), 2.44 (s, 3H), 1.13 (m, J=2.1 Hz, 12H), 0.93 (s, 3H).

[0231] ESI−MS [M+H].sup.+ m/z calculated for C.sub.31H.sub.31NO.sub.3.sup.+: 465.230 measured: 465.241.

##STR00083##

[0232] .sup.1H NMR (500 MHz, Chloroform-d) δ 7.79-7.74 (m, 2H), 7.73-7.67 (m, 2H), 7.59-7.53 (m, 1H), 7.51-7.45 (m, 2H), 6.88 (dd, J=10.0, 8.6 Hz, 1H), 6.79 (dd, J=10.2, 0.6 Hz, 1H), 6.56 (dd, J=11.2, 6.7 Hz, 1H), 6.51 (dd, J=7.9, 0.8 Hz, 1H), 5.70 (d, J=10.2 Hz, 1H), 2.81 (s, 3H), 1.34 (s, 3H), 1.19 (s, 3H).

[0233] ESI−MS [M+H]+/z calculated for C.sub.26H.sub.22F.sub.2NO.sub.2.sup.+: 418.161 measured: 418.169.

##STR00084##

[0234] .sup.1H NMR (500 MHz, Chloroform-d) δ 7.68 (s, 1H), 7.64-7.56 (m, 3H), 7.46-7.39 (m, 2H), 7.35 (t, J=7.5 Hz, 2H), 6.77 (d, J=10.3 Hz, 1H), 6.44 (d, J=8.1 Hz, 1H), 5.68 (d, J=10.3 Hz, 1H), 3.80 (s, 3H), 2.67 (s, 3H), 1.22 (s, 3H), 1.10 (s, 3H).

[0235] ESI−MS [M+H].sup.+ m/z calculated for C.sub.27H.sub.24IN.sub.2O.sub.5.sup.+: 583.072 measured: 583.084.

##STR00085##

[0236] .sup.1H NMR (500 MHz, Chloroform-d) δ 7.79-7.74 (m, 2H), 7.70 (d, J=1.6 Hz, 1H), 7.67 (dd, J=8.1, 1.8 Hz, 1H), 7.55-7.51 m, 1H), 7.49-7.43 (m, 2H), 7.23 (d, J=3.1 Hz, 1H), 6.93-6.85 (m, 2H), 6.50 (d, J=8.2 Hz, 1H), 5.88 (d, J=10.3 Hz, 1H), 3.79 (s, 3H), 2.81 (s, 3H), 1.38 (s, 3H), 1.21 (s, 3H).

[0237] ESI−MS [M+H].sup.+ m/z calculated for C.sub.27H.sub.25N.sub.2O.sub.5.sup.+: 457.176 measured: 457.168.

##STR00086##

[0238] .sup.1H NMR (500 MHz, Chloroform-d) δ 7.83 (s, 1H), 7.77-7.73 (m, 2H), 7.73-7.70 (m, 2H), 7.58-7.53 (m, 1H), 7.50-7.45 (m, 2H), 6.91-6.85 (m, 1), 6.55 (d, J=8.1 Hz, 1H), 6.41 (s, 1H), 5.72 (d, J=10.3 Hz, 1H), 3.86 (s, 3H), 2.84 (s, 3H), 1.34 (s, 3H), 1.21 (s, 3H).

[0239] ESI−MS [M+H].sup.+ m/z calculated for C.sub.27H.sub.25N.sub.2O.sub.5.sup.+: 457.176 measured: 457.165.

##STR00087##

[0240] .sup.1H NMR (500 MHz, Chloroform-d) δ 7.74-7.67 (m, 3H), 7.65 (dd, J=8.1, 1.8 Hz, 1H), 7.54-7.49 (m, 11H), 7.48-7.41 (m, 2H), 7.32 (d, J=23 Hz, 1H), 6.99 (d, J=2.3 Hz, 1H), 6.82 (d, J=10.2 Hz, 1H), 6.47 (d, J=8.2 Hz, 1H), 5.66 (d, J=1.1 Hz, 1H), 2.79 (s, 3H), 1.33 (s, 3H), 1.25 (s, 9H), 1.18 (s, 3H).

[0241] ESI−MS [M+H].sup.+ m/z calculated for C.sub.30H.sub.31BrNO.sub.2.sup.+: 516.153 measured: 516.171.

##STR00088##

[0242] .sup.1H NMR (500 MHz, Chloroform-d) δ 7.71 (td, J=4.3, 1.8 Hz, 21), 7.59 (d, J=1.8 Hz, 1H), 7.51 (dd, J=7.7, 1.8 Hz, 1H), 7.23 (d, J=7.7 Hz, H), 7.12 (ddd, J=8.1, 7.4, 1.7 Hz, 1H), 7.07 (dd, J=7.5, 1.7 Hz, 1H), 6.89 (dd, J=10.2, 0.7 Hz, 1H), 6.86 (td, J=7.4, 1.1 Hz, 1H), 6.74 (dt, J=8.3, 0.9 Hz, 1H), 6.50 (d, J=8.6 Hz, 1H), 5.68 (d, J=10.2 Hz, 1H), 2.83 (s, 3H), 2.35 (s, 3H), 2.34 (s, 3H), 1.36 (s, 3H), 1.20 (s, 3H).

[0243] ESI−MS [M+H].sup.+ m/z calculated for C.sub.28H.sub.28NO.sub.2.sup.+: 410.211 measured: 410.222.

##STR00089##

[0244] .sup.1H NMR (400 MHz, Chloroform-d) δ 7.45 (dd, J=8.4, 2.2 Hz, 2H), 7.40-7.31 (m, 6H), 6.85 (d, J=8.5 Hz, 2H), 6.75 (d, J=84 Hz, 2H), 6.48-6.42 (m, 2H), 0.85 (d, J=8.4 Hz, 2H), 2.81 (s, 6H), 1.32 (s, 6H), 1.20 (s, 6H).

[0245] ESI−MS [M+H].sup.+ m/z calculated for C.sub.41H.sub.35N.sub.4O.sub.3.sup.+: 631.270 measured: 631.284.

##STR00090##

[0246] .sup.1H NMR (500 MHz, Methylene Chloride-d.sub.2) δ 7.72 (dd, J=8.4, 1.9 Hz, 1H), 7.51 (dd, J=2.0, 1.0 Hz, 1H), 7.15-7.09 (m, 1H), 7.08 (td, =7.8, 1.5 Hz, 1H), 6.80 (d, J=8.5 Hz, 1H), 6.66-6.59 (m, 1H), 6.54 (dd, J=7.9, 1.4 Hz, 1H), 6.46 (dd, J=8.6, 1.0 Hz, 1H), 5.84 (d, J=8.6 Hz, 1H), 2.81 (s, 3H), 2.28 (s, 6H), 1.36 (s, 3H), 1.30-1.26 (m, 6H), 1.19 (s, 3H).

[0247] ESI−MS [M+H].sup.+ m/z calculated for C.sub.25H.sub.31N.sub.2O.sub.2.sup.+: 391.238 measured: 391.230.

##STR00091##

[0248] .sup.1H NMR (500 MHz, Chloroform-d) δ 7.80-7.73 (m, 2H), 7.69-7.62 (m, 1H), 7.49-7.39 (m, 3H), 7.26 (dd, J=2.0, 1.0 Hz, 1H), 7.11 (dd, J=8.2, 1.7 Hz, 1H), 7.04 (td, J=7.7, 1.4 Hz, 1H), 6.61 (d, J=8.4 Hz, 1H), 6.54-6.44 (m, 3H), 5.90 (d, J=8.8 Hz, 1H), 4.11-4.00 (m, 2H), 3.58-3.49 (m, 2H), 1.35 (s, 3H), 1.25 (s, 3H).

[0249] ESI−MS [M+H].sup.+ m/z calculated for C.sub.27H.sub.26NO.sub.3.sup.+: 412.508 measured: 412.499.

##STR00092##

[0250] .sup.1H NMR (500 MHz, Acetonitrile-d.sub.3) δ 7.87-7.79 (m, 2H), 7.65-7.57 (m, 1H), 7.56-7.48 (m, 2H), 7.48-7.41 (m, 2H), 7.21 (dd, J=7.7, 1.5 Hz, H), 7.11-7.06 (m, 1H), 6.97 (d, J=8.1 Hz, 1H), 6.88 (td, J=7.8, 1.6 Hz, 1H), 6.65 (dd, J=7.8, 14 Hz, 1H), 6.54 (dd, J=8.6, 1.0 Hz, 1H), 5.83 (d, J=8.5 Hz, 1H), 3.80-3.72 (m, 1H), 3.62-3.51 (m, 1H), 3.50-3.42 (m, 2H), 3.09 (s, 9H), 2.21-2.10 (m, 2H), 1.3 (s, 3H), 1.14 (s, 3H).

[0251] ESI−MS [M].sup.+ m/z calculated for C.sub.31H.sub.35N.sub.2O.sub.2.sup.+: 467.269 measured: 467.278.

##STR00093##

[0252] .sup.1H NMR (500 MHz, Methylene Chloride-d.sub.2) δ 7.80-7.71 (m, 2H), 7.53-7.45 (m, 1H), 7.40-7-31 (s, 4H), 7.25 (dd, J=7, 1.5 Hz, 1H), 7.17 (dd, J=7.7, 1.8 Hz, 1H), 7.01 (td, J=7, 1.6 Hz, 1H), 6.77-6.67 (m, 2H), 6.60-6.58 (m, 1H), 2.99 (s, 3H), 2.31 (d, J=1.1 Hz, 3H).

[0253] ESI−MS [M+H].sup.+ m/z calculated for C.sub.24H.sub.20NO.sub.2S.sup.+: 386.121 measured: 386.125.

Synthesis of compounds 10-12

[0254] The corresponding acid chloride derivative (15 mmol) and unsubstituted spiropyran (5 mmol) or 8′-methoxyspiropyran (5 mmol) are dissolved in dichloromethane (50 mL) and cooled to 0° C. AlCl.sub.3 (17 mmol) is added in small portions over 1 h. The resulting mixture is stirred at room temperature for 2 h. The mixture is poured on ice (200 g) and extracted with dichloromethane. The combined organic layers are dried over anhydrous MgSO.sub.4 and the solvent is evaporated under reduced pressure. The solid residue is purified by recrystallization from ethanol or silica gel column chromatography using acetone/petroleum ether mixtures as eluent.

##STR00094##

[0255] .sup.1H NMR (500 MHz, Methylene Chloride-d.sub.2) δ 7.87-7.81 (m, 4H), 7.70 (d, J=1.9 Hz, 1H), 7.64-7.55 (m, 2H), 7.43-7.35 (m, 5H), 7.11-7.04 (m, 2H), 6.79 (d, J=8.3 Hz, 1H), 6.44 (dd, J=8.6, 1.0 Hz, 1H), 6.05 (d, J=8.5 Hz, 1H), 3.81 (s, 3H), 2.83 (s, 3H), 1.31 (s, 3H), 1-14 (s, 3H).

[0256] ESI−MS [M+H].sup.+ m/z calculated for C.sub.34H.sub.30NO.sub.4.sup.+: 516.217 measured: 516.210.

##STR00095##

[0257] .sup.1H NMR (500 MHz, Methylene Chloride-d.sub.2) δ 7.75-7.67 (m, 4H), 7.59 (d, J=1.8 Hz, 1H), 7.43-7.31 (m, 3H), 6.96-6.90 (m, 4H), 6.74 (dd, J=8.5, 5.4 Hz, 2H), 6.34 (dd, J=8.7, 0.9 Hz, 1H), 5.84 (d, J=8.6 Hz, 1H), 3.74 (s, 6H), 2.80 (s, 3H), 1.34 (s, 3H), 1.14 (s, 3H).

[0258] ESI−MS [M+H].sup.+ m/z calculated for C.sub.35H.sub.32NO.sub.5.sup.+: 546.227 measured: 546.218.

Synthesis of Compounds 22, 25, 64, 68

[0259] 6′-Bromospiropyran (3 mmol) is dissolved in dry tetrahydrofuran (15 mL) and cooled to −78° C. n-Butyllithium (3.1 mmol) is added drop-wise and the solution is stirred for 30 min. The corresponding nitrile derivative (5 mmol) is added over 15 min and the reaction is allowed to warm to room temperature. Stirring is continued at room temperature for 2 h, after which water is added and the reaction mixture is extracted with dichloromethane. The combined organic layers are dried over anhydrous MgSO.sub.4 and the solvent is evaporated under reduced pressure. The solid residue is purified by recrystallization from ethanol or silica gel column chromatography using acetone/petroleum ether mixtures as eluent.

##STR00096##

[0260] .sup.1H NMR (400 MHz, Chloroform-d) δ 7.70 (dd, J=8.6, 2.3 Hz, 1H), 7.64 (d, J=2.2 Hz, 1H), 7.24-7.16 (m, 1H), 7.10 (dd, J=7.3, 1.3 Hz, 1H), 6.94-6.85 (m, 2H), 6.71 (d, J=8.6 Hz, 1H), 6.56 (d, J=7.7 Hz, 1H), 5.75 (d, J=10.3 Hz, 1H), 2.75 (s, 3H), 1.39 (s, 9H), 1.32 (s, 3H), 1.19 (s, 3H).

[0261] ESI−MS [M+H].sup.+ m/z calculated for C.sub.24H.sub.28NO.sub.2.sup.+: 362.21 measured: 362.219.

##STR00097##

[0262] .sup.1H NMR (500 MHz, Chloroform-d) δ 7.30-7.26 (m, 1H), 7.20 (dd, =8.3, 1.8 Hz, 1H) 7.15-7.09 (m, 2H), 7.00-6.94 (m, 1H), 6-75 (d, J=8.3 Hz, 1H), 6.56-6.50 (m, 1H), 6.30 (dd, J=8.6, 1.0 Hz, 1H), 5.78 (d, J=8.5 Hz, 1H), 2.99 (s, 3H), 130 (s, 3H), L25 (s, 6H), 1.14 (s, 3H), 0.12 (s, 9H).

[0263] ESI−MS [M+H].sup.+ m/z calculated for C.sub.26H.sub.34NO.sub.3Si.sup.+: 436.230 measured: 436.238.

##STR00098##

[0264] .sup.1H NMR (500 MHz, Chloroform-d) δ 7.45-7.37 (m, 2H), 7.21-7.13 (m, 2H), 6.99-6.92 (m, 1H), 6.65 (d, J=8-3 Hz, 1H), 6.62-6.58 (m, 1H), 6-54 (dd, J=8.6, 1.0 Hz, 1H), 5.80 (d, J=8.6 Hz, 1H), 2.81 (s, 3H), 2.69-2.52 (m, 2H), 1.83-1.74 (m, 2H), 1.62-1.46 (m, 4H), 1.33 (s, 3H), 1.17 (s, 2H), 0.19 (s, 6H).

[0265] ESI−MS [M+H].sup.+ m/z calculated for C.sub.29M.sub.38NO.sub.3Si.sup.+: 476.262 measured: 476.269.

Synthesis of Compounds 23, 24

[0266] 2-Mercaptobenzoic acid (0.5 mmol) or phthalic acid anhydride (0.5 mmol) is slowly dissolved in sulfuric acid (1 mL) and stirred for 15 min. 5-Trifluoromehylspiropyran (0.5 mmol) is added slowly over 30 min and stirring is continued for 2 h. Ice (10 g) is added and the mixture is neutralized with aqueous Na.sub.2CO.sub.3 (10%). The reaction mixture is extracted with ethyl acetate. The combined organic layers are dried over anhydrous MgSO.sub.4 and the solvent is evaporated under reduced pressure. The residue is purified by silica gel column chromatography using a ethyl acetate/petroleum ether mixture as eluent.

##STR00099##

[0267] .sup.1H NMR (400 MHz, Benzene-d.sub.6) δ 8.99 (dd, J=10.8, 0.7 Hz, 1H), 8.84-8.75 (m, 1H), 7.51 (ddd, J=8.1, 1.9, 0.9 Hz, 1H), 7.47 (d, J=1.8 Hz, 1H), 7.15-7.11 (m, 1H), 7.11-7.03 (m, 2H), 6.81 (d, J=8.7 Hz, 1H), 6.67-6.59 (m, 1H), 6.21 (d, J=8.1 Hz, 1H), 5.7 (d, J=10.8 Hz, 1H), 2.54 (s, 3H), 1.24 (s, 3H), 0.99 (s, 3H).

[0268] ESI−MS [M+H].sup.+ m/z calculated for C.sub.27H.sub.21F.sub.3NO.sub.2S.sup.+: 480.124 measured: 480.116.

##STR00100##

[0269] .sup.1H NMR (500 MHz, Chloroform-d) δ 8.06-7.98 (m, 3H), 7.91-7.84 (m, 2H), 7.64 (s, 1H), 7.34 (d, J=2.1 Hz, 1H), 7.26 (dd, J=8.3, 2.2 Hz, 1H), 6.62 (d, J=8.5 Hz, 1H), 6.34 (dd, J=8.6, 1.0 Hz, 1H), 5.91 (d, J=8.6 Hz, 1H), 2.81 (s, 2H), 1.39 (s, 2H), 1.19 (s, 2H).

[0270] ESI−MS [M+H].sup.+ m/z calculated for C.sub.28H.sub.21F.sub.3NO.sub.3.sup.+: 476.147 measured: 476.152.

Synthesis of Compound 26

[0271] Compound 25 (3 mol) is dissolved in tetrahydrofuran, tetrabutylammonium fluorid (1 M in THF, 4.5 mol) is added. The mixture is stirred for 1 h and extracted with ethyl acetate. The combined organic layers are washed with water dried over anhydrous MgSO.sub.4. The solvent is evaporated under reduced pressure and the residue is purified silica gel column chromatography using an ethyl acetate/petroleum ether mixture as eluent. The obtained alcohol is dissolved in acetonitrile. Iodomethan (6 mmol) and Cs.sub.2CO.sub.3 (6 mmol) are added and the mixture is heated to 70° C. over night. After cooling to room temperature, water is added, and the mixture is extracted with ethyl acetate. The combined organic layers are dried over anhydrous MgSO.sub.4 and the solvent is evaporated under reduced pressure. The residue is purified by silica gel column chromatography using an acetone/petroleum ether mixture as eluent.

##STR00101##

[0272] .sup.1H NMR (400 MHz, Chloroform-d) δ 7.48-7.44 (m, 1H), 7.41 (dd, J=8.2, 1.9 Hz, 1H), 7.00 (dd, J=8.0, 1.0 Hz, 1H), 6.91 (td, J=7.6, 1.2 Hz, 1H), 6.70 (d, J=8.3 Hz, 1H), 6.55-6.46 (m, 2H), 6.40 (dd, J=8.8, 1.0 Hz, 1H), 5.78 (d, J=8.8 Hz, 1H), 3.30 (s, 3H), 2.78 (s, 3H), 1.48 (s, 6H), 1.29 (s, 3H), 1.18 (s, 3H).

[0273] ESI−MS [M+H].sup.+ m/z calculated for C.sub.24H.sub.27NO.sub.3.sup.+: 378.206 measured: 378.219.

Synthesis of compound 27

[0274] 2-Bromo-2-ethylpropionyl bromide (5.25 mmol) is dissolved in dichloromethane (50 mL) and cooled to 0° C. AlCl.sub.3 (5.5 mmol) is added in small portions and stirring is continued for 15 min. 5-Trifluoromethylspiropyran (5 mmol) is added over 30 mi and stirring is continued for 2 h. The reaction is poured on ice (50 g) and extracted with dichloromethane. The combined organic layers are dried over anhydrous MgSO.sub.4 and the solvent is evaporated under reduced pressure. The residue is purified by silica gel column chromatography using an ethyl acetate/petroleum ether mixture as eluent.

[0275] The obtained alpha-bromobutyrate (2 mmol) is dissolved in acetonitrile (25 mL) and sodium tolylsulfinate (2.5 mmol) is added. The mixture is heated to reflux for 4 h. After cooling to room temperature, water is added, and the mixture is extracted with ethyl acetate. The combined organic layers are dried over anhydrous MgSO.sub.4 and the solvent is evaporated under reduced pressure. The residue is purified by silica gel column chromatography using an acetone/petroleum ether mixture as eluent.

##STR00102##

[0276] .sup.1H NMR (400 MHz, Chloroform-d) δ 7.43 (dd, J=1.8, 1.1 Hz, 1H), 7.40-7.33 (m, 3H), 7.28-7.22 (m, 2H), 7.01 (dd, J=7.8, 1.0 Hz, 1H), 6.89 (td, J=7.5, 1.0 Hz, 1H), 6.73 (d, J=8.3 Hz, 1H), 6.46-6.35 (m, 3H), 5.74 (d, J=8.6 Hz, 1H), 2.78 (s, 3H), 2.35 (s, 3H), 1.49 (s, 6H), 1.29 (s, 3H), 1.17 (5, 3H).

[0277] ESI−MS [M+H].sup.+ m/z calculated for C.sub.30H.sub.32NO.sub.4S.sup.30 : 502.205 measured: 502.216.

Synthesis of Compound 30

[0278] 2,2,2-Trichloroacetyl chloride (2.1 mmol) is dissolved in dichloromethane (20 mL) and cooled to 0° C. AlCl.sub.3 (2.2 mmol) is added in small portions and stirring is continued for 15 min. 5-Trifluoromethylspiropyran (2 mmol) is added over 30 min and stirring is continued for 2 h. The reaction is poured on ice (20 g) and extracted with dichloromethane. The combined organic layers are dried over anhydrous MgSO.sub.4 and the solvent is evaporated under reduced pressure. The residue is purified by silica gel column chromatography using an ethyl acetate/petroleum ether mixture as eluent.

##STR00103##

[0279] .sup.1H NMR (500 MHz, Chloroform-d) δ 7.59 (dd, J=84, 1.7 Hz, 1H), 7.44 (dd, J=1.9, 1.0 Hz, 1H), 7.34 (d, J=2.1 Hz, 1H), 7.19 (dd, J=8.3, 2.1 Hz, 1H), 0.69 (d, J=0.4 Hz, 1H), 0.60 (d, J=8.5 Hz, 1H), 6.37 (dd, J=8.6, 1.0 Hz, 1H), 5.86 (d, J=85 Hz, 1H), 2.80 (s, 3H), 1.21 (s, 3H), 0.09 (s, 3H).

[0280] ESI−MS [M+H].sup.+ m/z calculated for C.sub.22H.sub.18Cl.sub.3F.sub.3NO.sub.2.sup.+: 490.035 measured: 490.180.

Synthesis of Compounds 58-60, 63

[0281] 5-Trifluoromethylspiropyran (5 mmol), MgCl.sub.2 (75 mmol), triethylamine (18-75 mmol), and paraformaldehyde 7 mmol) are dissolved in THF and heated to 70° C. for 3 days. The mixture is cooled to room temperature, neutralized with 1 M aqueous HCl, and is extracted with ethyl acetate. The combined organic layers are dried over anhydrous MgSO.sub.4 and the solvent is evaporated under reduced pressure. The residue is purified by silica gel column chromatography using an ethyl acetate/petroleum ether mixture as eluent. The reaction is performed in the same manner using 5-trifluoromethyl-5′,7′-dimethylspiropyran, 5-trifluoromethyl-5′,7′-dimethoxyspiropyran, or 5-trifluoromethyl-6′,7′-difluoro-N-(3,5-dimethylbenzyl)-spiropyran.

[0282] 5-Trifluoromethyl-6′-formylspiropyran (2.5 mmol) and diphenylphosphinoxide (2.5 mmol) are dissolved in THF (25 mL) under an argon atmosphere. Triethylamine (2.5 mmol) is added dropwise and stirring is continued for 18 h. Water is added and the mixture is extracted with ethyl acetate. The combined organic layers are dried over anhydrous MgSO.sub.4 and the solvent is evaporated under reduced pressure. The residue is purified by silica gel column chromatography using an ethyl acetate/petroleum ether mixture as eluent. The reaction is performed in the same manner using 5-trifluoromethyl-5′,7′-dimethyl-6′-formylspiropyran, 5-trifluoromethyl-5′,7′-dimethoxy-6′formylspiropyran, or 5-trifluoromethyl-6′,7′-difluoro-N-(3,5-dimethyl-4-formylbenzyl)-spiropyran.

[0283] The corresponding formylspiropyran derivative (1.5 mmol) and MnO.sub.2 (30 mmol) are mixed in dichloromethane and stirred over night. The reaction is filtered over celite and the solvent is evaporated under reduced pressure. Silica gel column chromatography is performed using ethyl acetate/petroleum ether mixtures as eluent to yield the desired products.

##STR00104##

[0284] .sup.1H NMR (400 MHz, Chloroform-d) δ 8.47 (d, J=2.2 Hz, 1H), 8.32 (dd, J=8.7, 2.2 Hz, 1H), 7.92-7.83 (m, 5H), 7.56 (td, J=7.3, 1.5 Hz, 2H), 7.48 (tdd, J=10.3, 7.5, 4.8 Hz, 6H), 6.98 (d, J=10.4 Hz, 1H), 6.81-6.75 (m, 1H), 6.54 (d, J=8.2 Hz, 1H), 5-74 (d, J=10.4 Hz, 1H), 2.75 (s, 3H), 1.28 (s, 3H), 1.17 (s, 3H).

[0285] ESI−MS [M+H].sup.+ m/z calculated for C.sub.33H.sub.28F.sub.3NO.sub.3P.sup.+: 574.175 measured: 574-189.

##STR00105##

[0286] .sup.1H NMR (400 MHz, Chloroform-d) δ 8.01-7.94 (m, 4H), 7.61-7.52 (m, 2H), 7.44-7.32 (m, 5H), 7.28 (dd, J=8.3, 1.8 Hz, 1H), 6.75-6.63 (m, 2H), 6.5 (d, J=8.7 Hz, 1H), 5.80 (d, J=−5 Hz, 1H), 2.87 (s, 3H), 2.44 (s, 6H), 1.31 (s, 3H), 1.11 (s, 3H).

[0287] ESI−MS [M+H].sup.+ m/z calculated for C.sub.35H.sub.32F.sub.3NO.sub.3P.sup.+: 602.207 measured: 602.199.

##STR00106##

[0288] .sup.1H NMR (400 MHz, Chloroform-d) δ 8.01-7.95 (m, 4), 7.58-7.50 (m, 2H), 7.42-7.35 m, 5H), 7.31 (dd, J=8.4, 1.7 Hz, 1H), 6.80 (d, J=8.3 Hz, 1H), 6.74 (d, J=8.9 Hz, 1H), 6.44 (s, 1H), 5.82 (d, J=8.8 Hz, 1H), 3.84 (s, 6H), 2.87 (s, 3H), 1.29 (s, 3H), 1.14 (s, 3H).

[0289] ESI−MS [M+H].sup.+ m/z calculated for C.sub.35H.sub.32F.sub.3NO.sub.5P.sup.+: 634.196 measured: 634.182.

##STR00107##

[0290] .sup.1H NMR (400 MHz, Chloroform-d) δ 7.87-7.81 (m, 41), 7.54-7.47 (m, 2H), 7.42-7.34 (m, 5H), 7.30-7.20 (m, 1H), 7.18 (ddd, J=7.9, 4.9, 1.0 Hz, 1H), 7.15 (t, J=1.0 Hz, 2H), 6.89 (d, J=8.3 Hz, 1H), 6.62 (dd, J=8.0, 5.0 Hz, 1H), 6.53 (dd, J=8.7, 0.9 Hz, 1H), 5.82 (d, J=8.5 Hz, 1H), 4.80 (dt, J=13.0, 1.0 Hz, 1H), 4.41 (dt, J=13.0, 1.0 Hz, 1H), 2.41 (s, 6H), 1.34 (s, 2H), 1.23 (s, 2H).

[0291] ESI−MS [M+H].sup.+ m/z calculated for C.sub.41H.sub.34F.sub.5NO.sub.3P.sup.+: 714.219 measured: 714.211.

Synthesis of Compound 61

[0292] 5-Trifluoromethyl-6′-formylspiropyran (5 mmol) and 1,3-propanedithiol (5 mmol) are dissolved in chloroform (10 mL) and cooled to −10° C. Gaseous HCl is passed through the solution for 45 mi and stirring is continued for 30 min at 0° C. and over night at room temperature. The solvent is evaporated under reduced pressure and the residue is suspended in methanol (5 mL). The slurry is stirred over night and filtered. The solid residue is dried under reduced pressure.

[0293] The dithian derivative (5 mmol) is dissolved in dry tetrahydrofuran (10 mL) under an argon atmosphere and cooled to −78° C. n-butyl lithium (1.6 M in hexanes, 5 mmol) is added dropwise. The solution is warmed to 0° C. and stirred for 30 min. Dimethylgermanium dicholoride (2 mmol) in dry tetrahydrofuran (5 mL) is added dropwise and stirred for 3 h at 0° C. and continued over night at room temperature.

[0294] Water is added and the mixture is extracted with ethyl acetate. The combined organic layers are washed with water and dried over anhydrous MgSO.sub.4. The solvent is removed under reduced pressure. Ethyl acetate (2.5 mL) is added to the solid residue to give a suspension. After stirring over night, methanol (5 mL) is added stirring is continued for 24 h. The suspension is filtered, washed with ethyl acetate/methanol (1/1), and dried under reduced pressure.

[0295] The dithian diethylgermanium derivative (1.5 mmol) is dissolved in tetrahydrofuran (10 mL) and water is added (2 mL). CaCO.sub.3 (1.8 mmol) and iodine (1.8 mmol) are added in portions over 4 h accompanied by intermittent ice-cooling. The reaction mixture is stirred over night at room temperature and filtered over silica gel. Saturated aqueous sodium dithionite solution is added until the color of the resulting suspension changes to yellow. The mixture is filtered and washed with water. The residue is taken up in ethyl acetate and washed with water. The organic phase is dried over anhydrous MgSO.sub.4 and the solvent is evaporated under reduced pressure. Silica gel column chromatography is performed using ethyl acetate/petroleum ether as eluent to yield the desired product.

##STR00108##

[0296] .sup.1H NMR (500 MHz, Chloroform-d) δ 8.15-8.03 (m 4H), 7.51 (dd, J=8.4, 2.1 Hz, 2H), 7.45 (d, J=2.0 Hz, 2H), 7.32 (d, J=8.4 Hz, 2H), 7.12 (d, J=8.2 Hz, 2H), 6.48-6.42 (m, 2H), 5.80 (d, J=8.7 Hz, 2H), 2-75 (s, 6H), 2.08 (q, J=6.7 Hz, 4H), 1.39 (s, 6H), 1.33 (t, J=6.8 Hz, 6H), 1.19 (s, 6H).

[0297] ESI−MS [M+H].sup.+ m/z calculated for C.sub.46H.sub.45F.sub.6GeN.sub.2O.sub.4.sup.+: 877.249 measured: 877.221.

Synthesis of Compound 65

[0298] 2-Bromo-2-methylpropionyl bromide (5.25 mmol) is dissolved in dichloromethane (50 mL) and cooled to 0° C. AlCl.sub.3 (5.5 mmol) is added in small portions and stirring is continued for 15 min. 5-Trifluoromethylspiropyran (5 mmol) is added over 30 min and stirring is continued for 2 h. The reaction is poured on ice (50 g) and extracted with dichloromethane. The combined organic layers are dried over anhydrous MgSO.sub.4 and the solvent is evaporated under reduced pressure. The residue is purified by silica gel column chromatography using an ethyl acetate/petroleum ether mixture as eluent.

[0299] The obtained alpha-bromobutyrate (2 mmol) is dissolved in morpholine (10 mL) and heated to 80° C. for 2 days. After cooling to room temperature, water is added, and the mixture is extracted with ethyl acetate. The combined organic layers are dried over anhydrous MgSO.sub.4 and the solvent is evaporated under reduced pressure. The residue is purified by silica gel column chromatography using an acetone/petroleum ether mixture as eluent.

[0300] Alternatively, the obtained alpha-bromobutyrate (2 mmol) is dissolved in toluene (2 mL) and added dropwise to a solution of sodium methylate in methanol (30%, 10 mL at 0° C. and stirred for 8 h. The suspension is filtered, morpholine (20 mL) is added to the solid residue and the mixture is heated to 13° C. for 24 h. After cooling to room temperature, water is added, and the mixture is extracted with ethyl acetate. The combined organic layers are dried over anhydrous MgSO.sub.4 and the solvent is evaporated under reduced pressure. The residue is purified by silica gel column chromatography using an acetone/petroleum ether mixture as eluent.

##STR00109##

[0301] .sup.1H NMR (400 MHz, Chloroform-d) δ 7.50 (dd, J=8.4, 1.9 Hz, 1H), 7.48-7.41 (m, 2H), 7.37 (dd, J=8.4, 1.9 Hz, 1H), 6.85 (d, 8.4 Hz, 1H), 6.83 (d, 8.4 Hz, 1H), 6.52 (dd, J=8.6, 1.0 Hz, 1H), 5.84 (d, J=8.6 Hz, 1H), 3.72-3.65 (m, 2H), 3.64-3.58 (m, 2H), 2.88 (s, 3H), 2.70-2.63 (m, 4H), 1.35 (s, 3H), 1.30 (s, 6H), 1.19 (s, 3H).

[0302] ESI−MS [M+H].sup.+ m/z calculated for C.sub.28H.sub.32F.sub.3N.sub.2O.sub.3.sup.+: 501.236 measured: 501.240.

Synthesis of Compound 66 and 67

[0303] 2-Bromobutyryl bromide (5.25 mmol) is dissolved in dichloromethane (50 mL) and cooled to 0° C. Al.sub.3 (5.5 mmol) is added in small portions and stirring is continued for 15 min. 5-Trifluoromethylspiropyran (5 mmol) is added over 30 min and stirring is continued for 2 h. The reaction is poured on ice (50 g) and extracted with dichloromethane. The combined organic layers are dried over anhydrous MgSO.sub.4 and the solvent is evaporated under reduced pressure. The residue is purified by silica gel column chromatography using an ethyl acetate/petroleum ether mixture as eluent.

[0304] The obtained alpha-bromobutyrate (2 mmol) is dissolved in tetrahydrofuran and added dropwise to a solution of the corresponding amine in tetrahydrofuran (2 M, 10 mmol) at 0° C. The mixture is stirred at 0° C. for 2 h and for a further 4 h at room temperature. The solvent is evaporated under reduced pressure to yield an alpha-aminobutyrate which is directly used in the next step.

[0305] The obtained alpha-aminobutyrate (2 mmol) is dissolved in acetonitrile (10 mL), benzyl bromide (2.5 mmol) and heated to 70° C. for 2 h. After cooling to room temperature, the solvent is evaporated under reduced pressure and the remaining crude product is suspended in ethanol (to mL). NaOH in water (30%, 10 mL) is added, and the mixture is heated to 60° C. for 4 h. After cooling to room temperature, the mixture is neutralized with 1 M aqueous HCl and extracted with ethyl acetate. The combined organic layers are dried over anhydrous MgSO.sub.4 and the solvent is evaporated under reduced pressure. The residue is purified by silica gel column chromatography using an acetone/petroleum ether mixture as eluent.

##STR00110##

[0306] .sup.1H NMR (500 MHz, Chloroform-d) δ 7.65-7.56 (m, 2H), 7.44 (d, J=1.8 Hz, 1H), 7.38-7.28 (m, SH), 7.27-7.15 (m, 3H), 6.82 (dd, J=8.3, 0.9 Hz, 2H), 6.54 (dd, J=8.6, 1.0 Hz, 1H), 5.81 (d, J=8.6 Hz, 1H), 3.50 (t, J=1.0 Hz, 2H), 2.82 (s, 3H), 2.42 (s, 6H), 1.98-188 (m, 2H1), 1.35 (s, 3H), 1.19 (s, 2H), 0.91 (t, J=7.2 Hz, 3H).

[0307] ESI−MS [M+H].sup.+ m/z calculated for C.sub.33H.sub.36F.sub.3N.sub.2O.sub.2.sup.+: 549.272 measured: 549.284.

##STR00111##

[0308] .sup.1H NMR (400 MHz, Chloroform-d) δ 7.56 (d, J=1.8 Hz, 1H), 7.44-7.38 (m, 2H), 7.37-7.28 (m, 2H), 7.31-7.21 (m, 41), 6.65 (dd, J=8-5, 0.9 Hz, 2H), 6.35 (dd, J=8.6, 1.0 Hz, 1H), 5.81 (d, J=8.5 Hz, 1H), 3.61 (t, J=5.9 Hz, 4H), 3.51 (t, J=0.9 Hz, 2H), 2.84 (s, 3H), 3.06-2.93 (m, 3H), 2.44-2.38 (m, 2H), 1.93-1.82 (m, 2H), 1.32 (s, 3H), 1.20 (s, 3H), 0.96 (t, J=7.1 Hz, 3H).

[0309] ESI−MS [M+1].sup.+ m/z calculated for C.sub.35H.sub.38F.sub.3N.sub.2O.sub.3.sup.+: 591.283 measured: 591.288.

Synthesis of Compound 69

[0310] Compound 68 (3 mmol) is dissolved in tetrahydrofuran, tetrabutylammonium fluorid (1 M in THF, 4-5 mmol) is added. The mixture is stirred for 1 h and extracted with ethyl acetate. The combined organic layers are washed with water dried over anhydrous MgSO.sub.4. The solvent is evaporated under reduced pressure and the residue is purified silica gel column chromatography using an ethyl acetate/petroleum ether mixture as eluent.

##STR00112##

[0311] .sup.1H NMR (400 MHz, Chloroform-d) δ 7.95 (dd, J=8.7, 2.2 Hz, 1H), 7.90 (d, J=2.2 Hz, 1H), 7.20 (td, J=7.7, 1.2 Hz, 1H), 7.09 (d, J=7.1 Hz, 1H), 6.92 (d, J=10.3 Hz, 1H), 6.87 (t, J=7.4 Hz, 1H), 6.73 (d, J=8.6 Hz, 1H), 6.55 (d, J=7.8 Hz, 1H), 5.76 (d, J=10.3 Hz, 1H), 3.54 (s, 1H), 2.74 (s, 3H), 2.13-1.98 (m, 2H), 1.89-1.63 (m, 8H), 1-30 (s, 3H), 1.18 (s, 3H).

[0312] ESI−MS [M+H].sup.+ m/z calculated for C.sub.26H.sub.3NO.sub.3: 404.222 measured: 404.228.

Synthesis of Compounds 71-74

[0313] Compound 70 (2 mmol) is dissolved in dry dichloromethane (mL) and the corresponding isocyanane is added dropwise. The reaction mixture is stirred for 1 h and the solvent is removed under reduced pressure. The residue is purified silica gel column chromatography using an acetone/petroleum ether mixture or a methanol/dichloromethane mixture as eluent.

##STR00113##

[0314] .sup.1H NMR (500 MHz, Chloroform-d) δ 7.87-7.80 (m, 2H), 7.65-7.64 (m, 2H), 7.48-7.40 (m, 3H), 7.5-7.05 m, 2H), 7.04 (ddd, J=7.9, 7.2, 1.9 Hz, 1H), 6.76 (d, J=8.4 Hz, 1H), 0.5 (dd, J=7.9, 1.4 Hz, 1H), 6.28 (dd, J=8.6, 1.0 Hz, 1H), 6.18-6.14 (m 1H), 5.93-5.82 (m, 2H), 5.36 (t, J=4.2 Hz, 1H), 4.52-4.44 (m, 1H), 4.32-4.22 (m, 3H), 3.91-3.82 (m, 1H), 3.78-3.69 (m, 1H), 3.69-3.60 (m, 1H), 3.31-3.21 (m, 1H), 193 (t, J=0.9 Hz, 3H), 1.29 (s, 3H), 1.15 (s, 3H).

[0315] ESI−MS [M+H].sup.+ m/z calculated for C.sub.34H.sub.35N.sub.2O.sub.6.sup.+: 567.249 measured: 567.241.

##STR00114##

[0316] .sup.1H NMR (500 MHz, Chloroform-d) δ 7.71-7.64 (m, 2H), 7.49-7.42 (m, 1H), 7.39-7.28 (m, 4H), 7.14-7.04 (m, 2H), 7.00 (ddd, J=7.9, 7.1, 1.9 Hz, 1H), 6.70 (d, J=8.3 Hz, 1H), 6.52 (dd, J=8.0, 1.4 Hz, 1H), 6.31 (dd, J=8.7, 1.0 Hz, 1=), 6.08 (dd, J=10.1, 9.4 Hz, 1H), 5.94 (d, J=8.8 Hz, 1H), 5.78 (d, J=9.9 Hz, 2H), 5.53 (t, J=4.4 Hz, 1H), 4.58-4.48 (m, 2H), 4.47-4.38 (m 1H), 4.33-4.26 (m, 1H), 3.82-3.73 (m, 1H), 3.71-3.62 (m, 1H), 3.60-3.50 (m, 2H), 1.29 (s, 3H), 1.21 (s, 3H).

[0317] ESI−MS [M+H].sup.+ m/z calculated for C.sub.33H.sub.33N.sub.2O.sub.6.sup.+: 553.233 measured: 553.245.

##STR00115##

[0318] .sup.1H NMR (500 MHz, Chloroform-d) δ 7.98 (d, J=2.3 Hz, 2H), 7.77 (s, 2H), 7.60 (s, 2H), 7.40-7.36 (m, 2H), 7.30-7.11 (m, 20H), 7.03-6.92 (m, 4H), 6.67 (dd, J=8.4, 2.1 Hz, 2H), 6.50 (d, J=8.3 Hz, 2H), 6.29 (dd, J=8.6, 0.9 Hz, 2H), 5.62-5 (m, 2H), 5.03-4.97 (m, 2H), 4.54-4.42 (m, 4H), 4.02-3.91 (m, 4H), 3.85-3.74 (m, 32H), 3.56-3.42 (m, 641), 3.42-3.35 (m, 4H), 2.30 (s, 6H), 1.39 (d, J=6.4 Hz, 6H), 1.32-1.24 (m, 96H), 1.24 (s, 6H), 1.14 (s, 6H).

[0319] ESI−MS [M+2H].sup.2+ m/z calculated for C.sub.174H.sub.270N.sub.6O.sub.45.sup.2+: 1582.452 measured: 1582.436,

##STR00116##

[0320] .sup.1H NMR (500 MHz, Chloroform-d) δ 7.85-7.79 (m, 2H), 7.54-7.44 (m, 2H), 7.44-7.35 (m, 3H), 7.16-7.07 (m, 2H), 7.06-7.01 (m, 1H), 6.99-6.92 (m, 2H), 6.47 (dd, J=8.6, 1.0 Hz, 1H), 5.83 (d, J=8.5 Hz, 1H), 0.6 (t, J=4.4 Hz, 1H), 4.54 (d, J=3.1 Hz, 2H), 4.30-4.19 (m, 2H), 3.83-3.72 (m, 2H), 3.71-3.55 (m, 44H), 3.43-3.30 (m, 2H), 3.25 (s, 3H), 1.27 (s, 3H), 1.19 (s, 3H).

Synthesis of Compounds 75 and 76

[0321] Compound 70 (3 mmol) is dissolved in acetonitrile (25 mL) and cooled to 0° C. Tosyl chloride (10 mmol) or 2-bromomethyl-1,4-benzodioxane (10 mmol) and K.sub.2CO.sub.3 (11 mmol) are added and the mixture is heated to 70° C. for 2 days. The reaction mixture is stirred for 1 h and the solvent is removed under reduced pressure. The residue is purified silica gel column chromatography using an acetone/petroleum ether mixture or a methanol/dichloromethane mixture as eluent. Water is added and the mixture is extracted with ethyl acetate. The combined organic layers are dried over anhydrous MgSO.sub.4 and the solvent is evaporated under reduced pressure. The residue is purified by silica gel column chromatography using an acetone/petroleum ether mixture as eluent.

##STR00117##

[0322] .sup.1H NMR (500 MHz, Chloroform-d) δ 7.71-7.64 (m, 2H), 7.61-7.50 (m, 2H), 7.49-7.41 (m, 3H), 7.12-7.02 (m, 2H), 7.01 (td, J=7.5, 1.5 Hz, 1H), 6.97-6.79 (m, 5H), 6.66 (dd, J=7.7, 1.6 Hz, 1H), 6.32 (dd, J=8.7, 1.1 Hz, 1H), 5.84 (d, J=8.6 Hz, 1H), 5.54 (t, J=4.8 Hz, 1H), 4.31 (dd, J=12.3, 4.9 Hz, 1H), 4.11 (dd, J=12.1, 4.9 Hz, 1H), 3.89-3.76 (m, 2H), 3.75-3.67 (m, 1H), 3.51-3.45 (m, 1H), 1.31 (s, 3H), 1.16 (s, 3H).

[0323] ESI−MS [M+H].sup.+ m/z calculated for C.sub.35H.sub.32NO.sub.5.sup.+: 546.227 measured: 546.239.

##STR00118##

[0324] .sup.1H NMR (500 MHz, Chloroform-d) δ 7.87-7.80 (m, 2H), 7.69-7.63 (m, 2H), 7.58-7.50 (m, 2H), 7.51-7.42 (m, 5H), 7.20 (dd, J=7.7, 1.5 Hz, 1H), 7.04 (td, J=7-5, 1.3 Hz, 1H), 6.99 (td, J=7.3, 1.5 Hz, 1H), 6.80 (d, J=8.4 Hz, 1H), 6.59 (dd, J=7.8, 1. Hz, 1H), 6.39 (dd, J=8.6, 0.9 Hz, 1H), 5.84 (d, J=8.8 Hz, 1H), 4.50-4.44 (m, 1H), 4.41-4.35 (m, 1H), 4.10-3.99 (m, 1H), 3.78-3.68 (m, 1H), 2.40 (s, 3H), 1.29 (s, 3H), 1.10 (s, 3H).

[0325] ESI−MS [M+H].sup.+ m/z calculated for C.sub.34H.sub.32NO.sub.5S.sup.+: 566.200 measured: 566.208.

Synthesis of Compounds 79 and 80

[0326] 4-Hydroxybenzophenone (4 mmol), the corresponding 1,1-diaryl-2-propyn-1-ol (4 mmol), and beta-cyclodextrin hydrate (320 mg) are dissolved in water (10 mL) and heated to 90° C. over night. The mixture is extracted with ethyl acetate. The combined organic layers are dried over anhydrous MgSO.sub.4 and the solvent is evaporated under reduced pressure. The residue is purified by silica gel column chromatography using an acetone/petroleum ether mixture as eluent.

##STR00119##

[0327] .sup.1H NMR (500 MHz, Chloroform-d) δ 7.79-7.71 (In, 2H), 7.64 (dd, J=8.4, 2.2 Hz, 1H), 7.58-7.54 (m, 2H), 7.51-7.43 (m, 2H), 7.37-7.31 (m, 4H), 6.95 (dd, J=8.4, 0.7 Hz, 1H), 6.90-6.85 (m, 4H), 6.62 (dd, J=10.0, 0.7 Hz, 1H), 6.17 (d, J=9.9 Hz, 1H), 3.80 (s, 6H).

[0328] ESI−MS [M+H].sup.+ m/z calculated for C.sub.30H.sub.25O.sub.4.sup.+: 449.175 measured: 49.184.

##STR00120##

[0329] .sup.1H NMR (500 MHz, Chloroform-d) δ 9.49 (d J=8.0 Hz, 1H), 9.33 (d, J=8.2 Hz, 1H), 7.42-7.30 (m, 4H), 7.28 (d, J=4.1 Hz, 3H), 7.24-7.17 (m, 4H), 7.12 (d, J=8.7 Hz, 1H), 6.83 (d, J=8.8 Hz, 1H), 6.75 (d, J=9.0 Hz, 2H), 6.48 (d, J=8.1 Hz, 1H), 6.38 (d, J=7.9 Hz, 1H), 3.83-3.71 (m, 4H), 3.21-3.12 (m, 4H).

[0330] ESI−MS [M+H].sup.+ m/z calculated for C.sub.32H.sub.28NO.sub.3.sup.+: 474.206 measured: 474.220.

Synthesis of Precursors

[0331] ##STR00121##

[0332] 1-Hydroxy-1-carbonitrilecyclohexane (10 g) was dissolved in THF (50 ml), cooled to −20° C., and then Et.sub.3N (13 mL) was added. A solution of trimethylsilyl chloride (12 g in 20 ml of THF) was added dropwise. The solution was stirred at −20° C. for 1.5 h and at rt overnight. The mixture was extracted with methy-tert-butyl ether and the combined organic layers were dried over anhydrous MgSO.sub.4. The solvent was evaporated under reduced pressure and the product obtained after distillation as a clear liquid.

[0333] .sup.1H NMR (500 MHz, Chloroform-d) 1.92 (dt, J=13.3, 3.3 Hz, 2H), 1.63 (dt, J=13.2, 3.8 Hz, 2H), 1.55-1.38 (m, 5H), 1.18-1.06 (m, 1H), 0.11 (s, 3H).

##STR00122##

[0334] 2-Hydroxy-2-carbonitrilepropane (25 g) was dissolved in THF (150 ml), cooled to −20° C., and then Et.sub.3N (46 mL) was added. A solution of trimethylsilyl chloride (42 g in 65 ml of TH) was added dropwise. The solution was stirred at −20° C. for 1.5 h and at room temperature overnight. The mixture was extracted with methyl-tert-butyl ether and the combined organic layers were dried over anhydrous MgSO.sub.4. The solvent was evaporated under reduced pressure and the product obtained after distillation as a clear liquid.

[0335] .sup.1H NMR (500 MHz, Chloroform-d) δ 1.58 (s, 6H), 0.22 (s, 9H).

General Synthesis of Salicylaldehydes

[0336] The corresponding phenol derivative (5 mmol) and NaOH (105 mmol) are dissolved in water (55 L) and heated to 70° C. to 90° C. Chloroform (75 mmol) is added and heating is continued until consumption of starting materials. In cases where the reaction stops without completion, further chloroform (75 mol) is added. After cooling to room temperature, the mixture is acidified with aqueous hydrochloric acid (10%) and extracted with methyl-tert-butyl ether. The combined organic layers are mixed with water (100 mL) and KOH (7.5 g). The aqueous layer is washed with chloroform and then acidified with aqueous hydrochloric acid (10%). The aqueous phase is extracted with methyl-tert-butyl ether and the combined organic extracts from the last step are dried over anhydrous MgSO4. The solvent is removed under reduced pressure and the obtained product is used without further purification directly in the next step.

Synthesis of Ortho-Nitrosophenols

[0337] The corresponding phenol (25 mmol) is dissolved, in acetic acid (150 mL) and NaNO.sub.2 (7 mmol) in water (17 mL) is added dropwise at 0° C. The mixture is stirred at 0° C. for 2 h and a further 4 h at room temperature. Water is added to precipitate the crude product, which is filtered off and used without further purification.

General Synthesis of Indolenium Salts

[0338] The corresponding aniline derivative (50 mmol) is dissolved in a mixture of concentrated aqueous hydrochloric acid (20 mL) and ice water (30 mL). NaNO.sub.2 (100 mmol) in water is added at 0° C. After stirring for 30 min, SnCl.sub.2 (28.4 g) in concentrated aqueous hydrochloric acid (35 mL) is added. The resulting mixture is stirred for 30 min, filtered, and washed with water or 1M aqueous hydrochloric acid to obtain the hydrazine hydrochloride which is used directly in the next step.

[0339] The corresponding hydrazine (as hydrochloride salt) (47.5 mmol), 3-methylbutan-2-one and concentrated aqueous sulfuric acid are dissolved in glacial acetic acid (68 mL). The mixture is refluxed for 24 h, after which the main fraction of the acetic acid is distilled of. After cooling to room temperature, the residue is neutralized with saturated aqueous NaHCO.sub.3 solution. The mixture is extracted with dichloromethane and the combined organic phases are dried over anhydrous MgSO.sub.4, followed by evaporation of the solvent under reduced pressure. Where the indole is not of sufficient purity for the next step, silicagel column chromatography is performed using petroleum ether/ethyl acetate mixtures as eluent.

[0340] The obtained indole (30 mmol) is dissolved in acetonitrile (150 mL) and the corresponding alkyl halide is added (60 mmol). The mixture is refluxed for 24 h. After cooling to room temperature, the product precipitates, is filtered and washed with acetonitrile. Where the product does not precipitate, the solvent is evaporated under reduced pressure. The indole is purified by recrystallization from acetonitrile or acetone.

##STR00123##

[0341] .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ 7.43 (s, 1H), 7.24 (m, 2H), 4.03 (m, 6H), 0.85 (s, 6H).

[0342] ESI−MS [M].sup.+ m/z calculated for C.sub.13H.sub.15N.sub.2.sup.30: 199.123 measured: 199.129.

##STR00124##

[0343] .sup.1H NMR (500 MHz, Acetonitrile-d.sub.3) δ 9.15 (dd, J=2.2, 0.5 Hz, 1H), 9.05 (dd, J=8.8, 2.2 Hz, 1H), 8.50 (d, J=8.8 Hz, 1H), 4.56 (q, J=0.9 Hz, 3H), 3.37 (q, J=0.9 Hz, 3H), 2.20 (s, 6H).

[0344] ESI−MS [M].sup.+ m/z calculated for C.sub.12H.sub.15N.sub.2O.sub.2.sup.+: 219.113 measured: 219.119.

##STR00125##

[0345] .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ 7.35 (dd, J=1.6, 0.7 Hz, 1H), 7.24-7.15 (m, 2H), 7.04-6.97 (m, 2H), 6.94-6.85 (m, 1H), 6.82-6.73 (m, 2H), 4.04 (s, 3H), 3.31 (s, 3H), 0.85 (s, 6H).

[0346] ESI−MS [M].sup.+ m/z calculated for C.sub.19H.sub.20NO.sup.+: 278.154 measured: 278-158.

##STR00126##

[0347] .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ 7.33 (dd, J=1.7, 0.7 Hz, 1H), 7.22-7.14 (m, 2H), 7.06-6.99 (m, 2H), 6.78-6.69 (m, 1H), 6.57-6.48 (m, 2H), 4.04 (s, 3H), 3.31 (s, 3H), 0.85 (s, 6H).

[0348] ESI−MS [M].sup.+ m/z calculated for C.sub.19H.sub.19FNO.sup.+: 296.145 measured: 296.155.

##STR00127##

[0349] .sup.1H NMR (500 MHz, Chloroform-d) δ 7.91 (dd, J=1.6, 0.6 Hz, 1H), 7.88 (dd, J=8-3, 1.5 Hz, 1H), 7.83 (dd, J=8.2, 0.6 Hz, 1H), 7-55 (dd, J=2.0, 0.9 Hz, 1H), 7.46 (dd, J=7.8, 1.9 Hz, 1H), 7.25-7.21 (s, 1H), 4.30 (d, J=1.0 Hz, 3H), 3.14 (d, J=1.0 Hz, 3H), 2.32 (d, J=14.8 Hz, 61), 1.98 (s, 2H), 1.69 (s, 6H).

[0350] ESI−MS [M].sup.+ m/z calculated for C.sub.21H.sub.24NO.sup.+: 306.185 measured: 306.181.

Synthesis of Co-Initiators

Example 1

[0351] Bisphenol A diglycidyl ether (10 g, 29.4 mmol) is added to triethanolamine (26.3 g, 176 mmol) and the mixture is stirred at room temperature overnight. The mixture is taken up in acetone/methanol (25/1) and filtered of silica gel. The solvent is removed under reduced pressure to yield the product as a viscous oil. Instead of triethanolamine other amines can be used, such as morpholine, dicyclohexylamine or dimethylamine.

Example 2

[0352] 2-Isocyanatoethylacrylate (1 g, 7.1 mmol) is added dropwise at 0° C. to a solution of N-butyl-diethanolamine (3.3 g, 28.4 mmol) in dichloromethane (1 mL). After stirring for 1 h at room temperature, dichloromethane is added, and the mixture is washed with water. After evaporation of the solvent under reduced pressure, the product is obtained as a viscous oil. The procedure can be applied to other ethanolamine derivatives and ° isocyanatoethylmethacrylate.

Composition of Exemplary Formulations

Example Formulation 1

[0353] Initiator 2 (2 mg) is dissolved in ethylacetate (0.5 g) and added to a mixture of triethanolamine (1 g) and pentaerythritol tetraacrylate (10 g). The mixture is stirred until homogenization and can be directly used for printing.

Example Formulation 2

[0354] Initiator 2 (2 mg) is dissolved in ethylacetate (0.5 g) and added to a mixture of triethanolamine (i g) and diurethane dime acrylate, mixture of isomers, CAS 72869-86-4 (10 g). The mixture is stirred until homogenization and can be directly used for printing.

Example Formulation 3

[0355] Initiator 2 (2 mg) is dissolved in ethylacetate (0.5 g) and added to a mixture of triethanolamine (1 g), bisphenol A glycerolate (1 glycerol/phenol) diacrylate (g), and pentaerythritol tetraacrylate (5 g). The mixture is stirred until homogenization and can be directly used for printing.

Example Formulation 4

[0356] Initiator 2 (2 mg) is dissolved in ethylacetate (0.5 g) and added to a mixture of triethanolamine (0.25 g), triethylamine (0.75 g), and pentaerythritol tetraacrylate (10 g). The mixture is stirred until homogenization and can be directly used for printing.

Example Formulation 5

[0357] Initiator 2 (2 mg) is dissolved in ethylacetate (0.5 g) and added to a mixture of triethanolamine (0.75 g), acetic acid (0.25 g), and pentaerythritol tetraacrylate (10 g). The mixture is stirred until homogenization and can be directly used for printing.

Example Formulation 6

[0358] Initiator 65 (to mg) and 2-isopropylthioxanthone (too mg) are dissolved in ethylacetate (2 g) and added to a pentaerythritol tetraacrylate (10 g). The mixture is stirred until homogenization and can be directly used for printing.

Example Formulation 7

[0359] Initiator 66 (too mg) and 2-isopropylthioxanthone (too mg) are dissolved in ethylacetate (2 g) and added to a pentaerythritol tetraacrylate (to g). The mixture is stirred until homogenization and can be directly used for printing.

Example Formulation 8

[0360] Initiator 28 (too mg) and 2-isopropylthioxanthone (too mg) are dissolved in ethylacetate (2 g) and added to a pentaerythritol tetraacrylate (to g). The mixture is stirred until homogenization and cane directly used for printing.

Example Formulation 9

[0361] Initiator 2 (2 mg) is dissolved in ethylacetate (0.5 g) and added to a mixture of viscous co-initiator (Example 2, t g), and diurethane dimethacrylate, mixture of isomers, CAS 72869-864 (to g). The mixture is stirred until homogenization and can be directly used for printing.

Example Formulation to

[0362] Initiator 65 (2 mg) is dissolved in ethylacetate (0.5 g) and added to a pentaerythritol tetraacrylate (10 g). The mixture is stirred until homogenization and can be directly used for printing.

Example Formulation 11

[0363] Initiator 66 (2 mg) is dissolved in isoborny lacrylate (1 g) and added to diurethane dimethacrylate, mixture of isomers, CAS 72869-86-4 (10 g). The mixture is stirred until homogenization and can be directly used for printing.

Example Formulation 12

[0364] Initiator 2 (2 mg) is dissolved in ethanol (0.5 g) and added to a mixture of triethanolamine (1 g) and acrylamide/Bis-acrylamide (19/1; 40% solution in water, 10 g). The mixture is stirred until homogenization and can be directly used for printing.

[0365] The above described formulations are used for volumetric printing in a setup, where a cuvette with four transparent windows is irradiated in one direction with a light sheet of wavelength 1, while an image is projected onto the light sheet from a different angle with wavelength 2. The image is changed to produce a movie, while the cuvette or the light sheet is moved through the cuvette. The prints result in solidification only in volumes where the light of both wavelengths intersects. The residual uncured resin is removed to obtain the shaped body, which is further washed with solvent and post-cured. Specifically, the following conditions are used for the given example formulations:

[0366] Wavelength 1: 375 nm, wavelength 2: 565 nm, temperature 5°, 25° C., or 45° C.:

[0367] Formulation 1-5 and 9-12

[0368] Wavelength 1: 405 nm, wavelength 2: 6 nm, temperature 25° C.:

[0369] Formulation 6, 7, 8

[0370] Xolographic Experiments (FIGS. 1-3)

[0371] One part of a mixture of pentaerythritol tetraacrylate (20 g), triethanolamine (1 g) and initiator 2 (2.3 mg) in 1, ml ethanol is irradiated simultaneously by two LEDs with emission maxima of about 375 nm and 617 nm, respectively. The irradiation by the two LEDs is partially blocked by non-transparent layers. The non-transparent layers can be changed during irradiation, for example in their position. The material hardens at the points where both light beams hit the sample for a sufficient time. After irradiation is completed, the sample is washed with EtOH to obtain a solid three-dimensional body.

[0372] The features disclosed in the above description, claims and drawing may be relevant to the realisation of the various designs either individually or in any combination.