Coupling of two arenes with selenium dioxide to give a selenobiaryl ether

Abstract

The present invention relates to a method for coupling two arenes with selenium dioxide to give a selenobiaryl ether. The method of the present invention includes: adding a first arene to the reaction mixture, adding a second arene to the reaction mixture, adding selenium dioxide to the reaction mixture, adding an acid having a pKa in the range from 0 to 5 to the reaction mixture, and adjusting the reaction temperature of the reaction mixture such that the first arene and the second arene are converted to a selenobiaryl ether. The present invention also relates to novel selenobiaryl ethers.

Claims

1. A method for preparing selenobiaryl ethers comprising: I) forming a reaction mixture by: a) adding a first arene to the reaction mixture, b) adding a second arene to the reaction mixture, c) adding selenium dioxide to the reaction mixture, d) adding an acid having a pKa in the range from 0 to 5 to the reaction mixture, II) adjusting the reaction temperature of the reaction mixture to a temperature in the range from 20 C. to 100 C. such that the first arene and the second arene are converted to the selenobiaryl ether, wherein the second arene does not include phenols, and wherein the wherein the first arene in method step a) is a compound of the general formula I: ##STR00007## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 are each independently selected from: H, (C.sub.1-C.sub.12)-alkyl, O(C.sub.1-C.sub.12)-alkyl, (C.sub.6-C.sub.20)-aryl, O(C.sub.6-C.sub.20)-aryl, -halogen, OCO(C.sub.1-C.sub.12)-alkyl, two adjacent radicals may additionally be joined to one another to form a condensed system, where the alkyl and aryl groups mentioned may be substituted, and at least one of the R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 radicals is H.

2. The method according to claim 1, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 are each independently selected from: H, (C.sub.1-C.sub.12)-alkyl, O(C.sub.1-C.sub.12)-alkyl, (C.sub.6-C.sub.20)-aryl, O(C.sub.6-C.sub.20)-aryl, where the alkyl and aryl groups mentioned may be substituted, and at least one of the R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 radicals is H.

3. The method according to claim 1, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, are each independently selected from: H, (C.sub.1-C.sub.12)-alkyl, O(C.sub.1-C.sub.12)-alkyl, where the alkyl groups mentioned may be substituted, and at least one of the R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 radicals is H.

4. The method according to claim 1, wherein the second arene in method step b) is a compound of the general formula II: ##STR00008## wherein R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10 are each independently selected from: H, (C.sub.1-C.sub.12)-alkyl, O(C.sub.1-C.sub.12)-alkyl, (C.sub.6-C.sub.20)-aryl, O(C.sub.6-C.sub.20)-aryl, -halogen, OCO(C.sub.1-C.sub.12)-alkyl, two adjacent radicals may additionally be joined to one another to form a condensed system, where the alkyl and aryl groups mentioned may be substituted, and at least one of the R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10 radicals is H.

5. The method according to claim 4, wherein R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10 are each independently selected from: H, (C.sub.1-C.sub.12)-alkyl, O(C.sub.1-C.sub.12)-alkyl, (C.sub.6-C.sub.20)-aryl, O(C.sub.6-C.sub.20)-aryl, where the alkyl and aryl groups mentioned may be substituted, and at least one of the R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10 radicals is H.

6. The method according to claim 4, wherein R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10 are each independently selected from: H, (C.sub.1-C.sub.12)-alkyl, O(C.sub.1-C.sub.12)-alkyl, where the alkyl and aryl groups mentioned may be substituted, and at least one of the R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10 radicals is H.

7. The method according to claim 4, wherein the first arene corresponds to the second arene.

8. The method according to claim 1, wherein the selenium dioxide is added in method step c) in a molar ratio based on the sum total of the first and second arenes within a range from 0.25 to 1.5.

9. The method according to claim 1, wherein the acid is acetic acid.

10. A compound of the formula 1 or 2: ##STR00009##

11. The method according to claim 1, wherein the added acid in step d) is present in amounts that forms a solution of dissolved first and second arenes and selenium dioxide.

Description

ANALYSIS

(1) NMR Spectroscopy

(2) The NMR spectroscopy studies were conducted on multi-nucleus resonance spectrometers of the AC 300 or AV II 400 type from Bruker, Analytische Messtechnik, Karlsruhe. The solvent used was CDCl.sub.3. The .sup.1H and .sup.13C spectra were calibrated according to the residual content of undeuterated solvent using the NMR Solvent Data Chart from Cambridge Isotopes Laboratories, USA. Some of the .sup.1H and .sup.13C signals were assigned with the aid of H,H-COSY, H,H-NOESY, H,C-HSQC and H,C-HMBC spectra. The chemical shifts are reported as values in ppm. For the multiplicities of the NMR signals, the following abbreviations were used: s (singlet), bs (broad singlet), d (doublet), t (triplet), q (quartet), m (multiplet), dd (doublet of doublets), dt (doublet of triplets), tq (triplet of quartets). All coupling constants J were reported in hertz (Hz) together with the number of bonds covered. The numbering given in the assignment of signals corresponds to the numbering shown in the formula schemes, which need not correspond to IUPAC nomenclature.

(3) Bis(6-methyl-2,3,4-trimethoxyphenyl)selenium

(4) ##STR00005##

(5) In a 25 mL round-bottom flask, 0.27 g of selenium dioxide (2.4 mmol) was added to 0.80 g of 3,4,5-trimethoxytoluene (4.3 mmol) dissolved in 6 mL of acetic acid and the mixture heated to 85 C. in a hot oil bath. After 12 days, the reaction mixture was filtered, the filtrate diluted with dichloromethane and washed with saturated sodium chloride solution. The organic phase was dried over magnesium sulphate and the solvent distilled off under reduced pressure. The crude product was purified by column chromatography. The column length was 24 cm with a diameter of 3 cm. Cyclohexane/ethyl acetate was used as eluent in a ratio of 9:1.

(6) Yield: 0.399 g (0.9 mmol; 41%)

(7) GC: R (hard method, HP-5)=16.250 min

(8) TLC: R.sub.f (CH:EE, 2:1)=0.4 .sup.1H-NMR: (400 MHz, CDCl3) [ppm]=2.37 (s, 6H), 3.59 (s, 6H), 3.78 (s, 6H), 3.82 (s, 6H), 6.54 (s, 2H).

(9) .sup.13C-NMR: (100 MHz, CDCl3) [ppm]=23.52 56.00, 60.60, 60.86, 109.17, 118.21, 137.07, 140.44, 153.06, 154.19.

(10) HRMS (ESI, pos. mode):m/z for [M+Na+]: calculated: 465.0792 found: 465.0780

(11) Bis(4,5-dimethoxy-2-methylphenyl)selenium

(12) ##STR00006##

(13) In a 25 mL round-bottom flask, 1.00 g of 3,4-dimethoxytoluene (6.5 mmol) was dissolved in 9 mL of acetic acid, 0.40 g of selenium dioxide (3.6 mmol) was added and the mixture heated to 85 C. in a hot oil bath. After 12 days, the reaction mixture was filtered, the filtrate diluted with dichloromethane and washed with saturated sodium chloride solution. The organic phase was dried over magnesium sulphate and the solvent distilled off under reduced pressure. The crude product was purified by column chromatography. In this case, an automated column system from BCHI-Labortechnik GmbH, Essen was used. The column length was 16 cm and the diameter 6 cm. The eluent used was cyclohexane/ethyl acetate, operating with an ethyl acetate gradient of: 0% (over 5 min), 1-5% (over 5 min), 5-10% (over 8 min), 10-20% (8 min), 20-40% (10 min), 40-100% (10 min). The pumping rate was 100 mL/min.

(14) Yield: 0.637 g (1.6 mmol), 51%

(15) GC: R (hard method, HP-5)=15.968 min

(16) .sup.1H-NMR: (400 MHz, CDCl3) [ppm]=2.34 (s, 6H), 3.70 (s, 6H), 3.86 (s, 6H), 6.76 (s, 2H), 6.77 (s, 2H)

(17) .sup.13C-NMR: (100 MHz, CDCl3) [ppm]=21.96, 56.07, 56.16, 113.47, 116.51, 121.55, 132.50, 147.54, 148.70.

(18) HRMS (ESI, pos. mode):m/z for [M+Na+]: calculated: 405.0581 found: 405.0484

(19) Both compounds 1 and 2 could each be synthesized in very good yields. Therefore, the stated problem is solved by the inventive method.