Reaction of 2-( α -bromoacetyl)-phenoxathiin with substituted o -, m -, or p -formyl-aroxides

Solid sodium-or potassium aroxides with formyl and alkoxy substituents were reacted with 2-( α - bromoacetyl)-phenoxathiin 3 in the presence of crown ethers (15C5 or 18C6, respectively). When the formyl and hydroxy groups were in meta-or para-positions the resulting fluorescent compounds were 2-( α -formylaryloxyacetyl)-phenoxathiins 4a – d ; however, when these substituents were in the ortho position, the fluorescent products were benzo[ b ]furyl 2-phenoxathiinyl ketones 5e–h , or naphtho[3,2-b ]furyl 2-phenoxathiinyl

eq. 1 eq. 2 This reaction was monitored by TLC, both by following the formation of fluorescent compounds 4a-d and by the disappearance of reactant 3. The duration of the reaction differed according to the structure of the nucleophile, as will be seen in the Experimental Part.The organic solution was washed successively with aqueous acid and base, then concentrated, and the product (4a-d) was purified by preparative TLC.Yields are presented in Table 2.

Preparations of 2-benzo[b]furyl 2-phenoxathiinyl ketones (5e-h) and naphtho[3,2-b]furyl-2,2-phenoxathiinyl ketone (8)
2][33] Phenols 1e-h and compound 6 were treated with alkali hydroxides.The solid formylphenoxides 2e-h were thus prepared in the yields that are presented in Table 1.For the potassium naphthoxide 7 the yield was 56%.The reaction with the haloketone 3 was carried out as indicated in the preceding case, but the S N 2product reacted further by intramolecular dehydration, affording furan derivatives.Whereas the Rap-Stoermer cyclization occurs under drastic conditions, in the present case the reaction proceeded at room temperature, probably due to the high nucleophilicity of the supramolecular complex.Table 3 presents the structures and yields for compounds 5e-h.NMR Spectra of compounds 4a-d, 5e-h and 8. Table 4 gives the 1 H-NMR and 13 C-NMR spectra of the new compounds 4a-d, identifying the atoms in the phenoxathiin and phenyl rings, the aldehyde group, the alkoxy groups, and the ketone carbon.It is seen that the methylene C-12 group of compound 4c is shifted about 2.5 ppm to lower field, probably because of the two neighboring methoxy groups.The quaternary carbons in 13 C-NMR spectra are indicated as Cq.

Table 1. Phenols 1a-h (R = H) and the corresponding aroxides
The 1 H-and 13 C-NMR data (Table 5) confirmed also the structures of the new compounds 5e-h and 8 by identifying: (i) the presence of the phenoxathiin moiety; (ii) the presence of the benzo[b]furyl and naphtho [3,2-b]furyl ring, and of the substituents (CHO group for 8f-h in C-16 position, MeO groups for 5f in the C-18 position, an EtO group for 5g in C-18 position); (iii) the presence of a carbonyl (C-11) group for 8e-h, 9 and a new carbonyl (C-22) group for 8h; (iv) the presence of a methylene (C-21) group for 8h.

Hydrophobicity/hydrophilicity of compounds 4a-d, 5e-h and 8
The hydrophobicity and hydrophilicity properties of compounds 4a-d, 5e-h and 8 are important for their possible biomedical applications.They determine how substances interact with biomembranes and receptors, influencing their bioavailability and biospecificity.The octanolwater partition coefficient (P) and its logarithm (logP) are the usual parameters for estimating quantitatively these characteristics, 34 and they can be measured or computed.In our case, this property for compounds 4a-d, 5e-h and 8 was studied experimentally by reversed phase TLC (RP-TLC) 1,18,35,36 and compared with the phenols 1a-h (Table 1) and 6 (Scheme 2), with compounds 3, with 2-(α-acetyl)-phenoxathiin 9, and phenoxathiin 10.Scheme 2. Synthesis of compound 8.
Thus, R f values were measured, using precoated C 18 -chain layers as stationary phases and various ethanol-water mixtures as mobile phases (Table 6).The molecular hydrophobicity, R M0 , determined as a result of experimental data depending on R M0 values calculated with eqs. 3 and 4, [35][36][37][38] is the R M value extrapolated to zero concentration of organic component in the alcoholwater mixture; b is the change in the R M value caused by increasing the concentration (K) of the organic component in the mobile phase.Statistical analysis involved the correlation coefficient (R), the Fisher parameter [39][40][41] (F), and the standard deviation (SD) (Table 6).In attempting to calculate logP values using fragmental constants, 34 a good correlation (R =0.934) with experimental data for R M0 was obtained for compounds 4a-d, 5e-h and 8 (Figure 1).The 2-(α-acetyl)-phenoxathiin moiety is relatively hydrophobic, with logP = 1.08, 1 conferring hydrophobicity to compounds 4a-d, 5e-h and 8.
1.5 2.0  The experimental results concerning the hydrophobic/hydrophilic character (R M0 values, Table 6) allowed the following observations: (i) compared with phenols 1a-h, compounds 4a-d and 5e-h are more hydrophobic (due to the acetylphenoxathiin moiety); (ii) the hydrophobicity of compounds 3, 4a-d, 5e-h, 8, 9 and 10 decreases in the order: course, the hydrophilicity increases in reverse order); (iii) the acetyl and bromoacetyl moieties reduce the hydrophobicity of the phenoxathiine, and the bromo-atom of the acetyl moiety increases the hydrophobicity (R M0 10> R M0 3> R M0 9); (iv) aside from the compound 5h (with benzofuran and acetylphenoxathiin moieties present in molecule), due to the naphthofuran and benzofuran moieties, the compounds 5e-g and 8 are more hydrophobic than the compounds 4a-d (alone with acetylphenoxathiin moiety present in molecule), i.e., R M0 8> R M0 5e-g > R M0 4a-d> R M0 5h.

TLC behavior
The TLC behavior was investigated because this characteristic has practical and theoretical importance.For this purpose we have chosen pure solvents (Table 7) with different values of the E T (30) (Dimroth-Reichardt`s) parameter. 42The experimental results with pure solvents for compounds 4a-d, 5e-h and 8 (Table 7) can be interpreted as follows: (i) the R f values depend on the solvent polarity (E T (30)

Formation of stable cation radicals
The newly synthesized compounds 4a-d, 5e-h and 8 have yellow fluorescence (λ max = 366 nm) both in solution and in the crystalline state.[11]

Synthesis of phenoxides 2a-h and 7
The solid aroxides were obtained as described previously, 1,27,28 in yields indicated in Table 1.

Synthesis of compounds 4a-d, 5e-h, and 8. General procedure
The solid aroxides 2a-h and 7 were suspended in dichloromethane under stirring (25 mL for 1 g of aroxide), then the corresponding crown ether (Table 1), and finally 2-(α-bromoacetyl)phenoxathiin 3 were added in the following molar ratio 2:3:C.E.= 1.5:1:1.5 for the synthesis of 4a-d, 5e-g and 8; and 1:2.1:1.1 for compound 5h.The reaction mixture rapidly became yellow, and was left at room temperature for 24 h for compounds 4a,b,d; 48 h for 4c; 72 h for 5e-g; 192 h for 5h.The course of the reaction was monitored by TLC, following the formation of fluorescent products and the disappearance of the bromoketone.The reaction mixture was washed three times by liquid/liquid extraction with 1N hydrochloric acid for removing the C.E., and then three times with aqueous 1N sodium hydroxide for removing unreacted phenols.The fluorescent organic layer (excitation at 366 nm) was dried on anhydrous sodium sulfate, and the solvent was removed by rotary evaporation.The crude products were purified by preparative TLC using silica gel plates 60GF 254 (with dichloromethane once for 5e-g, twice for 4a and 5h, three times for 4b and 4d, five times for 4c; and for 8 twice with toluene).
values) and decrease in the following order: 1,2-dichloroethane > dichloromethane > toluene; (ii) irrespective of the mobile phases, the compounds with naphtho[b]furan or benzo[b]furan moieties have higher R f values comparatively with the formylaryloxy-phenoxathiin compounds (R f 8 > R f 5e-h > R f 4a-d); (iii) irrespective of the mobile phases, for compounds 5e-h the formyl group decreases the R f values, the ethoxy group increases R f values and the acetylphenoxathiin moiety decreases the R f values (R f 5e > R f 5g > R f 5f > R f 5h); (iv) for formyl derivatives 4a-d, the R f values depends on the mobile phases, on the number, nature and position of alkoxy groups present in the molecule (in 1,2-dichloroethane and toluene R

Table 6 .
R f values and hydrophobic characteristics (R M0 and b) of the new compounds

Table 7 .
42C behavior (R f ) a of compounds 4a-d, 5e-h and 8 on silica gel 60 GF 254 plates (Merck) with three mobile phases (solvents with different E T(30)values)42 a For five determinations.