Benzisoxazole Synthesis Essay


In the past few decades luminescent transition metal complexes based on polypyridine ligands, owing to their long-lived metal-to-ligand charge-transfer (MLCT) excited states, have already been used in various fields such as solar energy conversion [1], information storage [2], photocleavage of DNA [3], and oxygen sensors [4]. Although the photophysics and photochemistry of [Ru(bpy)3]2+ (bpy = 2,2’ bipiridine) have been the subject of extensive research [1,2,3,4], few other bidentate ligands, i.e. having two aza binding sites, have been prepared and the photophysical and/or photochemical properties of their complexes with transition metals studied [5]. As a continuation of previous studies in this field [6], we now report the synthesis and characterization of the ligands shown in Scheme 1, with the aim of studing the photochemical properties of their complexes with transition metals such as ruthenium, osmium or iridium. Three of these asymmetric bidendate ligands (L2L4) are new. All the compounds were characterized by elemental analysis, EI or FAB mass, 1H and 13C NMR spectroscopies. Complete assignments of the 1H spectra of the various compounds were accomplished by using a combination of one- and two-dimensional NMR techniques.

Scheme 1.


Results and discussion

The literature describes numerous different ways to prepare substituted quinoline rings: i.e., by exploiting quinoline carboxamides [7], acid-catalyzed condensation of o-aminobenzophenones [8] with ketones [9], sequential vinylic substitution/annelation processes [10], reactions of N-arylnitrilium salts with acetylenes [11], cyclodehydration of o-vinyl anilides [12], intramolecular Wittig reactions [13], and cyclization of oximes [14]. Using o-isocyanostyrenes only symmetric biquinoline may be prepared [15]. Following the synthetic pathway previously used for the preparation of the unsubstituted ligand 4-phenyl-2-(2’-pyridyl)quinoline (L1, ph-pq) [16], namely the acid-catalyzed condensation of o-amino-benzophenone with 2- acetylpyridine derivatives, as shown in Scheme 2, we have now synthetized the ligands 4-phenyl-7-methyl-2-(2’-pyridyl)quinoline (L2, mph-pq) and 4-phenyl-7-methyl-2-[2’-(6’-methyl)pyridyl]-quinoline (L3, mph-mpq).

Scheme 2.

The ligand 4-phenyl-6-bromo-2-[2’-(6’-methyl)-pyridyl]quinoline (L4, brph-mpq) was obtained in a three synthetic steps (Scheme 3) starting from p-nitrobromobenzene.

Scheme 3.

2-Amino-5-bromobenzophenone (2) was obtained by condensation of p-nitrobromobenzene with phenylacetonitrile in a basic methanol/tetrahydrofuran medium to give 3-phenyl-5-bromo-2,1-benzisoxazole (1) (66%), which upon reductive cleavage (Fe/CH3COOH) of the benzisoxazole ring was converted to the desired aminoketone 2 (70 %). A subsequent Friedlander reaction [17] of the o-aminobenzophenone 2 with 2-acetyl-6-methylpyridine, using a mixture of m-cresol and phosphorous pentoxide gave ligand L4 (71%). Table I reports the results of a complete 1H-NMR analysis of ligands L1L4. Proton chemical shifts and J(H,H) values were measured at 500 MHz.

Table I.1H NMR parameters of ligands L1L4

38.53 s8.47 s8.48 s8.57 s
57.96 d7.85 d7.22 d8.06 d
67.56-7.507.34 bd7.34 dd-
mJ=6.0J=8.5, 1.5
77.75 dt--7.79 dd
J=7.0, 1.5J=7.0, 2.0
88.26 d8.05 bs8.04 bs7.23 d
3’8.71 d8.69 d7.83 d8.45 d
4’7.90 dt7.88 dt7.77 t7.77 t
J=8.0, 2.0J=8.0, 1.5J=7.5J=8.0
5’7.37 bt7.36 dt8.47 d8.10 d
J=6.5J=7.5, 1.5J=7.5J=8.5
6’8.74 d8.73 dd--
J=4.5J=4.5, 1.0
Py-CH3--2.65 s2.64 s
q-CH3-2.60 s2.59 s-

Assignments were aided by the use of 2D homonuclear chemical shift correlated 1H-NMR (COSY) [18]. As an example, Figure 1 shows the COSY–45 experiment of L1 and includes as the upper and left traces the related 1H-NMR spectrum, both run in deuterated chloroform (CDCl3). The 1H singlet at 8.53 ppm was easily assigned by the integration ratio to the quinoline proton H3. A four-spin system is identified, through the COSY spectrum, as connecting the 1H signals at 8.26, 7.96, 7.75, and 7.57-7.50 ppm. The doublet (ortho coupling) at 8.26 ppm and the double triplet at 7.75 ppm have been assigned to H8 and H7, respectively, by comparison with the literature 1H data for L1 in deuterated acetone [16].

The resonances for H5 and H6 could be assigned to the signals at 7.96 and 7.57-7.50 ppm, respectively. The 1H double triplet at 7.90 ppm, diagnostic for a γ-pyridine [19], and involved in another four spin system connecting the 1H signals at 8.74, 8.71, 7.90, and 7.37 ppm, was assigned to the pyridine proton H4’. As a consequence of the meta and ortho couplings showed by H4’, the doublets at 8.74, 8.71, and the broad triplet at 7.37 ppm, that in turn are correlated themselves, were easily assigned at H6’, H3’, and H5’, respectively. It is worth noting that ortho, meta, and para cross-peaks are observable in the COSY-45 spectrum and can be distinguished from the number and/or the intensity of the spots.

Figure 1. 500 MHz 1H/H1 COSY-45 spectrum of L1 in deuterated chloroform. The upper and left traces are 1D proton spectrum of L1.

Figure 1. 500 MHz 1H/H1 COSY-45 spectrum of L1 in deuterated chloroform. The upper and left traces are 1D proton spectrum of L1.

The highest downfield shift experienced by the H3’ protons, due to deshielding by the non-bonding electrons of the nitrogen on the pyridine ring, is indicative of an anti conformation for the ligands, in agreement with the conformation considered the most probable for bipyridine [5]. According to literature data [19], confirmed by our 1H-NMR analyses, these uncomplexed molecules show an anti conformation (as depicted in Scheme 1, Scheme 2 and Scheme 3) that changes to a syn one when they act as ligands by using the nitrogen of the pyridine and quinoline rings as binding sites. According to the inductive and/or mesomeric effects of the substituents, their introduction onto the skeleton of the N-N bidendate ligand L1 influence the upfield and/or downfield chemical shift of the nearest protons, and the reactivity of these molecules as well. The structures of ligands L1-L4 was further confirmed by their 13C-NMR spectra (see Table II), which displayed the expected patterns.

Table II.13C NMR parameters of ligandsf L1L4


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