Synthesis of 2-chromanol by hydroformylation of 2-hydroxystyrene derivatives
2-Benzyloxystyrene and 2-tosyloxystyrene were hydroformylated under different reaction conditions with the aim to obtain the corresponding linear aldehydes, valuable intermediates to 2-chromanol, a structural moiety present in several interesting therapeutically active molecules.
Introduction
Several therapeutically active molecules as the antipsycotic Sarizotan [1], the neuroprotectant Repinotan [2] and others [3], [4] embody in their framework structural moieties deriving from 3,4-dihydrobenzopyran (chroman). In this connection we focused our attention on 2-chromanol (II) as one of the most interesting precursors of the above class of pharmaceuticals. This structurally simple intermediate is prepared in good yields by several methods: however, none of them seems to be fully suitable for a semi-industrial scale production. A survey of the literature reveals that 2-chromanol is generally obtained from easily accessible coumarin or dihydrocoumarin by reduction under various experimental conditions [5], [6], [7]. However, this reduction requires low temperature reaction (<−20 °C) with DIBAL, preferential reagent but very sensitive towards air oxidation and moisture [8]; it is possible to work at higher temperature by using more expensive metal hydrides or homogeneous metal catalysts but very often a substantial amount of o-(3-hydroxypropyl)phenol is produced as by-product [9].
In principle, the hydroformylation of 2-hydroxystyrene (I) could represent a convenient route to 2-chromanol (II), if the linear aldehyde 3-(2-hydroxyphenyl)propanal is produced with high regioselectivity (Scheme 1).
The substrate I is accessible through several expeditous experimental procedures that could be suitable for industrial production, especially by using continuous processes and heterogeneous acid catalysts. They include the alkylation reaction of phenol with ethylene oxide promoted by an acid catalyst [10], the condensation between phenol and vinyl acetate under similar conditions [11], the rearrangement of 2-phenoxyethanol in the presence of sulfuric acid [12], the decarboxylation of o-hydroxycinnamic acid [13] and the pyrolysis of 2,4-dimethyl-1,3-benzodioxane [14]. As laboratory procedure, 2-hydroxystyrene may be produced by Wittig reaction of salicylaldehyde and methylene triphenylphosphorane [15]. In all cases, an extensive amount of dimerization and polymerization by-products is formed, due to the rather low stability of the hydroxy olefin I, even at room temperature. The formation of the dimer is very likely due to a Diels–Alder reaction between the obtained 2-hydroxystyrene and the diene derivative 2-ethylidencyclohexadienon, a product formed by 1,5-sigmatropic transposition of 2-hydroxystyrene [16] (Scheme 2).
In this paper we wish to describe the results obtained during our study on the hydroformylation of 2-hydroxystyrene derivatives catalyzed by different rhodium and platinum carbonyl complexes with the aim to obtain II in satisfactory yield.
Section snippets
Materials
HRh(CO)(PPh3)3 [17], [Rh(COD)Cl]2 [18], Pt(COD)Cl2 [19], (DPPB)PtCl2 [20] and Pt(Xantphos)Cl2 [21] were prepared following well-known procedures. Rh(CO)2acac was purchased from Aldrich and TPPTS from Fluka. Xantphos was prepared as described in the literature [22]. 2,7-bis(SO3Na)2Xantphos was a generous gift from Prof. P. van Leeuwen. Merck silica gel 60 (240–400 mesh) was used for column chromatography. NMR spectra were measured for solutions in CDCl3 using a Bruker AC 200 spectrometer
Results and discussion
Hydroxystyrenes are substrates which have not attracted the interest of researchers involved in the oxo-process to date [28], [29], [30]. Only 3-hydroxy- and 4-hydroxystyrenes were subjected to hydroformylation and in this latter case 90% yield of 2-(4-hydroxyphenyl)propanal was reported, operating at 65 °C and 60 atm in the presence of HRh(CO)(PPh3)3 [31], [32].
We prepared 2-hydroxystyrene (I) by decarboxylation of o-hydroxycinnamic acid [13b] with no more than 30% yield: owing to the pronounced
Conclusions
2-Hydroxystyrene is a thermally unstable compound, therefore it brings about a considerable amount of undesired polymerization products during the hydroformylation under standard oxo-conditions. Much better chemoselectivity results were obtained using a protected hydroxystyrene, such as 2-tosyloxy- or 2-benzyloxystyrene, as the substrate for the oxo-reaction.
However, we were not able to obtain more than 70% of the desired linear aldehydes VII and IX using Rh(CO)2acac with excess Xantphos as
References (37)
- et al.
J. Organomet. Chem.
(1998) - et al.
Organometallics
(1995) - et al.
J. Organomet. Chem.
(1990) - et al.
J. Org. Chem.
(1967) - G. Bartoszyk, R. Devant, H. Boettcher, H. Greiner, J.-J. Berthelon, M. Brunet, M. Noblet, J.-J. Zeiller, Merck, EP...
- B. Junge, R. Schohe, P.-R. Seidel, T. Glaser, J. Traber, U. Benz, T. Schuurman, J.-M. De Vry, Bayer AG, US Patent...
- G. Yiannikouros, P. Kalaritis, J.G. Steenrod, R. Scarborough, Cor Therapeutics Inc., USA, WO 0187871...
- et al.
J. Med. Chem.
(1991) - et al.
J. Org. Chem.
(1997) - et al.
J. Am. Chem. Soc.
(1995)
Can. J. Chem.
J. Med. Chem.
J. Am. Chem. Soc.
J. Am. Chem. Soc.
Chem. Ber.
J. Am. Chem. Soc.
Acta Chem. Scand.
Cited by (26)
Multi-phase CFD modelling for hydroformylation of 1-hexene with microbubbles
2022, Chemical Engineering and Processing - Process IntensificationCitation Excerpt :The aldehydes produced from the reaction can include straight chain and branched chain aldehydes, which are further transformed into alcohols, esters and acetals [5,6]. These compounds have been widely used as the high value-added components in many industries, such as fuel, fine chemicals, medicine, pharmacy and food, to synthesize surfactants, plasticizers, flavors, and pharmaceutical intermediates [7–10]. The continuous progress of the hydroformylation reaction technology has helped the society to favor low carbon and high quality.
Aqueous phase catalytic hydroformylation reactions of alkenes
2015, Catalysis TodayCitation Excerpt :Paganelli et al. studied the hydroformylation of substituted olefins (Scheme 8) for the synthesis of fine chemicals using Rh/TPPTS catalyst. Later this study was extended to the aqueous phase hydroformylation of 2-benzyloxystyrene (Scheme 9) to produce pharmacological active compounds using TPPTS (1, Fig. 3) and SulfoXantPhos (3, Fig. 3) ligands [89]. In case of TPPTS ligand, 99% conversion of 2-benzyloxystyrene with 30% selectivity to linear aldehyde were achieved in 24 h reaction time, whereas, SulfoXantPhos showed very slow reaction rate (55.4% conversion of 2-benzyloxystyrene in 240 h) with higher selectivity to the linear aldehyde (85.6%) than the TPPTS ligand.
Platinum complexes of P,N- and P,N,P-ligands and their application in the hydroformylation of styrene
2013, Journal of Organometallic ChemistryCitation Excerpt :The search for novel platinum-based hydroformylation catalysts has led to the application of novel achiral diphosphines [18]. In particular, xantphos [19] and its analogues [20] have proven the most successful for these transformations. The applicability of tin(II) halide-free hydroformylation catalysts based on platinum–alkyl/aryl complexes and boron additives was shown in our laboratory [21].
Platinum complexes of 2-diphenylphosphinobenzaldehyde-derived P-alkene ligands and their application in the hydroformylation of styrene
2010, Journal of Organometallic ChemistryCitation Excerpt :The search for higher-activity platinum-based hydroformylation catalysts has led to the application of novel achiral diphosphines [8]. In particular, xantphos [9] and its analogues [10] have proven the most successful for these transformations. The applicability of tin(II) halide-free hydroformylation catalysts based on platinum–alkyl/aryl complexes and boron additives was shown in our laboratory [11].
Synthesis of the novel ligand tris-(3,4-dimethoxylphenyl)phosphine and its catalytic performance in 1-dodecene hydroformylation
2010, Cuihua Xuebao/Chinese Journal of CatalysisPlatinum complexes of malonate-derived monodentate phosphines and their application in the highly chemo- and regioselective hydroformylation of styrene
2009, Journal of Organometallic Chemistry