Yield:-

Reaction Conditions:

with hypophosphorous acid;isopropyl alcohol;zinc(II) iodide in water at 150 - 200; for 3 - 66 h;Product distribution / selectivity;

Steps:

17; 18; 19; 22; 24; 26; 30; 31; 32; 33; 34
Experiments Using Hypophosphorous Acid:[0059] Hypophosphorous acid, H₃PO₂ is commercial available as an aqueous solution (50%) and the most stable tautomer is H₂P(O)OH.[0060] In a typical experiment, an aqueous solution of hypophosphorous acid was charged into a thick-wall pressure vessel and was subjected to a vacuum for 12-36 hours, followed by the addition of zinc iodide (ZnI₂) (32 mol%), methanol (791 mg), and, if applicable, iso-propanol (/-PrOH). The reaction vessel was dipped into a preheated oil bath and was heated for a certain time, during which time white precipitates appeared. In most cases, the mixture was heated for 6-66 hours till the precipitates disappeared, depending on the loading of hypophosphorous acid and whether iso-propanol was used. In the cases where the amount of hypophosphorous acid was above 7.4 mol%, no dissolving of these precipitates had been observed and the reaction vessel was removed from the oil bath before the mixture turned light orange. The vessel was cooled to room temperature and the products were analyzed by GC or NMR.[0061] As a comparison between H₃PO₃ and H₃PO₂ (7.4 mol%) (Examples 17 and 18), the reaction at 200 ⁰C showed an increase of yield (based on total carbon) from to 26% for phosphorous acid (H₃PO₃) to 33% for hypophosphorous acid (H₃PO₂). The most striking differences between the reaction mixtures is that the thptane to triptene ratio is over 20:1 for the reaction using hypophosphorous acid based on both GC and ¹³C NMR analysis. Figure 1 shows the ¹³C NMR spectrum of organic products obtained using the present methods with H₃PO₂ provided as an additive, and Figure 2 shows the ¹³C NMR spectrum of the organic products obtained without any phosphorus compound present. The ¹³C NMR spectrum (Figure 1 ) of the organic products with H₃PO₂ additive had a higher concentration of thptane than that without (Figure 2) although hexamethylbenzene, isopentane, and 2,3-dimethylbutane are also present. The GC trace of the organic products also showed the presence of less aromatic compounds, including hexamethylbenzene (HMB).[0062] Further experiments were performed using hypophosphorous acid and the results are shown in Table 4. Unless specified, the amount of zinc iodide was 32 mol%. The lowest effective amount of H3PO2 was 5.5 mol% and the presence of /-PrOH was necessary at this amount of H3PO2, but it proved not necessary for temperatures over 170 ⁰C with an amount of hypophosphorous acid above 7.4 mol%. The maximum yields obtained at different temperatures are in the range of 33-37% (based on total carbon atom). Reproducibility of these reactions with respect to the reaction time is not as good as that with respect to the maximum yields, possibly due to the presence of different amounts of water and/or the nature of the heterogeneity of this reaction. Water in the H₃PO₂ solution slows down the reaction as shown in a reaction at 200 ⁰C where no water in the aq H₃PO₃ solution was removed, but there is little effect on the ultimate yield. From Table 4, it is clear that reactions at lower temperatures tend to give higher yields and the maximum yield obtainable is about 37%.Table 4 H₃PO₂ as additives at various conditions a) H₃PO₂ (50% aq) vacuumed over 12hour, b) H₃PO₂ solution used directly, c) reactions run for too long with black solutions and a higher hexamethylbenzene to triptane ratio obtained, (d) p-TSA = para toluene sulphonic acid.[0063] The ³¹P NMR studies indicated that H₃PO₂ was a stoichiometric reducing reagent. Three further experiments were performed (Examples 36 to 38). The first reaction with H₃PO₂ (8.8 mol%) and ZnI₂ (32 mol%) in methanol (1.0 ml_) produced triptyls in 36% yield (180 ⁰C, 24 h). The volatile components were then removed under reduced pressure and the reaction vessel with residue was charged with methanol and methyl iodide (6.5 mol%). A yield of 27 mol% triptyls was obtained for the second experiment (180 ⁰C, 24h). However, the yield decreased to 19% triptyls for a further reaction. The analysis of the aqueous solution by ³¹P NMR analysis revealed that H₃PO₄ was the only phosphorus species after the third experiment. Without being bound by any theory, this is consistent with the role of H₃PO₂ or H₃PO₃ as stoichiometric reducing reagents and it is ultimately oxidized to H₃PO₄.[0064] These experiments show that H₃PO₂ is a most effective additive for the homologation of methanol to triptane. The reaction proceed with improved selectivity of triptane and the triptane to thptene ratio is over 20:1.

References:

CALIFORNIA INSTITUTE OF TECHNOLOGY;BP CHEMICALS LIMITED WO2008/24896, 2008, A2 Location in patent:Page/Page column 15-18