James Cairns

Influence of metal–support interactions on the hydrogenolysis of methylcyclopentane over supported Rh catalysts

Titania- and silica-supported Rh catalysts have been prepared, pretreated in various ways and their activity and selectivity for the hydrogenolysis of methylcyclopentane determined. Over Rh/silica catalysts the major products are 2-methylpentane and 3-methylpentane. When Rh/titania catalysts are reduced at low temperatures the product distribution differs from that obtained over Rh/silica. More n-hexane is formed and the temperature dependence of the product distribution is different. The results provide evidence of a real support effect. The most remarkable result obtained is that after reduction of the titania-supported catalysts at high temperatures, which leads to a suppression of hydrogen adsorption due to contamination of the Rh by TiOx, the activity of the Rh remains high. The product distribution, in contrast, is only slightly modified. When the catalyst reduced at high temperature is partially oxidised by exposure to oxygen at 298 K ca. 50% of the Rh surface is freed from contamination. However, the activity and turnover numbers decrease as a result of this treatment. It is concluded that only a small fraction of the surface Rh atoms have high turnover numbers for the methylcyclopentane reaction. It is suggested that the active centre is a small Rh ensemble (1 or 2 Rh atoms) in a planar surface.

Alkylated steroids. Part 3. The 21-alkylation of 20-oxopregnanes and synthesis of a novel anti-inflammatory 16α,17α,21-trimethyl steroid (Org 6216)

The development of a 21-alkylation reaction which proceeds via the lithium 20(21)-enolate is described and its scope demonstrated by the preparation of a variety of 21-alkylpregnane derivatives. Application of this process to 11β-acetoxy-16α,17α-dimethyl-5α-pregnane-3,20-dione (28a) and its 5β-analogue (28b) led to the corresponding 16α,17α,21-trimethyl derivatives. Several routes from these saturated trimethylpregnane-3,20-diones to 11β-hydroxy-16α,17α,21-trimethylpregna-1,4-diene-3,20-dione (Org 6216) were explored. The best method gave Org 6216 in 75% yield.

Alkylated steroids. Part 2. 16α,17α-Dimethylpregnanes functionalised in ring C

An improved process for the preparation of 16α,17α-dimethylpregnanes (1b)–(9b) from pregn-16-en-20-ones has been developed and applied to ring C functionalised steroids (1a)–(9a) as a route to corticosteroid analogues. Good to excellent yields of the 16α,17α-dimethyl derivatives were achieved in all cases except with 11β-hydroxy-compounds and this was overcome by using the acetate. Two by-products, formed in variable amounts, were the 16α-methyl and 16α,17α,21-trimethyl derivatives (c) and (d) respectively.

Alkylated steroids. Part 1. 16α-Substituted 17α-methylpregnanes

The sequential reaction of 3β-acetoxypregna-5,16-dien-20-one (1) with methylmagnesium bromide and then methyl iodide has been examined in detail. The major product (85%) was 3β-hydroxy-16α,17α-dimethylpregn-5-en-20-one (2). Other products identified were 3β-hydroxy-16α-methylpregn-5-en-20-one (4); the 21-methyl derivatives [(5) and (10)] of (2) and (4); the 21-(1-hydroxy-1-methylethyl) derivative (11) of (2); and a trace of the 21,21-dimethyl derivative (12) of (2). The scope of the reaction with regard to the range of substituents that can be introduced at positions 16 and 17 has been established by preparing a series of 16α-substituted 17α-methylpregnenolones with a variety of alkyl, aryl, and aralkyl groups. Some of these have been converted into the corresponding 16α,17α-disubstituted progesterones.

Rapid, efficient regeneration of steroidal ketones from thioacetals by periodic acid

Periodic acid smoothly regenerates a variety of steroidal ketones from their thioacetals at room temperature in common solvents and generally in high yield.

The nature of the active centres in hydrocarbon reactions over platinum catalysts

Use of the skeletal rearrangement and the hydrogenolysis of n-hexane as probe reactions, and interaction with titania as a means of modifying catalytic properties, has provided evidence that the active centre in Pt catalysts consists of only a single metal atom in a unique environment.