Hydrogenation reactions can provide selective enantiomers of chirals but the high pressures required can create a bar to r&d in this area. AllessaSyntec argues that this is where those with specialist knowhow and equipment can help
Enantioselective hydrogenation is a smart and economic way to obtain chiral products. The desired enantiomer can be synthesised specifically by choosing the right chiral catalyst. Many of these hydrogenations can be performed at relatively low pressure of less than 20 bar; however, some enantioselective hydrogenations need elevated or even high pressure, for which many companies do not have the appropriate equipment in house. AllessaSyntec, based in Frankfurt-Höchst, Germany, is equipped with state-of-the-art autoclaves and is experienced in catalytic high-pressure reactions and other technologies that are growing in demand.
The catalytic hydrogenation is a reaction of growing importance in modern chemistry, as more and more effective catalysts are developed. The selectivity of modern catalysts extends the applicability of the reduction with hydrogen gas. A further boost for the hydrogenation technology is the increasing demand of chiral compounds in the pharmaceutical industry, which can be produced through new catalysts with sophisticated ligands.
Although the lab development of enantioselective hydrogenations is aimed at establishing a procedure that works at a pressure range from 1 to 20 bar, there are still many reactions that need really high-pressure facilities. One example is the (R)-2,2’-Bis(diphenyl-phosphino)-1,1’binaphthyl (BINAP) ruthenium complex-catalysed hydrogenation of a racemic methyl _-(benzamidomethyl)-acetoacetate at 100 bar to yield 93% (S, R)-4-acetoxy-azetidinone (see Figure 1), a synthetic intermediate for carbapenem antibiotics, with an enantiomeric excess of 99.5%.1
Despite the great potential that lies in these reactions, one problem limiting the broader implementation of the high-pressure hydrogenation technology in industrial syntheses is that many research laboratories lack the appropriate equipment to evaluate such pathways and, hence, they are not used to the technical scale-up either.
To test the feasibility of high-pressure reactions on cubic metre scale, AllessaSyntec, therefore, offers a development lab. Enantio-selective hydrogenations can be tested in 200ml laboratory autoclaves. The lab procedure is then scaled up to cubic metre scale employing pressures of up to 200 bar.
For the up-scaling, piloting and manufacturing, autoclaves in sizes of 5 litres,
10 litres, 150 litres, 250 litres, 1600 litres and 1800 litres are available in stainless steel or hastelloy.
Furthermore, for multi-step syntheses, the company can use its autoclaves for carbonylations, hydroformylations and air oxidations.
The second core technology, which has been developed over the past 15 years, is the low-temperature reaction down to 100°C in cubic metre scale.
AllessaSyntec can master the whole range of modern chemistry with its total reactor volume of more than 50m3 in 80 different stirred vessels in its modern facilities. The company’s capacities range from 100–5,000 litres and allow the fast scale-up of new chemical products from a laboratory process to industrial scale and the manufacture of high quality products from tens of kilograms up to 50 tons per year.
references:
1. Proceedings of the National Academy of Sciences, 2004, 101(15), 5356-62.
