High Pressure Services

Peakdale Molecular’s laboratory capabilities include specialisation and vast experience in high pressure chemical transformations built over many years of safe operation. We can apply our expertise to develop safe, efficient and cost effective routes for your high pressure chemistry.

High pressure chemistry plays an increasingly important role in modern organic synthesis and particularly in the production of APIs, intermediates and products for the fine chemical industry. At Peakdale, we now execute in excess of 500 synthetic chemistry projects annually where a high pressure reactor vessel is used, with an extremely high level of success.

High Pressure reactions carried out at Peakdale Molecular include:

  • Hydrogenation applying both homogeneous and heterogeneous catalysts

  • Amination

  • Hydrolysis

  • Carbonylation

  • Chlorination

  • Hydrazine Formation

  • Hydroformylation

  • Displacement Reactions

  • Full Range of Catalysts available based on Ni, Pd, Pt, Rh, Ru

HIGH PRESSURE REACTION EQUIPMENT

Peakdale Molecular has a large array of Parr instruments - high pressure reactors from 300 ml to 7.8 L - to ensure that we deliver material from reaction screen (mg) to scale up (kg).

In addition to this we also have the ability to carry out reactions in highly corrosive media by using our 300 ml, 450 ml and 2 L Parr Instruments Alloy C-276 reactors.

CASE STUDY

A client requested a synthesis of (150g) of the substituted pyridine-2-carboxamide derivative (2). After the synthesis of pyridine (1), Palladium catalysed carbonylation was attempted under 1 atmosphere (atm) of carbon monoxide. The reaction did not proceed to completion, even with the additional catalyst and reaction time. Formation of the debrominated impurity (3) was observed (Table 1).

 

 

The reaction was then optimized under high pressure conditions using a 300 ml autoclave. The reaction was performed at 10, 20 and 30 atm’s of carbon monoxide and then analysed by LCMS. At lower pressure 10 and 20 atm the formation of impurity (3) was still observed. However, gratifyingly, only the desired product (2) was observed at 30 atm.

Safe in the knowledge of the optimal reaction conditions, the synthesis was scaled up using  the 2 L autoclave. The reaction completed as expected and the crude product was purified by crystallization.  

 

Compound (2) was then returned to the 2 L autoclave with methanolic ammonia, which upon heating to 100°C in the sealed system gave rise to the final target (4). Compound (4) was isolated by pouring the reaction mixture on to water and precipitation gave 167g of the customer’s desired compound which was delivered on time and in full.