Figure 1. Kinematic viscosity, or the absolute viscosity of the fluid divided by its density, is shown for the perfluoropolyether.

Because of their molecular structure, these fluids remain in a liquid state over a wide temperature range and do not degrade at temperatures up to 572^oF (300^oC). Perfluoropolyether fluids, commonly known as PFPEs, contain only carbon, fluorine and oxygen atoms in the molecule and offer the following properties:

• High chemical/oxidation stability.

• Excellent chemical inertness.

• No flash- or fire-point.

• Good compatibility with metals, plastics and rubbers.

• Good dielectric properties.

• No toxicity.

• Do not deplete ozone.

• Available over a range of boiling points.

In addition, the presence of the ether link - O - (oxygen) imparts high mobility to the PFPE molecule, which is manifested as a high viscosity index. The safety in use and pumpability of these fluids at low temperatures, as well as relatively high boiling points, make them candidates for processes operated at temperatures as low as -112^oF (-80^oC) and as high as 572^oF. And, their thermal and oxidation stability, along with high chemical inertness, make perfluoropolyethers well suited for aggressive environments.

Perfluoropolyether fluid characteristics can best be described by looking at two examples where they are used as heat transfer media: in the manufacture of pharmaceuticals, and in an aggressive chemical environment during the manufacture of phosphorous oxychloride.

Perfluoropolyether fluid compatibility with selected elastomers, plastics and metals is shown.

Developing Drugs

Heat Transfer System. Eisai's heat transfer system consists of a reservoir, magnetic drive centrifugal pump and a heat exchanger. The fluid is used at four points in the system:

• A glass-lined stainless steel reactor.

• Two rotovap evaporators.

• A ridge vent condenser.

Fluid temperature at each of the use points can be individually controlled.

Reservoir. The reservoir is an agitated tank that holds up to 416 gal (1,600 l) of the fluid. Space above the fluid level is filled with dry nitrogen at an overpressure of 7" of water (approximately 13 torr). Originally, the reservoir had external cooling coils carrying liquid nitrogen, but it was difficult to reach the desired low temperatures with this arrangement. Therefore, an external heat exchanger was installed. Fluid level is maintained at the minimum required by the pump.

Pump. A centrifugal pump with magnetic drive coupling is used to pump the fluid around the system. Motor speed can be varied through a frequency controller, thus allowing the fluid flow rate to be varied. Typical flow rate is 80 gal/min (364 l/min) at 100 psi (approximately 6.8 atm). So far, no backpressure buildup or temperature increase at the pump outlet has been observed.

Heat Exchanger. Initially, it was difficult to reach the desired low temperatures by cooling only the reservoir. A shell and tube heat exchanger was added in the return line on top of the reactor to augment cooling. With a capacity of 60 kW, this heat exchanger uses liquid nitrogen in the U-tube and perfluoropolyether fluid inside the shell. Pressure drop across the heat exchanger is approximately 5 psi (260 torr). The heat exchanger's location on the return line allows the maximum driving force, or temperature differential, between the liquid nitrogen and the perfluoropolyether fluid.

Reactor. The main reaction occurs in a 26 gal (100 l) glass-lined, agitated vessel. Perfluor-opolyether fluid is circulated inside an external jacket.

Rotovap Evaporators. Two rotovaps are used to evaporate solvents in the bulk product.

Ridge Vent Condenser. This condenser is used to remove volatile organic chemicals (VOCs) before the gases are vented to atmosphere. The condenser operates between -40 and -112^oF (-40 and -80^oC).

Pipes and Fittings. The system contains about 1,000' (approximately 305 m) of 3" (7.6 cm) dia. pipeline. The pipes are stainless steel and have welded joints wherever possible. Graphite gaskets are used where needed.

The heat transfer fluid reservoir can be located in a general work area because the fluid does not present an explosion hazard.

Application Assessment

Safety. Because no fire or explosion hazards are encountered with these fluids, the reservoir can be placed in a general process area without requiring explosionproof components and rooms. Other heat transfer fluids such as silicones and mineral or synthetic oils may have required that the reservoir be placed in an explosionproof room.

When performing maintenance work, Eisai's technicians simply isolate the section of interest, drain the perfluoropolyether fluid completely and carry out the required maintenance work, including welding. This saves a lot of downtime. If a different type of heat transfer fluid were used, the lines would have to be drained and cleaned thoroughly to remove traces of fluid residue to avoid fire and explosion hazards, which could increase downtime.

Wide Operating Temperatures. The system was designed to operate between -112 to 158^oF (-80 and 70^oC). In fact, the system has been validated for operation at -121^oF (-85^oC), which is 9^oF (5^oC) lower than the design temperature. Eisai plans to test and validate the system at temperatures up to 194^oF (90^oC) and at elevated pressures, should the need arise. Thus, a single fluid could be used to operate at low and high temperatures, increasing operation flexibility and eliminating the need (and expense) of installing another system to operate at two different temperature levels.

The perfluoropolyether fluid used in this system has a normal boiling point of 158^oF, but it can be heated to 194^oF by operating the system at higher pressures. Increased system pressure also would help to reduce the degassing of the dissolved nitrogen in the fluid.

Chemical Inertness. During a purification process, the perfluoropolyether fluid leaked into the reactor due to a defective rupture disk. Thanks to its chemical inertness and its immiscibility with nonfluorinated materials, the fluid was removed completely from the pharmaceutical product by simple evaporation. This allowed the pharmaceutical manufacturer to avoid reprocessing contaminated material, which would have added approximately four months to the cycle.

No Rusting. Since system startup, no rusting or corrosion has been observed. In another system using propylene glycol, some corrosion has been observed.

Aggressive Chemical Environment

Phosphorus trichloride reacts violently with water. To prevent any risk of steam entering the distillation column, an indirect heating system is employed. In this system, steam at 235 psig (approximately 15 atm) heats the heat transfer fluid, which then is pumped through the reboiler to heat the products to be distilled. The heat transfer fluid used in this indirect heating system had to meet the following requirements:

• Chemically inert to phosphorus chlorides and oxygen.

• Capable of operating at temperatures around 400^oF (205^oC).

• Suitable for use in glandless, magnetically driven pumps.

• Compatible with materials of construction of the heating circuit.

The perfluoropolyether fluid satisfied all of the process requirements. Engineers carefully designed the circuit to minimize the working inventory and the risk of fluid spillage.

Heat Transfer System. The heat transfer circuit consists of a column reboiler, steam heater, expansion tank, drain tank and circulating pump. All components in the system, including piping, are 316 stainless steel, except the column reboiler, which is Hastelloy. Heat transfer capacity is 340 kW, and the system contains 96.2 gal (370 l) of the perfluoropolyether fluid. The active volume, excluding the expansion and drain tanks, is 72.8 gal (280 l).

The heater and column reboiler are welded plate exchangers. The outer casing of the pump enclosing the magnetic drive was fitted with an ultrasonic level switch to detect can failure. When activated, this switch closes the automatic valves on the suction and delivery and trips the motor. A power monitor also trips the motor if the pump is dead headed or running dry.

A computer controls the heat transfer system, monitoring and sequencing all operations, including:

• Filling from the drain tank, with the balance venting from high points back to the tank.

• Warming up, including venting of dissolved gases into the expansion tank.

• Normal running.

• Quick reboiler drainage for rapid distillation column shut down.

• Total drainage of the circuit.

Appropriate automatic isolation and control valves as well as level and temperature measurement are provided for these operations.

The expansion and drain tanks are padded with dry nitrogen to exclude moisture, and a relief valve discharges to atmosphere. The whole system is mounted above ground level so the fluid can be drained completely into dedicated stainless steel storage drums. To avoid spillage, the drums are never completely filled. The fluid is transferred from the storage drums into the drain tank by applying vacuum to the drain tank and sucking in the fluid through a hose provided with a strainer.

The system has met all the requirements and has been in operation for four years without any reportable problems.

Perfluoropolyethers are used extensively as heat transfer fluids in equipment employed during semiconductor manufacturing due to their combination of characteristics such as dielectric strength, resistance to microwaves, nonflammability and thermal stability. The two case histories show that these fluids can be used effectively in other industries where operating conditions can vary from extremely low temperatures to aggressive environments at high temperatures.