[ProdigyLee]

Hi, I'm currently doing an undergraduate study and is currently working on an assignment.
The below is copied directly from my assignment brief.
"The aim of this project is to design an efficient process for the synthesis, isolation and
purification of Aspirin. You may assume that you are a member of a design team
employed in a design company. The work of your team will be assessed to prepare a feasibility study and a detailed design report for aspirin production, specifically to design and optimise a process, which can then be put
into full scale production by the company by 2013."


The details after were quite vague so I began to list things I may have to take note of, please help me by adding in your own ideas or correcting me on any incorrect information.
I've only looked into what I've listed so far (so ideas are here but most of the information I have isn't here)
We're only in the concept phase so ideas would be great. Specifications are welcome too anyway and will help us later on.

PROCESSING/SYNTHESIS
-Result/expected product. purity and yield.
-Will/Should we consider Recrystallization for purity?

-Reactants required to produce.
The most basic is Salicylic acid and Acetic Anhydride, taking into account that using Acetic acid will produce water (promoting reverse reaction)
Catalyst, Sulphuric acid chosen over Phosphoric acid. My friend said that Sulphuric acid can be more concentrated/pure, meaning less water in solution.

-How can unused material be recycled?

-Some Reactions are performed at 90'C, What kind of fuel will the heat source come from?
Our teacher advised that Fossil fuels(Coal).

-Speed of processing. How long will it take for each cycle? How much would it yield?

MACHINARY AND STRUCTURES(Not sure what to title this):
-What material should the structures be made of?
They should be able to contain all materials used (noting some are strong acids)

We're to include a process flow diagram but it's a work in progress because we're adding things in bit by bit.
But mostly in contains:
*Containers of used reactants
*Where reactions are being performed.
*Mixers and Seperators(Filters)
*How/Where components are monitored


This is all I have so far.
Like I said before, we're only in the concept phase so ideas would be great. Specifications are welcome too anyway and will help us later on.

Sorry if this is vague/unorganised.

[fledarmus]

One thing you need to consider when you start scaling up any reaction is the heat flow. Are the reactions exothermic or endothermic? If endothermic, how much energy do you need to add? If exothermic, how are you going to get rid of the energy so your reaction doesn't explode?

[discodermolide]

Waste disposal is also crucial.

Safety, for example, what can happen if the mixture is left standing for any length of time, can it decompose?
What happens if too much or too little of a reagent is added?
What happens if all your solvent evaporates off during a cooling failure?
What happens if the stirrer stops? Can you safely re-start stirring?
You need to ask and answer questions like that and do a complete safety analysis and thermal analysis of the starting materials, reaction mixtures, and product (that have not been thermally stressed).
Separation of incompatible reagents.
Correct identification of reagents.
Detailed plant procedure and so on.
What about worker exposure and protective equipment?

Polymorphs, what happens if you obtain a different polymorph?
Drying of the product, static drying or are you going to paddle dry it.
It it stable to the drying conditions (safety)
Particle size (milling) again is it stable to the conditions, safety.
Bulk density

[ProdigyLee]

Thank you very much for all your input, it is very helpful.

Heat flow-
Since the reaction to form aspirin is exothermic, keeping a stable temperature will be important.
I'm not sure what kind of heat exchanger I can use.
I was thinking of a refrigeration unit but I still have to look into something but that operate at temperatures around 90'C compared to regular fridges working at Room temp.

Polymorphs-
I did find an article about the differences in using a polar or non-polar solvent.
I've decided to go with a polar solvent.
Their example used ethanol but I always read that Ethyl Acetate is the best option as a solvent.

[discodermolide]

Thank you very much for all your input, it is very helpful.

Heat flow-
Since the reaction to form aspirin is exothermic, keeping a stable temperature will be important.
I'm not sure what kind of heat exchanger I can use.
I was thinking of a refrigeration unit but I still have to look into something but that operate at temperatures around 90'C compared to regular fridges working at Room temp.

Polymorphs-
I did find an article about the differences in using a polar or non-polar solvent.
I've decided to go with a polar solvent.
Their example used ethanol but I always read that Ethyl Acetate is the best option as a solvent.

The reaction exotherm should not be a problem as long a you use a high boiling solvent. The exotherm will be removed by heating the solvent to reflux. The only problem is  making sure you have enough solvent so that if your cooling system fails you won't loose a significant amount.
Ethanol is better than ethyl acetate. The latter is too reactive and undergoes transesterification reactions.
You need 100% ethanol, no denaturants, as they tend to get included in the crystal and you can't get them out. And it increases the work for the analytical people, so 100% ethanol.

[eazye1334]

Are you planning to use a CSTR, PFTR, or a batch operation? Also, whenever possible, try to conserve energy use by designing in a manner that will allow you to use the energy in one flow stream to heat another flow stream and vice-versa. If you can figure out a way, use that exotherm to your advantage to recycle some heat.

And, as discodemolide already said, never forget about waste treatment. Too often I've seen people try to design a system and focus on the reaction itself making the products but then have absolutely nothing in place to deal with any waste disposal. It's really a sign of your thorough consideration and thoughtfulness if you include something to address the inevitable waste accumulation.

[ProdigyLee]

The reaction is exothermic, the problem we currently have is that we need a solvent that has a boiling point over 95'C which is the temperature the reaction is happening at.
 
EDIT: "Changing operating temperature of reactor to 70'C(under ethanol Boiling point)
Crystalliser operating temperature to udner room temp (mayeb 20'C)."

Currently, We planning to make it a batch process at first because we're not sure how fast each component works.

About waste management
We are using 2 filters which will collect the solvents after they are used.
The first filter is after Crystalliser (straight after the Reactor) which will seperate the impure aspirin from the mixture.
 The mixture collected will contain:
-Solvent
-Unreacted material
-Catalyst.

The impure aspirin will enter a slurry tank which will be filled with water(room temperature or cooler). The water will dissolve everything but the aspirin (including the solvent if it is polar).
Then this second mixture will be sent to a second filter which will remove the aspirin(hopefully pure) from the second mixture.
The second mixture will contain:
-Water(mostly)
-Any dissolved material found in the first mixture.

About heat management:
The reactor is operating over 95'C and the crystalliser we're still unsure but want it to operate under 50'C.
Since these processes happen one after the other, we're thinking about how we can use a heat exchanger which will tranfer heat:
-From between the Reactor and Crystalliser.
-To the Drier at the end after the second filtration (dries pure aspirin)


Thank you very much guys
'Safety First' is important so yes it will discussed when we start thinking about employees operating.
For now, we're still planning

[discodermolide]

Use toluene, BPt. 110°C
Do not fiddle around with the crystallisation temperature. You may get polymorphs, change the particle size, bulk density of the product etc.

[ProdigyLee]

I'll, discuss with our group about using Toluene for a solvent because of it's higher BPt.
But like you said about looking into the polymorphs, using a non-polar solvent will give us a different polymorph of solid aspirin.
I also wanted to ask: Will changing the solvent cause a change in the amount of aspirin produced?

[discodermolide]

I'll, discuss with our group about using Toluene for a solvent because of it's higher BPt.
But like you said about looking into the polymorphs, using a non-polar solvent will give us a different polymorph of solid aspirin.
I also wanted to ask: Will changing the solvent cause a change in the amount of aspirin produced?

Actually a polymorph of aspirin was only recently discovered!
But you should treat this as if there was the possibility of polymorphs.
Changing the solvent may well change the yield, you may need a more concentrated reaction mixture or may need a solvent change etc.

[curiouscat]

Use toluene, BPt. 110°C

What prevents water from being used as a co-solvent to get rid of the heat by reflux?

[discodermolide]

Use toluene, BPt. 110°C

What prevents water from being used as a co-solvent to get rid of the heat by reflux?

Nothing. Except you may be going from a suspension to a suspension, so reaction control is then vital to know when it is finished, otherwise you will get product mixtures.
I have no idea if this reaction works in water.

[amir885]

Have you  got any idea about the material selection for equipments of Aspirin production ? I'm looking for it.

[discodermolide]

Have you  got any idea about the material selection for equipments of Aspirin production ? I'm looking for it.

Use enamelled reactors, as you have conc. sulphuric acid as well as other corrosive materials. Transfers with glass or hasteloy piping.
You can filter the product with a pressure filter or use a centrifuge. Drying in a standard oven under vacuum.
Watch out for electrostatic solids.
That's about it really, pretty standard equipment.

[ProdigyLee]

The use of water as a solvent will cause a reverse reaction.
Areas of high pressure, will it affect where using glass piping is appropriate?

We are planning to use fractional distillation to seperate:
-water
-unreacted materials (acetic-anhydride, salicylic acid)
-Catalyst(sulfuric acid)
-by-product(acetic acid, in the sense that it's not going to be used for 'this' process)

Will there be any problems to the seperation such as difficulty maintaining a specific chemical compound after it is condensed?
(I'm not sure hot to say it)
Will any compounds have trouble condensing back after evaporation?