Description

Acetyl-salicylic acid is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system. But still a very large part of the world’s population has inadequate or no access to such essential and life-saving medicines like acetyl-salicylic acid. In the following I will research a chemical synthesis route for acetyl-salicylic acid, which is feasible by everyone, everywhere, using a lab-on-a-chip system or a chem printer.

Details

The basic idea

In common syntheses of aspirin, salicylic acid is treated with acetic anhydride, causing a chemical reaction that turns salicylic acid's hydroxyl group into an ester group. Because acetic anhydride is used for the synthesis of heroin by the diacetylation of morphine, acetic anhydride is listed as a U.S. DEA List II precursor, and therefore it is restricted in many other countries including mine, so I won't use it. Instead I'll follow a slightly different path as a starting point:

As acetic acid is less reactive than acetic anhydride, the reaction yield will be lower. Furthermore the purity level of the acetyl-salicylic acid will be lower.

Balanced equation:

$\color{White} \large C_7H_6O_3+C_2H_4O_2 \rightarrow C_9H_8O_4+H_2O$ Molar mass salicylic acid: 138.122 g/mol

Molar mass acetic acid: 60.052 g/mol

Molar mass acetyl-salicylic acid: 180.157 g/mol

Molar mass water: 18.015 g/mol

Theoretical yield:

138.122 g salicylic acid + 60.052 g acetic acid → 180.157 g acetyl-salicylic acid

But I expect the actual yield will be only half of the theoretical one.

Synthesis of aspirin at a laboratory scale

Measure 1 g of salicylic acid ( ± 0.01 g)
Place it under fume hood into 50-ml Erlenmeyer flask
Cover salicylic acid crystals with 2 - 2.5 ml glacial acetic acid
Swirl flask and add 2.5 drops of concentrated sulfuric acid
Heat flask gently in a 70°C hot water bath for 10 minutes

Remove flask from water bath, add 15 ml distilled ice water
Allow mixture to stand for 5 minutes
Chill solution in an ice bath until crystallization of aspirin occurs
Stir occasionally
If crystallization does not occur, scratch walls and bottom of flask with a glass stirring rod to promote crystallization
If an oil appears instead of a solid, re-heat flask in hot water bath until oil disappears and cool again

Set up a vacuum filtration apparatus with Hirsch funnel
Transfer solid aspirin onto filter paper
Add small amounts of distilled ice water and repeat until transfer of aspirin crystals is complete
Wash aspirin crystals on filter paper with 10 ml of distilled ice water
Pour filtrate in the sink

Transfer aspirin crystals from filter paper to a 100-ml beaker
Dissolve crystals in a minimum volume of 10 ml pure ethanol
Warm solution in a 60°C hot water bath
Pour 25 ml distilled water into solution after solution has reached 60°C
If a solid forms, continue warming until solid dissolves

Remove beaker from heat
Cover beaker with a watch-glass
Set beaker aside to cool slowly. Do not disturb solution
Needle-like crystals of pure aspirin should form overnight

Testing for Impurities

Iron(III) chloride can be used to determine the purity of the synthesized aspirin. Iron(III) chloride forms a purple complex with the phenol group. Salicylic acid is a phenol. It cannot be removed by using cold distilled water as its solubility in water is poor. So if salicylic acid is still present, the product will turn purple when Iron(III) chloride is added.

Synthesis of salicylic acid at a laboratory scale

Salicylic acid can be synthesized by a base-catalyzed hydrolysis of methyl salicylate, commonly known as oil of wintergreen or wintergreen oil:

Balanced equation:

$\color{White} \large C_8H_8O_3+2~NaOH+H_2SO_4 \rightarrow C_7H_6O_3 + Na_2SO_4 + CH_3OH + H_2O$ As we can see, side products are water, sodium sulfate and methanol. The hydrate of sodium sulfate is known as Glauber's Salt, a formerly used general purpose laxative. Methanol is the simplest alcohol and highly toxic.

Molar mass methyl salicylate: 152.15 g/mol

Molar mass sodium hydroxide: 39.9971 g/mol

Molar mass sulfuric acid: 98.079 g/mol

Molar mass sodium sulfate: 142.04 g/mol

Molar mass methanol: 32.04 g/mol

Therefore theoretically:

152.15 g methyl salicylate + 79.9942 g sodium hydroxide + 98.079 g sulfuric acid → 138.122 g salicylic acid + 142.04 g sodium sulfate + 32.04 g methanol + 18.015 g water

Lab synthesis procedure:

Set up water jacketed condenser apparatus with 50 ml round bottom flask
Pour 3.5 ml of distilled water into the flask
Add 0.448 g sodium hydroxide
Swirl until solid dissolved
Add 0.23 ml of methyl salicylate to the NaOH solution
Drop boiling stone to bottom of flask
Attach...

Components

1 × Sulfuric acid 96%

1 × Sodium hydroxide

1 × Methyl salicylate

1 × Deionized water

Project Logs

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Synthesis of salicylic acid

M. Bindhammer • 08/08/2015 at 13:30 • 0 comments

My lab in Germany is ready for small chemical experiments. I still do not have a water jacketed condenser apparatus, so I tried it without, see Stage 2 video.

Synthesized salicylic acid, the chemical precursor for Aspirin:

3-D printing Aspirin?

M. Bindhammer • 05/19/2015 at 09:14 • 0 comments

Salicylic acid sublimes at at 76 °C. This makes it easy to vapor coat a kind of hot bed with salicylic acid. A ball pen like extruder moves then over the thin layer of salicylic acid and dispenses acetic acid/catalyst to form a layer of acetyl-salicylic acid.

We can use solvents as well to dispense solid substances equally on a plane surface. We do that every day, writing notes on a paper, painting...

A simple 'chemical ball pen'. A cleaned ball pen tip (0.5 mm) was glued into the tip of a 2.5 ml syringe with 2-component 5-minutes epoxy resin adhesive. Now we can dispense any chemical on a carrier:

Word 'Hackaday' written on a microscope slide with NaCl crystals. I used saturated NaCl solution with a drop of dish soap to reduce the surface tension of water.

Lab-on-a-chip synthesis of Aspirin?

M. Bindhammer • 04/30/2015 at 07:04 • 0 comments

Complete aspirin synthesis lab: reaction apparatus with heating element, water/oil bath, flask and Allihn condenser, funnel with vacuum filtering flask...

Power supply/measurement unit added:

Discussions

helge wrote 01/08/2016 at 02:40

This project made me research a little and since there's not much going on here right now let me take the liberty to elaborate.

It seems most likely that where simple meds like Aspirin aren't available, proper lab conditions and reagents of sufficient quality are also not available. So as long as you can grow willows - which are fairly robust - and get powdered silica it is possible to brew a watery extract of willow bark (which has around 1% salicin) and extract the salicin by column chromatography (required to get rid of the tannins).

Salicin will be metabolized to salicylic acid by gut microbes and that's it. It lacks the boost in efficacy caused by the acetyl group but that's as sustainable as is possibly gets with growing shrubs and filtering tea through ground rocks.

Now if we could only find a nifty way to get that acetylation going. Some fungus or bacterium that can pull of acetyl transferase action perhaps? Sadly not really my field of expertise.

---------------------

https://bioweb.uwlax.edu/BIO203/2011/girard_stev/habitat.htm

Periodic Videos on youtube: v=amTAuK25P6c

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M. Bindhammer wrote 01/22/2016 at 18:35

There is a lot of going on here, but I didn't post my results yet. Please stay tuned! Will rework this site soon.

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Peter Walsh wrote 06/16/2015 at 18:46

Have you received the prototypes I sent? I'm curious to know how they turned out.

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M. Bindhammer wrote 06/17/2015 at 04:22

Received but still no time to work on it, Peter.

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i.abdalkader wrote 06/16/2015 at 17:21

We need to cook...

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jens.andree wrote 05/10/2015 at 01:11

What a cunning contraption! I really don't like all the mega-corporations that charge way too much for products that cost very little to manufacture, with the results that it's unavailable for those who can't afford it...

This is the reason why I'm here with my project and it makes me very happy to see others flying the same flag! Particularly the medical industry (whether it's medicine, therapy, tools (autism e.g)) they tend to charge 1000 times or more than it costs to produce, and that's just wrong!

You kind sir certainly have my vote! Meds-on-the-fly!

Thank you for subscribing to my little project as well. It helps to spread the word and thus making it reality in the end :)

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Owen Trueblood wrote 05/09/2015 at 18:40

Have you considered using PDMS for your lab-on-a-chip? It's pretty much the standard in academic work on microfluidics nowadays so there's lots of good information on using it available. And its properties make it perfect for what you are doing - it stands up very well to heat and most chemicals. I suspect it might be better suited to the task than laser cut parts that might leak, react, degrade, or contaminate.

If you haven't encountered it before, the basic procedure is: 1) Make your design as an image on a computer. 2) Print the design on an overhead transparency with a wax printer (I've also used laser cutter to etch acrylic with some success). 3) Put the printed design in a container and pour on your PDMS. 4) After curing finishes peel off the print from the PDMS. 5) Treat PDMS and a glass slide with oxygen plasma to remove organic surface contaminants (not as hard as it sounds - coronal discharge from high voltage works fine, or you can use a regular microwave to make the plasma). 6) Stick the PDMS down on the glass slide. 7) Done! Now you've got a very robust lab-on-a-chip. Poke some needles into it to supply and drain your chemicals.

I've played around with microfluidics for fun and have collected a lot of tidbits of information. Would love to offer them up if you'd find them useful. Just send me a message.

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Dylan Bleier wrote 05/09/2015 at 19:42

PDMS is good but it's mechanically weak and not as chemically inert as other materials like glass or fluoropolymers. So it might be good for one-time use. The connectors can get ripped out easily and block the channels or cause it to leak, and I don't think you can make really small diameter channels with it reliably.

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Owen Trueblood wrote 05/09/2015 at 20:54

Yeah I agree those are drawbacks worth considering. I've never made anything with it that was meant to stay around for a long time. But machining glass seems really hard? Are you thinking about etching it?

I've never worked with fluoropolymers. Are you thinking of using a CNC to mill the apparatus features into the material?

The feature size I've reliably gotten with PDMS using DIY stuff is ~50 um. But it can mold itself around individual molecules and retain the shape. So the difficulty is usually in producing the pattern. Though I'm sure your project doesn't need features anywhere near that size - I just think it's pretty neat.

Good luck! I'll be following along with interest.

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Dylan Bleier wrote 05/10/2015 at 00:59

from what I know glass or quartz glass is etched with HF over a mask of some sort, and then multiple layers are fused together. I think most polymers or aluminum can be CNC'd using extremely small, delicate end mills. Or maybe a pattern could be made with a metal die, and then you could use it in a heated press to injection mold a whole bunch of chips.

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Owen Trueblood wrote 05/10/2015 at 01:41

HF is really scares me. I've heard of it being used to take oxide layers off of silicon dies in reverse engineering (something I'd love to try) but I don't want to melt my bones out. If you have courage and go that route I've heard that you can obtain it from places that supply dentists - lower concentration HF in gel form is used in dental surgeries for etching fixtures.

Using a die to manufacture on a large scale is a really cool idea. I think that's how CDs are made, and the dots there are smaller than a micron. Actually, I wonder if you could press a microfluidic system into the bottom of a CD? That would be fun to try.

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Peter Walsh wrote 05/10/2015 at 08:25

HF comes in a cream for hobbyist use. I've used it to etch glass, it's a little safer than the raw acid.

Gloves and clean work area seemed to work well for me. Also, I used a silk screen to apply the pattern. HF didn't touch the pattern, and patterns are easy to make with photographic methods.

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Dylan Bleier wrote 05/10/2015 at 10:13

Yeah I wouldn't use HF without calcium gluconate gel on hand, and I'd be extremely careful.

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M. Bindhammer wrote 05/10/2015 at 13:50

Yes, stay safe!

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M. Bindhammer wrote 05/09/2015 at 23:54

Thank you, sir. I am always interested to learn. Would be quite useful for my medical tricorder project where I want to add a LOC too.

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Peter Walsh wrote 05/07/2015 at 02:52

I'm pretty handy with the laser cutter at my hackerspace.

If you want, I will run up a design, cut out a few, and send them to you gratis. I don't foresee the design work taking more than 2 hours, and it'll free you up for other tasks.

Contact me if you're interested.

(P.S. - Awesome project!)

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M. Bindhammer wrote 05/07/2015 at 03:14

Wow! Thank you very much, Peter! Yes, I am interested :) What kind of material do you want to use? The unit containing the flask, condenser and heater should be heat resistant.

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Peter Walsh wrote 05/07/2015 at 04:07

Check your messages, under "menu" from your Hackaday.io page.

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Dylan Bleier wrote 05/05/2015 at 00:37

Fuck the DEA. Acetic anhydride is the proper way to do this. I'm so angry that you can't get the chemicals you need.

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counter.culture wrote 05/07/2015 at 22:55

that's the spirit!!! they can't have the slaves running around making their own medicines...or food...or alcohol...or just about anything you can think of.

welcome to the prison planet.

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M. Bindhammer wrote 04/27/2015 at 15:18

Thanks. I am using ChemSketch and Accelrys Draw 4.0. Both freeware

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Jake Robinson wrote 04/27/2015 at 13:40

You have by far some of the best detail sections on you projects. Especially the lab setup diagrams. How did you make those?

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Aspirin for everyone

Description

Details

The basic idea

Synthesis of aspirin at a laboratory scale

Testing for Impurities

Synthesis of salicylic acid at a laboratory scale

Components

Project Logs

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Synthesis of salicylic acid

3-D printing Aspirin?

Lab-on-a-chip synthesis of Aspirin?

Discussions

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Aspirin for everyone

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Synthesis of aspirin at a laboratory scale

Testing for Impurities

Synthesis of salicylic acid at a laboratory scale

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