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FOR ORGANIC CHEMISTS:

Pure Synthetics' unusual
synthetic method for MCP

 Essentials of new method posted:
November 7, 1998, 11:00am Pacific Time
       Latest update: August, 2008
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Incorporated in 1973 and dissolved in 1995, Pure Synthetics, Inc. made and marketed the maple-flavoring chemical variously called MCP, Cyclotene (an old Dow trade name) or methyl cyclopentenolone (formal name: Tautomeric forms of MCP3-methylcyclopent-2-en-2-ol-1-one). Its animated structure given on the left shows it to be a mixture of tautomers of 3-methyl-1,2-cyclopentanedione. In the solid state, it exists completely as the 2-en-2-ol-1-one, the most stable enol, and is colorless. Solutions in water or other protic solvents become yellowed after a short time as an equilibrium mixture forms between the enol forms (colorless) and the diketo form (yellowish). The enol tautomers are relatively stable because dipolar repulsion of the small-ring 1,2-diketone is relieved when the molecule enolizes.

MCP occurs naturally in coffee, cocoa, and fenugreek after the roasting process. Also it is the principal maple flavoring in natural maple syrups being formed when the maple tree sap is concentrated. The rules of the FDA require that syrups with imitation-maple flavoring not contain the word "maple" in their names: Log Cabin, Mrs. Butterworth's, etc. However, every one of these syrups do contain MCP either from added MCP or some other flavor ingredient like roasted fenugreek which contains MCP. Pure MCP has a sweet maple or licorice taste and possesses flavor-enhancing properties. I always thought that a chocolate milk shake with a dash of MCP had a wonderfully rich taste. It is used in food products at the rate of about 10 parts/million.

For much of the time between 1974 and 1990, with its plant in Paterson, NJ, Pure Synthetics, Inc. was the only domestic prime manufacturer of this pure flavor chemical. Its product was acclaimed for its high purity---achieved by a simple but imaginative new distillation method developed at Pure Synthetics ( See our NEW PURIFICATION for volatile solids.

Pure Synthetics' method follows:

  Dimethyl glutarate plus diethyl oxalate

3,5-dicarbalkoxy-1,2-cyclopentanedione


 

   

  MCP structure

 

  Product of methylation



Please note that in this discussion of the details of this process, I will omit the exact weights and volumes in most cases. I will try to fill these in as soon as I can:

Contribution from the R&D Laboratory of Pure Synthetics, Inc. (corporation of New Jersey now dissolved)
"A New Method to Prepare 3-Methylcyclopent-2-en-2-ol-1-one Commercially"
By J. S. Paul Schwarz & Helen K. Schwarz (deceased)

Disclaimer: The procedures described below, while detailed in many ways, are still incomplete. I hope to give more details as time goes on until there will be detailed directions of these processes. However, be advised that I give this and subsequent information at no charge with no warranties expressed nor implied that this procedure will either work or be safe since I have no control over who might be trying to use the method nor over the quality of the chemicals that might be employed. The user is responsible for determining the fitness and safety of the method in his or her own particular case.

It would be well to send an e-mail to me (organichem@aol.com) if you plan to actually pursue any of these ideas, for then I can alert you to future updates of this page like the warning I put up on Nov 30, 1998 about the mysterious flammable waste gas generated in the first reaction.


1 - The double Claisen condensation of diethyl oxalate with dimethyl glutarate was already known early in the 20th century. Because this product (isolated as the disodium salt) was so impure, we did not try to alkylate it directly. Parenthetically, the disodium salt is insoluble in every solvent we tried with the exception of water. The usual practice described in the old German literature was to dissolve the disodium salt of the condensation product in water and to acidify the resulting solution to give the desired 3,5-dicarboalkoxy-1,2-cyclopentanedione (top, right-hand structure). I give it the ambiguous ester name of dicarboalkoxy- because the starting materials were dimethyl glutarate, diethyl oxylate, sodium methoxide using methanol as solvent. Some transesterification undoubtedly occurs rendering the product as an outlandish mixture of mostly the dimethyl ester but containing some mixed ester and a little diethyl ester. You may justifiably inquire as to why we didn't use dimethyl oxalate to insure getting a pure dimethyl-ester product. Well, dimethyl oxalate is not available commercially in drum quantities. The reason is that it is a solid at room temperature making diethyl oxalate (a liquid) more desirable commercially. Liquids are much easier to handle in chemical processing than solids. We, ourselves, always strove to design a synthesis with as many liquid intermediates (or solutions) as possible. Our dream synthetic method for any of our four products would have no solid reaction products until the last step and then only because our four flavor-chemical products are crystalline solids at room temperature.

WARNING: One of the waste products of this reaction is a FLAMMABLE gas which is almost certainly carbon monoxide. I believe it comes from slow decarbonylation of the alpha-keto ester intermediate (first-step condensation product).

Indeed, Dickens & coworkers [J. Chem Soc. 121, 1496 (1922)] report that they isolated this intermediate and that it decomposed completely to the triester and carbon monoxide upon attempted distillation.

It is not ethylene (ethene) because it doesn't decolorize bromine water. This gas evolution was not mentioned by Dickens & coworkers or in any other of my literature references to this reaction. I just noticed that the reaction mixture appeared to be "gassing" or, in other words, forming a gaseous product. This is a rather subtle thing that might be missed if you work on a millimole scale. Conduct the reaction in a hood or with other suitable venting.

In practice, we only ran the first-cycle reaction amounts to start out the winter's campaign, the remainder of the reactions being recycles. I will describe the recycle conditions. We almost half-filled each of our four 72-liter, 4-necked flasks with filtrate saved from the previous isolation of disalt double Claisen product. To this slurried filtrate, we added two moles of powdered sodium methoxide/mole of diethyl oxalate & dimethyl glutarate mixture (to be added later) raising the temperature of the slurried mixture. The premixed esters were then added at such a rate to raise the slurried mixture to reflux and maintain it thus until all the esters were added, whereupon the heat could be turned on the 72-liter, 220-volt heating mantles (but 110 volts applied to each heating mantle were sufficient to maintain a slow reflux). After four hours of reflux, the heat was turned off and the stirring continued while the contents cooled naturally (plant is close to freezing) for several hours. The stirring was terminated with the contents still somewhat warm, for the sodium disalt is very insoluble in even hot methanol. At this point, the contents were pumped into 50-gal filters known to engineers as nutsches and to laboratory chemists as Buchner funnels ---the contents of two flasks into each nutsch.Four 50-gal polyethylene nutsches (Buchner funnels) The photo to the right shows four such nutsches being prepared for the winter campaign. The one in the foreground is brand new; thus, it is still very white. The machine seen on the right with the two big blue "ears" is our air-pressure powered diaphragm pump used to pump the slurry from the flasks into the nutsches. It required about five minutes to empty each flask. The diaphram pump was then cleared of slurry by pumping several gallons of fresh methanol through the pump and into one of the nutsches. Then two five-gallon bottles were filled with fresh methanol for use the next day as wash. The next morning, vacuum was applied to the nutsch (mixture now cold) to remove the mother liquor. The wash was poured on; allowed to soak; and sucked through. To obviate cracking of the cake, we routinely used 40-inch square pieces of gum rubber dental dam as covering on the round nutsches, the dam being held in place with a circle of rubber (bicycle inner-tube). You removed this "rubber band" by grabbing on the fill-stem of the inner tube. (Never fear, the tubes had lost their value to the bicyclist because they were unrepairable.) The crude disalt condensation product was then ready for partial purification.

We effected the needed partial purification of this condensation product by converting the solid disalt product to free diester. We soon discovered that about 5% of the yield of disalt is destroyed when it is added to water. This is explicable because no organic reaction goes totally to completion; therefore, the little sodium methoxide left over forms some sodium hydroxide to saponify the esters or reverse the condensation. After the small amount of base is used up, this destruction stops. First Trick: The solution was to charge a portion of the dilute sulfuric acid to the water prior to adding any of the anhydrous disalt. The sulfuric acid instantly neutralized any excess base protecting the reaction product from any destruction. We alternated the additions of disalt and acid to the stirred slurry until almost half of the acid had been added. At this point, we added the remainder of the disalt and continued stirring until complete solution was effected. We had at this point essentially a solution of the monosalt at a pH of around 9 where the condensation product was reasonably stable. The monosalt is much more soluble than the disalt in water or in other polar solvents. We would then add the remainder of the sulfuric acid (to pH 2 using pH paper) to precipitate the white, powdery (when dry) diester.

30-inch Wooden Plate and Frame Filter PressWe pumped this slurry into our 30" wooden plate-and-frame filter press (a real antique) to isolate the wet cake. In the photo on the right, as an additional gauge for the scale, I colored my meter-stick red. In addition, the 24 plates and frames were about 30-inches square. We used polypropylene filter cloths which we made ourselves: you can see our second set hanging on the wooden saw-horse to the right of the press. This cast iron behemoth weighed 1000 to 2000 lbs.

At first, we had tried to use the raw mono-salt solution described above in the methylation step, but there were too many impurities to give a successful result. The purification achieved by isolating the diester product (water-wet filter-press cake) was considerable. In the laboratory, we did dry this cake for control purposes. Based on starting materials (diethyl oxalate and dimethyl glutarate), we obtained about 65%. Hesse and Buecking [Ann. 563, 31 (1949)] reported the same yield using slightly different reagents and conditions. Dieckmann [Ber. 27, 965 (1894)], who gave his name to this type of ring closure, reported running this reaction (all-ethyl derivatives) and purifying the product but didn't give a yield. In a later publication, Dieckmann [Ber. 32, 1934 (1899)] did report obtaining an 80% yield of pure product. However, other old German literature always claimed about 90% yield in this reaction using all ethyl esters, sodium ethoxide and ethanol solvent. We never tried those exact reagents because ethanol, diethyl glutarate and sodium ethoxide are not inexpensive. Parenthetically, making sodium ethoxide from ethanol and sodium would still have been expensive as well as dangerous - - - HYDROGEN! - HINDENBURG! (Incidentally, our plant was about 5 miles from Lakehurst, New Jersey!)

 

2 - The methylation in the older literature was usually done in ethanol using sodium ethoxide to form the enolate followed by treatment with a methyl halide (usually iodide). Second Trick: We used less costly reagents: sodium hydroxide(!) and water(!!). Sodium hydroxide delivered to our plant in tankers as 50% aqueous solution cost on the order of 2 cents/pound and the water - - - well, it came out of the tap.

The idea that we could alkylate this intermediate in water using NaOH as base came from the realization that the monosalt was very stable over the course of many hours in water solution as long as the pH was not higher than required to form the monosalt: pH 9. The Russian chemist Knunyants (spelling approximate) [Zh. Obsh. Khim. 7, 2832 (1937) (in Russian)] described how he alkylated a simple beta-keto ester in water using dimethyl sulfate and sodium hydroxide. Nobody took any note of this because chemists used to scoff at Russian chemistry. About 20 or more years later, another Russian tried to repeat the results of Knunyants and failed. I figure that Knunyants was just ahead of his time, for the pH meter wasn't invented by Beckman until about 1937 or '38, and it was the availability of the pH meter which made our synthetic method possible! Because of extensive destruction of the dimethyl sulfate in the high pH aqueous solution, we used about two moles of dimethyl sulfate for each mole of intermediate.

Now a word about temperature! My personal view of plant-scale chemical processing is that the major problem that the operator has to deal with is HEAT-TRANSFER. Almost everything that you do in a chemical-process plant involves heat transfer: you are heating something up; you are cooling an exothermic reaction so that it doesn't get away from you; or you are cooling something down to effect crystallization. In this case, the methylation is highly exothermic. We had to control the temperature because the yield is lowered if the temperature goes much above 20 degrees-C. In fact, if you don't control the temperature you could get the boiling point!

We soon discovered that the dead of winter in New Jersey was the best time to run this reaction. Actually, everything went so much better in the dead of winter that we soon ran the plant to make this product only from November to March, inclusive. You may be surprised to learn that we never turned on the heat inside the plant building during these times when we were processing - - - and those days in the winter were every day including Saturdays, Sundays and holidays. If we did take a short holiday or if the weather forecast was for severe sub-freezing temperatures, yes, we turned the heat on just to keep the water pipes from freezing. We liked to keep the plant at refrigerator temperatures during the winter-processing campaign - - - we just dressed like Eskimos!

2000-gal carbon steel tankWe always diluted the 50% sodium hydroxide to twice the original volume and allowed this solution to cool before using it. The first reason was, as I have already noted, that 50% sodium hydroxide produces an undesirable exotherm upon dilution. The second reason is that 50% sodium hydroxide would have crystallized at the temperature of our plant. In practice, this dilution was effected just after we received about 900 gals in our 2000-gal steel tank from a tank-truck from a nearby supplier. In the picture to the right, again I made the meter stick red (PhotoShop) to show the scale. The two long natural-colored sticks leaning against the tank were our 21st-century depth gauges to measure the contents of the tank. There were three openings along the top of the tank. Using vacuum, we moved the diluted base through a half-inch, black-iron pipe from the large tank to our small (ca 30-gal) charge tank mounted above the 315-gal reactor (see the next paragraph). An example of the ease of handling liquids!

Getting back to the reaction at hand, we would charge the contents of the filter press to a 315-gal, enclosed stainless-steel tank fitted with agitator and vented through a caustic scrubber (to destroy any methylating agent vapor that might escape the tank). We would then add the required amount of water to the semipurified diester. Because, in the dead of winter, the water came into the plant just a few degrees above the freezing point, that was our starting temperature. We would then turn on the agitator to slurry the solid and begin the addition of the diluted sodium hydroxide. After a considerable amount of solution had occurred, with the temperature rising to about 8-10 degrees C, we would insert the pH probe (just an inexpensive laboratory pH meter) so that that the tip extended no more than about a half-inch into the swirling liquid. We actually used two pH meters for this monitoring because then we would have a backup if the tip of one probe clogged during the reaction. When the pH reached 9.0, we turned the blower and scrubber on and began to add the dimethyl sulfate in a small stream. The reactions occurring in this melange are quite complex. For an explanation, click here and then return.

Because of this complexity, it is necessary to add base slowly to maintain the pH at 9.0 (+ or -0.1) so that the reaction proceeds without much undesired saponification.

At 10 degrees C, the methylation is rather slow, but we would allow the temperature to rise to about 20 degrees and would control it at this point by addition of crushed ice - - - several hundred pounds in total for one batch that produced about 20 kgs of maple-flavoring product (after the completion of the next step and after purification).

Eventually the reaction temperature began to fall all by itself without any more ice addition. When the rate of sodium hydroxide addition (required to maintain the pH at 9) had fallen to less than one drop per second, we could leave the reaction to its own devices (unattended) for about four hours. After the four hours, we acidified to about pH 2 using diluted sulfuric acid and pH paper. Toluene was added and, after agitating for 10 minutes, we turned the agitator off, sealed up the tank and allowed the layers to separate overnight. At this time, a test of the air space in the reactor always revealed that the dimethyl sulfate had been completely consumed (less than 1 ppm).

Three extracts with toluene (including the one started the day before) were completed the next day with the extracts being charged to the reactors used in the third step - - - coming up below.

3 - The extracts were distributed between three 72-l, 4-necked flasks fitted as stills. The toluene was recovered for reuse by distillation. The black oily residue was now ready to hydrolyze in the same stills where we had stripped the toluene. In the old German literature, the hydrolysis and decarboxylation were usually effected using boiling aqueous dilute sulfuric acid. This worked, but we soon found that, because sulfuric acid is an oxidizing agent, we could do far better using very dilute hydrochloric acid - - - not at the reflux temperature - - - but at 90 degrees-C. Here we were au courant using 220-v Therm-O-Watch temperature-controllers to maintain the temperature in the reactors. Thus, 24 liters of water and 800 ml of 20-degree Baume hydochloric acid (about 21%) were added to each flask

The contents were vigorously stirred with a 6" glass stirring blade in each flask (Stirring motor: Black and Decker drill powered by variable transformer). The vigorous stirring was necessary because this was a heterogeneous mixture of the diluted hydrochloric acid and the immiscible methylation product. The hydrolysis required about 22 hours. During this reaction time, a small amount of additional toluene azeotroped during the first few hours. Also swept into the condenser by the evolving carbon dioxide were the alcohols (from ester hydrolysis) and water vapor which collected in the receiver over the entire course of the reaction. Another valuable thing we learned was that, as in most organic processes, there are more things going on than the desired reaction. Therefore, we did not continue this hydrolysis and decarboxylation until the carbon dioxide evolution had totally ceased, because the product is undergoing slow destruction at the same time it is forming. When the rate of destruction equaled the rate of formation - - - it was time to stop!

We put the aqueous reaction mixture under vacuum and distilled an additional portion of it principally to remove most of the remaining alcohols because they would solubilize too much of the product even after cooling. We removed the warm, black solution from the stills, and allowed it to cool in the plant (remember - - - it was at refrigerator temperature). We stirred it by hand with a large plastic paddle several times over the course of about six hours. After cooling overnight, we put the crystalline mass into our cold room for several days to make sure that the crystallization was complete.

Finally, the thick mush was filtered and washed with refrigerated water (in practice, the refrigerated filtrate from our NEW PURIFICATION for volatile solids was used instead of water) mainly to displace the mother liquor. We dug out the cake of dark-red to black crystals and spread them on a table to dry over the course of several days to the fairly-stable monohydrate stage.

The crystals were now ready for our state-of-the-art purification method - - - see our NEW PURIFICATION for volatile solids

The following picture shows my late wife busy painting one summer after we had made many new wooden pieces to handle the increased production we were planning the next winter. Everything is helter-skelter in this picture because we are in summer maintenance mode. Things were different during the winter process campaign.
Picture of plant during summer maintenance
The drums of secret ingredient were not for the MCP process but were for another of our flavor products.

I would appreciate any comments and questions you may have, and I particularly appreciate being told about errors in the text.
Send your comments, etc to the WEBMASTER



PURE SYNTHETICS' OTHER PRODUCTS

In addition to MCP, we manufactured three other related compounds:
3-ethylcyclopent-2-en-2-ol-1-one
3,4-dimethylcyclopent-2-en-2-ol-1-one
3,5-dimethylcyclopent-2-en-2-ol-1-one.


Disclaimer: The procedures described above, while detailed in many ways, are still incomplete. I hope to give more details as time goes on until there will be detailed directions of these processes. However, be advised that I give this and subsequent information at no charge with no warranties expressed nor implied that this procedure will work out safely since I have no control over who might be trying to use the method nor over the quality of the chemicals that might be employed. The user is responsible for determining the fitness and safety of the method in his or her own particular case.


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