Thread: Schiff's bases
I only ever tried making Indolene (Indole plus Hydroxycitronellal), so cannot answer your question Justin. I still don't know if what I made was Indolene, it certainly didn't smell the same as the commercial stuff we used which was much more floral, and less Indolic. I'm sure the HCA made a contribution, but I'm also sure that there was less free Indole in the commercial stuff.
At these temperatures, won't the water evaporate if you open the bottle once in a while (and if working on small quantities)?
The Indole + hydroxycitrollal combo from yesterday has been on the hot plate for over an hour and it is turning dark brown. The "moth-ball" edge is smoothing out a little although it's still far too indole smelling and definitely moreso than Indolene 50 but it seems like a good sign that it's smoothing out and turning brown. I don't expect it to become Indolene 50, as David said it's more complicated than just heating it like the others but I am interested in seeing what happens to the color and odor as it continues to heat.
The bases that came off cloudy were re-heated, more water vapor was evaporated, condensation formed inside the vial so I swabbed the condensation from the inside of the 1 dram vial with a 6" cotton swab and let them cool. They are no longer cloudy. Helional took the longest to clarify and Lilial was the second longest to clarify.
I remade the C-11 and diluted with alcohol only this time, it turned out perfectly, no clouding no solubility problems. I suspect that the first vial of C-11, that is cloudy, might have one of three problems:
1. The C-11 Schiff base is not entirely soluble in DPG
2. I overcooked the first C-11 schiff base and it is partially solidified and not entirely soluble in alcohol or DPG (most likely the case)
3. My DPG is of poor quality or somehow contains water
I'm making a third C-11 schiff base according to the same specifications as the second in terms of time, heat, color and clarity and then I will dilute with DPG + alcohol to compare. If it is cloudy once again then I will assume my DPG is bad because David says that the C-11 base is soluble in DPG, if it is clear then it will tell me that I overcooked the first sample and everything else is fine (although this still doesn't settle the mystery as to why some of my absolutes are cloudy when using DPG + Ethyl Alc...).
Justin E. Beasley
Justin E. Beasley
lets say it is ran at near 28 inches of vacuum,, doable with a home vacuum pump, so that is around 49-50 torr
water boils at 40C, so an 80C reaction temp is double the boiling point of the water,
check this link out
it lists a number of aldehye reactions with MA
here is the reaction of MA and Bergamal
Preparation of Schiff Base of Methyl Anthranilate and Bergamal
Into a 2 liter, 3 neck reaction flask equipped with stirrer, thermometer, glass "Y" adapter, 1 liter addition funnel, steam distillation head with a 45/50 bottom male joint attached to the reaction flask, head thermometer, curved fraction cutter with a 50 ml receiver, heating mantle controlled with a "Therm-O-Watch", dry ice trap, Bennert Manometer, vacuum bleed valve and vacuum pump is placed 302.0 grams of methyl anthranilate having the structure: ##STR148##
With stirring using the 1 liter addition funnel, 332.0 grams of Bergamal having the structure: ##STR149## is added dropwise to the reaction mass over a one hour period while slowly heating the reaction mass to 50° C.
The 1 liter addition funnel is then removed from the reaction flask and vacuum (50.0 mm/Hg.) is applied to the system.
With stirring, the reaction mass is gradually heated to 100° C. over a 45 minute period.
Heating is continued at 100° C. for a period of eight hours while removing water at a vapor temperature of 35°-45° C.
The reaction flask is then cooled to 50° C.
The resulting product has an intense lemony and floral aroma.
Justin E. Beasley
don't think i know the answer to your second question, given what apparatus you have...
certainly you could try/test that....
since you mentioned you see the water, do you have any pH strips, if so could you try to test the pH?
the large ones 1L - 2L for vacuum filtering
or small ones like this one for small reactions
make sure you buy the heavy wall, a small tap, bump under vacuum will cause these to fracture
Justin E. Beasley
my vison is all but gone due to MS, so many times, i don't read / see things right.....
so titrating in the aldehyde ensures the leaving group / water can be removed as it forms....
these reactions are what are called reversible reactions, so if the water remains in the mixture, and if there is the slightest
amount of an acid level, the products turn back into the reactants, or form un wanted side reactions,
maybe not in your case but in general
also some aldehydes are to sensitive to high heat, so added them in slowly will get that small amount to form the intermediate product which is much more stable to high heat, then when all of the aldehyde has gone thru the first reaction phase, then the higher heat can be used to drive the reaction to completion, which causes the water to form as one of the products...and the schiff base to form
Last edited by luigi_g; 12th February 2014 at 09:52 PM.
I found my PH strips but they are old so hopefully they still work.
I tested two different vials but I had to re-heat them as the bases were sufficiently clear - I already swabbed all of the vials out. From the tiny drips I was able to capture it looks as though one sample tested around 4.5 and the other around 5.0 so they both have acidic condensation. I'll test a few more later but I have to go pick up my daughter from school, it will take me a couple of hours to get back to this most likely.
Justin E. Beasley
I tested the PH papers with my PH meter calibration solutions (7.0 & 4.0) and they are still accurate.
Justin E. Beasley
Is there anything I'm missing? Are there any other aroma chems, besides aldehydes and ketones, that react with Methyl Anthranilate to form ANY kind of base?
EDIT: From the linked patent paper luigi_g posted I found out that Melonal and Floralozone can be made into a schiff base as well, WOHOO!
EDIT2: I just read that the ionones, hedione and damascones are considered "rose ketones" are these also candidates for schiff bases? What about Iso E Super? According to wikipedia it's a "synthetic ketone"...
Last edited by JEBeasley; 13th February 2014 at 07:59 PM.
Justin E. Beasley
Seems like there's no escaping learning some organic chemistry
I'm still struggling with MA and benzaldehyde.. They just won't form a basis, even though there seem to be a lot of water evaporating from the mix (I think it should lose around 6% its weight to water, but there's no way of telling what has evaporated)..
And I know there's no base created since after a couple of hours it still smells like MA on the strip..
Everything I've done so far changes color, some change faster than others and some colors are darker and richer but most of them range from light yellow to orange with a couple brown and one brown-black. I found one source online stating that ketones need to be heated at higher temps for longer and I found this to be true prior to finding this source. Most of my aldehydes showed color change and condensation after 15-20 minutes and seem complete after 30 min, a few took an hour or more, the ketones usually took one to two hours at higher temps. A couple aldehyde bases I remade because I cooked them too long and they had non-dissolving solids in dilution. A couple were cloudy after they cooled indicating water content so I put them back on the burner for fifteen to twenty minutes. Helional took longer than most of the other ketones to clarify.
The indolene 50 experiment I tried eventually turned dark, somewhat opaque, brown and mellowed out, it smelled like it was blended with castoreum oddly enough and finally gave up the hydroxy citronellal note but it's not as deep, sweet and floral as what I purchase and the indolene 50 from PA is more transparent and stays glossy on paper for half a day. I gave up on the indole experiment after eight hours of continuous heating 50-60C.
I still have to finish making a few ketones, dilute and test on strips so we'll see how it goes. If all goes well I should be done by this weekend.
Last edited by JEBeasley; 14th February 2014 at 04:21 AM.
Justin E. Beasley
It has been heating for hours.. It did change color, but isn't very thick.. But for some reason it just smells like MA on the dry out..
It has been heating for hours.. It did change color, but isn't very thick.. But for some reason it just smells like MA on the dry out.. Did you check the bases you made with more volatile aldehydes? Do they still smell different from MA after a couple of hours?
Looks like you guys have things well in hand.
Just dropped by to double facepalm and say ignore/forget nearly everything I said about indole; I forgot the aromaticity means it does not react like a typical secondary amine and does not form enamines with aldehydes/ketones. It generally reacts with them at carbon #3, not the nitrogen. I went back and crossed out all my references to it acting like a base that I could find. If I missed some feel free to drop me a message.
I'm happy to see the thread bubbling away. Carry on.
What are the practical implications of this?
They'll still react, just differently than I had been thinking. See pages 39-40. luigi_g already touched on this in passing.
Practically? It's acid-catalyzed and readily-available HCl would probably speed things up, but then you'd have to neutralize it afterwards and lose product cleaning it, plus account for the water that was added with the HCl, so driving off the water with heat is still the most user-friendly idea if the reaction will go under those conditions. I just didn't want to leave my errors sitting there without saying anything.
Last edited by JEBeasley; 14th February 2014 at 06:17 AM.
Justin E. Beasley
Nizan, mabe the benzaldehyde just takes an incredibly long amount of time. That indole I tried took over eight hours for considerable change to occur. I heated C14, C16 & C18, while I know they are not true aldehydes, they did change color and form condensation in the vial but it took around 3-4 hours and higher temps similar to the ketones. I still don't know if they are truly bases but they act like it on a smelling strip and that's all I care about.
Justin E. Beasley
Update - how do I know the condensation in the bottle is water and not something else? It smells of the whole mixture..
Last edited by Nizan; 14th February 2014 at 01:00 PM.
Try this: Bring the water exactly up to the point of boiling (100C) - no more, look at where the thermostat is and turn it down half the distance of the regulator knob position to off, let the water come down to temp - assuming you are using a hot plate and the potentiometer temp control doesn't matter (linear or logarithmic potentiometer) I might be wrong in assuming that a hot plate potentiometer is a logarithmic taper...
The first ones I made I really cooked the hell out of them so don't worry too much about it being perfect, if you cook one too long then start over and reduce the temp a little until you get it right. The first Cinnamic Aldehyde I made at 70C and cooked for far too long. David was right about it being a poor quality material as there are undissolved solids in the diluted bottle that don't dissolve into an alcoholic solution with heat either. It also has less tenacity on a strip compared to the second cinnamic aldehyde I made @ 50-60C for 30min (Although, the first cinnamic aldehyde is a little different and no less interesting). There were four more I cooked at the same higher temp as the cin ald. - C11, hyxyl Cin. Ald., Anisic Ald. & Methyl Cedryl Ketone. The only other one that did not fare well at the higher temp for a longer time is the C11 - it's dark brown and has solubility issues (I remade it). The rest turned out fine and in fact seemed to require higher temps to get them there. It seems to me from your comments that benzaldehyde might need more extreme treatment. Even amongst the ketones, which normally require higher temps for longer, there were a couple that reacted very quickly and finished in the same time as a typical aldehyde (Beta Damascone) so there is not a single correct temp and time for all AC's of any given type, just "typical" heat and times for most of a given type (aldehyde/ketone). Also, they are not all thick as honey, some are considerably thinner but more thick than the original materials and not until they cool down to room temps.
The water condensation has all of the properties of water but you are right in that I don't actually know if it's water or not but I can say that it contains water because I can test it's PH with PH paper (PH 4.5-5.0). When I swab the "water" out of the vial the swab smells of the material, it does not smear or feel sticky and evaporates like water off of the swab, the consistency is that of water. I don't know what other clear liquid would condense on the inside of the bottle with all of the properties of water and not be water...
Last edited by JEBeasley; 14th February 2014 at 05:34 PM.
Justin E. Beasley
you can't use HCL, when the carbonyl O accepts the H+ from the HCL, you have a free CL ion, way to reactive
you need to use H2SO4, that would also make H2SO4 as the leaving group, so H2O is only an intermediate
so you would only need to remove the acid from the product as you mentioned.
I'm ready to move onto the next step - testing all of them on smelling strips, side by side, with their mother AC to see how they differ and see if there is any hint of MA left in product. Is it customary to test them neat before diluting? Should I dulute them prior to testing? Oranger crystals, Raspberry ketone and Ethyl Vanillin are crystals so I don't think that it's possible to test without diluting first.
I have 35 different materials that I experimented with but I'll exclude the one indole experiment so there are 34. Probably half of them are no doubt legit because they clearly have the word "aldehyde" or "ketone" in the name of the AC. The rest are AC's that I found reference to being made into bases in patents or from web sites referring to them as ketones (ex. "Rose Ketones": damascones, ionones & hedione). Some are questionable in terms of whether or not they are definitely bases but I don't know how to rule them out because they changed color, changed viscosity and seem to act like bases on a smelling strip so, even if they aren't traditional bases they act like one as far as I can tell. That said, for some of the more difficult ones that showed no change at normal temps of 50-60C (color, condensation, viscosity, etc) I raised the temp and left them on the burner for longer until they showed some change and they all had the aforementioned changes (color, condensation, viscosity, etc) eventually - Some were heated for up to four hours @ 50C and some up to three hours at 70C. Every AC was different in terms of how dramatic and how fast the changes occured. I have already ruled out my innitial attempts that were clearly flawed and exhibited signs such as poor solubility and poor odor strength along with extremely dark coloration - These were all re-made and are included in the list. If any were cloudy after cooling then I put them back on the hot plate for another 15-20 minutes. After each base had cooled completely I swabbed out the condensation from the upper half of the vial with a 6" cotton swab.
Through this evaluation process I fully expect that some will be eliminated as forgeries so it will be very interesting to see what is left over. I'm also not ruling out the possibility that I will be fooled by a few but I will post about that so that anyone willing to join in can try to replicate and give their opinion as well.
For anyone wishing to repeat any part of this experiment please keep in mind that my samples were all in the micro range of .250g - .400g beginning weight in a 1 dram dropper bottle - DROPPER REMOVED - vial tops open (three experiments were made in larger amounts 3-4g ea with the same results as micro amounts). The aroma chemicals were heated in the dropper bottles. This will make a difference considering how much material you are heating, if you are heating a considerable amount of material you might not get good evaporation and vacuum may be required to complete the process. Please be sure to ventilate your work space sufficiently and be attentive.
Following the materials list there is the list of potential aldehyde and ketone bases made with Methyl Anthranilate: Please let me know if there are any on the following list that are definitely NOT reactive with MA (neither an Aldehyde nor a Ketone and do not hold the capability to react) and I will test them with extreme prejudice.
Digital temp controlled hot plate
1 dram glass vials (dropper tops removed)
500ml borosilicate glass beaker (water bath)
6" cotton swabs (hobby or medical supply)
Ventilation fan + window
Watchful eye - Don't let your water bath evaporate completely below the temp probe, keep your temp probe touching the bottom of the vessel as a safeguard.
Paper strips for evaluation
1. Cyclamen Aldehyde
9. C-12 Lauric
10. C-12 MNA
11. Phenyl Acetaldehyde
13. Hexyl Cinnamaldehyde
17. Ethyl Vanillin
19. Cinnamic Aldehyde
20. Anisic Aldehyde
21. Mandarine Aldehyde
23. Methyl Cedryl Ketone
24. Raspberry Ketone
25. Methyl Hexyl Ketone
26. Oranger Crystals
27. Iso E Super
28. Dihydro Ionone Beta
29. Ionone Alpha
30. Damascone Beta
31. Jasmone Cis
There are a few I have that I did not experiment with, they will be for a later date (Namely, Ionone Beta, Delta Damascone, etc)
Last edited by JEBeasley; 14th February 2014 at 08:01 PM.
Justin E. Beasley
And we are back to the size of our retorts. I give up. I will not be participating in this thread any more.
[x] [x] to using HCl as the catalyst, but it doesn't seem to be generally practiced. H2SO4 looks much more promising. Phosphoric acid also came up, interestingly enough.
This mentions using lemon juice. Potentially very DIY friendly if you have an ultrasonic cleaner.
Justin E. Beasley
Lemon flavor isn't a bonus?
Okay, I kid, I kid.
Vinegar should work. I think typical household vinegar is close to the same pH as lemon juice, though they both vary. You're right the citric acid might be complicated to remove, though I like its status as one of few chemicals outright embraced by the "naturals" crowd. The acetic acid in the vinegar should evaporate out even before the water does...something to keep in mind but it's a possibility for removal and it doesn't look like this reaction necessarily needs to be dry. The chemists in the link were reporting good yields with water deliberately included, and I don't think it's as easily reversible as the formation of a Schiff base.
Look up bis-indolyl methanes. Apparently there's a lot of work being done on this for one reason or another.
EDIT: Actually, the first page of the link mentions acetic acid being used. Maybe it will benefit from ultrasound as well.
Justin - that's pretty awesome! Can't wait to hear your insights!
I kept warming the base I was trying to make.. There's still condensation going on, and
it thickened a bit.. Now sure at what stage to stop and test it out..
After that initial overcooking experience I watched each vial as I put it on the hot plate for the first time. As soon as I noticed condensation and color change I would check on it every ten minutes to see how fast it was changing color and pay attention to the amount of condensation in the vial. If the color and condensation came on fast then it seemed like the reactions were happening fast and I made the assumption that it didn't need to be heated for as long as some others. After about 15-30 minutes I would pick up the vial and check for consistency and give it a quick whiff. Once the color became very bright and rich and it smelled more homogenized and clear (very little trace of MA) and the thickness had changed then I would watch it for another ten and then take it off of the heat. After a couple hours of cooling some of them were cloudy, those got put back on the hot plate for another 15-20 minutes.
There were a few exceptions to my methodology, helional needed more time even though it seemed finished but after it cooled it was still cloudy... twice, third time was a charm as they say. The other curious one was beta damascone, even though it's described as a rose ketone it turned a brilliant shade of pink-orange (salmon?) pretty quickly and just kept getting richer. In evaluating the smell of it it didn't seem finished even though the color came on strong, I let it heat for longer based on it's smell mostly as the MA seemed as though it were still too present.
So, really, my methods are pretty unorthodox and more based on an intuitive sense about how fast the reactions SEEM to be happening but I don't really know for sure, I'll see how they turned out. I wasn't able to record every aspect of every base I made but I figure this won't be my last base making excursion so next time I make each base I'll write down more specific heating times, temps, color changes, ratios, etc and really hone in on minor details. For this run it was more about getting my feet wet, figuring out the process and assessing how worth while it is to make these bases.
If my weekend goes the same way as the past two days then I'm not sure I will get back to it until next week. For whatever reason everything that could have gone wrong yesterday happened so I'm now in a game of catching up with neglected household chores and necessities in addition to cleaning up after an all night puke fest because my daughter was up sick all night.
Last edited by JEBeasley; 15th February 2014 at 09:10 PM.
Justin E. Beasley
Tuesday, I made the Phenylacetaldehyde MA schiff base, simply by adding the appropriate amounts of the material, shook it up, and put it on the shelf for two days. This Morning, it is bright yellow fluid, It's a little thick (clouded), it has a small air bubble slowly rising in the soup, can't see any stratification of water, smells nice, strong, seems like it just worked itself out very nicely with simple prep.
Try it out!
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Paul - so what's your impression? Together with some Clary it reminds me of Cestrum
Well, the MA Phenylacetaldehyde Schiffs base hase some of the Phenylacetaldehyde odor profile, And I'll agree with Bill at TGSC:
hyacinth green foliage floral mandarin sweet pea
But also a touch of orangleblossom.
Is it still yellow?
My base with benzaldehyde turned from orange to brown over time..
yup, still yellow...
I do like the enthousiasm about chemistry here, but be warned that just because something changes colour, appearance or scent does not mean youve succesfully made a Schiff base. Unless you have the analytical tools, there is no way of knowing what happened.
Some of the procedures mentioned here will deliver some amount of the desired product, but as a mixture with the starting material and side products.
Take it from someone who has been making and isolating chemicals for the last 10 years.
That said, where a material is being used for a practical (including aesthetic) purpose, then ultimately the concern of interest is ordinarily whether that purpose is fully met without any problems, or is not. Even where purity may be lacking, or even if none of the intended compound is generated.
As you say, without analysis one won't actually know what one has however. But the procedure to get it could be reproducible, and the product could be of use.
Not that you were saying different!
For those trying to make a Schiff base for which they have no authentic sample, an idea might be to also try making a Schiff base by the same procedure for which one does have an authentic sample. If the products can't be told apart, then it might be that the method is capable of generating a usefully pure intended Schiff base. If the products can be told apart, then likely the procedure cannot. But it might generate something functionally useful anyway.
I agree that any material may be useful, irregardless its purity, but:
Regarding your last suggestion: this could work, but only for very similar starting materials (think C12 and C10). In other cases the optimal procedure varies quite a bit depending on the substrates.
I really didn't write clearly. Mostly I meant that if a self-invented procedure (not in any way verified by analysis) fails where it can be tested by sense of smell against an authentic sample, then it's relatively unlikely that it will give high purity Schiff bases in other cases either.
It might but that wouldn't be my odds-on bet.
It was meant more as a method of deflating an unrealistic balloon of hope (if that were the case) than a means of assuring anything or utterly ruling anything out.
Last edited by Bill Roberts; 5th August 2014 at 06:00 PM.
I don't know jack about chemistry (disclaimer ;P) however the Phenylacetaldehyde that I cooked up with MA smells similar Paul, take from that what you will. Also, the PADMA I've combined with MA lasts longer on a smelling strip than it's counterparts but has a lower odor profile. I've lost steam with this schiffs base project, partly due to the negative criticism but I'm slowly integrating the materials I've bastardized into what I'm doing - atm I'm reconstructing and converting accords, bases and historical perfume blends. Also, the Ethyl Vanilin/MA combination worked well for an Ambrein base I recently made, it really gave it that extra musky-dirty, orange-vanilla, cream-sickle kick... Thought it might be worth mentioning even if it's not a real schiffs base.
Last edited by JEBeasley; 6th August 2014 at 08:00 AM.
Justin E. Beasley
Just to point out that PADMA will not react with Methyl Anthranilate to form a Schiff's Base. PADMA stands for Phenylacetaldehyde Dimethyl Acetal; it cannot react.