Sciencemadness Discussion Board - Real chemistry is dying out, why?

Real chemistry is dying out, why?

kristofvagyok - 7-10-2012 at 09:34

Dear everyone,

Lot of you know my work, you know that I work in an orgo lab with real amounts, but I am confused, does my work have a future? Every journal what I open has awesome experiments, 99% yields with amounts like mmol, mg, and such like it. They measure the reagents with hamiltons and micropipettes and they call it chemistry.

My question is: WHY?

I know that small amounts are cheaper to work with but with 1-2mg? The only thing what conforms the reaction is a little peak in the NMR spectra what could be anything else also.

This was my last reaction (last week made), it was started with 1 mol, currently I have circa 700mmol from it and I had performed 3 steps, this means 300g raw product in that beaker up there what is 8000cm3 large, and I simply love to work with this large amounts.

So if anyone have an opinion about this, pro or versus please tell it.

P.S.: Every time when I tried to scale up a reaction from 1mmol to "workable" amounts it simply didn't worked...

Hexavalent - 7-10-2012 at 09:49

I appreciate that the costs are less, but surely accuracy and precision go down at some point when working with increasingly small amounts?

Personally, this weekend I've just recrystallized 1kg of urea from a commercial de-icing product....finally got to use my 3L erlenmeyer

kavu - 7-10-2012 at 10:10

In academic settings running reactions in large scale is costly and produces a lot of waste. Usually method development is easier to do in smaller scale. I'm also somewhat involved in total synthesis and we just don't have enough starting material to waste. In all work first start small and then do the scaleup. Easier to handle, no runaway reactions, no large and expensive glassware and so forth.

[Edited on 7-10-2012 by kavu]

kristofvagyok - 7-10-2012 at 10:36

Quote: Originally posted by kavu

Easier to handle, no runaway reactions, no large and expensive glassware and so forth.

Small glassware is also expensive, runaway reactions are rare, I didn't have any in the few years... The solvents and the reactants are usually not that much more expensive in larger amount. E.G.: 25cm3 benzyl alcohol is just 5 USD cheaper than 100cm3, because the glass what is it cost's more.

The waste recycling is the biggest deal, but with a proper solvent redistilling and re-usage this could also reduce the price of this...

So: small chemistry is NOT CHEAPER!

Siggebo - 7-10-2012 at 10:38

As a half-serious remark, I have troubles working even in semi-micro scale because of shaky hands.

And I don't even drink coffee.

kavu - 7-10-2012 at 11:14

Quote: Originally posted by kristofvagyok

So: small chemistry is NOT CHEAPER!

Let's say that you have a linear sequence of 25 steps in your synthesis with a 80% yield in each step. If you want to do this on a large scale it will cost you a LOT. It depends on what you are doing, in total synthesis large scale is in most cases out of question. I've also been working on organocatalysis where large quantities are needed.

Tsjerk - 7-10-2012 at 11:15

When you are working with stuff like benzyl alcohol, it doesn't really matter how much you take... But if you are doing a novel 7 step synthesis starting with some expensive terpinoid, you will end up working in the milligram range at some point.

I did a couple of projects working with small amounts. But while I was working with 50mg at most at some points, the total cost of that amount was several thousand euro's, because of all the expensive reagents and liters and liters of solvents used in chromatography purification after each step.

So small scale isn't cheaper perse, but in some cases you don't have a choice, especially when working with large organic molecules and doing multiple step synthesis with them.

Edit: What Kavu says, and a lot of chemists would give up a finger for a 80% yield in every step.

[Edited on 7-10-2012 by Tsjerk]

Sublimatus - 7-10-2012 at 11:31

I worked in a university lab in the 0.3 to 1 gram range.

Our lab wasn't exactly wealthy, and many of our starting materials were rather complex. It was generally easier to buy those initial compounds from a company synthesizing them on a large scale for relatively cheap, rather than spend two months to get their ourselves.

That said, when 5 grams of your starting material costs $400, it makes more sense to do the research on a small scale. Botching the synthesis somewhere along the long series of manipulations could be a costly mistake, especially if you blew the whole 5 grams on that one attempt.

One should also consider that disposal of hazardous waste generated during lab work can get expensive. Working on a large scale naturally produces more waste, and if your kilo of expected-to-be product goes south during a manipulation you'll be paying to try again and to get rid of the mess.

triplepoint - 7-10-2012 at 11:36

Quote: Originally posted by Siggebo

As a half-serious remark, I have troubles working even in semi-micro scale because of shaky hands.

And I don't even drink coffee.

It's not a joke. Macroscale reactions are easier to perform. It is easier to see what you are doing and easier to be adequately precise in all of the mechanical actions necessary to perform chemistry.

From a raw materials and equipment perspective, micro is often more efficient, but that efficiency comes at an additional cost to the experimenter. Micro is sometimes more reasonable or even the only way to go, but the human costs should not be disregarded.

kristofvagyok - 7-10-2012 at 11:48

Quote: Originally posted by kavu

Total synthesis is an expensive thing, I agree, catalyst and any other "modern" chemical way is also expensive, but if the reaction route what have been worked out is just good for mg scale than it is useless. To optimalize it to "workable" amounts will be as hard, or even harder to perform than the microscale synthesis.

But if everywhere they work with microsyngres and stuff like that who will make the "normal part"? If there is a good project than it would be good to make it in useable amounts.... Or just bigger than an NMR sample.

kavu - 7-10-2012 at 11:53

This is merely dependent on what the goal of the research is. If you want to have a preparative route to a compound, yes a good scaleable route is your choice. If you are however interested in screening a reaction, doing physical organic chemistry, total synthesis and so forth you don't have to go that far. In most cases the most expensive thing is paycheck of the chemist. Right Tool for the Right Job works in synthesis as well

Scaling up is a huge part of chemistry and in industry many chemists specialize in optimizing routes to be used in large scale. This is really a demanding job and requires a rigorous analysis of different aspects of a reaction. It's not dying out as far as I know, quite the opposite. As synthesis develops we get new materials and the pilot synthesis of these requires this "real chemistry".

[Edited on 7-10-2012 by kavu]

Sublimatus - 7-10-2012 at 11:58

You're right that eventually someone will have to figure out a large-scale route if the compound proves to be commercially viable.

The issue, though, is that it makes little sense to invest so much in a compound until its utility has been demonstrated. Where I worked we were systematically investigating new compounds to be used as MRI contrast agents. It would have been prohibitively expensive to synthesize on a large scale each compound that we checked. We screened a ridiculous amount of structures and motifs in search of something suitable. Nearly all of them were not up to snuff, so there would have been no return on invest toward the material cost.

It's difficult to receive grants for research in many fields these days, so we have to make the most of what money we can get. If you have the luxury of not facing monetary concerns, know that there are many bench chemists who would love to be in your position.

sargent1015 - 7-10-2012 at 12:00

While I love macroscale, I do know that some of the compounds in my lab are over $1000 per gram, not ideal if you want to perform even a 1 g scale synthesis

froot - 8-10-2012 at 02:29

I would also suggest that it has much to do with the growing awareness of the health hazards from exposure to countless compounds. Smaller quantities are easier to crisis manage and dispose of without major expense. The newer school of thought: "if it's toxicity is unknown, then it's deadly" springs to mind which is not exactly in favour of old style bench top chemistry.

Dr.Bob - 8-10-2012 at 10:37

A lot of scale depends on the purpose. If preparative, or for in-vivo testing, then you must scale things up. But 10 mg of a compound can provide enough material for many biological screens, anywhere from 100-1000 high throughput binding screens, or dozens of other assays. And while I am the first to agree that it is nice to have more material ready should a hit be found, the likely answer is that it is very expensive to store 1,000,000 vials of material.

I try to scale up common intermediates to a few grams or more, if they are useful for multiple reactions or steps, but most organic chemistry I do is now in the 100 mg to 2 gram scale. The cost for some materials may be cheap, but silica gel is not cheap, and most reactions require purification, so scale costs there, in chromatography silica or recrystallization solvents.

As for "does my work have a future?" that is more a question of free trade and cheap labor. China can provide cheap chemists, cheap energy and raw materials, and little regulations, all of which are what are killing jobs in the US and Europe, along with MBAs, lawyers, CPAs, banks, "free trade" and politics. I am the first to want to protect my safety and the environment, but the current desire for everything to be "100% safe" and "absolutely no chemicals" is killing industry in the US. That is what will determine your work future.

kristofvagyok - 8-10-2012 at 10:40

Quote: Originally posted by sargent1015

While I love macroscale, I do know that some of the compounds in my lab are over $1000 per gram, not ideal if you want to perform even a 1 g scale synthesis

Sigma sells the stuff what is in my beaker at price 200usd for 5g. Calculate

I agree that every "extreme" price compound couldn't be synthetised in bulk quantities, but if everything is performed in micro scale... It is also not the best.

Quote: Originally posted by froot

I would also suggest that it has much to do with the growing awareness of the health hazards from exposure to countless compounds. Smaller quantities are easier to crisis manage and dispose of without major expense. The newer school of thought: "if it's toxicity is unknown, then it's deadly" springs to mind which is not exactly in favour of old style bench top chemistry.

I work with benzene, CCl4, chlorine, bromine, brucine, several organic halogens, carcinogen stuffs and a lot "hazardous" material and I'm still alive. If everyone is a pussy to work with real reagents then I would suggest to don't work as a chemist. Chemistry is about hazardous materials, just don't be afraid from it and there will be no problem, according to my experiences.

And for the "new school thought", that if it's unknown it will kill you... No comment.

Magpie - 8-10-2012 at 15:49

As strictly a home chemist, I like to work on the scale of a few grams. I keep it small to minimize materials, equipment, waste management, and risk. But if I had to work with just a few mg or less I would get no satisfaction from it.

My old school lab manual (1960) has about the right level of macroscale for me. However, when using a procedure from OrgSyn or Vogel, I will usually scale it down.

woelen - 15-1-2013 at 06:19

@Magpie: In home chemistry it hardly is possible to work on true microscale with just a milligram of reagent. I like to do my experiments on a test tube scale, which means that I use a few ml of solvent (in most cases this is distilled water) and 50 ... 500 mg of reagents, the precise amount depending on properties like solubility, price and intensity of color.

Synthesis of new chemicals I usually do at a scale of 10 grams, sometimes a few grams, sometimes a few tens of grams.

Too small a scale makes yields nearly zero. Mechanical losses are fairly constant and if I make 1 gram of a compound and 500 mg sticks into a filter and cannot be scraped from it then the mechanical loss is 50%. If I make 10 gram and I still have 500 mg sticking to a filter, then the mechanical loss is only 5%. The same is true for distilling volatile liquids. E.g. when I use a 100 ml flask and I distill 5 ml, then quite a high percentage is lost as vapor, while in distilling 50 ml the same loss is a 10 times lower percentage. So, in general I try to do a synthesis on a minimum scale, with the constraint that mechanical losses should remain acceptable. A mechamical loss of 10% is something I can live with, but a loss of 50% is too bad for me.

With mg quantities my mechanical losses would be nearly 100% (or even completely 100%), simply ebcause I do not have the equipment to handle such extremely small amounts.

arsphenamine - 15-1-2013 at 06:36

I appreciate that working on a micro scale is ungratifying by its seeming abstract nature.
Sometimes you just want to blow shit up for the unambiguously palpable thrill.

Those little bumps in the NMR spectra usually coincide with other spectral data,
most of which may be computationally approximated so that you know what to expect.

Macro-scale preparative chemistry has the disadvantages of cost and hazmat disposal.

If you review Woodward's total synthesis of chlorophyll,
you infer a proliferation of false turns in the process, and
reach the glum realization that he started with a drumfulls of feedstock.

In the last para, the phrase ...performed Herculean preparative tasks.. stands out.

Ozone - 15-1-2013 at 06:51

Four words: "Office of Risk Management".

The intrinsic risks associated with the teaching and practice of Chemistry cause fear of legal retribution. This is used by policy makers and/or campus officials looking to save money buy minimizing perceived risks. Not only is chemical-free Chemistry cheaper, but it is also safer, ergo win-win for the politically expeditious bureaucrat-trolls in charge. The public approves of this because they are ignorant and believe that the "use of advanced technology and information science" will keep them, their 18 year-old "children" and the environment safe.

These are the same people who are excited about "virtual labs". No chemicals = no risk. It also equals "no practical experience". I am already running into people with degrees in Chemistry who are scared to death of...chemicals. Even "seasoned" Chemists and Techs seem the wet their pants over dichloromethane.

Worse, the same fears (propagated by the EPA, DHS, etc. and years of public ignorance) have made the practice of Chemistry (indeed of most "scary science") practically illegal outside of the institution.

It's sad and it's going to get worse.

elementcollector1 - 15-1-2013 at 17:56

Quote: Originally posted by Ozone

Four words: "Office of Risk Management".

The intrinsic risks associated with the teaching and practice of Chemistry cause fear of legal retribution. This is used by policy makers and/or campus officials looking to save money buy minimizing perceived risks. Not only is chemical-free Chemistry cheaper, but it is also safer, ergo win-win for the politically expeditious bureaucrat-trolls in charge. The public approves of this because they are ignorant and believe that the "use of advanced technology and information science" will keep them, their 18 year-old "children" and the environment safe.

These are the same people who are excited about "virtual labs". No chemicals = no risk. It also equals "no practical experience". I am already running into people with degrees in Chemistry who are scared to death of...chemicals. Even "seasoned" Chemists and Techs seem the wet their pants over dichloromethane.

Worse, the same fears (propagated by the EPA, DHS, etc. and years of public ignorance) have made the practice of Chemistry (indeed of most "scary science") practically illegal outside of the institution.

It's sad and it's going to get worse.

I'm writing an essay on this topic, in fact. Hopefully my English class will listen to the 3-page, 6-paragraph rant I have prepared for them.

Ozone - 15-1-2013 at 19:37

Please post it here.

Cheers,

O3

bfesser - 15-1-2013 at 19:49

Quote: Originally posted by kristofvagyok

small chemistry is NOT CHEAPER!

kristofvagyok, are you trolling us, or are you really as ignorant as you're making yourself out to be?

What's cheaper, 1 gram of chamazulene, or 5 kg of it? A 5L beaker, or a case of 5 mL beakers? Seriously, look it up. Don't confuse your lack of skill and knowledge in microscale chemistry, with an inferiority in the established techniques.

Basically, what I'm saying is; your 'argument' is idiotic and uninformed.

[Edited on 1/16/13 by bfesser]

woelen - 15-1-2013 at 23:18

I summarize my way of working as follows: "As micro as possible". I prefer to use small amounts (and yes, it IS cheaper to use small amounts), but the amounts should not be so small that I hardly can handle them anymore and hardly can see what is going on.

kmno4 - 16-1-2013 at 00:27

Quote: Originally posted by bfesser

kristofvagyok, are you trolling us, or are you really as ignorant as you're making yourself out to be?

This is what I was going to write.
Just plain trolling.
ps. mg-scale procedures are very often not scalable to multi-gram preparations; besides, some procedures and yields exist only on paper and no-one is able to confirm them.

jamit - 16-1-2013 at 00:38

... for the home chemist you really can't go too microscale into the mg. This is especially true for synthesis of compounds. If its just to see the chemical reaction or observe a physical property, then doing it in mg sample is fine -- examples would include the diffusion of KMnO4 or test for chloride ion using silver nitrate.

However, I do lots of experiments with my kids and so we work in 1g-100g batches mainly because we're doing lots of synthesis. Plus like Woelen, we like to make and purify and finally collect our final product for storage in 20ml vials.

kristofvagyok - 16-1-2013 at 03:12

Quote: Originally posted by bfesser

Thanks!

The price between 1g chamazulene and 5kg chamazulene is not that big. 1g chamazulene is usually made on a small scale extraction while 5kg is made on an industrial scale what is always cheap, almost the cheapest. So the price difference between that two is not big as the difference should be.

E.G.: carbon nanotubes was 20USD/kg price from the manufacturer 5 years ago...

Quote: Originally posted by kmno4

ps. mg-scale procedures are very often not scalable to multi-gram preparations; besides, some procedures and yields exist only on paper and no-one is able to confirm them.

-I would agree with this, because often (almost always) this happens.

bfesser - 16-1-2013 at 11:28

Quote: Originally posted by kristofvagyok

The price between 1g chamazulene and 5kg chamazulene is not that big. 1g chamazulene is usually made on a small scale extraction while 5kg is made on an industrial scale what is always cheap, almost the cheapest. So the price difference between that two is not big as the difference should be.

My post was meant to challenge you to actually look up the prices and do the calculations. Go ahead, do them. Show them clearly here.

Also, I highly doubt the purity of whatever sludge that was in your beaker matches that of whatever (analytical standard grade) commercially available product you arbitrarily chose to compare to.

DJF90 - 16-1-2013 at 13:06

Economy of scale is not the same thing as saying its cheaper to work on a larger scale. If you wish to make a gram of compound, the overall cost of a gram from a 500g batch is obviously going to cheaper than a gram from a single gram reaction. However, the overhead for the larger scale reaction is of course much larger, as is the cost of the glassware and equipment required (compare say a benchtop buchi with a 20L process one...).

And then theres the sad fact of chemistry: Not every reaction works as described, especially not on the first attempt. Reactions that give no or little product (with tedious isolation in the latter case) are obviously money going down the drain, and time wasted too (especially after you have to wash all the glass from the reaction too!). I routinely perform the reaction using a gram or two before scaling up. This way you can assess how the reaction works (and identify any exotherms/gas evolutions) before commiting time, money and material to the preparation of a main batch.

smaerd - 16-1-2013 at 13:18

I've carelessly tried some micro scale type procedures(not 1mg but 100mg's). And I'm with woelen in that the loss on a filter just makes it not worth the time or investment. That "oh cool if I breath to hard I will lose my entire yield" feeling isn't one I enjoy. Or "could I drip some solvent in to a melting point capillary to get this back"

. Or "is that scraped cellulose from the filter paper, or my product"...

On the flip-side if I go macro the conditions change and the waste can be a real burden(home-chemist). Volume of solvents and as Dr. Bob said silica gel go up almost exponentially. Some procedures are just awful, using 2 liters of solvent to pull a gram of material(end product). Let alone doing that on a 10 gram scale, simply no point in either experiments. Also large-scale has a lot more risk, runaways are more fierce, more risk for exposure, more fumes, etc. At home it's just not comfortable and not really all that fruitful. I'd rather do a 1/20th a mole 5 times then a 1/4th a mole off the bat in many scenarios. It's no short-cut for someone who loves being in the lab enough to live in one hehehe.

For home experimentation which is the only side of chemistry I have an opinion on other then academic(student), there's a happy medium. Go too small, and what's the point, go to big and what a mess. 5-10 grams is what I like to work with. 50-250mL flasks feel right in my hand. I don't even own a 1 liter flask. For tricky procedures and new chemicals I stay in the millimole scale. For more basic chemicals and or reactions I don't mind doing 1/5-1/3 a mole(acidifying sodium benzoate). For really basic chemicals(nitric acid preparation etc), the only real limit is the glass-ware size, how much I need, and how long do I want to sit by a distillation, and do I have a container and location to store it safely.

I probably just reiterated a lot of what other people said, oh well, hahaha.

[Edited on 16-1-2013 by smaerd]

elementcollector1 - 18-1-2013 at 10:46

Wow. I do reactions much more scaled-up than you gentlemen, apparently. I *do* have a 1-liter flask, and am almost always using it for something or other. Reactions I do are almost always 50-500g, and I simply don't have the patience for going smaller.

Nickbb - 18-1-2013 at 14:27

I feel that small scale reactions are good for testing and trying out some kind of possible route to a chemical, especially if you have no clue what yield you might get or if it will work; otherwise you'd be wasting a lot of chemicals. On the other hand when I'm doing something that I know works and gives good yield than I usually work on a scale that I like, maybe 50-100g... Only other reason to work on a very small scale is to prove a point like oxidation states of a metal.

kristofvagyok - 18-1-2013 at 14:56

This topic is not what I planned about, sorry for that.

My main question was that in published papers where research groups make chemistry from lot money, why do they publish reactions made on 1mmol scale, yield calculated by NMR/MS data and write down reactions what are impossible to scale up or to repeat. What's the reason for that?

Now if I go down to the library, start to read a recent published jornal (Tetrahedron, Synlett, Angewandte Chemie, ect) main part of the reactions are on mmol scale and only a few of these are reproducible. Why do they publish these things? Impact factor? If noone can reproduce the experiment than no impact factor will be gained.

Ozone - 18-1-2013 at 17:06

"...yield calculated by NMR/MS data...", or as a gross product % of area-sum by LC/GC. The answer? "Lazy".

O3

AJKOER - 18-1-2013 at 17:41

Quote: Originally posted by kristofvagyok

Quote: Originally posted by froot

OK, an extreme example, let's assume you just have an accidentally large dose of H2S. But you are still breathing and otherwise feel OK. So your fine, right? Wrong, possibly dead wrong. Hydrogen sulfide has a delayed mortality profile, you may in fact be dead, a walking dead, but you just don't know it yet.

This is a parallel to other chemicals that facilitate your death to cancers, but because it doesn't kill you quickly, it does mean your OK.

Dr.Bob - 18-1-2013 at 17:47

Yields look better when artificially boosted. Just like how Harvard gives more "A"s now, politicians all claim that they will cut your taxes and increase your benefits, and "in search of" ads always talk about romantic notions.

Human nature is that people want to do the least work, get the most credit, and look the best. If you have worked 5 years towards a PhD, and you think that your adviser will let you finally graduate if you just finish that paper and get it published, you might tend to make the work look as good as possible. I have tried to repeat work, tried to create new chemistry, and worked to publish as well. I have been published, as well as rejected, and sometimes the reasons for each are very unclear, so I can understand why people might think that yields matter to publishing. Some professors are quite notorious in demanding high yields, and if you are a tired graduate student, you might just make the yield work. I never had that particular problem, as my adviser was not as worried about yield in my project, much more about novel mechanism and creating lots of data.

But having to repeat others work has shown me that it is hard to 1) create knowledge 2) repeat others work, and 3) make sure that you are doing your work as well as the original author. I have seen people do a sloppy job of repeating a reaction and then be surprised that they got low yields, even through they used 1) non dry glassware 2) un-titrated base 3) very old reagents which were not checked in any manner 4) not been careful in addition speed or order of addition 5) and skipped steps in the work up. Conversely, there are some reactions which do not require as much care, and I have seen people get good yields with very little effort (my favorite kind of chemistry). So before you are critical of someones work, make sure that you are doing your work right.

The recheck on every reaction is what I like about Organic Syntheses and their verified reactions.

bfesser - 18-1-2013 at 20:12

Quote: Originally posted by kristofvagyok

This topic is not what I planned about, sorry for that.

My main question was that in published papers where research groups make chemistry from lot money, why do they publish reactions made on 1mmol scale, yield calculated by NMR/MS data and write down reactions what are impossible to scale up or to repeat. What's the reason for that?

Now if I go down to the library, start to read a recent published jornal (Tetrahedron, Synlett, Angewandte Chemie, ect) main part of the reactions are on mmol scale and only a few of these are reproducible. Why do they publish these things? Impact factor? If noone can reproduce the experiment than no impact factor will be gained.

Are you serious? Chemistry is a science. Don't you know what science is!? You sound like you belong in engineering...

kavu - 19-1-2013 at 09:46

Just out of curiosity, what do you kristofvagyok think about computational/physical chemistry?

kristofvagyok - 19-1-2013 at 15:36

Quote: Originally posted by kavu

Just out of curiosity, what do you kristofvagyok think about computational/physical chemistry?

It is useful if something useful is calculated e.g.: will a medicine molecule fit in the cyclodextrine and is it possible to put it in it or not and not even worth a try.

But when they calculate e.g.: the n+1-th metastable state of ice what could only exisist on X pressure and Z temperature and will probably never ever exist in real life... I think that's just waste of time.

Quote: Originally posted by bfesser

You sound like you belong in engineering...

I am not an engineer, but I think that if something is not scaleable, not reproduceable and just good for gathering some impact factor than it is useless.

kavu - 20-1-2013 at 02:20

You do realize that efficent applications require the study of simple and theoretical things at first? In order to screen the scope of reactions small scale experimentation is needed. These results can then be applied by others to see if it can be done in a large scale or modified to fit their needs. I find it somewhat rude and ignorant to claim some of the most fundimental scientific research (the results of which you use daily in the lab) to be a waste of time.

[Edited on 20-1-2013 by kavu]

Endimion17 - 20-1-2013 at 05:18

Quote: Originally posted by kristofvagyok

But when they calculate e.g.: the n+1-th metastable state of ice what could only exisist on X pressure and Z temperature and will probably never ever exist in real life... I think that's just waste of time.

You are very wrong. The very same example you mention plays a great role in astrophysics and planetary geology, which translates to greater understanding of evolution of solar systems, which is helpful to a myriad of other sciences.

It's like saying all those obscure and complicated mathematical (ok, math is not a natural science, but for the sake of an argument let's pretend it is) problems that have been solved have no purpose and are a waste of time. Some of them gain purpose after more than half of century.
Nothing in science is a waste of time if done properly. Even failures, if you know it's a failure.

Even if it doesn't find a real world application as soon as it's discovered, it's valuable cause it's knowledge.
If we did only the stuff that has immediate real life application, I guarantee you we wouldn't be typing this right now on a computer because there'd be no digital computers. Perhaps we'd be stuck in some weird 18th century world with cogwheels and brass, ornamented, primitive scientific equipment.

Imagining weird things and trying to find whether they work or not is what pushes humans forward.

bfesser - 20-1-2013 at 17:21

Quote: Originally posted by kristofvagyok

I am not an engineer, but I think that if something is not scaleable, not reproduceable and just good for gathering some impact factor than it is useless.

You must be trolling.

[Edited on 7/12/13 by bfesser]

Size really (might) matter

Xenon1898 - 21-1-2013 at 16:19

I didn't see it mentioned that if certain reactions only work on a tiny scale then they may have great utility at that small size. Think analytical lab on a chip, micro-reactors, in addition to the possibility of screening an array of many samples at once as scoping tests. The results could be useful for additional related work at the small scale.

If the complaint is that the experiment is not reproducible, well, that's obviously pretty worthless no matter what the scale used.

Xenon1898 - 21-1-2013 at 16:31

Forgot to add - I sympathize with someone's individual idea of what good/fun chemistry is, each to his own. But while some may feel more satisfaction with producing large batches of a product, it seems there could be an important set of skills on the small scale worth developing, especially for the home chemist. Imagine if you could miniaturize your own home "lab" and it fit it into a shoebox. You could fit it under your bed, in a drawer, alot of places. Heck at that size that set of experiments would be portable, say for a field kit for testing samples in places away from the lab. Seems like there could be a set of useful techniques worth honing there.

Having said that I have to admit when I bought a chemistry set for my kid a few years back I was quite dissapointed that the entire set was super miniature. They expected a child to get just as excited when half a drop of liquid turned green as if it was half a jar full. I think if there is an emotional reason, like the excitement of learning, then there is some real value in having a bit larger scale than a couple drops for the visual display. It all depends on what is trying to be achieved.

woelen - 22-1-2013 at 01:18

Quote: Originally posted by kristofvagyok

[...]
But when they calculate e.g.: the n+1-th metastable state of ice what could only exisist on X pressure and Z temperature and will probably never ever exist in real life... I think that's just waste of time.

Quote: Originally posted by bfesser

You sound like you belong in engineering...

I am not an engineer, but I think that if something is not scaleable, not reproduceable and just good for gathering some impact factor than it is useless.

Sometimes indeed you need to be practical. I am a software engineer and in many applications time and limited resources are a fact of life and then one has to work straight towards the goal and one has to build something, which is useful and is such as the customer has asked for. This is engineering and has nothing to do with science. Just use proven technology so that there are no strange (costly) surprises while developing the system.

But... if all people always were thinking like that and if there was no real science, then we would not have been where we are now.
A very nice example is the (for most people rather obscure) field of number theory, a branch of mathematics which deals with the structure of numbers and special sets of numbers. Much of this mathematics is from around 1900 and at that time it was only theory, a lot of theory. Nowadays not a single electronic bank transfer and not a single https-session would be possible if that kind of mathematics did not exist. Now we use RSA, DSA, elliptic curves and so on for nearly every form of secure electronic communication and all of these things are based heavily on the structures of numbers, discovered a century or so ago. The mathematicians of 100 years ago never could have imagined how their work would be used in real-life practical application one century in the future. Those people have been struggling and doing painstakingly long and intense computations, all by hand and they just did these things because they liked to do it. What if all of those people just considered this a waste of time?

learningChem - 29-1-2013 at 22:34

Quote:

main part of the reactions are on mmol scale and only a few of these are reproducible. Why do they publish these things?

It's all about money. People in the academic establishment are paid for publishing stuff. So they publish stuff that looks 'very learned'...

learningChem - 29-1-2013 at 22:39

Quote:

Nowadays not a single electronic bank transfer and not a single https-session would be possible if that kind of mathematics did not exist. Now we use RSA, DSA, elliptic curves and so on for nearly every form of secure electronic communication and all of these things are based heavily on the structures of numbers

Did the guy who invented the enigma machine (an engineer...) rely on number theory at all?

[Edited on 30-1-2013 by learningChem]

White Yeti - 30-1-2013 at 14:54

I think it's simply less wasteful and more meaningful to use small amounts when studying a reaction, or a set of reactions.

I remember not too long ago, I competed in the ACS Chemistry Olympiad on the state level. Of course, it consisted of a test involving fundamental chemistry and physical concepts.

The "experiments" that we were required to conduct were rather lame. The key however, was to be able to conduct as many tests as possible to support or refute a hypothesis. In many cases, the strength of data can lie in repeatability on a small scale, rather than synthesis on a large scale. From a large set of data, you can do statistical analysis. Naturally I would be skeptical of a paper that mentions a small scale synthesis that is not also repeated numerous times. If a reaction is not tested in a real environment, it's as good as bullshit. After all, a computer or a piece of paper is not able to make proteins or synthesise heterocycles.

I think amateur chemistry is often similar to chemical engineering (in that it often focuses on scaling up reactions), but with a hint of fundamental chemistry. Amateur chemistry is (as I see it) "the pursuit of a better way" through personal ingenuity and perseverance. The pressures in a home lab are different from those in a commercial lab. My best guess about the limitations of a commercial lab is that time, purpose, and success are probably the largest pressures, while an amateur lab has different constraints, most notably financial constraints, limits on accessible scientific literature, and limits on physical capital like analytical equipment.

benzylchloride1 - 31-1-2013 at 00:27

I am of the opinion that one should work on as large a scale as possible especially during the initial steps of a natural product synthesis. One runs out of material pretty quickly after 15 or more steps due to non-quantitative yields. The microscale chemistry is useful for scouting reactions or during advanced stage work with precious compounds that took months to synthesize. I personally own vial scale glassware, 14/20, and 24/40 up to 12 L. I like running NMR on concentrated samples, less scans, less time and with a CW spectrometer, better resolution.

woelen - 31-1-2013 at 01:12

Quote: Originally posted by learningChem

Did the guy who invented the enigma machine (an engineer...) rely on number theory at all?
[Edited on 30-1-2013 by learningChem]

I am not sure about the Enigma machine and don't know the details of it, but at that time I think that application of number theoretic algorithms for cryptographic purposes was not feasible. You need a lot of computational power to make these things working. E.g. a 1024 bit RSA operation for encryption takes two 512 bit modular exponentiation steps, which means computing A^B (mod C), with A, B and C being numbers of 512 bits. This is well beyond the 1940's hardware capabilities.

whats a typical experimental batch size?

Furboffle - 9-7-2013 at 10:45

I'm curious how much you guys run for experimental batches/first time experiments?
like grams or milligrams?
I've done experiments trying to make beta-carbolines, tryptamines, and various nitro-styrenes.
First time I made a nitro styrene I used the nitro-aldol reaction via 1g trimethoxybenzaldehyde. it proved extremely straight-forward and I was able to then increase the quantity size successfully.
indoles and beta-carbolines on the otherhand were the first things I tried my hand at and had much difficulty. Due to loss of reagents and realizing better equipment is necessary I ended up giving up on them after wasting a lot of time, money, and chemicals.
so I've come to realize its hit or miss on success depending on the nature of the target compounds being created. so I'd like to wise up with new reactions I try my hand at.
whats a good rule of thumb for quantity in a first time experiment? how small is too small?

sargent1015 - 9-7-2013 at 11:12

Well, I guess it all depends. If you are following a paper from literature, it's never a bad idea to follow their scale, usually 1-10 mmol for my research. My rule of thumb is to run a reaction with at least .1g (mainly due to losing yield in workups, which are much greater on small scale).

But, it really depends on the reaction you are running.

If you are "inventing" something new or trying a new reaction scheme, usually it's better to start smaller, especially if the material you are working with is valuable. There are inherent problems with working with small scales, such as not having enough material for analytics, a problem I run into sometimes when I am starting a scheme. If you ask one of our members, Kristof, he will tell you to run it on molar scales.

In the end, I guess what I am dancing around here, is that there is no perfect amount of material to run with. Guessing, performing research, and preparation are important not only for safety, but also for obtaining high yields. Remember, this is experimentalism, so you will run into problems some of the times and your yields may not match literature, but repetition is key. That is what makes chemistry so exciting is that one little variable (Temp, humidity, looking at it funny) will produce different results.

Keep on experimenting and don't get discouraged. Size doesn't matter

(I don't work with energetic material, so the above statement DOES NOT APPLY when working with them

)

kristofvagyok - 9-7-2013 at 13:00

Oh, someone mentioned me, thanks!(:

Yesterday I started to work at a chemical company where they produce several N protected amino acids (BOC, Cbz, Fmoc) and related stuff. I work at the research and development department and we design reactions from mmol scale to industrial size.

We usually start from 1-20g, depending on the value of the substance and if it works we do it on a nice 200-500g size, just before the industrial synthesis (10-100kg).

Acidum - 9-7-2013 at 13:03

Depends on your lab setup.
Usually good starting point is around 100-500 mg.
During my graduation work (or however you call "diplomski rad") I did syntheses and experiments with starting amounts ranging from 10 mg to 50 g.
General considerations and "rules of thumb":
- You can not use amounts of chemicals that you cannot weight on your lab balance, either starting reagents or products - same goes for fluid measurements, graduated cylinders, pipettes, burettes...
- adjust amount of reagents considering various apparatus for reactions and purifications - reaction vessels, destilation apparatus, separation funnels, chromatography columns...
- Yield. Less you expect, more starting material you need. Or you will not be able to detect/isolate desired product. Also consider loses during purifications.
- Number of steps. More steps, cumulative losses, more starting material.
- Price. More expensive chemicals you need, less you will use. You definitely do not want to throw gram of precious metal complex on a tryout... Or half liter of some exotic solvent...

That should cover everything that crossed my mind for now...
...of course, these are guidelines for first time experiments. Production batches follow somewhat different rules, with desired amount of product dictating starting amounts of reagents, not minimizing initial expenses...

sargent1015 - 9-7-2013 at 17:01

Quote: Originally posted by kristofvagyok

Oh, someone mentioned me, thanks! (:

Oh, of course I had to mention you

I feel like this similar topic was covered quite some time ago. Plus, everyone needs to follow that Tumblr

bfesser - 9-7-2013 at 17:51

<a href="viewthread.php?tid=21684#pid271706">Real chemistry is dying out, why?</a>

adamsium - 9-7-2013 at 18:08

bfesser - I have never understood why some people like to perform every experiment at the Ymol <img src="../scipics/_wiki.png" /> scale (slight exaggeration there, perhaps - but only slight). I recall that thread and recall being irked by it. Small scale work has many, many advantages - for anyone, but particularly for the amateur chemist. I, personally, also find it more elegant than large scale work, which is often cumbersome and unwieldy (even more so in a home lab).

As for the original question; as small as is practicably reasonable is a good approach. This will, of course, mean different things according to the requirements and the desired outcome (as others have pointed out).

[<a href="u2u.php?action=send&username=bfesser">bfesser</a>: Ymol made me laugh; hard! You've earned a mystical <img src="../scipics/_wiki.png" />,]

[Edited on 7/10/13 by bfesser]

BromicAcid - 9-7-2013 at 18:22

Quote: Originally posted by kristofvagyok

Oh, someone mentioned me, thanks!(:

Yesterday I started to work at a chemical company where they produce several N protected amino acids (BOC, Cbz, Fmoc) and related stuff. I work at the research and development department and we design reactions from mmol scale to industrial size.

Neat! I've probably used your chemicals! When I was doing phosgene chemistry I was making all sorts of N-carboxyanhydrides from protected amino acids on the large and small scale and we almost always bought from Europe

Regarding the thread though, for me I've always been more concerned with the macroscopic properties of a reaction and find it intensely non-rewarding to run at a scale of less than a hundred milliliters of solvent. I love seeing things thicken and thin and change colors and with the small scale it's more like: Hummm... that's kind of dark, or is it getting thick?

It makes sense to run on the small scale, saves reagents, cheaper, less danger for unexplored reactions. But on the larger scale you combat loss of yields, crummy reactions, and your devo run might turn out to be your final run.

amazingchemistry - 9-7-2013 at 19:22

I will put in my 2 cents here: Like many things in chemistry, it depends on what you are looking for. Multistep syntheses cannot be done entirely in microscale unless you have sharpshooter-stable hands and an unnatural ability to prevent mechanical loss. Likewise, if your goal is to observe what's going on (watch stuff changing color, boiling, or doing other interesting things) microscale can be unrewarding. However, I will say that I personally like microscale and mini (meso) scale better than macroscale. Here's why:

-Less waste
-Less risk of exposure to toxic chemicals
-Less wait time (for heating, distilling and the like)
-Less setup and teardown time
-Literally forces you to think about what you're doing and to develop a plan for the most efficient way of doing things
-Increases (IMHO) your skill as a chemist, at least as far as dexterity goes.
-Allows you to use more expensive and exotic reagents.

The last point is in my opinion critical. My undergrad orgo lab was in micro/meso scale and I was able to use things like iodine monochloride, currently priced at 2 dollars a gram. If you think about it, if we had to use say, 5g my school would not have been able to buy that reagent for all of us (We were 100 in all) and the experiment may have been scrapped. My old lab manual even has a section on palladium on carbon hydrogenation. At 10 dollars a gram this experiment is out of reach for most of us if we want to do it macro. This is one of the biggest reasons for liking small scale. It expands the chemist's range.

testimento - 9-7-2013 at 19:44

First you do the math and theory speculations and shit
Then you do it in mg-scale to prove that it works
Then you can scale it in oil drum an cook away for streets.

watson.fawkes - 9-7-2013 at 19:52

Quote: Originally posted by adamsium

I have never understood why some people like to perform every experiment at the Ymol <img src="../scipics/_wiki.png" /> scale (slight exaggeration there, perhaps - but only slight).

And there I was thinking that a yotta-molecule scale reaction is only about about 66% larger than a one-mole scale reaction. That is a pretty slight exaggeration.

bfesser - 9-7-2013 at 20:08

1024 ( 6.022141 × 1023 ) = 6.022141 × 1047 = 602 214 100 000 000 000 000 000 000 000 000 000 000 000 000 000

That's a rather large number.

adamsium - 9-7-2013 at 20:40

No, watson. 'mol' is the abbreviation for mole, not for molecule. A 'Ymol' would be 10²⁴ moles, not 10²⁴ molecules. bfesser showed the number of molecules above.

sonogashira - 9-7-2013 at 23:44

Quote: Originally posted by kristofvagyok

Every time when I tried to scale up a reaction from 1mmol to "workable" amounts it simply didn't worked...

The reaction will work with 6.022x10^20 molecules but not with 6.022x10^23 molecules?!

Eddygp - 10-7-2013 at 01:02

Well, I usually work with 0.4 moles or so in my reactions. Working with like 0.02 or less would be a bit hilarious and boring, because I don't think anyone would be able to see something there except a spectroscope. The beauty of chemistry is not zurking with Ymol scales but not with zeptomol scales either. I like to see the changes, to be able to use the product for other different reactions.

EDIT: I realised that one yoctomole contains no particles. Actually, it contains 0.6021 particles...

[Edited on 10-7-2013 by Eddygp]

watson.fawkes - 10-7-2013 at 02:48

Quote: Originally posted by adamsium

No, watson. 'mol' is the abbreviation for mole, not for molecule. A 'Ymol' would be 10²⁴ moles, not 10²⁴ molecules. bfesser showed the number of molecules above.

Oh, I know. My first reaction, however, was "that's not an exaggeration; that's about a mole".

bfesser - 10-7-2013 at 06:03

For a little perspective on that number, the <a href="https://en.wikipedia.org/wiki/Observable_universe" target="_blank">observable universe</a> <img src="../scipics/_wiki.png" /> is calculated to contain about a tenth of a mole (6 × 1022

of stars, by one estimation. The approximate number of atoms in the universe is calculated to be nearly 1080 (again, estimates vary). Finally, by one estimate, the mass of the observable universe has been calculated to be 8 × 1052 kg.

1080 atoms = 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 × 10 atoms

= 100 000 000 000 000 000 000 000 000 000 000 000 000 000 000 000 000 000 000 000 000 000 000 000 000 000 000 atoms

This image contains 1.25 × 107 pixels (scaled to 800px &times 400px = 3.2 × 105 pixels for display, click for full resolution) and ~ 3.994 × 107 bits of data:
<a href="https://upload.wikimedia.org/wikipedia/commons/0/0f/Earth%27s_Location_in_the_Universe_SMALLER_%28JPEG%29.jpg" target="_blank"><img src="https://upload.wikimedia.org/wikipedia/commons/0/0f/Earth%27s_Location_in_the_Universe_SMALLER_%28JPEG%29.jpg" width="800" /></a><img src="../scipics/_wiki.png" />

Do you feel <a href="http://www.worldometers.info/world-population/" target="_blank">insignificant</a> <img src="../scipics/_ext.png" /> yet?

[Edited on 7/10/13 by bfesser]

GreenD - 11-7-2013 at 16:29

uh - on this note I came from a lab that used 'brute force chemistry'

It was really old techniques, and basically if we couldn't do it for under 300 bucks and get 10+g of our final product, we didn't want to even look into it.

Now, I work with herbicides. You know the active dose of some of these? 1uM.

So, we order 500mg for THE ENTIRE YEAR.

Needless to say, coming from a bruteforce lab, and now I'm synthesizing things on the <100mg scale, I really, REALLY hate forgetting to close my stoppers on my funnels >

Random - 11-7-2013 at 18:13

I like doing experiments in few mL test tube scale because it is a lot safer. Especially if I put on the gloves I can handle pretty toxic stuff and not be worried.

On another side handling a half a jam jar of toxic stuff would get hard. Especially if the reaction goes out of control. Lately I love to do a very small reaction in a test tube just to see how it goes. And if the reaction gets out of hand, on a small scale I can just throw the stuff in a bucket of water and forget about it. Doing this with 200-500g of something is not so viable.

Fantasma4500 - 12-7-2013 at 06:52

i would like to second that, but this is mainly if you have something you know youre gonna do several times...

take this site as a really good examble..

http://www.artsuppliesonweb.com/restauratie-chemie/chemicali...

as you see 100g copper nitrate is 6.25 euro
now if we go up to 1000g, 10 times as much we get it for 25
by advanced math we can say that if we buy 1 kg, each 100g in that would have a price of 2.5 euro, whereof buying 10 x 100g would cost 62.5 euro

in chemistry where you need to filter and such, yes there is waste when you filter it etc. so some processes might not be anywhere near worth it to do in small scale..

CuCl2 + Al + HCl > CuCl + AlCl3 + H2
the CuCl can be precipitated by being dumped in water, this is a nice little reaction for demonstration, however if you want this to have any use you might want to scale it up, otherwise very likely the precipitated CuCl will be clogged in the filter

the costs are relative, if you can only see whats in front of you at the moment then yes it will be very costly per kg
but if you have a company and you can buy home 50kg of reagent or perhaps tonnes, then it can be taken as an investment, its not that hard to figure out guys, come on, how can you not agree on a such simple thing?

adamsium - 12-7-2013 at 07:34

Antiswat:

No, no and no!

Just because it might be cheaper, per unit of weight, to buy in bulk, one does not have to scale up their experiments to be 'saving', even if they do buy in bulk. We're not talking about the scale at which we purchase reagents, but the scale at which we perform experiments. These are not the same thing!

The fact is that, when doing amateur chemistry, many of the procedures we do are purely for the enjoyment of it. It's our hobby; we do it because we like it. We are not generally doing it because we need large quantities of the end product.

We are not Sigma-Aldrich who can say "we can make 10 kg of this compound for $80/kg or 1000 kg for $20/kg" and, if they know that they can sell the 1000 kg, this is obviously in their best interests. However, for a home chemist, using these figures, 10 kg @ $80/kg = $800; 1000 kg @ $20/kg = $20,000. It really doesn't matter what the exact figures are, even if buying more starting material is cheaper per kilogram, buying more will still cost more and one does not have to use it all right away just because they have it.

The important point is that it still costs more to make more. There is no point in making more product than you need; it is still going to cost more, be more risky and be more of a disposal hassle.

Also, for amateur chemists who do work on a small scale, there is more to be gained in buying smaller quantities of different reagents rather than a large quantity of a single reagent. For the example you cite, you could buy 4 x 100g of different reagents (of that same price) OR you could buy 1 x 1000 g of that one reagent. The former will allow you to do a range of experiments with just those reagents and nothing else (save for perhaps water), while the latter will likely allow you to do.... not much.

How can you not agree on such a simple thing?

<hr>
[edit:] removed quoted text

[Edited on 12-7-2013 by adamsium]

amazingchemistry - 12-7-2013 at 20:45

I would like to add that given that a lot of us work out of our homes, I don't see how the so-called 'economy of scale' benefits us when you consider the logistical problem that arises from trying to store kilogram and liter amounts of potentially dangerous reagents as opposed to gram and milliliter amounts. On another thread, I suggested that flammable organics be stored in a modified fireproof safe (these can be found even at walmart for relatively cheap). However, if you are storing 2 liter bottles of stuff like acetone or diethyl ether you are going to need a dedicated cabinet if you want to have some measure of safety for yourself and your family, and those can run you in the hundreds or even thousands of dollars. Ditto for other nasty stuff. To me, having the amount of chemicals in stock required to do macroscale chemistry is a major logistical problem for the home chemist and not worth the money you're supposedly saving by buying reagents in bulk

ElizabethGreene - 14-7-2013 at 09:57

Large scale chemistry is certainly not dead. It's only wounded.

On How it's made yesterday I saw this beautiful copper smelting operation. The ore was contained in these massive ponds and leached with thousands of gallons of sulfuric acid. The runoff went to a mindbogglingly massive settling tank to concentrate and then they plated it out on thousands of starter copper sheets. It was beautiful.

I love to see big chemistry. That said, I read about this "slightly pyrophoric" pentabromide compound in Max Gegel's biography. His was near the end of a very long list of companies that refused to synthesize it. To put it in perspective, this refusal came from a person that repeatedly described retrieving reaction products from the ceiling, floor, and faces near the work area. If I get --suicidal-- ambitious enough to synthesize it, "tiny" amounts might be best.

In the youtube "PeriodicElements" video on Plutonium, the professor describes accidentally losing the UK's entire supply of plutonium (in Mg) one evening. He recovered most of it by sawing out the spilled section of the workbench, burning it, and leaching the salt from the ashes. Fun? Certainly!

bfesser - 14-7-2013 at 13:56

Wow, a megagram of plutonium‽ That's a metric ton!

Pickardjr - 14-7-2013 at 15:09

I used to be able to buy my stock cheap, then the economy took a dump and cost went up.All the reactions I used to do on a one mole maximum are now scaled down to mmol. scale and it sucks. aside from that the usa schooling isnt what it used to be and when I went to school, and I was a chem major the chemistry was just for demonstration and theory, bullshit stuff. All the skills I have now I learned from books on my own and own expense, very costly. my 2 cents.

ElizabethGreene - 30-7-2013 at 19:27

Mg, mg, it's so close, right? (I know, I know, close only counts in hand grenades and nuclear war.)

The compound in question was Pentaborane. Wikipedia has this to say.

Quote:

Above 30 °C it can form explosive concentration of vapors with air. Its vapors are heavier than air. It is pyrophoric—can ignite spontaneously in contact with air, when even slightly impure. It can also readily form shock sensitive explosive compounds, and reacts violently with some fire suppressants, notably with halocarbons and water. It is highly toxic and symptoms of lower-level exposure may occur with up to 48 hours delay. Its acute toxicity is comparable to some nerve agents.

franklyn - 12-8-2013 at 14:41

www.sciencemadness.org/talk/viewthread.php?tid=15549