So what's the downside of using a stainless steel distillation kit? The chemist can't see shit! There is a definite advantage of being able to see a reaction as it takes place and to see when something starts to distill over. All Strike can say is that the chemist must rely much more heavily on the readings of her thermometer and have a greater faith in the chemistry she is doing. By this Strike means that since there is probably going to be no more than different chemicals in the reaction flask, then all the chemist need be aware of is what thing comes over first , second and last.
Strike knows. It's a little more complex than that. But if a chemist gets the hang of distillation it really can be as simple as that. It is just a device to hold high boiling or high-pressure reactions in an enclosed cell. The bomb should be made from a stainless steel pipe that has as big of an inner diameter as possible width, bubba! There are two good configurations which can be seen in figure 5. One end is permanently sealed by welding.
The other end, no matter which configuration is used, should have as much and as fine a threading as possible. Also, when sealing up the pipe bomb, it is a great idea to wrap a lot of teflon tape around the threa. This will form an absolutely air tight seal. It is also possible to substitute a stainless steel pressure cooker for some sealed, pressured reactions.
Usually if something smells bad then it's probably bad for the chemist to smell it. Some reactions are, by design, supposed to vent bad things that, when unchanneled, have nowhere to go but into the living room of the chemist. Sometimes there is no guarantee that a method will go as planned.
There may be a mistake or unforseen side reaction and some of the most deadly shit imaginable can be evolved. That is why the chemist will construct the one thing that may end up saving her life: a fume hood. The blower motor is constantly sucking the air from the hoods to the outside so that chem'1sts will not be exposed to the vapors of chemicals they are working with inside the hood. The same precautions are taken by non-dead underground chemists.
A fume hood is constructed in the manner shown in figure 6. Strike drew the frame as being made of lumber but it can be made of rebar or, preferably, from PVC pipes and joints so that it can be assembled and disassembled with ease. The frame is enclosed with plastic drop cloths or any semiclear plastic sheeting. The front face of the hood is halfway covered with plastic white the bottom half is exposed to allow one to move objects in or out and to manipulate things.
On top of the chamber is attached some clothes dryer duct or some such crap which is led to a leaf blower or blower motor. The exhaust from the blower is led away to the outside. If so, then the hood works just fine. Many houses have outside-venting blowers over their stoves. Chemists in these situations can actually drape some plastic around their stovetop to make a perfectly adequate hood. However, chemists who live in apartments never, ever attempt any chemistry at all in their pads.
Well, not only do apartment stoves lack an outside vent; but to vent a constructed hood through a chimney or out a window with so many close neighbors liVing about is just plain stupid. If a chemist fucks up and blows herself up or starts a fire then she is not only harming herself but is also going to put a lot of her neighbors out on the street, in the hospltal or in the morgue.
No one making drugs has the right to jeopardize others in this manner. That is why drug making is always done in a house, barn, mobile home watch out for tornados , submarine or cave. These are the most basic lab techniques and almost every method in this entire book will require many, if not all, of the protocols to follow.
So pay attention! Well, when one puts something into the readion flask and heats it, low boiling stuff like organic solvents acetone, ether, DCM etc. They then drip down into the receiving flask. Next usually comes water, then finally as far as drug chemistry is concerned comes high boiling drug oils. Distillation is the most preferred and reliable way to purify substances from one another. There are three basic forms of distillation: simple, vacuum and fractional distillation, which can be an extension of the first two.
Simple distillation is just plain old distillation with no vacuum and is used for purification of low boiling mixes or for removing solvents such as ether. For vacuum distillation a thick walled or reinforced hose is connected from a vacuum pump to the nipple tee hee! Application of a vacuum greatly reduces the temperature of boiling and is a must for most of the distillation in this book. Fractional distillation is merely vacuum distillation except an added glassware component such as a small Vigreux column or a Clalsen adaptor packed with shards of glass is placed between the reaction flask and the 3-way joint of a normal setup.
Either of these additions create a gauntlet of extra surface area elements that distilling liquids must pass through in order to condense. This affords a greater degree of separation between mixes of oils that have similar boiling points. However, it has been Strike's observation that most of the bulk separation in this book using distillation can be achieved with regular old vacuum distillation. If the chemist only has a hotplate then the chemist is going to have to add some boiling stones to the flask.
Boiling stones can be either little chips of teflon, little wadded up balls of teflon tape or little pieces of a shattered porcelain counter top tile. All of these things have lots of microscopic pockets of air in them that help to faeilitate the start of boiling. Many of the solutions in this book, especially organic solvent solutions, need these boiling stones in them if they are going to be heated.
If there are no boiling stones, then a phenomenon called superheating may occur whereby the solution will start to get hotter than its actual boiling point temperature. Eventually it will burst into boiling but a lot of it will have gone sploosh! Not good. Another thing or two to remember when distilling is to wrap aluminum foil around the reaction flask. This will help stop heat loss so that things will distill quicker and at lower temperatures.
Sometimes, if one is going to distill a solution that is just solvent and product, all that pure solvent that comes over first is perfectly reusable and should be saved for future extractions. The last thing about distillation that needs mentioning is the swapping out of collection flasks. When distilling under vacuum it witt be necessary to remove the flask that has collected all the solvent or crap and replace it with a dean one to coiled all the product that will be coming over shortly.
This swapping of flasks needs to be done quickly as soon as the vacuum hose is disconnected. By quick Strike does not mean lightning fast.
Just quick enough so that the hot solution in the reaction flask does not get too much hotter from the heat source it is sitting on, because if it does, and the vacuum is reapplied, it may pull a little form of that superheating stunt and go sploosh!
The most general thing that can be said - 25 - about refluxing is that it's just plain old boiling except that there is a condenser attached to the flask so that nothing escapes. The condenser must be Supplied with really cold water, especially when refluxing high boiling solutions. One side note about the drying attachment is that it need not be a vacuum adapter. Anything, such as a funnel, that can hold a plug of drying material and fit snugly into the condenser will work.
The most basic way to extract is to pour the water solution into a PP container, add some solvent and stir the two as fast as possible for a few minutes. Most equipped labs use a large separatory funnel to shake the two liquids. When using a separatory funnel it is very important to vent the funnel as soon as the stopper is smacked into the top.
This is done by immediately inverting the funnel so that the stopcock end is facing upward, opening the stopcock to release the pressure then closing the stopcock. The sep funnel is given a quick shake then vented again. This is repeated a couple more times after which the pressure production will have pretty much ceased. The rule is to then shake for 2 minutes and allow the layers to separate for 10 min utes. And which layer is going to which? Ether and benzene are always on top of water and DCM and hexane are always on the bottom.
Most science papers call for things to be extracted 3 times 3X with a solvent. Strike feels that this is overkill and that one or two times is usually sufficient. Sometimes one has so much product oil that it forms its own heavy layer usually at the bottom.
There is no need to extract such a large amount with solvent. In such a case one would merely drain the oil from the water or, if using a PP container, decant the water from the oil. The water itself can then be extracted once with solvent and the solvent added to the oil.
Well, a closer look at it in fig. The drying agent can be either a commercial product called Drierite or calcium chloride. This attachment is placed on top of a condenser when refluxing solutions that have no water in them n? All thiS IS to prevent moisture in the outside air from coming Into contact with the cold surface of the of the inside walls of the condenser.
This will surely happen and the condensed outside-air water will drip down into the reaction flask and ruin the experiment. This is not so much a - 26 - WASHING Washing is almost always the act of taking an organic solvent layer most likely the one that was obtained from the extraction of some previous aqueous solution which usually contains product oil and mixing washing it with clean water then discarding the water.
A solvent layer is often washed with a dilute acid or base salt solution to neutralize anything the solvent may have absorbed from previous extractions. These salt solution washings are then followed by clean water washings. Since we're on the subject of clean water, this is as good a time as any to discuss what kind of water is used in all this chemistry. By clean water Strike means distilled water dH All reactions are to use distilled water dH2 0 only. All solutions and dilutions are to be made with dH20 as well.
Tap water is an absolute no-no 1n chemistry except for deaning the glassware. Drying isn't absolutely necessary, but it is a good bet that if a recipe stresses its use then an evil underground chemist will do so.
Figure 8 shows the proper apparatus to use. The collecting flask is called a side arm flask and to that extended nipple tee hee!
The thing that is shoved through the rubber stopper is called a Buchner funnel and is usually made of white porcelain or, preferably, PP. The Buchner funnel, when viewed from above, can be seen to have lots of pin holes in the bottom surface of its reservoir. Over this surface is layered a single sheet of rounded filter paper or paper towel. To filter a solution one attaches a vacuum and pours the solution into the Buchner funnel.
All the solution will go whoosh! The liquid that has collected in the flask is now called the filtrate. Usually, the filter cake is then washed with a little bit of clean whatever-kind-of-solvent-it-was-just-tiltered-from. That extra washing is then combined with the other filtrate. The most action this procedure is going to see in a clandestine chemistry lab is at the very end of the drug-making process where the chemist will have crystallized her freebase oil into a final, marketable form and then needs to separate those crystals from the solvent they are in.
DRYING Just as it is with laundry, drying often follows washing and is used to rid the solvent of any water that it absorbed. All solvents absorb some water although you can't see it. All one has to do to dry something is to take a sheet of filter paper or paper towel, fold it into a cone and place it into a funnel. About a shot glass full of sodium sulfate Na2 or magnesium sulfate Is dumped into the filter and the solvent poured through it.
It is also a good idea to follow up by rinsing the Na2 S04 with a little extra, clean solvent to insure that everything gets washed out of the drying agent. The Na2 S04 is a white crystalline salt that tastes like table salt. It binds water molecules without readily dissolving and leaves the solvent water free.
Where to begin! Well, starting with this chapter is a good idea! Every amphetamine is a chemical. And s nce. For ecstasy, that starting chemical is almost always Safrole. Safrole is the 1 starting material for making X today.
As a pure chemical it is a schedule 1 controlled substance and, obviously, is illegal to own or buy without a permit. Sassafras has a I strong licorice smell which is imparted to. Cammercially, there are two kinds of sassafras. Other places to order essential oils would be home care products houses, toiletry base companies, soap companies, flavoring companies, aromatherapy stores and organic foodstuff companies. As of the year , small quantities of sassafras oil are still being sold on retail shelves without any scrutiny.
Usually in oz sizes. Anything larger is usually sold only through distributors and manufacturers. And as of , the DEA has informed most of these distributors that they the DEA want lists kept or sales reported of most, if not all, sassafras oil purchases. Mind you it is not illegal to buy the oil.
It's just that you will be put on a list if you do. The operative term here is 'Watched Substance'. Solution: have someone else buy it for you.
Strike has also been poking around the DEA and is getting the distinct impression that they will very soon reschedule sassafras oil as schedule I. Then one won't be able to get it at all without a permit or some serious deception. There are some rather exotic sources of safrole for the desperate, governmentally-challenged citizens of the future. Also, there is a spice bush that grows in India called Betel.
Betel leaf oil can. The sassafras tree itself grows like a weed in the wilds and along disturbed fence lines throughout the south, southeast. Well, if one were to go down to one of those sickenlng hippie health food stores or incense shops there, on the shelves, will be small ottles of o ecstacy starting material labeled as sassafras Larger quantities are ordered rather cheaply from fragrance or perfume supply companies that one can find in any big city yellow pages.
Now the people at these companies aren't stupid. They have a general idea of what some of their essential oils can be used for so they might ask. But they still have no legal reason. After all, the same stuff Is bemg sold over the counter to hippies just down the street. Just to make every- - seaboard, and Appalachian mountain regions of the United States.
The trunk and root bark of older, mature sassafras trees can be steam distilled to afford the safrole-containing oil. Another source of safrole would have to the be leaf oil of a little shrub that grows down in the low woods and swamps throughout the coastal plains from Florida to Georgia. The plant is known as Illicium parviflorum michx and Strike has no idea what the hell it looks like.
A new source of safrole that Strike has just stumbled upon is in Strike's back yard. Momma comes home from the local nursery with two plants that have these enonnous leaves. They are succulents and grow like crazy. Strike: "What ya got there Momma? Let's not get into this again. Strike doesn't.. Oh Yeah! That's the bomb! The plant is called Piper auritum.
Its common name is Hojo Santa. Strike loves Strike's mother. Suffice to say that anything that remotely smells like Sassafras oil or licorice or any of those strong rustic spices is going to have some amphetamine precursor, maybe not safrole exactly, but definitely something. There is just no other substitute in nature for the aroma these unique compounds give.
The sassafras oil that one gets these days is not only going to have the safrole but is usually going to have some amount of each of the compounds seen in Table 1 . Little white crystals of eugenol anion will form in the water layer. The water layer is poured off and saved. That eugenol is valuable. Eugenol is usually the main contaminant in safrole in more ways than one. It is the only molecule in sassafras oil that will react the same way as safrole so if it hangs around with the safrole it will compete with safrole in the conversion reactions.
Also, eugenol is about the closest to safrole in both structure and boiling point so that trying to get rid of it by fractioncil distillation will be very tough indeed. The cleaned oil will look a little cloudy now. Strike still does not know why. His impact on chemistry, biology, and medicine flows from his works in organic synthesis described in nearly publications and 70 patents as well as his dedication to chemical education, as evidenced by his training of over graduate students and postdoctoral fellows.
Sorensen, is used around the world as a teaching tool and source of inspiration for students and practitioners of organic synthesis. Dionisios Vourloumis, born in in Athens, Greece, received his B. Magriotis, in , working on the synthesis of novel enediyne antibiotics. He joined Professor K.
Nicolas Winssinger was born in Belgium in He received his B. Before joining The Scripps Research Institute as a graduate student in chemistry in , he worked for two years under the direction of Dr. Pavia at Sphinx Pharmaceuticals in the area of molecular diversity focusing on combinatorial chemistry. At Scripps, he joined the laboratory of Professor K.
Nicolaou, where he has been working on methodologies for solid-phase chemistry and combinatorial synthesis. His research interests include natural products synthesis, molecular diversity, molecular evolution, and their application to chemical biology. Phil S. Baran was born in Denville, New Jersey in Schuster and S.
Wilson, exploring new realms in fullerene science. Upon entering The Scripps Research Institute in as a graduate student in chemistry, he joined the laboratory of Professor K. Nicolaou where he embarked on the total synthesis of the CP molecules. His primary research interest involves natural product synthesis as an enabling endeavor for the discovery of new fundamental processes and concepts in chemistry and their application to chemical biology.
Corey has thus been awarded with the Prize for three intimately connected contributions, which form a whole. Through retrosynthetic analysis and introduction of new synthetic reactions, he has succeeded in preparing biologically important natural products, previously thought impossible to achieve. It has been on the move and center stage throughout the twentieth century and continues to provide fertile ground for new discoveries and inventions. Its central role and importance within chemistry will undoubtedly ensure its present preeminence into the future.
The practice of total synthesis demands the following virtues from, and cultivates the best in, those who practice it: ingenuity, artistic taste, experimental skill, persistence, and character. In turn, the practitioner is often rewarded with discoveries and inventions that impact, in major ways, not only other areas of chemistry, but most significantly material science, biology, and medicine. The harvest of chemical synthesis touches upon our everyday lives in myriad ways: medicines, high-tech materials for computers, communication and transportation equipment, nutritional products, vitamins, cosmetics, plastics, clothing, and tools for biology and physics.
There must be several reasons for this phenomenon. To be sure, its dual nature as a precise science and a fine art provides excitement and rewards of rare heights. Happily, the practice of total synthesis is being enriched constantly by new tools such as new reagents and catalysts as well as analytical instrumentation for the rapid purification and characterization of compounds.
Thus, the original goal of total synthesis during the first part of the twentieth century to confirm the structure of a natural product has been replaced slowly but surely with objectives related more to the exploration and discovery of new chemistry along the pathway to the target molecule. More recently, issues of biology have become extremely important components of programs in total synthesis. It is now clear that as we enter the twenty-first century both exploration and discovery of new chemistry and chemical biology will be facilitated by developments in total synthesis.
In this article, and following a short historical perspective of total synthesis in the nineteenth century, we will attempt to review the art and science of total synthesis during the twentieth century. There are clearly overlaps in the last three eras and many more practitioners deserve credit for contributing to the evolution of the science during these periods than are Angew. As in any review of this kind, omissions are inevitable and we apologize profusely, and in advance, to those whose brilliant works were omitted as a result of space limitations.
But if a chemist gets the hang of distillation it really can be as simple as that. The collecting flask is called a side arm flask and to that extended nipple tee hee! Today, natural product total synthesis is associated with prudent and tasteful selection of challenging and preferably biologically important target molecules; the dis- 1. Because an alternative reaction for isomerization would be to use a saturated aqueous water, Zak KOH solution instead of an alcoholic one. And which layer is going to which? The safrole can then be separated from its still oily buddies by vacuum filtration.
Many houses have outside-venting blowers over their stoves. Being both a precise science and a fine art, this discipline has been driven by the constant flow of beautiful molecular architectures from nature and serves as the engine that drives the more general field of organic synthesis forward. The harvest of chemical synthesis touches upon our everyday lives in myriad ways: medicines, high-tech materials for computers, communication and transportation equipment, nutritional products, vitamins, cosmetics, plastics, clothing, and tools for biology and physics. In the course of the investigation of a complicated substance, the investigator is sooner or later confronted by the problem of synthesis, of the preparation of the substance by chemical methods. One side note about the drying attachment is that it need not be a vacuum adapter. Of course, one should use only the amount of alcohol necessary to dissolve the expected yield of Safrole.
Here nature is the uncontested master, but I dare say that the prize-winner of this year, Professor Woodward, is a good second. Eventually it will burst into boiling but a lot of it will have gone sploosh! Also, there is a spice bush that grows in India called Betel. A fume hood is constructed in the manner shown in figure 6. Total Synthesis in the Nineteenth Century The birth of total synthesis occurred in the nineteenth century. The funnel part is just a PP funnel from the grocery store and what it is attached to is a stainless steel ball valve.
The alkaline solution is placed in a round-bottom flask provided with a reflux condenser microwave or conventional systems.
The most basic way to extract is to pour the water solution into a PP container, add some solvent and stir the two as fast as possible for a few minutes. One side note about the drying attachment is that it need not be a vacuum adapter. Also, eugenol is about the closest to safrole in both structure and boiling point so that trying to get rid of it by fractioncil distillation will be very tough indeed. If one has a round-bottom flask or a low output heatng source, a shallow oil bath can be employed to get even heatmg.
The crud remaining in the filter is the junk that was causing all the trouble.
This description and praise for total synthesis resonates today with equal validity and appeal; The water layer is poured off and saved. He was kinda right But, those Brazilian improvements above aren't here just to take up space! Sound easy? The most general thing that can be said - 25 - about refluxing is that it's just plain old boiling except that there is a condenser attached to the flask so that nothing escapes. Shake for a coupe of minut s.
There are clearly overlaps in the last three eras and many more practitioners deserve credit for contributing to the evolution of the science during these periods than are Angew. Filtered or not, the ethanolfisosafrolef sometimes junk is relieved of its ethanol by openly boiling it on the stove or by distillation. WATER PUMP This is going to supply the cold water that courses through the condenser whether that condenser is set up for reflux or is part of a distillation configuration.
Every amphetamine is a chemical. Strike loves Strike's mother.
Just quick enough so that the hot solution in the reaction flask does not get too much hotter from the heat source it is sitting on, because if it does, and the vacuum is reapplied, it may pull a little form of that superheating stunt and go sploosh! The harvest of chemical synthesis touches upon our everyday lives in myriad ways: medicines, high-tech materials for computers, communication and transportation equipment, nutritional products, vitamins, cosmetics, plastics, clothing, and tools for biology and physics. This description and praise for total synthesis resonates today with equal validity and appeal; Strike drew the frame as being made of lumber but it can be made of rebar or, preferably, from PVC pipes and joints so that it can be assembled and disassembled with ease. As in any review of this kind, omissions are inevitable and we apologize profusely, and in advance, to those whose brilliant works were omitted as a result of space limitations.
The Na2 S04 is a white crystalline salt that tastes like table salt. Just to make every- - seaboard, and Appalachian mountain regions of the United States. My process that I am proposing takes advantage of differential solubility among the various oils in acetic acid to separate the mixture down to only two components. Chemists in these situations can actually drape some plastic around their stovetop to make a perfectly adequate hood. He received his B.
There are two good configurations which can be seen in figure 5.