THE SALICYLATES, ASPIRIN, AND THE BIRTH OF ORGANIC SYNTHESIS:
Organic compounds were so called originally because they were made by populating beings. Now, it is possible to do 1000000s of organic compounds in the research lab. What they all have in common is a C anchor.
1. Identify the ACETYL GOUP, THE CARBOXYLIC ACID GROUP, the HYDROXYL GROUP AND THE METHYL GROUP on acetylsalicylic acid and methyl salicylate.
2. Trace the salicylate C skeleton on salicylin.
The undermentioned essay was written by Professor A.C. Gibson for his class in Economic Botany at UCLA:
SALICACEAE, Willow Family
The history of medical specialty has been enriched by 1000s of works species, but one works — the willow — has likely been used and prescribed more than any other powdery drug. Willow is the original beginning of acetylsalicylic acid. Even today, when acetylsalicylic acid replacements are available, up to 80 million tablets of acetylsalicylic acid are used each twenty-four hours in North America, and up to 50 million lbs each twelvemonth are swallowed throughout the universe. Now aspirin can be easy made [ industrially ] by responding phenol and C dioxide.
Hippocrates of Cos ( 460-377 B.C. ) noted that masticating foliages of willow ( Salix ) reduced hurting, and he prescribed this redress for adult females in labour. Hippocrates surely did non detect this drug, which was used for centuries earlier in European common people medical specialty. ( We should be cautious in crediting Hippocrates with everything because research workers have suggested that the extended aggregation of medical Hagiographas found in Alexandria, once ascribed to Hippocrates, may hold been written by several people, the most influential of whom was Hippocrates. ) Subsequent antediluvian Greek doctors recommended willow for relieving hurting and cut downing febrility and redness. In North America, likely even before the Greeks, the Alabama, Chickasaw, and Montagnai Indians used willow to alleviate febrilities, achings, and strivings, and the good effects were besides known to the Hottentots of southern Africa.
Advocates of the Doctrine of Signatures described how willow worked to cut down redness of articulations because the “ crying ” subdivisions were really flexible, like human limbs. Equally tardily as 1763, an English reverend named Edward Stone ( besides known as Edmund Stone ) wrote that willow is utile for take downing febrility because both willow and fever thrive in moist parts.
In the 1820s, European chemists, thirstily analyzing the chemical science of workss, were able to insulate from willow a glycoside, which was named salicin, after the genus. Salicin was besides discovered in poplars and aspens ( besides Salicaceae ) . In the research lab, Karl Lowig ( 1839 ) treated salicin with acid — as salicin is acted on in the human tummy — to do salicylic acid, and about that clip salicylic acid was besides discovered happening of course in a European species of Spiraea ( dropwort ) . Salicylic acid had major medicative utilizations and shortly became a Panacea. A related compound being used at that clip was methyl salicylate, found in an oil from birch bark ( Betula lenta ) and oil of pyrola ( Gaultheria procumbens ) , long used to alleviate achings. In this century, oil of pyrola was once used in “ anodynes ” ( rubefacients ) for jocks. [ And still is in SportsBalm ]
The job with salicylic acid was that, for many, it caused sickness and great stomachic uncomfortableness. A different compound was synthesized in 1853 by Carl von Gerhardt by seting an acetyl group on salicylic acid, doing acetylsalicylic acid, which is a chemical salt ( solid ) . Nonetheless, no 1 was cognizant of the more soft belongingss of this compound until 1893, when Felix Hoffman, an employee of Friedrich Bayer and Company, found an easier manner to do this salt and so tested it on his male parent, who had arthritis. In 1899, Bayer, which started in 1863 as a dye production company, marketed this medical specialty as “ acetylsalicylic acid ” — coming from the words ‘acetyl ‘ and Spiraea. The monetary value of acetylsalicylic acid ab initio was expensive until Bayer learned how to mass green goods tablets. Aspirin was therefore the first major medical specialty in the universe to be sold in tablet signifier.
As the ancients already knew, acetylsalicylic acid is a singular analgesic, i.e. , an analgetic. Research indicates that painkilling consequences from the depressant action of acetylsalicylic acid on the cardinal nervous tissue, somehow by cut downing mild to chair hurting messages from making the encephalon. A really of import usage of acetylsalicylic acid is as an antipyretic, i.e. , to take down organic structure temperature ( febrility ) , via the dissipation of heat through effects on the hypothalamus, increasing perspiration. The 3rd major usage of acetylsalicylic acid is as an anti-inflammatory agent ( cut down swelling ) , as for victims of arthritis and “ rheumatism. ”
American consumers spend $ 700,000,000 to $ 800,000,000 per twelvemonth on analgesics ( excepting opiates ) , particularly aspirin and Datril, the really common option that is marketed under names such as Tylenol, Datril, and Liquiprin. Both chemicals allay hurting, but there are of import differences. Aspirin, which is significantly cheaper, has the extra anti-inflammatory effects and therefore is critical for arthritis patients ( much cheaper than the viing drugs ) . However, as arthritis hurting intensifies, aspirin doses must besides be made stronger, and high doses are potentially more unsafe. Maximal aspirin day-to-day dose should be 60 grains per 24 hours.
Medical surveies on the consequence of acetylsalicylic acid on interrupting up blood coagulums ( an antithrombotic drug ) are now reasonably conclusive, and many doctors prescribe day-to-day acetylsalicylic acid after bosom onslaughts or even as a preventive plan because acetylsalicylic acid inhibits release of prostaglandin and thereby platelet agglutination. There are more effectual, but non cheaper, antithrombotic drugs, e.g. , sulfinpyrazone.
There are over 500 aspirin deceases in this state every twelvemonth, from big accidental ( kid ) or largely self-destructive ( grownup ) overdoses or, seldom, from allergic reactions. [ In 1989, there were 1.28 million consumption toxic conditions, of which 5889 were of acetylsalicylic acid, and ten times more of Datril. ] Actually, in the United States, kids aspirin deceases have declined from 40 to merely 2 within the last 20 old ages. The unsafe side consequence of acetylsalicylic acid is GI annoyance and tummy hemorrhage, which contribute to stomach ulcers ( caused by bacteriums ) . For handling simple achings and strivings, painkilling pills that combine aspirin with Datrils do non look to be any more utile than a individual chemical.
Possibly a piece of judiciary history is needed here. Aspirin was a patented name by Bayer, but this German company had struggles with France and Great Britain, who fought against Germany in World War I and did non admit that patent. Australia besides began its ain production when acetylsalicylic acid could non be supplied at that place. A legal conflict ensued when Monsanto in the United States began its ain production in 1917, and this finally reached the U.S. Supreme Court, which ruled that “ acetylsalicylic acid ” had become so widely advertised and common that Bayer no longer owned the name. Hence, acetylsalicylic acid is now a slang name, which is why big companies of other merchandises now sharply take anyone to tribunal when a popular merchandise name is unlawfully used.
Excerpted from: Gibson, A. C. Economic Botany, UCLA, hypertext transfer protocol: //www.botgard.ucla.edu/html/botanytextbooks/economicbotany/Salix/
See besides: Insel, Paul, “ Analgesic-Antipyretics and Antiinflaamatory Agents ” in: Goodman & A ; Gilman ‘s The Pharmacological Basis of Therapeutics, 8th ed. , A. G. Goodman, T.W. Rall, A. S. Nies and P. Taylor, eds. McGraw-Hill, NY, 1993.
In this lab, you will synthesis acetylsalicylic acid and oil of pyrola from salicylic acid:
Balanced equation for the reaction of salicylic acid and acetic anhydride
To do acetylsalicylic acid, you will respond salicylic acid with a beginning of ethanoyl group groups called acetic anhydride. An acetyl group from acetic anhydride reacts with the hydroxyl group on salicylic acid, doing an ester, which you will come to cognize and love in Organic following twelvemonth.
In the presence of acid and some heat, this reaction occurs rapidly. Aspirin is less soluble in H2O than salicylic acid, and will precipitate out of solution, doing it easy to insulate and sublimate. It wo n’t be pure plenty to utilize against a concern, nevertheless.
BEFORE YOU COME TO LAB:
IDENTIFY THE ESTER GROUP ON ASPIRIN.
Following hebdomad you will measure the pureness of your acetylsalicylic acid by titration.
To do oil of pyrola, you will utilize methyl alcohol to do an ester, but this clip on the carboxylic acid group of salicylic acid. You will happen that many esters smell good, and oil of pyrola is no exclusion.
BEFORE YOU COME TO LAB:
Where does the methyl group on methyl alcohols end up?
We wo n’t make anything farther with oil of pyrola.
Balanced equation for the reaction of salicylic acid and methyl alcohol
BEFORE LAB PREPARATION:
Set up a Table of Reagents in your lab notebook, and in Excel. See page 10.
I. SYNTHESIS OF ASPIRIN FROM SALICYLIC ACID:
FIRST things foremost:
I. Set up a boiling H2O bath in a 400 or 600 mL beaker on a hot home base.
two. Start chilling approximately 100 milliliter of ice H2O in a 250 milliliter beaker.
B. Get the REACTION traveling:
I. Weigh out 4.0 gms ( +/- 0.0001 g ) of salicylic acid. ( SalH ) . What is means is: you need more than 3.9 gms and less than 4.1 gms of salicyclic acid, and DO NOT blow your clip seeking to acquire precisely 4.0000 gms of salicylic acid. DO record the exact mass of salicylic acid you use, to the nearest 0.0001 g. , in your notebook.
Caution: Salicylic acid is a skin thorn. Do n’t take a breath the dust, clean up the balance country and rinse your custodies.
two. Clean up the balance.
iii.The TA or lab teacher will distribute for you, in the goon, 10 milliliter of acetic anhydride. Twirl the flask to blend the SalH, add 10 beads of 18 M ( conc ) H2SO4, and heat the flask in your boiling H2O bath for about 15 proceedingss. Keep an oculus out for bumps.
Caution: Acetic anhydride is an oculus thorn. Avoid contact with tegument & A ; eyes.
Conc. H2SO4 is strongly caustic. Keep it off your tegument, out of your eyes, and in the glass part of the Pasteur pipet. Keep the pipet straight up & A ; down. Do n’t lean it and allow sulphuric acid run into the bulb. If you spill any on yourself, wash up with tonss of H2O.
C. While you WAIT: Put up the Oil of Wintergreen homework ( portion 2 ) .
D. CRYSTALLIZE out the acetylsalicylic acid you made from the remainder of the material:
Carefully take the reaction flask out of the boiling H2O bath and add 20 milliliter of ice H2O to it. This will break up extra acetic anhydride:
Put your flask on ice and stir it on occasion until the acetyl salicylic acid has come out of solution. Aspirin ( acetyl salicylic acid ) is much less soluble in cold H2O than salicylic acid, which will remain in the supernatant. Crystallization can be rapid and dramatic, with big white crystals crashing out of solution ; it can besides be stunningly slow. In general, fast crystallisation, while fulfilling to the Type A Personality, consequences in less pure crystals. If you do n’t see crystals in 5 proceedingss or so, confer with your teacher for tips. If you do n’t acquire crystals at all, but see “ oiling out ” , put the flask back in the boiling H2O bath, reheat it until it no longer looks oily, and cool it once more on ice ( do n’t add more ice H2O ) .
E. FILTER the solid acetylsalicylic acid off from the remainder of the material:
Set up a vacuity filter setup ( there will be a demo setup on the front bench ) , utilizing a Buchner funnel and side arm flask. Put in a piece of filter paper, start the vacuity, and wash the filter paper with distilled H2O to seal it down.
Pour the contents of your reaction vas onto the filter paper. You ‘ll detect that the 2nd jurisprudence of Lab Science is in consequence, viz. that a batch of acetylsalicylic acid is lodging to the glass. Rinse the reaction vas with 10 milliliter of ice cold H2O, twirl it about to acquire the acetylsalicylic acid, and add that to the filter. Repeat one or two more times to acquire the remainder of the acetylsalicylic acid.
If you see any crystals organizing in your side arm flask, pour T he filter into your reaction vas, re-assemble the filter, and re-filter.
Wash the acetylsalicylic acid crystals on the filter paper with about 10 milliliter of ice cold H2O.
F. RECRYSTALLIZE the acetylsalicylic acid:
The acetylsalicylic acid sitting on your filter paper is assorted with unreacted salicylic acid, and acetic acid and sulphuric acid that have n’t washed off. To clean it up:
Scrape the crystals into a 100 milliliter beaker. Add ethyl alcohol, 1 milliliter at a clip, with VIGOROUS SWIRLINGaˆ¦ ( 3rd Law of Lab Scienceaˆ¦STIR IT UP! ) until the aspirin dissolves. Do n’t add any more ethyl alcohols than you need to ( 20 milliliter should make it ) and STIR between ethanol add-ons.
Get down about 50 milliliters of H2O warming up on a hot home base.
Warm the ethanol/aspirin solution on a hot home base ( NO OPEN FLAME ) to about 60oC. Pour in approximately 50 milliliter of warm H2O into the ethanol/aspiring solution, stir it, cover it with a ticker glass, and set it in an ice bath to crystallise. Aspirin is much less soluble in H2O than ethyl alcohol, and much less soluble in cold H2O than hot. Salicylic acid is more soluble than acetylsalicylic acid in H2O, and will remain in solution. You will lose some acetylsalicylic acid in this measure, but what you have left will be purer.
Be certain you describe in your notebook what the colour and form of the acetylsalicylic acid crystals are.
G. RECOVER your acetylsalicylic acid, DRY it, WEIGH it and Salvage it for following hebdomad.
I. Vacuum filter your crystals, and rinse them with two 10 mL parts of ice cold H2O.
Scrape your crystals into a clean 100 milliliter beaker, LABEL THE BEAKER with your name & A ; subdivision, cover it with parafilm with holes punched in it, and topographic point it in the country provided. Following hebdomad, you will acquire the mass of the acetylsalicylic acid, cipher the % output, and assess the pureness of your merchandise by titration against standard NaOH.
II. SYNTHESIS OF OIL OF WINTERGREEN:
A. SYNTHESIZE Oil of Wintergreen:
In a 10 milliliter Ehrlenmeyer flask, blend 0.10 g of salicylic acid with 10 beads ( & lt ; 0.5 milliliter ) of anhydrous methyl alcohol.
Add 1 bead concentrated ( 18 M ) H2SO4 and a boiling bit, and heat the mixture gently for approximately 5 proceedingss.
B. Detect the merchandise.
Remove the reaction vas from the heat, stir the mixture with a clean stirring rod, and carefully smell what you have made.
ALL WASTE FROM THIS EXPERIMENT GOES IN THE JUG LABELLED “ ORGANIC WASTE ” IN THE HOOD
Equipment for 2 pupils
400 or 600 milliliter Beaker for boiling H2O bath
( larger size preferred )
Demonstrations: Vacuum filtration apparatus1
250 milliliter beaker for ice H2O
125 milliliters Ehrlenmeyer
Hot home base
Clamp for Ehrlenmeyer cervix
Ice bath in gray plastic bath
Buchner funnel & A ; neckband
+ filter paper to suit
250 mL Side arm flask & A ; tubing
Wash bottles of H2O
100 milliliter beaker
10 milliliter grad cylinder
Oil OF WINTERGREEN
10 milliliters Ehrlenmeyer flask
Pastuer pipet & A ; bulb
Reagents needed ( for 2 pupils )
( distribute little volume for each
subdivision, maintain phial tightly closed )
1 wash bottle
Oil OF WINTERGREEN
1 fictile dropper bottle