Synthesis of Acetylsalicylic Acetylsalicylic Acid (Aspirin) Mary Coleen A. David, Eunice Mae D. del Valle, Sean Romeo . Desa!on, Maria Cauline M. "an!, #enicca $amela %. &o, #an Chr'tien M. &uillo Group 3, 2F-Pharmacy, Organic Chemistry Laboratory, Faculty of Pharmacy, University of anto !omas
ASRAC Acetlysalicylic acid, also no*n as Aspirin, is one of the most *idely used medications to reduce fever and is also used u sed as a pain iller. +t is an acetyl derivative of salicylic acid. he o-ectives of this eperiment are to calculate the percenta!e yield of aspirin and eplore the chemical process in the synthesis of aspirin. Aspirin is synthesi/ed via an esterification reaction et*een Salicylic Acid Acid and Acetic Anhydride in the presence of concentrated sulfuric acid actin! as a catalyst. est for impurities impurities such as the "erric Chloride test, Starch test, and preparation of methyl salicylate *ere performed. +t *as concluded that impurities *ere present in the crude sample of Acetylsalicylic Acetylsalicylic Acid.
+0R1D2C+10 Aspirin, a common name for compound acetylsalicylic acid, is a prototypical anal!esic used in the treatment of mild to to moderate pain. +t is an acetyl derivative of salicylic acid. +t is a *hite, crystalline, *ealy acidic sustance *hich melts at 3456C (7886") and has a oilin! oilin! point of 39:6C (7;96"). he name, salicylic acid, came from the *ord ali" *hich ali" *hich is the *illo* family of plants. +t *as derived from *illo* ar etracts. +n fol medicine, *illo* ar teas *ere used as headache remedies and other tonics. o reduce irritation to the stomach, salicylic acid is no* administered in the form of aspirin rather than salicylic acid. Aspirin acts as an inhiitor of cyclooy!enase (C1<) *hich result in the inhiition of iosynthesis of prosta!landins. +t acts as a chelatin! a!ent *here an acetyl
!roup is covalently attached to a serine residue in the active site of the C1< en/yme. Salicylic acid is reacted *ith an ecess of acetic anhydride to prepare the aspirin. A small amount of a stron! acid is used as a catalyst *hich speeds up the reaction. he synthesis reaction of aspirin is sho*n elo*. A vine!ar=lie smell can e e oserved in formulations containin! hi!h concentrations of aspirin. his is due to the decomposition throu!h hydrolysis in moist conditions *hich can yield salicylic and acetic acid.
Crystalli/ation is chemical solid> li?uid separation techni?ue. +t is a process of crystal formation in a solution. +t is ased on the principle of soluility. Solutes can e more solule in hot li?uid solvents compared to cold li?uid solvents. $ure solid crystals after crystalli/ation process can e separated from the dissolved impurities y filtration. he ferric chloride test is used to determine the presence of salicylic acid in commercial aspirin. A purple color can e oserved *hen ferric chloride reacts *ith phenols. he starch test is used to determine the presence of starch. A purple=lac color can e oserved *hen there is an iodine solution reacts *ith starch. "or Aspirin, starch test is used to identify *hether the dru! contains pure aspirin or has used starch as an additive.
MAER+A@S A0D ME1D
solution, and methyl alcohol are also the rea!ents used for this eperiment. ME1D After preparin! the materials needed for the eperiment, to synthesi/e aspirin, a 7:=ml eaer filled *ith three=fourths of tap *ater *as su-ected to oil. he eaer is supported y the iron rin! and iron stand. A 7:=ml plastic *ash ottle filled *ith distilled *ater *as paced ice *hich *as placed in a lar!er eaer. Fhile oilin!, eactly 7.:: ! salicylic acid *as tared in a *atch !lass throu!h the use of analytical alance and it *as transferred in a clean, dry 7:=cm test tue. .:: ml of acetic anhydride *as dispensed to the test tue and drops of concentrated sulfuric acid
( H SO ) 2
MAER+A@S he materials used in this eperiment areB analytical alance, hard !lass test tues (7:= 3:cm), !lass rod, eaer (3@, 7:m@, 3:m@), iron rin!tripod, plastic ottle, unsen urnerhot plate, clamp, $asteur pipette, microspatula, and *atch !lass. Salicylic acid, acetic anhydride, concentrated sulfuric acid *ere the rea!ents utili/ed. Commercial aspirin, en/oic acid, en/yl alcohol, 7 ferric chloride, iodine
4
*as added. 2sin! a stirrin! rod,
the miture *as stirred until the salicylic acid dissolved completely.
he urner *as turned off *hen the *ater in the eaer e!an to oil vi!orously. he test tue *as placed in a hot *ater ath to allo* the miture to react *ithin a temperature ran!e of 8:6C to ;:6C in 7:=4: minutes. he content of the test tue *as stirred *ell for 3 minute. he test tue *as then removed from the *ater ath and its contents *ere slo*ly and cautiously poured in a 3:=ml eaer filled *ith ml distilled *ater. 1nce the miture has susided, the miture *as stirred for a minute *hile room temperature *ater *as added slo*ly, a fe* drops at a time, a maimum of 9: drops *as reached or a cloudy solution *as formed. After *hich, the solution *as removed from the setup. hen the inner *alls of the eaer *as scratched !ently usin! the stirrin! rod to induce crystal formation. 1nce the crystals of aspirin has appeared, the test tue *as rinsed *ith a small volume of ice=cold *ater. A 7:=ml of ice cold *ater *as added into the 3:=ml eaer then the eaer *as paced in ice for at least 3: minutes to accumulate the crystals. he aspirin crystals *ere filtered usin! a pre=*ei!hed filter paper and *as dried overni!ht. hen, dried aspirin crystals *ere *ei!hed. Confirmatory tests *ere performed net. he crystals *ere first su-ected to ferric chloride test for salicylic acid. 5 test tues *ere prepared, each containin! 3m@ of *ater. Small amount of salicylic acid, po*dered commercial aspirin, synthesi/ed aspirin, en/oic acid, and 3m@ of en/oyl alcohol *ere each placed in their correspondin! test tues usin! the microspatula. he sith test tue filled *ith
3 ml *ater *as the controlled variale. All si tues *ere shaed and dissolved in 3 ml of *ater. hen, usin! a $asteur pipette, a drop of 7 a?ueous solution of ferric chloride *as added. he resultin! color *as oserved and noted. he second confirmatory test *as the starch test. hree 3:cm test tues, each containin! 7m@ of *ater *ere prepared. Small amount of prepared aspirin and commercially availale aspirin *ere each added to their correspondin! test tues. he third test tue filled *ith *ater *as the controlled variale. A drop of iodine solution *as added in each test tue. he resultin! color *as oserved and noted.
Methyl salicylate *as prepared in a similar manner as aspirin ut at a lo*er temperature. Eactly 3.:: ! of salicylic acid *as placed in a 7:=cm test tue. ml of methyl alcohol and 4 drops of concentrated sulfuric acid
( H SO ) 2
4
*as then added to
the test tue. he contents of the miture *ere stirred until a dissolution of salicylic acid in alcohol *as formed. he test tue *as then placed in a 8:6C *ater ath for 3 minutes. he mint aroma produced inferred the presence of methyl salicylate.
RES2@S A0D D+SC2SS+10 A.
Reaction of Acetic Anhydride and Salicylic Acid
Fei!ht of *atch !lass G salicylic acid
9H.8 !
Fei!ht of empty *atch !lass Fei!ht of salicylic acid Volume of acetic anhydride Volume of concentrated sulfuric acid Fei!ht of filter paper G product Fei!ht of dry filter paper Fei!ht of product
98.8 ! 7.:: ! .:: m@ drops 5.:: ! 4.:: ! 4.:: !
Synthesis of Acetylsalicylic AcidB
o calculate for the actual yield of synthesi/ed aspirin, the theoretical yield of acetylsalicylic acid *ill e ased on the limitin! rea!ent. he limitin! rea!ent in the reaction is salicylic acid. he purpose is to identify if the actual eperiment has
otained a complete reaction of salicylic acid and acetic anhydride. "rom the calculation, 33 *as synthesi/ed aspirin *hich presents that the demonstrated eperiment has sli!ht impurities otained. hese impurities refer to the presence of salicylic acid.
CalculationsB Chemical E?uationB C 7 H 6 O3+ C 4 H 6 O 3 ⟶ C 9 H 9 O4 + CH 3 COOH @imitin! rea!entB Salicylic AcidB 2.00 g C 7 H 6 O 3 ×
1 mol 138.12 g C 7 H 6 O3
×
180.16 g C 9 H 9 O 4 1 mol
2.61 g C 9 H 9 O 4
=
Acetic AnhydrideB 5.00 ml C 4 H 6 O3 ×
1.082 g 1 ml
×
1 mol 102.09 g C 4 H 6 O3
×
180.16 g C 9 H 9 O 4 1 mol
=9.55
g C 9 H 9 O 4
heoretical yieldB 2.00 g C 7 H 6 O 3 ×
1 mol 138.12 g C 7 H 6 O3
×
180.16 g C 9 H 9 O 4 1 mol
=2.6082
g C 9 H 9 O 4
$ercenta!e yieldB 3.00 g synthesized aspirin 2.6082 g C 9 H 9 O4
× 100
115
=
. "erric Chloride est "erric chloride is used for determination of purity of a sustance. +t is used to determine the presence or asence of phenols in a !iven sample. +llustration of the reaction of ferric chloride is sho*n elo*.
Test Tube
Observations
Inference
Salicylic acid Commercial aspirin Synthesi/ed aspirin en/oic acid
$urple solution $in solution $urple solution Clear solution *ith *hite crystalline ppt uly solution Colorless
(G) Salicylic acid present (>) 0o presence of salicylic acid (G) Salicylic acid present (>) 0o presence of salicylic acid
en/yl alcohol Control
he reaction of salicylic acid *ith
( Fe ( H O ) ) +3
a?ueous ferric
2
6
ion
produced an intense purple color. he oy!en atoms of the caroylic acid !roup
(−COOH ) and hydroyl !roup (−OH ) on salicylic acid can form a comple !roup
( Fe ( H O ) )
(>) 0o presence of salicylic acid (>) 0o presence of salicylic acid
positive result. his means that commercial aspirin reacted to iodine and that it contains starch. 0o reaction occurred in the synthesi/ed aspirin and the controlled variale. he result inferred that there is no starch present in oth synthesi/ed aspirin and *ater. D. $reparation of Methyl Salicylate
+3
*ith ferric
2
6
ion. he purple
color indicates the presence of salicylic acid. +n aspirin, the hydroyl !roup replaced y ester
(
(−OH ) *as
OCOC H 3) durin!
−
esterification and nucleophilic sustitution *hich prevents the comple or second ond formation. his *ill emanate a yello* solution.
Methyl alcohol *as used to dissolve salicylic acid. +t *as su-ected to *ater ath for it to produce an odor. he presence of methyl salicylic acid *as confirmed in the miture *hen it produced a mint=lie odor. Methyl salicylate and acetylsalicylic acid are derivatives of salicylic acid. +llustration for the reaction of methyl salicylate is sho*n elo*.
C. Starch est he iodine test or starch test is used to test for the presence of starch. Test Tube
Observation
Commercial aspirin Synthesi/ed aspirin Control
(G) $urple colored solution (>) 0o reaction (>) 0o reaction
Commercial aspirin formed a lue= lac colored solution *hich indicates a
ReferencesB
3. Syntesis of Aspirin. Retrieved from httpBmason.!mu.eduI-schorniche m733laChem7:733= 7377:Aspirin.pdf 7. @ehman, #. (7::7). #ultiscale Operational Organic Chemistry$ % problem olving %pproach to the Laboratory Course& 0e* #erseyB $rentice all. $!. 9:=9;, 78=759, 4: 4. $avia, D., @ampman, &., Jri/, &., K En!el, R. (3HHH). 'ntro(uction to Organic Laboratory !echni)ues * % #icroscal %pproach +3r( e(&&
Saunders Colle!e $ulishin!. $!. 5:= 8:, 3::=3:H 9. Aspirin Synthesis. Retrieved from httpB***.lahc.educlasseschemistr yariasEp7:7:= 7:Aspirin"33.pdf 5. Loprin, ayer uffered Aspirin (aspirin) dosin! indications, adverse effects, and more. Medscape Reference. FeMD. Retrieved from httpBreference.medscape.comdru! /orprin=ayer=uffered=aspirin= 49478H
