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1.1 Background
This paper is made to fulfill the task of the subject of Organic Chemistry Practice as a
condition to follow the response of the course. this paper is titled ASPIRIN As the title
suggests, the contents of this paper are also related to the manufacture of aspirin (salicylic
acid) with the principle of esterification and recrystallization. This paper describes the
process of making and the structural forms of its compounds. Thus it is hoped that by making
this paper can be useful for our daily life, and increase our knowledge about the drug aspirin

2.1 Problem Formulation

The problem in this experiment is how to manufacture aspirin with the principle of
esterification and the principle of recrystallization, and how the reactions that occur therein.

3.1 Purpose
The purpose of this paper is to know the process of making aspirin with the principle of
esterification and recrystallization. And to know the reaction that occurred during the process.

4.1 Benefits
Whatever the benefits of this paper are:
4.1 As a condition to follow the response of the organic chemistry lab course
4.2 Can provide a great insight into how aspirin is made, from its principles, its
characteristics, to the benefits of aspirin in everyday life.


2.1 Definition of Chemical Synthesis

Chemical synthesis is the activity of doing chemical reactions to obtain a chemical product,
or some products. This happens based on physical and chemical events involving one or more
reactions. Chemical synthesis is a process that can be reproduced as long as the required
conditions are met. With this chemical synthesis we can synthesize the aspirin.

2.2 Aspirin Introduction

Aspirin or salicylic acid or acetosal is a drug derived from salicylate which is often used as
an analgesic (pain or pain relief), as an antipyretic (fever reliever), and anti-inflammatory (for
inflammation). Aspirin has anticoagulant effects. Aspirin began to be used as a drug since
1918 which at that time terjado pandemic flu in various regions of the world.
Aspirin can also inhibit hormones in the body known as prostaglandins.
Aspirin is able to stop the formation of prostaglandins by acting on the enzyme
2.2.1 Synonym:
2-acetyloxybenzoic acid
2- (acetyloxy) benzoic acid
acetylsalicylic acid
O-acetylsalicylic acid
2.2.2 Water solubility:
10 mg / mL (20 ° C) Acetosal contains not less than 99.5% and not more than 100.5%
C9H8O4 is calculated against the dried substance.

2.2.3 Pemerian:
white crystals, generally like needles or arranged plates, or white crystal powders; odorless or
weak-smelling. Stable in dry air; in moist air is gradually hydrolyzed to salicylic acid and
acetic acid.
2.2.4 Solubility:
soluble in water; easily soluble in ethanol; soluble in chloroform, and in ether; rather difficult
to dissolve in absolute ether.

2.3 The process of making aspirin

The process of making aspirin is done by 2 methods, that is
1. The principle of esterification
2. The principle of recrystallization
Both of these methods will be combined in the process of making the aspi. these two methods
will support each other and produce good aspirin. Here are the two methods.

2.3.1 Reaction Esterification

The esterification reaction is the principle of making aspirin. By way of reacting salicylic
acid with acetic acid anhydride with the aid of heating. Esters can be formed one way by
reacting alcohol with acid anhydride. In this case salicylic acid acts as alcohol because it has
a -OH group, and acetic acid anhydride as an acid anhydride. Esther formed is acetyl salicylic
acid (aspirin). The acetyl group (CH3CO-) is derived from acetic acid anhydride, while the R
group derived from salicylic acid by-products is acetic acid. Thereafter, added concentrated
sulfuric acid which acts as a hydrating agent of the byproduct and will form acetic acid
anhydride. Acetic acid anhydrides will return to action with salicylic acid to form aspirin and
its byproducts of acetic acid. Then the reaction will stop after salicylic acid runs out due to
sulfuric acid. as well as heating in the control, because the reaction will take place either at
50-60 C, after which it will form white precipitate (aspirin) after heating, then the solvent
dissolved in water and strained to separate aspirin with impurities. However, aspirin is not
really pure, so for purification use Na.HCO3 ¬ solution.

With added sodium acetyl salicylic solution, aspirin will dissolve but the byproducts are
insoluble, then if filtered will be obtained purified aspirin filtrate in the form of clear solution.

2.3.2 Principles of Recrystallization

After the esterification is performed which results in a solution, the filtrate is then stirred to
form a white precipitate. Then cooled with ice water to form a crystal. The crystal will be
purer after washing with ice water. Then chrysis dried in a way placed in a watch glass and
found dry crystals. Dry crystals are then dissolved with hot benzene and then heat. Benzene
serves as a good solvent in the appeal of water in the manufacture of aspirin, because water is
polar, while non polar aspirin, so used benzene. Then the solution is filtered and the filtrate is
taken and dried in the oven. So as to obtain completely pure aspirin crystals. This process is
called recrystallization.

2.4 Benefits of Aspirin

As we know that aspirin is often we hear in everyday life. But we will know more about the
benefits of aspirin as follows

2.4.1 To relieve pain especially headache, dizziness, pain

teeth, muscle aches
2.4.2 As an antipyretic to reduce fever
2.4.3 Aspirin can fight cardiovascular disease in men
And women. In men aspirin reduces the risk of heart disease (myocardial infarction) In
women, aspirin reduces the risk of stroke (ischemic stroke)
2.5 Contra indications Aspirin
It is common knowledge that excessive consumption of drugs will contraindicate to patients
who consume them. Excessive consumption of aspirin will result in:
2.5.1 Aspirin can cause the risk of intestinal gut bleeding of food for both men and women if
taken daily
2.5.2 Dangerous for gastric ulcer (gastritis) because it is sensitive to salicylic acid and aspirin
properties that can irritate the stomach of gastritis.
2.5.3 Not good for patients who have bleeding under the skin.
2.5.4 is not good for hemophilia and platelets.

3.1 Therapeutic Response And Aspirin Toxicity

The therapeutic effect of the drug depends on many factors, including the manner and form of
its administration, its physicochemical properties that determine its resorption,
biotransformation and excretion in the body. Similarly, the physiological condition of the
user (liver, kidney, intestine, and blood circulation). Other individual factors, such as
ethnicity, sex, body surface area and eating habits are also very important. Any drug in a high
enough dosage may cause toxic effects. In general, toxic reactions are directly related to high
doses, when the dose is lowered, toxic effects can be reduced as well.

The nature and intensity of the effects of a chemical depends on its level in the workplace, ie
its effective dose. Generally, levels within the target organ are a function of blood levels.
However, increased toxicity in the tissues will increase the level, while the network barrier
tends to reduce the levels. Because blood levels are more easily measured, especially over a
period of time, these are the parameters that are often used in toxicokinetic research.

This article will discuss the various forms and mechanisms of drug interactions and their
clinical impact and how to avoid the possibility of adverse impacts. Drug interactions are
events in which the action of a drug is altered or affected by other drugs given concurrently.

The likelihood of interaction occurrence should always be considered in the clinic, when two
or more drugs are given simultaneously or almost simultaneously. Interaction can have a
detrimental effect if the interaction is not recognized so that optimization efforts can not be
made. In summary the negative impact of this interaction is likely to arise side effects and not
achieving the desired therapeutic effect.

Drug interaction based on the mechanism can be divided into 3 major groups, namely:
3.3.1 Pharmaceutical interactions
Is the physico-chemical interaction that occurs when the drug is formulated before the drug is
used by the patient. For example, two drugs mixed in the same solution may be chemical
reactions or deposits of one of the compounds, or there is crystallization of one of the
compounds. Interaction form:
a. Physical interaction
For example: There is a change of solubility and decrease of freezing point
b. Interaction is khemis
For example: The occurrence of reactions to one another or hidrolisisnya a drug during the
manufacturing process or during storage.

3.3.2 Pharmacokinetic interactions

In this interaction the drug undergoes a change in the ADME process caused by a drug / other
compound. This is generally measured by changes in one or more pharmacokinetics
parameters, such as maximum serum concentration, area under the curve, time, half-life, total
amount of drug excreted through urine, etc.
3.3.3 Pharmacodynamic interactions
It is a drug that causes a change in the patient's response due to the pharmacokinetics change
of the drug because of other drugs seen as drug action changes without changing plasma
concentrations. For example, the increased toxicity of digoxin caused by concomitant
administration of potassium-sparing diuretics such as furosemide

3.2 Metabolism of Drugs

Hepar is the main organ in drug metabolism, especially oral medications. Basically hepatic
enzymes change the drug into a more polar material and easily soluble in water so that, easily
excreted through the kidneys and bile.Metabolisme drug in the liver there are 2 stages. In
stage I, there is reduction of hydrolysis and oxidation. At this stage there has not been a
process of detoxification, hence sometimes formed a metabolite material that is actually
toxic. In the second stage, there is a conjugate reaction with glucoronic acid, glycine sulfate,
resulting in less toxic, water soluble and biologically inactive. This metabolism occurs in
liver cell microsomes, and which plays a role: NADPH C reductase and cytochrome p 450.

One of the drugs we discussed in this article that have a therapeutic effect and toxicity is
Aspirin. Aspirin / acetyl salicylic acid / acetosal is a hepatotoxic drug (a drug that can cause
hepatic abnormalities and depends on the size of the dose (Predictable)). Symptoms of
hepatotoxic arise bilakadar salicylate serum more than 25 mg / dl (dose: 3 - 5 g / day).

This state seems to be very closely related to blood albumin levels, because this form of free
salicylate can damage the liver. The selection of drugs in children is limited to the NSAIDs
that have been tested for use in children: aspirin, naproxen or tolmetin, except aspirin on the
possibility of Reye's Syndrome, aspirin to reduce heat can be replaced with acetaminophen,
nimesulide, as with other NSAIDs, children under 12 years of age because aspirin is irritating
to the stomach, increasing the risk of ulcers, bleeding, to perforation, and inhibiting platelet
activity (functioning in blood clots), which can trigger the risk of bleeding).

3.3 Aspirin Work Mechanism

3, 3; 1 Acetylate cyclooxygenase enzyme and inhibit
formation of enzimcyclicendoperoxides.
3.3.2 Inhibits thromboxane A-2 (TXA-2) synthesis in platelets, thereby inhibiting platelet
3.3.3 Inactively inactivating the enzymes in the platelets. This inhibition is a powerful way of
working aspirin in the prevention of stroke and TIA (Transient Ischemic Attack).
3.3.4 In vascular endothelium, inhibit prostanjsiklin formation. This helps reduce platelet
aggregation in damaged blood vessels.

Started work:
20 minutes -2 hours.
Peak plasma level:
plasma salicylate levels are not proportional to the size of the dose.
Half time:
acetyl salicylic acid 15-20 rnenite; salinity of 2-20 hours depending on the given dose.

depending on the dose, form, time of gastric emptying, gastric pH, antacid drug and particle

partially hydrolyzed into salicylic acid as absorbed and distributed throughout the tissues and
body fluids at the highest levels in plasma, liver, renal cortex, heart and lungs.
eliminated by the kidneys in the form of salicylic acid and oxidation and metabolite

The presence of food in the stomach slows its absorbs; co-administration of antacids may
reduce gastric irritation but increase solubility and absorption. Approximately 70-90%
salicylic acid of the active form is bound to a plasma protein.

Reduce the risk of TIA or recurrent stroke in patients who have suffered brain ischemia
caused by embolus. Reduce the risk of suffering a stroke in high-risk patients as in patients
with non valvular atrial tibrillation which can not be given anti coagulant.

Hypersensitive to salicylate, bronchial asthma, hay fever, nasal polyps, severe anemia,
clotting disorders
Anti-coagulant drugs, heparin, insulin, sodium bicarbonate, alcohol clan, angiotensin
converting enzymes.

Epigastric pain, nausea, vomiting, gastric bleeding.

Not recommended for stroke treatment in children under 12 years of age due to the risk of
Reye syndrome. In the elderly should be careful because more often cause cardiovascular
side effects. This drug is not recommended in the last trimester of pregnancy because it can
cause disturbance to the fetus or cause complications during partus. Not recommended also in
women breastfeeding because it is secreted through milk.

The FDA recommends a dose: orally 1300 mg / day divided by 2 or 4 times of
administration. As an anti-thrombocyte dose of 325 mg / day is quite effective and fewer side
3.4 Efforts to Avoid Negative Impacts
3.4.1 Avoid combined drug use (polifarmation), unless the condition of the treated disease
requires a combination of medications and the combined treatment has been accepted and
scientifically proven.
3.4.2 Identify as many possible interactions as they arise in drugs that are often given
concurrently in the practice of polypharmacy.
3.4.3 In the event of any interaction, measures shall be taken, eg dose reduction or
substitution of other drugs having the same therapeutic effect but not causing adverse
3.4.4 Evaluation of effects after concurrent administration of drugs to assess the presence or
absence of side / toxic side effects of one or both drugs.