Gugus Fungsi

Prof. Dr. Sudibyo Martono, M.S., Apt.

GUGUS FUNGSI 2
 USP 39 NF 34

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 Kelarutan Zat

GUGUS FUNGSI 4
 2011

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 Literature:
Moffats, A.C., Osselton, M.D., and Widdop. B., 2011,
(consulting editors), Clarke’s Analysis of Drug and
Poisons, in pharmaceuticals, body fluids, and
postmortem material, Fourth Edition, Pharmaceutical
Press, London.
Informasi yang ada a.l.,:

- Solubility - Colour Test

- pKa - log P
- UV-VIS and IR Spectrum; Mass Spect
- Chromatography: TLC ; HPLC; GC

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 Dalam penyiapan sampel,
Informasi mana yang lebih berguna:

Rumus molekul
ataukah
Rumus Bangun
???
4
 Rumus molekul [ RM ]:

C7H6O3

Informasi apa yang dapat diperoleh

dari RM
???

5
 Rumus bangun:

C7H6O3 C7H6O3 C7H6O3

O O O
C C C
OH OH OH

OH HO
OH

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Dipyrone/Antalgin/Novalgin
7
 Liquid-Liquid Extraction

Kd = P

GUGUS FUNGSI 11
 Log Kd = Log P = Log Kow

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 Calciferol

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GUGUS FUNGSI 14
 Aspirin

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 Dexametason

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GUGUS FUNGSI 17
 Gugus Fungsi

Instead of trying to memorize both equations, we can build a

general rule that bromine reacts with compounds that contain
a C=C double bond to give the product expected from addition
across the double bond. [ Reaksi adisi ]

This approach to understanding the chemistry of organic

compounds presumes that certain atoms or groups of atoms
known as functional groups give these compounds their
characteristic properties.

GUGUS FUNGSI 18
 The C=O group plays a particularly important role in organic
chemistry. This group is called a carbonyl, and some of the
functional groups based on a carbonyl are shown in Table
O2.2.

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GUGUS FUNGSI 20
 Aspirin, Tylenol, Ibuprofen
Exercise O2.2

The following compounds are the active ingredients in over-

the-counter drugs used as analgesics (to relieve pain without
decreasing sensibility or consciousness), antipyretics (to
reduce the body temperature when it is elevated), and/or anti-
inflammatory agents (to counteract swelling or inflammation of
the joints, skin, and eyes).

Identify the functional groups in each molecule.

GUGUS FUNGSI 21
 Solution:
All three compounds are aromatic. Aspirin is also a carboxylic
acid (-CO2H) and an ester (-CO2CH3). Tylenol is also an
alcohol (-OH) and an amide (-CONH-). Ibuprofen contains
alkane substituents and a carboxylic acid functional group.
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 Tetrasiklin

Identify the functional groups in Tetracyclin.

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 Solution:

The compound contains an aromatic ring fused to three six-

membered rings.
It is also an alcohol (with five -OH groups), a ketone (with C=O
groups at the bottom of the second and fourth rings), an amine
[the -N(CH3)2 substituent at the top of the fourth ring], and an
amide (the -CONH2 group at the bottom right-hand corner of
the fourth ring.)
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 Alcohol

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 Kelarutan alkohol

As a general rule, polar or ionic substances dissolve in polar

solvents; nonpolar substances dissolve in nonpolar solvents.
As a result, hydrocarbons don’t dissolve in water.

They are often said to be immiscible (literally, “not mixable”) in

water. Alcohols, as might be expected, have properties
between the extremes of hydrocarbons and water.

When the hydrocarbon chain is short, the alcohol is soluble in

water. There is no limit on the amount of methanol (CH3OH)
and ethanol (CH3CH2OH), for example, that can dissolve in a
given quantity of water.

GUGUS FUNGSI 26
 lanjutan
As the hydrocarbon chain becomes longer, the alcohol
becomes less soluble in water, as shown in Table O2.4.
One end of the alcohol molecules has so much nonpolar cha-
racter it is said to be hydrophobic (literally, “water-hating”).

The other end contains an -OH group that can form hydrogen
bonds to neighboring water molecules and is therefore said to
be hydrophilic (literally, “water-loving”).

As the hydrocarbon chain becomes longer, the hydrophobic

character of the molecule increases, and the solubility of the
alcohol in water gradually decreases until it becomes
essentially insoluble in water.

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GUGUS FUNGSI 28
 Cinchocain

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 Carboxylic acids and Carboxylate ions

When one of the substituents on a carbonyl group is an OH

group, the compound is a carboxylic acid with the generic
formula RCO2H. These compounds are acids, as the name
suggests, which form carboxylate ions ( RCO2- ) by the loss
of an H+ ion.

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 The carboxylate ion formed in the reaction is a
hybrid of two resonance structures.

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 Resonance delocalizes the negative charge in the carboxylate
ion, which makes the ion more stable than the alkoxide ion
formed when an alcohol loses an H+ ion.

By increasing the stability of the conjugate base, resonance

increases the acidity of the acid that forms the base.

Carboxylic acids are therefore much stronger acids than the

analogous alcohols.

The Ka value for a typical carboxylic acid is about 10-5,

whereas alcohols have Ka values only 10-16.

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 Amines, Alkaloids, Amides
Amines are derivatives of ammonia in which one or more
hydrogen atoms are replaced by alkyl groups.

We indicate the degree of substitution by labeling the amine as

either primary (RNH2), secondary (R2NH), or tertiary (R3N).

The common names of the compounds are derived from the

names of the alkyl groups.

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 The chemistry of amines mirrors the chemistry of ammonia.
Amines are weak bases that pick up a proton to form
ammonium salts.

Trimethylamine, for example, reacts with acid to form the

trimethylammonium ion.

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 Pengaturan pH [ Basa ]

+ Basa

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 Pengaturan pH [ Asam ]

H2N Cl

p-chloroaniline

+ Asam
HO

O
benzoic acid

GUGUS FUNGSI 38
 The salts are more soluble in water than the corresponding
amines, and the reaction can be used to dissolve otherwise
insoluble amines in aqueous solution.

The difference between amines and their ammonium salts

plays an important role in both over-the counter and illicit
drugs.

Cocaine, for example, is commonly sold as the hydrochloride

salt, which is a white, crystalline solid. By extracting the solid
into ether, it is possible to obtain the “free base.”

A glance at the side panel of almost any over-the counter

medicine will provide examples of ammonium salts of amines
that are used to ensure that the drug dissolves in water (see
Figure O2.9).
GUGUS FUNGSI 39
 Cinchocain

A white crystalline, slightly volatile, powder. Mp 980. Solubility:

Soluble 1 in 600 of water (1 in 270 of water at 800), 1 in 6.5 of ethanol, 1 in
0.7 of chloroform and 1 in 3.5 of ether; also soluble in acetone, ethyl
acetate and carbon disulfide. pKa 8.7 [Needham et al. 2000], 8.6 (20).
Log P (octanol/water), 2.3.

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 Caffeine, Theobromine, Theophylline

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 Some of the organosulfur compounds associated with garlic .

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 Solubility of Organic Compounds

For organic compounds- e.g., with regard to their functional

groups, generally applicable rules do not exist.
In Organic Chemistry we primarily rely on the rule “like
dissolves like”.

The following table shows that the hydrophobic/hydrophilic

properties of an organic compound can be correlated rather
directly to its functional groups. However, the table does not
consider the total structure of a molecule and merely indicates
a “local polarity” in the vicinity of a functional group.

GUGUS FUNGSI 45
 Generally, most organic compounds are (very) readily soluble
in diethyl ether (Et2O, frequently called just ether) and only
sparingly soluble in water.

Exceptions from this rule are functionalized compounds with

only a few carbon atoms (1 to about 5 C atoms, depending on
the functional group), polyfunctionalized compounds, and
organic salts.

Some of them are very poorly soluble in organic solvents but,

as a rule, readily soluble in water instead.

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 Acidity and Basicity of Organic Compounds
Exploiting their acid and base properties, respectively, the
solubility of organic substances can be modified.

A basic compound is converted into a salt by protonation; the

same applies for an acid by deprotonation. The obtained salts
are significantly more polar and, thus, noticeably more soluble
in water (and less readily soluble in an organic solvent) as
compared to the educts bearing no charged functionality.

Organic compounds with different acid/base strengths can

often be converted selectively into the corresponding salts by
controlled protonation/deprotonation using differently strong
acids/bases.
This can be used to distinguish and separate them.
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 Compounds with Acidic OH Groups

The OH functionality contains a polarized bond between the

strongly electronegative O atom and the less electronegative H
atom. This promotes dissociation as a principle. Nevertheless,
the most typical compounds with OH groups, the alcohols, do
not belong to the actual organic acids.

Their pKa values usually lie about 1–3 pKa units above that of
water; alcohols are, thus, only marginally dissociated in water.

Typical organic acids are sulfonic acids and carboxylic acids;

phenols and 1,3-diketones (in the enol form, see below) are
acidic as well, but to a considerably lesser degree.

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 Sulfonic acids, carboxylic acids, and phenols are stronger
acids than alcohols because the charges of the anions formed
by dissociation (of the conjugate bases = sulfonates,
carboxylates, and phenolates) are stabilized by resonance (=
delocalization).
The corresponding resonance formulae (= mesomeric forms or
resonance structures) for sulfonate (= the deprotonated
sulfonic acid) are shown in the following:
GUGUS FUNGSI 51
 While the strongly acidic sulfonic acids dissociate in water
almost completely, the considerably less acidic carboxylic
acids only dissociate partially.
Aqueous solutions of both compound types show acidic pH
values, though.

Phenol:
On the other hand, solutions of phenols usually react neutral.
Only hydroxyls attached to very electron poor aromatic
frameworks dissociate sufficiently to yield a pH < 7.
GUGUS FUNGSI 52
 Carboxylic acid and Phenol

The carboxylic acids, having pKa values of < ca. 5, get usually
fully deprotonated by relatively weak bases. Therefore, they
generally dissolve already in 0.5 M aqueous NaHCO3 solution
in the form of the carboxylates.

To fully deprotonate phenols, stronger bases are required:

normally, however, they already dissolve in 0.5 M aqueous
NaOH in the form of phenolates.

GUGUS FUNGSI 53
 Compounds with Acidic NH Groups
Nitrogen-containing compounds in low oxidation states, except
for protonated species like protonated amines, normally are
basic and therefore only release their protons reluctantly (see
below).

However, if the anions that are formed by deprotonation of NH

groups are very well stabilized, NH compounds can also be
weak acids.

The conjugate bases of sulfonamides and of imides show a

particularly high resonance stabilization; the respective parent
compounds are, thus, rather acidic.

GUGUS FUNGSI 54
 Sulfonamides anf Imides
 Sulfonamides and imides having pKa values of
about 10, are significantly weaker acids than
 sulfonic or carboxylic acids. They are comparable
in their acidity to phenols, though, and, like
 them, are usually deprotonated by aqueous NaOH,
but generally not by aqueous NaHCO3.

Sulfonamides and imides having pKa values of about 10, are

significantly weaker acids than sulfonic or carboxylic acids.

They are comparable in their acidity to phenols, though, and,

like them, are usually deprotonated by aqueous NaOH, but
generally not by aqueous NaHCO3.
GUGUS FUNGSI 55
 Organic Bases
Possible bases generally are all organic compounds that have
functional groups with high electron density, e.g., electron lone
pairs.

However, here we again consider as bases only those charge-

neutral compounds that can be converted into salts by
protonation in an aqueous environment. Thus, the compounds
must be comparable or even stronger bases than water.

GUGUS FUNGSI 56
 The strength of a base depends on two factors:

1. on the availability of the electron lone pair and

2. on the stabilization of the cation produced by protonation.

The availability of the electron lone pair is closely related to its

orbital energy. The higher the orbital energy is, the more
reactive and, consequently, the more basic the electron pair is.

Because the orbital energies decrease with increasing

electronegativity of the elements, it is obvious that amines
(ENN = 3.1) must be more basic than alcohols (ENO = 3.5).

GUGUS FUNGSI 57
 The basicity of N-containing organic compounds varies in
a wide range, though, because the availability of the electron
lone pair can be limited due to conjugation.

Possible basic compounds that get fully protonated by 0.5 M

aqueous HCl and, therefore, can often (but not always) be
dissolved in water in form of their ammonium salts are
alkyl amines (primary, secondary, and tertiary, cf. the table),
aryl amines, and heterocyclic nitrogen compounds.

Other N- (and O-) containing functional groups can also be

protonated, if the acids used are sufficiently strong and
concentrated, e.g., conc. H2SO4 (see below).

GUGUS FUNGSI 58
 Senyawa basa

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 Neutral Substances
We regard as neutral substances all those organic compounds
that are not converted, for the major part, into a deprotonated
or protonated form by the action of diluted aqueous HCl or
NaOH, respectively.

Nevertheless, many of these substances react as acids and

bases — but not completely, just to a minor degree. Because
protonated or deprotonated neutral substances usually are
very reactive, they are of great chemical importance in spite of
the low amounts in which they are produced.

GUGUS FUNGSI 60
 They are, e.g., the reactive intermediates in acid- and base-
catalyzed reactions. Moreover, many neutral substances can
be completely protonated and deprotonated, respectively, in an
anhydrous environment by very strong acids or very strong
bases.

For this reason, almost all N- and O-containing compounds

(except for diaryl ethers and nitro compounds) as well as
unsaturated hydrocarbons (except for aromatic compounds)
can be converted into the conjugate acids by conc. H2SO4.

GUGUS FUNGSI 61
 On the other hand, almost all carbonyl and carboxyl
compounds can be deprotonated to the corresponding
enolates by amide bases (= deprotonated amides).

Typical neutral substance classes are compiled in the following

table, with one example for each.

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 Neutral compounds

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GUGUS FUNGSI 64
 Asam Kuat, Asam Lemah
Strong Acids:
Relatively strong organic acids (pKa ≤ ca. 7–8) with sufficiently
large apolar structural parts:
carboxylic acids with larger hydrocarbon residues and
substituted electron-deficient phenols

Weak acids:
Weak organic acids (approx. 8 ≤ pKa ≤ ca. 14) with sufficiently
large apolar structural parts:

substituted electron-rich phenols, enols (dicarbonyl compounds),

primary and secondary nitroalkanes, and N-mono/N-unsubtitu-
ted sulfonamides.
GUGUS FUNGSI 65
 Seny. Basa dan Netral
Organic bases:
Organic bases (pKb ≤ approx. 15, mostly N-containing
compounds) with sufficiently large apolar structural parts:
amines, aryl amines, and aromatic heterocycles.

Neutral compounds:
Neutral substances with N- and/or S-containing groups and
sufficiently large apolar residues.

GUGUS FUNGSI 66
 Progesteron

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 Guaifenesin

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 Terima Kasih

E-mail: sudib_kekes@yahoo.co.id

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Prof. Dr. Sudibyo Martono, M.S., Apt.