Isoquinoline is a
heterocyclic aromatic
In chemistry, aromaticity is a chemical property of cyclic ( ring-shaped), ''typically'' planar (flat) molecular structures with pi bonds in resonance (those containing delocalized electrons) that gives increased stability compared to satur ...
organic compound
In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. Th ...
. It is a
structural isomer of
quinoline. Isoquinoline and quinoline are
benzopyridines, which are composed of a
benzene
Benzene is an organic chemical compound with the molecular formula C6H6. The benzene molecule is composed of six carbon atoms joined in a planar ring with one hydrogen atom attached to each. Because it contains only carbon and hydrogen atoms ...
ring fused to a
pyridine
Pyridine is a basic heterocyclic organic compound with the chemical formula . It is structurally related to benzene, with one methine group replaced by a nitrogen atom. It is a highly flammable, weakly alkaline, water-miscible liquid w ...
ring. In a broader sense, the term isoquinoline is used to make reference to isoquinoline
derivatives.
1-Benzylisoquinoline
Substitution of the heterocycle isoquinoline at the C1 position by a benzyl group provides 1‑benzylisoquinoline, the most widely examined of the numerous benzylisoquinoline structural isomers. The 1-benzylisoquinoline moiety can be identified ...
is the structural backbone in naturally occurring
alkaloids including
papaverine. The isoquinoline ring in these natural compound derives from the aromatic
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...
tyrosine
-Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the G ...
.
Properties
Isoquinoline is a colorless
hygroscopic
Hygroscopy is the phenomenon of attracting and holding water molecules via either absorption or adsorption from the surrounding environment, which is usually at normal or room temperature. If water molecules become suspended among the substance' ...
liquid at temperatures above its melting point with a penetrating,
unpleasant odor. Impure samples can appear brownish, as is typical for nitrogen heterocycles. It crystallizes in platelets that have a low
solubility
In chemistry, solubility is the ability of a substance, the solute, to form a solution with another substance, the solvent. Insolubility is the opposite property, the inability of the solute to form such a solution.
The extent of the solubi ...
in water but dissolve well in
ethanol
Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an alcohol with the chemical formula . Its formula can be also written as or (an ethyl group linked to a ...
,
acetone
Acetone (2-propanone or dimethyl ketone), is an organic compound with the formula . It is the simplest and smallest ketone (). It is a colorless, highly volatile and flammable liquid with a characteristic pungent odour.
Acetone is miscibl ...
,
diethyl ether
Diethyl ether, or simply ether, is an organic compound in the ether class with the formula , sometimes abbreviated as (see Pseudoelement symbols). It is a colourless, highly volatile, sweet-smelling ("ethereal odour"), extremely flammable li ...
,
carbon disulfide, and other common
organic solvents. It is also soluble in dilute
acids as the protonated derivative.
Being an
analog of pyridine, isoquinoline is a weak
base, with a
p''Ka'' of 5.14.
It protonates to form
salts upon treatment with
strong acids, such as HCl. It forms
adducts with
Lewis acids, such as BF
3.
Production
Isoquinoline was first isolated from
coal tar
Coal tar is a thick dark liquid which is a by-product of the production of coke and coal gas from coal. It is a type of creosote. It has both medical and industrial uses. Medicinally it is a topical medication applied to skin to treat pso ...
in 1885 by Hoogewerf and van Dorp. They isolated it by
fractional crystallization of the acid sulfate. Weissgerber developed a more rapid route in 1914 by selective extraction of coal tar, exploiting the fact that isoquinoline is more basic than quinoline. Isoquinoline can then be isolated from the mixture by fractional crystallization of the acid sulfate.
Although isoquinoline derivatives can be synthesized by several methods, relatively few direct methods deliver the unsubstituted isoquinoline. The
Pomeranz–Fritsch reaction provides an efficient method for the preparation of isoquinoline. This reaction uses a
benzaldehyde and aminoacetoaldehyde diethyl acetal, which in an
acid medium
Medium may refer to:
Science and technology
Aviation
* Medium bomber, a class of war plane
* Tecma Medium, a French hang glider design
Communication
* Media (communication), tools used to store and deliver information or data
* Medium ...
react to form isoquinoline. Alternatively,
benzylamine and a
glyoxal
Glyoxal is an organic compound with the chemical formula OCHCHO. It is the smallest dialdehyde (a compound with two aldehyde groups). It is a crystalline solid, white at low temperatures and yellow near the melting point (15 °C). The li ...
acetal can be used, to produce the same result using the Schlittler-Müller modification.
Several other methods are useful for the preparation of various isoquinoline derivatives.
In the
Bischler–Napieralski reaction
The Bischler–Napieralski reaction is an intramolecular electrophilic aromatic substitution reaction that allows for the cyclization of β-arylethylamides or β-arylethylcarbamates. It was first discovered in 1893 by August Bischler and , in affi ...
an β-
phenylethylamine is acylated and cyclodehydrated by a Lewis acid, such as
phosphoryl chloride or
phosphorus pentoxide. The resulting 1-substituted 3,4-dihydroisoquinoline can then be dehydrogenated using palladium. The following Bischler–Napieralski reaction produces papaverine.
The
Pictet–Gams reaction and the
Pictet–Spengler reaction
The Pictet–Spengler reaction is a chemical reaction in which a β-arylethylamine undergoes condensation with an aldehyde or ketone followed by ring closure. The reaction was first discovered in 1911 by Amé Pictet and Theodor Spengler (February ...
are both variations on the Bischler–Napieralski reaction. A Pictet–Gams reaction works similarly to the Bischler–Napieralski reaction; the only difference being that an additional hydroxy group in the reactant provides a site for dehydration under the same reaction conditions as the cyclization to give the isoquinoline rather than requiring a separate reaction to convert a dihydroisoquinoline intermediate.
In a
Pictet–Spengler reaction
The Pictet–Spengler reaction is a chemical reaction in which a β-arylethylamine undergoes condensation with an aldehyde or ketone followed by ring closure. The reaction was first discovered in 1911 by Amé Pictet and Theodor Spengler (February ...
, a condensation of a β-
phenylethylamine and an
aldehyde
In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl gro ...
forms an imine, which undergoes a cyclization to form a
tetrahydroisoquinoline instead of the
dihydroisoquinoline. In
enzymology, the
''(S)''-norcoclaurine synthase () is an
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
that
catalyzes a biological Pictect-Spengler synthesis:
Intramolecular aza Wittig reactions also afford isoquinolines.
Applications of derivatives
Isoquinolines find many applications, including:
* anesthetics;
dimethisoquin is one example (shown below).
*:
* antihypertension agents, such as
quinapril
Quinapril, sold under the brand name Accupril among others, is a medication used to treat high blood pressure (hypertension), heart failure, and diabetic kidney disease. It is a reasonable initial treatment for high blood pressure. It is taken ...
and
debrisoquine (all derived from 1,2,3,4-tetrahydroisoquinoline).
* antiretroviral agents, such as
saquinavir with an isoquinolyl
functional group
In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the r ...
, (shown below).
*:
* vasodilators, a well-known example,
papaverine, shown below.
*:
Bisbenzylisoquinolinium compounds are compounds similar in structure to
tubocurarine. They have two isoquinolinium structures, linked by a
carbon
Carbon () is a chemical element with the symbol C and atomic number 6. It is nonmetallic and tetravalent—its atom making four electrons available to form covalent chemical bonds. It belongs to group 14 of the periodic table. Carbon ma ...
chain, containing two
ester
In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ...
linkages.
In the human body
Parkinson's disease
Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms beco ...
, a slowly progressing movement disorder, is thought to be caused by certain
neurotoxins. A neurotoxin called
MPTP (1
'N''methyl-4-phenyl-1,2,3,6-
tetrahydropyridine), the precursor to MPP
+, was found and linked to Parkinson's disease in the 1980s. The active neurotoxins destroy
dopaminergic neurons, leading to parkinsonism and Parkinson's disease. Several
tetrahydroisoquinoline derivatives have been found to have the same neurochemical properties as MPTP. These derivatives may act as precursors to active neurotoxins.
Other uses
Isoquinolines are used in the manufacture of
dye
A dye is a colored substance that chemically bonds to the substrate to which it is being applied. This distinguishes dyes from pigments which do not chemically bind to the material they color. Dye is generally applied in an aqueous solution and ...
s,
paints,
insecticides and
antifungals
An antifungal medication, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as cryp ...
. It is also used as a
solvent
A solvent (s) (from the Latin '' solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. Water is a solvent for ...
for the
extraction Extraction may refer to:
Science and technology
Biology and medicine
* Comedo extraction, a method of acne treatment
* Dental extraction, the surgical removal of a tooth from the mouth
Computing and information science
* Data extraction, the pr ...
of
resin
In polymer chemistry and materials science, resin is a solid or highly viscous substance of plant or synthetic origin that is typically convertible into polymers. Resins are usually mixtures of organic compounds. This article focuses on nat ...
s and
terpenes, and as a
corrosion
Corrosion is a natural process that converts a refined metal into a more chemically stable oxide. It is the gradual deterioration of materials (usually a metal) by chemical or electrochemical reaction with their environment. Corrosion engi ...
inhibitor.
See also
*
Eletefine (1998), an isoquinoline alkaloid.
*
Naphthalene, an analog without the nitrogen atom.
References
External links
{{Authority control
Simple aromatic rings