Cinnoline
Encyclopedia
Cinnoline is an aromatic
heterocyclic compound
with the formula C8H6N2. It is isomer
ic with quinoxaline
, phthalazine and quinazoline
.
with base. It co-crystallizes with one molecule of ether as white silky needles, (m.p. 24-25 °C) upon cooling ethereal solutions. The free base
melts at 39 °C. It has a taste resembling that of chloral hydrate
and leaves a sharp irritation for some time. Cinnoline derivatives are obtained from oxycinnolin carboxylic acid, which is formed by digesting orthophenyl propiolic acid diazo chloride with water. Oxycinnolin carboxylic acid on heating gives oxycinnoline, melting at 225 °C, which with phosphorus pentachloride gives chlorcinnolin. This substance is reduced by iron filings and sulfuric acid
to dihydrocinnolin.
o-C6H4(NH2)C≡CCO2H in water to give 4-hydroxycinnoline-3-carboxylic acid. This material could be decarboxylated and the hydroxyl group reductively removed to give the parent heterocycle. This reaction is called the Richter cinnoline synthesis Improved methods exist for its synthesis. It can be prepared by dehydrogenation
of dihydrocinnoline with freshly precipitated mercuric oxide. It can be isolated as the hydrochloride
.
Cinnolines are cinnoline derivatives. A classic organic reaction
for synthesizing cinnolines is the Widman-Stoermer synthesis, a ring-closing reaction of an α-vinyl- aniline
with hydrochloric acid
and sodium nitrite
:
The sodium nitrite is first converted to nitrous acid
which then forms the electrophilic
intermediate dinitrogen trioxide
. The next intermediate is the stable Nitrosamine
with goes on to lose water forming the diazonium salt which then reacts with the vinyl group in the ring-closing step. A conceptually related reaction is the Bamberger triazine synthesis
towards triazines.
Another cinnoline method is the Borsche cinnoline synthesis.
Aromaticity
In organic chemistry, Aromaticity is a chemical property in which a conjugated ring of unsaturated bonds, lone pairs, or empty orbitals exhibit a stabilization stronger than would be expected by the stabilization of conjugation alone. The earliest use of the term was in an article by August...
heterocyclic compound
Heterocyclic compound
A heterocyclic compound is a cyclic compound which has atoms of at least two different elements as members of its ring. The counterparts of heterocyclic compounds are homocyclic compounds, the rings of which are made of a single element....
with the formula C8H6N2. It is isomer
Isomer
In chemistry, isomers are compounds with the same molecular formula but different structural formulas. Isomers do not necessarily share similar properties, unless they also have the same functional groups. There are many different classes of isomers, like stereoisomers, enantiomers, geometrical...
ic with quinoxaline
Quinoxaline
A quinoxaline, also called a benzopyrazine, in organic chemistry, is a heterocyclic compound containing a ring complex made up of a benzene ring and a pyrazine ring...
, phthalazine and quinazoline
Quinazoline
Quinazoline is a compound made up of two fused six-membered simple aromatic rings, a benzene ring and a pyrimidine ring. Its chemical formula is C8H6N2. Quinazoline is yellow and crystalline...
.
Properties
The free base can be obtained as an oil by treatment of the hydrochlorideHydrochloride
In chemistry, hydrochlorides are salts resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base . This is also known as muriate, derived from hydrochloric acid's other name: muriatic acid....
with base. It co-crystallizes with one molecule of ether as white silky needles, (m.p. 24-25 °C) upon cooling ethereal solutions. The free base
Base (chemistry)
For the term in genetics, see base A base in chemistry is a substance that can accept hydrogen ions or more generally, donate electron pairs. A soluble base is referred to as an alkali if it contains and releases hydroxide ions quantitatively...
melts at 39 °C. It has a taste resembling that of chloral hydrate
Chloral hydrate
Chloral hydrate is a sedative and hypnotic drug as well as a chemical reagent and precursor. The name chloral hydrate indicates that it is formed from chloral by the addition of one molecule of water. Its chemical formula is C2H3Cl3O2....
and leaves a sharp irritation for some time. Cinnoline derivatives are obtained from oxycinnolin carboxylic acid, which is formed by digesting orthophenyl propiolic acid diazo chloride with water. Oxycinnolin carboxylic acid on heating gives oxycinnoline, melting at 225 °C, which with phosphorus pentachloride gives chlorcinnolin. This substance is reduced by iron filings and sulfuric acid
Sulfuric acid
Sulfuric acid is a strong mineral acid with the molecular formula . Its historical name is oil of vitriol. Pure sulfuric acid is a highly corrosive, colorless, viscous liquid. The salts of sulfuric acid are called sulfates...
to dihydrocinnolin.
Discovery and synthesis
The compound was first obtained in impure form by cyclization of the alkyneAlkyne
Alkynes are hydrocarbons that have a triple bond between two carbon atoms, with the formula CnH2n-2. Alkynes are traditionally known as acetylenes, although the name acetylene also refers specifically to C2H2, known formally as ethyne using IUPAC nomenclature...
o-C6H4(NH2)C≡CCO2H in water to give 4-hydroxycinnoline-3-carboxylic acid. This material could be decarboxylated and the hydroxyl group reductively removed to give the parent heterocycle. This reaction is called the Richter cinnoline synthesis Improved methods exist for its synthesis. It can be prepared by dehydrogenation
Dehydrogenation
Dehydrogenation is a chemical reaction that involves the elimination of hydrogen . It is the reverse process of hydrogenation. Dehydrogenation reactions may be either large scale industrial processes or smaller scale laboratory procedures....
of dihydrocinnoline with freshly precipitated mercuric oxide. It can be isolated as the hydrochloride
Hydrochloride
In chemistry, hydrochlorides are salts resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base . This is also known as muriate, derived from hydrochloric acid's other name: muriatic acid....
.
Cinnolines are cinnoline derivatives. A classic organic reaction
Organic reaction
Organic reactions are chemical reactions involving organic compounds. The basic organic chemistry reaction types are addition reactions, elimination reactions, substitution reactions, pericyclic reactions, rearrangement reactions, photochemical reactions and redox reactions. In organic synthesis,...
for synthesizing cinnolines is the Widman-Stoermer synthesis, a ring-closing reaction of an α-vinyl- aniline
Aniline
Aniline, phenylamine or aminobenzene is an organic compound with the formula C6H5NH2. Consisting of a phenyl group attached to an amino group, aniline is the prototypical aromatic amine. Being a precursor to many industrial chemicals, its main use is in the manufacture of precursors to polyurethane...
with hydrochloric acid
Hydrochloric acid
Hydrochloric acid is a solution of hydrogen chloride in water, that is a highly corrosive, strong mineral acid with many industrial uses. It is found naturally in gastric acid....
and sodium nitrite
Sodium nitrite
Sodium nitrite is the inorganic compound with the chemical formula NaNO2. It is a white to slight yellowish crystalline powder that is very soluble in water and is hygroscopic...
:
The sodium nitrite is first converted to nitrous acid
Nitrous acid
Nitrous acid is a weak and monobasic acid known only in solution and in the form of nitrite salts.Nitrous acid is used to make diazides from amines; this occurs by nucleophilic attack of the amine onto the nitrite, reprotonation by the surrounding solvent, and double-elimination of water...
which then forms the electrophilic
Electrophile
In general electrophiles are positively charged species that are attracted to an electron rich centre. In chemistry, an electrophile is a reagent attracted to electrons that participates in a chemical reaction by accepting an electron pair in order to bond to a nucleophile...
intermediate dinitrogen trioxide
Dinitrogen trioxide
Dinitrogen trioxide is the chemical compound with the formula N2O3. This deep blue liquid is one of binary nitrogen oxides. It forms upon mixing equal parts of nitric oxide and nitrogen dioxide and cooling the mixture below −21 °C :Dinitrogen trioxide is only isolable at low...
. The next intermediate is the stable Nitrosamine
Nitrosamine
Nitrosamines are chemical compounds of the chemical structure R1N-N=O, some of which are carcinogenic.-Usages:Nitrosamines are used in manufacture of some cosmetics, pesticides, and in most rubber products. -Occurrences:...
with goes on to lose water forming the diazonium salt which then reacts with the vinyl group in the ring-closing step. A conceptually related reaction is the Bamberger triazine synthesis
Bamberger triazine synthesis
The Bamberger triazine synthesis in organic chemistry is a classic organic synthesis of a triazine first reported by Eugen Bamberger in 1892 ....
towards triazines.
Another cinnoline method is the Borsche cinnoline synthesis.