Ludwig Knorr
Encyclopedia
Ludwig Knorr was a German chemist. Together with Carl Paal, he discovered the Paal-Knorr synthesis
, and the Knorr quinoline synthesis
and Knorr pyrrole synthesis
are also named after him. The synthesis in 1883 of the analgesic drug Antipyrin, now called Phenazone
, was a commercial success. Antipyrin was the first synthetic drug and the most widely used drug until it was replaced by Aspirin
in the early 20th century.
. After the early death of his father, the education of him and his four brothers lay in the hands of their mother. In 1878 Knorr received his Abitur
and started to study chemistry at the University of Munich.
In the beginning, he studied under Jacob Volhard
; then, after Volhard left for the University of Erlangen, Hermann Emil Fischer
became his tutor. In the summer of 1880 Knorr worked with Robert Wilhelm Bunsen at the University of Heidelberg, and later assisted Adolf von Baeyer
in Munich. When Emil Fischer became professor at the University of Erlangen, he asked Knorr to follow him.
In 1882 Knorr received his PhD for a thesis titled Über das Piperyl-Hydrazin. His habilitation
followed three years later in 1885 with a thesis titled Über die Bildung von Kohlenstoff-Stickstoff-Ringen durch Ein-wirkung von Amin-und Hydrazinbasen auf Acetessigester und seine Derivate ("On the formation of carbon-nitrogen rings through the action of amine and hydrazine bases on acetoacetate and its derivatives"). In that time, during his search for quinine
related compounds, Knorr discovered the unmethylated Phenazone
. As another quinine-related compound kairin showed analgesic
and antipyretic
properties, Knorr and Fisher asked Wilhelm Filehne at the Hoechst company
to check the unmethylated and the methylated Phenazone for its pharmacological properties. Knorr patented the compound in 1883. Filehne later suggested the names Höchstin or Knorrin for the substance but Knorr telegraphed from his honeymoon that his variant of the name, Antipyrin, is not to be changed. (German: Antipyrin bleibt!). In 1885 Knorr married Elisabeth Piloty, the sister of his laboratory college Oskar Piloty
at the University of Munich.
and Knorr followed him and was made associate professor. Knorr described the time in Würzburg as most untroubled and most productive period of his life. Reactions of ethyl acetoacetate
with numerous other compounds were the main focus of his work there. After the death of Johann Georg Anton Geuther
in 1889, the University of Jena was searching for a new full professor and Ernst Haeckel
was sent to Würzburg to evaluate whether Knorr was qualified for the position.
s to the more general concept of tautomerism. In collaboration with various other chemists, Knorr proved the concept that ethyl acetoacetate existed in a keto and an enol
forms
. In his later years, the structural conformation of morphine
became his main point of interest. During the World War I
, Knorr served in the medical corps and returned to the University of Jena after the war ended. Knorr died after a short illness on June 4, 1921.
Paal-Knorr synthesis
The Paal–Knorr Synthesis in organic chemistry is a reaction that generates either furans, pyrroles, or thiophenes from 1,4-diketones. It is a synthetically valuable method for obtaining substituted furans and pyrroles, common structural components of many natural products...
, and the Knorr quinoline synthesis
Knorr quinoline synthesis
The Knorr quinoline synthesis is an intramolecular organic reaction converting a β-ketoanilide to a 2-hydroxyquinoline using sulfuric acid. This reaction was first described by Ludwig Knorr in 1886...
and Knorr pyrrole synthesis
Knorr pyrrole synthesis
The Knorr pyrrole synthesis is a widely used chemical reaction that synthesizes substituted pyrroles '. The method involves the reaction of an α-amino-ketone ' and a compound containing a methylene group α- to a carbonyl group '.-Method:The mechanism requires zinc and acetic acid as catalysts...
are also named after him. The synthesis in 1883 of the analgesic drug Antipyrin, now called Phenazone
Phenazone
Phenazone , phenazon, antipyrine , or analgesine is an analgesic and antipyretic. It was first synthesized by Ludwig Knorr in 1883. It is formed by reducing diortho- dinitrodiphenyl with sodium amalgam and methyl alcohol, or by heating diphenylene-ortho-dihydrazine with hydrochloric acid to...
, was a commercial success. Antipyrin was the first synthetic drug and the most widely used drug until it was replaced by Aspirin
Aspirin
Aspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. It was discovered by Arthur Eichengrun, a chemist with the German company Bayer...
in the early 20th century.
Early life
Ludwig Knorr was born to the wealthy merchant family in 1859. He grew up in the Sabbadini-Knorr company headquarter, located in the Kaufingerstraße in the center of Munich, and in the family house near the Lake StarnbergLake Starnberg
Lake Starnberg , 25 kilometers southwest of Munich in southern Bavaria, is Germany's fifth largest freshwater lake and, due to its large average depth, the second richest in water...
. After the early death of his father, the education of him and his four brothers lay in the hands of their mother. In 1878 Knorr received his Abitur
Abitur
Abitur is a designation used in Germany, Finland and Estonia for final exams that pupils take at the end of their secondary education, usually after 12 or 13 years of schooling, see also for Germany Abitur after twelve years.The Zeugnis der Allgemeinen Hochschulreife, often referred to as...
and started to study chemistry at the University of Munich.
In the beginning, he studied under Jacob Volhard
Jacob Volhard
Jacob Volhard was the German chemist who discovered, together with his student Hugo Erdmann, the Volhard-Erdmann cyclization reaction. He was also responsible for the improvement of the Hell-Volhard-Zelinsky halogenation....
; then, after Volhard left for the University of Erlangen, Hermann Emil Fischer
Hermann Emil Fischer
Hermann Emil Fischer, Emil Fischer was a German chemist and 1902 recipient of the Nobel Prize in Chemistry. He discovered the Fischer esterification. He developed the Fischer projection, a symbolic way of drawing asymmetric carbon atoms.-Early years:Fischer was born in Euskirchen, near Cologne,...
became his tutor. In the summer of 1880 Knorr worked with Robert Wilhelm Bunsen at the University of Heidelberg, and later assisted Adolf von Baeyer
Adolf von Baeyer
Johann Friedrich Wilhelm Adolf von Baeyer was a German chemist who synthesized indigo, and was the 1905 recipient of the Nobel Prize in Chemistry. Born in Berlin, he initially studied mathematics and physics at Berlin University before moving to Heidelberg to study chemistry with Robert Bunsen...
in Munich. When Emil Fischer became professor at the University of Erlangen, he asked Knorr to follow him.
University of Erlangen
Habilitation
Habilitation is the highest academic qualification a scholar can achieve by his or her own pursuit in several European and Asian countries. Earned after obtaining a research doctorate, such as a PhD, habilitation requires the candidate to write a professorial thesis based on independent...
followed three years later in 1885 with a thesis titled Über die Bildung von Kohlenstoff-Stickstoff-Ringen durch Ein-wirkung von Amin-und Hydrazinbasen auf Acetessigester und seine Derivate ("On the formation of carbon-nitrogen rings through the action of amine and hydrazine bases on acetoacetate and its derivatives"). In that time, during his search for quinine
Quinine
Quinine is a natural white crystalline alkaloid having antipyretic , antimalarial, analgesic , anti-inflammatory properties and a bitter taste. It is a stereoisomer of quinidine which, unlike quinine, is an anti-arrhythmic...
related compounds, Knorr discovered the unmethylated Phenazone
Phenazone
Phenazone , phenazon, antipyrine , or analgesine is an analgesic and antipyretic. It was first synthesized by Ludwig Knorr in 1883. It is formed by reducing diortho- dinitrodiphenyl with sodium amalgam and methyl alcohol, or by heating diphenylene-ortho-dihydrazine with hydrochloric acid to...
. As another quinine-related compound kairin showed analgesic
Analgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
and antipyretic
Antipyretic
Antipyretics ; an-tee-pahy-ret-iks; from the Greek anti, against, and pyreticus, are drugs or herbs that reduce fever. Normally, they will not lower body temperature if one does not have a fever. Antipyretics cause the hypothalamus to override an interleukin-induced increase in temperature...
properties, Knorr and Fisher asked Wilhelm Filehne at the Hoechst company
Hoechst AG
Hoechst AG was a German chemicals then life-sciences company that became Aventis Deutschland after its merger with France's Rhône-Poulenc S.A. in 1999...
to check the unmethylated and the methylated Phenazone for its pharmacological properties. Knorr patented the compound in 1883. Filehne later suggested the names Höchstin or Knorrin for the substance but Knorr telegraphed from his honeymoon that his variant of the name, Antipyrin, is not to be changed. (German: Antipyrin bleibt!). In 1885 Knorr married Elisabeth Piloty, the sister of his laboratory college Oskar Piloty
Oskar Piloty
-Life:Oskar Piloty was born the son of the painter Karl von Piloty in Munich. Due to the closeness of the Piloty family to the chemist Ludwig Knorr, who later married the sister of Oskar Piloty, he started studying chemistry at Adolf von Baeyer's laboratory at the University of Munich in 1888....
at the University of Munich.
University of Würzburg
In 1885 Fischer became professor at the University of WürzburgUniversity of Würzburg
The University of Würzburg is a university in Würzburg, Germany, founded in 1402. The university is a member of the distinguished Coimbra Group.-Name:...
and Knorr followed him and was made associate professor. Knorr described the time in Würzburg as most untroubled and most productive period of his life. Reactions of ethyl acetoacetate
Ethyl acetoacetate
The organic compound ethyl acetoacetate is the ethyl ester of acetoacetic acid. It is mainly used as a chemical intermediate in the production of a wide variety of compounds, such as amino acids, analgesics, antibiotics, antimalarial agents, antipyrine and aminopyrine, and vitamin B1; as well as...
with numerous other compounds were the main focus of his work there. After the death of Johann Georg Anton Geuther
Johann Georg Anton Geuther
Johann Georg Anton Geuther was a German chemist. His work in organic and inorganic chemistry influenced the development of coordination chemistry...
in 1889, the University of Jena was searching for a new full professor and Ernst Haeckel
Ernst Haeckel
The "European War" became known as "The Great War", and it was not until 1920, in the book "The First World War 1914-1918" by Charles à Court Repington, that the term "First World War" was used as the official name for the conflict.-Research:...
was sent to Würzburg to evaluate whether Knorr was qualified for the position.
University of Jena
Knorr became full professor at the University of Jena in 1889. In the following two years, he planned and built a new laboratory suitable for his research. His focus gradually shifted from the structure of pyrazolePyrazole
Pyrazole refers both to the class of simple aromatic ring organic compounds of the heterocyclic diazole series characterized by a 5-membered ring structure composed of three carbon atoms and two nitrogen atoms in adjacent positions, and to the unsubstituted parent compound...
s to the more general concept of tautomerism. In collaboration with various other chemists, Knorr proved the concept that ethyl acetoacetate existed in a keto and an enol
Enol
Enols are alkenes with a hydroxyl group affixed to one of the carbon atoms composing the double bond. Alkenes with a hydroxyl group on both sides of the double bond are called enediols. Deprotonated anions of enols are called enolates...
forms
Keto-enol tautomerism
In organic chemistry, keto-enol tautomerism refers to a chemical equilibrium between a keto form and an enol . The enol and keto forms are said to be tautomers of each other...
. In his later years, the structural conformation of morphine
Morphine
Morphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...
became his main point of interest. During the World War I
World War I
World War I , which was predominantly called the World War or the Great War from its occurrence until 1939, and the First World War or World War I thereafter, was a major war centred in Europe that began on 28 July 1914 and lasted until 11 November 1918...
, Knorr served in the medical corps and returned to the University of Jena after the war ended. Knorr died after a short illness on June 4, 1921.