Bonded to Compounds Providence

by Prof Dr Dr Randolph Riemschneider, L B Fel
Institute of Biochemistry, Free University of Berlin (FUB), Germany
and the Central Institute of Chemistry, Universidade Federal de Santa Maria (UFSM),
Santa Maria, Rio Grande do Sul, Brazil

Life BWW Fellow Prof R Riemschneider, has summarized his life-time’s work in a soon to be published book (1) in which will be found a number of chemical compounds and natural products that, in a certain way, seem to have developed a life of their own.

Editor

In Riemschneider's NACHLESE - 66 JAHRE CHEMIE (Re-reading 66 years of chemistry / 66 years of chemistry re-read) subdivided into XXVI projects (1), some compounds and natural products are conspicuous which have played a special role in the author's life over many years - one could almost say that they have "pursued" him to this day, to wit:

a) o-diacetylbenzene (o-di) - from 1937

b) hydride ions - from 1940 (2)

c) yeasts - from 1937

d) ATP - from 1941

e) aspirin - from 1941

f) thalidomide - from 1958 (3)

g) heptachloro-1,4-dioxane(s) - from 1943

h) dichlorodiphenyltrichloromethylmethane - from 1942

i) hexachlorocyclopentadiene, cylopentadiene - from 1943

Reports on two of these research complexes [b) and f)] were published in this journal recently (2,3), and were followed by an article on "heptachlorodioxane(s)" dealing with a purely academic problem.

Elucidations for a) to i) follow:

a) ortho-diacetylbenzene (o-di) [in loc cit (1) PROJECT I]:

This compound, when finely divided an inconspicuous white powder that stains the skin, ie suited for marking, already came into play during the author's school days (4). o-di and analogues [polyacetyl chemistry developed by the auhor] have resulted in more than 100 publications, lectures and patent applications. o-di can be used as an amino acid reagent [ninhydrin substitute (5)], was tested and used as a marking agent by the CID in Munich. It is suitable for temporary tattoos (6). The Schuchart[1] company of Munich put o-di produced according to the author's

instruction on the market for many years. The numerous theses submitted for a degree or doctorate in this field were scietifically very useful and also enjoyable for the students, as eg the “telephone receiver affair” or “psoriasis treatment” have shown: PROJECT I (1).

b) Hydride ions [in loc cit (1) and (2)]:

Since 1939, while studying chemistry, the author concerned himself with hydride ions, to be more precise with the questions of their existence in aqueous solutions, detecting them, their stability and action as free-radical scavengers, whether they occur in mountain waters, in water from Lourdes, in fruit juices. Of primary interest with respect to the fruit juices was Prof WALKER's hypothesis (in the author's view, based on the action of hydride ions), proposed in 1930, about the therapeutic use of fruit and vegetable juices, which he then proceeded to follow consistently for many years (8).

c) Yeast [in loc cit (1) PROJECT XXII]:

Like o-diacetylbenzene, yeast has also played a role in the author's life since his school days: 1937/38 "Studying the influence of baker's yeast on the potency of male mice" (9). Followed while studying chemistry by: A bibliographical paper on "Yeast and yeast extracts" in the colloquium of the Institute of Chemistry at the University of Göttingen (10) and a lecture on "Respiration and Fermentation" in the Organic Institute at the University of Hamburg (11), followed by practical experiments in the Institute of Hygiene at the University of Jena with the WARBURG-method: manometric measurements to determine the absorption or release of smallest quantities of the gases O₂ or CO₂ (12). Then continuing work on several yeast "topics" for over 40 years: PROJECT XXII. Via newly developed yeast cell preparations, the author came to the vegetal feed additive known as PROVAL or H 2000 (25, 26), as well as to cosmetic additives, called CYTOCATALYZER, a commercial preparation in Asia for 15 years.

d) ATP [in loc cit (1) above all PROJECTS XXII and XXIII]:

ATP (adenosine triphosphoric acid), isolated from muscle tissue and elucidated by Prof Dr K Lohmann in 1937, is a compound which plays a central role in the intermediary metabolism, to be precise as the "high-energy" reaction product of the most important exergonic reactions like respiration (biological oxidation) or glycolysis (in yeast: fermentation), localized in the mitochondria or cytoplasm of the cell. Mitochondria are also known as the "cell's power stations".

The author first met Prof Dr K Lohmann, the discoverer of ATP, in his capacity as the director of the Institute of Physiological Chemistry at the Kaiser Wilhelm University of Berlin in 1946, when submitting to him, on the recommendation of Prof Rienäcker (Rostock), his professorial thesis on the "Constitution and Action of Insecticides", that had been partially written in industry and at Jena University. After careful perusal, Lohmann accepted the paper and offered the author a position in his institute for the duration of the proceedings, and the opportunity to do his own research, both as a research assistant and lecturer. Special circumstances resulted in the author having to conduct the repeat intermediary preclinical exams in physiological chemistry for medical students, meaning that accordance with the regulations he had to go with the candidates to a full professor, and so got to know the famous surgeon Prof Sauerbruch. After one such exam he asked: "Why do wounds heal faster if one puts organ material or muscle flesh on them?" The author instantly saw a possible link with the ATP isolated by Lohmann from muscle tissue, and proposed the hypothesis that “more proteins are formed through increased ATP production (energy increase) and available for the healing process”. Following up the hypothesis and putting it into action from 1947 to 1970 led to very important results in the field of organ extracts and led, for example, to a remedy licenced in Japan since 1972 as well as certain bases for assessing the quality of cosmetic additives: measuring the increase in the skin's metabolic activity after applying extracts of placenta, thymus and blood. CELLRYL, the medicine based on calf blood extracts developed by the author for treating stomach ulcers, was in use in Japan for more than 25 years - till the BSE crisis reached Japan too in Dec 2000. The same is true of placenta extracts as cosmetic additives. And in the vegetal sector, these investigations led, through the simultaneous action of several physical in-fluences on yeast cells, to new, previously unknown yeast cell preparations with highly interesting properties which also led to commercial products: PROJECT XXII, XXIII (1).

e) Aspirin [in loc cit (1) PROJECT I]

Aspirin is among the compounds that "had a decisive influence on the author's life". The substance "developed a sort of life of its own": at the request of Prof Dr C Weygand, head of a department in the Institute of Organic Chemistry at the University of Leipzig, the author gave two lectures[2] on aspirin in 1941 at the

colloquia for deepening training in organic chemistry (13). The author learned a great deal about aspirin's properties and effects by studying the literature and in personal discussions with Weygand. Immediately after graduating as a chemist (diploma of 01 Oct 41), the author was, on 03 Oct 41, called up into the infantry, where he got to know a demoted police officer named Erdmann who became his teacher in matters of "how to get away from the infantry". Aspirin the author got from Erdmann helped here, namely 7 tablets to cause his heart and pulse to race. It worked, the captain in the medical corps transferred the author to the National Guard, in any event far away from the terrible infantry service and the attendant risks.

The next help from aspirin came in autumn 1945, when the Soviet occupiers in Erfurt conducted large-scale raids over three days and searched all the flats and houses. A sign saying "scalattina" (Russian for scarlet fever) on the door. Seven aspirins in the morning, more later, so that it came to "high fever", faking scarlet fever. We knew that the Soviets feared infectious diseases so, as expected, only a German policeman came into our apartment. Nothing happened, in view of the author's "condition". Aspirin had helped again.

Then in old age, the author took a 100 mg "aspirin protect" every day for several years in order to prevent infarct - but according to recent research aspirin apparently merely stops inflammation. To stop atherothrombosis and so infarct or stroke “iscover” for instance, based on clopidogrel might be a viable alternative.

Aspirin also played a role in the field of research over the years: the author tried to undertake something against the salicylic acid that forms in the stomach after the acetyl group splits off (13, lecture III) and suggested developing an "apririn protekt" (encapsulated) to Prof Dr Otto von Bayer, head of research at BAYER Werke, in 1953 - both in talks and in writing. But the cooperation envisaged did not materialize. The author's suggestion and request to test the aspirin analogues he to be synthesized by him - in which the carboxyl group is replaced by another - for antiphlogistic action (14), was also not accepted. It was realized from 1977 by experiments in Brazil (15).

f) Thalidomide [loc cit (1) PROJECT XXI and (3)]

The author has been interested in thalidomide since 1958, ie immediately after it came on the market as a seditative, inasmuch as he saw in it an unphysiological amino acid derivative, derived from glutamic acid. The author had sought such compounds since 1947, in order to disrupt the metabolism of insects, ie to put a less dramatic process alongside “halo compound-based chemical pest control”. As the manufacturers of thalidomide did not see fit to make it available to the author, he synthesized it in his own lab [loc cit (3), cit 9, 16]. Deformities were observed during experiments in various directions with thalidomide on tadpoles [loc cit (3) cit 17, 18], as well as inhibition of ascites cells [loc cit (3), cit 3].

When he was in Hamburg for his birthday, he had the opportunity to listen to a lecture by Dr Lenz, who on 18 Nov 61 had voiced his suspicion that thalidomide given to pregnant women was the cause of deformed infants, even though tests on rats and mice had indicated nothing of the like. After a mere four months, the author, in co-operation with Drs K Brockmeyer and H Sommer, had succeeded in proving teratogenicity on rabbits which had been offered to him by a 90-year-old friend of the family in Hamburg (at a reasonable price, including hutches) [loc cit (3) cit 15a, 13]. The author did not, however, give up on the compound, despite thalidomide’s negative characteristics. What else might it be good for? Can a non-teratogenic thalidomide analogue be found? Cancer patients were then treated with positive results by reason of the observed inhibition of ascites and angiogenesis [Prof Gerhartz, loc cit (3), cit 6]. Prof Dr H Gerhartz, Klinikum Westend, Berlin and Prof Dr Mariano da Rocha Filho, rector UFSM and director of the university hospital, used the thalidomide synthesized by the author for these experiments (3).

Thalidomide is licensed as a cancer therapeutic agent in the USA for some years now. As noted above, the author first reported on his own experiments in a paper entitled “Thalidomide, a curative drug with two faces” on 15 July 79 (3).

g) Heptachloro-1,4-dioxane(s)

A short report on this purely academic subject from the field of stereochemistry follows these explanations later in the text (45 years of research).

h) Dichlorodiphenyltrichloromethylmethane [loc cit (1) in PROJECTS VI to VIII]:

In 1942 fell Gesarol, a pest control agent against the potato beetle, into the author’s hands for analysis. It proved to be C₁₄H₉Cl₅, synthesized from chloral and 2 mol chlorobenzene (Bayer condensation), become famous late in the second world war as DDT (16, 17). In 1942 experiments on flies with Gesarol showed that the agent only acted after some time by contact (flies are sucking insects and can not imbibe a practically water-insoluble compound like food). Under the title “Halo carbon-based contact insecticides” (18), the author synthesized approx 70 analogues (note: before the compound became famous as DDT) and several hundred other halo compounds that were systematically tested after the war, of course continuous orientation experiments with flies and bollweevils from 1942 (cit 16).

DDT led the author systematically to new, more effective contact insecticides, as is shown in i). These investigations enabled the author to qualify early as a professor as both his doctoral and professorial theses were written simultaneously while working in petro-industry. In addition, he wrote two monographs about contact insecticides (19) in 1947 and 1949 that led to important international contacts.

i) Hexachlorocyclopentadiene (C₅Cl₆), cyclopentadiene (C₅H₄), [loc cit (1) in PROJECT XI]:

The author made C₅Cl₆ by the action of hypochlorite on C₅H₆ in the Explosives and Warfare Agents Establishment in Prague in order to study its characteristics and compare them with the explosive dichloroacetylene (C₂Cl₂) (20). Employed at RUHRÖL GmbH’s hydrogenation works from 01 Apr 43, the author pulled (in addition to his regular work) C₅Cl₆ as the starting material for the synthesis of “Halo compounds with new spatial distribution of chlorine” (21, 22) in the frame of the subject “Constitution (configuration) and activity of halocarbon-based contact insecticides”, cf h) too. This work led to the discovery of a new group of insecticides that was 1000 times more potent than DDT, namely M 410 (23, 24) – aka chlordan in America. Contrary to all expectations, C₅Cl₆ entered into a DIENE synthesis, in part under exothermic reaction. In collaboration with Farbwerke HOECHST this work later led to the insecticide and commercial product THIODAN: loc cit (1) PROJECT XI.

The author sees in what is described above a sort of natural act of fate, similar to the events described below relating to “Prague” and “survival” – as if guided by an invisible hand. This red thread of providence is still spun today.

The author was evidently intended to go to Prague:

When he was discharged from the military hospital in Furth im Wald just before Christmas 1943, the Catholic nun who had been his nurse gave him a medallion with the inscription “Prager Herzliebjesukind”. While on convalescent leave in Hamburg he was very impressed with Prague’s flair, portrayed in the film “Die goldene Stadt”. At the beginning of 1943 he had to guard captured Maroccans in Laon, France for the army. In breach of all regulations, he gave the one or other prisoner “leave” for an hour so that he could “indulge in love” or pop round the corner to go shopping at the baker’s, for example. This got noticed and resulted in disciplinary proceedings for conniving with prisoners. He occupied himself in the evenings in the soldier’s recreation centre with integral calculus, and the guy sitting at the same table was interested in it, so they got talking. It turned out that he came from Prague, where the author was to be posted to as an army chemist. And it also turned out that he was the one who had the file about conniving with the prisoners on his desk. He intimated that he wanted help. Shortly after that the author was indeed working at the German Army Explosives Research Establish-ment in Prague. The author was discharged there from the army on 01 Mar 43 into the mineral oil industry in the frame of (Rü-Tausch) 43.

The author was evidently intended to survive:

Several times his life was in danger, “escaped bombs”once in Jena on 12 Feb 45, and then the events of 22 Sept 42, 22 Sept 43 and 22 Sept 45.

The author was awarded his doctorate in Jena just before the end of the war. In preparation for the physics exam he attended a lecture by Prof Raether on 12 Feb 45 , given in the University of Jena’s Institute of Physics in the Oberen Philosophenweg. There was an air raid warning after the lecture. As everything stayed quiet, he decided to leave the institute and go into town. He passed one of the trenches, but didn’t jump in. He also passed the university library – on to the main bunker in the town centre. After the all clear all these places that should have been safe were destroyed: dead in front of the main bunker from bombs at the main entrance, a direct hit on the library, the trench flattened. Providence had preserved the author.

Thrice 22 Sept:

On 22 Sept 42: army doctor in Dniepropetrovsk diagnosed infectious jaundice: repatriated to Germany, thus escaping Stalingrad, where the company had been posted shortly after.

On 22 Sept 43: explosion in the lab of the hydogenation works where the author was meanwhile employed, only 1^st and 2^nd degree burns in the face.

On 22 Sept 44: in hospital in Erfurt with “sham” jaundice. The chief physician, a friend of the author’s father, couldn’t make anything of this sort of “jaundice”, he unsuspectingly injected cyclotropin, a coffein-urotropin-mix, for clarification. But this caused an unexpected reaction, resulting in very high fever, the author’s life was in danger.

Bibliography

(1) R Riemschneider: “Re-reading 66 years of chemistry” with approx 1,500 citations (own publications, lectures, lab reports, patents) and descriptions of projects I - XXVI plus vita (in preparation).

(2) R Riemschneider: Nutritional Supplement by Hydrid Ions acting as Antioxidants and Hydrid Ions and H Atoms as “Energy Currency” for Living Systems, 5 p. The Bi-Monthly Journal of the BBW Society, 2004

http://www.bwwsociety.org/journal/html/hydrid.htm

(3) R Riemschneider: Thalidomide: A remedy with two faces, 15 p, The Bi-Monthly Journal of the BBW Society, 2004

http://www.bwwsociety.org/journal/html/thalidomide.htm

(4) R Riemschneider: Oxidation of ethyl benzene, o-,m-,p-diethylbenzene nd o-ethyl acetophenone with potassium permanganate in buffered solution – o-diacetylbenzene, (Oxidation von Ethylbenzol, o-,m-,p- Diethylbenzol und o-Ethylacetophenon mit Kalium-permanganat in gepufferter Lösung – o-Diacetylbenzol) year’s course work in chemistry for graduating from college, 1939, 96 p; pulished in Gazz Chim Italiana 77, 607-611 (1947), submitted on 12 Sept 40.

(5) R Riemschneider, C Weygand, M Somplatzki, J Wierer

o-diacetylbenzene as amino acid reagent (o-Diacetylbenzol als Aminosäure-Reagens)

Lab reports 1947-51, 105 p; Mh Chem 86, 201-209 (1955); Z analyt Chemie 193, 186-189 (1962)

(6) loc cit (1) in PROJECT I (74, 87)

(7) R Riemschneider, K Nolde, K Henning, S Foerster

Preparing o-diacetylbenzene (Darstellung von o-Diacetylbenzol)

Mh Chem 104, 987-989 (1973)

o-di from 1,4 dimethylnaphthalene (o-Di aus 1,4-Dimethyl-naphthalin)

Mh Chem 93, 616-617 (1962)

(8) Norman W Walker

“Fresh vegetable and fruit juices”, Norwalk Press, Pressot, USA

“Become younger”, “Strahlende Gesundheit” Mosaik, W Goldmann-Verlag, Munich,

(9) R Riemschneider, A Suhr, H Kahl

On the negative influence of normal, intact yeast (baker’s yeast) on the potency of male mice (administered in drinking water) (Über den negativen Einfluß normaler intakter Hefe (Bäckerhefe) auf die Potenz von Mäuseböcken (verabreicht im Trinkwasser),

Lab report, 15 p, June 38. Abridged version published in school magazine of Wilhelm Grammar School, Hamburg-Dammtor, 1938. Result: inhibition of potency approx 20%.

(10) R Riemschneider, A Suhr, A Kersting

“Yeast and yeast extracts – Saccharomyces cerevisiae HANSEN – biocomplex yeast” („Hefe und Hefe-Extrakte – Saccharomyces cerevisiae HANSEN – Biokomplex Hefe“)

Lecture, given in chemical colloquium of Anat Chem Dept, Inst of Chem, Univ of Göttingen, mid-Dec 39

(11) R Riemschneider

“Fermentation and respiration” (Gärung und Atmung)

Part of lecture given in colloquium of Inst of Org Chem, Univ of Hamburg, Nov 40

(12) R Riemschneider

WARBURG method – first practical experiments on “Fermentation and respiration” (WARBURG-Methodik – Erste praktische Versuche zum Thema „Gärung und Atmung) in Inst of Hygiene, Univ of Jena, Lab reports, 17 p, Nov 44

(13) R Riemschneider

“o-acetylsalicyclic acid (aspirin)” (Acetylsalizylsäure (Aspirin): 3 lectures:

1 : “Acetylsalicylic acid and its relationships to salicin [Salix Cortex salicis (willow bark), methyl salicylate [gaultheria varieties wintergreen leaves) and salicylaldehyde [Spiraeae (Meadowsweet Flower)] (Acetylsalizylsäure und ihre Beziehungen zum Salizin [Salix Cortex Salicis (Weidenrinden)], zum Methylsalizylat [Gaultheria-Arten (Wintergrünblätter)] und zum Salizylaldehyd [Spiraeae (Meadowsweet Flower)])

Lecture given in colloquium of Org Chem Dept, Inst of Chem, Univ of Leipzig, May 41

2 : “On the history of aspirin[3] and its effects” (Zur Geschichte des Aspirins und seine Wirkungen)

Lecture given as lecture 1, June 41

3: “Aspirin: hypothesis on antiphlogistic action of aspirin” (Aspirin: Hypothese zur entzündungshemmenden Wirkung des Aspirins)

Lecture given in colloquium of Inst of Hygiene, Univ of Jena, 15 Oct 44

Presentation of hypothesis in lecture 3 that aspirin’s antiphlogistic effect is due to it acetylizing certain NH or OH groups (serine, thereonine?) in the union of peptide chains of enzymes (E) (Eq 1).

(Eq 1): Aspirin + E = E-COCH₃ + salicylic acid

Certain (eg gastrointestinal) side effects are caused by the formation of salicylic acid (Eq 1). To avoid forming salicylic acid, aspirin’s ortho position acid group had to be replaced by other substituents, naturally while maintaining the aspirin analogue’s antiphlogistic action.

Another possibility was gone into at the end of the, namely enclosing aspirin in capsules that could pass through the stomach uneffected, ie would only dissolve in the intestines.

(14) R Riemschneider, F R Pesserl, O Goehring, M M Faria, H Kahl

Synthesizing 55 aspririn analogues as per 1944 hypothesis (Synthese von 55 Aspirin-Analogen, gemäß Hypothese aus dem Jahr 1944)

Lect 3 (13). From: Inst of Biochem, FU Berlin, Central Inst of Chem; fed univ of S Maria (UFSM), Santa Maria, RS, Brazil; lab of Consulting, Development and Engineering, S Paulo and Rio de Janiero, Brazil.

8 lab reports from 19676-87, 121 p

(15) M M Faria, R Riemschneider, F R Pesserl, H Ferreira

Cyclooxygenase-inactivation by aspirin analogues (Cyclooxygenase-Inaktivierung durch Aspirin-Analoge)

Lab reports 1987, institutions as above (14)

(16) R Riemschneider

Extracting active agent of Gesarol and identifying lipoid-soluble part as C₁₄H₉Cl₅ (Extraktion des Wirkstoffes Gesarol und Identifizierung des lipoidlöslichen Anteils als C₁₄H₉Cl₅ ) - with the aid of GEIGY patents reviewed in Chem Zentralblatt – more precisely as condensation product of chloral and chlorobenzene (17)

Lab reports, 8 p, May 43

(17) Preparing b,b,b-trichloro-a,a-bis-[4-chlorophenyl]-ethane (dichlorodi-phenyltrichloromethylethane) from 1 mol chloral and 2 mol chlorobenzene as proof of structure of isolated Gesarol active agent (Herstellung von β,β,β-Trichlor-α,α-bis-[4-chlor-phenyl]-ethan (Dichlordiphenyltrichlormethylmethan) aus 1 Mol Chloral und 2 Mol Chlorbenzol, zum Konstitutionsbeweis des isolierten Gesarol-Wirkstoffes)

Lab reports, 6 p, June 43. Experiments conducted in works lab of RUHRÖL GmbH, Bottrop

(18) R Riemschneider

Coining the term “halocarbon-based contact insecticides” (Prägung des Begriffes „Kontakt-Insektizide auf Halogenkohlenwasserstoffbasis) June 43 –planning,

Lab reports 1943

(19) R Riemschneider

Contact insecticides I and II (Zur Kenntnis der Kontakt-Insektizide I und II)

1^st suppl vol, 2^nd and 9^th special issue of “Die Pharmazie” 1947 and 1949, pp 77-99 and 649-800

(20) R Riemschneider (lecturer), A Kühnl, O Schmidt

Hexachlorocylopentadiene, C₅Cl₆: 2 lectures

1: “The action of sodium hypochlorite on cylopentadiene: hexachloropenta-diene and higher-melting reaction products” (Über die Einwirkung von Natriumhypochlorit auf Cyclopentadien: Hexachlorpentadien und höher schmelzende Reaktionsprodukte)

Lecture given on 15 Feb 43 (20 p)

2: “Properties and reactions of C₅Cl₆” (Eigenschaften und Reaktionen des C₅Cl₆)

Lecture given in German Army Explosives and Warfare Agents Research Estab-lishment in Prague on 15 Mar 43

The “example” of dichloroacetylene, C₂Cl₂, made it seem appropriate to test if C₅Cl₆ was also suited for an explosive or warfare agent. Result: negative

(21) R Riemschneider

Constitution and properties of wax-like side products, and their properties, obtained when preparing hexachlorocyclopentadiene from cyclopentadiene and hypochlorite. Possible new DIELS-ADLER adducts (Konstitution und Eigenschaften der bei der Herstellung von Hexachlorcyclopentadien aus Cyclopentadien und Hypochlorit entstehenden wachsartigen Nebenprodukte und deren Eigenschaften. Mögliche neue DIELS-ALDER-Addukte,)

Lab reports, 30 p, RUHRÖL GmbH, Bottrop, Feb 44

(22) R Riemschneider

On using hexachlorocyclopentadiene as starting material for “synthesis of chlorine compounds with new spatial distribution of chlorine”: OET group (later: DIENE group) (Über den Einsatz von Hexachlorcyclopentadien als Ausgangsmaterial zur „Synthese von Chlorverbindungen mit neuer Verteilung von Chlor im Raum“: OET-Gruppe (später DIEN-Gruppe))

Lab reports, 9 p, Dec 44. Experiments conducted at RUHRÖL GmbH, Bottrop, 1943-44 and in Chem Lab, Inst of Hygiene, Univ of Jena, from Oct 44. Project XXI

(23) R Riemschneider

“A new type of insecticidal halogen compounds, starting from C₅Cl₆ – after first tests, very promising: M 410” (Ein neuer Typ insektizider Halogenverbindungen, ausgehend von C₅Cl₆ - nach ersten Testversuchen vielversprechend: M 410.)

Lecture given in Inst of Pharmaceutics, Univ of Jena on 31 Jan 45

Insecticidal activity of M 410 on Calandra granaria & Blatta orientalis greater than DDT

(24) R Riemschneider

On the remarkable properties of post-chlorinated adducts from hexachloro-cyclopentadiene and cyclopentadiene, C₁₀H₆Cl₆ – M 410 identified as octa-chloroendomethylenetetrahydrohydrindene (OET), C10H6Cl8 (mol wt 410) (Über die bemerkenswerten Eigenschaften nachchlorierter Addukte aus Hexachlorcyclopentadien und Cyclopentadien, C₁₀H₆Cl₆. – M 410 identifiziert als Oktachlorendomethylen-tetrahydrohydrinden (OET), C₁₀H₆Cl₈ (Molgewicht 410))

C₁₀H₆Cl₆+ Cl₂ C₁₀H₆Cl₈

Lab reports 1944 and to Mar 45. Experiments conducted at RUHRÖL GmbH and in Inst of Hyg, Univ of Jena

(25) R Riemschneider

Cytocatalyzer, Seryel, and Collaplant PO, Plant-Based Cosmetic Additives 2003

http://www.bwwsociety.org/journal/html/cytocytalyzer.htm

(26) R Riemschneider

Two Notes on Progress in BSE-Crisis (H 2000), 2002

http://www.bwwsociety.org/journal/html/bsicrisis.htm

About so-called heptachloro-1,4-dioxane from m p 122^oC

Prof Dr Dr Randolph Riemschneider, L.B.Fel.

Institute of Biochemistry, Free University (FU) Berlin, Germany

and

Central Institute of Chemistry, Universidade Federal de Santa Maria (UFSM),

Santa Maria, Rio Grande do Sul, Brazil

rriemschneider @yahoo.de

Abstract: For studying the problem of chair-conversion-isomery during 1947-1986 (4) we prepared many 1,4-dioxan chlorination products and analysed them for the two theoretically possible heptachloro-1,4-dioxane (I)-isomers. Of the two described I-isomeres, melting at 57° C and at 122° C, only the first does actually exist.

Keywords: dioxane – heptachloro-1,4-dioxanes (I) – chair-conversion-isomery

We researched the chlorination of 1,4-dioxane and some of its crystallized Cl-substitution products intensively at the FU Berlin and in various institutions in Brazil from 1947 to 1986, and we were able to isolate only one heptachloro-1,4-(I)-isomer from all the final chlorinated products, namely the one that melts at 56-57^oC – unlike H Stumpf (3) who some 50 years ago described a second I-isomer from m p 122^oC. Two I-isomers would have been interesting inasmuch as we would have had two partners in a conversion relationship to one another seperate in substance for the first time (4): Diag 1

Diag 1: The chair configurational partners 6a(H)2ea3ea5ea6e(Cl) and 6e(H)2ea3ea5ea6a(Cl) of 2.2.3.3.5.5.6-heptachloro-1,4-dioxane [lit (4)]

Key to diag 1: In an imagined conversion of the 1,4-dioxane chair, in which eg the C atoms 2 and 6 and the O atom 4 migrate down and the C atoms 3 and 5 and the O atom 1 up, 2 chair configurations of 1,4-dioxane substitution products pass over into one another, that we combine to chair configuration pairs. Of the partners in such a configuration pair, we call the original chair configuration “body” and the converted one “counter body”. In the case of 2.2.3.3.5.5.6-heptachloro-1,4-dioxane, the body has the configuration 6a(H)2ea3ea5ea6e(Cl) and the counter body 6e(H)2ae3ae6a(Cl), ie on conversion all e-connected substituents convert to a-connected and vice versa (e as in equatorial, a as in axial).

In the case of monofluoro-enkekachlorocyclohexane, the body has the chair configuration 1e(F)1a2ea3ea4ea5ea6ea(Cl) and the counterbody 1a(F)1e2ae3ae4ae5ae6ae(Cl), both realized (5,6).

We sought representatives, above all among high-substituted polyheterohalo-cyclohexanes, which were in a conversion relationship to one another and could be synthesized separated in substance; we succeeded in this at the time in the case of the two monofluoro-endekachloro-cyclohexanes in collaboration with Y Morino, Tokio and W Plieth, Berlin (5, 6).

The author already cast doubt on the existence of the “I-isomer from m p 122^oC” described by W Stumpf at the Chemists Congress in Innsbruck on 01 Apr 53 immediately after Stumpf’s lecture, saying it was improbable that a heptachloro-dioxane would melt higher than the symmetrically formed octachloro-1,4-dioxane (II), for which the author had determined a melting point of 110-112^oC and a dipole moment of 0.2 D (7, 9) in 1948.

At the time W Stumpf was unable to make the isomer from m p 122^oC available when asked by our co-worker G Seeliger. Research commissioned, plus several examination theses, confirmed the non-existence of I from m p 122^oC (8). We had characterized the existant I-isomer from m p 56-57^oC both chemically by conversion to 2,3,5,5,6,6-hexachloro-1,4-dioxen from m p 20-22^oC and further chlorination to II as well as spectroscopically (9).

References:

(1) From lecture and publication Special structure of heptachloro-1,4-dioxanes and related compounds. Cit (677) in: R Riemschneider “Re-reading 66 years of chemistry” (in preparation)

(2) Loc cit (1) cit (656-659), (662-667), (669-674), (677 and 678). Authors: R Riemschneider with (in chronological order): K.Schürken, K.Lohmann, W.Gerischer, W.Cohnen, A.Heymons, F.Scherer, G.Seeliger, R.Wasicky, W.Stuck, E.B.Grabitz, D.Takei, P.Nowack, H.Fereira ,M Azhar (1947-1986) und M.M.Faria, H.S.Chang, Chemical-Engineering-Development (1977 –1982); cf (8)

(3) W Stumpf

Chemistry and applications of 1,4-dioxane (Chemie und Anwendugen des 1,4-Dioxans)

Verlag Chemie GmbH 1956, p 130-133

(4) R Riemschneider

About the configurations of 1,4-dioxane substitution products (Über Konfigurationen von 1,4-Dioxan-Substitutionsprodukten)

Z Naturforschg 8B, 745-751 (1954), Free University of Berlin

(5) Y.Morino, R.Riemschneider, (lecturer) M.Z. Azhar, W. Plieth: X-ray of 2 C₆FCl₁₁ – isomers, report, 1986, 9 pp; Lecture from May 15, 1986, given in the Chemical Institute of SAITAMA University, Urawa, Japan. loc cit (1) Projekt II: cit (215, 214, 211, 212).

(6) R Riemschneider, W Pollack, F R Pesserl et al (1969-76)

a) Long-term chlorination experiments to isolate monofluoroendekachloro-hexane(s), starting from fluorobenzene, difluorobenzenes, monofluorotri-chlorobenzene, pentachloromonofluorobenzene, monofluoroheptachloro-cyclohexane from m p 218oC, from monofluorohexachlorocyclohexane oils and many other fluorine derivatives: (Langzeit-Chlorierungsversuche zur Isolierung von Monofluor-endekachlorcyclohexan(en), ausgehend von Fluorbenzol, Difluorbenzolen, Monofluortrichlorbenzol, Penta-chlormonofluorbenzol, Monofluorheptachlorcyclohexan vom Schmp. 218°C, von Monofluorhexachlorcyclohexan-Ölen und vielen anderen Fluorderivaten) PROJECT II 6 (1)

b) Negative results with respect to the further search for a second hepta-chloro-1,4-dioxane isomer in chlorinated products of tetra- and hexachloro-1,4-dioxanes. (Negative Ergebnisse hinsichtlich der weiteren Suche nach einem zweiten Heptachlor-1,4-dioxan-Isomeren in Chlorierungsprodukten von Tetrachlor- und Hexachlor-1,4-dioxanen)

Mss, 12 p, 1976. Experiments from the Central Chem Inst, Univ Fed of Santa Maria (UFSM), S Maria, RG, Brazil.

The long-term chlorinations were conducted in Carius (bomb) tubes that were exposed to sunlight on the institute roof for up to two years. Of 300 tubes some 180 were lost through explosion.Such experiments were no longer possible in Germany after 1969.

(7) F Scherer, R Riemschneider (discussant), R Wasicky

Critical comments during discussion of lecture by W Stumpf on “Dioxane-chlorinated products as insecticides” (Kritische Diskussionsbemerkung zum Vortrag von W. Stumpf über „Dioxan- Chorierungsprodukte als Insektizide)

Chemists Congress, Innsbruck, 01 Apr 53

Text of comments sent to Österreichische Chemiker-Zeitung, Vienna on 02 Apr 53

(8) Loc cit (2) eg

a) R Riemschneider, A Heymons, G Seeliger, E B Grabitz (1954-56)

Experimental testing of question of existence of second “heptachloro-1,4-dioxane” (m p 122^oC) (Experimentelle Prüfung der Frage der Existenz des zweiten „Heptachlor-1,4-dioxans“ (Schmp. 122°C))

Ms 10 p, 1956. Unpublished experiments in Dept of Biochem, FU Berlin and G Seeliger’s 30-page degree thesis, Tech Univ of Berlin, 1956

Despite the most intensive efforts, it did not prove possible to isolate a second heptachloro-1,4-dioxane isomer by the time the manuscript was written, nor in-deed later.

b) R Riemschneider (lecturer), E B Grabitz, J Takei, P Nowack (1958-62)

Continuing experimental work in search of two 2,2,3,3,5,5,6-heptachloro-1,4-dioxane isomers in 1,4-dioxane chlorinated products (starting from 1,4-dioxane as well as defined tetra- and hexachloro-1,4-dioxanes and from dioxadiene) (Fortsetzung der experimentellen Arbeiten zur Suche nach

zwei 2,2,3,3,5,5,6-Heptachlor-1,4-dioxan-Isomeren in 1,4-

Dioxan-Chlorierungsprodukten (ausgehend von 1,4-Dioxan

sowie definierten Tetra- und Hexachlor-1,4-dioxanen und

vom Dioxadien).

Lecture in colloquium of Dept of Biochem, FU Berlin on 20 Jan 61

Lab reports from 1958-62 from above dept. Result up to 1986: negatice. There is only one heptachlorodioxane isomer (680)

Continuing 1,4-dioxane chlorination experiments. The heptachloro-1,4-dioxane problem (Fortsetzung der 1,4-Dioxan-Chlorierungsversuche. Das Heptachlor-1,4-dioxan-Problem) (commissioned research)

24-page report, 1983, of experiments conducted by Chemical Engineering-Development of S Paulo, Brazil

The non-existence of so-called heptachlorodioxane from m p 122oC was also confirmed by this independent institution.

(9) R Riemschneider, K Lohmann, W Gerischer, W Cohnen, A Heymons (1947-49)

About preparing and identifying 10 Cl-substituted 1,4-dioxanes, dioxens and subsequent products as well as testing them for contact-insecticidal activity (direct chlorinations of 1,4-dioxane and 1,4-dioxane chlorinated products);

2,2,3,3,5,5,6-heptachloro-1,4-dioxane from m p 56-57^oC and octachloro-1,4-dioxane from m p 110-112^oC (Über die Herstellung und Identifizierung von 10 Cl-substituierten 1,4-Dioxanen, -Dioxenenund Folgeprodukten sowie ihre Prüfung auf kontakt-insektizide Wirksamkeit (direkte Chlorierungen von 1,4-Dioxan und 1,4-Dioxan-Chlorierungsprodunkten);

2,2,3,3,5,5,6-Heptachlor-1,4-dioxan vom Schmp. 56 – 57°C,

Oktachlor-1,4-dioxan vom Schmp. 110 – 112°.)

Mitt Physiolog Chem Inst Berlin, 15 p, Jan 49, secreted at the instigation of Dr F Scherer, Farbwerke Hoechst AG; cf loc cit (1): (553); cf lect of Apr and May 52 in Berlin and Vienna loc cit (1): (446)

[1] later bought up by MERCK

[2] a third lecture followed in 1944 (13)

[3] Aspirin was brought to medicine by BAYER in 1899. “A” from acetyl and “spir” from spiraeic (later: salicylic) acid

[ back to "Publications & Special Reports" ]
[ BWW Society Home Page ]