Saturday, January 17, 2015

Book Reading Update - Fontana History of Chemistry Chap 16

Chapter 16: At the Sign of the Hexagon

The chapter title, At the Sign of the Hexagon, pertains to the benzene molecule, whose discovery by Michael Faraday has resulted in the development of the chemical industry that gave people products such as colorful fabrics, perfumes, synthetic materials like bakelite, plastics, artificial silks, etc., led to knowledge about the chemistry in the human body, and brought improvements in health through the drug industry.  As a preview of the last chapter, the author writes “Underlying what the American chemical firm of Du Pont called ‘better living with chemistry’ has been the chemists’ ability to synthesize new products and the chemical engineers’ ingenuity in industrializing invention. However, with the increasing penetration of chemistry into the weft and warp of rural and urban civilization have come problems of pollution and safety that have damaged the science’s reputation and produced a chemophobia among some sections of the public.”

In the section on Synthesis, the author summarized progress in synthetic chemistry beginning in the 1930's.  There was a particular focus on the progress in structural analysis and synthesis of natural products and the advent of sophisticated instrumentation as tools for structural analysis,.  By the 1930’s, chemical synthesis had proved useful not just as a way of making new compounds but also in establishing and verifying chemical structures, studying ‘humanly produced substances’, and testing general theories.  Some of those highlighted by the author include:
The Germans Adolf Baeyer and Emil Fischer at the turn of the 20th century “had made the art of structure determination and synthesis at ne and the same time the most glamorous and prestigious [due to the number of Nobel Prizes awarded], as well as tedious and plodding [due its mechanically routine nature]”.
In 1877, Fiedel and Crafts discovered the reactions which converted organic chlorides into hydrocarbons or acid halides into ketones with the help of aluminum chloride catalyst (now taught as the Friedel-Craft reactions familiar to any organic chemistry student).  This reaction was useful in synthesizing homologues of benzene and played a big role in petrochemical industry in the 1950’s.
Robinson, although eclipsed by Ingold in establishing structural theory, achieved fame in his prolific structural determination of natural products such as the alkaloids, strychnine, and coloring substances in flowers such as anthocyanins and anthoxanthins. (Germany)
Richard Kuhn synthesized vitamin A in 1938 and vitamin B6 in 1939.  (Germany)
Otto Diels and Kurt Alder, in 1928, developed the addition reaction now named after both of them in which double-bonded dienes added to form cyclic compounds.  This later on proved to be a useful step in the synthesis of natural products. (Germany)
Ernest Fourneau in France worked on the synthesis of anesthetics like stovaine and chemotherapeutic agents such as the sulfanilamide agent Prontosil Album in 1935.
A Pasteur Institute team of chemists following the work of Gerhard Domagk synthesized and tested 18 derivatives of sufanilaide chrysoidine (prontosil) which were found to decompose in the body to the actual bactericide, para-aminobenzene sulfanilamide in 1937. (Sulfanilamide was synthesized in 1908 by Paul Gelmo using some other synthetic method but was not patent protected).
In America, during the first world war, Roger Adams pioneered the use of paid student workers in synthesizing reagents for undergraduate laboratories and for research during summer breaks. Much of the synthetic work was later transferred to a commercial chemistry after the war but the synthetic work from this provided the impetus for Organic Syntheses, an annual series of volumes started by Adams.
Roger Adams also achieved fame and success in industrial consultancy and government advising after discovering the catalytic power of platinum oxide in hydrogenation reactions and syntheses in 1922.
The next generation of structural chemists included Robert Woodward, Carl Djerassi, and Donald J. Cram.
In the 1930’s, there was a big focus on steroid synthesis driven by the scarcity of natural sources of hormones used in treating hormone deficiency diseases.  Many of these syntheses made use of other naturally occurring steroids like diosgenin as starting compounds.  Russell Marcker worked with a Mexican company (diosgenin was found in large quantities in one Mexican plant) n developing the commercial manufacture of progesterone , ‘seeding the contraceptives revolution’.
Carl Djerassi continued and refined Marcker’s work on steroid synthesis in the same company.  In 1955, Djerassi successfully developed a simple synthesis of cortisone from starting materials extracted from Mexican yams and sisal.
Along with developments in laboratory synthesis of natural products, fermentation procedures in the field of biotechnology were also being utilized to synthesize natural products.
After the discovery of penicillin as an antibiotic, its importance during the second world war prompted several groups of chemists to find a synthetic pathway.  Unsuccessful, pharmaceutical companies turned instead to a fermentation process to grow penicillium notatum.  In 1957, John Sheehan successfully synthesized the molecule.
In the 1960’s, structural determination by reverse chemistry (“the degradation of products that were reassembled after their own separate synthesis”) was replaced by instruments that allowed direct identification of functional groups (mass spectrometry, IR and UV spectrophotometry), elemental composition such as H and P, kinetic-mechanistic information (NMR spectroscopy), “optical rotator dispersion with the spectropolarimeter for the determination of conformation and configuration of molecules”.
In the 1930’s and beyond, photochemistry developed with work done by Ronald Norrish on photochemical reactions, investigating the photolysis of aldehydes and ketones and the formation of free radicals under irradiation using a flash lamp.  Weaker flashes enabled spectroscopic photography to be used in identifying reaction intermediates.  The development of laser beams in 1960 led to the use of flash photolysis in mechanistic studies, investigations of excited states, and photochemical ring closure (as opposed to thermal treatment).
After the war, there was a notable shift by chemists toward biochemistry and structure-function relationships in living systems.  Some of the work noted in this section include:
Djerassi’s synthesis of a more powerful contraceptive by methylation of progesterone to produce norethindrone.  Djerassi also solved many complex stereochemical problemns through his development of optical methods for determining structural details.
Donald Cram’s work on host-guest complexation contributed to understanding of enzyme function and provided insight on the design of synthetic hosts as counterparts to receptor sites which earned him a Nobel Prize in 1987.
Teruazaki Mikaiyama, another prolific synthetic chemist, emphasized the “continuing importance of purely exploratory experimentation and the pursuit of the unexpected” as “overzealous use of mechanistic analysis could stifle the creativity of synthesizers”.  His work later on narrowed its focus on the use of dehydrating agents on synthetic pathways.

The author devoted a relatively detailed account of Robert Woodward's work, referring to him as ‘the most extraordinary” of modern synthetic chemists.  Robert Woodward’s prolific success in synthetic chemistry owed much to his use of modern instrumentation and use of the molecular orbital theory in understanding structure and mechanism.  Known for avoiding racemates ‘at any stage of a synthesis’, Woodward was known to have stated that “mixtures of stereoisomers were an ‘inelegance, not to say impracticality’”.  He used mechanistic studies by Ingold and others to predict “bonds to be made and broken in three dimensions” and to gauge the feasibility of a proposed reaction.  His fame was such that a student’s synthesis of a ‘Woodward molecule’ became a ‘badge of entry’ into academia or industry. In the words of the author, Woodward and his competitors made organic chemistry a ‘big science’ like particle physics. The development of what is now known as the Woodward-Hoffman rules began with Woodward’s qualitative insight on the need for two atoms to be in phase for a bond to form and the role of light in this effort.  “A given stereochemistry arose precisely because molecules were able to twist around until their appropriate bonding orbitals were in the correct phase.”  He then recognized that while heat can only induce vibrations and other motions in molecules, light photons can promote electrons to orbitals of a higher energy and potentially different phase.  This promotion and different phase may then facilitate the twisting of the molecule to better positions its orbitals for overlapping and bonding.  Roald Hoffman provided the quantitative explanation cementing the foundation for the Woodward-Hoffman rules or principle of orbital symmetry.
Further progress in synthetic chemistry led chemists to increasingly seek out synthesis of exotic molecules like fullerenes.  Also, computational methods became increasingly useful for chemists to study and design molecules with more precision before trying their synthesis in the lab.

Industrial chemistry in the 1900's
In this section, the author gives a history of the growth of the chemical industry, the resulting need to scale-up synthetic procedures and the chemical engineers to carry out the process, and the most significant products that came out of this expansion.

By the 1880’s, industrialists have recognized the need for a specialized type of chemists to work on scaling up reaction procedures, referring to it as a “chemical engineering” problem.  In 1887, George Davis, secretary of the Society of Chemical Industry, defined chemical engineering as the study of the “application of machinery and plant to the utilization of chemical action on the large scale”.  The type of plant addressed in the course involved large-scale industrial operations such as drying, crushing, distillation, fermentation, evaporation, and crystallization.  It was not until 1909 that the first chemical engineering course was taught in Britain while in America, Norton at MIT offered the first course modeled after Davis’ description.  Around the same time, in 1915, companies began creating their own research laboratories with Germany leading the effort so that “invention and discovery became industrialized”.

One example of a significant undertaking by the chemical industry was the development and use of the Haber-Bosch process for ammonia synthesis. At the end of the 19th century, William Crookes voiced the following concern regarding the need to “tap the vast reservoir of nitrogen in the air” if food supplies are to meet the demands of a growing population noting that “It is the chemist who must come to the rescue of the threatened communities.  It is through the laboratory that starvation may ultimately turn to plenty.”  This was referred to by chemists as the problem of nitrogen fixation.  In addition to the need for nitrogen fertilizers, the increased use of explosives based on nitroglycerine and dynamite also increased the need for nitric acid and its synthesis from nitrogen. Fritz Haber starting in 1903 studied the synthesis of ammonia from hydrogen and nitrogen and in 1909 determined the optimal conditions to maximize product:  using an osmium uranium carbide or iron catalyst, a pressure of 200 atmospheres and temperature of 500 Celsius.  In 5 years, Carl Bosch and Alwin Mittasch designed a system to scale up the process.  He also determined that passing steam over coke to produce hydrogen was cheaper than electrolysis of water.  Nitrogen was sourced from a method of liquefaction of air.  This industrial scale process for producing ammonia became known as the Haber-Bosch Process.  BASF at Ludwigshafen ran the first pilot plant for ammonia synthesis in 1913.  Because of blockades preventing Britain from access to nitrates, they developed the cyanamide process to produce the fertilizer calcium cyanamide which can also be used to make ammonia tinking that the Haber-Bosch process was prohibitively expensive.  After the war, in the 1920’s, the Haber-Bosch process was introduced in both Britain and America.  The industrial scale Haber-Bosch process with its special requirements for equipment able to withstand high pressures and temperatures became the model and stimulus for subsequent construction of industrial plants. As the author notes, the Haber-Bosch process was of “considerable social, economic, and scientific importance.  Scientifically it was an elegant study of the thermodynamics of gaseous reactions and a demonstration of its commercial significance; socially and economically, it resolved the spectre of Malthus and of starving millions; environmentally, with its absence of waste products and polluting odours, it was a model for a cleaner and more socially responsible industry.”

Issues of “economics of scale and scope, including the transfer from wasteful and inefficient batch manufacture to continuous flow”  led to the wider use of catalysts and the development of process control by instrumental monitoring.  A pioneering move toward this was the development of automatic control technology by the Dow Company.

One of the biggest contributions by the chemical industry to societal material progress was its ability to produce cheaper synthetic substitutes to natural products, xylonite for combs, shirts, and knives, celluloid for billiard balls and film rolls, Bakelite for electrical insulators, telephones, and other household items, etc.  The plastic age “was born in trial and error and the dogged exploitation of well tried chemical reaction on pre-existing natural polymers such as cellulose”. Even with all these new inventions, the study of plastics and eventually polymers did not take its full form until after the 1920’s.  Carothers , hired by Du Pont in 1928, “brought fundamental order to the production of polymers by showing that the principal methods of generation were by addition and condensation.   Carothers developed the new polyamide fiber marketed by Du Pont as “Nylon”.  About the same time, R.O. Gibson and E.W. Fawcett with ICI in England discovered polyethylene.  Ziegler and Natta developed catalytic methods using transition-metal complexes for making polythene and other similar polymers at atmospheric pressure.

The invention of the car by Henry Ford led to a huge demand for gasoline which forced petroleum industries to devise ways to increase the gasoline fraction derived from petroleum.  Standard Oil in 1913 invented the process of cracking, the application of heat and pressure to decompose high molecular weight paraffins to lower molecular weight olefins that gave petrol its desirable properties.  Thermal cracking was succeeded by catalytic cracking in the 1940s, leading to a doubling of the petrol output by the petroleum industry.  Because of its high concentration of reactive olefins, petroleum chemists started to look at petrochemicals as a potential starting reactant for the synthesis of other chemicals.  In the 1930s, American chemical firms began using petrochemicals to synthesize ketones as solvents, antifreeze, ethylene glycol, and styrene for artificial rubber.  In the 1950s, “the age of coal had passed” and the chemical industry became reliant upon petroleum and natural gas.

Chemistry and the Environment
In this closing section for the last chapter in the text, the author gave a brief synopsis of the rise of the environmental movement as a result of what was perceived as the irresponsibility of the chemical industry to consider the environmental consequences of their processes and products.   As the author noted in the beginning, “the petroleum chemists’ synthetic success and prowess in providing housewares, processing foods, devising new medicines, beautifying gardens and decors and increasing agricultural yields came the side effects of pollution and danger and the whole question of cost-benefit.” In the 1960’s the environmental movement was launched and Rachel Carson published her influential book on the environmental havoc being wrought by humans, Silent Spring.  As a response to this, the US Environmental Protection Agency was born to “monitor the effects of a number of laws passed to protect air, water, soil, plants, and animals endangered by the presence of the chemicals that were being produced by humankind”.  Following this, it became clear that technologies are “being assessed in terms of benefits weighed against risks, rather than for benefits alone, and that governments worldwide were concerned with legislation to ensure (though not to guaranty) human safety”.  The most egregious example of “long-term ignorance” in the 1950s was the use of thalidomide by pregnant women to prevent nausea.  The two enantiomers of thalidomide had very different effects in the body: the dextro form is safe and effective while the laevo form was a mutagen.  It was banned in 1961.  With this came a call for responsible science.  “Given that financial support for pure science is now closely geared to the needs and priorities of governments and commercial industries, sociologists of science agree that science can no longer claim neutrality.  As far as moral accountability is concerned, neither academic nor industrial chemists can separate basic research from its applications and consequences.”


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