SCIENCE: THE ONE IN ALL

FROM CARBONYL TO ALKENE,

FROM WORLD WAR I TO 1979 NOBEL.....

1.Sir George Wittig

The Wittig reaction also known as the Wittig olefination is regarded among the revolutionary reactions in organic chemistry. In this blog I will give a brief account on this reaction, the way it works, the industrial application and, of course, the inspiring journey of its inventor.

Olefination is the process of formation of olefins. Olefin is another name for alkenes. In organic chemistry there are groups of atoms like carbon, hydrogen, oxygen, nitrogen etc. which give characteristic properties to the organic molecules. These are called the functional groups. For example, consider Alkanes- the simplest of organic compounds consisting only of carbon and hydrogen atoms( hydrocarbons) held together with a single bond (A bond between atoms of a molecule could be simply understood as the force that holds them together). A single bond is made up of one electron pair shared between 2 atoms. Now in these alkanes, if one more bond is added between the atoms, it forms a double bond. Such doubly bonded compounds are alkenes. If an -OH group consisting of 1 hydrogen and 1 oxygen atom is added, then the properties of original alkane change and it becomes an alcohol. If a C=O group is added, it becomes a ketone and if a -CHO group is added at the terminal position of the molecule, then, it is an aldehyde. All these functional groups-alkenes, alcohols, ketones, aldehydes have properties different than the original alkanes or hydrocarbons. Its just like the concept of secondary colors. If you have red color and you add yellow to it, it becomes orange. Orange is different from red. yet it contains the red color.

2. alkene

3. aldehyde

5. alcohol

4. ketone

In this reaction the C=O present in the aldehydes and ketones discussed above, gets replaced by a C=C to form an alkene. The interesting part is that this new C=C is formed exactly at the same position where the initial C=O was present. It happens through the Phosphorous ylide which is the Wittig reagent.

6. Formation of phosphorous ylides from phosphonium salts

7. Triphenyl phosphorous ylide

8. Trimethyl phosphorous ylide

9. A Bar magnet

The Phosphonium salts are converted to the Phosphorous ylides as shown in Fig 6. The phosphorous ylide is a dipolar molecule. The phosphorous atom has a positive charge and carbon has a negative charge. Just like the north and south poles of a bar magnet. The overall molecule is neutral.

10. Mechanism of Wittig Olefination

When it comes to learning anything new, it is very important to understand the basics. A Pianist cannot play the symphony without knowing the octaves. Similarly, if we want to study the mechanism of any organic reaction it is mandatory to know the basic components that make the reaction happen. Two such components are the nucleophile and the electrophile. A nucleophile is a molecule that has more number of electrons than the electrophile and is capable of donating its electrons to the electrophile. It could be either negatively charged or neutral. On the other hand, the electrophile is electron deficient. Hence, it is attacked by the electron rich nucleophile. In the above reaction the electron rich CH2 group of the Wittig reagent attacks on the carbon of C=O( called as carbonyl). This carbon is electron deficient since it is next to O atom which is highly electronegative and hence pulls the carbon electron density towards itself making the carbon electron deficient. In the next step, the Wittig reagent has attached to the carbonyl and the oxygen has now acquired a negative charge due to shift of one of the bonded electron pair of C=O towards itself. This structure is called Betaine. Again in the next step the negatively charged oxygen attacks the positively charged phosphorous and leads to the formation of oxaphosphetane.

11. Betaine analogy

12. Oxaphosphetane analogy

Betaine and oxaphosphetane could be imagined as the three and four pieces of a puzzle joined together respectively.

13. Mechanism by George Wittig

Above is the original mechanism of the Wittig reaction from the lecture given by George Wittig when he received the Nobel Prize in chemistry for the discovery of this reaction. This reaction opened up the possibilities for industrial synthesis of vitamins, steroids, Hormones and other important compounds. Vitamin A was among the first compounds to be synthesized industrially using this reaction which is crucial in preventing visual problems and pre mature deaths. Beta Carotene another dietary supplement is also synthesized. According to the current research many Pharmaceutically important compounds like Sanshools, Aryl acrylic acid derivatives and Spilanthes are being synthesized using this reaction.

14. Vitamin A and Beta Carotene

Just like this reaction, the life of Sir George Wittig is very interesting. He was born in Berlin, Germany and had started his career in chemistry at Tubingen. But due to the onset of the World war I, he had to join the Army. After the war was over, it was very difficult for him to start with chemistry all over again. But due to his determination and Professors and colleagues like Karl Ziegler, Karl Fries, Hermann Staudinger, Wilhelm Schlenk, Herbert C Brown, he was able to overcome the tough times. He also published his book 'Stereochemie'. He also formed a research group along with his younger colleagues and encouraged students who returned from World war II to pursue their Scientific careers because of his own experience from the 1st World War.

Below is an extra note for Chemistry students and Researchers. Others can directly jump to the next paragraph.

His research work initially began by studying ring strain for aromatic compounds. He began with the question as to how the ring strain acts if the presence of phenyl groups on the 2 adjacent carbons of the ring weakens the C-C bond and leads to the formation of a diradical(diyl). From the stability of diradicals and the use of phenyl lithium for the modification of p- Bromo anisole they could prove the exchange of halide with electropositive metal of phenyl lithium, calling this Umpolung or reversal of polarity. The reaction of mono halobenzene with phenyl lithium lead to the formation of o- lithio biphenyl instead of biphenyl due to the formation of dehydrobenzene intermediate. Phenyl lithium had actually opened up many areas of research. Later tetra methyl ammonium chloride was reacted with phenyl or methyl lithium to give trimethyl ammonium methylide. These were called nitrogen ylides. But later it was found that phosphonium salts could be converted to phosphorous ylides more readily than ammonium salts to nitrogen ylides due to the ability of phosphorous to expand its electron shell to decet which offers resonance stability of ylide and ylene forms. phosphorous ylides reacted readily than nitrogen ylides. This is what led to the Wittig reaction. He was awarded the Nobel Prize In Chemistry along with Herbert C Brown. I have shared the link of the lecture in the references. If you want to read about his research in detail, then, please go through it.

According to George Wittig, it was a journey from diyl to ylide which finally ended at his idyll that is his interest in fine arts. Apart from chemical research he was also interested in mountaineering and playing the piano. He was very particular about the way in which the experiments were carried out and the purity of the reagents used. He made sure that he was always present when an important experiment was started, saying that 'four eyes see more than two'.

He said during his Noble Prize lecture:

In chemical research as far as a new territory is concerned, the results may sometimes be quite different: they may be disappointing or delightful. Chemical research and mountaineering have much in common. If the goal or the summit is to be reached, both initiative and determination as well as perseverance are required. But after the hard work, it is a great joy to be at the goal or the peak with its splendid panorama.

©Neha kanase

References:

1. Georg Wittig - Nobel Lecture: From Diyls to Ylides to My Idyll (nobelprize.org)

2. Georg Wittig - Nobel Lecture (nobelprize.org)

3. Georg Wittig | Encyclopedia.com

4. Georg_Wittig (chemeurope.com)

5. Advanced Organic Chemistry by Carey and Sundberg

6. Organic Chemistry by J Clayden, N Greeves, S. Warren and P. Wothers

7. Image 1: Wikipedia

8. Image 2: Illustrated glossary of Organic Chemistry

9. Image 3: Wikimedia commons

10. Image 4: Wikimedia commons