Molecular Rearrangements (presentation)

Molecular rearrangement mechanisms involved in some chemical reactions

1. 1 Dr Kofi Busia Email : [email protected] Tel: [phone] CHEM 346 MOLECULAR REARRANGEMENT REACTIONS

2. Course Outline 2 Definition of chemistry and an outline of the four traditional areas of study that includes; organic, inorganic, physical and analytical chemistry. Define a chemical reaction. What are reaction mechanisms? What is the difference between a double headed arrow and a single headed arrow? What is organic chemistry? With the exception of hydrogen, halogen and silicon, discuss the uniqueness and or relevance of the five main elements that constitute molecules of all living systems. Why are these five elements so versatile during chemical transformations or reactions? What are reaction intermediates? What are the main characteristic features of reaction intermediates? Name the three principal reaction intermediates in organic chemistry and discuss the factors that account for their behavior during the chemical reaction .

3. What is Chemistry? 3 Chemistry: the scientific study of the properties and behaviour of matter . C overs the composition, structure, properties, behaviour of the elements matter is composed of, compounds consisting of atoms, molecules and ions, and the changes they undergo during a reaction with other substances . Also covers the nature of chemical bonds in chemical compounds. Often referred to as the central science, because it is involved in botany, geology, ecology, cosmochemistry , pharmacology, medicine, pharmacy and forensics 4 traditional areas of study of chemistry: organic chemistry inorganic chemistry analytical chemistry physical chemistry Biochemistry

4. What is Organic Chemistry 4 One of the areas of study of chemistry The study of the structure, properties, composition, reactions and preparations of compounds containing carbon Organic compounds form the basis of all earthly life and constitute the majority of known chemicals. Most organic compounds contain carbon and hydrogen, but they may also contain other elements (e.g., nitrogen, oxygen, halogens, phosphorus, silicon, sulphur ). Provides leads to the synthesis of numerous useful products: agrochemicals, drugs, food additives, plastics, paint, enzymes, cosmetics, etc.

5. What is a Chemical Reaction? 5 A process in which one or more substances (reactants), are converted to one or more different substances (products). A chemical reaction is complete if the reactants are completely transformed in products at the end of the process .

6. Reaction Mechanism in Organic Chemistry 6 It is the sequence of elementary steps used in chemistry, specifically organic chemistry, to show how reactions proceed. A reaction that occurs in two or more elementary steps is called a multistep or complex reaction. The slowest step in a reaction mechanism is known as the rate-determining step . A common method for showing the progress of a reaction is a potential energy diagram (free energy of the system vs the completion of the reaction. The highest point along the reaction pathway, called the transition state , indicates how easily the reaction can occur.

7. What are Reaction I ntermediates ? 7 A reaction intermediate is a chemical species that is formed in one elementary step and consumed in a subsequent step. Transient species formed from the reactants (or preceding intermediates), within a multi-step reaction mechanism , but is consumed in subsequent steps, to generate the final reaction product . For example, consider this hypothetical stepwise reaction: Examples : carbocation, carbanion, free radicals, carbenes , etc .

8. Reaction I ntermediate 8

9. Characteristics of Reaction Intermediates 9 Low concentrations in relation to the reaction substrate and final reaction product  Frequently generated during the chemical decomposition of a chemical compound Existence can be proved using spectroscopic methods Existence in a chemical reaction can also be proved using chemical trapping (a chemical compound used to detect unstable compounds). Stabilisation by conjugation or resonance is often difficult to distinguish from a transition state

10. Curly arrows 10 Used to show how a reaction mechanism proceeds. They represent the movement of a pair of electrons in the breaking or forming of a covalent bond. If a covalent bond is breaking, the curly arrow will originate at that bond If a covalent bond is being formed then the curly arrow should start on the atom that is providing the lone pair of electrons. The electron pair must be shown and the arrow should begin between them. As electrons are negatively charged, the curly arrow will always move towards an atom with a total or partial positive charge . The arrow tail is where the electron pair starts from The arrow head is where you want the electron pair to end up.

11. Curly arrows 11 For example, in the reaction between ethene and hydrogen bromide, one of the two bonds between the two carbon atoms breaks. That bond is simply a pair of electrons . Those electrons move to form a new bond with the hydrogen from the HBr . At the same time the pair of electrons in the hydrogen-bromine bond moves down on to the bromine atom .

12. Using Curly Arrows 12 The most common use of "curly arrows" is to show the movement of pairs of electrons. Similar arrows can also be used to show the movement of single electrons - except that the heads of these arrows only have a single line rather than two lines .

13. Homolytic and Heterolytic Cleavage 13 Homolytic cleavage gives rise to the formation of free radicals , that is , neutral species that carry an unpaired electron . Heterolytic cleavage gives rise to the formation of ions ( species that carry a positive or a negative charge) When the atom in question is a positively charged carbon , the resulting species is called a carbocation. If it is negatively charged , it is called a carbanion .

14. Homolytic and Heterolytic Cleavage 14 The following represent all three species with carbon as the central atom. These three species are the most common types of reaction intermediates that occur in organic reactions .

15. Carbocations 15 Carbocations ( carbonium ): a chemical species bearing a positive charge on carbon The central carbon is SP 2 hybridized, planar with a vacant p-orbital, which will be perpendicular to the plane (above at 90 o to the page) There are two types of carbocation: Short lived C + : ( CH 3 ) 3 C + , (CH 3 ) 2 CH + Stable C + : ( Ph ) 3 C + , ( Ph ) 2 CH +

16. Types of Carbocations 16 3 types: Primary carbocation Secondary carbocation Tertiary carbocation

17. Primary Carbocations 17 In a primary (1°) carbocation, the carbon which carries the positive charge is only attached to one other alkyl group . Some examples of primary carbocations include : Using the symbol R for an alkyl group, a primary carbocation would be written as in the box.

18. Secondary Carbocations 18 In a secondary (2°) carbocation, the carbon with the positive charge is attached to two other alkyl groups, which may be the same or different. A secondary carbocation has the general formula shown in the box. R and R' represent alkyl groups which may be the same or different.

19. Tertiary Carbocations 19 In a tertiary (3°) carbocation, the positive carbon atom is attached to three alkyl groups, which may be any combination of same or different. A tertiary carbocation has the general formula shown in the box. R , R' and R" are alkyl groups and may be the same or different.

20. Formation of Carbocations 20 Formation of C + by heterolytic cleavage: By direct breaking of C-X bond in presence of highly polar solvent

21. Stability of Carbocations 21 Rate- limiting step of an S N 1 reaction is the first step The rate of this step – and therefore , the rate of the overall substitution reaction – depends on the activation energy for the process in which the bond between the carbon and the leaving group breaks and a carbocation forms The more stable the carbocation intermediate is , the faster this first bond- breaking step will occur Thus the likelihood of a nucleophilic substitution reaction proceeding by a dissociative (S N 1) mechanism depends to a large degree on the stability of the carbocation intermediate that forms .

22. Stability of Carbocations 22 Question: what stabilizes a carbocation ? An electron withdrawing group (EWG) stabilises a negative charge An electron donating group (EDG) stabilizes a positive charge . A positively charged species such as a carbocation is very electron-poor ( electron-deficient ): Anything which donates electron density to the electron - poor centre will help to stabilize it Carbocation will be destabilized by an electron withdrawing group.

23. Stability of Carbocations 23 Alkyl groups – methyl , ethyl , propyl , etc. – are weak electron donating groups, and thus stabilize nearby carbocations In general , more substituted carbocations are more stable: e.g . a tert-butyl carbocation is more stable than an isopropyl carbocation. Primary carbocations are highly unstable and not often observed as reaction intermediates ; methyl carbocations are even less stable. Alkyl groups are electron donating and carbocation- stabilizing This is because the electrons around the neighboring carbons are drawn towards the nearby positive charge, thus slightly reducing the electron-deficiency of the positively-charged carbon .

24. Stability of Carbocations 24 Carbocations with higher substitution are not always more stable than those with less substitution Just as electron-donating groups can stabilize a carbocation, electron-withdrawing groups act to destabilize carbocations Carbonyl groups are electron-withdrawing , due to the polarity of the C=O double bond. Thus in the figure below carbocation A is more stable than carbocation B, even though A is a primary carbocation and B is secondary . The difference in stability is due to: Inductive effects - whether electron-withdrawing or donating - decreases rapidly as the number of intermediary vovalent bonds increases (inductive effect decreases with distance). In species B the positive charge is closer to the carbonyl group, thus the destabilizing electron-withdrawing effect is stronger than it is in species A.

25. Stability of Carbocations 25 Stabilization of a carbocation can also occur through resonance effects As a rule , resonance effects are more powerful than inductive effects . Consider the simple case of a benzylic carbocation: This carbocation is comparatively stable. In this case, electron donation is a resonance effect. 3 additional resonance structures can be drawn for this carbocation in which the positive charge is located on one of three aromatic carbons. The positive charge is not isolated on the benzylic carbon, rather it is delocalized around the aromatic structure: this delocalization of charge results in significant stabilization.

26. Stability of Carbocations 26 Benzylic and allylic carbocations (where the positively charged carbon is conjugated to one or more non-aromatic double bonds) are significantly more stable than even tertiary alkyl carbocations . V inylic carbocations , in which the positive charge resides on a double-bonded carbon, are very unstable and thus unlikely to form as intermediates in any reaction.

27. S tability of C arbocations 27 The "electron pushing effect" of alkyl groups Using bromine as an example: bromine is more electronegative than hydrogen In H-Br bond the electrons are held closer to the bromine than the hydrogen Bromine atom attached to a carbon atom would have precisely the same effect - the electrons being pulled towards the bromine end of the bond. Bromine has a negative inductive effect . Alkyl groups do precisely the opposite and ,, tend to "push" electrons away . Thus the alkyl group becomes slightly positive (+) and the carbon they are attached to becomes slightly negative (-). Alkyl group has a positive inductive effect. Sometimes shown as, for example:

28. The stability of the various carbocations 28 The importance of spreading charge around in making ions stable General rule-of-thumb: if a charge is very localised (all concentrated on one atom) the ion is much less stable than if the charge is spread out over several atoms. Applying that to carbocations of various sorts Note that the electron pushing effect of the CH 3 group is placing more and more negative charge on the positive carbon going from primary to secondary to tertiary carbocations At the same time, the region around the various CH 3 groups is becoming somewhat positive The net effect , then , is that the positive charge is being spread out over more and more atoms going from primary to secondary to tertiary ions. The more the charge can be spread around , the more stable the ion becomes .

29. The stability of the various carbocations 29 Order of stability of carbocations primary < secondary < tertiary

30. The stability of the carbocations in terms of energetics 30 Stability of carbocations actually refers to energetic stability - secondary carbocations are lower down an energy " ladder " than primary ones . This means that it is going to take more energy to make a primary carbocation than a secondary one. If there is a choice between making a secondary ion or a primary one, it will be much easier to make the secondary one. Similarly , if there is a choice between making a tertiary ion or a secondary one, it will be easier to make the tertiary one. Has important implications in the reactions of unsymmetrical alkenes

31. Order of Stability of Carbocations 31 Stability Order: n ormal order of stability of carbocations over all order of stability of carbocations

32. Carbanions 32 Organic species with negative charge on the central carbon atom having one pair of electron present in the SP 3 orbital. Can be said to be the opposite of carbocation. Exist in a trigonal pyramidal arrangement. Examples: benzylic anion (C 6 H 5 CH 2 - ) and methide ions (CH 3 - ) Formed by: i ) Formation of C - by h eterolytic cleavage of C-H bond. ii) Breaking of C-M (M= Metal) bond .

33. Carbanions 33 Stability order of carbanion 3 o is least stable as there are three methyl group which donate electron to the central carbanion so on that carbon negative charge is more compared to other, making it least stable.

34. Free Radicals 34 Free Radicals: Atom or group of atoms having an odd or unpaired electron is known as free radicals A free radical can be formed in a number of ways : P roduced when a covalent bond is homolytic or symmetrically cleaved , either by heating or in the presence of ultraviolet radiation, which is also a source of energy .

35. Free Radicals 35 The attack of a free radical on a covalent molecule produces a free radical .

36. Free Radicals 36 A species having a C-atom with one free electron and no charge is called as free radical . Structure: Free radicals are generally SP 2 hybridized Stability:

37. Free Radicals 37

38. Carbenes 38 A neutral divalent carbon species in which the carbon atom is bonded to two monovalent atoms or groups and contains two non-binding electrons is called carbenes Like carbocations , carbenes are highly reactive chemical species that are short-lived because the central carbon atom has only six electrons in its valence shell and thus has a strong tendency to complete its octet by gaining two more electrons. As a result, carbenes behave as Lewis acids or electrophiles . Methylene carbene can be synthesised by decomposing diazomethane or ketene in the presence of heat or light

39. Nitrenes 39 Nitrenes are neutral monovalent nitrogen species that have two unshared pairs of electrons and are linked to only one monovalent atom or group. Like carbenes , nitrenes exist in both singlet and triplet states. The triplet state is the more stable of the two. Because nitrene is an electron-deficient species, it is highly reactive. Thermal decomposition ( thermolysis ) of alkyl azide results in the formation of alkyl nitrene as follows : The photolysis of alkyl isocyanate can also prepare nitrene .

40. Summary 40 Carbocations ( carbonium ions in the older literature) are electrophiles Carbanions are nucleophiles Carbenes : have only a valence shell sextet of electrons therefore electron deficient (are electrophiles); dominates carbene reactivity But the non-bonding electron pair also gives carbenes nucleophilic character Carbon radicals: have only seven valence electrons may be considered electron deficient b ut, in general they do not bond to nucleophilic electron pairs so their chemistry exhibits unique differences from that of conventional electrophiles. radical intermediates often called free radicals.

41. Essential Elements 41

42. Essential Elements 42 “CHNOPS elements” – carbon, hydrogen, nitrogen, oxygen, phosphorous, and sulphur These 5 elements also constitute the bulk of our diet Out of the 92 naturally occurring elements, only a handful make up all life on Earth. Four elements are common to all living things: carbon (C), hydrogen (H), oxygen (O), and nitrogen (N). These four elements alone make up approximately 96% of all living matter. Sulphur (S), phosphorus (P), calcium (Ca), potassium (K), and a few other elements constitute the other 4% of an organism’s mass.

43. Essential Elements 43 Element Function Oxygen Involved in respiration, growth, and producing energy: Plays a key role in cellular respiration where glucose is broken down to yield energy in the form of ATP. Exchanged with carbon dioxide in the lungs during respiration. Carbon Main atom in carbohydrates, proteins, nucleic acids, and lipids Makes large, complex molecules by forming bonds with other atoms Energy is generated when carbon molecules are broken down, which may then be used to power numerous biological operations. Nitrogen Forms the amine group in amino acids, which make important proteins Serves as a crucial part of DNA- consists of nitrogenous bases bound to each other, which are pyrimidines and purines. Hydrogen Formation of bonds between molecules such as DNA Formation of water molecules Involved in ammonia synthesis Vital component of compounds such as proteins, carbohydrates, and lipids.

44. Essential Elements 44 Element Function Phosphorus Important part of DNA and RNA (sugar-phosphate backbone); nucleic acids Component in ATP- energy currency of the cells Component of many enzymes Contributes to the function of the cell membrane Maintaining acid-base balance Iron Found in haemoglobin - substance responsible for carrying oxygen from the lungs to the rest of the body. Copper Combines with certain proteins to produce enzymes Involved in the transformation of melanin Form cross-links in collagen and elastin and thereby maintain and repair connective tissues. Important for the heart and arteries; deficiency is one factor leading to an increased risk of developing coronary heart disease.