1. The document provides an overview of common elementary steps in bioorganic chemistry, including curved arrow notation, proton transfers, SN2 reactions, and addition and elimination steps. 2. It discusses the characteristics of nucleophiles and electrophiles and how they participate in reactions. Bond formation, bond breaking, rearrangements, and tautomerizations are described. 3. The driving forces of chemical reactions are explained as charge stability and bond energy. Ketone-enol tautomerization is used as an example where bond energies are the major driving force due to relative stabilities.

1. An Overview of the Most Common Elementary Steps
,,Mkhitar-Gosh’’ Armenian-Russian International University
Bioorganic Chemistry
1st year of General Medicine
Lecturer: Dr. Assosiate Prof., Hasmik Khachatryan

2. Curved Arrow Notation: Electron Rich to Electron Poor
1. Opposite charges attract; like charges repel.
2. Atoms in the first and second rows of the periodic table
must obey the duet and octet rules,
respectively.

3. Simplifying Assumptions Regarding
Electron-Rich and Electron-Poor Species
? Draw the necessary curved arrows for the proton
transfer between KOCH3 and HCN in solution.

4. Similar ideas allow us to make simplifying assumptions for
organometallic compounds, which contain a metal atom
bonded directly to a carbon atom.

5. ? What are the products of the proton transfer step
between C6H5MgBr and H2O?

6. Simplifying assumptions in hydride reagents

7. Bimolecular Nucleophilic Substitution (SN2) Steps
In a bimolecular nucleophilic substitution (SN2) step, a molecular species, called a substrate,
undergoes substitution in which one atom or group of atoms is replaced by another.

8. Species that act as nucleophiles generally have the
following two attributes:
1. A nucleophile has an atom that carries a full negative
charge or a partial negative
charge. The charge is necessary for it to be attracted to
an atom bearing a positive charge.
2. The atom with the negative charge on the nucleophile
has a pair of electrons that can be used to form a bond to
an atom in the substrate.

9. Recall from Section 7.1a that the electrons in an elementary step
tend to flow from an electron-rich site to an electron-poor site.

10. Bond-Forming (Coordination) and Bond-Breaking
(Heterolysis) Steps
In both the proton transfer and the SN2 steps we have examined so far, a bond is formed and a separate
bond is broken simultaneously. It is possible, however, for bond formation and bond breaking to occur as
independent steps. In Equations 7-5 and 7-6, for example, only a single covalent bond is formed. These
are called coordination steps.

11. An elementary step can also occur in which only a single bond is broken and both
electrons from that bond end up on one of the atoms initially involved in the bond, as shown
in Equations 7-7 and 7-8. These are called heterolytic bond dissociation steps, or
heterolysis steps (hetero 5 different; lysis 5 break).

12. Nucleophilic Addition and Nucleophile Elimination Steps
A nucleophile adds to the polar π
bond in these steps, so they are
called nucleophilic addition steps.

15. Bimolecular Elimination (E2) Steps

16. C atom is no longer electron poor in the products because it is no longer
bonded to the electronegative leaving group.

17. Electrophilic Addition and Electrophile Elimination Steps
An electrophilic addition step occurs when a species containing a nonpolar π bond (as part of a double
or triple bond) approaches a strongly electron-deficient species — an electrophile — and a bond forms
between an atom of the π bond and the electrophile (Equations 7-18 and 7-19).

18. In the reverse step, called electrophile elimination, an electrophile is eliminated from the carbocation,
generating a stable, uncharged, organic species. Equations 7-20 and 7-21 show examples in which H1 is the
electrophile that is eliminated.

20. Carbocation Rearrangements: 1,2-Hydride Shifts and 1,2-Alkyl Shifts

21. The Driving Force for Chemical Reactions
The driving force for a reaction reflects the extent to which the reaction favors
products over reactants, and that tendency increases with increasing stability of
the The driving force for a reaction reflects the extent to which the reaction favors
products over reactants, and that tendency increases with increasing stability of the

22. Charge stability and bond energy do not always work in the same direction. Consider the proton
transfer step in Equation 7-29.
When charge stability and bond energy favor opposite sides of a chemical reaction, charge stability
usually wins.

23. Keto–Enol Tautomerization: An Example of Bond Energiesas the Major Driving Force
In aqueous basic or acidic conditions, ketones and aldehydes exist in rapid equilibrium with a
rearranged form, called an enol:

26. Relative stabilities of enol and keto forms
(a) Energies of the bonds that appear in the enol form but not in the keto form. The sum of the
energies is 1430 kJ/mol (342 kcal/mol). (b) Energies of the bonds that appear in the keto form but
not in the enol form. The sum of the energies is 1477 kJ/mol (353 kcal/mol). Because of its greater
total bond energy, the keto form is more stable than the enol form.

27. Sugar Transformers: Tautomerization in the Body

28. Thank you