Chem 464 Fall 2024 General & Organic Chemistry Review PDF

Fall 2024 Gen Chem / Org Chem Review for Biochemistry Chem 464 (Expanded from Dr. Fischaber’s and Dr. Crowhurst’s Guides) Abrol Section A. General Chemistry A1. Local geometries around atoms in molecules based on VSEPR...

Fall 2024 Gen Chem / Org Chem Review for Biochemistry Chem 464 (Expanded from Dr. Fischaber’s and Dr. Crowhurst’s Guides) Abrol Section A. General Chemistry A1. Local geometries around atoms in molecules based on VSEPR (Valence Shell Electron Pair Repulsion) Theory: Example Orbital Hybridizations sp sp2 sp3 sp3d sp3d2 A2. Electronegativities of some Elements in the periodic table: Page 1 of 10 Fall 2024 Gen Chem / Org Chem Review for Biochemistry Chem 464 (Expanded from Dr. Fischaber’s and Dr. Crowhurst’s Guides) Abrol Section A3. Non-Covalent Interactions Page 2 of 10 Fall 2024 Gen Chem / Org Chem Review for Biochemistry Chem 464 (Expanded from Dr. Fischaber’s and Dr. Crowhurst’s Guides) Abrol Section Some non-covalent interaction examples: Hydrogen bonds Van der Waals interactions Cation-π interactions Page 3 of 10 Fall 2024 Gen Chem / Org Chem Review for Biochemistry Chem 464 (Expanded from Dr. Fischaber’s and Dr. Crowhurst’s Guides) Abrol Section Resonance structures guided by electronegativities: Example 1: Carbonyl group Example 2: Carboxylate group Page 4 of 10 Fall 2024 Gen Chem / Org Chem Review for Biochemistry Chem 464 (Expanded from Dr. Fischaber’s and Dr. Crowhurst’s Guides) Abrol Section Example 3: Amide bond Page 5 of 10 Fall 2024 Gen Chem / Org Chem Review for Biochemistry Chem 464 (Expanded from Dr. Fischaber’s and Dr. Crowhurst’s Guides) Abrol Section Oxidation States in organic molecules guided by relative electronegativities: Page 6 of 10 Fall 2024 Gen Chem / Org Chem Review for Biochemistry Chem 464 (Expanded from Dr. Fischaber’s and Dr. Crowhurst’s Guides) Abrol Section B. Organic Chemistry Some key terms: nucleophile – an electron-rich group which is either negatively charged or contains unshared electron pairs that easily form covalent bonds with electron-deficient centers (electrophiles) electrophile – an electron-deficient group which is either positively charged, contains an unfilled valence electron shell, or is adjacent to an electronegative atom and has a strong tendency to accept electrons from a nucleophile lone pair – pair of electrons residing on one atom and not shared by other atoms; unshared electron pair leaving group – an atom or a group of atoms that is displaced as a stable species during a substitution or displacement reaction. What molecular properties make good leaving groups? i. Amines - are nucleophilic in the “free base” form (on the right side in the examples below). Primary amines are the most nucleophilic, secondary less nucleophilic, and tertiary amines are generally too sterically hindered to carry out nucleophilic attack. The pKa of a typical ammonium is pH 9-10. Most of the molecules in a solution of amines are therefore protonated (i.e “ammonium salts”) if the sample is at biological pH (~7.0). N-H bonds are highly polar and nitrogen lone pairs readily form hydrogen bonds. A. Example 1: Ethylamine Hydrochloride, a primary amine, both basic AND nucleophilic. NH3 + Cl NH2 + H + Cl B. Example 2: Tris Hydrochloride, a tertiary amine: basic but NOT nucleophilic. H OH OH HO HO N + Cl N + H + Cl OH OH Trishydroxymethylaminomethane Hydrochloride (a.k.a. “Tris HCl”) shown in both the protonated ammonium form (left) and deprotonated amino form (right). Tris is a useful buffer in biochemistry laboratories because its pKa (~8.1) is close to biological pH. It is a tertiary amine, however, which means that it is not nucleophilic because the nitrogen lone pair (right structure) is too sterically hindered to attack an electrophile. ii. Carbonyls - have an electrophilic “pecking order”. Here is the order from most electrophilic (left) to least electrophilic (right): O O O O O O O O N Cl O H O OH Acyl Carboxylic chloride Anhydride Aldehyde Ketone Ester acid * Amide Hydrolyze readily in water (Aldehydes and ketones Hydrolyze slowly in acid don’t hydrolyze – they (Min-Hrs) (Days-Weeks) have no leaving group) Page 7 of 10 Fall 2024 Gen Chem / Org Chem Review for Biochemistry Chem 464 (Expanded from Dr. Fischaber’s and Dr. Crowhurst’s Guides) Abrol Section *The carboxylic acid technically does hydrolyze, but the product is the exact same molecule as the starting material, so you wouldn’t be able to “see” it hydrolyze unless you labeled it somehow, for instance, by making the oxygen atoms 18O and hydrolyzing it in regular water containing 16O. A. As an exercise, draw all the resonance structures for an ester. Which resonance structure most clearly illustrates the electrophilic character of an ester? Now draw all the resonance forms for a ketone. Which resonance form(s) illustrate why the ester is less electrophilic than a ketone (i.e. the ones not common to both structures). B. Is it more appropriate to think of a carbonyl carbon as an “electron-rich” carbon or an “electron poor” carbon? Explain your answer. C. Consider the resonance forms of an amide, below. Why is the amide nitrogen not very nucleophilic?.... O O N N D. Would the molecule above be good at forming hydrogen bonds in aqueous solution? Does this enable its water solubility? iii. Chirality, leaving groups and substitution – Use your organic chemistry textbook to help you review: chiral centers: be able to recognize, assign R vs S nucleophilic substitution: know SN1 versus SN2, be able to recognize which is the nucleophile and which is the electrophile, understand what is a good versus a bad leaving group, etc. pKa: understand how pKas work, and how it affects the reactivities of molecules iv. Nomenclature - Just as though you were in a foreign language class, a firm understanding of the functional group terminology from your pre-requisite organic chemistry classes is KEY to being able to follow your instructor during lectures in CHEM 464 and to understand what you read in the textbook. Draw generic structures (like those shown for the carbonyls above) for each of the following functional groups. Practice imagining the functional groups in your head (in their appropriate states of protonation) as you say their names, much like you will need to be able to quickly recall the functional group structures as your instructor says them while lecturing. ** you should also be familiar with their reactivities (i.e. which part of the molecule is nucleophilic or electrophilic, etc.) ** methyl sulfhydryl / thiol ethyl thiolate isopropyl disulfide hydroxyl / alcohol thioester phenyl sulfate phenol / phenolate Imine enol / enolate N-substituted imine carboxylate pyridine / pyridinium carbonyl – aldehyde guanidinium / guanidine carbonyl – ketone imidazole ester phosphate anhydride phosphoryl amine / amino / ammonium phosphoanhydride amide / amido acyl phosphate (mixed anhydride) Page 8 of 10 Fall 2024 Gen Chem / Org Chem Review for Biochemistry Chem 464 (Expanded from Dr. Fischaber’s and Dr. Crowhurst’s Guides) Abrol Section Additional functional groups of interest: CH3 O Isopropyl R Sulfate R S - H O - CH3 O Pyridine O - R P - N Thiolate R S O Phosphate - O Page 9 of 10 Fall 2024 Gen Chem / Org Chem Review for Biochemistry Chem 464 (Expanded from Dr. Fischaber’s and Dr. Crowhurst’s Guides) Abrol Section Appendix: Le Chatelier’s Principle: Let us take an exothermic chemical reaction shown below at equilibrium: A(g) + 2B(g) ⇌ C(g) + D(g) + Heat Le Chatelier’s principle states that if the equilibrium of this reaction system is changed by any means, the equilibrium will shift in a direction that will resist the change Three types of changes are easy to understand: 1. Change in concentration a. If the concentration of B is decreased, the equilibrium will shift to the left to create more B molecules. b. If the concentration of C is decreased, the equilibrium will shift to the right to create more C molecules. 2. Change in pressure (3 gas reactant molecules are being converted to 2 gas product molecules reducing pressure) a. If the pressure is decreased, the equilibrium will shift to the left to increase the pressure. b. If the pressure is increased, the equilibrium will shift to the right to decrease the pressure. 3. Change in temperature a. If the temperature is increased, the equilibrium will shift to the left to consume heat and lower the temperature. b. If the temperature is decreased, the equilibrium will shift to the right to produce heat and increase temperature. Page 10 of 10