Organic Chemistry II Study Guide.pdf

Organic Chemistry Study Guide Please note that the study guide is purely meant to guide your learning. There may be topics on the exam not provided below but were covered in the lecture and/ or textbook. Mass Spectrometry • • • • • • • • • • • • Mass spectrometry; technique, application, measuremen...

Organic Chemistry Study Guide Please note that the study guide is purely meant to guide your learning. There may be topics on the exam not provided below but were covered in the lecture and/ or textbook. Mass Spectrometry • • • • • • • • • • • • Mass spectrometry; technique, application, measurements Schematic of a mass spectrometer; sample, electron beam, magnet, analyzer, ions, mass spectrum Function of a mass spectrometery; radical cation, mass to charge ratio Understanding mass spetra; base peak, m/z, relative abundance, mass fragments The nitrogen rule Proposing molecular formula; even/odd mass, sum combinations of C/H/O Alkyl Halides and the M+2 peak; major isotopes General features of fragmentation Fragmentation patterns in hexane Fragmentation patterns of carbonyls, alcohols, amines High resolution mass spectrometers; m/z ratios to 4+ decimal places Gas chromatography-Mass spectrometry; column separation, retention time Infrared Spectroscopy • • • • • • • • • • • • • • • • • Electromagnetic radiation; photons, wavelength, frequency Electromagnetic spectrum Properties of electromagnetic radiation; speed of light, energy of photon, energy/wavelength Absorption of electromagnetic radiation; UV-Vis/infrared excitation Absorption of IR light; vibrational modes Bond stretching and bending Characteristics of an IR spectrum frequencies, wavenumber, % transmittance, peaks, functional group region, fingerprint region Bonds and IR absorption; single/double/triple bonds, lighter atoms, springlike behavior Hooke’s Law Four regions of IR spectrum Bond strength and % s character Symmetry and IR absorption; IR inactive Effect of resonance on IR absorption Effect of basicity on IR absorption Analyzing an IR spectrum IR absorptions of alkanes, alkenes, alkynes, aromatic compounds, alcohols, ethers, aldehydes, ketones, carboxylic acids, amides, amines, nitriles IR and structure determination Page 1 Nuclear Magnetic Resonance Spectroscopy • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • NMR; radio waves, nuclear spin Magnetic fields in NMR Energy and nuclear spin Resonance energy; applied magnetic field, frequency Resonance frequency NMR schematic; sample, superconducting magnet Electron environment 1 H NMR spectra; chemical shift, ppm Interpreting 1H NMR spectra; upfield, downfield, external standard Chemical shift Structural information from features in 1H NMR spectrum; number, position, intensity, spin-spin splitting of signals Number of signals in 1H NMR; types of H signals, alkenes, cycloakanes Types of protons; homotopic, enantiotopic, diastereotopic Shielding of nuclei Shielding and resonant frequency Shielding and chemical shift Shielding and signal position Characteristic chemical shifts Substitution and chemical shifts Aromatic deshielding Alkene chemical shifts Alkyne chemical shifts Intensity of 1H NMR signals; integral, area under the curve 1 H NMR intergration; ratio of protons 1 H NMR Spin Spin Splitting Coupling constants Triplets; adjacent to absorbing H, spacing between peaks Splitting patterns; nonequivalent protons, n+1 peaks Proximity and splitting; 3 σ bond rule Complex splitting patterns Coupling constants for alkenes; disubstituted double bonds Splitting patterns for alkenes 1 H NMR of OH protons Cyclohexane conformers; ring flipping, axial/equatorial Protons on benzene rings; deshielded protons 1 H NMR structure determination 13 C NMR spectrum Splitting in 13C NMR; singlets Details of 13C NMR; chemical shift, number of signals Page 2 • • Chemical shifts in 13C NMR MRI Introduction to Carbonyl Chemistry • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • Compounds containing carbonyl groups; aldehydes, ketones, carboxylic acid, acid chloride, ester, amide Carbonyl group structure Polarity of carbonyl groups; resonance structures General reactions of carbonyl compounds Nucleophilic addition; reaction of aldehydes and ketones, steric/electronic reactivity Nucleophilic substitution; leaving groups, increasing activity Comparison of carbonyl reaction types; addition, acyl substitution, intermediates Preview of oxidation-reduction; change in number of C-H/C-Z bonds Oxidation and reduction of carbonyl compounds; reduction to alcohols/carboxylic acids Reduction of aldehydes and ketones; metal hydride reagents Catalytic hydrogenation of carbonyls; using H2 gas, metal catalyst Stereochemistry of carbonyl reduction; racemic products, new stereogenic centers Enantioselectivity of NADH reduction Other metal hydride reducing agents; DIBAL-H Reduction of acid halides and esters Reduction of esters; leaving group, reducing agent Reduction of acyl phosphates; reactions with NADH LiAlH4 reductions; amides to amines Summary of metal hydride reducing agents Oxidation of aldehydes; Tollen’s reagent Organometallic reagents, reactivity, Grignard reagents, organocuprates, organolithium Preparation of organometallics Preparation of acetylide ions; organosodium reagents, lithium acetylides Acid-Base reactions of organometallics Use of organometallic compounds; forming C-C bonds Functional group transformations involving organometallic compounds Addition of organometallics to aldehydes and ketones Nucleophilic addition of Grignard reagents; general mechanism Alcohols formed by organometallic addition Retrosynthesis analysis of Grignard products; find C-OH bond Limitations of organometallic reagents Use of protecting groups Preparing silyl ethers Organometallic reactions with esters and acid chlorides Organocuprates a less reactive organometallic; leaving group reactivity Grignard reaction with CO2; Organometallic reactions with epoxides; ring opening Page 3 • • • • Organometallic reactions with α,β-unsaturated carbonyl compounds; resonance structures α,β-unsaturated carbonyl compounds; 1,2 addition and 1,4 addition Summary of organometallic reactions Synthesis; oxidation/reduction reactions, conversion of functional groups, retrosynthetic analysis, preparing reagents Aldehydes and Ketones Nucleophilic Addition • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • Aldehydes and ketones; carbonyl group Reactions of aldehydes and ketones; reactivity towards nucleophiles, steric hindrance IUPAC naming of aldehydes; common names, greek letters, IUPAC naming of ketones; common names Naming ketones, acyl groups, enals, enones Physical properties of aldehydes and ketones; boiling/melting point, solubility H and C NMR absorptions Interesting Aldehydes and Ketones; formaldehyde, acetone, vanillin, cinnamaldehyde Steroids with carbonyls Preparation of aldehydes; oxidation, reduction, hydroboration-oxidation Preparation of ketones; oxidation, reduction, hydration Oxidative cleavage of alkenes General reactions of aldehydes and ketones; reaction at carbonyl C, reaction at α C Nucleophilic addition; general mechanism, acid catalyzed Good nucleophiles Effective nucleophiles in nucleophilic addition Nucleophilic addition of hydride; NaBH4, LiAlH4, 2 step mechanism Nucleophilic addition of R-; organolithium, Grignard reagent Nucleophilic of –CN; C-C bond forming Hydrolysis of cyanohydrins Wittig reaction; alkene formation Witing reagent; organophosphorus, ylide Synthesis of Witting reagents Nucleophilic addition of R-; form Wittig reagent in 2 steps, mechanism of Witting reaction Use of Witting reaction; limitations, formation of stereoisomers Retrosynthetic analysis of Witting reactions Addition of primary amines; reactions with aldehydes, ketones, Schiff base Imine properties; formation from aldehyde or ketone Addition of secondary amines; forming enamines from aldehydes or ketones Formation of imines vs enamines; differences in H removed Imine and enamine hydrolysis; reaction with acid Imines in biological systems Pyridoxal phosphate and the deamination of amino acids; mechanism Hydration of aldehydes and ketones; forming gem-diol Page 4 • • • • • • • • • • • • • • Hydration level vs stability Electronic factors affecting hydrate stability; stabilizing/destabilizing carbonyl group Base catalyzed hydration; reaction rate under basic conditions Acid catalyzed hydration; protonation of carbonyl group Addition of alcohols-acetal formation; diols, hemiacetal mechanism, Hydrolysis of acetals Acetals as protecting groups; block more reactive carbonyl Protection-deprotection process Cyclic hemiacetals; formation, intermolecular cyclization, Acid-catalyzed hemiacetal formation Intramolecular hemiacetal formation; new stereogenic center Cyclic acetals from a cyclic hemicatal Cyclic hemiacetals; resonance stabilized carbocation Carbohydrates; hemiacetals/acetals, OH groups, stereogenic centers Carboxylic Acids and Nitriles • • • • • • • • • • • • • • • • • • • • • • • • Carboxylic acid structure; carboxy group Bonds in carboxylic acid; bond length, bond polarity Nitriles; cyano group; electrophilic carbon atom IUPAC naming for carboxylic acids, diacids, metal salts of carboxylate anions IUPAC naming for nitriles Hydogen bonds cause dimers; dipole dipole and hydrogen bonding in carboxylic acids Physical properties of carboxylic acids; boiling/melting point, solubility Spectroscopy of carboxylic acids; IR, NMR, Types of carboxylic acids and their salts; acetic acid, hexanoic acid, oxalic acid, lactic acid, sodium benzoate, potassium sorbate Aspirin and related compounds, salicin, salicylic acid, sodium salicylate Preparation of carboxylic acids Acid-base reactions of carboxylic acids Deprotonation of carboxylic acids; pKa values Resonance of carboxylate anions Acidity of common organic acids; relative stability Acidity of ethanol; stability of conjugate base Acidity of phenol; resonance stabilized conjugate base, energy of resonance structures Henderson-Hasselbalch equation; pH, pKa, HA versus conjugate base Inductive effects in carboxylic acids; electronegative substituents Organic extraction; separation of mixtures Separating benzoic acid and cyclohexanol; solubility, acid/base effects Organic acids that contain phosphorus Amino acids; zwitterion character, reaction as acid/base Summary of acid-base reactions Page 5 • • • • • • Isoelectric point Formation of nitriles; prepared via Sn2 substitution Reaction of nitriles; hydrolysis, reduction, reaction with organometallics Hydrolysis; amide tautomers, base hydrolysis Reduction of nitriles; reduced via metal hydrides, mechanism, with LiAlH4, DIBAL-H Addition of Grignard reagents to nitriles; formation of ketones Carboxylic Acids and Their Derivatives • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • Carboxylic acids, acid chlorides, anhydrides, acyl phosphate, ester, thioester, amide Anhydrides and amides; primary, secondary, tertiary Lactones and lactames Reactivity pattern of carboxylic acid derivatives; nucleophilic acyl substitution Structural features of the carbonyl group Resonance of carboxylic acid derivatives; stability as basicity increases IUPAC naming for acid chlorides IUPAC naming for anhydrides Composition of anhydrides; without water IUPAC naming of esters IUPAC naming of amides Intermolecular attractions of N-H bonds; physical properties Physical properties of carboxylic acid derivatives; melting/boiling point, solubility Spectroscopic properties; IR absorption, NMR Interesting esters and amides; low MW esters, biologically active esters, proteins, drugs containing lactams Nucleophilic acyl substitution; mechanisms, drawing products, leaving group reactivity compared to nucleophile General reactions of acid chlorides; HCl byproducts, nucleophile reactivity Reactions of acid chlorides and oxygen nucleophiles; forming anhydrides, carboxylic acids, esters Reactions of acid chlorides and amines; forming amides Mechanisms of acid chloride substitutions General reaction of anhydrides; 2nd carbonyl as leaving group Mechanism of anhydride substitution; additional proton transfer General reaction of carboxylic acids Acyl substitution reactions of carboxylic acids Formation of acyl halides; use of thionyl chloride Conversion of carboxylic acids to acid chlorides; mechanism Dehydration of carboxylic acids Fischer esterification of carboxylic acids; mechanism, acid catalyzed, base n/a, intramolecular Fischer esterification Amide formation from carboxylic acids; two steps, DCC Reaction of esters; acid catalyzed, base hydrolysis Page 6 • • • • • • • • • • Lipid hydrolysis Fat substitutes Soap formation; saponification Reactions of amides; amide hydrolysis Mechanism of action of β-lactam antibiotics Acyl phosphates-biological anhydride Carboxylates converted to acyl phosphates Reactions of acyl phosphates; mechanism Biological acylation reactions; thioesters Acyl transfer reactions Substitution Reactions of Carbonyl Compounds at the α Carbon • • • • • • • • • • • • • • • • • • • • • • • • • • • • • Reactions α to carbonyl group; enols and enolates Keto-enol tautomer; equilibrium 1,3 dicarbonyl compounds; conjugation, intramolecular hydrogen bonding Tautomerization catalyzed by acids and bases; mechanisms Enols in biological systems Enol structures Formation of enolates; resonance-stabilized anion Enolates from esters, amides, and nitriles Β-dicarbonyl compounds; acidity, resonance delocalized Equilibrium of enolate formation; LDA a strong nonnucleophilic base; preparations and use Chemistry of enolates; nucleophiles, reaction sites Enolate of unsymmetrical carbonyl compounds; kinetic vs thermodynamic stability Formation of kinetic enolates; favored by strong nucleophilic baes, polar aprotic solvent, low temperature Formation of thermodynamic enolates; strong base, polar protic solvent, room temperature Enolate structure; delocalization of election density Racemization at the α carbon atom; products from stereogenic centers Reactions at the α carbon; reaction with electrophiles Halogenation at the α carbon; acid/base reaction mechanism Acid-catalyzed halogenation at the α carbon; 2 part mechanism Elimination reaction of α-halo carbonyls Substitution reaction of α-halo carbonyls Direct enolate alkylation Enolate addition with esters and nitriles Stereochemistry of enolate alkylation Kinetic product of enolate alkylation Thermodynamic product of enolate alkylation Malonic ester synthesis; mechanism, deprotonation, alkylation, hydrolysis and decarboxylation Decarboxylation of malonic esters; formation of 1,3 diacid, loss of CO2 Page 7 • • • • • Repeated malonic ester synthesis, intramolecular synthesis Retrosynthetic analysis of malonic esters Acetoacetic ester synthesis; ketone product, repeated synthesis Retrosynthetic analysis of acetoacetic esters Biological decarboxylation; mechanism Carbonyl Condensation Reactions • • • • • • • • • • • • • • • • • • • • • • • • • Condensation reactions between two carbonyl compounds; enolates and enols Aldol reaction; mechanism Nucleophilic addition of enolates; reaction of aldehydes and ketones Joining carbons to form aldol products Retro aldol reaction; mechanism Condensation reactions Dehydration of aldol product Dehydration of β=hydroxyl carbonyl compounds with base E1cB mechanism Retrosynthetic analysis of aldol products Crossed aldol reactions; 4 different products Active methylene compounds; base reactivity Directed aldol reactions Intramolecular aldol reactions; mechanism Use of crossed aldol reactions Claisen reactions; mechanism, nucleophilic substitution Crossed claisen reaction Forming β-dicarbonyl compounds Preparing β-keto esters Dieckmann reaction Biological aldol reactions; retro aldol reactions, claisen reactions The Michael reaction; mechanism Michael acceptor; α,β unsaturated carbonyl component Michael reaction products Robinson annulation; mechanism, drawing products Page 8