Organic chemistry with a biological emphasis volume i

University of Minnesota Morris Digital Well University of Minnesota Morris Digital Well Chemistry Faculty Chemistry 1-2016 Organic Chemistry with a Biological Emphasis Volume I Timothy Soderberg Follow this and additional works at: http://digitalcommons.morris.umn.edu/chem_facpubs Part of the Biochemistry Commons, and the Organic Chemistry Commons Recommended Citation Soderberg, Timothy, "Organic Chemistry with a Biological Emphasis Volume I" (2016) Chemistry Faculty http://digitalcommons.morris.umn.edu/chem_facpubs/1 This Book is brought to you for free and open access by the Chemistry at University of Minnesota Morris Digital Well It has been accepted for inclusion in Chemistry Faculty by an authorized administrator of University of Minnesota Morris Digital Well For more information, please contact skulann@morris.umn.edu Organic Chemistry With a Biological Emphasis Volume I: Chapters 1-8 Tim Soderberg University of Minnesota, Morris January 2016 Organic Chemistry With a Biological Emphasis Tim Soderberg This work is licensed under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License https://creativecommons.org/licenses/by-nc-sa/4.0/ Organic Chemistry With a Biological Emphasis (2016 ed.) Tim Soderberg Notes to the reader: This textbook is intended for a sophomore-level, two-semester course in Organic Chemistry targeted at Biology, Biochemistry, and Health Science majors It is assumed that readers have taken a year of General Chemistry and college level Introductory Biology, and are concurrently enrolled in the typical Biology curriculum for sophomore Biology/Health Sciences majors The book is meant to be a constantly evolving work in progress, and as such, feedback from students, instructors, and all other readers is greatly appreciated Please send any comments, suggestions, or notification of errors to the author at soderbt@morris.umn.edu If you are looking at a black and white printed version of this textbook, please be aware that most of the figures throughout are meant to contain color, which is used to help the reader to understand the concepts being illustrated It will often be very helpful to refer to the full-color figures and internet links in a digital PDF version of the book, which is available for free download at: http://facultypages.morris.umn.edu/~soderbt/textbook_website.htm The digital book is continuously being updated, so please check back to this site periodically to download the most recent version Organic Chemistry With a Biological Emphasis (2016 ed.) Tim Soderberg Organic Chemistry With a Biological Emphasis (2016 ed.) Tim Soderberg Table of Contents Volume I: Chapters 1-8 Chapter 1: Introduction to organic structure and bonding, part I Introduction: Pain, pleasure, and organic chemistry: the sensory effects of capsaicin and vanillin Section 1: Drawing organic structures A: Formal charge B: Common bonding patterns in organic structures C: Using the 'line structure' convention D: Constitutional isomers Section 2: Functional groups and organic nomenclature A: Functional groups in organic compounds B: Naming organic compounds C: Abbreviating organic structure drawings Section 3: Structures of some important classes of biological molecules A: Lipids B: Biopolymer basics C: Carbohydrates D: Amino acids and proteins E: Nucleic acids (DNA and RNA) Chapter 2: Introduction to organic structure and bonding, part II Introduction: Moby Dick, train engines, and skin cream Section 1: Covalent bonding in organic molecules A: The bond in the H2 molecule B: sp3 hybrid orbitals and tetrahedral bonding C: sp2 and sp hybrid orbitals and  bonds Section 2: Molecular orbital theory A: Another look at the H2 molecule using molecular orbital theory B: MO theory and conjugated bonds C: Aromaticity Section 3: Resonance A: What is resonance? B: Resonance contributors for the carboxylate group C: Rules for drawing resonance structures D: Major vs minor resonance contributors Organic Chemistry With a Biological Emphasis Tim Soderberg Table of Contents Section 4: Non-covalent interactions A: Dipoles B: Ion-ion, dipole-dipole and ion-dipole interactions C: Van der Waals forces D: Hydrogen bonds E: Noncovalent interactions and protein structure Section 5: Physical properties of organic compounds A: Solubility B: Boiling point and melting point C: Physical properties of lipids and proteins Chapter 3: Conformation and Stereochemistry Introduction: Louis Pasteur and the discovery of molecular chirality Section 1: Conformations of open-chain organic molecules Section 2: Conformations of cyclic organic molecules Section 3: Chirality and stereoisomers Section 4: Labeling chiral centers Section 5: Optical activity Section 6: Compounds with multiple chiral centers Section 7: Meso compounds Section 8: Fischer and Haworth projections Section 9: Stereochemistry of alkenes Section 10: Stereochemistry in biology and medicine Section 11: Prochirality A: pro-R and pro-S groups on prochiral carbons B: The re and si faces of carbonyl and imine groups Chapter 4: Structure determination part I - Infrared spectroscopy, UV-visible spectroscopy, and mass spectrometry Introduction: A foiled forgery Section 1: Mass Spectrometry A: An overview of mass spectrometry B: Looking at mass spectra C: Gas chromatography-mass spectrometry D: Mass spectrometry of proteins - applications in proteomics Section 2: Introduction to molecular spectroscopy A: The electromagnetic spectrum B: Overview of the molecular spectroscopy experiment Section 3: Infrared spectroscopy Section 4: Ultraviolet and visible spectroscopy A: The electronic transition and absorbance of light B: Looking at UV-vis spectra C: Applications of UV spectroscopy in organic and biological chemistry ii Organic Chemistry With a Biological Emphasis Tim Soderberg Table of Contents Chapter 5: Structure determination part II - Nuclear magnetic resonance spectroscopy Introduction: Saved by a sore back Section 1: The origin of the NMR signal A: The magnetic moment B: Spin states and the magnetic transition Section 2: Chemical equivalence Section 3: The 1H-NMR experiment Section 4: The basis for differences in chemical shift A: Diamagnetic shielding and deshielding B: Diamagnetic anisotropy C: Hydrogen-bonded protons Section 5: Spin-spin coupling Section 6: 13C-NMR spectroscopy Section 7: Solving unknown structures Section 8: Complex coupling in 1H-NMR spectra Section 9: Other applications of NMR A: Magnetic Resonance Imaging B: NMR of proteins and peptides Chapter 6: Overview of organic reactivity Introduction: The $300 million reaction Section 1: A first look at some organic reaction mechanisms A: The acid-base reaction B: A one-step nucleophilic substitution mechanism C: A two-step nucleophilic substitution mechanism Section 2: A quick review of thermodynamics and kinetics A: Thermodynamics B: Kinetics Section 3: Catalysis Section 4: Comparing biological reactions to laboratory reactions Chapter 7: Acid-base reactions Introduction: A foul brew that shed light on an age-old disease Section 1: Acid-base reactions A: The Brønsted-Lowry definition of acidity B: The Lewis definition of acidity Section 2: Comparing the acidity and basicity of organic functional groups– the acidity constant Organic Chemistry With a Biological Emphasis Tim Soderberg iii Table of Contents A: Defining Ka and pKa B: Using pKa values to predict reaction equilibria C: Organic molecules in buffered solution: the Henderson-Hasselbalch equation Section 3: Structural effects on acidity and basicity A: Periodic trends B: Resonance effects C: Inductive effects Section 4: Acid-base properties of phenols Section 5: Acid-base properties of nitrogen-containing functional groups A: Anilines B: Imines C: Pyrroles Section 6: Carbon acids A: The acidity of -protons B: Keto-enol tautomers C: Imine-enamine tautomers D: The acidity of terminal alkynes Section 7: Polyprotic acids Section 8: Effects of enzyme microenvironment on acidity and basicity Chapter 8: Nucleophilic substitution reactions Introduction: Why aren't identical twins identical? Just ask SAM Section 1: Two mechanistic models for nucleophilic substitution A: The SN2 mechanism B: The SN1 mechanism Section 2: Nucleophiles A: What is a nucleophile? B: Protonation state C: Periodic trends in nucleophilicity D: Resonance effects on nucleophilicity E: Steric effects on nucleophilicity Section 3: Electrophiles A: Steric hindrance at the electrophile B: Carbocation stability Section 4: Leaving groups Section 5: SN1 reactions with allylic electrophiles Section 6: SN1 or SN2? Predicting the mechanism Section 7: Biological nucleophilic substitution reactions A: A biochemical SN2 reaction B: A biochemical SN1 reaction C: A biochemical SN1/SN2 hybrid reaction Section 8: Nucleophilic substitution in the lab A: The Williamson ether synthesis B: Turning a poor leaving group into a good one: tosylates iv Organic Chemistry With a Biological Emphasis Tim Soderberg Table of Contents Volume II: Chapters 9-17 Chapter 9: Phosphate transfer reactions Introduction: Does ET live in a lake in central California? Section 1: Overview of phosphate groups A: Terms and abbreviations B: Acid constants and protonation states C: Bonding in phosphates Section 2: Phosphate transfer reactions - an overview Section 3: ATP, the principal phosphate group donor Section 4: Phosphorylation of alcohols Section 5: Phosphorylation of carboxylates Section 6: Hydrolysis of organic phosphates Section 7: Phosphate diesters in DNA and RNA Section 8: The organic chemistry of genetic engineering Chapter 10: Nucleophilic carbonyl addition reactions Introduction: How much panda power will your next car have? Section 1: Nucleophilic additions to aldehydes and ketones: an overview A: The aldehyde and ketone functional groups B: Nucleophilic addition C: Stereochemistry of nucleophilic addition Section 2: Hemiacetals, hemiketals, and hydrates A: Overview B: Sugars as intramolecular hemiacetals and hemiketals Section 3: Acetals and ketals A: Overview B: Glycosidic bond formation C: Glycosidic bond hydrolysis Section 4: N-glycosidic bonds Section 5: Imines Section 5: A look ahead: addition of carbon and hydride nucleophiles to carbonyls Organic Chemistry With a Biological Emphasis Tim Soderberg v Tables List of tables: Table 1: Some characteristic absorption frequencies in IR spectroscopy Table 2: Typical values for 1H-NMR chemical shifts Table 3: Typical values for 13C-NMR chemical shifts Table 4: Typical coupling constants in NMR Table 5: The 20 common amino acids Table 6: Structures of common coenzymes Table 7: Representative acid constants Table 8: Some common laboratory solvents, acids, and bases Table 9: Examples of common functional groups in organic chemistry Organic Chemistry With a Biological Emphasis Tim Soderberg Tables Table 1: Some characteristic absorption frequencies in IR spectroscopy Bond type frequency (cm-1) C-H alkanes 2950 – 2850 C-H alkenes 3080 – 3020 C-H aldehyde ~2900 C-H alkyne ~3300 alkyne triple bond 2250 – 2100 (s) alkene double bond 1680 - 1620(s) carbonyl, ketone 1725 – 1700 (s) carbonyl, aldehyde 1740 – 1720 (s) carbonyl, ester 1750 – 1730 (s) carbonyl, acid 1725 – 1700 (s) carbonyl, amide 1690 – 1650 (s) O-H, alcohols 3600 – 3200 (s, broad) O-H, acids 3000 – 2500 (broad) C-O, alcohols, esters, ethers 1300 - 1000 s = strong absorbance Organic Chemistry With a Biological Emphasis Tim Soderberg 439 Tables Table 2: Typical values for 1H-NMR chemical shifts Hydrogen type Chemical shift (ppm) RCH3 0.9 - 1.0 RCH2R 1.2 - 1.7 R3CH 1.5 – 2.0 O C R CH3 R 2.0 – 2.3 CH3 C C R 1.5 – 1.8 R RNH2 1-3 ArCH3 2.2 – 2.4 R C C H O R CH3 O 2.3 – 3.0 3.7 – 3.9 C R CH3 O ROH 3.7 – 3.9 1-5 H R C C R R 3.7 – 6.5 O R C N R 5-9 H 6.0 – 8.7 ArH O R C H 9.5 – 10.0 O R C OH 10 - 13 Chemical shift values are in parts per million (ppm) relative to tetramethylsilane 440 Organic Chemistry With a Biological Emphasis Tim Soderberg Tables Table 3: Typical values for 13C-NMR chemical shifts Carbon type Chemical shift (ppm) RCH3 13 - 16 RCH2R 16 - 25 R3CH 25 - 35 O R O C CH3 18 - 22 O C R CH3 28 - 32 RCH2NHR 35 - 45 RCH2OH 50 - 65 R C C R 65 - 70 ROCH2R 50 - 75 O R O CH2R R 50 - 75 H C C R H R 115 - 120 H C C R H 125 - 140 aromatic carbon O 125 - 150 C R X (carboxylic acid derivatives) 165 - 185 O R C 190 - 200 H O R C 200 - 220 R Organic Chemistry With a Biological Emphasis Tim Soderberg 441 Tables Table 4: Typical coupling constants in NMR H-H coupling J (Hz) C-H coupling R R R R C C R -8 R H H C C H C H H R 2-3 H H 125 - 130 R R O R C C R R R C C H R R 12 - 18 R C C H H - 12 H R C C H R 0-2 H H - 10 H 1- H 442 J (Hz) Organic Chemistry With a Biological Emphasis Tim Soderberg 150 - 170 Tables Table 5: The 20 common amino acids H H3N CH3 H H3N CO2 H CO2 Glycine (Gly, G) H H3N Alanine (Ala, A) CO2 Valine (Val, V) H3N Leucine (Leu, L) N H3N CO2 CO2 Tyrosine (Tyr, Y) HO H Serine (Ser, S) H 3N H 3N CO2 Arginine (Arg, R) O O H Proline (Pro, P) CO2 Glutamate (Glu, E) Cysteine (Cys, C) NH N NH2 H H 3N CO2 H N H3N Threonine (Thr, T) CO2 H3N Methionine (Met, M) H CO2 H CO2 CO2 H O N H2 S H3N Tryptophan (Trp, W) CH3 H CO2 Isoleucine (Ile, I) SH H 2N H3N CO2 H H3N OH H 3N H H Phenylalanine (Phe, F) CO2 H HO H3N H H H H3N H H3N H CO2 Lysine (Lys, K) H 2N H 3N Histidine (His, H) O O O CO2 Aspartate (Asp, D) Organic Chemistry With a Biological Emphasis Tim Soderberg CO2 H H H3N CO2 Glutamine (Gln, Q) H3N NH2 CO2 Asparagine (Asn, N) 443 Tables Table 6: Structures of common coenzymes NH2 N O HS O N N H H O OH O O P O P O O O Coenzyme A (HSCoA) N O O O N N OH P O O NH2 N O O O O P O P O P O O O O N H 3N N N O NH2 CO2 S N N N O N H 3C HO OH HO adenosine triphosphate (ATP) OH S-adenosyl methionine (SAM) thiazole ring H O O O P O H NH2 OH S O N N N PPO CH3 N CH3 H CH3 thiamine diphosphate TPP) pyridoxal phosphate (PLP) O NH3 H N O 2C S CO2 S lipoate 444 O H N CO2 H O N H N H H HS S Glutathione (GSH) biotin Organic Chemistry With a Biological Emphasis Tim Soderberg CO2 Tables Table O H NH2 NH2 O N O O P O P O nicotinamide group HO N O O O N N N O OH HO OH nicotinanide adenine dinucleotide - oxidized form (NAD+, or NADP+ if phosphorylated at arrow position) O H NH2 H N NH2 O HO O O O P O P O O N O OH O HO N N N OH nicotinanide adenine dinucleotide - reduced form (NADH, or NADPH if phosphorylated at arrow position) O CO2 N H O H H2N H N N N CO2 H N O H H N H2N H R C N N N H N N H H tetrahydrofolate (THF) H 5,10-methylenetetrahydrofolate Organic Chemistry With a Biological Emphasis Tim Soderberg 445 Tables O N N H flavin group O N N N CH2 N NH2 HO OH N O H 2C O P O P O O O N OH N O HO H 2C O P OH flavin mononucleotide, oxidized form (FMN) O N N H H O N N N CH2 H N O NH2 HO OH N O O H2C O P O P O O O O N N N N CH2 H O OH N HO OH flavin adenine dinucleotide, reduced form (FADH2) H HO O H2C O P HO 446 O O flavin adenine dinucleotide, oxidized form (FAD) HO O HO O HO H N H CH2 N O HO N O O O flavin mononucleotide,reduced form (FMNH2) Organic Chemistry With a Biological Emphasis Tim Soderberg Tables Table 7: Representative acid constants acid pKa conjugate base O O HO S OH HO S O -10 O HCl -7 Cl- H3O+ -1.7 H2O O sulfuric acid O O N O OH nitric acid -1.4 O N O O O R O P OH 1.0 (i) R O P O OH OH O O HO P OH OH HO P 2.2(ii) O OH phosphoric acid HF F- 3.2 NH3 NH2 4.6 O R C O OH 4-5 N H R C O N 5.3 (ii) pyridinium Organic Chemistry With a Biological Emphasis Tim Soderberg pyridine 447 Tables acid pKa conjugate base O O C HO OH HO 6.4 carbonic acid O R R O P O 6.5 OH O P (i) O O 7.2 (ii) O P OH H3C C C C CH3 O 9.0 O H3C C C C CH3 H H HCN CN- 9.2 NH3 NH4 ammonium OH 9.2 ammonia O 9.9(ii) phenolate phenol O O O 10.3(ii) O C O carbonate bicarbonate RSH 10-11 RS- RNH3+ 10 -11 RNH2 O O P O O 12.3 (i) H2O O P O OH 448 O OH O H O C O O O HO O bicarbonate O HO P C 15.7 Organic Chemistry With a Biological Emphasis Tim Soderberg OH- O Tables acid pKa conjugate base O O R 17 C R NH2 RCH2OH C NH RCH2O- 16 O R C O C R H H 19-20 R C C R H RCCH terminal alkyne 25 RCC- H2 35 H- NH3 ammonia 38 NH2- All pKa values, unless otherwise noted, are taken from March, Jerry, Advanced Organic Chemistry, Fourth Edition, Wiley, New York, 1992 (i) Silva, J.J.R Fraústo da, The Biological Chemistry of the Elements: the Inorganic Chemistry of Life, nd Edition, Oxford, New York, 2001 (ii) Lide, David R (ed.) The CRC Handbook of Chemistry and Physics, CRC Press, Boca Raton, FL, 1995 Organic Chemistry With a Biological Emphasis Tim Soderberg 449 Tables Table 8: Some common laboratory solvents, acids, and bases (fig 10) Solvents CH3CH2OH CH3OH H 2O ethanol methanol water O H 3C O O C S CH3 H3C N C CH3 acetonitrile acetone H CH3 C N CH3 CH3 dimethyl sulfoxide (DMSO) dimethylformamide CH3 O O diethylether tetrahydrofuran (THF) H benzene H Cl C H Cl C toluene Cl Cl Cl Cl dichloromethane (methylene chloride) chloroform Cl C Cl Cl carbon tetrachloride Acids O O HO S OH O sulfuric acid 450 HO S O p-toluenesulfonic acid (TsOH) O CH3 HO P OH OH phosphoric acid Organic Chemistry With a Biological Emphasis Tim Soderberg HCl hydrochloric acid Tables Bases very strong bases: Li N Li lithium diisopropylamide (LDA) CH2CH2CH2CH3 N-butyllithium NaH Na NH2 sodium hydride sodium amide weaker bases: CH2CH3 CH3 N CH2CH3 H3C C O K N CH2CH3 pyridine triethylamine CH3 potassium tert-butoxide O Na O C O OH sodium bicarbonate NaHCO3 K O C O K potasium carbonate K2CO3 NaOH sodium hydroxide Organic Chemistry With a Biological Emphasis Tim Soderberg 451 Tables Table 9: Examples of common functional groups in organic chemistry alkane H H H C C H alkene ketone H H3C H H O H aldehyde alkyne H H C C H H3C imine (Schiff base) carboxylic acid ester H H C Cl H3C C OH H3C C SH amine phenol H3C S C O O P CH3 acid chloride O CH3 OH phosphate ester Cl O O phosphate diester C P OCH3 O O O P OCH3 OCH3 452 CH3 O H3 C sulfide N O H3C H O CH3 O acyl phosphate H H3C CH3 H H3C C NH2 ether S H3C H OH O amide H CH3 O H3C H CH3 O thioester H thiol C H3C H alcohol C H O H3C alkyl halide C N H3C aromatic hydrocarbon CH3 O C C H C Organic Chemistry With a Biological Emphasis Tim Soderberg O ... definition of acidity B: The Lewis definition of acidity Section 2: Comparing the acidity and basicity of organic functional groups– the acidity constant Organic Chemistry With a Biological Emphasis. .. bases Table 9: Functional groups in organic chemistry Organic Chemistry With a Biological Emphasis Tim Soderberg ix Organic Chemistry With a Biological Emphasis Tim Soderberg Chapter Introduction.. .Organic Chemistry With a Biological Emphasis Volume I: Chapters 1-8 Tim Soderberg University of Minnesota, Morris January 2016 Organic Chemistry With a Biological Emphasis Tim Soderberg This