Organic chemistry an acid base approach

xv The Author...xvii Chapter 1: Introduction...1 1.1 A Brief History of Organic Chemistry 1.2 The Variety and Beauty of Organic Molecules Chapter 2: Why Is an Acid–Base Theme Important?.

ORGANIC CHEMISTRY

An Acid–Base Approach

This page intentionally left blank

CRC Press is an imprint of the

Taylor & Francis Group, an informa business

Boca Raton London New York

ORGANIC CHEMISTRY

M I C H A E L B S M I T H

An Acid–Base Approach

CRC Press

Taylor & Francis Group

6000 Broken Sound Parkway NW, Suite 300

Boca Raton, FL 33487-2742

© 2011 by Taylor & Francis Group, LLC

CRC Press is an imprint of Taylor & Francis Group, an Informa business

No claim to original U.S Government works

Version Date: 20110720

International Standard Book Number-13: 978-1-4398-9462-0 (eBook - PDF)

This book contains information obtained from authentic and highly regarded sources Reasonable efforts have been made to publish reliable data and information, but the author and publisher cannot assume responsibility for the validity of all materials

or the consequences of their use The authors and publishers have attempted to trace the copyright holders of all material duced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained If any copyright material has not been acknowledged please write and let us know so we may rectify in any future reprint.

repro-Except as permitted under U.S Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers.

For permission to photocopy or use material electronically from this work, please access www.copyright.com right.com/) or contact the Copyright Clearance Center, Inc (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400 CCC is a not-for-profit organization that provides licenses and registration for a variety of users For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged.

(http://www.copy-Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for

identifica-tion and explanaidentifica-tion without intent to infringe.

Visit the Taylor & Francis Web site at

http://www.taylorandfrancis.com

and the CRC Press Web site at

http://www.crcpress.com

Contents

Preface xi

Acknowledgments xv

The Author xvii

Chapter 1: Introduction 1

1.1 A Brief History of Organic Chemistry 1.2 The Variety and Beauty of Organic Molecules Chapter 2: Why Is an Acid–Base Theme Important? 19

2.1 Acids and Bases in General Chemistry 2.2 Acids and Bases in Organic Chemistry 2.3 How Are the Two Acid–Base Definitions Related? 2.4 Acid and Base Strength 2.5 Lewis Acids and Lewis Bases 2.6 Why Is Acid–Base Chemistry a Theme for Organic Chemistry? 2.7 Biological Relevance Chapter 3: Bonding 45

3.1 The Elements 3.2 What Is a Chemical Bond? Ionic versus Covalent 3.3 The Covalent Carbon–Carbon Bond 3.4 Molecular Orbitals 3.5 Tetrahedral Carbons and sp3 Hybridization 3.6 How Strong Is a Covalent Bond? Bond Dissociation Energy 3.7 Polarized Covalent σ-Bonds 3.8 Biological Relevance Chapter 4: Alkanes, Isomers, and an Introduction to Nomenclature 87

4.1 The Fundamental Structure of Alkanes Based on the sp3 Hybrid Model 4.2 Millions of Hydrocarbons: Alkanes 4.3 Combustion Analysis and Empirical Formulas 4.4 The Acid or Base Properties of Alkanes 4.5 Isomers 4.6 Naming Millions of Isomers: Rules of Nomenclature The IUPAC Rules of Nomenclature 4.7 Rings Made of Carbon Cyclic Compounds 4.8 Biological Relevance Chapter 5: Functional Groups 121

5.1 Introducing a Functional Group: Alkenes

5.2 Another Hydrocarbon Functional Group: Alkynes

5.3 Hydrocarbons with Several Multiple Bonds

5.4 Reactivity of Polarized Covalent σ-Bonds

5.5 Formal Charge

Chapter 14: Spectroscopic Methods of Identification 641

Chapter 23: Difunctional Molecules: Dienes and Conjugated

assessment is wrong on so many levels that it.

serves as a starting point to describe this book

One reason for the fable is that it may be

diffi-cult to ascertain a fundamental theme that ties

and bases provide the theme It is important to

understand the relationships among functional

The theme of this book is the premise that

many if not most reactions in organic chemistry

can be explained by variations of fundamental

know before reading the chapter is listed at the

beginning of virtually every chapter A list of

concepts.that.should.be.known.after.the.chapter

is.completed.is.also.provided.at.the.beginning.of

most.chapters Each.chapter.concludes.with.this

same list of the concepts that should now have

been learned, and a correlation of each concept

with the homework problems is provided The

intent is.to.help.identify concepts.that need.work apart.from.those.that are.readily.understood.

Each.chapter.has.a.number.of.embedded.problems They.will.help.the.student.think.about.the.concept.and.possibly.review.something.from.a.previous.chapter.that.is.pertinent,.with.the.goal.of.better.understanding.that.section The.answers.to.these.problems.are.provided.at.the.end.of.each.chapter Regular.homework.problems.are.given.with.the.intention.of.offering.help.in.understanding.the.con-cepts.in.the.chapter For.additional.material.and.a.solutions.manual,.please.see.the.book.Web.site.(http://www.crcpress.com/product/isbn9781420079203)

tion The.point.is.to.show.that.the.experiment.shows.a.result.and.then.we.try.to.understand.that.result.in.the.context.of.the.structural.features.of.the.reactive.species Mechanisms.are.given.as.part.of.the.discussion.of.key.reactions The.mechanism.is.discussed.in.most.cases.first.as.a.walk-through.of.the.reaction.to.understand.how.the.transformation.occurred,.and.then.structures.for.the.walk-through.are.provided.that.constitute.the.mechanism Many.of.these.mechanis-tic.steps.will.involve.acid–base.reactions—both.Brønsted–Lowry.and.Lewis.The.book.begins.with.an.introduction.to.organic.chemistry.that.describes.what it is as well as individuals who have contributed to building organic.chemistry.as.a.scientific.discipline Chapter.2.provides.a.bridge.between.the.acid–base discussions in a typical general chemistry book and those in this.organic.chemistry.book An.understanding.of.bonding.is.critical.to.understand-ing.the.structure.of.organic.molecules;.this.is.provided.in.Chapter.3,.followed.by.Chapter.4.with.an.introduction.to.alkanes,.the.basic.structure.of.organic.molecules,.and.the.fundamental.rules.of.nomenclature Chapter.5.introduces.the.concept.of.functional.groups.as.well.as.several.important.functional.groups.that appear in organic molecules This chapter includes an extension of the.basic.nomenclature.rules.to.include.functional.groups

Experimental.details.are.provided.for.key.reactions.to.introduce.the.reac-Chapter 6 returns to the acid–base theme to give a direct correlation.between.acid–base.reactions.and.organic.chemical.reactions.that.involve.the.functional.groups.just.introduced.in.Chapter.5 Chapter.7.extends.the.acid–base.concept.of.equilibrium.reactions.to.discuss.bond.energetics.and.kinetics Rotation.about.single.covalent.bonds.leads.to.different.orientations.of.atoms.and.groups.within.a.molecule,.known.as.conformations;.this.is.presented.in.Chapter.8 Chapter.9.introduces.the.concept.of.chirality.and.the.relationship.between.chirality.and.structure

Chapter.10.introduces.the.acid–base.chemistry.of.molecules.that.contain.the.C=C.and.C≡C.functional.groups Related.reactions.that.do.not.fall.under.the.acid–base.category.are.also.presented Chapter.11.uses.nucleophiles,.which.are.loosely.categorized.as.specialized.Lewis.bases,.in.reactions.with.alkyl.halides These.are.substitution.reactions Chapter.12.shows.the.acid–base.reaction.of.alkyl.halides.that.leads.to.alkenes.(an.elimination.reaction),.and.Chapter.13.ties.Chapters.11.and.12.together.with.a.series.of.simplifying.assumptions.that.allows.one.to.make.predictions.concerning.the.major.product

Chapter 14 introduces methods used to identify the structure of organic.molecules: mass spectrometry, infrared spectroscopy, and nuclear magnetic

resonance.spectroscopy This.chapter.is.in.the.middle.of.the.book,.but.it.may.be.presented.in.either.semester,.and.homework.problems.associated.with.this.chapter are incorporated throughout All homework problems requiring the.information.in.Chapter.14.are.clearly.marked.and.segregated.from.the.other.problems Therefore,.this.chapter.may.be.introduced.in.either.semester.and.the.associated.homework.problems.can.be.easily.found.

Chapter.15.provides.a.brief.introduction.to.commonly.used.organic.molecules.that also have a carbon–metal bond—organometallics Chapter 16 introduces.the.fundamental.characteristics.of.molecules.that.contain.the.carbon.functional.group,.along.with.a.review.of.the.nomenclature.of.carbonyl-containing.molecules Carbonyl.compounds.are.often.prepared.by.oxidation.reactions,.and.several.key.oxidation reactions are discussed in Chapter 17 Oxidation reactions of a few.other.functional.groups.are.included Chapter.18.elaborates.the.chemical.reac-tions.of.the.carbonyl-containing.molecules.known.as.aldehydes.and.ketones This.chemistry.is.dominated.by.the.acyl.addition.reaction.introduced.in.Chapter.16.Chapter.19.in.effect.continues.the.chemistry.of.carbonyls.by.introducing.reduction.reactions Carbonyl-containing.molecules,.as.well.as.molecules.that.contain.other.functional.groups,.may.be.reduced.to.different.functional.groups,.and.such.reactions.are.discussed.in.this.chapter Chapter.20.continues.carbo-nyl.chemistry.by.discussing.chemical.reactions.of.the.carboxylic.acid.deriva-tives.introduced.in.Chapter.16,.with.a.focus.on.acyl.substitution.reactions.Chapter.21.discusses.the.concept.of.aromaticity.as.well.as.the.nomenclature.and.the.specialized.chemical.reactions.of.aromatic.compounds.such.as.benzene.and.its.derivatives This.chapter.comes.late.in.the.book,.with.the.notion.that.the chemistry of aliphatic compounds is simply used more often The acid–base.theme.is.continued.with.the.recognition.that.the.fundamental.substitu-tion.chemistry.associated.with.benzene.derivatives.may.be.explained.by.the.reaction of aromatic rings as Lewis bases or nucleophiles with electrophilic.reagents The reactions of benzene derivatives with strong bases and good.nucleophiles.are.also.presented

Chapter 22 returns to carbonyl chemistry and a discussion of the acid–base.properties.of.carbonyl.compounds The.proton.on.the.α-carbon.(directly.attached.to.the.carbonyl).is.slightly.acidic.and.removal.with.a.suitable.base.leads to an enolate anion Enolate anions react as nucleophiles in aliphatic.substitution,.acyl.addition,.and.acyl.substitution.reactions

Chapter 23 begins a discussion of multifunctional molecules that will.conclude the book and, in many courses, may be considered as special topic.material, beginning with simple conjugated dienes and conjugated carbonyl.compounds Ultraviolet.spectroscopy.is.discussed.in.the.context.of.identifying.conjugated compounds Chapter 24 continues this discussion with pericyclic.reactions.that.involve.dienes.and.other.multifunctional.compounds Chapter 25

is a stand-alone chapter to introduce the retrosynthetic approach to sis It.is.presented.as.part.of.the.discussion.on.multifunctional.molecules,.but.it.may.be.taught.at.any.point.in.the.course As.with.spectroscopy,.synthesis.problems.are.clearly.marked.homework.problems.in.several.chapters.and.are.segregated.from.the.other.problems.so.that.they.are.easily.found

synthe-cules Heterocycles.are.introduced.in.Chapter.26,.with.nomenclature.and.struc-ture as well some elementary chemical reactions of heterocyclic compounds Amino.acids.and.peptides.are.discussed.in.Chapter.27.and.carbohydrates.and.nucleic.acids.are.discussed.in.Chapter.28 These.last.three.chapters.are,.argu-ably,.the.most.important.to.biological.chemistry.

The.book.concludes.with.three.chapters.that.involve.multifunctional.mole-This.book.constitutes.an.important.introduction.to.organic.chemistry The.reactions.and.mechanisms.contained.herein.describe.its.most.fundamental.concepts, which are used in industry, biological chemistry and biochemis-try,.molecular.biology,.and.pharmacy These.concepts.constitute.the.funda-mental basis of life processes, which means that they are pertinent to the.study of medicine For that reason, most chapters end with a brief section.that.describes.biological.applications.for.each.concept The.last.two.chapters.(27.and.28).have.more.than.one.section.that.discusses.biological.applications.because.these.molecules.make.up.the.proteins,.enzymes,.cellular.structure,.and.DNA.and.RNA.found.in.living.systems It.is.hoped.that.this.course.will.provide the skills to go to the next level of study using this fundamental.understanding of acids and bases applied to organic transformations and.organic.molecules

edgments

Acknowl-There.are.many.people.to.thank.for.a.book.such

as this one First, let me thank my students,

whose enthusiasm and interest have pushed me

to.develop.better.ways.to.communicate.and.better

ways to describe organic chemistry I thank my

colleagues in the organic chemistry community,

particularly the synthetic organic community,

for.allowing.me.to.keep.my.knowledge.and.skills

honed.over.the.years

In addition, myriad discussions with my

colleagues have helped me to become a better

organic chemist and be better able to

commu-nicate that knowledge I particularly want to

thank Spencer Knapp (Rutgers University) and

John D’Angelo (Alfred University) for providing

All structures and reactions were drawn

using ChemBioDraw Ultra, v 11.0.1 I thank

CambridgeSoft, Inc for a gift of this software

All.3-D.drawings.and.molecular.models.were.pre-pared.using.Spartan06.software,.v.1.0.1 I.thank

Warren.Hehre,.Sean.Ohlinger,.and.Wavefunction,

Inc for.the.gift.of.this.software

I thank my editor, Lance Wobus of Taylor &

Francis, for giving me the opportunity to write

this.book.and.working.with.me.over.these.many

months His support, vision, and ability to solve

the inevitable issues that arise in such a

proj-ect.have.been.essential.for.getting.this.book.into

print I also thank Dr Fiona Macdonald for her

support in getting this book off the ground and

David Fausel and Judith Simon for their

excel-lent work in converting the manuscript to the

finished book I also want to thank Jim Smith,

who.was.instrumental.to.this.project.in.its.early

days I thank.Warren.Hehre.(Wavefunction,.Inc.),

Finally,.I.thank.my.wife,.Sarah,.and.my.son,.Steven,.for.their.support.and.encouragement over the years That support has helped more than can be.properly.expressed.in.words

The Author

Michael B Smith is professor of chemistry in.

the Department of Chemistry at the University

of Connecticut at Storrs His research interests

focus.on.the.identification.of.bioactive.lipids.from

the dental pathogen Porphyromonas gingivalis,.

exploration of the use of conducting polymers as

a.reaction.medium.for.chemical.transformations,

development.of.fluorescent.probes.for.the.detection

of.cancerous.tumors,.and.the.synthesis.of.phenan-thridone alkaloids He is the author of volumes

6–12 of the Compendium of Organic Synthetic

This page intentionally left blank

class of students with a wide range of interests.

and career choices Why is organic chemistry

ago, a T-shirt at an American Chemical Society

meeting in Dallas sported the logo “Chemistry:

(United States; 1899–1977) Advanced Organic

Chemistry.1 This book gave a perspective to my

studies.and.helped.me.to.understand.many.of.the

concepts better I believe that putting a subject

into.its proper.context

makes.it.easier.to.under-stand,.so.I.am.introducing.an.abbreviated.history

of.organic.chemistry.as.the.beginning.to.this.book

I will include material from Fieser’s book and

also from a book on the history of chemistry by

Leicester.2.It.is.important.to.remember.the.great

organic.chemists.of.the.past,.not.only.because.their

work.is.used.today.but.also.because.it.influences

the.way.that.we.understand.chemistry

1.1  A Brief History of Organic Chemistry

Humans.have.used.practical.applications.of.chemistry.for.thousands.of.years The.discovery.and.use.of.folk.medicines,.the.development.of.metallurgical.tech-niques,.and.the.use.of.natural.dyes.are.simple.examples For.most.of.history,.humans.were.able.to.use.simple.chemicals.or.a.complex.mixture.of.chemicals.without.actually.understanding.the.science.behind.them Organic.chemistry.became a defined science (the chemistry of carbon compounds) in the nine-teenth.century,.but.organic.compounds.have.been.known.and.used.for.millen-nia Plants.have.been.“milked,”.cut,.boiled,.and.eaten.for.thousands.of.years

as folk medicine remedies, particularly in Africa, China, India, and South.America Modern.science.has.determined.that.many.of.these.plants.contain.organic.chemicals.with.effective.medical.uses,.and.indeed.many.of.our.mod-ern.medicines.are.simply.purified.components.of.these.plants.or.derivatives.of.them.made.by.chemists

N H

OH

H N

ancient.antipyretic.treatment.(this.means.that.it.lowers.a.fever).involved.chew-side.salicin.(3),.a.derivative.of.salicylic.acid.(4a) Eventually,.chemists.learned.

how to make new organic molecules rather than simply isolating and using.those.that.were.found.in.nature,.although.isolation.from.nature.remains.an.important.source.of.new.compounds

In.the.mid-nineteenth.century.a.new.compound.was.synthesized.(chemi-cally prepared from other chemicals) called acetylsalicylic acid (4b; better.

known as aspirin), and it was found to be well tolerated by patients as an.effective.analgesic.(this.means.that.it.reduces.some.types.of.pain) These.few.examples are meant to represent the thousands of folk medicine remedies.that.have.led.to.important.medical.discoveries All.of.these.involve.organic.compounds

O O

H

OH HO

HO

HO

OH

RO O

symbols.(1–5).used.to.represent.the.chemicals.require.some.explanation,.and.

ethyl.alcohol.is.a.simple.example Each.“line”.is.a.chemical.bond Therefore,.C–C.is.a.carbon–carbon.bond.and.“–”.is.used.as.a.shorthand.notation.to.represent.that.bond The.symbol.C–N.is.a.carbon–nitrogen.bond,.C–O.is.a.carbon–oxygen

bond,.and.O–H.is.an.oxygen–hydrogen.bond In.5,.–OH.represents.–O–H Each.

intersection.of.bonds,.such.as.[ ⦧ ],.is.a.carbon.atom Various.groups.may.be.attached.to.these.carbon.atoms.(OH,.NH2,.CH3,.etc.) This.notation,.called.line

notation,.is.used.to.draw.most.of.the.chemical.structures.in.this.book.

H

H C H

H

O H

5

OH

Line notation uses one line for each bond, so C=C indicates two bonds.between.the.carbon.atoms.(a.carbon–carbon.double.bond),.and.C=O.indicates.two.bonds.between.carbon.and.oxygen.(a.carbon–oxygen.double.bond) Similarly,.C≡C.represents.three.bonds.between.the.two.carbon.atoms,.a.carbon–carbon.triple.bond Many.molecules.have.double.and.triple.bonds Examples.are.com-

pounds.1–4,.as.well.as.compounds.6.and.7.

Line.notation.is.used.for.simple.compounds.such.as.5;.however,.as.shown.in structures.1–3,.it.is.applicable.to.very.complicated.structures In.ancient.India,.

in.Java,.and.in.Guatemala.certain.plants.provided.a.deep.blue.substance.used.to

color.clothing In.recent.times,.the.main.constituent.was.found.to.be.indigo.(6)

The.ancient.Phoenicians.used.an.extract.from.a.snail.(Murex brandaris).found.

tiful.and.very.expensive.dye.called.Tyrian.purple This.dye.was.so.prized.that.Roman.emperors.used.it.to.color.their.clothing,.and.for.many.years.no.one.else.was.permitted.to.wear.this.color.(hence.the.term.“born.to.the.purple”) The.actual

off.the.coast.of.Tyre.(a.city.in.modern-day.Lebanon).to.color.cloth It.was.a.beau-structure.of.the.organic.chemical.Tyrian.purple.is.7 Note.that.the.only.difference.

ter Structural.differences.that.on.the.surface.appear.to.be.minor.can.lead.to.sig-nificant.changes.in.the.physical.properties.of.organic.compounds,.such.as.color

Atropa belladonna.(deadly.nightshade).has.been.used.for.centuries.as.a.poison

The.plant.extract.is.a.deadly,.but.the.“poison”.isolated,.found.to.be.atropine.(8).is.not.produced.by.the.plant,.but.produced.from.a.natural.alkaloid.by.the.acid-base.extraction.procedure.used.for.isolation

N

N O

O H

H

N N O

O H

H Br

Br

These.few.examples.show.that.organic.chemicals.are.important.to.humans.and.have.been.for.a.very.long.time For.most.of.this.time,.however,.the.actual.chemical.structure.of.these.compounds.was.unknown Indeed,.the.fact.that.the.chemicals.were.discrete.molecules.was.unknown It.was.known.that.a.multi-tude.of.materials.could.be.obtained.from.natural.sources,.primarily.from.living.organisms This.knowledge.sparked.a.curiosity.that.eventually.led.to.modern.organic.chemistry.as.a.science In.the.following.paragraphs,.a.few.of.the.chem-ists.who.advanced.organic.chemistry.as.a.science.are.introduced

O

H H

O

H O

As.pointed.out.earlier,.natural.materials.have.been.used.for.many.years It.was.not.until.the.eighteenth.century.that.people.began.to.look.for.specific.chemicals.in.these.natural.materials One.of.the.first.to.report.discrete.chemi-

cals.was.Carl Wilhelm

Scheele.(Sweden;.1742–1786),.who.isolated.acidic.com-ponents.from.grapes.and.lemons.by.forming.precipitates.with.calcium.or.lead.salts,.and.then.added.mineral.acids.to.obtain.the.actual.compounds The.com-

pound.from.grapes.is.now.known.to.be.tartaric.acid.(9).and.that.from.lemon.is now.known.to.be.citric.acid.(10) Scheele.also.isolated.uric.acid.(11).from.urine.

Friedrich W Sertürner (Germany;.1783–1841).isolated.a.compound.from.

In 1818–1820, Pierre J Pelletier (France; 1788–1842) and Joseph

Caventou (France; 1795–1877) isolated a poisonous compound from Saint.

Ignatius’ beans (S ignatii) that they called an alkaloid (an alkali-like base).

now known to be strychnine (16; found in the seeds of the nux vomica tree.

[S. nux-vomica].and.also.from.related.plants.of.the.genus.Strychnost) Alkaloids.

are.a.large.group.of.diverse.compounds.that.contain.nitrogen.and.are.primarily.found.in.plants Although.difficult.to.define.because.of.their.structural.diver-sity, alkaloids are commonly assumed to be basic nitrogenous compounds of.plant origin that are physiologically active The practice of isolating specific.compounds.(now.known.to.be.organic.compounds).from.natural.sources.contin-ues.today Such.compounds.are.called.“natural.products.”

H

OH O

H3C(H2C)16 O – Na +

O

N

NH2H-N

that.the.structures.of.most.of.these.compounds.were.known.absolutely Justus

Liebig.(Germany;.1803–1873).perfected.the.science.of.analysis.of.organic.com-pounds,.based.on.the.early.work.of.Antoine Lavoisier (France;.1743–1794).

Late.in.the.eighteenth.century,.Lavoisier.made.a.monumental.contribution.to.the.science.of.chemistry.that.was.important.to.understanding.organic.chem-istry He.used.the.discovery.that.air.was.composed.mainly.of.oxygen.(O2).and.nitrogen.(N2).and.burned.natural.materials.in.air He.discovered.that.carbon.in.the.burned.material.was.converted.to.carbon.dioxide.(CO2).and.that.hydrogen.in.the.material.was.converted.to.water.(HOH) By.trapping.and.weighing.the.carbon.dioxide.and.the.water,.he.was.able.to.calculate.the.percentage.of.car-bon.and.hydrogen.in.molecules,.which.led.to.a.determination.of.the.empirical.formula Because.we.now.know.that.organic.molecules.are.composed.mainly

of carbon and hydrogen, this elemental analysis procedure was and is an.

In.1807,.a.Swedish.chemist.named.Jöns J von Berzelius.(Sweden;.1779– 1848) described the substances obtained from living organisms as organic

compounds,.and.he.proposed.that.they.were.composed.of.only.a.few.selected.

elements, including carbon and hydrogen Because all organic compounds.known.at.that.time.had.been.isolated.as.products.of.“life.processes”.from.liv-

ing.organisms.(hence.the.term.organic),.Berzelius.and.Charles F Gerhardt

(France;.1816–1856).described.what.was.known.as.the.vital force theory This.

theory subscribed to the notion that “all organic compounds can arise with.the.operation.of.vital.force.inherent.to.living.cells.”.The.vital.force.theory.was.widely.believed.at.the.time

In.1828.Friedrich Wöhler.(Germany;.1800–1882).synthesized.(prepared from.other.chemicals).the.organic.molecule.urea.(18).from.chemicals.that.had.

not been obtained from living sources When he heated ammonium cyanate

(17),.the.product.was.urea.(18) Urea.is.a.component.of.urine.and.also.a.com-ponent.of.bird.droppings.that.have.been.used.for.centuries.as.fertilizer This.work,.along.with.that.of.others,.was.contrary.to.the.vital.force.theory.because.it.showed.that.an.organic.compound.could.be.produced.from.a.“nonliving”.sys-

tem However,.it.was.not.until.Pierre-Eugene-Marcellin Berthelot.(France;.

1827–1907).showed.that.all.classes.of.organic.compounds.could.be.synthesized.that.the.vital.force.theory.finally.disappeared

pound.from.more.structurally.simple.compounds.in.several.chemical.steps).began

At.about.the.same.time,.Alexander W Williamson.(England;.1824–1904).

showed.how.ethers.(ethers.contain.the.C–O–C.linkage).could.be.prepared.from.

sium.salt.is.the.conjugate.base.of.that.alcohol,.C–O–K+,.and.the.oxygen.atom.of.that.species.reacts.with.an.alkyl.halide,.which.contains.a.C–X.bond In.this

the.potassium.salt.of.an.alcohol.(an.alcohol.contains.a.C–O–H.unit) The.potas-representation,.X.is.a.halogen.and.alkyl.is.the.term.used.for.a.unit.containing.

carbons.and.hydrogen.atoms The.nomenclature.for.all.of.these.compounds.will.be.described.in.Chapters.3.and.4

21 20

In.1863,.William H mercially.useful.synthetic.dye.(a.dye.made.by.humans),.mauveine.(19),.which.

Perkin.(England;.1838–1907).prepared.the.first.com-showed.a.purple.color.that.had.not.been.previously.isolated.from.nature In.

1869,.the.synthesis.of.a.natural.dye.was.reported.by.Carle Graebe.(Germany; 1841–1927).and.Carl Liebermann.(Germany;.1882–1914) They.prepared.the natural.dye.alizarin.(20).from.anthracene.(21),.which.is.obtained.from.petro- leum.distillates Adolf von Baeyer (Germany;.1835–1917).was.the.first.to synthesize.the.dye.indigo.(6) Aspirin.(4).was.first.prepared.in.the.mid-nine-

teenth.century.and.commercialized.later.in.that.century The.synthesis.of.the.various.dyes.and.of.aspirin.was.important.to.the.economies.of.both.England.and.Germany.in.the.late.nineteenth.and.early.twentieth.centuries Clearly,.a.major.step.in.organic.chemistry.involved.the.chemical.synthesis.of.the.com-pounds.that.could.be.isolated.from.nature,.and.this.knowledge.was.expanded

to prepare compounds that were not known in nature Once accomplished,.these.products.were.commercialized.and.this.led.to.the.development.of.chemi-cal.industries

By the mid-nineteenth century, chemists were beginning to understand.that organic molecules were discrete entities and they were able to prepare.them Determining the structures of these compounds (how the atoms are

in.22.(methane),.where.each.line.connecting.the.atoms.represents.a.chemical bond.as.mentioned.earlier.(see.compound.5).

In 1859, however, precisely how these four other atoms were attached.remained.unknown The.concept.of.a.bond.was.vague.and.largely.undefined

It.was.not.until.1916.that.Gilbert N Lewis

(United.States;.1875–1946).intro-duced.the.modern.concept.of.a.bond formed by sharing two electrons He.called.

a.bond.composed.of.shared.electrons.pairs.a.covalent bond Erich Hückel.

(Germany; 1896–1980) developed theories of bonding and orbitals and also

speculated.on.the.nature.of.the.C=C.unit However,.Alexander Crum Brown.

(England;.1838–1922).first.wrote.a.“double.bond”:.C=C,.for.ethylene.(H2C=CH2),

in.1864 Emil Erlenmeyer.(Germany;.1825–1909).wrote.acetylene.(HC≡CH).with.a.triple.bond.in.1862.

ecules.are.put.together.and.that.each.covalent.bond.consists.of.two.electrons

Understanding.covalent.bonds.allows.us.to.understand.how.organic.mol-shared.by.the.two.atoms.in.the.covalent.bond Returning.to.methane.(22),.the four.covalent.bonds.to.carbon.could.now.be.represented.as.23,.where.each.“:” represents.two.shared.electrons A.structure.such.as.23.is.commonly.known.as.

a.Lewis electron dot structure,.after.G N Lewis In.1923,.Lewis.suggested.that.

a molecule that accepts an electron pair should be called an acid.and.

a molecule that donates an electron pair should be called a base These.

are.called.Lewis acids.and.Lewis bases.to.this.day.

Understanding.where.electrons.are.in.an.organic.molecule.and.how.they.are transferred is important for an understanding of both the structure of

molecules.and.also.their.chemical.reactions In.1925.two.physicists,.W Karl

Heisenberg.(Germany;.1901–1976).and.Erwin Schrödinger.(Austria;.1887–

1961).described.the.orbital.concept.of.molecular.structure In.other.words,.they

introduced.the.idea.of.orbitals in chemistry and bonding.(see.Chapter.3)

Today we combine these ideas by saying that orbitals contain electrons and.that.orbital.interactions.control.chemical.reactions.and.explain.chemical.bond-ing Clearly,.this.area.of.organic.chemistry.involved.identifying.the.chemical.structure.of.organic.molecules.and.relating.that.structure.to.organizations.of.atoms.held.together.by.shared.electrons

In.structures.1.and.16,.the.lines.used.for.chemical.bonds.have.been.replaced with.solid wedges.or.with.dashed lines,.which.are.used.to.indicate.the.spa-

tial.relationship.of.atoms.and.groups.within.these.compounds The.solid.wedge

indicates.that.the.group.is.projected in front of the plane of.the.page,.and.the dashed.line.indicates.that.the.group.is.projected.behind the plane.of.the.page

This.three-dimensional.representation.corresponds.to.the.spatial.relationship

of the atoms or groups and is known as the stereochemistry of that atom or.

pounds It was not until the mid- to late twentieth century that the stereo-chemistry.of.organic.compounds.could.be.accurately.determined,.although.its.discovery.dates.to.the.mid-nineteenth.century

group Stereochemistry.is.also.a.part.of.the.structure.of.many.organic.com-

Indeed,.the.concept.of.stereochemistry.is.almost.as.old.as.organic.chem-istry.itself In.1848,.Louis Pasteur.(France;.1822–1895).found.that.tartaric acid.(9).existed.in.two.forms.that.we.now.know.differ.only.in.their.ability.to.

reoisomers) Pasteur observed that the crystals had a different morphology,.defined here as their external structure, and he was able to separate these.two.forms.by.peering.through.a.microscope.and.using.a.pair.of.tweezers.to.separate.them.physically Because.of.this.difference,.the.two.forms.of.tartaric

rotate.plane-polarized.light.in.different.directions.(they.are.examples.of.ste-acid.are.considered.to.be.different.compounds,.now.called.enantiomers.(see.

Chapter.9)

Van’t.Hoff.found.that.alkenes.existed.as.a.different.type.of.stereoisomer.that.is.not.an.enantiomer,.but.is.also.discussed.in.Chapter.9 Pasteur,.Van’t.Hoff,

and.Le.Bel.are.widely.considered.to.be.the.founders.of.stereochemistry Emil

standing.not.only.their.chemistry,.but.also.their.structures.and.stereochem-istry Many.scientists.have.helped.develop.this.concept.into.the.powerful.tool

and.early.twentieth.centuries.and.made.many.major.contributions.to.under-it.is.today,.including.John Cornforth.(Australia/England;.1917–),.Vladimir

Prelog.(Yugoslavia/Switzerland;.1906–1998),.and.Donald J Cram.(United.

States;.1919–2001)

As.in.the.beginning.of.organic.chemistry,.isolation.of.organic.compounds.from.natural.resources.continues.to.be.important New.organic.molecules.are.isolated.from.natural.sources.such.as.terrestrial.and.marine.plants,.fungi,.and.bacteria,

as.well.as.some.animals G Robert Pettit.(United.States;.1929–).and.S Morris

Kupchan.(United.States;.1922–1976).are.two.organic.chemists.who.have.discov-cal.activity.against.cancer.and.other.human.diseases The.synthesis.of.organic.compounds.has.also.continued.unabated.since.the.nineteenth.century Over.the.years,.increasingly.more.complex.molecules.have.been.synthesized

Fe

26

It.is.useful.to.examine.a.handful.of.syntheses.of.organic.molecules.to.show.the.structural.challenges.and.also.how.more.sophisticated.methods.and.reagents.have.become.an.important.part.of.synthesis The.choice.of.the.compounds.pre-

sented.here.is.largely.due.to.the.book.by.Elias J Corey.(United.States;.1928–),3.who.described.the.theory.and.practice.of.modern.organic.synthesis In.1904,

William H Perkin, Jr (England;.1860–1929).synthesized α-terpineol.(24).and,.

in 1917, Sir Robert Robinson (England; 1885–1975) synthesized tropinone (25) Terpineol.is.isolated.from.pine.oil.and.used.as.an.ingredient.in.perfumes,.

flavors,.and.cosmetics The.synthesis.of.tropinone.was.important.because.that

synthesis.led.to.the.synthesis.of.atropine.(8),.which.was.used.as.an.immediate.

antidote.after.exposure.to.certain.chemical.nerve.agents.used.in.gas.attacks.during.World.War.I.and.was.in.short.supply Atropine.is.still.used.today

In.1929,.Hans Fischer.(Germany;.1881–1945).synthesized.protoporphyrin (hemin,.26),.and.quinine.(1).was.synthesized.in.1944.by.Robert B Woodward (United States; 1917–1979) and William von E Doering (United States;.

1917–) Hemin.contains.the.unit.found.in.hemoglobin,.the.oxygen-carrying.com-ponent.of.blood,.and.quinine.is.an.effective.antimalarial.drug In.1951,.Sir.Robert

Robinson.and.Robert B Woodward.synthesized.strychnine.(16),.and.ever.

more.complex.organic.molecules.are.being.synthesized.today

A.huge.number.of.syntheses.have.been.reported.in.the.last.50.years.that.have.contributed.enormously.to.organic.chemistry Apart.from.simply.synthe-sizing.the.molecules,.many.chemists.develop.new.chemical.reactions.as.well.as.new.chemical.reagents.(molecules.that.induce.a.chemical.transformation.in.another.molecule) There.is.no.question.that.another.area.of.organic.chemistry.involves.developing.new.or.modified.chemical.reactions.to.the.point.that.virtu-ally.any.molecule.can.be.prepared Understanding.chemical.reactions.and.the.reagents.used.in.those.reactions.and.developing.new.reagents.and.reactions.are.a.critical.part.of.the.synthesis.of.organic.molecules.(including.those.shown.here).and.have.profound.influences.in.all.areas.of.organic.chemistry

Prior.to.the.late.1940s.and.1950s,.chemists.did.not.really.understand.how.

chemical.reactions.occurred In.other.words,.what.happened.during.the.bond.making and bond breaking processes remained a mystery Understanding

these processes, now called reaction mechanisms, required an enormous.

amount.of.work.in.the.period.of.the.late.1940s.throughout.the.1960s,.and.it

continues.today Pioneers.in.this.area.include.Frans Sondheimer.(Germany; 1926–),.Saul Winstein.(Canada/United.States;.1912–1969),.Sir.Christopher

K Ingold.(England;.1893–1970),.John.D Roberts.(United.States;.1918–2001), Donald J Cram.(United.States;.1919–2001),.Herbert C Brown.(England/

United.States;.1912–2004),.George A Olah.(Hungary/United.States;.1927–),.

and many others They studied reactions that have reactive ionic

interme-diates such as carbocations (a carbon having three covalent bonds and a positive.charge.on.carbon;.a.positively.charged.carbon.atom).or.carbanions.

(a  carbon having three covalent bonds and two extra electrons on carbon; a.negatively.charged.carbon.atom) Another.type.of.intermediate.called.a.carbon.radical.(a.carbon.having.three.covalent.bonds.and.one.extra.electron).has.been.identified

An.intermediate.is.a.transient.and.usually.high-energy.molecule.that.is.

formed.initially.and.then.reacts.further.to.give.a.final,.more.stable.product The.nature.and.structure.of.these.intermediates.were.determined,.and.meth-ods.were.developed.to.ascertain.the.presence.of.these.intermediates.and.how.long.they.were.present.in.the.reaction.(in.other.words,.how.reactive.they.were)

The.idea.of.reaction.kinetics.was.developed.for.organic.chemistry,.describing.

mation.gives.clues.as.to.how.the.reaction.proceeded.and.what,.if.any,.interme-diates.may.be.involved

the.rate.at.which.products.were.formed.and.reactants.disappeared This.infor-Roald Hoffman.(Poland/United.States;.1937–).and.Robert Woodward.

(United.States;.1919–1979).and.Kenichi Fukui.(Japan;.1918–1998).described.

the.concept.of.frontier.molecular.orbitals.and.the.use.of.orbital.symmetry.to.explain many reactions that did not appear to proceed by ionic intermedi-ates The.concept.of.reaction.mechanism.allows.a.fundamental.understanding

of how organic reactions work, and it is a relative latecomer to the study of.organic.chemistry It.is.perhaps.the.most.important.aspect,.however,.because

Finally, how does a chemist know the structure of any organic

chemical? How are organic compounds isolated and identified? In.

early.work,.inorganic.materials.such.as.metal.salts.and.acids.or.bases.were.added to force precipitation of organic compounds In other cases, liquids.were.distilled.out.of.“organic.material”.or.solids.were.crystallized.out In.the

1950s,.Archer J P Martin.(United.States;.1910–2002).and.Richard Synge.

(England;.1914–1994).developed.the.concept.of.chromatography;.this.allowed.

vidual.components

chemists.to.separate.mixtures.of.organic.compounds.conveniently.into.indi-Light.has.always.been.an.important.player.in.chemistry In.the.early.to.mid-twentieth.century,.ultraviolet.light.was.shown.to.interact.with.organic.mol-ecules.at.certain.wavelengths In.the.1940s.and.1950s,.molecules.were.exposed.to.infrared.light.and.found.to.absorb.only.certain.wavelengths Identification.of.which.wavelengths.of.light.were.absorbed.and.correlation.of.this.informa-tion.with.structure.comprised.a.major.step.in.the.identification.of.organic.mol-

ecules Even.today,.ultraviolet spectroscopy.and.infrared spectroscopy.are.

major.tools.for.the.identification.of.organic.compounds

oped that were based on the discovery that organic molecules interact with.electromagnetic radiation with wavelengths in the radio signal range if the.molecules.are.suspended.in.strong.magnetic.fields Initially,.it.was.discovered.that.hydrogen.atoms.interacted.in.this.manner.and.chemical.differences.could.often.be.discerned If.the.different.hydrogen.atoms.in.an.organic.molecule.could.be.identified,.the.chemical.structure.could.be.puzzled.together,.giving.a.major.boost.to.the.identification.of.organic.compounds This.technique.is.now.known

In.the.1950s.and.especially.in.the.1960s,.practical.instruments.were.devel-as.nuclear.magnetic resonance.(NMR).and.it.is.one.of.the.most.essential.

tools for an organic chemist With the power of modern computers, we can.now.use.NMR.to.determine.the.numbers.and.types.of.carbon.atoms,.nitrogen.atoms,.fluorine.atoms,.lithium.atoms,.and.many.more.in.an.organic.molecule To.do.this,.we.use.stable.natural.isotopes.of.these.atoms:.13C,.15N,.19F,.6Li,.etc It.is.noteworthy.that.the.important.modern.tool.of.medicine.(MRI.or.magnetic.resonance.imaging).is.in.reality.an.NMR.technique.applied.to.medicine,.and.it.was.developed.in.the.1970s

The 1950s and especially the 1960s and 1970s (although the origins of.this.method.date.to.the.1890s).saw.the.development.of.instruments.that.could.exploit.the.concept.of.bombarding.an.organic.molecule.with.a.high-energy.elec-tron.beam.to.induce.fragmentation.of.that.molecule.and.then.identifying.these.fragments.to.give.important.structural.formation This.technique.is.known.as

mass

spectrometry.and.this.methodology.has.been.greatly.expanded.and.mod-ified.in.recent.years.to.become.a.very.powerful.tool.for.structural.identification.of.organic.molecules Other.tools.are.constantly.being.developed.and.each.of.the.techniques.mentioned.has.“cutting.edge”.methodology.that.allows.a.chemist.to.probe.very.complex.structures

Other.methods.include.the.use.of.X-ray crystallography.(known.for.many.

years).to.identify.crystalline.molecules When.X-rays.interact.with.a.molecule.with.a.distinct.crystal.structure,.the.resulting.X-ray.scattering.patterns.can.often.be.analyzed.to.provide.clues.to.its.chemical.structure With.modern.com-puter.technology,.a.picture.of.the.structural.features.of.a.molecule.can.be.pro-duced.and.the.methodology.has.been.expanded.to.include.structures.of.proteins.and.even.biologically.active.small.molecules.docked.to.a.protein With.modern.electron.tunneling.microscopes,.pictures.of.atoms.have.been.made

Using.these.techniques.to.give.more.information.and.develop.new.techniques.is.another.major.area.of.organic.chemistry The.work.continues.as.new.areas.of.organic.chemistry.are.discovered,.including.studies.in.biochemistry.and.the.exploration.of.the.interface.between.molecular.biology.and.organic.chemistry

1.2  The Variety and Beauty of Organic Molecules

Section.1.1.described.how.organic.chemistry.came.to.be.a.science Why is it

important? You are alive because of chemical reactions involving organic.

molecules,.and.the.science.we.know.as.biology.results.from.organic.chemical.reactions.of.simple.and.complex.organic.chemicals The.DNA.(deoxyribonucleic.acid).and.the.proteins.in.your.body.are.organic.molecules They.are.made.and.they.work.by.a.series.of.organic.chemical.reactions Proteins.are.large.struc-tures.composed.of.many.small.organic.chemical.units.known.as.amino.acids,

such.as.serine.(27),.and.DNA.is.made.up.of.many.units.called.nucleotides,.such as.cytosine.(28).

HO

N+O

OH

OH

N O

If.you.are.blinking.an.eye.while.reading.or.moving.your.arm.to.turn.the.page,.that.nerve.impulse.from.your.brain.was.induced,.in.part,.by.one.of.sev-eral.important.organic.molecules.called.neurotransmitters One.important.neu-

rotransmitter.is.acetylcholine.(29) If.you.see.this.page,.the.light.is.interacting with.a.photopigment.in.your.eye.called.rhodopsin,.which.releases.retinal.(30).

upon.exposure.to.the.light Retinal.reacts.with.a.lysine.fragment.(another.amino.acid;.see.Chapter.27).of.a.protein.as.part.of.the.process.we.call.vision Note.the

similarity.of.retinal.to.vitamin.A.(2),.which.is.simply.the.reduced.form.of.30

Oxidation.and.reduction.are.discussed.in.Chapters.16.and.18,.respectively

in 31 means there is an interaction between N and Mg (a coordinate bond).

rather.than.a.formal.covalent.N–Mg.bond Many.other.things.about.human.physiology.involve.organic.chemistry There.are.more.fundamental.physiologi-cal.influences.of.organic.chemicals If.you.are.female,.one.of.the.principal.sex.hormones.for.your.gender.is.β-estradiol.(32),.but.if.you.are.male,.your.principal

38 39

O

CCl3Cl

Cl

Cl Cl

Cl Cl

Many.things.around.you.involve.subtle.uses.of.organic.molecules If.you.see.a.housefly,.know.that.it.uses.a.chemical.called.a.pheromone.(in.this.case,.mus-

The.term.PCB.(41;.short.for.polychlorinated.biphenyl).is.in.the.news.as.

an.environmental.pollutant PCBs.have.been.used.as.pesticide.extenders,.but.also in transformers and as stabilizers in poly(vinyl chloride) coatings (PVC.coatings) When PCBs leach into soil and water, they have serious environ-mental.consequences Yet,.chemicals.such.as.these.have.played.a.positive.role

in the industrialization of humans, as well as the negative role described Understanding.these.chemicals,.how.they.work,.and.when.to.use.them.is.obvi-ously.important.and.a.thorough.understanding.of.organic.chemistry.is.impor-tant This.understanding.and.the.research.that.flows.from.it.are.important.if.we.are.to.develop.new.and.environmentally.safer.compounds

H

H

NH2

O N H

CH3

CH3

(44) Do you like the taste of red chili peppers?.If.so,.the.hot.taste.is.due to.an.organic.chemical.called.capsaicin.(45) In.both.cases,.these.chemicals.

interact.with.your.taste.buds.to.produce.that.characteristic.taste Capsaicin.is.also.found.in.some.topical.creams.used.to.alleviate.symptoms.of.arthritis.and.muscular.aches

O OH

H O

O OH

H O

Most.medicines.used.today.are.organic.chemicals Clearly,.this.is.of.vital

importance.to.the.health.and.well-being.of.humans Do you have a headache

after reading all of this stuff?.If.so,.you.are.probably.looking.for.a.bottle.of.

aspirin.(4).or.Tylenol.(which.contains.acetaminophen,.46) Have you been to

the dentist recently?.If.so,.you.might.have.had.a.shot.of.Novocain.(47;.the.

actual.name.of.this.chemical.is.procaine.hydrochloride).so.that.you.would.not.feel.the.pain.(it.is.a.local.anesthetic) If.you.have.recently.been.ill,.your.physi-cian.may.have.given.you.a.prescription.for.an.antibiotic Commonly.prescribed

cline.antibiotic.such.as.aureomycin.(50).

antibiotics.could.include.amoxicillin.(48),.penicillin.G.(49),.or.even.a.tetracy-Clearly, much more serious and devastating diseases can afflict humans

Has a friend or relative been treated for cancer? The physician might.

have.used.vinblastine.(51).to.treat.the.cancer Do you smoke?.If.so,.you.are breathing.nicotine.(52).as.well.as.many.other.organic.compounds.into.your.lungs, which.then.make.their.way.into.your.bloodstream Have you heard of the use

of AZT for the treatment of AIDS?.The.structure.of.AZT.is.shown.in.53.

50 51

OH N

CH3

H3CO N N

H

H OH O

OH

H O OCH3

O

CH3

O OCH3

has.the.chemical.structure.55.

N

N

CH3H

O HO

N3

N

N O

O

O

O

CH3O

N H

natural.rubber.is.poly(isoprene).(57) You.might.be.using.a.piece.of.paper.to.

describe.your.thoughts.about.organic.chemistry.at.this.moment If.so,.you.are

probably writing on something with cellulose (58) in it Notice that rayon is.

essentially.a.derivative.of.cellulose,.the.main.constituent.of.wood.fiber When.you.crumple.up.the.paper.and.throw.it.into.a.“plastic”.waste.container,.that

container.might.be.made.of.poly(ethylene).(59).

This page intentionally left blank

The.operational.theme.of.this.book.is.that.under-standing acid and base chemistry will lead to.

a better understanding of organic chemistry

Applying acid–base principles to many reactions

allows one to understand and predict the

reac-

tion.rather.than.simply.memorizing.it To.exam-ine.this.premise,.the.acid–base.reactions.found.in

general chemistry must be reexamined to

deter-mine how they can be applied directly or when

• Define and recognize the structures

of simple Brønsted–Lowry acids and

bases as well as simple Lewis acids

and bases.

• Understand the definitions of

conju-gate acid and conjuconju-gate base.

• Understand the fundamentals of acid–

base strength in aqueous media.

• Understand the role of water in acid–base equilibria.

• Understand K a and pK a and how to manipulate them.

• Recognize classical mineral acids.

• Recognize classical Brønsted–Lowry bases.

This.chapter.will.review.the.principles.of.acid–base.chemistry.from.general.chemistry.in.order.to.make.a.link.with.modern.organic.chemistry The.chapter.will.introduce.the.theme.of.acid–base.chemistry.as.a.basis.for.understanding.each.chemical.transformation.where.it.is.appropriate

ing.points:

When.you.have.completed.this.chapter,.you.should.understand.the.follow-• There is an inverse relationship between K a and pK a , and a large

K a or a small pK a is associated with a stronger acid.

• It is important to put water back into the acid–base reaction for

aqueous media.

• The fundamental difference between a Brønsted–Lowry acid

and a Lewis acid is that the former is a proton that accepts trons and the latter is any other atom that accepts electrons The fundamental difference between a Brønsted–Lowry base and a Lewis base is that the former donates electrons to a pro- ton and the latter donates electrons to another atom.

elec-• Curved arrows are used to indicate electron flow from a source

of high electron density to a point of low electron density.

• Acid strength in an acid X–H is largely determined by the

sta-bility of the conjugate acid and base and the strength of the X–H bond For example, HI is a stronger acid than HF due to

a weaker X–H bond and charge dispersal in the larger anionic conjugate base An acid such as perchloric acid is stronger than sulfuric acid due to charge dispersal in the conjugate base that results from resonance.

• Base strength is largely determined by the stability of the

con-jugate acid and base and the electron-donating ability of the basic atom Water is a stronger acid than ammonia because hydroxide ion is more stable than the amide anion and the

OH bond is weaker than the NH bond Ammonia is a ger base than water because oxygen is more electronegative than nitrogen, and the ammonium ion is more stable than the hydronium ion.

stron-• Reaction of a Lewis acid and a Lewis base leads to an ate

com-plex as the product.

• Acid–base reactions have biological relevance.

2.1  Acids and Bases in General Chemistry

rial.that.can.release.a.proton.or.hydrogen.ion.(H+) When.hydrogen.chloride.(HCl) is dissolved in water, a solution is formed via ionization that leads

In.1884,.Svanta.Arrhenius.(Sweden;.1859–1927).defined.an.acid.as.a.mate-to hydrated hydrogen ions and hydrated chloride ions Using the original.definition, a base (then called an alkali) is a material that can donate a.hydroxide.ion.(–OH) Sodium.hydroxide.in.water.solution.ionizes.to.hydrated.sodium ions and hydrated hydroxide ions This concept led to a definition.of.acids.and.bases.as.reported.independently.in.1923.by.Thomas.M Lowry.(England; 1874–1936) and Johannes Nicolas Brønsted (Denmark; 1879–1947) According to this definition, an acid is a material that donates a proton and a base is a material that can accept a proton1,2—the Brønsted–Lowry defi- nitions mentioned before..If.a.high.concentration.of.hydrogen.ions.is.observed.when.an.acid.is.added.to.water.(an.aqueous.solution.of.the.acid),.that.acid

must.have.an.ionizable hydrogen (known.as.a.proton) Such.acids.typically.

take.the.form.H–X,.where.X.is.an.atom.other.than.carbon.or.hydrogen.(O,.S,.N,.etc.)

2.1 Write out the structures of hydrochloric acid, hydrobromic acid, sulfuric acid, and nitric acid

According.to.Brønsted.and.Lowry,.an.acid–base.reaction.is.defined.in.terms.of.a.proton.transfer By.this.definition,.the.reaction.of.HCl.in.water.is.the.following:

HCl(aq) + H2O Cl–(aq) + H3O+(aq)

Water is the base in this reaction.istry.are.always.done.in.water When.a.Brønsted–Lowry.acid.such.as.HCl.is.placed.in.water,.a.proton.is.transferred.to.a.water.molecule.(water.is.the.base);.a.conjugate.acid.is.formed.(the.hydronium.ion.H3O+).as.well.as.a.conjugate.base.(the.chloride.ion) In.neutral.pure.water.(no.acid.is.present),.the.hydrogen.ion.concentration.is.about.1.0.×.10–7.M.(pH.of.7) An.increase.in.the.concentration.of.hydrogen.ions.above.1.0.×.10–7.M.gives.an.acidic.solution,.with.a.pH.less.than 7 If.the.pH.is.greater.than.7,.it.is.considered.a.basic.solution

.Acid.and.base.reactions.in.general.chem-2.2 What is the conjugate base formed when HCl reacts with ammonia?

If the criterion for acid strength is the extent of ionization in water, the.mineral acids HCl, HBr, HI, H2SO4, HNO3, and HClO4 are all strong acids Likewise,.strong.bases.are.extensively.ionized.in.water;.common.strong.bases.include.NaOH.(soda.lye),.KOH.(potash.lye),.LiOH,.CsOH,.Mg(OH)2,.Ca(OH)2,.and Ba(OH)2 Using the definitions given previously, weak acids and weak.bases.will.ionize.to.a.lesser.extent.in.water.relative.to.the.strong.acids.or.bases Indeed,.weak.acids.are.solutes.that.react.reversibly.with.water.to.form.H3O+ ions