CHEM 222, Organic Chemistry II - · PDF file2/1/2016 · textbook problems most closely resemble ... • Organic chem. requires daily attention & practice – don ......

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CHEM 222, Organic Chemistry II Instructor Dr. Pat Forgione Office hours: T, 1:15 - 2:15 or by email appointment, put CHEM222 in subject line of all emails!) Contact info: SP-275.11, ×5802, [email protected]

Course Format Lectures: 2.5 h / week, Mond. 18:00-20:30 in HC-157 Labs: 4 h / week, starting January 19th, check your portal for section

Materials required 1)  Chem 222 Course 2) Lab text: J. W. Lehman, Operational Organic Chemistry, 3rd Ed. 3)  Lab manual: Organic Chemistry II, Dept. of Chem. & Biochem. 4)  any molecular model kit, PLUS lab coat & safety glasses

Useful resources 1) Course website (moodle): lecture notes, handouts, problem sets

2) SmartWorks Website http://smartwork.wwnorton.com/sw/ 3) Other texts (Vanier library reserve): alternate explanations, etc.

4) Jones/Fleming, Organic Chemistry, 4th or 5th Edition + solution manual 5) Strategic learning (SL) sessions

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CHEM 222, Organic Chemistry II GRADING SCHEME, DEADLINES & ABSENCES To pass: ≥ 50% theory AND ≥ 60% laboratory work (>50% lab exam)

Weighting: 9-10 On-Line Quizzes: Pre-Req quiz (2%) plus best 6/8 (3%) bonus added to final grade if you complete all 8 (up to 0.2% each). In-Class Quizzes: 10% (2 x 5 % each, 10 multiple choice, 1 short answer) Mid-term Exam: 20% (during class March 2nd) Lab Marks: 25% (reports 15%; lab exam 10% March 30th) Final Exam: 40% (3h, April/May, cumulative)

Details: Keep up with the homework! The course quizzes (online and in-class) are to help you keep up with the material so you don’t fall behind, however the textbook problems most closely resemble the problems you should expect on the exams. If absent from an exam / lab: official, signed note (doctor / employer)

No later than one week after exam / lab. No valid excuse produced: zero grade..

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INTRODUCTORY ORGANIC CHEMISTRY II – Chem 222

LABORATORY INFORMATION -- 4h every week, Coordinator: Maria Dochia (All initial questions to her.)

Lab sections: you must attend your registered section only Problems, notes, exemption requests: see Rita ASAP

Lab absence: max. 1; bring medical / employer note, or receive zero Lab grades: based on quality of the experimental work AND report Lab TA: 1-2 per lab section; get their contact information Preparation: pre-lab, lab coat & glasses required, or entrance denied

Your safety is important to us and this means NO EXCEPTIONS to the lab preparation requirements!

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LECTURE INFORMATION: SCHEDULE, READINGS, PROBLEMS

•  Use lecture schedule to plan readings & study schedule. •  Print slides (if any) before class, & take DETAILED NOTES in class ! •  Read textbook Preface, “To the student” - suggestions on how to use

textbook & excellent advice on how to study organic chemistry. •  Organic chem. requires daily attention & practice – don’t just cram !

Strategic Learning

Counselling and Development

Website: cdev.concordia.ca

Location: AD-103 (Loyola) & H-440 (SGW)

Services: Ø New students Ø Counselling Ø Job search & resume building Ø Learning support → STRATEGIC LEARNING

(SL) Concordia Counselling and Development ·∙ cdev.concordia.ca ·∙ AD-‐103 & H-‐440

Counselling and Development

Concordia Counselling and Development ·∙ cdev.concordia.ca ·∙ AD-‐103 & H-‐440

What are SL sessions?

Ø Collaborative study groups outside class time

Ø  Facilitated by student leader

Ø Offered in dif-icult/demanding courses

Ø Attendance -‐ voluntary but highly

recommended


Why should you a:end SL?

SL

5%



Ø  Higher grades on average

Ø  Less likely to drop/fail the course

Ø  Save time by focusing on important topics

Ø  Network/connect with other students

Ø  Acquire effective & efficient study skills for

university success Concordia Counselling and Development ·∙ cdev.concordia.ca ·∙ AD-‐103 & H-‐440



Non-‐SL Group -‐ 58%

Non-‐SL Group 41.80%

SL Group -‐ 39.60%

SL Group -‐ 60.40%

0% 10% 20% 30% 40% 50% 60% 70%

D F DISC

A B C

Percentage of Group

Fina

l Grade

GEOG 272 Final Grade DistribuDon (Winter 2010)

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STRATEGIC LEARNING (SL) http://learning.concordia.ca/SL_basics.shtml CHEM 222- Fall 2008

Dr. Pat Forgione SL Attendance vs. Final Grade

50

55

60

65

70

75

80

85

90

Non-SLAverage

ClassAverage

SLAverage

Attend >5Sessions

Attend>10

Sessions

Attend>15

Sessions

Attend>20

Sessions

Attend>25

Sessions

Number of Times Attended SL

Fina

l Gra

de

Jones and Fleming, Organic Chemistry, 4th Edition 1. Atoms & Molecules; Orbitals & Bonding (Jones - Chapter 1) 2. Alkanes (Jones - Chapter 2) 3. Alkenes & Alkynes (Jones - Chapter 3)

4. Stereochemistry (Jones - Chapter 4) 5. Rings (Jones - Chapter 5) 6. Alkyl Halides, Alcohols, Amines, Ethers (Jones - Chapter 6) 7. Nucleophilic Substitution and Elimination Reactions (Jones - Chapter 7) 8. Equilibria (Jones Chapter 8) 9. Addition to Alkenes and Alknes (Jones - Chapter 9 & 10) 10. Radicals (Jones - Chapter 11)

Sections of Textbook you should already know…

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CHEM 222 LECTURE #01

INTRODUCTORY ORGANIC CHEMISTRY II ASAP: Review Chem 221…

- drawing organic structures - acidity/basicity, nucleophilicity - reactions: electrophilic additions substitutions, eliminations - mechanisms: step-by-step electron (e-)-pushing

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Remembering how to draw organic structures §  Remember the rules:

§ 2nd row elements cannot exceed octet rule ! § Trends: C (4 bonds), N (3 bonds, 1 LP), O (2 bonds, 2 LP), X (1 bond,3 LP) § Against trend: atom will have formal charge +/- open valence § Most stable structure: minimized formal charges, atoms with full valence

§  Resonance structures: § Only lone pairs & π-electrons move (nuclei & σ-bonds stay unchanged) § Most stable structure contributes most to the resonance hybrid (reality) §  Less stable structures still contribute to reactivity patterns…

§  Representing structures: formal charges always shown, but… § Kekule structures: Lewis structures without LPs - except if involved in rxn § Skeletal (line) structures: bonds as lines, C’s & H’s not shown § 3-D drawings: dashes/wedges/lines to visualize geometry & stereochem. §  Condensed formulae: summarize connectivity without pictures

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Substituent (hydrocarbon-based group) (symbol, abbreviation & name)

Class of compounds Comments

―(CH2)nCH3

or branched… ―R alkyl CnHn+2 Alkanes See Table 2.2

―CH3

―CH2CH3 ―Et ethyl

―(CH2)2CH3 ―Pr propyl

―CH(CH3)2

―(CH2)3CH3 ―Bu butyl

―C(CH3)3

―t-Bu tert-butyl

―CH=CH2 vinyl R2C=CR2 Alkenes

―C≡CH acetylide RC≡CR Alkynes

―C6H5 ―Ph

“ ”

C6H5R Aromatic hydrocarbons

Discussed in Chem222

A benzene ring as a substituent…

R

Must know these!

Discussed in Chem221

Remembering functional groups: 1) hydrocarbons

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Functional group (symbol & name)

Class of compounds (based on functional gp)

Descriptors

―X Halide R―X 1o

2o

3o

RCH2-X R2CH-X R3C-X

―OH

R―OH

Alcohols 1o

2o

3o

RCH2-OH R2CH-OH R3C-OH

―NH2

R―NH2

Amines 1o

2o

3o

R-NH2 R2NH R3N

―O―

Oxy R―O―R Symmetric Asymmetric

R-O-R R-O-R’

O ll ―C―

Carbonyl

O ll R―C―R

Ketones; OR

if ≥1 R=H: Aldehydes

O ll Acyl halides OR R―C―X Acid halides

O ll ―C―OH

Carboxyl

O ll R―C―OH

Carboxylic acids

O ll R―C―OR Esters

O ll R―C―NR2 Amides

―C≡N Cyano R―C≡N Nitriles

―NO2

Nitro

R―NO2 Alkyl nitrates

Chemistry discussed later in Chem222

Remembering functional groups: 2) with heteroatoms

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Remember the general principle of reactivity: δ- δ+ Nucleophiles attack electrophiles

Nucleophiles: “Nu” §  electron-rich atom or functional group

•  lone pair of e- (a base of some sort) ? •  polarizable π-electrons (alkenes, etc) ?

§  functionally δ-, even if no true polarity §  Nu’s ATTACK δ+ REGIONS

To predict reactivity: Draw polarity on molecule! §  If non-polar: identify polarizable e-s §  Can be activated by more reactive rgt

Electrophiles: “E+” §  electron-deficient

•  empty orbital ? •  positive charge ?

§  functionally δ+ §  E+’ s GET ATTACKED

Weak Nu / E+’s are still reactive: §  if presented with stronger E+ / Nu’s §  OR at high concentrations §  OR at elevated temperatures

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A stronger base = a better Nu

Provided: §  low steric demand (backside attack...) §  not overly screened by the solvent

TRENDS in basicity & nucleophilicity (except #3: Nu’s only, in protic solvent)

•  A - charged Nu is stronger than a similar neutral species (…more δ-). •  More electronegative atoms are less nucleophilic (…hold e-s tightly). •  Larger, more polarizable atoms are more nucleophilic (…shielded less).

Bruice 8.3

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Remembering relative acidities: pKas (see Appendix II)

hydrogen H–H 35 conj.base H– eg. NaH sodium hydride

What could deprotonate acetone?

When did you complete the essential pre-requisite for this course, Chem221 (Org 1) or its equivalent?

A.  0 - 6 months ago B.  6 - 12 months ago C.  12 - 18 months ago D.  18 - 24 months ago E.  > 24 months ago

How scared of Chem222 are you?

A.  Not at all, I love Organic Chemistry! B.  Somewhat C.  What is Chem222? D.  Scared to death E.  Still too hungover from NYE to care at this point

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Polar Covalent Bonds

•  An unequal sharing of electrons between two atoms leads to a polar bond.

•  The more electronegative atom “holds” bonding electrons closer (leads to a dipole moment).

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Resonance Structures •  More than one Lewis structure can be used

to represent a given species. •  Each valid Lewis structure is a different

resonance form. •  Atoms remain in the same place between

resonance forms.

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Resonance Structure Formalism

•  Resonance arrow(s), curved arrow formalism/electron pushing, lone-pairs, and formal charge (where applicable) are shown to indicate relationships between forms

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Determining the Most Likely Resonance Structure •  The more bonds in a resonance form, the more

likely it is the major resonance form. •  Less charge separation is preferred.

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Determining the Most Likely Resonance Structure (cont.)

•  In ions, delocalization of electrons is important. •  Negative charge is more stable on a more

electronegative atom. •  Resonance forms that are equivalent contribute to a

resonance hybrid. •  All resonance forms for a given species must have

the same number of paired and unpaired electrons.

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Acids and Bases

•  An atom or molecule that is an electron pair donor is a Lewis base.

•  An atom or molecule that is an electron pair acceptor is a Lewis acid.

•  Electrophiles are Lewis acids. •  Nucleophiles are Lewis bases.

The SN2 Reaction (cont.)

•  This Substitution with a Nucleophile involving 2 species in its rate law is called the SN2 reaction.

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SN2 Reaction Stereochemistry (cont.)

•  The inversion of stereochemistry can help us posit a mechanism for the SN2 reaction. A concerted reaction featuring backside attack by the nucleophile would be consistent with the observation:

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C C

(+)-Carvone(Caraway)

(-)-Carvone(Spearmint)

Mirror PlaneO O

HH

Left Hand Right Hand

Mirror Plane

Organic Molecules Can Have “Handedness” - They Can Be “Chiral”. Pair of Chiral Molecular are Referred to as Enantiomers.

Tetrahedral Carbon Centers Possessing Four Different Groups Can Exist as Non-Superimposable Mirror Images – They are Enantiomers.

Organic Chemistry In Our Everyday Life Professor Michael J. Krische

C C

(+)-Carvone(Caraway)

(-)-Carvone(Spearmint)

Mirror PlaneO O

HH

Left Hand Right Hand

Mirror Plane

Organic Molecules Can Have “Handedness” - They Can Be “Chiral”. Pair of Chiral Molecular are Referred to as Enantiomers.

Tetrahedral Carbon Centers Possessing Four Different Groups Can Exist as Non-Superimposable Mirror Images – They are Enantiomers.


Slide used with permission of Dr. M. Krische, U. Texas at Austin

SN2: Effect of Leaving Group (LG) (cont.)

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SN2 on Alcohols: LG Activation

•  A hydroxyl group can also be changed to a good leaving group by a two-step route with a sulfonyl chloride:

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SN2 on Alcohols: LG Activation (cont.)

•  Or with thionyl chloride:

•  Reagents such as PBr3, PCl5, or PPh3/CCl4 also work.

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The SN1 Reaction

•  An odd observation is that bulky tertiary bromides do not react with good nucleophiles, but do react with poorer nucleophiles!

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The SN1 Reaction (cont.)

•  A mechanism consistent with this rate law would be unimolecular ionization to form a carbocation prior to Nu attack:

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SN1 Stereochemistry

•  The different mechanism of the SN1 reaction led to a different stereochemical outcome than SN2:

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The properties of organic molecules depend upon their structures

Digitoxin - A Drug Based onDigitalis Extract Used toTreat Congestive Heart

Failure and Atrial Fibrillation

H3C

OH

H3C

OO

H3C

OHO

H

H

O

O

OH3C

OHO

OH3C

OHHO

HH

Purple Foxglove, i.e.Digital is Purpur ea

Glycone - Modulates DrugDelivery and Metabolism

Steroidal Aglycon -The "War-Head" of

Digitoxin

Plant Extraction

A Broad Scientific Question: What is the nature of matter? Organic Chemistry: The study of carbon containing compounds. Since virtually all naturally occurring compounds contain carbon, organic chemistry is inextricably tied to living systems. N

C

N

O

O

O OH

NC

N

O

O

OOH

(+)-Thalidomide(Sedative, anti-Nausea)

(-)-Thalidomide(Severe Birth Defects)

H H

Mirror Plane

OH HS

Antidote forHg Poisening

Optical Atrophy(Blindness)

Mirror Plane

O

HO

O

SH

H3CH3C

NH2H H2N HCH3CH3

Different Enantiomers Can Have Wildly Different Biological Profiles

O

O

OH

NH

O

OO

O

CH3

OH

OOOHH

OOO

H3CIf a molecule has n-chiral centers, there are 2n possible combinations possible, termed “stereoisomers.” The FDA now requires that chiral molecules be prepared as single entities. Over 50% of the world’s top-selling drugs are single enantiomers and it is estimated that 80% of all drugs currently entering development are chiral and will be marketed as single-enantiomer entities. Taxol - Bark of Pacific Yew Tree Potent Anti-Cancer Agent 11 Stereocenters → 2048 Possible Isomers!

Organic Chemistry In Our Everyday Life Professor Michael J. Krische ç


SN1 Stereochemistry and R Group (cont.)

•  The R group has a strong effect on rate. More stable cations are formed much more quickly:

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Summary: SN1 vs. SN2

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Summary: SN1 vs. SN2 (cont.)

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Unimolecular Elimination: E1 (cont.)

•  In the case of the SN1 reaction, the competing elimination follows a unimolecular rate law and is called the E1 reaction.

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•  Because Nu deprotonates the carbocation in E1, it is favored where the nucleophile is more basic.

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(Product is formed mostly via E2; 93:7 is the ratio of the small percentage of product that forms via E1 and SN1)


•  Often there are multiple potential alkenes that could form in an E1 reaction. The more stable (more substituted) alkene is formed (Saytzeff Rule):

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Bimolecular Elimination: E2 (cont.)

•  The mechanism of the E2 reaction is thought to be:

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Oenanthotoxin: Oenanthotoxin is a toxin extracted from Oenanthe crocata; it is a central nervous system poison that causes facial muscles spasm resulting in a grinning appearance, a trait that is anciently known as risus sardonicus – the “sardonic smile”. This plant was used in ritual killings in ancient pre-Rome times in Sardinia. Elderly citizens who were unable to support themselves were seen as a burden to society. Hence, they were intoxicated with this sardonic herb prior to being killed by beating or dropping from a high rock, so they would have a defiant grin in the face of death. Researchers later discovered that the plant toxins oenanthotoxin and dihydrooenanthotoxin block the receptors to the neurotransmitter -aminobutyric acid (GABA), which is directly involved in muscle tone regulation. The sardonic smile could be explained on the basis of this observation.

Organic Chemistry In Our Everyday Life Professor Michael J. Krische ç


Effects on E2/–SN2 Ratio

•  The SN2 reaction is hindered by substrate branching and substitution more than the E2 reaction:

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Effects on E2/–SN2 Ratio (cont.)

•  With less substituted halides, SN2 becomes more competitive:

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E2 Stereochemistry

•  In the E2 reaction, the relative orientation of the two eliminated groups is important:

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E2 Stereochemistry (cont.)

•  Because of the orbitals involved in the transition state, the two groups to be eliminated must be antiperiplanar:

49

E2 Selectivity

•  The Saytzeff Rule typically governs selectivity in E2:

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E2 Selectivity (cont.)

•  A product that is not the one favored by the Saytzeff rule is called the Hoffmann product. The bulkier the base, the more of the Hoffmann product is formed…

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E2 Selectivity (cont.)

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Organic Synthesis (cont.)

•  One especially important substitution reaction is the Williamson Ether Synthesis:

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Regiochemistry in Addition of HX to Alkenes •  If the two sides of a double bond are differently

substituted, there are two possible cations that could be formed:

Resonance and Stability of Carbocations (cont.)

•  In cases where carbocation stabilization by resonance is not possible, the more substituted carbocation is more stable:

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Hydration

•  Hydrohalogenation is not the only type of addition reaction involving alkenes

•  Catalytic acid is necessary to create the carbocation intermediate; water is not a strong enough acid on its own

Hydration (cont.)

•  A hydration reaction involving addition of water to an alkene to make an alcohol is possible, but requires an acid catalyst:

Hydration (cont.)

•  Acid-catalyzed hydration follows Markovnikov’s Rule (adds more eletronegative atom to the more substituted side):

Hydroboration

•  Consider borane (BH3), a compound you may have learned about in general chemistry as being an ‘exception’ to the octet rule because in it, B has only 6 valence electrons:

Hydroboration (cont.)

•  Because of the empty p orbital on the B, borane is a good Lewis acid.

•  We have seen alkenes act as Lewis bases. What happens when borane and an alkene undergo a Lewis acid-base reaction?


•  The reaction proceeds via a concerted pathway:


•  This reaction is regiospecific, with the B adding to the less substituted side of the double bond (H is more electronegative than B):


•  The greater stability of positive charge on the more substituted side helps rationalize this observation:


•  Because addition of H and BH2 fragments is concerted, the reaction proceeds stereoselectively:


•  The proposed concerted mechanism accounts for this:

Hydroboration in Alcohol Synthesis •  Once alkyl boranes are formed, the boron can

be replaced with other groups, such as an OH to make an alcohol:

Hydroboration in Alcohol Synthesis (cont.)

•  The net result of the mechanism of this oxidation is that the OH ends up where the boron was attached to carbon:

Hydroboration in Alcohol Synthesis (cont.)

•  The net result of the hydroboration / oxidation is the formation of the “anti-Markovnikov” alcohol:

Addition of H2 to Alkenes

•  Alkenes do not react with hydrogen gas alone, but H atoms can add in the presence of a heterogeneous or homogeneous catalyst:

Addition of X2 to Alkenes

•  Alkene halogenation by reaction with X2 (X = Cl or Br) leads to vicinal dihalides:

CHEM 222, Organic Chemistry II - · PDF file2/1/2016 · textbook problems most closely resemble ... • Organic chem. requires daily attention & practice – don ......

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