EM 232 Organic hemistry I at hicago Lecture 9 Organic hemistry 1 Prof. Duncan J. Wardrop 02/09/2010 1
Functional Group larification Although they can be viewed as ethers, epoxides are classified as distinct, three-atom functional groups... O O Ether Epoxide q. Why? a. Epoxides display distinctly different reactivity to ethers, which arises from their considerable ring strain. University of Illinois at hicago EM 232, Spring 2010 Slide 2 Lecture 5: January 26 2
Defining Regioselectivity Regioselectivity (regioselective) A regioselective reaction is one in which one direction of bond making or breaking occurs preferentially over all other possible directions. Reactions are termed completely (100%) regioselective if the discrimination is complete, or partially (<100%), if the product of reaction at one site predominates over the product of reaction at other sites. The discrimination may also semi-quantitatively be referred to as high or low regioselectivity. IUPA ompendium of hemical Terminology 2nd Edition (1997) O Br N O l 4, hν l l l Regioselective hlorination......not stereoselective! at hicago EM 232, Spring 2010 Slide 3 3
Mechanism of Alkane hlorination Initiation l l homolysis light (hν) l + 7 valence electrons l Propagation l l l hydrogen abstraction 3 3 3 ~1,000,000 cycles per initiation step halogen abstraction l 7 valence electrons 3 + + l l at hicago EM 232, Spring 2010 Slide 4 Note that typically, this type of chain reaction can continue for 1,000,000 steps for each initiation event. 4
Useful Bond Dissociation Energies: - (1 ; 423 kj/mol); - (2 ; 410 kj/mol); - (3 ; 397 kj/ mol); -l (431 kj/mol); -Br (366 kj/mol); Br-Br (192 kj/mol) Factors Governing Regioselectivity l 2 hν l + l 45% 55% Strength of - Bond Broken l 2 hν l + l Number & Type of Substrate - Bonds Br 2 63% Br 37% + Br Strength of -X Bond Formed and X-X Bond Broken hν >99% <1% at hicago EM 232, Spring 2010 Slide 5 Remember that regioselectivity is only an issue in those substrates that more than one type of - bond. yclohexane, for example, undergoes monochlorination to yield on cyclohexyl chloride. 5
Bromination is More Selective Than hlorination l Br chlorination bromination 3 3 3 3 = early transition state structures = late transition state structures 3 2 3 3 Relative Rates (k rel ) of alogenation R 3 (tertiary, 3º) R 2 2 (secondary, 2º) Ea (chlorination) Ea (bromination) Ea (bromination) > Ea (chlorination) Bromination is more selective. R 3 (primary, 1º) 5.2 3.9 1.0 1640 82 1.0 ammond Postulate chlorine radicals are higher in energy than bromine radicals = transition states in chlorination are earlier = look more like reactants = less difference in TS energy = less selective = greater mixture bromine radicals are lower in energy than chlorine radicals = transition states in bromination are later = look more like products (radical interm.) = greater difference in TS energy = more selective = less of a mixture at hicago EM 232, Spring 2010 Slide 6 6
Quantifying Selectivity of alogenation Relative Rates (krel) of alogenation R3 R22 (tertiary, 3º) (secondary, 2º) 5.2 3.9 1.0 1640 82 1.0 chlorination bromination Predicted Product Ratios R3 (primary, 1º) Product Relative Yield Absolute Yield % = (krel) x (statistical factor) total chlorination A (2 2º s) 2 x 3.9 = 7.8 7.8/13.8 = 57% B (6 1º s) 6 x 1 = 6.0 6.0/13.8 = 43% Sum 13.8 100% l 2 3 3 l 3 3 + 3 2 l A: 57% B: 43% bromination A (2 2º s) 2 x 82 = 164 164/170 = 96% B (6 1º s) 6 x 1 = 6.0 6.0/170 = 4% Sum 170 100% Br Br 2 + 3 3 3 3 3 2 Br A: 96% B: 4% at hicago EM 232, Spring 2010 Slide 7 7
Self Test Question Determine the predicted product distribution for A in the following chlorination. Br 2 Br A + Br Relative Rates (k rel ) of alogenation R 3 R 2 2 R 3 (tertiary, 3º) (secondary, 2º) (primary, 1º) chlorination 5.2 3.9 1.0 bromination 1640 82 1.0 B A. >99% B. 97%. 95% D. 93% E. 91% at hicago EM 232, Spring 2010 Slide 8 Relative Rates for 3 and 1 positions = 1640 and 9, respectively. Absolute yields = 99.4% and 0.6%. The Answer is A. 8
EM 232 Organic hemistry I at hicago hapter 5 Nomenclature & Stereoisomerism in Alkenes Section 5.1-5.11 9
The Terms Alkene and Olefin are Synonymous ethylene 2 4 Alkenes are hydrocarbons that are characterized by a - double bond Also called olefins General molecular formula = n2n Described as unsaturated since they have two fewer atoms than equivalent alkanes at hicago EM 232, Spring 2010 Slide 10 10
Index of ydrogen Deficiency (ID) ID is synonymous with degrees of unsaturation and indicates the number of double/triple bonds and/or rings in a molecule ID = 1 (1 double bond) ID = 4 (3 double bonds & 1 ring) ID = 2 (2 rings) ID = 1 (one ring) at hicago EM 232, Spring 2010 Slide 11 11
alculating ID 1. ydrocarbons ( n x ) and Oxygenates ( n x O y ): Ignore O (2n+2) - X ID = 2 2. ompounds with N ( n x N y ): Subtract # N from # ID = (2n+2) - (X-Y) 2 3. alogens ( n x X y ): Add # alogens to # ID = (2n+2) - (X+Y) 2 at hicago EM 232, Spring 2010 Slide 12 12
ID & The hemistry of Margarine Employing equation 1 (slide 12)... O O linolenic acid m.p. -11 O linoleic acid m.p. -5 O oleic acid m.p. 16 O stearic acid m.p. 71 1830O2 ID = 4 2 / Ni O 1832O2 ID = 3 2 / Ni O 1834O2 ID = 2 2 / Ni O 1836O2 ID = 1 at hicago EM 232, Spring 2010 Slide 13 13
IUPA Naming of Alkenes 1 2 4-chloro-1-pentene or 4-chloropent-1-ene Steps: 1. Number longest chain that includes both alkene carbons so that they have the lowest locants. 2. Replace -ane ending of parent alkane with -ene (alkene). 3. In the name, list the locant of only the first alkene carbon. onventions/rules: l 3 4 5 2 3 alkenes have higher priority over alkane and halide substituents when numbering the longest chain alcohols have higher priority over alkenes when numbering the longest chain locant may be placed in front of parent name (e.g. 2-pentene) or in front of suffix (e.g. pent-2-ene). l locant substituent 1st alphabetically parent base alkene locant ene University of Illinois at hicago EM 232, Spring 2010 Slide 14 Lecture 8: February 4 14
IUPA Naming of Alkenols 6 5 4-hexen-2-ol or hex-4-en-2-ol Steps: 1. Number longest chain that contains both the alkene and the alcohol and so that the alcohol group has lowest locant value. 2. Replace -ane ending of parent alkane with -ene (alkene). 3. In the name, list the locant of only the first alkene carbon. onventions/rules: alkenes have higher priority over alkane and halide substituents when numbering the longest chain alcohols have higher priority over alkenes when numbering the longest chain locant may be placed in front of parent name (e.g. 2-pentene) or in front of suffix (e.g. pent-2-ene). when ene does not occur at the end of a name, drop the last e parent base 4 3 2 O 1 alkene locant en O 3 2 3 3 -O locant ol University of Illinois at hicago EM 232, Spring 2010 Slide 15 Lecture 8: February 4 15
IUPA Functional Group Priorities for Numbering Longest hains Priority Functional Group Suffix Substituent Name Increasing Priority 3 halide n.a. halo 3 alkane -ane alkyl 2 alkene -ene -en (or alkenyl) 1 alcohol (-O) -ol hydroxy We will add to this table as we encounter more functional groups in IUPA nomenclature. at hicago EM 232, Spring 2010 Slide 16 16
ommon Alkenyl Group Names Vinylic -atoms R R Methylene R R R Vinyl R Allylic -atoms R Allyl R R Propenyl R at hicago EM 232, Spring 2010 Slide 17 17
Alkene Structure & Bonding carbons in an alkenes are sp 2 hybridized bond angles are ~120º around sp 2 hybridized carbons geometry around sp 2 -carbons is planar (flat) 110 pm 117.2 121.4 134 pm at hicago EM 232, Spring 2010 Slide 18 18
Double Bond = 1 π-bond + 1 σ-bond A double bond is formed by two orbital overlaps 1 pi (π) bond side-to-side overlap of two p-orbitals; 2 π-electrons 1 sigma (σ) bond head-to-head overlap of two sp 2 -orbitals at hicago EM 232, Spring 2010 Slide 19 19
Bond Rotation of Alkanes vs. Alkenes relative E 3 3 anti-butane 3 3 E a 3 3 3 3 Rotational Barrier = 19.26 kjmol -1 (rotation about single - bond) 3 3 relative E E a trans-butene Rotational Barrier = 260 kjmol -1 (rotation involves breaking = bond) 3 3 cis-butene at hicago EM 232, Spring 2010 Slide 20 Note that while rotation around = bonds is restricted, rotation about the - and - single bonds is not. 20
Alkenes Resist Rotation Round = Bond 90º rotation π-bond prevents full rotation around double bond 90º rotation would break π-bond to generate diradical substituents on alkene locked in spacial relationships some rotation is possible through pyramidalization (more on this topic later) at hicago EM 232, Spring 2010 Slide 21 21
Photolysis Mediates = Bond Rotation light (hν) 3 3 3 3 3 3 3 3 diradical has - single bond mixture of cis and trans π* antibonding M.O. light (hν) promotion of electron to antibonding orbital cancels out = bond π bonding M.O. at hicago EM 232, Spring 2010 Slide 22 22
Geometrical Stereoisomers of Alkenes 2 3 3 3 3 3 3 3 1-Butene 2-Methylbutene cis-2-butene trans-2-butene Identical 2 3 No possible stereoisomers 3 3 Identical 1-Butene 2-Methylbutene restricted rotation around double bond gives cis and trans geometrical isomers (stereoisomers) cis and trans: relationship between two vicinal groups on alkene cis: same side; trans: opposite sides at hicago EM 232, Spring 2010 Slide 23 23
onstitutional vs. onfigurational Isomers isomers constitutional (structural) trans (E) cis (Z) Do the molecules have the same connectivity? no yes stereoisomers an the molecules be interconverted by rotation around single bonds? yes no conformational configurational at hicago EM 232, Spring 2010 Slide 24 24
Stereoisomers stereoisomers an the molecules be interconverted by rotation around single bonds? yes no conformational configurational trans (E) cis (Z) geometrical Is the isomerism at a doulbe bond? yes no optical at hicago EM 232, Spring 2010 Slide 25 25
E-Z Nomenclature for Alkenes igher ranked substitutuents on the same side igher ranked substitutuents on the opposite side igher Lower l Br F igher Lower igher Lower l F Br Lower igher Z configuration E configuration Groups are ranked according to atomic number igher atomic number = higher rank Z (zusammen) = together; highest priority group on each alkene carbon on same side E (entgegen) = opposite; highest priority group on each alkene carbon on opposite sides at hicago EM 232, Spring 2010 Slide 26 26
ahn-ingold-prelog (IP) Rules for Prioritizing (,,) (,,) (,,) Br Br l l (,,) Z (,,) (,,) E when geminal atoms are identical, compare forward atoms attached to these on the basis of atomic weight (list in decreasing order) work outward (one atom at a time) until point of difference is reached at hicago EM 232, Spring 2010 Slide 27 27
ahn-ingold-prelog (IP) Rules for Prioritizing (O,O,) l O 3 O O E (O,,) an atom that is multiply bonded to another atom is listed as two separate atoms for nomenclature purposes remember to list attached atoms in decreasing order of atomic weight highest priority = highest atomic weight at first point of difference at hicago EM 232, Spring 2010 Slide 28 28
Why Alkene Geometry Matters Geometry influences molecular shape and, in turn, physical, chemical & biological properties.... O OMe Z onfiguration MeO MeO OMe Vascular targeting agent ombretastatin A4 (A-4) MeO O OMe E onfiguration OMe OMe epi-ombretastatin A4 (A-4) Biologically Inactive! ombretum caffrum S.A. bush willow tree at hicago EM 232, Spring 2010 Slide 29 29
IUPA: Stereoisomeric Alkenes 1 2 3 4 2 3 5 3 3 Steps: (E)-3-methyl-2-pentene or (E)-3-methylpent-2-ene 1. Number the longest chain. 2. Replace -ane ending of parent alkane with -ene or -en, depending on priority. 3. In the name, list the locant of only the first alkene carbon. 4. Indicate geometrical isomers with (Z) or (E) at the beginning of the name. onventions/rules: Z and E are italicized Z and E are placed within parentheses at beginning of name: (Z) & (E). cis and trans may be substituted for E/Z when alkene is 1,2-disubstituted (E) (Z) parent base alkene locant ene University of Illinois at hicago EM 232, Spring 2010 Slide 30 Lecture 8: February 4 30
EM 232 Organic hemistry I at hicago Relative Stabilities of Alkenes Sections 5.5-5.6 31
Relative Stabilities of Alkenes Observations: more stable = lower in energy = lower heat of combustion cis alkenes higher in energy than trans alkenes more alkyl group on alkene = more stable at hicago EM 232, Spring 2010 Slide 32 32
Relative Stabilities of Alkenes 1. Steric Effects van der Waals strain strain between cis groups (Z)-2,2,5,5-tetramethylhex-3-ene (less stable) (E)-2,2,5,5-tetramethylhex-3-ene (more stable) Energy Difference = 44 kjmol -1 at hicago EM 232, Spring 2010 Slide 33 33
Relative Stabilities of Alkenes 2. Substituent Effects alkyl groups stabilize alkenes through donation (via induction and hyperconjugation) to the more electronegative sp 2 -hybridized carbon atoms Stability R monosubstituted R R R trisubstituted R R geminally disubstituted R R R R vicinally disubstituted R R tetrasubstituted at hicago EM 232, Spring 2010 Slide 34 34
EM 232 Organic hemistry I at hicago Preparation of Alkenes Elimination Sections: 5.8-5.11 35
β-elimination Reactions Summary of β-elimination (1,2-elimination) Reactions 1 2 X Y α β 1 2 α β + X Y 1 2 α β Dehydrogenation 1 2 α β + 1 2 α O β Dehydration 1 2 α β + O 1 2 α X β Dehydrohalogenation 1 2 α β + X at hicago EM 232, Spring 2010 Slide 36 36
Dehydrogenation limited to industrial synthesis of ethylene, propene, 1,3-butadiene and styrene important economically, but rarely used in laboratory-scale syntheses living systems utilize enzymes to catalyze this process at hicago EM 232, Spring 2010 Slide 37 37
Strong Acids atalyze the Dehydration of 2 & 3 Alcohols β O 2 SO 4 O 140 º 3 PO 4 β 140 º O KSO 4 2 SO 4 and 3 PO 4 are most common acids used for dehydration: protonation of O group is first step dehydration is reversible (hydration) in aqueous acid (hapter 6) β 140 º at hicago EM 232, Spring 2010 Slide 38 38
Industrial Example of Dehydration NMe 2 NMe 2 NMe 2 O 2 SO 4 O O O O Tamoxifen (Nolvadex ) O Estradiol Tamoxifen mimics estrogens, such as estradiol, and inhibits their binding to the estrogen receptor in breast tissue Tamoxifen blocks cancer cell growth at hicago EM 232, Spring 2010 Slide 39 39
Dehydration can be oupled with Other hemical Transformation N O l F N O l F N l N Me N Me N Me Loratidine (laritin ) Two-step, one-pot transformation involves a Friedel-rafts reaction (see, hapter 12) and dehydration of the resulting 3 alcohol at hicago EM 232, Spring 2010 Slide 40 40
Rate of Alcohol Dehydration Mirrors Ease of arbocation Formation rate of dehydration = 3º > 2º > 1º alcohol tertiary alcohol (3º) O tertiary cation (3º) secondary alcohol (2º) O Reactivity Stability secondary cation (2 ) primary alcohol (1º) O primary cation (1 ) at hicago EM 232, Spring 2010 Slide 41 41
Self Test Question Predict the product for the following reaction scheme. O 2 SO 4 140 º? A. B. - β + β O β - 2 O β β. D. β β β β E. no reaction University of Illinois at hicago EM 232, Spring 2010 Slide 42 42
Self Test Question Predict the product for the following reaction scheme. O 2 SO 4 140 º? A. B. - β + or - β + O - 2 O β β β β β β. D. β E. no reaction University of Illinois at hicago EM 232, Spring 2010 Slide 43 43
Quiz This Week Topic = hapter 4 Bonding in Alcohols & Alkyl alides Bonding of Alkyl alides from Alcohols & X The SN1 & SN2 Mechanisms arbocations: Structure, Bonding & Stability alogenation of Alkanes Radicals: Structure, Bonding & Stablity Mechanism of Alkane alogenation University of Illinois at hicago EM 232, Spring 2010 Slide 44 Lecture 5: January 26 44
EM 232 Organic hemistry I at hicago Next Lecture... hapter 5: Sections 5.12-5.18 Reminder - Bring ID to Exam! 45