Substitution/Elimination Reaction Properties & Conditions Determining ...
Substitution/Elimination Reaction Properties & Conditions Mechanism
Substrate
Nu: Strength
Nu: Conc.
Solvent
Kinetics.
preference Sn2
1>2>3
Prefers strong Nu:
High [Nu:] favours Sn2
Aprotic favors Sn2 if either of the reactants is charged
2nd order r=k[Nu:][Sub]
E2
3>2>1*
Prefers strong base
High [Nu:] favours E2
Aprotic favors E2 if either of the reactants is charged
2nd order r=k[Nu:][Sub]
Sn1
3>2>1
Not affected by
Not affected
Protic favors Sn1
1st order
Nu: strength, but
but low [Nu:]
if the reactant is
r=k[Sub]
weak Nu:
disfavors a SN2
not charged
disfavors Sn2
reaction
Not affected by Nu: strength, but weak Nu: disfavors E2
Not affected but low [Nu:] disfavors a E2 reaction
E1
3>2>1
Protic favors E1 if the reactant is not charged
1st order r=k[Sub]
*For a tertiary substrate, the transition state exhibits a partial double bond that is more highly substituted therefore the transition state will be lower in energy.
Determining Likelihood of Elimination and Substitution Reactions E1 & Sn1 For an E1/Sn1 mechanism the stability of the substrate and of the leaving group plays the major role in determining whether or not a reaction will occur. The Nu: does play a role to a lesser extent. The stability of the substrate can be determined with a concept similar to ARIO, as the leaving group plays a big role in determining whether or not E1/Sn1 reactions occur. Using ARIO, we find that the Atom will always be a carbon, but possibility of Resonance structures, Inductive effects and Orbital hybridization all play a big role in determining strength. The 3>2>1 rule essentially covers inductive effects, that is extra carbon groups can donate electron density, increasing the stability of the carbocation intermediate. The presence of a resonance structure will helps increase the stability of the intermediate. As the number of reasonable resonance structures that are possible increases, so does the relative stability of the corresponding carbocations. Finally the role of hybridization is important, as sp3 carbon will more readily carry a positive charge than a sp2 carbon or sp carbon, which makes sense considering their electronegativities. Notice how certain trends of this ARIO are opposite when you consider ARIO with regards to hydrogen deprotonation. This is due to fact that
one forms a carbocation and the other an anion. For determining stability of leaving groups, an easy method is to look at the pka of conjugate acid of the leaving group. The lower the pka or stronger the acid is, the better the leaving group. Ex. HI is a better acid than HF, likewise I is a better leaving group than F The only shortcoming of this method is -
.
that it does not take into account kinetics, so pka trends don’t perfectly match the LG trends. Sometimes poor LGs can be converted into better LGs (see other reactions section). E2 & Sn2 (wip) Size/kinetics, polarizability and electronegativity play a role in Nu: strength. The LG is important to a lesser degree in E2/Sn2 than E1/Sn1. You’ll notice a that size and polarizability are in contest This is beyond me.
Prediction of Elimination and Substitution Products and their Stereochemistry Sn2: Always undergoes 100% inversion at the chiral centre only. This may induce other chiral centres to flip configuration, but their physical connectivity is not changed. Sn1: Forms racemic mixtures which sometimes favor the inverted structure due to ion pairing. Additionally, Sn1 can undergo hydride shifts, methyl shifts and resonance shifts due to formation of a carbocation intermediate, moving the location of the + charge. This results in a mixture of products, depending on how probable the shift is. E2: Follows 3 rules Antiperiplanar/Anti-coplanar rule, Zaitsev's rule and E/Z Isomerism rule. The first rule trumps the second two. Antiperiplanar/Anti-coplanar Rule - The hydrogen to be deprotonated must be antiperiplanar (180 degrees apart) from the leaving group. In cyclic compounds only axial groups can be removed. Zaitsev's Rule - If multiple products are possible, the the more substituted alkene is favored unless *the base is large *the alkyl halide is an alkyl fluoride *the alkyl halide contains one or more double bonds. In both cases the minor products occur. E/Z Isomerism rule - If multiple products are possible, the product with Z or trans isomerism is favoured, though minor cis products occur. E1: This mechanism forms racemic mixtures which tend to favour Zaitsev products and trans products.
Alkene Addition Reactions Reaction mechanisms are given under the table. Reaction mechanisms and intermediates are not given for mechanisms you aren’t required to know, and are marked N/A. The reaction conditions given are to favour products. Know the relationship between reversible reactions, and how reaction conditions change to favor each side. Reaction name
Reaction
Product
Markov. ’
Syn/Anti &
Rxn
Conditions
Catalytic Hydrogenation
H /Pt
Alkane
2
Hydrohalogenation
HX
Hydration
s Rule
Intermediat e
Mechanis m and Extra Notes
N/A
Syn; unnamed intermediat e
Mechanism #1
Both; planar carbocation intermediat e
Mechanism #2
Also see Wilkinson’s catalyst note
Saturated alkyl halide
Followed
Dil. H SO / Low Temp.
Alcohol
Followed
Both; planar carbocation intermediat e
Mechanism #3
1.Hg(OAc) / HO 2. NaBH / H O/Et O
Alcohol
Followed Nu: goes on more sub’d carbon
Anti; cyclic mercuriniu m ion intermediat e
Mechanism #4
Hydroboration Oxidation
1. BH /THF 2. H O /NaO H
Alcohol
Broken
Syn; N/A
N/A
Halogenation
Cl or Br in CCL
Vicinal dihalide
N/A
Anti; cyclic halonium intermediat e
Mechanism #5
Cl or Br in HO
Vicinal halohydrin
Followed
Anti, cyclic halonium intermediat e
Mechanism #6
Peroxyacids (Ex. RCO H)
Epoxide
N/A
N/A; Unnamed intermediat e
Mechanism #7
1. O 2. DMS
Aldehydes and/or ketones *depends on
N/A
N/A; N/A
N/A
Oxymercuration-Demercurat ion
2
4
2
*Rearrangeme nt can occur
2
4
2
2
3
2
2
2
2
2
2
Epoxidation
OH goes to more sub’d C
3
Oxidative Cleavage (Ozonolysis)
3
See: Demercurati on note for full details of this rxn.
2
4
Halohydration
unless R-OO-R is present
how substituted double bond was
Antidihydroxylation
Add H O /H O to epoxide substrate
Vicinal diol
Syn-
See syn-
Vicinal diol
dihydroxylation
dihydroxylation
3
+
2
N/A
Anti; cyclic protonated epoxide ion intermediat e
Mechanism #8
Syn; N/A
N/A
No alkene substrate used.
note for all rxn conditions
Alkene Addition Reaction Mechanisms Mechanisms in the table marked with N/A aren’t required knowledge for this course.
#1 Hydrogenation (metal catalyst) #2 Electrophilic HX Addition #3 Hydration Notice use of equilibrium arrows; this reaction is reversible via changing rxn conditions #4 Oxymercuration Intermediate shown twice, with and without resonance, Nu: is generally H O 2
#4 cont. Demercuration This one’s a complete mess, and probably not required knowledge, see notes #5 Halogenation #6 Hydrohalogenation (Water does the nucleophilic attack due to its abundance, despite being weak) #7 Epoxidation #8 Anti-Dihydroxylation Notes General rules: When you have two equal saturated carbons with a double or triple bond between them, and the reaction follows Markovnikov’s rule (ie. is not a symmetrical addition) then you will form two products. In some cases these products may end up being identical. Wilkinson's’ Catalyst: Ligands can act as chiral catalysts, and will attach to Wilkinson’s catalyst in a way to make it favor one enantiomer over the other. Heterogeneous catalyst has advantage of improving surface area so less is used. They work by changing activation energy for the reaction profile of each enantiomer. The difference in the E values dictates how selective the chiral catalyst is. A
Demercuration: Reactions conditions are ambiguous in lecture notes. The ones given are from Wikipedia. Syn-dihydroxylation: Occurs in two steps; step 1. OsO4 and step 2 with one of the following; Na SO /H O, NaHSO /H O, NMO, or tert-Butyl hydroperoxide. The latter 2 mechanisms regenerate 2
3
2
3
2
OsO . Alternatively use: cold dil. KMnO 4
4
Alkyne Addition Reactions Reaction name
Reaction Conditions
Product
Markov. ’s Rule
Syn/Anti & Intermediate
Rxn Mechanism and Extra Notes
Catalytic Hydrogenation
H2/Pt *Pt can be replaced with Pd, Rh, Ru or Ni
Alkane
N/A
Syn x2; Z-Alkene intermediate, + 2 others, see rxn mechanism.
Mechanism #1 x2 (see above)
Poisoned Catalytic Hydrogenation
H2/Lindlar’s Catalyst
Z-Alkene
N/A
Syn; N/A
N/A
Dissolving Metal Reductions (Hydrogenation)
Na/NH at low temp.
E-Alkene
N/A
Anti; multiple intermediates, see rxn mechanism
Mechanism #9
Hydration
1. H SO /H O 2. HgSO
?-Enol
Followed
??, N/A
N/A
Hydroboration Oxidation
1. BH /THF 2. H O /NaOH
Z-Enol
Broken
Syn, N/A
N/A
Halogenation
X (1 equiv.) /CCl
Mjr: Z-alkene Mnr: E-alkene
N/A
Both, N/A
N/A
Hydrohalogenation
HX
Mjr: Z-Alkene Mnr:E-Alkene
Followed
Oxidative Cleavage (Ozonolysis)
1. O 2. H O
Carboxylic Acid(s) (+ CO for terminal alkynes)
N/A
3 (L)
2
4
2
4
3
2
2
4
3
2
2
Undergoes Enol Tautomerization
Undergoes Enol Tautomerization
2
Undergoes both Syn & Anti addition unlike alkenes
unless R-OO-R is present
Both, planar carbocation intermediate
Mechanism #6
N/A
N/A
#9 Dissolving Metal Reductions (Hydrogenation) Enol Tautomerization Mechanism & Notes Tautomers are a set of constitutional isomers which exist in equilibrium with each other, and are interchanging; notice use of equilibrium arrows in the mechanism. This equilibrium favors the ketone/aldehyde product. Ketones are produced when terminal alkynes are hydrated in a Markovnikov fashion or when non terminal alkynes are hydrated. Aldehydes are produced when terminal alkynes are hydrated in an anti Markovnikov fashion.
NMR Spectroscopy Chemical shifts Increasingly electronegative compounds are associated with increasingly downfield chemical shifts. Below are some important ones to know. You don’t have to know exact values, but knowing the approximate values helps. Effect of sp2 carbon (double bond) - Vinylic Hydrogens attached to carbon-carbon double bonds resonate between 4.5 - 7 ppm - Allylic hydrogens are shifted downfield Effect of Aromaticity - Aromatic hydrogens resonate between 7 - 8 ppm. The hydrogens appear as multiplet(s) depending on if they’re in unique environments from each other. Effect of Aldehydes - Aldehyde protons resonate between 9 - 10 ppm. Effect of sp carbon (triple bond) -Hydrogen resonates between 1.7 - 3.1 ppm Alkyl shifts Element
H
I
Br
Cl
F
Chemical Shift
0.23
2.16
2.68
3.05
4.26
Long range coupling - In cyclic, aromatic and sp hybridized carbons, hydrogens can undergo long range coupling. This is when coupling occurs over 4 bonds. Second-Order Spectra and Coincidental Overlap When non-equivalent H atoms are coupled to each other, and happen to have very similar chemical shifts, unusual splitting patterns can be observed. This type of peak can be referred to as a multiplet and it contains peak splitting which can range from fewer to more peaks than expected as well as unusual relative peak intensities, however integration values remain constant. Spectra with this unusual splitting are referred to as second-order spectra. Moreover, within peaks when coupling constants are very small, peak splitting is hard to see in a spectrum. High resolution spectrometers are required to distinguish all of the peaks in a highly split signal.
Mass Spec Isotopes Only includes the ones we learned in class, obviously there’s tons more. but only the Cr/Br patterns are generally expected knowledge due to formation of nice 1:3 and 1:1 fragments respectively. Isotope
% nat. abundance
37Cl
24.23
35Cl
75.77
79Br
50.69
81Br
49.31
Other Reactions Epoxidation of Halohydrins - Epoxides can also be made by treating halohydrins with base (the methyl doesn’t need to be present in the reaction mechanism below, it there because this picture was extracted from a multistep reaction mechanism) Preparation of Alkynes Double elimination with a strong base. Terminal alkynes form ions, which must be protonated again. Full reaction shown. Alkylation of Terminal Alkenes Fairly simple mechanism to generate larger carbon chains. This reaction can be controlled with stoichiometry to get very specific products (unique R chain on each end). See above mechanism for how to get an Alkynide ion. . Conversion of OH leaving group (E1/Sn1 Mechanism) Protonate the OH group with any acid, and it will become a good LG. Mechanism omitted because it’s fairly obvious to guess. Conversion of OH leaving group (Sn2/E2 Mechanism) -Hydroxides can be made to leave through E2 elimination. Recall that E2 elimination is advantageous as we can select Zaitsev or Hoffman product by changing base size, this is something we can’t do with E1. However E2 requires the presence of a slightly better leaving group that won’t spontaneously form carbocations. We use the following reaction. Free Radical Halogenation of Alkanes (from lab, the full mechanism is not required knowledge)
Resonance -Stabilizes molecules via delocalization which is spreading of charge(s) over multiple atoms. -The total charge on a compound must be the same for all resonance structures, and there are no exceptions to this rule. -In reality a molecule that undergoes resonance is a weighted average of its states. It does NOT flip back and forth between states. -When drawing arrow pushing mechanisms avoid breaking a single bond. Also never exceed an octet for second-row elements (C, N, O, or F) . This is important in determining which resonance structures are valid, so I'll repeat it; don’t break the octet rule. Common Resonance Patterns 1. Allylic lone pair 2. Allylic Positive Charge
3. A lone pair adjacent to a positive charge
4. A π bond between two atoms of differing electronegativity
5. Conjugated π bonds enclosed in a ring
Substrate
Nu: Strength
Nu: Conc.
Solvent
Kinetics.
preference Sn2
1>2>3
Prefers strong Nu:
High [Nu:] favours Sn2
Aprotic favors Sn2 if either of the reactants is charged
2nd order r=k[Nu:][Sub]
E2
3>2>1*
Prefers strong base
High [Nu:] favours E2
Aprotic favors E2 if either of the reactants is charged
2nd order r=k[Nu:][Sub]
Sn1
3>2>1
Not affected by
Not affected
Protic favors Sn1
1st order
Nu: strength, but
but low [Nu:]
if the reactant is
r=k[Sub]
weak Nu:
disfavors a SN2
not charged
disfavors Sn2
reaction
Not affected by Nu: strength, but weak Nu: disfavors E2
Not affected but low [Nu:] disfavors a E2 reaction
E1
3>2>1
Protic favors E1 if the reactant is not charged
1st order r=k[Sub]
*For a tertiary substrate, the transition state exhibits a partial double bond that is more highly substituted therefore the transition state will be lower in energy.
Determining Likelihood of Elimination and Substitution Reactions E1 & Sn1 For an E1/Sn1 mechanism the stability of the substrate and of the leaving group plays the major role in determining whether or not a reaction will occur. The Nu: does play a role to a lesser extent. The stability of the substrate can be determined with a concept similar to ARIO, as the leaving group plays a big role in determining whether or not E1/Sn1 reactions occur. Using ARIO, we find that the Atom will always be a carbon, but possibility of Resonance structures, Inductive effects and Orbital hybridization all play a big role in determining strength. The 3>2>1 rule essentially covers inductive effects, that is extra carbon groups can donate electron density, increasing the stability of the carbocation intermediate. The presence of a resonance structure will helps increase the stability of the intermediate. As the number of reasonable resonance structures that are possible increases, so does the relative stability of the corresponding carbocations. Finally the role of hybridization is important, as sp3 carbon will more readily carry a positive charge than a sp2 carbon or sp carbon, which makes sense considering their electronegativities. Notice how certain trends of this ARIO are opposite when you consider ARIO with regards to hydrogen deprotonation. This is due to fact that
one forms a carbocation and the other an anion. For determining stability of leaving groups, an easy method is to look at the pka of conjugate acid of the leaving group. The lower the pka or stronger the acid is, the better the leaving group. Ex. HI is a better acid than HF, likewise I is a better leaving group than F The only shortcoming of this method is -
.
that it does not take into account kinetics, so pka trends don’t perfectly match the LG trends. Sometimes poor LGs can be converted into better LGs (see other reactions section). E2 & Sn2 (wip) Size/kinetics, polarizability and electronegativity play a role in Nu: strength. The LG is important to a lesser degree in E2/Sn2 than E1/Sn1. You’ll notice a that size and polarizability are in contest This is beyond me.
Prediction of Elimination and Substitution Products and their Stereochemistry Sn2: Always undergoes 100% inversion at the chiral centre only. This may induce other chiral centres to flip configuration, but their physical connectivity is not changed. Sn1: Forms racemic mixtures which sometimes favor the inverted structure due to ion pairing. Additionally, Sn1 can undergo hydride shifts, methyl shifts and resonance shifts due to formation of a carbocation intermediate, moving the location of the + charge. This results in a mixture of products, depending on how probable the shift is. E2: Follows 3 rules Antiperiplanar/Anti-coplanar rule, Zaitsev's rule and E/Z Isomerism rule. The first rule trumps the second two. Antiperiplanar/Anti-coplanar Rule - The hydrogen to be deprotonated must be antiperiplanar (180 degrees apart) from the leaving group. In cyclic compounds only axial groups can be removed. Zaitsev's Rule - If multiple products are possible, the the more substituted alkene is favored unless *the base is large *the alkyl halide is an alkyl fluoride *the alkyl halide contains one or more double bonds. In both cases the minor products occur. E/Z Isomerism rule - If multiple products are possible, the product with Z or trans isomerism is favoured, though minor cis products occur. E1: This mechanism forms racemic mixtures which tend to favour Zaitsev products and trans products.
Alkene Addition Reactions Reaction mechanisms are given under the table. Reaction mechanisms and intermediates are not given for mechanisms you aren’t required to know, and are marked N/A. The reaction conditions given are to favour products. Know the relationship between reversible reactions, and how reaction conditions change to favor each side. Reaction name
Reaction
Product
Markov. ’
Syn/Anti &
Rxn
Conditions
Catalytic Hydrogenation
H /Pt
Alkane
2
Hydrohalogenation
HX
Hydration
s Rule
Intermediat e
Mechanis m and Extra Notes
N/A
Syn; unnamed intermediat e
Mechanism #1
Both; planar carbocation intermediat e
Mechanism #2
Also see Wilkinson’s catalyst note
Saturated alkyl halide
Followed
Dil. H SO / Low Temp.
Alcohol
Followed
Both; planar carbocation intermediat e
Mechanism #3
1.Hg(OAc) / HO 2. NaBH / H O/Et O
Alcohol
Followed Nu: goes on more sub’d carbon
Anti; cyclic mercuriniu m ion intermediat e
Mechanism #4
Hydroboration Oxidation
1. BH /THF 2. H O /NaO H
Alcohol
Broken
Syn; N/A
N/A
Halogenation
Cl or Br in CCL
Vicinal dihalide
N/A
Anti; cyclic halonium intermediat e
Mechanism #5
Cl or Br in HO
Vicinal halohydrin
Followed
Anti, cyclic halonium intermediat e
Mechanism #6
Peroxyacids (Ex. RCO H)
Epoxide
N/A
N/A; Unnamed intermediat e
Mechanism #7
1. O 2. DMS
Aldehydes and/or ketones *depends on
N/A
N/A; N/A
N/A
Oxymercuration-Demercurat ion
2
4
2
*Rearrangeme nt can occur
2
4
2
2
3
2
2
2
2
2
2
Epoxidation
OH goes to more sub’d C
3
Oxidative Cleavage (Ozonolysis)
3
See: Demercurati on note for full details of this rxn.
2
4
Halohydration
unless R-OO-R is present
how substituted double bond was
Antidihydroxylation
Add H O /H O to epoxide substrate
Vicinal diol
Syn-
See syn-
Vicinal diol
dihydroxylation
dihydroxylation
3
+
2
N/A
Anti; cyclic protonated epoxide ion intermediat e
Mechanism #8
Syn; N/A
N/A
No alkene substrate used.
note for all rxn conditions
Alkene Addition Reaction Mechanisms Mechanisms in the table marked with N/A aren’t required knowledge for this course.
#1 Hydrogenation (metal catalyst) #2 Electrophilic HX Addition #3 Hydration Notice use of equilibrium arrows; this reaction is reversible via changing rxn conditions #4 Oxymercuration Intermediate shown twice, with and without resonance, Nu: is generally H O 2
#4 cont. Demercuration This one’s a complete mess, and probably not required knowledge, see notes #5 Halogenation #6 Hydrohalogenation (Water does the nucleophilic attack due to its abundance, despite being weak) #7 Epoxidation #8 Anti-Dihydroxylation Notes General rules: When you have two equal saturated carbons with a double or triple bond between them, and the reaction follows Markovnikov’s rule (ie. is not a symmetrical addition) then you will form two products. In some cases these products may end up being identical. Wilkinson's’ Catalyst: Ligands can act as chiral catalysts, and will attach to Wilkinson’s catalyst in a way to make it favor one enantiomer over the other. Heterogeneous catalyst has advantage of improving surface area so less is used. They work by changing activation energy for the reaction profile of each enantiomer. The difference in the E values dictates how selective the chiral catalyst is. A
Demercuration: Reactions conditions are ambiguous in lecture notes. The ones given are from Wikipedia. Syn-dihydroxylation: Occurs in two steps; step 1. OsO4 and step 2 with one of the following; Na SO /H O, NaHSO /H O, NMO, or tert-Butyl hydroperoxide. The latter 2 mechanisms regenerate 2
3
2
3
2
OsO . Alternatively use: cold dil. KMnO 4
4
Alkyne Addition Reactions Reaction name
Reaction Conditions
Product
Markov. ’s Rule
Syn/Anti & Intermediate
Rxn Mechanism and Extra Notes
Catalytic Hydrogenation
H2/Pt *Pt can be replaced with Pd, Rh, Ru or Ni
Alkane
N/A
Syn x2; Z-Alkene intermediate, + 2 others, see rxn mechanism.
Mechanism #1 x2 (see above)
Poisoned Catalytic Hydrogenation
H2/Lindlar’s Catalyst
Z-Alkene
N/A
Syn; N/A
N/A
Dissolving Metal Reductions (Hydrogenation)
Na/NH at low temp.
E-Alkene
N/A
Anti; multiple intermediates, see rxn mechanism
Mechanism #9
Hydration
1. H SO /H O 2. HgSO
?-Enol
Followed
??, N/A
N/A
Hydroboration Oxidation
1. BH /THF 2. H O /NaOH
Z-Enol
Broken
Syn, N/A
N/A
Halogenation
X (1 equiv.) /CCl
Mjr: Z-alkene Mnr: E-alkene
N/A
Both, N/A
N/A
Hydrohalogenation
HX
Mjr: Z-Alkene Mnr:E-Alkene
Followed
Oxidative Cleavage (Ozonolysis)
1. O 2. H O
Carboxylic Acid(s) (+ CO for terminal alkynes)
N/A
3 (L)
2
4
2
4
3
2
2
4
3
2
2
Undergoes Enol Tautomerization
Undergoes Enol Tautomerization
2
Undergoes both Syn & Anti addition unlike alkenes
unless R-OO-R is present
Both, planar carbocation intermediate
Mechanism #6
N/A
N/A
#9 Dissolving Metal Reductions (Hydrogenation) Enol Tautomerization Mechanism & Notes Tautomers are a set of constitutional isomers which exist in equilibrium with each other, and are interchanging; notice use of equilibrium arrows in the mechanism. This equilibrium favors the ketone/aldehyde product. Ketones are produced when terminal alkynes are hydrated in a Markovnikov fashion or when non terminal alkynes are hydrated. Aldehydes are produced when terminal alkynes are hydrated in an anti Markovnikov fashion.
NMR Spectroscopy Chemical shifts Increasingly electronegative compounds are associated with increasingly downfield chemical shifts. Below are some important ones to know. You don’t have to know exact values, but knowing the approximate values helps. Effect of sp2 carbon (double bond) - Vinylic Hydrogens attached to carbon-carbon double bonds resonate between 4.5 - 7 ppm - Allylic hydrogens are shifted downfield Effect of Aromaticity - Aromatic hydrogens resonate between 7 - 8 ppm. The hydrogens appear as multiplet(s) depending on if they’re in unique environments from each other. Effect of Aldehydes - Aldehyde protons resonate between 9 - 10 ppm. Effect of sp carbon (triple bond) -Hydrogen resonates between 1.7 - 3.1 ppm Alkyl shifts Element
H
I
Br
Cl
F
Chemical Shift
0.23
2.16
2.68
3.05
4.26
Long range coupling - In cyclic, aromatic and sp hybridized carbons, hydrogens can undergo long range coupling. This is when coupling occurs over 4 bonds. Second-Order Spectra and Coincidental Overlap When non-equivalent H atoms are coupled to each other, and happen to have very similar chemical shifts, unusual splitting patterns can be observed. This type of peak can be referred to as a multiplet and it contains peak splitting which can range from fewer to more peaks than expected as well as unusual relative peak intensities, however integration values remain constant. Spectra with this unusual splitting are referred to as second-order spectra. Moreover, within peaks when coupling constants are very small, peak splitting is hard to see in a spectrum. High resolution spectrometers are required to distinguish all of the peaks in a highly split signal.
Mass Spec Isotopes Only includes the ones we learned in class, obviously there’s tons more. but only the Cr/Br patterns are generally expected knowledge due to formation of nice 1:3 and 1:1 fragments respectively. Isotope
% nat. abundance
37Cl
24.23
35Cl
75.77
79Br
50.69
81Br
49.31
Other Reactions Epoxidation of Halohydrins - Epoxides can also be made by treating halohydrins with base (the methyl doesn’t need to be present in the reaction mechanism below, it there because this picture was extracted from a multistep reaction mechanism) Preparation of Alkynes Double elimination with a strong base. Terminal alkynes form ions, which must be protonated again. Full reaction shown. Alkylation of Terminal Alkenes Fairly simple mechanism to generate larger carbon chains. This reaction can be controlled with stoichiometry to get very specific products (unique R chain on each end). See above mechanism for how to get an Alkynide ion. . Conversion of OH leaving group (E1/Sn1 Mechanism) Protonate the OH group with any acid, and it will become a good LG. Mechanism omitted because it’s fairly obvious to guess. Conversion of OH leaving group (Sn2/E2 Mechanism) -Hydroxides can be made to leave through E2 elimination. Recall that E2 elimination is advantageous as we can select Zaitsev or Hoffman product by changing base size, this is something we can’t do with E1. However E2 requires the presence of a slightly better leaving group that won’t spontaneously form carbocations. We use the following reaction. Free Radical Halogenation of Alkanes (from lab, the full mechanism is not required knowledge)
Resonance -Stabilizes molecules via delocalization which is spreading of charge(s) over multiple atoms. -The total charge on a compound must be the same for all resonance structures, and there are no exceptions to this rule. -In reality a molecule that undergoes resonance is a weighted average of its states. It does NOT flip back and forth between states. -When drawing arrow pushing mechanisms avoid breaking a single bond. Also never exceed an octet for second-row elements (C, N, O, or F) . This is important in determining which resonance structures are valid, so I'll repeat it; don’t break the octet rule. Common Resonance Patterns 1. Allylic lone pair 2. Allylic Positive Charge
3. A lone pair adjacent to a positive charge
4. A π bond between two atoms of differing electronegativity
5. Conjugated π bonds enclosed in a ring
