What are the reagents in halogenation? [EAS]
2. FeX3 (catalyst)
How is the electrophile formed in halogenation? [EAS]
- X2 bonds with FeX3
- X-X electrons collapse onto the X bonded to Fe
- X+ and FeX4- formed
What is the electrophile in halogenation? [EAS]
What are the reagents in nitration? [EAS]
What is the electrophile in nitration? [EAS]
How is the electrophile formed in nitration? [EAS]
- Proton transfer from H2SO4 to HNO3
- Conjuate acid of HNO3 (H2NO3) loses water
- NO2+ is formed
What are the reagents in sulfonation? [EAS]
What is the electrophile in sulfonation? [EAS]
What group is substituted on the ring with sulfonation? [EAS]
What are the two types of Friedal-Crafts reactions?
What are the reagents in friedel-crafts alkylation? [EAS]
What is the electrophile in friedel-crafts alkylation? [EAS]
What are the reagents in friedel-crafts acylation? [EAS]
Why do halogen atoms on sp2 hybridized carbons not react react to produce electrophiles under conditions of Friedel-Crafts alkylation?
There is a high activation energy to form vinyl and aryl carbocations.
What are three limitations of the Friedel-Crafts alkylation reaction?
- Fails altogether with benzene having one or more strongly electron-withdrawing groups
- Hard to stop reaction at monoalkylation
What are two advantages of Friedel-Crafts acylation over alkylation?
- Rearrangements do not occur
2. Reaction stops at monosubstitution
What reagents are used to reduce an NO2 group to an NH2 group? [EAS modification]
What reagents are used to reduce a carbonyl group to a methylene group (e.g. to go from acylation -> alkylation resembling product)
What is the general three (3) step mechanism for Electrophilic Aromatic Substitution?
- Generation of electrophile
- Attack by electrophile on aromatic ring forming sigma complex
- Loss of H+ to reestablish aromaticity
What are the two ways an existing group can influence further substitution? [EAS]
What is an activating group?
A substituent on a benzene ring that increases rate of substitution
What is a deactivating group?
A substituent on a benzene ring that decreases rate of substitution
What is an ortho-para directing group?
A substituent on a benzene ring that directs substituted groups to ortho-para position
What is a meta directing group?
A substituent on a benzene ring that directs substituted groups to meta position
What are three (3) groups that are generally ortho-para directing and activators, in order of strength?
- Groups where atom adjacent to ring has an unshared pair of electrons
- Phenyl groups
- Alkyl groups
What is unique about halogen influence on a benzene ring?
They are weak deactivators because their electronegativity pulls electron density away from ring, but they are ortho-para directing because they have unshared pairs of electrons.
What is the rate determining step for EAS?
Attack of the electrophile by the aromatic ring forming a sigma complex.
How do substituents effect the rate and orientation of EAS?
Their electron-donating or electron-withdrawing properties can affect activation energy (rate) at certain positions of attack (orientation) when forming the sigma complex.
What is a sigma complex?
A benzene derivative with a strong electrophile attached at Sp3 carbon and positive charge distributed around the ring, but concentrated in the ortho and para positions.
What are two ways that substituents effect the electron density in the ring?
- Resonance (stabilizing sigma complex by using lone pairs)
- Inductive effect (partial positive or partial negative charges on adjacent atom can stabilize ring; includes hyperconjugation of alkyl groups.)
What happens when there are two substituents that direct to different positions?
strongly activating groups influence the outcome more than weakly activating or deactivating groups
What are the reagents for the reaction that will remove an -SO3H from a benzene ring?
- dilute H2SO4
What are the reagents for a reaction that will oxidie a methyl group on a benzene ring to a -COH=O?
What is nucleophilic aromatic substitution?
A reaction in which a nucleophile on an aromatic ring, commonly a halogen, is replaced by another nucleophile.
What are 3 examples of strong nucleophiles that can be used for nucleophilic aromatic substituion?
Describe/draw a Meisenheimer complex
A resonance stabilized carbanion intermediate.
- The pi bond shared by now sp3 carbon collapses onto the adjacent carbon forming a lone pair.
- This lone pair forms a pi bond to the adjacent carbon, and its former pi bond collapses onto the carbon it shared with.
- Strong electron withdrawing group (such as NO2) is part of this resonance structure and brings the negative charge out of the ring.
What are two requirements for nucleophilic aromatic substitution by addition-elimination?
- strong nucleophiles are required
2. deactivating groups are ortho-para to leaving group
What are two ways the rate of nucleophilic aromatic substitution is influenced?
- Concentration of nucleophile (greater concentration, greater rate)
- Leaving group influences the rate (F- > Cl-, Br-, I-)
Why must the electron withdrawing group be o-p to leaving group?
If the electron withdrawing group were meta, a resonance structure with negative charge outside of the ring would be impossible.
Comparing the naming (numbering) priorities of -OH, double and triple bonds, and alkyl groups
- double and triple bonds
- alkyl groups
What is the process for the common names of alcohols?
Name the alkyl group and add the word alcohol. (e.g. CH3 is methyl alcohol)
What is the process for the IUPAC names of alcohols?
- identify longest carbon chain containing OH
- drop e from alkane name and add ol
- locate the position of the OH group and other substituents by number
What is the dominating intermolecular force between alcohols?
What two factors determine the solubility of an alcohol in H2O?
- Length (shorter is more soluble)
2. Compactness of H20 (compact is more soluble)
How do you rank the BP of alcohol isomers?
The alcohol with the most number of carbons
How do you rank the BP of non-isomer alcohols?
Glycols > Alcohols
primary > secondary > tertiary (more highly branched, lower boiling point)
Are alcohols an acid or a base?
Alcohols are amphoteric like water.
How do you predict the extent of completion for an alcohol acting like an acid?
Compare pKas. Stronger acids (lower pKas) form weaker acids (higher pKas)
What is an azeotrope?
A constant boiling mixture (cannot be further distilled)
What are the concentrations of the azeotrope of ethanol and water?
95% ethanol and 5% water
Define an alcohol
R-OH (R is an alkyl group. Does not include arene and carboxylic acids)
What are three non-Grignard ways to prepare an alcohol?
- Reduction of carbonyl groups
What is the product of the reduction of an aldehyde?
R-CH=O –> RH2-OH (primary alcohol)
What is the product of the reduction of a ketone?
R-R’-C=O –> R-R’-CH-OH (secondary alcohol)
What are thee methods for reducing a carbonyl group to form an alcohol?
- H2 and Pt
- NaBH4 and ethanol/methanol
- LiAlH4 and THF/ether –> H2O (weak acid)
What is the purpose of NaBH4 and LiAlH4 in the reduction of a carbonyl group?
Furnishes a hydride (H-) to attack the C=O carbon
What is the purpose of the ethanol/methanol and H2O/weak acid in the reduction of a carbonyl group?
Furnishes a H+ to attack the C=O oxygen
What is a limitation of the method “reduction of carbonyl groups” to form an alcohol?
They cannot form a tertiary alcohol because a H must always be added to the C=O carbon.
Compare the use of LiAlH4 vs. NaBH4 in the “reduction of carbonyl groups” to form an alcohol
LiAlH4 reduces these as well:
- Carboxylic acids
- Alkyl halides
- Nitro compounds
When will LiAlH4 NOT cause reduction? (What kind of bonds are required)?
Addition of hydride (H-) requires a partial positive charge on the carbon, so a normal alkene will not be reduced.
Describe an organometallic reagent
- Polarization of a carbon-halogen bond is reversed by insertion of an active metal (like Mg)
- Carbon has carbanion character so it is a good nucleophile and a strong base.
Describe the three (3) steps of a Grignard reaction
- Organometallic reagent is formed (Mg and ether on an alkyl halide)
- Organometallic reagent reacts with a highly polarized function group or a highly strained epoxide (carbanionic carbon attacks partial positive carbon; MgX attacks partial negative oxygen)
- Water protonates alkoxide salt; (O- MgX+ becomes -OH and MgX leaves)
What are the four (4) steps of developing a synthesis using a Grignard reagent?
- Identify the C and the O of the original carbonyl group (C-OH)
- Identify the alkyl group of the aldehyde (either R- attached to C-OH)
- Identify the alkyl group of the Grignard reagent (the R group that attached the C=O) [It will be the R that you didn’t choose as aldehyde]
- Complete the reaction
How can you prepare a tertiary alcohol using a Grignard reagent?
Ketone (R-R’-C=O) or Ester (R-O-R’-C=O)
When using an ester there will be two moles of Grignard reagent. The nucleophile will add both where the O-R’ and where the C=O is.