What are four methods for preparing alcohols by reduction?
- Reductions of esters by LiAlH4
- Reduction of carboxylic acids by LiAlH4
- Reduction of aldehydes by sodium borohydride (or LiAlH4)
- Reduction of ketones by sodium borohydride (or LiAlH4)
What are three oxidation reactions of alcohols?
- Oxidation of primary alcohols to aldehydes by PCC
- Oxidation of secondary alcohols to ketones by PCC (or KMno4 or chromic acid)
- Oxidation of primary alcohols to carboxylic acids by KMnO4 (or chromic acid)
What are three ways to write chromic acid as a reagent?
What are four methods for preparing ethers?
- Williamson Ether synthesis
- Ethers from alkene/alcohol
- Ethers from alkenes through oxymercuration
- Ethers from alcohols through dehydration
Describe the Williamson Ether synthesis
Sn2 reaction between an alcohol and alkyl halide under basic conditions (NaOH). Alkyl group replaces the -H of the hydroxyl group.
Describe how to prepare an ether from an alkene/alcohol
H2SO4 attacked by pi electrons of alkene, forming carbocation. Alcohol acts as nucleophile; loss of proton forms stable ether.
Predict the products for the preparation of an ether from an alkene/alcohol under acidic conditions
Add H and -OR across double bond; -OR adds to the less sterically hindered carbon. Rearrangements possible.
What are the reagents for the preparation of an ether from alkenes through oxymercuration?
- Hg(OAc)2, ROH
Predict the products for the preparation of an ether from an alkene/alcohol under acidic conditions
Add H and -OR across double bond; -OR adds to the less sterically hindered carbon. No rearrangements possible.
Describe how to prepare an ether from alcohols through dehydration
Strong acid (H2SO4) and heat protonate alcohol, and a second molecule of alcohol acts as nucleophile to give the ether.
Predict the products for the preparation of an ether from alcohols through dehydration
Alkyl group of R-OH is made into R-O-R; only practical for the synthesis of symmetrical ethers (i.e. one alcohol is used).
What are two methods for preparing epoxides?
- Epoxides from alkenes and peroxyacids
2. Epoxides from halohydrins and base
Predict the product for the preparation of an epoxide from alkenes with peroxyacids
Tether an oxygen between Sp2 carbons
Predict the products for the preparation of an epoxide from halohydrins and base
Tether an oxygen between carbons containing -X and -OH
Why are epoxides highly reactive towards nucleophiles?
The ring strain from 3-membered ring makes it unstable.
Where does the nucleophile attack an epoxide under basic conditions?
Least sterically hindered carbon
Where does the nucleophile attack an epoxide under acidic conditions (and why?)
Epoxide is protonated under acidic conditions and the carbon-oxygen bond will be weaker on the carbon that can best stabilize positive charge; the nucleophile will thus attack the more substituted carbon.
What are two groups to which an alcohol can be converted to facilitate substitution reactions?
- Alcohols to alkyl halides
2. Alcohols to sulfonate (tosylate or mesylate)
What are three reactions used to convert an alcohol to an alkyl halide, and how do they affect stereochemistry?
- SOCl2 or SOBr2 [100% inversion of configuration]
- PCl3 or PBr3 [100% inversion of configuration]
- HCl/HBr/HI [Sn1 or Sn2 depending on structure of alcohol]
What are two reactions to convert an alcohol to a sulfonate, and how do they affect stereochemistry?
- Mesyl chloride, MsCl [methanesulfonyl chloride]
2. Tosyl chloride, TsCl [p-toluenesulfonyl chloride]
What are five reactions for electrophilic aromatic substitution?
- Friedel-Crafts Alkylation
- Friedel-Crafts Acylation
What are the reagents for chlorination/bromination EAS reaction?
Cl2/Br2 and FeCl3/FeBr3
What are reagents for nitration EAS reaction?
HNO3 and H2SO4
What are reagents for sulfonation EAS reaction?
What are reagents for friedel-crafts alkylation EAS reaction?
Alkyl halide (R-X) and AlCl3 (or FeCl3)
What are reagents for friedel-crafts acylation EAS reaction?
Acid chloride (RCOCl) and AlCl3 (or FeCl3)
Predict the product for chlorination/bromination EAS reaction
Substitute H on the ring for Cl or Br
Predict the product for nitration EAS reaction
Substitute H on the ring for NO2
Predict the product for sulfonation EAS reaction
Substitute H on the ring for SO3H
Predict the product for friedel-crafts alkylation EAS reaction
Substitute H on the ring for R of R-X
Predict the product for friedel-crafts acylation EAS reaction
Substitute Cl on acid chloride for aromatic ring.
What reagents transform an aromatic NO2 group to an NH2 group? (two possibilities)
- Metal catalyst (Fe, Sn, Zn) and HCl
2. Pd, H2
What reagents oxidize an aromatic alkyl group?
KMnO4 will oxidize a benzylic carbon containing at least one hydrogen into a carboxylic acid.
What reagents halogenate an aromatic alkyl group?
NBS (N-bromosuccinimide) and light (hv) will halogenate a benzylic carbon with at least one hydrogen.
What are three separate reaction conditions that will reduce a ketone to an alkane?
- NH2NH2/KOH (Wolf-Kishner)
- Zn(Hg)/HCl (Clemmensen)
- Pd/H2 (5 atm)
Can a phenone be converted to an alkane using the same reaction conditions as a normal ketone?
yes it can.
What reaction will convert a ketone to an ester?
What are two separate reaction conditions that will facilitate Baeyer-Villiger reaction?
2. H2O2, BF3
Predict the products for the reduction of a ketone to an alkane
Remove oxygen from carbonyl group and add two hydrogens to carbonyl carbon.
Predict the products for the baeyer-villiger reaction
Insert oxygen between carbonyl carbon and the more highly substitute alpha carbon.
What are two ways an activating group can stabilize a sigma complex?
2. Inductive effect
Why are activating groups ortho-para directors?
In the ortho and para adducts, a resonance structure exists that places the positive charge on the carbon attached to the activating group, allowing for enhanced stabilization.
Why are deactivating groups meta directors?
Deactivating groups are ortho-para avoiders because there will be a resonance structure that places the positive charge on the carbon attached to the deactivating group, reducing the stability of sigma complex.
What is an aryl diazonium ion/salt?
A phenyl group attached to an N triple bond N, resulting in a positive charge on internal nitrogen.
Why are aryl diazonium ions useful?
The N triple bond N is a very stable leaving group so many substitution reactions become thermodynamically favorable.
What reagents convert an aryl diazonium ion into a hydroxyl group?
What reagents convert an aryl diazonium ion into a fluoride?
HBF4 (Schiemann raction)
What reagents convert an aryl diazonium ion into a hydrogen?
H3PO2 (hypophosphorous acid)
What reagents convert an aryl diazonium ion into a nitrile?
CuCN (Sandmeyer reaction)
What reagents convert an aryl diazonium ion into a Bromine or chlorine?
CuBr or CuCl (Sandmeyer reaction)
What reagents convert an aryl diazonium ion into an iodide?
What is an azo compound?
A neutral compound formed by nucleophilic attack at terminal nitrogen of aryl diazonium ion.
What two factors influence the rate of substitution in the formation of an azo compound?
- electron-withdrawing groups on aryl diazonium ion
2. activating groups on aromatic nucleophile
What is the main class of reaction for aldehydes and ketones?
What three factors affect the rate of nucleophilic addition for aldehydes and ketones, and in what direction does it affect rate?
- Increased partial positive charge on carbonyl carbon increases rate.
- Increased steric hindrance at carbonyl carbon decreases rate.
- Acid catalysis protonates carbonyl oxygen and resonance structure puts positive charge on carbon, increase rate.
When will acid catalysis not increase the rate of nucleophlic addition for aldehydes and ketones, and why?
When you are using a strongly basic nucleophile (like a grignard reagent) because it will protonate the nucleophile irreversibly.
What are four methods for preparing aldehydes and ketones?
- Oxidation of alcohols
- Hydroboration/Oxymercuration of alkynes (forms an enol which tautomerizes to the ketone)
- Ozonolysis of alkynes
What reagents are used for the hydroboration of alkynes?
What reagents are used for the oxymercuration of alkynes?
What reagents are used for ozonolysis of alkenes?
Predict the product of the reaction of an aldehyde/ketone with a grignard reagent
reduce =O to -OH and attach alkyl group to former carbonyl carbon
Aldehyde: Secondary alcohol
Ketone: tertiary alcohol
Predict the product of the reaction of a nitrile with a grignard reagent
forms a ketone: transform C triple bond N to C=O and attach alkyl group to former nitrile carbon
Predict the product of the reaction between cyanide ion and an aldehyde/ketone
cyanohydrin: Convert =O to -OH and add -CN to carbonyl carbon
Predict the product of the reaction between an aldehyde/ketone with a hydroxide ion
Hydrate: convert =O to -OH and add -OH to carbonyl carbon
Predict the product of the reaction between an aldehyde/ketone with an alkoxide ion
Hemiacetal: convert =O to -OH and add -OR to carbonyl carbon
What is the difference in reaction conditions to form an acetal versus a hemiacetal?
Two equivalents (or excess) of alcohol will form an acetal, in which the product converts =O to -OR and adds an -Or to carbonyl carbon.
What is the only reagent an acetal or hemiacetal will react with, and what does it do?
Aqueous acid with an excess of water will hydrolyze the acetal or hemiacetal (it will revert it into an aldehyde/ketone and an alcohol)
What is the utility of the relatively low reactivity of acetal or hemiacetal?
Formation of an acetal or hemiacetal can be used to mask a carbonyl group, and it can be hydrolyzed once its use is over.
What is an imine?
R-N=C; nitrogen-containing analogue of ketones and aldehydes (ketimine/aldimine)
What is an enamine?
R2N-C(R’)=CH2; nitrogen-containing analogue of enols
How do you prepare an imine from an aldehyde/ketone?
Aldehydes/ketones treated with a primary amine will give an imine.
How do you prepare an enamine from an aldehyde/ketone?
Aldehydes/ketones treated with a secondary amine will give an enamine.
Predict the products of the Wittig reaction
Change the carbonyl oxygen of the aldehyde/ketone to a carbon and add the alkyl groups of the phosphorus ylide to the new carbon (the former carbonyl oxygen)
What is the main reaction classification of carboxylic acids and its derivatives?
Nucleophilic acyl substitution
What is the biggest factor in determining if a nucleophilic acyl substitution reaction proceeds?
If the base strength of the nucleophile is stronger than the leaving group, the reaction proceeds. Weaker bases are better leaving groups.
Rank the base strength of these “leaving groups” from weakest to strongest: carboxylate, alkoxide/hydroxide, NR2, H/R, Cl-
- H/R (Never leaving groups.)
What is an additional step necessary in the formation of carboxylic acids from a carboxylic acid derivative?
because of the basic reaction conditions to produce the -OH nucleophile, the product will be a carboxylate anion; treatment with acid is necessary to produce the carboxylic acid.
What is special about the addition of grignard reagents/LiAlH4 to esters, and what are the expected products for each?
These reagents will react twice with the ester: (1) react with ester to form ketone or aldehyde (grignard/LiAlH4 respectively) (2) react with ketone or aldehyde to form alkoxide (3) treatment with acid yields alcohol.
- R-MgX yields a tertiary alcohol.
- LiAlH4 yields a primary alcohol.
How do you convert a carboxylic acid to an acid chloride?
SOCl2 replaces -OH with -Cl
How do you prepare an anhydride?
Reaction between carboxylic acid and acid chloride.
What are two ways acid catalysis facilitates nucleophilic acyl substitution?
- makes carbonyl carbons more electrophilic, increasing rate of addition.
- improves leaving group ability, increasing rate of elimination
When can acid catalysis be used to facilitate nucleophilic acyl substitution?
With poor nucleophiles like H2O and alcohols
What are four nucleophilic acyl substitution reactions that employ acid catalysis?
- Fischer esterification: formation of esters from carboxylic acids with alcohols.
- Aqueous hydrolysis of esters to carboxylic acids (water nucleophile)
- Aqueous hydrolysis of amides to carboxylic acids (water nucleophile)
- Aqueous hydrolysis of nitriles to carboxylic acids (water nucleophile)
What are four important nitrogen-containing functional groups?
- Amines (primary, secondary, or tertiary; also quaternary ammonium)
- Amide (carbonyl group adjacent to amine nitrogen)
What are the two main characteristics of amines contributing to its reactivity?
What are three factors contributing to the basicity of nitrogen functional groups?
The more stable the lone pair, the less basic it will be.
- electron donating/withdrawing groups
Give two examples of how resonance decreases basicity of an amine
- cyclohexylamine is more basic than aniline (phenylamine)
2. ethanamine is more basic than acetamide
Explain how electron donating/withdrawing groups affect aromatic amide basicity
- Electron donating groups will make nitrogen more electron rich, and therefore more unstable. (more basic)
- Electron withdrawing group will make the nitrogen less electron rich, and therefore more stable. (less basic)
Explain how orbitals affect the basicity of nitrogen functional groups
The more s-character the orbital, the more stable the nitrogen lone pair will be (and therefore less basic): sp3 is more basic, sp2 is less basic and sp is least basic.
Explain how the basicity of the amine is related to the acidity of the ammonium salt
The weaker the base (the more stable the electron pair), the stronger the conjugate acid.
Describe the reaction for the alkylation of amines
sn2 reaction between an amine and an alkyl halide will react multiple times to form an ammonium salt.
Alcohols are indicated by what characteristic absorbance frequencies?
Nitrogen functional groups containing an N-H bond are indicated by what characteristic absorbance frequency?
Aromatics are indicated by what characteristic absorbance frequencies?
3100-3000; 1800-2000 (overtones)