Organic Chemistry 2 Final, Reagents and Reactions
Overall Reactivity of Carbonyl Groups
Acyl Chloride > acid anhydride > aldehyde > ketone > ester = carboxylic acid > amide
aldehyde plus Grignard forms a
When a carbon is bonded to 2 hydrogen and 2 non-identical groups
enantiotopic (1 signal)
When a carbon is bonded to 2 hydrogens in a compound with an asymmetric center
diastereotopic (2 signals)
(2C + 2 – #H – #X + #N)/2
Formula for degree of unsaturations
rings and double bonds count for how may degrees of unsaturation?
1 – One
Triple bonds count for how many degrees of unsaturation
2 – Two
What are the steps to determining NMR spectrum
1) Determine degree of unsaturation
2) Look of rings at 6.5 – 8.0
– Number of sub. = 6 – #aromatic protons
3) Look for aldehydes (sharp singlet past 9)
Look for alcohols (broad anywhere)
4) Add up integration and match to formula
5) Start putting the pieces together
Nucleophiles act by donating a pair of ________________________ or its electron _________________________.
Formaldehyde + Grignard
Ketone + Grignard
When an organometallic performs ring opening, it attacks the __________________ substituted side.
What are the three main oxidizing agents
1) Chromic Acid (H2CrO4) – Na2Cr2O7 / H2SO4
2) PCC / Ch2Cl2
3) NaOCl / Ch3COOH
Chromic Acid will oxidize a secondary alcohol to a __________________.
Chromic Acid will oxidize a primary alcohol to an __________________ and then to a ______________________.
aldehyde, carboxylic acid
PCC will oxidize a primary alcohol to an _____________________.
To oxidize a primary alcohol to an aldehyde, use ___________.
To oxidize a primary alcohol to carboxylic acid, use _________________.
Terminal alkyne + strong base (NaNH2) = _____________________
Acetylide + aldehyde/ketone + weak acid (pyridine) = __________________
alcohol with triple bond
Reaction of cyanide with an aldehyde/ketone = ___________________
cyanohydrin (alcohol with C triple bond N)
Acid catalyzed hydrolysis of cyanohydrin produces an _____________________________.
alpha carboxylic acid
What are the two main hydrides used in reduction reactions
Lithium aluminum hydride and sodium borohydride
Which hydride is used to reduce aldehydes and ketones
sodium borohydride reduces aldehydes to _________________ and ketones to __________________.
primary alcohols, secondary alcohols
What is required following the reaction of an aldehyde or ketone with a hydride?
acid work-up to protonate and create the alcohol
Catalytic addition of hydrogen with H2 to a cyanohydrin forms a ________________________.
What is the best way to make a terminal alkene
The Wittig reaction involved the reaction of an aldehyde or ketone with a _______________ _______________.
The Wittig reaction replaces the carbon oxygen double bond with a _______________, ________________ double bond.
Addition of water to an aldehyde or ketone, produces a ______________.
What is a hydrate and what reagents are need to form it.
Molecule with two -OH groups bonded to the same carbon.
H2O and Acid – acid catalyzed
Acid Catalyzed reaction of aldehydes and ketones with alcohols forms a ____________________ after one addition and a ________________ after the second addition.
Using a 1,2-diol as a protecting group forms a ___________ membered ring and the use of 1,3-diol forms a ___________ membered ring.
Reaction of aldehydes and ketones with a primary amine and trace acid produces an ___________________.
In the formation of an imine, the carbon, oxygen double bond is replaced by a __________________, ____________________double bond.
What reagents required for the synthesis of imine?
1) aldehyde / ketone
2) primary amine (RNH2)
3) trace acid
An enamine is a ________________ amine with a ______________ bond in the alpha, beta position relative to the nitrogen.
In the formation of an enamine…After reacting an aldehyde or ketone with a secondary amine, ________________ is eliminated forming the tertiary amine.
Integrated values on an NMR are reported in the _______________ form.
The peak intensity changes/remains constant in a double of doublets.
What determines the reactivity of organometallics?
The electronegativity of the metal. The more electronegative, the more reactive
Why are organolithiums more reactive than organocuprates?
The Organolithium bond is more polar than the organocuprate bond.
When determining the number of signals in a compound with cyclohexane, keep in mind that the ring can _____________.
Which reducing agent is used to reduce carboxylic acids and esters
Lithium aluminum hydride
What determines the ease in preparation of ylides?
sterics and degree of substitution.
When an ylide reacts with an aldehyde or ketone, the P-C bond is ________________ and a ______________ double bond forms between the ______________ carbon and the carbon from the ylide.
broken, new, carbonyl
How do you determine if hydrogens are homotopic. enantiotopic. or diastereotopic?
Steps for naming esters
1) R group attached to carboxylic oxygen named first
2) followed by name of acid with “ic acid” replaced by “ate”
___________________ agents convert alcohols to carbonyls
PCC oxidizes primary alcohols to ___________________ and secondary alcohols to ________________?
Chromic acid oxidizes secondary alcohols to _______________ and primary alcohols to ____________________?
ketones, carboxylic acids
Wittig reactions form terminal __________________.
Retrosynthetic analysis of Wittig reagents favor the ________________ substituted alkyl halide.
When a Grignard reacts with CO2, __________________ is produced.
a carboxylic acid
Strong base add _____________________ without the aid of an ___________________ catalyst.
What are the strong bases
When strong bases add to carbonyl carbons, they add 1,___ and acid is added in a ________________ step.
Weaker bases require the assistance of an acid _______________.
Reactivity within aldehydes and ketones is reliant on….
Substituents. (Both hydrogen is most reactive, 2 large bulky substituents are least reactive)
If a carbonyl is in the presence of acid, the oxygen acts as a ________________ base and is more _______________.
The addition of an acid catalyst increases the ________________ of the reaction only.
Why is hydrate formation reversible?
Water and alcohols are weaker nucleophiles
What conditions are required for hydrate formation and why?
acidic to increase the electrophilicity of the carbonyl carbon
Protecting groups, protect ___________________ carbons from reactions that they otherwise would not survive.
Grignards in the presence of an _______________ proton, will quench!
When a nucleophile attacks an sp2 carbon, ______________ products can form.
Conjugate addition is known as the _____________ product.
Direct addition is known as the _____________ product.
Enamines are similar to ___________, except that the carbonyl oxygen is replaced with NR2.
The formation of enamines is _________________ catalyzed.
Why is water/acid added stepwise with grignards?
What reagents make up pyridine chlorochromate
What conditions are necessary when using PCC and why
anhydrous to prevent further oxidation
Bleach oxidation turns secondary alcohols to ___________________ and primary alcohols to ___________________.
In the reduction reaction with hydrides, the nucleophile is the _________________.
hydride ion (H)
In a phosphonium ylide, the majority of electron density resides on which atom?
Wittig reactions are preferred for making ___________________ alkenes.
Alpha hydrogens are more acidic because the conjugate ________________ is more stable through _____________.
Aldehydes an ketones are more acidic because in an ester, two pairs of protons __________________ for delocalization.
LDA will convert ________________ of a carbonyl compound to enolate ions.
Halogenation of the alpha carbon uses what reagents?
X2 and acid
Halogenation can be _________________ catalyzed or _________________ promoted.
In a base promoted halogenation, the base removes an alpha proton and _______________ alpha protons are replaced by the halogen.
In an acid catalyzed halogenation, ______________ alpha proton is replaced.
In a base promoted halogenation, the _______________ attacks the electrophilic halogen.
Alpha carbon alkylation requires the removal of an alpha carbon with _______________.
____________________is the required solvent for LDA.
The kinetic alkylation product is formed _________________ and uses LDA at -78.
The thermodynamic alkylation product can be formed using 0.95% _________________ and 0.05% __________________.
In an aldol addition, the alpha carbon of one aldehyde/ketone acts as the ________________, and attacks the ________________ carbon of another.
The first step of an aldol addition is the removal of an alpha proton with a ________________.
An alcohol in the 3 position indicates a _________________ addition.
Dehydration of aldol addition forms _____________________________- aldehydes and ketones
alpha, beta unsaturated
Aldol condensation requires
heat and acid, or base and heat
The basic mechanism for aldol condensation begins with the base removing an alpha proton.
In a crossed aldol, one of the reactants must have no _________________ protons.
Aside from using one reactant without alpha protons, you can use _____________ and add the other slowly.
To determine the starting material of an aldol addition, locate the new ___________-____________ bond (formed with the alpha carbon, and draw the two reactants.
To determine the starting material of an aldol condensation, convert the _____________-______________ unsaturated carbonyl to a _________________-hydroycarbonyl.
alpha, beta, beta
When two ester molecules undergo condensation, the process is called a ____________ condensation.
The base used in a Claisen condensation is the same as the _________________________.
Claisen Condensation versus Aldol addition products.
Carboxylic acids with a carbonyl group at the 3 position will undergo _________________________ in the presence of acid and heat.
Decarboxylation is easier under ______________ conditions
The malonic ester synthesis combines the _______________ of an alpha carbon and the __________________ of a 3-oxocarboxylic acid.
Acetoacetic Ester Synthesis
The product of the acetoacetic ester synthesis is a ______________ __________________.
Mechanism for the intramolecular claisen (Dieckman)
Acyl chlorides can react with what to form what?
1) alcohols to form esters
2) water to form carboxylic acids
3) amines to form amides
Acyl chloride reaction with amines to form amides require ___________ equivalents of the _______________.
The first to attack and the second to deprotonate the intermediate
Esters can react with what to form what?
1) water to form carboxylic acids
2) alcohol to form new ester
3) amine to form amide (1 equivalent)
Reaction of an ester with an amine must be in what environment and why.
basic to avoid the protonation of the amine.
Ester hydrolysis is an _______________ catalyzed process which also has protonation of the leaving group.
How does an acid catalyst increase the rate of ester hydrolysis?
Increases formation of intermediate by protonating the carbonyl oxygen and increases the leaving ability of the LG by protonating it.
In the reaction of an ester with an alcohol, excess ______________ is required.
Carboxylic acids react with what to form what?
1) alcohols to form esters
Amides DO NOT react with…
halides, alcohols, or water
Amides will react with water and alcohol under ______________ conditions
acidic / heat
An amide will react with acid and heat will form a
An alkyl halide can react with _______________ to form a nitrile which is then converted to a ______________ ________________.
cyanide, carboxylic acid
An acid anhydride reacts with water to form two equivalents of a ____________________ __________________.
Esters and Acyl chlorides undergo _______________ successive reactions to form _________________ ________________.
two, tertiary alcohols
Acyl chlorides undergo __________________ successive reactions with hydrides to form a ___________________ alcohol.
An ester can be reduced to an aldehyde only by using ___________________ at _________________ Celsius.
A Michael reaction involves the attack of an ___________________ on a ________________ carbon of an a,b-unsaturated ketone.
Michael reactions form ________________ diketones.
Enolates are ____________ bases and therefore add _________,_________.
The Robinson Annulation combines the _______________ addition and the _____________ reaction.
The product of a Robinson Annulation is a _________,___________-_____________________ ketone.
Setting up for the Robinson annulation.
Retro synthesis of Robinson Annulation
Reaction of an aldehyde/ketone with a secondary amine forms a ________________.
Enamines resemble and react the same as _______________.
Aldehydes and ketones can be alkylated/acylated at the alpha carbon through an _______________ intermediate.
Using an enamine allows formation of a ___________________ alkylated product without using LDA.
Enamine can also act as an enolate and attack the ________________ position of an a,b-unsaturated.
The Diels-Alder reaction is a _________,__________ addition reaction.
A Diels-Alder reaction involves a conjugated _______________ and a ______________.
The reactivity of a dienophile is increased if an electron ___________________ group is attached to one of its sp2 carbons.
If the dienophile has two carbon carbon double bonds, _________________ successive reactions occur
What are the five common electrophilic aromatic substitution reactions
4) Friedel-Crafts acylation
5) FC alkylation
The _____________ acidic the proton, the _____________ enolate is formed.
Acid catalyzed ester hydrolysis produces a
What is an enamine
tertiary a,b-unsaturated amine
What reagents are used to remove the enamine protecting group?
acid and water
In a Diels-Alder reaction, when the conjugated diene is in the locked s-cis cyclic position, the product is a _____________________ bicyclic compound.
Which is formed faster, the endo or exo product in a diels alder?
Endo is formed faster when the dienophile has a substituent with pi electrons.
What reagents are required to activate the electrophile for bromination
Br2 + FeBr3
What reagents are required to activate the electrophile in nitration
HNO3 + H2SO4
What is the electrophile in nitration reactions
NO2+ (nitronium ion)
What reagents are required to activate the electrophile for sulfonation
H2SO4+ and heat
What is the electrophile in sulfonation reations
SO3H+ (sulfonium ion)
FC acylation does what to a benzene ring
places an acyl group on it
What is the electrophile in a FC acylation
acylium ion (R-C+=O)
How is the electrophile for FC acylation activated?
an acyl chloride (Cl) attacks the Al of AlCl3 and the Cl is then eliminated.
What happens to primary carbocations?
How can a benzene substituted with a straight-chain alkyl group be formed?
Through acylation reduction
What are the three different sets of reagents used to reduce a carbonyl to a methylene group?
1) H2 / Pd C
2) Zn(Hg), HCl, heat – acidic
3) H2NNH2, OH-, heat – basic
Which reducing reagents can reduce all carbonyl compounds
Clemmensen and Wolff-Kishner
What are the reagents in the Clemmensen reduction
Zn(Hg), HCl, heat – acidic
What are the reagents in the Wolff-Kishner reduction?
H2NNH2, OH-, heat – basic
What is the stipulation to use H2 / Pd,C
Only a ketone carbonyl adjacent to a benzene ring can be reduced
What is the slow step of EAS?
addition of the electrophile to the nucleophilic aromatic ring
What will increase the rate of the slow step (addition of electrophile) of EAS?
A substituent that makes benzene a better nucleophile (electron donating)
The transition state of EAS resembles what?
the carbocation intermediate
What are moderately activating substituents?
Can donate electrons in two directions. To the ring and away.
What are moderately deactivating substituents?
Carbonyl group attached to ring.
What are strongly deactivating substituents?
positive charge attached to ring
What are strongly activating substituents?
Donate electrons to ring only – OR attached
What are halogen substituents?
All activating and weakly deactivating direct…
ortho and para
All substituents with a positive or partial positive attached to the ring direct _________________.
The mirror image of a D-sugar is a ________ sugar
What is the Fisher projection of D-glucose
What are epimers?
Diastereomers that differ in configuration at only one asymmetric center
What is the Haworth Projection of D-glucose?
Groups on the Left in a Fisher are ____________ in a Haworth.
Groups that are Right on the Fisher are ___________ in a Haworth.
Two sugars that differ in configuration only at the carbon that was the carbonyl carbon in the open chain form are called ______________.
In the alpha anomer, the -OH group is ____________.
down (trans to the primary alcohol)
In the beta anomer, the -OH group is ____________.
up (cis to the primary alcohol)
In the Fisher projection, R equals ___________ and S equals __________.
To draw the Haworth, lay the Fisher down on its _________________ side.
The -OH on the number ____________ carbon attacks the carbonyl carbon.
What is the chair conformation of B-D-glucose.
The acetal of a sugar is called a ______________.
The bond between the anomeric carbon and the alkoxy oxygen is a ________________ bond.
What is the mechanism for a glycoside formation?
Acetals are _____________________ sugars.
What is an alpha-1,4-glycosidic linkage?
What is a beta-1,4-glycosidic linkage?
Acyl chlorides only react with alcohol and water
Grignards do not react with ______________ or _______________.
carboxylic acids, amides
When you see an alcohol with 2 identical groups, think __________________.
What reagent converts an alcohol into a carboxylic acid?
What reagents synthesize an alcohol to an alkyl chloride?
What reagents synthesize an acid chloride from a carboxylic acid?
Thionyl chloride in pyridine.
How does LiAlH4 react with benzoyl chloride?
How does LiAlH4 react with acetic benzoic anhydride?
How does LiAlH4 react with benzoic acid?
How does LiAlH4 react with methyl benzoate?
How does LiAlH4 react with benzamide?
What product is formed when 2-bromohexane reacts with KCN, DMSO followed by H30+ and heat?
What is the product of hydrolysis of an acid chloride?
What is transesterification?
What is the product of an acid anhydride treated with an alcohol under acidic conditions?
What reagent(s) will reduce an ester to an aldehyde?
Di-Isobutyl Aluminum Hydride (DIBAH)
How does butyramide react with ethanol in acidic solution?
What reagents converts a ketone to an enolate? What is it used for?
With an enolate, an alkyl substituent group can be added. LDA will alkylate on the less-hindered side of C=O.
Show the synthesis of a carboxylic acid from a malonic ester.
What is decarboxylation?
Decarboxylation is the loss of CO2.
What is an enamine?
An enamine is an unsaturated compound derived by the condensation of an aldehyde or ketone with a secondary amine.
What is the “Michael Reaction” and draw the mechanism.
The “Michael Reaction” or “Michael addition,” is the nucleophilic addition of a carbanion or another nucleophile to an α,β unsaturated carbonyl compound. It belongs to the larger class of conjugate additions.
Draw a mechanism for a base-catalyzed aldol condensation.
Draw a mechanism for an acid-catalyzed aldol condensation.
Draw a mechanism for the base-catalyzed dehydration of an aldol.
What is an iminium salt intermediate and give a mechanism?
What is the product when ethenylbenzene is treated with KMnO4 and aq. NaOH?
What is the claisen condensation? Draw a mechanism.
A claisen condensation is a carbon-carbon bond forming reaction that occurs between two esters or one ester and another carbonyl compound in the presence of a strong base, resulting in a β-keto ester or a β-diketone.
Strong Acid, H20
1. Hg(OAc)2, H2O 2. NaBh4, NaOH
Addition of a Hydrogen Halide: Reagents
Addition of a Hydrogen Halide: Products
Acid-Catalzyed Epoxide Ring Opening: Reagents
Acid-Catalzyed Epoxide Ring Opening: Products
(A diol contains two hydroxyl groups)
Formation of a Halohydrin: Reagents
Formation of a Halohydrin: Products
Halohydrin ( functional group in which a halogen and a hydroxyl are bonded to adjacent carbon atoms)
(Regioselective: Mark addition of -OH)
Addition of X2: Reagents
Addition of X2: Products
Addition of HBr and Peroxides: Reagents
Addition of HBr and Peroxides: Products
Oxidative Cleavage: Reagents
Oxidative Cleavage: Products
Ketones and Carboxylic Acids
Ozonolysis, Reductive: Reagents
Ozonolysis, Reductive: Products
Ketones and Aldehydes
Ozonolysis, Oxidative: Reagents
Ozonolysis, Oxidative: Products
Ketones and Carboxylic Acids
a. Mg, Ether b. Carbonyl c. strong acid
a. LI Alkane, Ether b. Carbonyl c. strong acid
(Regioselective: Reagent adds to the Carbonyl)
Synthesis of Dihalides: Reagents
NaOH, 200C *OR* NaNH3, H20
Synthesis of Dihalides: Products
Acetylide Anion: Reagents
Strong Nucleophile, H20
Acetylide Anion: Products
Oxidation of an Internal Alkyne: Reagents
Oxidation of an Internal Alkyne: Products
Oxidation of an Terminal Alkyne: Reagents
Oxidation of an Terminal Alkyne: Products
Carboxylic Acid with adjacent Ketone
Hydrogenation (Alkyne): Reagents
Hydrogenation (Alkyne): Products
Dissolving Metal Reduction: Reagents
Na(s), NH3, low temp
Dissolving Metal Reduction: Products
Addition of HBr with Peroxides: Reagents
Addition of HBr with Peroxides: Products
Addition of X2 (Alkyne): Reagents
Addition of X2 (Alkyne): Products
Addition of HX: Reagents
Addition of HX: Products
Hydration (Alkyne): Reagents
Hydration (Alkyne): Products
SiaBH, H20, Strong Base