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87 Cards in this Set
- Front
- Back
Aldehydes & ketones in solution are considerably __ basic than alcohols
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less (conjugate acids are more acidic because of solvent effect: in gas phase, aldehydes & ketones more basic, in solution, solvation of protonated alcohol by hydrogen bonding is evidently so effective that it outweighs resonance stabilization of protonated aldehyde/ketone
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Addition
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In all carbonyl-addition reactions, the more electropositive species adds to
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the carbonyl oxygen, & the more electronegative species adds to the carbonyl carbon
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Nucleophilic carbonyl addition
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Reaction of a nucleophile @ carbonyl carbon: i.e. cyanide ion donates e to carbonyl C of ald/ket & carbonyl o accepts displaced e pair & assumes neg charge, which is protonated by h2o or hcn
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Nucleophilic carbonyl addition occurs even though the C-O bond is stronger than the C-C pi bond because
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the unshared e pair & neg charge formed in the mech is transferred to the electroneg O & same rxn of alkene would place unshared pair & neg charge on C
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Can a nucleophile add to the carbonyl oxygen?
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No: nucs always react w carbonyl groups @ the carbonyl C
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How does the carbonyl carbon change hybridization when attacked?
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sp2 to sp3, trigonal planar to tetrahedral: angle compresses, groups bound to the carbonyl become closer together
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Why does the addition geometry occur?
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The bonding pi MO of the carbonyl group is fully occupied w 2 e and cannot have any more so e pair of nuc interacts w LUMO: antibonding MO w lobes above & below & the nuc must begin bonding w carbonyl from direction along which lUMO is conc
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When the antibondnig pi* MO is filled
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the C=O bond is weakened and breaks
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Second mechanism for carbonyl addition
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analogous to mech for addition of acids to alkenes: protonation of carbonyl O
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Mechanism 2.2 carbonyl addition
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Loss of a proton to solvent (weak base H2O can react because protonated O makes a strong Lewis acid)
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Does hydration of aldehydes & ketones occur in neutral & basic solutions?
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Yes
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Mechanism 2.2 direction of approach
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above or below bc of shape of LUMO
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Hydration & cyanohydrin formation are both __
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reversible rxns
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Whether the equilibrium favors addition product or carbonyl cmpd depends on
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the structure of the carbonyl cmpd
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Addition is more favorable for aldehydes or ketones?
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Aldehydes
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Electronegative groups near the carbonyl C make addition ___ favorable
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more
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Groups that donate e by resonance to the carbonyl C make addition ___ favorable
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less
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The equilibria for all addition rxns show similar effects of structure important bc
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the reactivities of carbonyl cmpds follow similar trends
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Reason for the effect of structure on carbonyl addition?
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The relative stabilities of the carbonyl compound & the addition product govern delta G for addition: the primary effect on the hydration equilibrium is the difference in the stabilities of the carbonyl compounds - Added stability in the carbonyl cmpd inc delta G & dec equilibrium constant for formation of an addition product
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Carbonyl cmpds are stabilized bc
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one resonance structure reflects polarity of carbonyl group w characteristics of a carbocation so anything that stabilizes carbocations also stabilizes carbonyl cmpds
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Why are ketones more stable than aldehydes?
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Alkyl groups stabilize carbocations, so the equilibria for additions are less favorable
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Formaldehyde has 2 hydrogens so its equilibrium constant for hydration is
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large
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Electronegative groups such as halogens ___ carbocations
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destabilize by polar effect & carbonyl cmpds, so make equilibria for addition more favorable
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Groups that are conjugated w the carbonyl group such as phenyl of benzaldehyde
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stabilize carbocations by resonance & hence stabilize carbonyl cmpds: cannot occur in hydrate bc carbonyl no longer present
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Aryl aldehydes & ketones have ___ hydration equilibria
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relatively unfavorable
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Steric effect of carbonyl addition
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As size of groups bound to carbonyl carbon inc, VDW in addition cmpds inc in importance
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Cmpds w favorable addition equilibria tend to react
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most rapidly in addition rxns
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Aldehydes are generally ___ than ketones in addition rxns
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more reactive
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Formaldehyde is ___ reactive than many other simple aldehydes
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more
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Reason for parallel trends in rates and equilibria
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Transition states for addition rxns resemble addition products
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LiAlH4 is a source of
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a hydride ion (very basic) & bc H is more electroneg than Al, the Al-H bonds of the -AlH3 ion carry a substantial fraction of the neg charge
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LiAlH4 must be used in __ solvents
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dry, such as anhydrous ether and THF
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The rxn of LiAlH4 w aldehydes & ketones involves nuc rxn of hydride @ __ and the lithium ion acts as a ___ by ___
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carbonyl C - Lewis acid catalyst by coordinating to the carbonyl oxygen
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The addition product (an alkoxide salt) can react w AlH3 & resulting product can serve as
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a source of hydride: similar process at each stage of reduction until all hydrides consumed
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After the reduction is complete, the alcohol prod exists as
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an alkoxide addition cmpd w aluminum, converted separately into alcohol (proton from HCl or aq. NH4Cl)
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Sodium ion is a __ LA than lithium ion
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weaker, so NaBH4 reductions carried out in protic solvents such as alcohols
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Hydrogen bonding btwn alcohol solvent & carbonyl group serves as
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weak acid catalysis that activates the carbonyl group
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Are all four hydride equivalents of NaBH4 active in reduction?
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Yes
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The net effect of the Grignard reaction followed by protonolysis is
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addition of R-H (R=alkyl or aryl group) across the C=O double bond
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When an aldehyde or ketone reacts w a large excess of an alcohol in the presence of a trace of strong acid
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an acetal is formed
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acetal
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cmpd in which 2 ether O are bound to same C (ethers of carbonyl hydrates, or gem-diols)
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How many equivalents of alcohol are consumed in each acetal-forming reaction?
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2
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One equivalent of a 1,2 or 1,3-diol can react to form a
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cyclic acetal in which the acetal group is part of a 5 or 6 membered ring, respectively
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Is the formation of acetals reversible?
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Yes
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The reaction is driven to the right by
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the use of excess alcohol as the solvent or the removal of the water by-product, or both
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benzene-water azeotrope
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mixture of benzene and water that has a lower boiling point than either benzene or water alone
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Mechanism for acetal formation
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acid-catalyzed addition of the alcohol to the carbonyl group to give a hemiacetal, which reacts when OH is protonated & water lost to give relatively stable carbocation, an a-alkoxy carbocation
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hemiacetal
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compound with an OR and OH group on same carbon
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Mechanism 2
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Loss of water from the hemiacetal is an Sn1 rxn -> nuc rxn of an alcohol w the cation & deprotonation of nuc O
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Mechanism for acetal formation is really combination of
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acid-catalyzed carbonyl addition followed by substitution by SN1 mechanism
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Acetal hydrolysis
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acetals in presence of acid & excess h2o transformed rapidly back into corresponding carbonyl cmpds & alcohols
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The formation of hemiacetals is catalyzed by
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acids and bases
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the conversion of hemiacetals into acetals is catalyzed
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only by acids
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In what solutions are acetals stable?
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basic and neutral
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Hemiacetals in most cases cannot be isolated because
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they react further to yield acetals (in alcohol solution under acidic conditions) or decompose to aldehydes or ketones and an alcohol
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Do simple aldehydes form appreciable amts of hemiacetals in alcohol solution?
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Yes, just as they form appreciable amounts of hydrates in H2O
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hydroxy aldehydes spontaneously form
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five and six membered cyclic hemiacetals, and most are stable cmpds that can be isolated
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Intramolecular rxns are faster and..
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favored thermodynamically (have larger equilibrium constants)
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Protecting group
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chemical disguise so that a reagent reacts w one mlc and not another: most common are acetals for aldehydes & ketones
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Acetals are commonly used to protect the carbonyl groups of aldehydes & ketones from
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basic, nuc reagents
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Once the protection is no longer needed
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The acetal protecting group is removed, carbonyl re-exposed by treatment w dilute aq. acid
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Primary amine
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organic derivative of ammonia in which only one ammonia hydrogen replaced by an alkyl or aryl group
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imine
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nitrogen analog of an aldehyde or ketone in which C=O group replaced by C=NR group
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reversible, generally w acid or base catalysis or w heat, typically driven to completion by ppt of imine removal of H2O or both
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Mechanism imine formation
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nuc addition to carbonyl to give unstable carbinolamine
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carbinolamine
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cmpd w amine group -NH2, -NHR or NR2 & hydroxy group on same C
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Mechanism imine formation 2
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carbinolamine undergoes acid-catalyzed dehydration to form imines, faster than dehydration of ordinary alcohol
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Why is imine formation catalyzed by acids?
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The dehydration is typically the rate-limiting step, but if acid conc is too high --> the protonated (pulls equilibrium to left) amine (basic) cannot act as a nuc
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Uses of imines
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preparation of amines, characterization of aldehydes & ketones
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derivatives
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crystalline cmpds: basis for ID of cmpd when isolated from a source or from a diff. rxn
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Why is it important to prepare derivatives?
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If two compounds have very similar mp or bp
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secondary amine
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R2NH
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Enamine
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amine nitrogen bound to a carbon that is part of a db
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provided that the carbonyl has an a-hydrogen, formation of a ___ occurs when a secondary amine reacts with an aldehyde or ketone
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Is this process reversible?
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Yes (formation of an enamine) & must be driven to completion by the removal of one of reaction products (usually H2O)
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In what do enamines revert to the corresponding carbonyl cmpds?
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aqueous acid
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Mechanism of enamine formation
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Nuc addition: carbinolamine w no hydrogen on nitrogen so imine formation cannot occur
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Enamine mech 2
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dehydration of carbinolamine: loss of H from an adjacent C
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Why don't primary amines react w aldehydes or ketones to form enamines rather than imines?
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The enamines bear the same relationship to imines that enols bear to ketones
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What is more stable, an imine or enamine?
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Imine
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tertiary amine
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R3N
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Do tertiary amines react w aldehydes or ketones to form stable derivatives?
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no
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Tertiary amines are good nuc but have no ____ so cannot form carbinolamines
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NH hydrogens - adducts w aldehydes & ketones are unstable, can only break down to starting materials
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