chapter 19. aldehydes and ketones: nucleophilic addition reactions based on mcmurry’s organic...
TRANSCRIPT
![Page 1: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/1.jpg)
Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions
Based on McMurry’s Organic Chemistry, 6th edition
![Page 2: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/2.jpg)
Aldehydes and Ketones
• Aldehydes and ketones are characterized by the the carbonyl functional group (C=O)
• The compounds occur widely in nature as intermediates in metabolism and biosynthesis
• They are also common as chemicals, as solvents, monomers, adhesives, agrichemicals and pharmaceuticals
![Page 3: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/3.jpg)
19.1 Naming Aldehydes and Ketones
• Aldehydes are named by replacing the terminal -e of the corresponding alkane name with –al
• The parent chain must contain the CHO group– The CHO carbon is numbered as C1
• If the CHO group is attached to a ring, use the suffix See Table 19.1 for common names
![Page 4: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/4.jpg)
![Page 5: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/5.jpg)
![Page 6: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/6.jpg)
![Page 7: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/7.jpg)
![Page 8: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/8.jpg)
![Page 9: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/9.jpg)
![Page 10: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/10.jpg)
![Page 11: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/11.jpg)
19.2 Preparation of Aldehydes and Ketones
• Preparing Aldehydes
• Oxidize primary alcohols using pyridinium chlorochromate
• Reduce an ester with diisobutylaluminum hydride (DIBAH)
![Page 12: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/12.jpg)
Preparing Ketones
• Oxidize a 2° alcohol (see Section 17.8)
• Many reagents possible: choose for the specific situation (scale, cost, and acid/base sensitivity)
![Page 13: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/13.jpg)
Ketones from Ozonolysis
• Ozonolysis of alkenes yields ketones if one of the unsaturated carbon atoms is disubstituted (see Section 7.8)
![Page 14: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/14.jpg)
Aryl Ketones by Acylation
• Friedel–Crafts acylation of an aromatic ring with an acid chloride in the presence of AlCl3 catalyst (see Section 16.4)
![Page 15: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/15.jpg)
Methyl Ketones by Hydrating Alkynes
• Hydration of terminal alkynes in the presence of Hg2+ (catalyst: Section 8.5)
![Page 16: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/16.jpg)
![Page 17: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/17.jpg)
19.3 Oxidation of Aldehydes and Ketones
• CrO3 in aqueous acid oxidizes aldehydes to carboxylic acids efficiently
• Silver oxide, Ag2O, in aqueous ammonia (Tollens’ reagent) oxidizes aldehydes (no acid)
![Page 18: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/18.jpg)
![Page 19: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/19.jpg)
![Page 20: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/20.jpg)
![Page 21: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/21.jpg)
Hydration of Aldehydes
• Aldehyde oxidations occur through 1,1-diols (“hydrates”)
• Reversible addition of water to the carbonyl group• Aldehyde hydrate is oxidized to a carboxylic acid by
usual reagents for alcohols
![Page 22: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/22.jpg)
Ketones Oxidize with Difficulty
• Undergo slow cleavage with hot, alkaline KMnO4
• C–C bond next to C=O is broken to give carboxylic acids
• Reaction is practical for cleaving symmetrical ketones
![Page 23: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/23.jpg)
19.4 Nucleophilic Addition Reactions of Aldehydes and Ketones
• Nu- approaches 45° to the plane of C=O and adds to C
• A tetrahedral alkoxide ion intermediate is produced
![Page 24: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/24.jpg)
Nucleophiles
• Nucleophiles can be negatively charged ( : Nu) or neutral ( : Nu) at the reaction site
• The overall charge on the nucleophilic species is not considered
![Page 25: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/25.jpg)
19.5 Relative Reactivity of Aldehydes and Ketones
• Aldehydes are generally more reactive than ketones in nucleophilic addition reactions
• The transition state for addition is less crowded and lower in energy for an aldehyde (a) than for a ketone (b)
• Aldehydes have one large substituent bonded to the C=O: ketones have two
![Page 26: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/26.jpg)
Electrophilicity of Aldehydes and Ketones
• Aldehyde C=O is more polarized than ketone C=O• As in carbocations, more alkyl groups stabilize +
character• Ketone has more alkyl groups, stabilizing the C=O
carbon inductively
![Page 27: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/27.jpg)
Reactivity of Aromatic Aldehydes
• Less reactive in nucleophilic addition reactions than aliphatic aldehydes
• Electron-donating resonance effect of aromatic ring makes C=O less reactive electrophilic than the carbonyl group of an aliphatic aldehyde
![Page 28: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/28.jpg)
19.6 Nucleophilic Addition of H2O: Hydration
• Aldehydes and ketones react with water to yield 1,1-diols (geminal (gem) diols)
• Hyrdation is reversible: a gem diol can eliminate water
![Page 29: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/29.jpg)
Relative Energies
• Equilibrium generally favors the carbonyl compound over hydrate for steric reasons
– Acetone in water is 99.9% ketone form
• Exception: simple aldehydes– In water, formaldehyde consists is 99.9% hydrate
![Page 30: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/30.jpg)
Base-Catalyzed Addition of Water
• Addition of water is catalyzed by both acid and base
• The base-catalyzed hydration nucleophile is the hydroxide ion, which is a much stronger nucleophile than water
![Page 31: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/31.jpg)
Acid-Catalyzed Addition of Water
• Protonation of C=O makes it more electrophilic
![Page 32: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/32.jpg)
Addition of H-Y to C=O
• Reaction of C=O with H-Y, where Y is electronegative, gives an addition product (“adduct”)
• Formation is readily reversible
![Page 33: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/33.jpg)
19.7 Nucleophilic Addition of HCN: Cyanohydrin Formation
• Aldehydes and unhindered ketones react with HCN to yield cyanohydrins, RCH(OH)CN
![Page 34: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/34.jpg)
Mechanism of Formation of Cyanohydrins
• Addition of HCN is reversible and base-catalyzed, generating nucleophilic cyanide ion, CN
• Addition of CN to C=O yields a tetrahedral intermediate, which is then protonated
• Equilibrium favors adduct
![Page 35: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/35.jpg)
Uses of Cyanohydrins
• The nitrile group (CN) can be reduced with LiAlH4 to yield a primary amine (RCH2NH2)
• Can be hydrolyzed by hot acid to yield a carboxylic acid
![Page 36: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/36.jpg)
![Page 37: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/37.jpg)
19.8 Nucleophilic Addition of Grignard Reagents and Hydride Reagents: Alcohol Formation
• Treatment of aldehydes or ketones with Grignard reagents yields an alcohol
– Nucleophilic addition of the equivalent of a carbon anion, or carbanion. A carbon–magnesium bond is strongly polarized, so a Grignard reagent reacts for all practical purposes as R : MgX +.
![Page 38: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/38.jpg)
Mechanism of Addition of Grignard Reagents
• Complexation of C=O by Mg2+, Nucleophilic addition of R : ,
protonation by dilute acid yields the neutral alcohol• Grignard additions are irreversible because a carbanion is
not a leaving group
![Page 39: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/39.jpg)
![Page 40: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/40.jpg)
Hydride Addition
• Convert C=O to CH-OH• LiAlH4 and NaBH4 react as donors of hydride ion• Protonation after addition yields the alcohol
![Page 41: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/41.jpg)
![Page 42: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/42.jpg)
19.9 Nucleophilic Addition of Amines: Imine and Enamine Formation
RNH2 adds to C=O to form imines, R2C=NR (after loss of HOH)
R2NH yields enamines, R2NCR=CR2 (after loss of HOH)
(ene + amine = unsaturated amine)
![Page 43: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/43.jpg)
![Page 44: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/44.jpg)
Mechanism of Formation of Imines
• Primary amine adds to C=O• Proton is lost from N and adds to O to yield a neutral
amino alcohol (carbinolamine)• Protonation of OH converts into water as the leaving
group• Result is iminium ion, which loses proton• Acid is required for loss of OH – too much acid blocks
RNH2
Note that overall reaction is substitution of RN for O
![Page 45: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/45.jpg)
![Page 46: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/46.jpg)
![Page 47: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/47.jpg)
![Page 48: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/48.jpg)
Imine Derivatives
• Addition of amines with an atom containing a lone pair of electrons on the adjacent atom occurs very readily, giving useful, stable imines
• For example, hydroxylamine forms oximes and 2,4-dinitrophenylhydrazine readily forms 2,4-dinitrophenylhydrazones
– These are usually solids and help in characterizing liquid ketones or aldehydes by melting points
![Page 49: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/49.jpg)
Enamine Formation
• After addition of R2NH, proton is lost from adjacent carbon
CC
O
C
C
O
H++ R2NH
NH
R
C
C
HON
R
C
C
H2ON
R
C
CN
R
+ H3O+
R
H
H HH
H H
R R R
H H H
![Page 50: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/50.jpg)
![Page 51: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/51.jpg)
![Page 52: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/52.jpg)
19.11 Nucleophilic Addition of Alcohols: Acetal Formation
• Two equivalents of ROH in the presence of an acid catalyst add to C=O to yield acetals, R2C(OR)2
• These can be called ketals if derived from a ketone
![Page 53: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/53.jpg)
Formation of Acetals
• Alcohols are weak nucleophiles but acid promotes addition forming the conjugate acid of C=O
• Addition yields a hydroxy ether, called a hemiacetal (reversible); further reaction can occur
• Protonation of the OH and loss of water leads to an oxonium ion, R2C=OR+ to which a second alcohol adds to form the acetal
![Page 54: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/54.jpg)
![Page 55: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/55.jpg)
Uses of Acetals
• Acetals can serve as protecting groups for aldehydes and ketones
• It is convenient to use a diol, to form a cyclic acetal (the reaction goes even more readily)
![Page 56: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/56.jpg)
![Page 57: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/57.jpg)
![Page 58: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/58.jpg)
![Page 59: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/59.jpg)
![Page 60: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/60.jpg)
![Page 61: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/61.jpg)
![Page 62: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/62.jpg)
19.12 Nucleophilic Addition of Phosphorus Ylides: The Wittig Reaction
• The sequence converts C=O is to C=C• A phosphorus ylide adds to an aldehyde or ketone to
yield a dipolar intermediate called a betaine • The intermediate spontaneously decomposes through
a four-membered ring to yield alkene and triphenylphosphine oxide, (Ph)3P=O
• Formation of the ylide is shown below
![Page 63: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/63.jpg)
A Note on the Word “Betaines”
• The term “betaines” is an extension from a specific substance (betaine) that has permanent + and – charges (as in a zwitterion) that cannot be neutralized by proton transfers (as in normal amino acids). Webster's Revised Unabridged Dictionary lists: Betaine \Be"ta*ine\, n. [From beta, generic name of the beet.] (Chem.) A nitrogenous base, {C5H11NO2}, produced artificially, and also occurring naturally in beet-root molasses and its residues. The listed pronunciation indicates it has the exact same emphasis as “cocaine”.
• Cocaine \Co"ca*ine\, n. (Chem.) A powerful alkaloid, {C17H21NO4}, obtained from the leaves of coca
• So – if you say “co-ca-een” (as this dictionary suggests) then you would also say “bee-ta-een”. If you sat “co-cayn” then say “beet-ayn”.
• Whatever you say, the “beta” in “betaine” refers to beets and not a letter in the Greek alphabet. There have been a lot of wagers on this over the years.
RK
![Page 64: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/64.jpg)
Uses of the Wittig Reaction
• Can be used for monosubstituted, disubstituted, and trisubstituted alkenes but not tetrasubstituted alkenes The reaction yields a pure alkene of known structure
• For comparison, addition of CH3MgBr to cyclohexanone and dehydration with, yields a mixture of two alkenes
![Page 65: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/65.jpg)
Mechanism of the Wittig Reaction
![Page 66: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/66.jpg)
![Page 67: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/67.jpg)
![Page 68: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/68.jpg)
![Page 69: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/69.jpg)
![Page 70: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/70.jpg)
19.14 Conjugate Nucleophilic Addition to -Unsaturated Aldehydes and Ketones
• A nucleophile can add to the C=C double bond of an ,-unsaturated aldehyde or ketone (conjugate addition, or 1,4 addition)
• The initial product is a resonance-stabilized enolate ion, which is then protonated
![Page 71: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/71.jpg)
Conjugate Addition of Amines
• Primary and secondary amines add to , -unsaturated aldehydes and ketones to yield -amino aldehydes and ketones
![Page 72: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/72.jpg)
![Page 73: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/73.jpg)
![Page 74: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/74.jpg)
![Page 75: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/75.jpg)
![Page 76: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/76.jpg)
Mechanism of Alkyl Conjugate Addition
• Conjugate nucleophilic addition of a diorganocopper anion, R2Cu, an enone
• Transfer of an R group and elimination of a neutral organocopper species, RCu
![Page 77: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/77.jpg)
Conjugate Addition of Alkyl Groups: Organocopper Reactions
• Reaction of an , -unsaturated ketone with a lithium diorganocopper reagent
• Diorganocopper (Gilman) reagents from by reaction of 1 equivalent of cuprous iodide and 2 equivalents of organolithium
• 1, 2, 3 alkyl, aryl and alkenyl groups react but not alkynyl groups
![Page 78: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/78.jpg)
![Page 79: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/79.jpg)
![Page 80: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/80.jpg)
![Page 81: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/81.jpg)
![Page 82: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/82.jpg)
![Page 83: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/83.jpg)
![Page 84: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/84.jpg)
![Page 85: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/85.jpg)
Enantioselective Synthesis
• When a chiral product is formed achiral reagents, we get both enantiomers in equal amounts - the transition states are mirror images and are equal in energy
• However, if the reaction is subject to catalysis, a chiral catalyst can create a lower energy pathway for one enantiomer - called an enantionselective synthesis
• Reaction of benzaldehyde with diethylzinc with a chiral titanium-containing catalyst, gives 97% of the S product and only 3% of the R
![Page 86: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/86.jpg)
Summary
• Aldehydes are from oxidative cleavage of alkenes, oxidation of 1° alcohols, or partial reduction of esters
• Ketones are from oxidative cleavage of alkenes, oxidation of 2° alcohols, or by addition of diorganocopper reagents to acid chlorides.
• Aldehydes and ketones are reduced to yield 1° and 2° alcohols , respectively
• Grignard reagents also gives alcohols • Addition of HCN yields cyanohydrins• 1° amines add to form imines, and 2° amines yield enamines• Reaction of an aldehyde or ketone with hydrazine and base yields an
alkane• Alcohols add to yield acetals• Phosphoranes add to aldehydes and ketones to give alkenes (the
Wittig reaction) -Unsaturated aldehydes and ketones are subject to conjugate
addition (1,4 addition)
![Page 87: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/87.jpg)
![Page 88: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/88.jpg)
![Page 89: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/89.jpg)
![Page 90: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/90.jpg)
![Page 91: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/91.jpg)
![Page 92: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/92.jpg)
![Page 93: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/93.jpg)
![Page 94: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/94.jpg)
![Page 95: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/95.jpg)
![Page 96: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/96.jpg)
![Page 97: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/97.jpg)
![Page 98: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/98.jpg)
![Page 99: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/99.jpg)
![Page 100: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/100.jpg)
![Page 101: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/101.jpg)
![Page 102: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/102.jpg)
![Page 103: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/103.jpg)
![Page 104: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/104.jpg)
![Page 105: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/105.jpg)
![Page 106: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/106.jpg)
![Page 107: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/107.jpg)
![Page 108: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/108.jpg)
![Page 109: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/109.jpg)
![Page 110: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/110.jpg)
![Page 111: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/111.jpg)
![Page 112: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/112.jpg)
![Page 113: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/113.jpg)
![Page 114: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/114.jpg)
![Page 115: Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions Based on McMurry’s Organic Chemistry, 6 th edition](https://reader035.vdocuments.mx/reader035/viewer/2022081801/56649cda5503460f949a3885/html5/thumbnails/115.jpg)