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Chemistry Guide
formed)
+ HCl Other reagents: sulfonic acid (sulfonyl) chlorides Mechanism! To other syntheses of esters
Intermediate is ROSOCl, the half-ester; the reaction is stereospecific. The reaction of PCl3 and PBr3 is similar; no rearrangements.
Mechanism!; SN2 reaction. Note that more substituted halides will undergo the E2 elimination instead.
Mechanism!; SN1 and E1; other reagents HCl, HI Reference McMurry 10.7, 11.10, 17.7, Fessenden 7.4-7.6, Schmid 11.17, 12.10, 12.11, 12.16
Elimination
+ H2 O Mechanism!: E1; other reagents H3PO4 (acid must be very concentrated). McMurry 17.3, 17.7, Fessenden 7.6
Oxidation
Other reagents: K2Cr2O7 + H2SO4 or CrO3 + H2SO4 or KMnO4 + OH- or KMnO4 + H3O+ Reference McMurry 17.8, Fessenden 7.8, Schmid 11.18
Note that all aqueous chromium reagents and permanganate oxidize primary aldehydes to carboxylic acids and cannot be used for this reaction; selective reagents are needed. Reference McMurry 17.8, Fessenden 7.8, Schmid 11.18
+ MnO2 Other reagents: H2CrO4 or K2Cr2O7 + H2SO4 or CrO3 + H2SO4 Reference McMurry 17.8, Fessenden 7.8, Schmid 11.18, 15.5
Mechanism! SN2 reaction. Will be SN1 for tertiary halides (carbocations, rearrangements) Competition also from E2 elimination in non-aqueous solvents McMurry 7.1, 10.7, 11.9, 17.7, Fessenden 5.4, 5.8, 5.9; Schmid 12.1, 12.2
+ H2O Oxidation, followed by reduction, giving the more substituted alcohol. Other reagents: acid and water, but these simple addition conditions give rearrangements if a more stable
Reduction followed by oxidation, giving the less substituted alcohol. McMurry 7.4, Fessenden 10.9; Schmid 8.1 - 8.4
Other reagents: KMnO4 with no heat. Heating an alkene with basic KMnO4 results in cleavage of the double bond to form ketones and carboxylic acids. McMurry 7.8, Fessenden 10.13A & B; Schmid 8.5
Other reagents: aqueous sodium hydroxide for epoxide opening. Both reactions are stereospecific and usually SN2 the base-catalyzed reaction occurs predominantly at the less substituted carbon, but the acid-catalyzed addition occurs predominantly at the more substituted carbon (if the starting material is a single enantiomer, the products of these two
methods of opening the ring are the enantiomers). McMurry 7.4, 17.4, Fessenden 8.2B & C, 10.13A, Schmid 8.6, 13.12
Stereospecific! Base-catalyzed ring opening is by SN2, at the less substituted carbon. Note that other nucleophiles, such as thiols, thiolates, cyanide, also will open the ring. McMurry 7.4, Fessenden 8.4A, Schmid 13.12
Mechanism! McMurry 6.8, 6.9, 7.2, 9.17, Fessenden 13.4, Schmid 14.9
A hemiketal (hemiacetal): half alcohol and half ether; unstable to conversion to ketal or ketone, depending on conditions. Mechanism! Reversible Fessenden 13.4B Schmid 14.11
+ CH3OH Other reagents: NaBH4, H2with Pt Other substrates: This reaction also works well with acid chlorides. However, if you use a carboxylic acid as reagent, the acidic hydrogen reacts first, converting the substrate to an anion and making it les reactive. Only LiAlH4 can do this reduction. Fessenden 15.5, 15.3, 14.7; Schmid 15.17
Note that two moles of Grignard reagent are required to do this reaction. The product from addition of one mole of Grignard is a ketone which also reacts with Grignard. If two moles of Grignard are not present, incomplete reaction yields a mixture of products and starting materials. McMurry 10.8, Fessenden 15.5; Schmid 16.13
Note that two moles of Grignard reagent are required to do this reaction. The product from addition of one mole of Grignard is a ketone which also reacts with Grignard. If two moles of Grignard are not present, incomplete reaction yields a mixture of products and starting materials. Fessenden 15.3; Schmid 16.13
Reference McMurry 6.8. 6.9, 7.2, 9.17, Fessenden 7.4, Schmid 11.17, 12.9
and / or Reference McMurry 6.8, 6.9, 7.1, 7.2, 9.17, Fessenden 7.4 - 7.6, Schmid 11.17, 12.10, 12.11, 12.16
McMurry 7.1, 10.7, 11.9, 17.7, Schmid Fessenden 7.3A, 12.1, 12.2
McMurry 6.8, 6.9, 7.2, 9.17, Reference 10.8, 10.9, Schmid 8.1 - 8.4
Reference McMurry 6.8, 6.9, 7.1, 7.2, 9.17, Fessenden 7.4, Schmid 11.17, 12.9
and / or Reference McMurry 17.8, Fessenden 7.4 - 7.6, Schmid 11.17, 12.10, 12.11, 12.16
Reference McMurry 10.8, Fessenden 15.3C, Schmid 16.13 For a review without problems go to graphical summaries of reactions of alcohols or syntheses of alcohols. For a different selection, go back to the Graphical Reactions Menu Reference McMurry 10.8, Fessenden 15.5C, Schmid 16.9
ALKANES
7 CO2 + 14 H2O Combustion occurs for all organic compounds except those that are perchlorinated or perfluorinated. The reaction can be used to determine simple formula or heat of combustion (from which can be determined relative stability). McMurry 4.4, Schmid 2.10, 7.5
Mechanism! Free radical reaction produces the most substituted halide in the highest concentration. Reaction accelerated by heat and/or light. McMurry 7.5, Fessenden 6.1-6.6, Schmid 18.1 - 18.4,
Activated alkanes
An adjacent carbon-carbon double bond or aromatic ring stabilizes the intermediate radicals (allyl and benzyl) and makes reaction at these sites easier than tertiary.
Other reagents: CrO3 + HOAc, CrO3 + H2SO4 + H2O, and other weakened chromium reagents.
Stereospecific! Surface reaction, complete reduction usually occurs McMurry 7.7, Schmid 8.11
+ ZnI2 Stereospecific! A dichlorocyclopropane ring can be made using chloroform and base (e.g. t-butoxide) McMurry 7.6, Schmid 8.7
McMurry 10.8, Moisture at any point after the Grignard is formed and before any other reaction will result in alkane formation.
Mechanism! May result in carbocation rearrangements. McMurry 6.8, 6.9, 7.2, 9.17, Fessenden 10.6, Schmid 7.8 - 7.17
Mechanism! May result in carbocation rearrangements. McMurry 7.4, Fessenden 10.7, Schmid 7.8 - 7.17
+ H2O Oxidation, followed by reduction, giving the more substituted alcohol. Other reagents: acid and water (see above), but these simple addition conditions give rearrangements if a more stable carbocation is possible. McMurry 7.4, Fessenden 10.8, Schmid 7.14, 8.10
Reduction followed by oxidation, giving the less substituted alcohol. 9-BBN and B2H6 can also be used to make amines and halides. McMurry , Fessenden 10.8-10.9, Schmid 8.1 - 8.4, 22.11
Reduction! BH3 does not exist as such, but dimerizes to form B2H6. Alternatives are available: 9-BBN, BH3 in an ether solvent or complexed to an amine. Click on the blue BBN box for more information. McMurry , Fessenden 10.8-10.9, Schmid 8.1 - 8.4
Symmetrical Reagents
Reduction
Stereospecific! Surface reaction, complete reduction usually occurs McMurry 7.7 , Fessenden 10.12B, Schmid 8.11
Oxidation
Mechanism! Stereospecific! Note that I2 adds like Br2; Cl2 adds too but is not stereospecific as it is too electronegative and too small to form a "chloronium" ion. F2 reacts explosively. McMurry 7.2, 10.3, Fessenden 10.10, Schmid 8.8
Sterospecific! Oxidation. Osmium can be reoxidized in the reaction with hydrogen peroxide. Other reagents: cold basic KMnO4 will also accomplish this seterospecific oxidation, but on heating cleaves the double bond like ozone (Schmid 14.3) McMurry 7.8, Fessenden 10.13, Schmid 8.5
+ RCO2H Stereospecific! See ethers for the opening of the epoxide ring. McMurry 17.4, Fessenden 10.13, Schmid 8.6
+ ZnI2 Stereospecific! A dichlorocyclopropane ring can be made using chloroform and base (e.g. t-butoxide) McMurry 7.7, Fessenden 10.13, Schmid 8.7
+ Diels Alder Reaction. Stereospecific! This is a reaction of the alkene and diene, not the C=O; it works best when the alkene is electron-deficient, so the C=O's function is to withdraw electrons McMurry 14.8, 30.6, Fessenden 16.3, Schmid 19.12 (NOT 19.10 and 19.11)
Mechanism!; SN1 and E1; other reagents: HCl, HI McMurry 5.1, 7.1, 11.10, 11.16, 11.19, 17.7, Fessenden 7.4-7.6, Schmid 11.17, 12.10, 12.11, 12.16
Elimination
Mechanism! E2, Stereospecific McMurry 11.12, 11.15, Fessenden 5.7-5.8, Schmid 12.12 - 12.15
By reduction
Stereospecific! For other reagents, click on the arrow above. McMurry 6.7, 8.6, 8.10, Fessenden 10.12B, Schmid 9.8
The Wittig reaction; works best with less substituted halides, aldehydes and ketones. Fessenden 13.4D, Schmid 14.16, 14.17
Miscellanea
+ Diels Alder Reaction. Stereospecific! This is a reaction of the alkene and diene, not the C=O; it works best when the alkene is electron-deficient, so the C=O's function is to withdraw electrons McMurry 14.8, 14.9, Fessenden 16.3, Schmid 19.12 (NOT 19.10 and 19.11)
McMurry 6.8, 6.9, 7.2, 9.17, Fessenden 10.6, Schmid 7.8 - 7.17
+ H2 O
McMurry 5.1, 6.8, 6.9, 7.1, 7.2, 9.17, 11.10, 11.16, 11.19, Fessenden 7.4 - 7.6, Schmid 11.17, 12.10, 12.11, 12.16
McMurry 1.2, 6.8, 6.9, 9.17, Fessenden 10.6, Schmid 7.8 - 7.17
+ H2 O Fessenden 7.6
Nucleophilic Substitution
Mechanism! Stereospecific SN2 reaction. Will be SN1 for tertiary halides (carboations, rearrangements) Competition also from E2 elimination in non-aqueous solvents McMurry 11.10, 16.8, Fessenden 5.4, 5.5, 5.10, Schmid 12.1, 12.2,
Mechanism! SN2 reaction. Note that more substituted halides will undergo the E2 elimination instead. McMurry 11.14, 11.15, 18.3, Fessenden 5.3, 8.2, Schmid 13.8C,
Mechanism! SN2 reaction. McMurry 11.21, 24.6, Fessenden 5.4, 5.10, Schmid 12.2 - 12.4,
The reaction is hard to control, because the products are at least as reactive; it works well for making amino acids from halo acids because the product is the conjugate acid of the amine (the carboxylic acid protonates it) Mechanism! McMurry 24.6, Fessenden 5.10, 18.4, Schmid 22.8,
The Wittig reaction; works best with less substituted halides, aldehydes and ketones. McMurry 19.12, Fessenden 13.5, Schmid 14.16, 14.17,
Elimination: Dehydrohalogenation
Mechanism! E2, Stereospecific, but may be E1 in polar solvents McMurry 11.10, 11.13, 11.15, Fessenden 5.7, 5.8, Schmid 12.12 - 12.15 ,
The Grignard reagent McMurry 10.8, 10.10, 17.6, Fessenden 7.3D, Schmid 11.7,
Note that aryl halides do not undergo any of these reactions except those with metals, e.g. the Grignard reaction. Nucleophilic aromatic substitution only occurs on rings with strongly electron-withdrawing substituents (Schmid 23.2, 23.3, Mc Murry 10.9).
Mechanism!; SN2; other reagents HCl, HI, H2SO4 McMurry 10.7, Fessenden 7.4-7.6, Schmid 11.17, 12.9
Mechanism!; SN1; other reagents HCl, HI McMurry 7.1, 10.7, 11.9, Fessenden 7.4-7.6, Schmid 11.17, 12.10, 12.16,
Intermediate is ROSOCl, the half-ester; the reaction is stereospecific. The reaction of PCl3 and PBr3 is similar; no rearrangements. McMurry 10.7, Fessenden 7.5, Schmid 11.17,
Mechanism! May result in carbocation rearrangements. McMurry 6.8, 6.9, Fessenden 10.6, Schmid 7.8 - 7.17,
Mechanism! Note that peroxides need to be present at the same time as the HBr for this free-radical antiMarkovnikov addition. McMurry 5.1, 5.6, 7.5, Fessenden 10.6, Schmid 18.5 - 18.6
Mechanism! Stereospecific! Note that I2 adds like Br2; Cl2 adds too but is not stereospecific as it is too electronegative and too small to form a "chloronium" ion. F2 reacts explosively. McMurry 10.10, Fessenden 10.9, Schmid 8.8
From Alkanes
Mechanism! Free radical reaction produces the most substituted halide in the highest concentration. Reaction
accelerated by heat and/or light. McMurry 5.1, 10.4, Fessenden 6.1-6.6, Schmid 18.1 - 18.4,
An adjacent carbon-carbon double bond or aromatic ring stabilizes the intermediate radicals (allyl and benzyl) and makes reaction at these sites easier than tertiary. McMurry 10.5, 10.6, Fessenden 6.5, Schmid 19.3, 20.9A,
Reference McMurry 7.1, 10.7, 17.7, Fessenden 7.4 - 7.6, Schmid 11.17, 12.10, 12.16
McMurry 11.10, 11.13, 11.15, Fessenden 5.7 - 5.8, Schmid 12.12 - 12.15
2 HINT: Same reaction as with Grignard if ether solvent concentration is not adequate. Note that aryl halides do not undergo any of these reactions except those with metals, e.g. the Grignard reaction. Nucleophilic aromatic substitution only occurs on rings with strongly electron-withdrawing substituents (McMurry, 10.9, Schmid 23.2, 23.3).
McMurry 6.8, 6.9, 7.2, 9.17, Fessenden 10.6, Schmid 7.8 - 7.17
Reference McMurry 10.7, 11.9, 7.1, 17.7, Fessenden 7.4 - 7.6, Schmid 11.17, 12.10, 12.16
McMurry 11.10, 11.13, 11.15, Fessenden 5.7 - 5.8, Schmid 12.12 - 12.15
McMurry 6.8, 6.9, 7.2, 9.17, Fessenden 10.6, Schmid 18.5 - 18.6
excess
2 HINT: Same reaction as with Grignard if ether solvent concentration is not adequate.
Note that aryl halides do not undergo any of these reactions except those with metals, e.g. the Grignard reaction. Nucleophilic aromatic substitution only occurs on rings with strongly electron-withdrawing substituents (Schmid 23.2, 23.3).
Simple Additions
Mechanism! Rearrangement of the enol. McMurry 8.5, Fessenden 10.7, Schmid 9.7A
+ H2O
The enol is formed and rearranges to the ketone, which is in turn reduced by the sodium borohydride; sodium borohydride is almost always used in excess because the hydrides react with air and water, making the number of moles uncertain. McMurry 8.5, 17.15, 19.8, Fessenden 10.8, Schmid 9.7A
See alkene reactions for details. McMurry 8.5, Fessenden 10.9, Schmid 9.7B
Reduction
Stereospecific! Surface reaction, complete reduction usually occurs McMurry 8.6, 8.7, Fessenden 10.12, Schmid 9.8
Oxidation
As Weak Acids
+ SN2 reaction, stereospecific if halide is secondary McMurry 8.6, 8.8, 8.9, Fessenden 10.4, Schmid 9.10
From halides
E2 elimination to form the haloalkene can be done with methoxide but a stronger base is needed to remove the
CH3CH2CH2Br +
Both SN2 and SN1 (and E1) reactions occur, depending on the substrate. If a phenyl ether is used, SN2/SN1 reaction occurs only on the alkyl carbon, leaving phenol as a product. McMurry 18.5, Fessenden 8.3, Schmid 13.9
Epoxides
These strained ethers are very easy to make but very reactive toward nucleophiles; think of them as spring-loaded ethers. One enantiomer is shown for each starting material and product.
Stereospecific! Base-catalyzed ring opening is by SN2 at the less substituted carbon. McMurry 18.8, Fessenden 8.4, Schmid 13.12
Stereospecific! Base-catalyzed ring opening is by SN2, at the less substituted carbon. Note that other nucleophiles , such as thiols, thiolates, cyanide, also will open the ring. McMurry 18.8, Fessenden 8.4, Schmid 13.12
Stereospecific, giving the enantiomer of that shown. Acid catalyzed ring opening occurs via SN1 on the protonated epoxide, on the more substituted carbon but with strong preference for the backside. McMurry 18.8, Fessenden 8.4, Schmid 13.12
Stereospecific, as shown. Acid catalyzed ring opening occurs via SN1 on the protonated epoxide, on the more
substituted carbon but with strong preference for the backside. McMurry 18.8, Fessenden 8.4, Schmid 13.12
Mechanism!; SN2 reaction, Williamson synthesis Note that some alkene is also formed, by competition from the E2 reaction; more substituted halides will undergo only the E2 elimination. McMurry 8.3, 11.5, 11.9, Fessenden 5.3A, 5.10, 8.2B, Schmid 13.8C, 12.2 - 12.5, 12.14
From alkenes
+ CH3OH
This method is better than the Williamson synthesis if the carbon is not primary. McMurry 18.4, Fessenden 10.8, Schmid 8.10, 13.8
Epoxides
These strained ethers are very easy to make (from alkenes) but very reactive.
McMurry 8.3, 11.5, 11.9, 18.3, Fessenden 5.3A, 5.10, 8.2B, Schmid 13.8C, 12.2 - 12.5, 12.14
+ CH3OH
CH3CH2CH2Br +
answer shows enantiomer - sorry for the confusion. McMurry 18.7, Fessenden 8.2, Schmid 13.10, 8.9
McMurry 8.3, 11.5, 11.9, 18.3, Fessenden 5.3A, 5.10, 8.2B, Schmid 13.8C, 12.2 - 12.5, 12.14
+ CH3OH
CH3CH2CH2Br +
answer shows enantiomer - sorry for the confusion. McMurry 18.7, Fessenden 8.2, Schmid 13.10, 8.9
Mechanism! Reversible, with equilibrium favoring C=O McMurry 19.11, Fessenden 13.4A, Schmid 14.10
Other reagents: NaBH4, H2, Pt McMurry 17.5, 19.8, Fessenden 13.6B, Schmid 11.7
Clemmensen reduction Other reagents: NH2NH2 + KOH (Wolff-Kischner) or ethanethiol in acid, followed by Raney nickel. If the aldehyde or ketone in conjugated with an aromatic ring, e.g. benzaldehyde, complete reduction can be done with H2, Pd (McMurry 16.11) Fessenden 13.6C, Schmid 21.10
An enamine, which reacts like an enolate McMurry19.9, Fessenden 13.5B, Schmid 14.13, 17.14
Wittig Reaction (also a reduction); see halide reactions for synthesis of the reagent. McMurry 19.12, Fessenden 13.5D, Schmid 14.16 - 14.17
Tollens' test Other reagents: Ag2O, Cu++ (Fehling's and Benedict's tests), all aqueous Cr(VI) reagents, KMnO4 McMurry 17.8, 19.2, 20.6 Fessenden 13.7, Schmid 14.18
Other reagents: K2Cr2O7 + H2SO4 or CrO3 + H2SO4 or KMnO4 + OH- or KMnO4 + H3O+ McMurry 17.8, 19.2, 19.3, Fessenden 7.8C, 13.2, Schmid 11.18
Note that all aqueous chromium reagents and permanganate oxidize primary aldehydes to carboxylic acids and cannot be used for this reaction; selective reagents are needed. McMurry 17.8, 19.2, 19.3, 20.6, Fessenden 7.8C, 13.2, Schmid 11.18
Other reagents: CrO3 + HOAc and several other chromium reagents. McMurry 19.2, 19.3, 19.10, 20.6, Fessenden 13.7, Schmid 20.9B
By Reduction
Note that Grignard reagents reduce ketones to tertiary alcohols and cannot be used for this reaction; selective reagents are needed. McMurry 19.2, 19.8, 21.8, Fessenden 15.3C, Schmid 16.14B
Note that LiAlH4 and NaBH4 reduce aldehydes and ketones to alcohols and cannot be used for this reaction; selective reagents are needed. McMurry 21.4, Fessenden 15.3C, Schmid 16.14A
By addition
By Substitution
+ 2 CH3CH2OH
Ketones and aldehydes are easily regenerated from their acetals, imines, enamines, etc. Since water has replaced something else, the process is called hydrolysis. Mechanism! Reversible
McMurry 17.8, 19.2, 19.3, 20.6, Fessenden 7.8C, 13.2, Schmid 11.18
+ 2 CH3CH2OH
McMurry 17.8, 19.2, 19.3, 20.6, Fessenden 7.8C, 13.2, Schmid 11.18
Addition / Reduction
Other reagents: NaBH4 is not a strong enough reducing agent to do this reaction (unless it has help from an acidic reagent). Nitrile reduction is essentially the same. McMurry 24.6, 21.7, Fessenden 15.8C, Schmid 16.12, 16.15 To other syntheses of amines
Other reagents: NaBH4 is not a strong enough reducing agent to do this reaction (unless it has help from an acidic reagent). McMurry 21.7, 24.7, Fessenden 15.8C, Schmid 16.12, To other syntheses of amines
This reaction cannot be done with primary and secondary amides which are acidic enough to destroy the Grignard Reagent. Tertiary amides react like the nitrile shown here but may be sterically hindered from reaction with some Grignards. This reaction produces an intermediate imine which is hydrolyzed to the ketone on neutralization in water. Reference McMurry 19.6, 21.6, Schmid 16.15 To other syntheses of ketones
Other reagents: H2O, OH-; primary, secondary and tertiary amides all undergo this reaction. Nitrile hydrolysis is essentially the same; in fact, amides are intermediates in nitrile hydrolysis. McMurry 21.6, Fessenden 15.8C, Schmid 15.11, 15.12
Addition / Elimination
+ HCl Anhydrides react similarly yielding one mole of the acid instead of HCl McMurry 21.4 24.7, Fessenden 15.3C, Schmid 16.5 Mechanism! To other reactions of acid chlorides
+ HCl Anhydrides react similarly yielding one mole of the acid instead of HCl McMurry 21.4, 24.7, Fessenden 15.3C, Schmid 16.5 Mechanism! To other reactions of acid chlorides
Other reagents: NaBH4 McMurry 21.7, 24.6, Fessenden 15.8C, Schmid 16.12, 16.15
Other reagents: NaBH4 McMurry 21.7, 24.6, Fessenden 15.8C, Schmid 16.12
Other reagents: NaBH4 McMurry 21.7, 24.6, Fessenden 15.8C Schmid 16.12, 16.15
Other reagents: NaBH4 McMurry 21.7, 24.6, Fessenden 15.8C Schmid 16.12
Note that the pKa of the conjugate acid is most commonly used instead of pKb of the amine. McMurry 24.6, Fessenden 18.6, Schmid 22.5
Reaction is very hard to control Mechanism! McMurry 11.2, 11.5, 24.6, Fessenden 18.7, Schmid 22.8
+ HCl Anhydrides react similarly yielding one mole of the carboxylic acid instead of HCl Mechanism! McMurry 21.7, 24.7, Fessenden 18.7, Schmid 16.5, 22.18 To other reactions of acid chlorides
An imine. Anhydrous conditions needed. This reaction works better if the amine has an electron-withdrawing group to make it less basic. In that case, the acid protonates the carbonyl, making it more reactive. Examples include substituted hydrazines (NH2NHR), where the other nitrogen makes the one on the left less basic. Mechanism! McMurry 23.12, Fessenden 13.5A, Schmid 14.13 - 14.15 To other reactions of aldehydes and ketones
An enamine, which reacts like an enolate. Anhydrous conditions needed. McMurry 23.12, Fessenden 13.5B, Schmid 14.13, 17.14 To other reactions of aldehydes and ketones
Oxidation
McMurry 24.8, Fessenden 12.3A, Schmid 22.14 - 22.15 Diazonium salts are very useful in synthesis.
+ H3O+ McMurry 24.6, Fessenden 18.4A, Schmid 22.5 Note the universal use of pKa in organic chemistry.
By nucleophilic substitution
The reaction is hard to control, because the products are at least as reactive; it works well for making amino acids from halo acids because the product is the conjugate acid of the amine (the carboxylic acid protonates it) Mechanism! McMurry 11.2, 11.5, 24.6, Fessenden 18.4A, Schmid 22.8
Other reagents for hydrolysis: NaOH, H2O and heat. You have learned the mechanisms for the steps of this synthesis: SN2, amide hydrolysis McMurry 24.6, Fessenden 18.4A, Schmid 22.9 (Gabriel synthesis), 16.8
Other reagents: NaBH4 Nitrile reduction is essentially the same. McMurry 24.6, Fessenden 18.4B, Schmid 16.12, 16.15
McMurry 24.6, Fessenden 18.4B, Schmid 22.10, 12.4 Azide ion (N3- is similar to CN-, except that the synthesis of cyanide (nitrile) from halide adds a carbon to the chain.
By addition to alkenes
McMurry 24.8, Fessenden 12.3, Schmid 22.14 - 22.15 Reactions of Aryl Diazonium Salts made from Anilines
McMurry 24.8, Fessenden 12.3A, Schmid 22.14 - 22.15 Reactions of Aryl Diazonium Salts made from Anilines
Br2 and FeBr3 will make bromobenzene, and Fe may be used instead of FeX3. McMurry 16.1 Fessenden 11.8A, Schmid 21.5 Mechanism!
Nitration
Sulfonation
McMurry 16.2, Fessenden 11.8F, Schmid 21.7 Mechanism! Note that sulfonation is the only reversible aromatic substitution. Moreover, fusing arylsulfonic acids with sodium hydroxide (that means melted pure NaOH!) will convert the sulfonic acid to a phenol.
Acylation - Friedel-Crafts
McMurry 16.3, Fessenden 11.8E, Schmid 21.9 Mechanism! To reactions of ketones (reduction to CH2 is in Schmid 21.10)
If There Is Already a Substituent, You Need to Know the Effect of Substituents on Aromatic Substitution:
The Table Below is in Order of Decreasing Reactivity of Ring Containing the Substituent Substituent Position of log(rate Reaction relative to H)
NR2 OH, OR R Ar F H NHCOR Cl, Br, I CO2H COR, CO2R CX3 SO3H CN NO2 NR3+
o, p o, p o, p o, p o, p "o, p" o, p o, p m m m m m m m
1.3 0.9 0.3 0.2 0.1 0 -0.1 -0.1 -0.4 -0.5 -0.5 -0.6 -0.7 -0.8 -0.9
McMurry 16.3-16.9 Fessenden 11.9, Schmid 21.11 Mechanisms! Some notes on multiple substitutions: No alkylation or acylation is possible with substituents labelled "m" above (meta-directors), i.e. with rings less reactive than the halobenzenes. Aniline is basic!!! In acids like H2SO4 or AlCl3 it becomes a meta-director. Use acetanilide, then hydrolyze.
Nucleophilic substitution of aromatic rings is possible, but especially if they are electron-deficient or a very strong base is used.
Please note that the reactions above may take place on rings that are already substituted. The position of substitution is determined by the substituent group or groups that were initially in the molecule, not by the incoming, new substituent. Please see reactions of aromatic compounds for details of substitution patterns.
Addition / Reduction
Other reagents: H2 / Pt, or similar catalyst; NaBH4 is a weaker reducing agent and reacts slower with esters than with ketones so that selective reductions can be done. McMurry 21.5, Fessenden 15.5C, Schmid 15.17 To other syntheses of alcohols
Note that two moles of Grignard reagent are required to do this reaction. The product from addition of one mole of Grignard is a ketone which also reacts with Grignard. If two moles of Grignard are not present, incomplete reaction yields a mixture of products and starting materials. McMurry 21.5, Fessenden 7.3D, 15.5C, Schmid 16.13 To other syntheses of alcohols
Addition / Elimination
This reaction is known as hydrolysis. Base-catalyzed hydrolysis, i.e. with H2O, OH-, is known as saponification McMurry 21.6, Fessenden 15.5C, Schmid 15.11, 15.12 To other syntheses of carboxylic acids
This reaction is known as interesterification or trans-esterification. Other reagents: any other alcohols McMurry 21.5, Fessenden 15.5C, Schmid 16.9
To synthesis of esters
Addition / Elimination
+ H2O McMurry 21.3, Fessenden 14.6, Schmid 15.11 To other reactions of acids
+ McMurry 11.15, 21.4, Fessenden 15.3, Schmid 16.5 To other reactions of acid chlorides
+ HCl
This reaction is called ester exchange or interesterification McMurry 21.5, Fessenden 15.5C, Schmid 16.9
+ McMurry 11.15, Fessenden 14.5, 15.5B, Schmid 12.18 Note that carboxylates are weak nucleophiles To other nucleophilic substitutions
+ NaBr
+ NaBr
+ NaBr
+ HCl
+ NaBr
Of the OH
+ H2O McMurry 21.3, Fessenden 14.5, Schmid 15.8 To: Carboxylic acid salt reactions
Of the Carbonyl
Reduction (Addition)
McMurry 17.5, 20.8, Fessenden 14.7, Schmid 15.17 To: Reactions of alcohols
Addition / Elimination
+ SO2 + HCl McMurry 21.3, Fessenden 15.3B, Schmid 16.5 To: Reactions of acid chlorides
+ H2O Mechanism! McMurry 21.4, Fessenden 14.6, Schmid 15.11 To: Reactions of esters To: Other ways of making esters
By Oxidation
+ MnO2 Other reagents: H2CrO4 or K2Cr2O7 + H2SO4 or CrO3 + H2SO4 or KMnO4 + H3O McMurry 17.8, 19.3, Fessenden 7.8C, 14.3, Schmid 11.18, 15.5 To: Other reactions of alcohols
+
+ Ag Other reagents: H2CrO4 or K2Cr2O7 + H2SO4 or CrO3 or KMnO4 or Tollens' or Benedict's reagents. McMurry 17.8, 19.3, 20.6, Fessenden 13.7, 14.3, Schmid 14.18, 15.5 To: Other reactions of aldehydes
+ MgBrOH McMurry 20.6, Fessenden 14.3, Schmid 15.6 For other reactions of Grignard reagents
Other reagents: CrO3 + H2SO4 or KMnO4 + KOH or KMnO4 + H2SO4 McMurry 20.6, Fessenden 10.13B, Schmid 15.5, 14.6 To other reactions of alkenes
Other reagents:K2Cr2O7 + H2SO4 or KMnO4 + H2SO4 or KMnO4 + OHMcMurry 21.4, Fessenden 7.8C, Schmid 15.5
Hydrolysis
+ HCl Mechanism! Other reagents: H2O, OH- or H2O McMurry 21.5, Fessenden 15.3C, Schmid 16.5 To: Other reactions of acid chlorides
2 Mechanism! Other reagents: H2O, OH- or H2O McMurry 21.5, Fessenden 15.5C, Schmid 16.9 Anhydrides react like acid chlorides
+ CH3CH2OH Mechanism! Other reagents: H2O, OH-, the reaction known as saponification McMurry 21.6, Fessenden 15.5C, Schmid 15.11, 15.12 To: Other reactions of esters
Other reagents: H2O, OH-; primary, secondary and tertiary amides all undergo this reaction McMurry 21.7, Fessenden 15.8C, Schmid 15.11, 15.12 To: Other reactions of amides
Other reagents: H2O, OHMcMurry 21.7, 21.8, Fessenden 15.11D, Schmid 15.7 Nitriles react like amides
+ HCl
+ HCl Mechanism! McMurry 21.4, Fessenden 15.3C, Schmid 16.5 To other syntheses of acids
+ HCl Mechanism! McMurry 21.4, Fessenden 15.3C, Schmid 16.5 To other syntheses of esters
+ NaCl
+ HCl Mechanism! McMurry 21.4, 24.9, Fessenden 15.3C, Schmid 16.5 To other syntheses of amides
+ HCl Mechanism! McMurry 21.4, 24.7, Fessenden 15.3C, Schmid 16.5 To other syntheses of amides
Addition / Reduction
Other reagents: NaBH4 McMurry 21.4, Fessenden 15.3C, Schmid 16.12 To syntheses of alcohols
Note that two moles of Grignard reagent are required to do this reaction. The product from addition of one mole of Grignard is a ketone which also reacts with Grignard. If two moles of Grignard are not present, incomplete reaction yields a mixture of products and starting materials. McMurry 21.4, Fessenden 15.3C, Schmid 16.13 To: Synthesis of alcohols
To: Synthesis of ketones HCl Other reagents: PCl3 (not as easy to use)
+ SO2 +
+ NaCl
+ HCl McMurry 21.4, 24.7, Reference 15.3C, 21.4, 24.7, Schmid 16.5
SO2 + HCl
+ HCl
McMurry 21.3, Fessenden 14.4, 14.5, Schmid 15.8 To: Carboxylic acid reactions
+ Mechanism! Just an SN2 McMurry 21.3, Fessenden 15.3C, 15.4B, Schmid 16.5 To: Other carboxylic acid chloride and anhydride reactions
+ Mechanism! Just an SN2. See halides McMurry 21.6, Fessenden 14.5, 15.5B, Schmid 12.18
+ NaBr
+ Br-
+ Mechanism! Not stereospecific. 1,4-addition dominates when at equilibrium, i.e. under thermodynamic control, at room temperature or higher. 1,2-addition dominates when not at equilibrium, i.e. under kinetic control, below 0oC.
Mechanism! 1,4-addition dominates when at equilibrium, i.e. under thermodynamic control, at room temperature or higher. 1,2-addition dominates when not at equilibrium, i.e. under kinetic control, below 0oC. Other acids react the same way to give alcohols, bromides, etc.
+ Diels Alder Reaction. Stereospecific! This is a reaction of the alkene and diene, not the C=O; it works best when the
Alkylation of an enamine, plus hydrolysis with water McMurry 24.7, Fessenden 17.5, Schmid 17.14
Mechanism! Note that there is a possibility that the ethoxide could react with the halide (SN2) to form an ether. However, the acid base equilibrium with the diketone is much faster. The equilibrium strongly prefers the more stable, less basic, enolate over the ethoxide, essentially consuming the ethoxide. Thus, the very stable enolates from 1,3-dicarbonyl compounds are able to do SN2 reactions without competition from the alkoxide catalyst. Other reagents: weaker bases Decarboxylation upon hydrolysis of 3-ketoesters McMurry 22.8, Fessenden 17.2B, Schmid 24.7
Mechanism! Bromination of the enolate (think of Br- as a leaving group) McMurry 22.7, Fessenden 13.10, 17.6, Schmid 17.4
+ OH-
+ OH- + H2O Mechanism! Aldol condensation. McMurry 22.7, Fessenden 17.6, Schmid 17.6
+ 2 CH3OMechanism! Claisen condensation; Claisen condensation is not reversed by alkoxide because the product is converted to its conjugate base. See carboxylic acids for decarboxylation. McMurry 23.6,Fessenden 17.8A, Schmid 17.7, 24.3
Mechanism! Mixed Claisen condensation. Remember that all condensation reactions occur at equilibrium. Thus the most stable product is formed. In this basic solution, that will be the weakest base, namely the conjugate base of the product shown. The additions ofother enolates occur, e.g. aldol condensations, but the equilibria eventually produce this most stable product. McMurry 23.2, Fessenden 17.8B, Schmid 17.7, 24.3
Mechanism!
Michael reaction; other bases can be used for this addition, such as alkoxides, amines, alkyl lithium, dialkyl copper lithium, giving a wide variety of products. See the next reaction. Lithium aluminum hydride and Grignard reagents add to the C=O. McMurry 23.4, Fessenden 17.9, Schmid 24.12
Mechanism! Michael condensation, used as the first and key step in the Robinson annulation. Note that there is a possibility that the ethoxide could react with the conjugated ketone (SN2) to form an ether. However, the acid base equilibrium with the diketone is much faster. The equilibrium strongly prefers the more stable, less basic, enolate over the ethoxide, essentially consuming the ethoxide. Thus, the very stable enolates from 1,3dicarbonyl compounds are able to do addition reactions without competition from the alkoxide catalyst.
This reaction is a simple acid-base reaction. Enolates may be formed from ketones or aldehydes using a variety of bases, including strong bases such as ethoxide and amide ions. To convert esters to their enolates it is essential to use the conjugate base of the alcohol from which they are formed to prevent hydrolysis or ester exchange. Enolates react very quickly with bromine or other carbonyl compounds
Stable lithium enolate, less substituted if an unsymmetrical ketone Other reagents: sodium hydroxide or alkoxides with also make enolates (see aldol condensations, for example). However, the acid-base equilibrium is well-balanced and thus the catalyst and both enolates are present if an unsymmetrical ketone is used and any of these may react, especially with a halide. Other substrates: For esters, the base catalyst must be the conjugate base of the alcohol part of the ester. 1,3dicarbonyl compounds are more acidic (in fact they existpredominantly in the enol form), so very weak bases can be used to convert them to their enolates.
An enamine
+ OH-
+ OH- + H2O
+ 2 CH3O-
+ OH- + H2O
+ 2 CH3O-