ha rash

+ 1/2 H2 Other reagents: any base stronger than alkoxide, such as H-, NH2

-, CH3MgBr, CH3Li (H2 not formed)

As nucleophiles with Carboxylic Acids

+ H2O Mechanism! To other syntheses of esters

As nucleophiles with Carboxylic Acid Chlorides

+ 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.

As nucleophiles with Esters

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http://pages.towson.edu/ladon/orgrxs/reagent/acids.htm#HX

+

Other reagents: any other alcohols Mechanism!

As nucleophiles with sp3 carbon

Mechanism!; SN2 reaction. Note that more substituted halides will undergo the E2 elimination instead.

Reactions which break the CO bond

Nucleophilic Substitution

Mechanism!; SN2; other reagents HCl, HI, H2SO4

Substitution and Elimination

http://pages.towson.edu/ladon/orgrxs/reagent/bases.htm#RO


+

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

+ H2O 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


http://pages.towson.edu/ladon/orgrxs/reagent/acids.htm#H2SO4

http://pages.towson.edu/ladon/orgrxs/reagent/oxidizer.htm#cr6

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

From Alkyl Halides - Nucleophilic Substitution

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

From Alkenes: Addition

+ 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


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http://pages.towson.edu/ladon/orgrxs/reagent/bases.htm#OH

http://pages.towson.edu/ladon/orgrxs/reagent/reducers.htm#nabh4

carbocation is possible. McMurry 7.4, Fessenden 10.8; Schmid 7.14, 8.10

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

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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 7.4, Fessenden 10.10; Schmid 8.9

From Carbonyl Compounds: Addition

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


http://pages.towson.edu/ladon/orgrxs/reagent/bases.htm#CN

From Carbonyl Compounds: Addition with Reduction

Other reagents: NaBH4, H2with Pt Fessenden Schmid 11.7

+ CH3OHOther reagents: NaBH4, H2with PtOther 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

Fessenden 7.3D, 13.4D, Schmid 11.7

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http://pages.towson.edu/ladon/orgrxs/reagent/reducers.htm#grignard


+

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 7.4, Fessenden 10.7, Schmid 7.14, 8.10

+ H2O Reference McMurry 7.4, Fessenden 10.8, Schmid 7.14, 8.10



McMurry6.8, 6.9, 7.2, 9.17, Fessenden 10.10D, Schmid 8.9

Reference McMurry7.4, Fessenden 10.8, 10.9, Schmid 8.1 - 8.4

Reference McMurry 7.8, Fessenden 10.13, Schmid 8.5

Reference McMurry 10.8, Fessenden 7.3D, 13.4D, Schmid 11.7




Reference: McMurry 17.8, Fessenden 7.7, 14.6, Schmid 11.16, 15.11

McMurry 7.4, Fessenden 7.6

McMurry 11.16, 11.7, Fessenden 7.5, Schmid 11.17

Reference Fessenden 7.3B, 13.6AB, 14.7, Schmid 11.7



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 8.3, 11.15, 18.3, Fessenden 5.3, 8.2B, Schmid 13.8C

McMurry 17.4, Fessenden 10.13, Schmid 8.6, 13.12

McMurry 7.4, Fessenden 8.4, Schmid 13.12

Reference Fessenden 5.10, 13.4C, Schmid 14.9

Fessenden 13.4B, Schmid 14.11

Reference McMurry 21.3, Fessenden 15.3C, Schmid 16.5

Reference Fessenden 15.3C, Schmid 16.9

+

Reference McMurry 10.8, Fessenden 10.5C, 15.5, Schmid 16.13


Reference McMurry 7.4, Fessenden10.7, Schmid 7.14, 8.10



+ H2O Reference McMurry 7.4, 10.8, Schmid 7.14, 8.10

McMurry 7.4, Fessenden 10.10D, Schmid 8.9

McMurry 6.8, 6.9, 7.2, 9.17, Reference 10.8, 10.9, Schmid 8.1 - 8.4


Reference McMurry 10.8, Fessenden 7.3D,13.4D, Schmid 11.7


+ H2O

McMurry 17.8, Fessenden 7.6

Reference: McMurry 17.4, Fessenden 7.7, 14.6, Schmid 11.16, 15.11


Reference Fessenden 7.3B, 13.6AB, Schmid 11.7


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 Fessenden 7.8, Schmid 11.18, 15.5

McMurry 8.3, 11.15, 18.3, Fessenden 7.3A, Schmid 12.1, 12.2

McMurry 17.4, Fessenden 5.3, 8.2B, Schmid 13.8C

McMurry 8.3, 11.15, 18.3, Fessenden 10.13, Schmid 8.6, 13.12

Fessenden 8.4, Schmid 13.12

Reference Fessenden 5.10, 13.4C, Schmid 14.9



Reference Fessenden 15.5C, Schmid 16.9

+



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


+


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,


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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.

McMurry 10.4, Schmid 19.3, 20.9A, Fessenden 6.5

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

McMurry 7.5, Schmid 8.1 - 8.4



http://pages.towson.edu/ladon/orgrxs/reagent/reducers.htm#h2pt


+ ZnI2 Stereospecific! A dichlorocyclopropane ring can be made using chloroform and base (e.g. t-butoxide) McMurry 7.6, Schmid 8.7

From alkyl halides

McMurry 10.8, Moisture at any point after the Grignard is formed and before any other reaction will result in alkane formation.

McMurry 10.8, Occurs if the ether concentration is too low.



2

7 CO2 + 14 H2O


McMurry 7.5, Fessenden 10.9, Schmid 8.1 - 8.4

+ ZnI2




McMurry 7.7, Fessenden 10.12B, Schmid 8.11

McMurry 7.2, Fessenden 6.1 - 6.6, Schmid 18.1 - 18.4

McMurry 10.6, 16.18, Fessenden 6.5, 12.1, Schmid 19.3, 20.9A

Fessenden 12.1, Schmid 20.9B

McMurry 10.8, Fessenden 7.3D 7.3D

2

7 CO2 + 14 H2O



+ ZnI2




McMurry 16.10, Fessenden 6.5, 12.1, Schmid 19.3, 20.9A


McMurry 10.8, Fessenden 7.3D

2

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

Mechanism! Stereospecific! McMurry 7.3, Fessenden 10.10D, Schmid 8.9

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



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+ RCO2H Stereospecific! See ethers for the opening of the epoxide ring. McMurry 17.4, Fessenden 10.13, Schmid 8.6

Miscellaneous carbon-carbon bond-forming reactions

+ 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)

By elimination from alcohols: Dehydration


+

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

+ H2O Mechanism!; E1McMurry 7.1, 11.10, Fessenden 7.6

By elimination from alkyl halides: Dehydrohalogenation

Mechanism! E2, Stereospecific McMurry 11.12, 11.15, Fessenden 5.7-5.8, Schmid 12.12 - 12.15

By reduction


http://pages.towson.edu/ladon/orgrxs/reagent/acids.htm#H2SO4


Stereospecific! McMurry 8.5, Fessenden 10.9, Schmid 9.8

Stereospecific! For other reagents, click on the arrow above. McMurry 6.7, 8.6, 8.10, Fessenden 10.12B, Schmid 9.8

Stereospecific! McMurry 8.6, 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


+ H2O

Reference McMurry 7.4 Fessenden 10.8, Schmid 7.14, 8.10

McMurry 7.5, Fessenden 10.8-10.9, Schmid 8.1 - 8.4, 22.11



+ RCO2H

McMurry 17.4, Fessenden 8.2C, 10.13, Schmid 8.6



+ ZnI2





+ H2O

McMurry 7.1, Fessenden 7.6; there are other possible answers.


McMurry 6.7, 8.6, 8.10, Fessenden 10.12B, Schmid 9.8


+

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 11.12, 11.15, Fessenden 5.7 - 5.8, Schmid 12.12 - 12.15

McMurry 19.12, Fessenden 13.4D, Schmid 14.16, 14.17

+




+ H2O


Fessenden 10.8-10.9, Schmid 8.1 - 8.4, 22.11

Fessenden 10.8 - 10.9, Schmid 8.1 - 8.4


+ RCO2H


+ ZnI2



Fessenden 10.10D, Schmid 8.9





+ H2O

Fessenden 7.6

+

Fessenden 7.4 - 7.6, Schmid 11.17, 12.10, 12.11, 12.16

Fessenden 5.7 - 5.8, Schmid 12.12 - 12.15

Fessenden 13.4D, Schmid 14.16, 14.17

+


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,

+ McMurry 8.8, 8.9, 8.10, Schmid 9.10 ,




+

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,

http://pages.towson.edu/ladon/orgrxs/reagent/bases.htm#NH3

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 ,

With Metals (Reduction)

The Grignard reagent McMurry 10.8, 10.10, 17.6, Fessenden 7.3D, Schmid 11.7,

2

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).

To synthesis of alkyl halides or back to the main graphical menu

From Alcohols: Nucleophilic Substitution

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http://pages.towson.edu/ladon/orgrxs/halide/halidesy.htm




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,

From Alkenes by Addition




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 anti-Markovnikov addition. McMurry 5.1, 5.6, 7.5, Fessenden 10.6, Schmid 18.5 - 18.6

Mc Murry 7.5, Fessenden 10.6, Schmid 8.1 - 8.4

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





Mechanism! Stereospecific! McMurry 7.3, Fessenden 10.10, Schmid 8.9,

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,

McMurry 6.8,6.9, Fessenden 10.6, Schmid 7.8 - 7.17






+ McMurry 8.8, 8.9, 8.10 Fessenden 10.4, Schmid 9.10

McMurry 10.8, 10.10 Fessenden 7.3D, 13.4D, Schmid 11.7


+

Reference McMurry 7.1, 10.7, 17.7, Fessenden 7.4 - 7.6, Schmid 11.17, 12.10, 12.16


McMurry 11.10, Fessenden 5.4 - 5.5, Schmid 12.1, 12.2

McMurry 11.21, 24.6, Fessenden 5.7, Schmid 12.2 - 12.4

McMurry 11.10, 11.13, 11.15, Fessenden 5.7 - 5.8, Schmid 12.12 - 12.15

McMurry 11.14, 11.15, Fessenden 5.3, 8.2B, Schmid 13.8C

+


McMurry 5.1, 5.6, 7.5, Fessenden 10.6, Schmid 18.5 - 18.6


McMurry 10.5, 10.6, Fessenden 6.5, Schmid 19.3, 20.9A

+

Reference McMurry 24.6, Fessenden 5.10, 18.4, Schmid 22.8

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 8.8, 8.9, 8.10, Fessenden 10.4, Schmid 9.10

McMurry10.8, 10.10, Fessenden 7.3D, 13.4D, Schmid 11.7

+

Reference McMurry 10.7, 11.9, 7.1, 17.7, Fessenden 7.4 - 7.6, Schmid 11.17, 12.10, 12.16


McMurry 10.10, Fessenden 5.4 - 5.5, Schmid 12.1, 12.2

McMurry 11.21, 24.6, Fessenden 5.7, Schmid 12.2 - 12.4

McMurry 11.10, 11.13, 11.15, Fessenden 5.7 - 5.8, Schmid 12.12 - 12.15

McMurry 11.14, 11.15, Fessenden 5.3, 8.2B, Schmid 13.8C

+

McMurry 19.12, Fessenden 13. 5, Schmid 14.16, 14.17



McMurry 10.4, Fessenden 6.5, Schmid 19.3, 20.9A

excess +

Reference Fessenden 5.10, 18.4, Schmid 22.8

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! McMurry 8.4, Fessenden 10.6, Schmid 9.6A


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



Stereospecific! McMurry 8.6, Fessenden 10.12B, Schmid 9.8

Oxidation





McMurry 8.4, Fessenden 10.5, Schmid 9.6B

As Weak Acids

+ SN2 reaction, stereospecific if halide is secondary

McMurry 8.6, 8.8, 8.9, Fessenden 10.4, Schmid 9.10

From other alkynes

+




Mechanism! An SN2 reaction. Another reagent is Fesenden 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

second HBr. An alternate reagent is

McMurry 6.8, 6.9, 8.4, Fessenden 10.6, Schmid 9.6A



McMurry 8.4, Fessenden 10.7, Schmid 9.7A

+ H2O









+

McMurry 8.9, 8.10 Fessenden 10.4, Schmid 9.10

+


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.


From alkyl halides and alcohols

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



http://pages.towson.edu/ladon/orgrxs/reagent/acids.htm#ROH2


+ 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.

Stereospecific! McMurry 17.4, 18.7, Fessenden 10.13, Schmid 13.10, 8.6

Mechanism! Stereospecific! McMurry 18.7, Fessenden 8.3, 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 +


McMurry 17.4, 18.7, Fessenden 10.13, Schmid 13.10, 8.6

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

Mechanism! Reversible McMurry 19.11, Fessenden 13.4B, Schmid 14.11

Mechanism! McMurry 19.7, 20.6, Fessenden 13.4C, Schmid 14.9

Irreversible Addition: Reduction




Other reagents: NaBH4, H2, Pt McMurry 17.5, 19.8, Fessenden 13.6B, Schmid 11.7

McMurry 17.6,19.8, Fessenden 13.4D, 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

Addition + Elimination = Substitution



http://pages.towson.edu/ladon/orgrxs/reagent/reducers.htm#ZnHCl

+

An imine Mechanism! McMurry 21.7, Fessenden 13.5A, Schmid 14.13 - 14.15

+

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

http://pages.towson.edu/ladon/orgrxs/halide/haliderx.htm

http://pages.towson.edu/ladon/orgrxs/enolate/condens.htm



Oxidation (Aldehydes only)

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

2 McMurry 7.8, 19.2, Fessenden 10.13B, Schmid 14.5

http://pages.towson.edu/ladon/orgrxs/reagent/oxidizer.htm#silver





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



http://pages.towson.edu/ladon/orgrxs/reagent/reducers.htm#r2culi



McMurry 8.5, Fessenden 10.9 Schmid 9.7B

By Substitution

+

Mechanism! McMurry 16.4, Fessenden 11.8E, 15.3C, Schmid 21.9

+ 2 CH3CH2OH

+



http://pages.towson.edu/ladon/orgrxs/reagent/acids.htm#AlCl3



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 17.5, 19.5, Fessenden 13.6B, Schmid 11.7


McMurry 17.8, 19.2, 19.3, 20.6, Fessenden 7.8C, 13.2, Schmid 11.18

McMurry 17.8, 19.2, 19.3, 20.6, Fessenden 7.8, Schmid 11.18

McMurry 19.11, Fessenden 13.4A, Schmid 14.10


McMurry 19.7, Fessenden 13.4C, Schmid 14.9

+

McMurry 19.9, Fessenden 13.5A, Schmid 14.13 - 14.15

+

McMurry 19.9, Fessenden 13.5B, Schmid 14.13, 17.14

McMurry 19.2 Fessenden 13.5B, Schmid 14.16 - 14.17


2


McMurry 21.8, Fessenden 15.3C, Schmid 16.14B

McMurry 21.4, Fessenden 15.3C, Schmid 16.14A

+ 2 CH3CH2OH

McMurry 19.11 Fessenden 13.4B, Schmid 14.11

+



Fessenden 13.6C, Schmid 21.10

+

McMurry 16.4, Fessenden 11.8E, 15.3C, Schmid 21.9





McMurry 17.8, 19.2, 19.3, 20.6, Fessenden 7.8C, 13.2, Schmid 11.18

McMurry 17.8, 19.2, 19.3, 20.6, Fessenden 7.8C, Schmid 11.18




+


+


McMurry 19.2, Fessenden 13.5D, Schmid 14.16 - 14.17


2


McMurry 21.8, Fessenden 15.3C, Schmid 16.14B

McMurry 21.4, Fessenden 15.3C, Schmid 16.14A

+ 2 CH3CH2OH


+




+

McMurry 16.4, Fessenden 11.8E, 15.3C, Schmid 21.9

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

Addition / Elimination: Hydrolysis

+

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

http://pages.towson.edu/ladon/orgrxs/carbox/clorrx.htm

http://pages.towson.edu/ladon/orgrxs/ketald/ketonesy.htm





+ 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

+

McMurry 21.5, Fessenden 15.4C, Schmid 16.9 To other reactions of esters

+


http://pages.towson.edu/ladon/orgrxs/carbox/estersy.htm




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

Reference McMurry 19.8, 21.7, Schmid 16.15

+ HCl

McMurry 21.4, 24.7, Fessenden 15.3C, Schmid 16.5

+ HCl


+

McMurry 21.6 Fessenden 15.4C, Schmid 16.9

+


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

Reference McMurry 19.8, 21.8, , Schmid 16.15

+ HCl


+ HCl


+


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

As nucleophiles - with sp3 carbon

http://pages.towson.edu/ladon/orgrxs/reagent/acids.htm


+

Reaction is very hard to control Mechanism! McMurry 11.2, 11.5, 24.6, Fessenden 18.7, Schmid 22.8

As nucleophiles - with sp2 carbon

+ 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

http://pages.towson.edu/ladon/orgrxs/amine/acidclor.htm


+

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

http://pages.towson.edu/ladon/orgrxs/ketald/ketonerx.htm




Carcinogenic! Fessenden 18.8, Schmid 22.14

McMurry 24.8, Fessenden 12.3A, Schmid 22.14 - 22.15 Diazonium salts are very useful in synthesis.

http://pages.towson.edu/ladon/orgrxs/reagent/oxidizer.htm#HNO3

http://pages.towson.edu/ladon/orgrxs/reagent/oxidizer.htm#HNO3

+ McMurry 24.8, Fessenden 12.3AB, Schmid 22.16 - 22.17

rom the conjugate acid

+ 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


By reduction of other nitrogen compounds

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.


Fessenden 12.3, 18.4B, Schmid 22.10





By addition to alkenes

Reference McMurry 7.5 Schmid 22.11

+



+


+ HCl



+

+

+


+ H3O+


+

McMurry 24.6, Fessenden 18.4A,Schmid 22.9 (Gabriel synthesis), 16.8

McMurry 24.6 Fessenden 18.4B, Schmid 16.12, 16.15




Reference McMurry 7.5, Schmid 22.11



Reactions of Aryl Diazonium Salts made from Anilines

+

McMurry 24.8, Fessenden 12.3AB, Schmid 22.16 - 22.17

+


+


+ HCl



+

McMurry 11.2, 11.5, 246, Fessenden 18.7, Schmid 22.8

+ H3O+


+

McMurry 24.6, Fessenden 18.4A, Schmid 22.9 (Gabriel synthesis), 16.8

Reference McMurry 7.5, Schmid 22.11



Reactions of Aryl Diazonium Salts made from Anilines

+

McMurry 24.8, Fessenden 12.3AB, Schmid 22.16 - 22.17

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

McMurry 16.2, Fessenden 11.8C, Schmid 21.6 Mechanism!

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.

Alkylation - the Friedel-Crafts Reaction


http://pages.towson.edu/ladon/orgrxs/reagent/acids.htm#SO3

http://pages.towson.edu/ladon/orgrxs/reagent/acids.htm#SO3

+

+ McMurry 16.2, Fessenden 11.8D, Schmid 21.8 Mechanism!

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 relative to H)



Reaction

NR2 o, p 1.3

OH, OR o, p 0.9

R o, p 0.3

Ar o, p 0.2

F o, p 0.1

H "o, p" 0

NHCOR o, p -0.1

Cl, Br, I o, p -0.1

CO2H m -0.4

COR, CO2R m -0.5

CX3 m -0.5

SO3H m -0.6

CN m -0.7

NO2 m -0.8

NR3+ m -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.



McMurry 16.3, Fessenden 11.8F, Schmid 21.7

+


+

McMurry 16.4, Fessenden 11.8E, Schmid 21.9

McMurry 16.1 Fessenden 11.8A, Schmid 21.5


McMurry 16.3 Fessenden 11.8F, Schmid 21.7

+


+

McMurry 16.4, Fessenden 11.8E, Schmid 21.9

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.


+

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

http://pages.towson.edu/ladon/orgrxs/alcohol/alcohosy.htm

http://pages.towson.edu/ladon/orgrxs/aromat/benzenrx.htm


+

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


+

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

http://pages.towson.edu/ladon/orgrxs/carbox/carboxsy.htm




+

This reaction is known as interesterification or trans-esterification.Other reagents: any other alcohols McMurry 21.5, Fessenden 15.5C, Schmid 16.9

+

McMurry 21.5, Fessenden 15.5C, Schmid 16.9 To other syntheses of amides

To synthesis of esters



http://pages.towson.edu/ladon/orgrxs/carbox/amidesy.htm



+ H2O McMurry 21.3, Fessenden 14.6, Schmid 15.11 To other reactions of acids

+ + HCl McMurry 11.15, 21.4, Fessenden 15.3, Schmid 16.5 To other reactions of acid chlorides

+

This reaction is called ester exchange or interesterification McMurry 21.5, Fessenden 15.5C, Schmid 16.9


http://pages.towson.edu/ladon/orgrxs/carbox/carboxrx.htm


http://pages.towson.edu/ladon/orgrxs/reagent/bases.htm#ROH


+ + NaBr McMurry 11.15, Fessenden 14.5, 15.5B, Schmid 12.18

Note that carboxylates are weak nucleophiles To other nucleophilic substitutions

+ + NaBr

McMurry 11.15, Fessenden 14.5, 15.5B, Schmid 12.18

+ + NaBr


+ H2O


+


+


+ + HCl


+


+


+


+ + NaBr


+ H2O


+


+


+ HCl


+

McMurry 21.5, Fessenden 15.5C Schmid 16.9

+


+


Of the OH

+ H2O McMurry 21.3, Fessenden 14.5, Schmid 15.8 To: Carboxylic acid salt reactions

http://pages.towson.edu/ladon/orgrxs/carbox/saltrx.htm


Of the Carbonyl

Reduction (Addition)

McMurry 17.5, 20.8, Fessenden 14.7, Schmid 15.17 To: Reactions of alcohols


+ 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





Decarboxylation of a 3-ketoacid or 1,3-diacid McMurry 21.3, Fessenden 14.8C, Schmid 24.6

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



http://pages.towson.edu/ladon/orgrxs/alcohol/alcohorx.htm




http://pages.towson.edu/ladon/orgrxs/reagent/oxidizer.htm#silver

+ 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 + OH- McMurry 21.4, Fessenden 7.8C, Schmid 15.5

Hydrolysis

+ HCl Mechanism! Other reagents: H2O, OH- or H2O


http://pages.towson.edu/ladon/orgrxs/alkene/alkenerx.htm





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

http://pages.towson.edu/ladon/orgrxs/carbox/esterrx.htm

http://pages.towson.edu/ladon/orgrxs/carbox/acidclor.htm





McMurry 21.7, Fessenden 15.8C, Schmid 15.11, 15.12 To: Other reactions of amides

+

Other reagents: H2O, OH- McMurry 21.7, 21.8, Fessenden 15.11D, Schmid 15.7 Nitriles react like amides

+ MnO2 McMurry17.8, 19.3, Fessenden 7.8C, Schmid 11.18, 15.5

+ Ag


http://pages.towson.edu/ladon/orgrxs/carbox/amiderx.htm

http://pages.towson.edu/ladon/orgrxs/carbox/amiderx.htm


+ MgBrOH


McMurry 7.8, 8.7, Fessenden 10.13B, Schmid 15.5, 14.6


+ H2O


+ H2O


+ CH3CH2OH


+


+

McMurry 21.7, 21.8, Fessenden 15.11D, Schmid 15.7


+ SO2 + HCl


+ HCl



2


+ MnO2

McMurry 17.8, 19.3, Fessenden 7.8C, Schmid 11.18, 15.5

+ Ag


+ MgBrOH


McMurry 7.8, 8.7, Fessenden 10.13B, Schmid 15.5, 14.6


+ H2O


+ H2O


+ CH3CH2OH


+


+

McMurry 21.7, 21.8, Fessenden 15.11D, Schmid 15.7


+ SO2 + HCl


+ HCl



2

McMurry 21.5, Fessenden 15.5C, Schmid 16.9 Addition / Elimination Reactions

+ 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

+ HCl Schmid 16.5

+ + NaClMechanism! McMurry 21.2, Fessenden 15.3C, 15.4B, Schmid 16.5


http://pages.towson.edu/ladon/orgrxs/carbox/carboxsy.htm



+ 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


Other reagents: NaBH4 McMurry 21.4, Fessenden 15.3C, Schmid 16.12 To syntheses of alcohols







McMurry 21.4, Fessenden 15.3C, Schmid 16.14, A To: Syntheses of aldehydes

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 + SO2 + HCl Other reagents: PCl3 (not as easy to use)

+ HCl








+ HCl


+ HCl

Schmid 16.5

+ + NaCl

McMurry 21.2, Reference 15.3C, 15.4B,, Schmid 16.5

+ HCl

McMurry 21.4, 24.7, Reference 15.3C, 21.4, 24.7, Schmid 16.5

+ SO2 + HCl

McMurry 21.3, Reference 15.3B, McMurry 21.4, 24.7, Schmid 16.5

+ HCl

McMurry 21.4, 24.7, Reference 15.3C, Schmid 16.5

Other reagents: NaBH4 McMurry 21.4, Reference 15.3C, Schmid 16.12


McMurry 21.4, Fessenden 15.3C, Schmid 16.14, A

McMurry 21.4, Fessenden 15.3C, Schmid 16.14,B

+ 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

+ + NaBr Mechanism! Just an SN2. See halides McMurry 21.6, Fessenden 14.5, 15.5B, Schmid 12.18

http://pages.towson.edu/ladon/orgrxs/halide/haliderx.htm


http://pages.towson.edu/ladon/orgrxs/carbox/carboxrx.htm


McMurry 21.3, Fessenden 14.4, 14.5, Schmid 15.8

+

McMurry 21.2, Fessenden 15.3C, 15.4B, Schmid 16.5

+ + Br-

M cMurry 21.6, Fessenden 14.5, 15.5B, Schmid 12.18


+

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 alkene is electron-deficient, so the C=O's function is to withdraw electrons


+

+

+

+ +

+

+ Nucleophilic Substitution by Enolates and Enamines

Mechanism! Alkylation of an enolate is an SN2 reaction

Alkylation of an enamine, plus hydrolysis with waterMcMurry 24.7, Fessenden 17.5, Schmid 17.14

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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

http://pages.towson.edu/ladon/orgrxs/carbox/carboxrx.htm#decarbox



Aldol and Claisen Condensations (Nucleophilic Addition)

+ OH-

+ OH- + H2O Mechanism! Aldol condensation. McMurry 22.7, Fessenden 17.6, Schmid 17.6

2 Reverse aldol condensation. McMurry 24.3, Fessenden 17.6, Schmid 17.10

+ 2 CH3O- Mechanism!

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

http://pages.towson.edu/ladon/orgrxs/carbox/carboxrx.htm#decarbox

http://pages.towson.edu/ladon/orgrxs/reagent/bases.htm#enolate



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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

Addition to Conjugated Unsaturated Carbonyl Compounds

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



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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 1,3-dicarbonyl 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 ketoneOther 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.

http://pages.towson.edu/ladon/orgrxs/enolate/condens.htm#aldol










Other substrates: For esters, the base catalyst must be the conjugate base of the alcohol part of the ester. 1,3-dicarbonyl 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

+ 2 CH3O-

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+ OH- + H2O

+ 2 CH3O-

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ha rash

Documents

b schmid

h2with pt fessenden

ch3oh fessenden

reversible fessenden

h2so4 reference mcmurry

hi reference mcmurry

form reference mcmurry7

reagents hcl