Main page REACTIONS
 

Here is just a list of the reactions that we discussed in detail in class.  We plan to add mechanistic schemes and other "goodies" slowly over the next few semesters.  For now, just to help you keep track of the transformations we offer some limited  "highlights".  Please note that no stereochemistry is implied in the reaction schemes.

 
 
 
Reaction 1.  Electrophilic addition of hydrogen halides (HX) to alkenes.
Reagents and conditions Mechanistic details
  • HCl, HBr in ether
  • KI + H3PO4
  • room temperature
  • electrophilic addition
  • carbocation intermediates
  • Markovnikov's rule apply
  • carbocation rearrangements possible
  • no relative stereochemical preference
 
 
Reaction 2.  Radical addition of hydrogen bromide (HBr) to alkenes.  (NOT COVERED THIS TIME)
Reagents and conditions Mechanistic details
  • radical initiators (usually peroxides)
  • heat or light
  • chain reaction
  • radical intermediates
  • anti-Markovnikov's products
  • no relative stereochemical preference
 
 
Reaction 3.  Electrophilic addition of halogens (X2) to alkenes.
Reagents and conditions Mechanistic details
  • Br2, Cl2 (or I2) in CH2Cl2 or CCl4
  • room temperature
  • electrophilic addition
  • bromonium or chloronium ion intermediates
  • anti addition
 
 

Reaction 4.  Electrophilic addition of halogens to alkenes in the presence of water.
Reagents and conditions Mechanistic details
  • Br2 or Cl2 in H2O or NBS in H2O/DMSO
  • room temperature
  • electrophilic addition of X2
  • bromonium or chloronium ion intercepted by H2O
  • Markovnikov's rule apply (with respect to H2O)
  • anti addition
 
 

Reaction 5. Electrophilic addition of water to alkenes.
Reagents and conditions Mechanistic details
  • acid catalyst needed with non-nucleophilic counter ion (H2SO4, HClO4, H3PO4)
  • high temperature required
  • often reversible (rather used to make alkenes from alcohols)
  • electrophilic addition
  • carbocations intermediates
  • Markovnikov's rule applies
  • no relative stereochemical preference
 
 
Reaction 6.  Oxymercuration of alkenes (formal addition of water).
Reagents and conditions Mechanistic details
  • Hg(OAc)2 in H2O (or THF/H2O)
  • reduction step required to replace mercury with hydrogen (NaBH4)
  • room temperature
  • electrophilic addition of mercury compound
  • mercurinium ion as the intermediate intercepted by H2O
  • Markovnikov's rule applies with respect to H2O
  • reduction step with a complicated mechanism
  • the addition of H2O is anti, but reduction scrambles the stereochemistry (i.e. no relative stereochemical preference is observed)
 
 
Reaction 7.  Hydroboration of alkenes (formal addition of water).
Reagents and conditions Mechanistic details
  • BH3-THF complex in THF
  • tri-fold addition (to borane) is common, giving trialkylboranes (R3B) 
  • oxidation step necessary (H2O2/OH)
  • room temperature or heat
  • electrophilic addition of BH3
  • cyclic transition state, putting boron at the least substituted carbon of the double bond
  • syn addition, preserved in the oxidation step (stereospecific replacement of BR2 with OH))
  • anti-Markovnikov alcohols
 
 
Reaction 8.  Hydrogenation of alkenes. 
Reagents and conditions Mechanistic details
  • H2 gas over heterogeneous catalysts (Pd/C, Pt, PtO2)
  • room temperature
  • very facile reaction (many other functional groups remain untouched)
  • surface reaction
  • syn addition from the less crowded face
  • mechanism is complicated 
  • redox reaction
 
 
Reaction 9.  Hydroxylation of alkenes.
Reagents and conditions Mechanistic details
  • KMnO4/OH (lower yield)
  • OsO4/pyridine (higher yield but toxic and expensive)
  • catalytic OsO4 with NMO
  • cyclic transition state and intermediate resulting in syn addition
  • redox reaction
 
 
Reaction 10.  Ozonolysis of alkenes.
Reagents and conditions Mechanistic details
  • ozone at low temperature followed by reduction with Zn/AcOH
  • complicated mechanism with O3
  • oxidation followed by (partial) reduction
 
 
Reaction 11.  Oxidation of diols.
Reagents and conditions Mechanistic details
  • 1,2-diol  treated by HIO4 in H2O/THF
  • equivalent to ozonolysis of the corresponding alkene
  • cyclic intermediate with HIO4
 
 
Reaction 12.  Oxidation of alkenes with permanganate under acidic conditions.
Reagents and conditions Mechanistic details
  • potassium permanganate under acidic or neutral conditions
  • redox reaction
  • oxygen inserts into all former vinylic C-H bonds
 
 
Reaction 13.   Electrophilic addition of hydrogen halides (HX) to alkynes.
Reagents and conditions Mechanistic details
  • HCl, HBr in acetic acid
  • electrophilic addition
  • vinyl carbocation as an intermediate
  • Markovnikov's rule apply
  • first addition usually trans
  • second addition often follows
  • less reactive than alkenes
 
 
Reaction 14. Electrophilic addition of halogens (X2) to alkynes.
Reagents and conditions Mechanistic details
  • Cl2, Br2 in CCl4    
  • electrophilic addition
  • Markovnikov's rule apply
  • first addition usually trans (anti) as if the halonium ion was an intermediate (but most likely it is not)
  • second addition often follows
  • less reactive than alkenes
 
 
Reaction 15.  Electrophilic addition of water to alkynes.
Reagents and conditions Mechanistic details
  • HgSO4/H2O/H2SO4
  • no NaBH4 necessary to replace mercury (Hg) with hydrogen
  • electrophilic addition catalyzed by Hg2+ (mercurinium ion not involved)
  • Markovnikov's rule apply
  • the primary product is an enol, a less stable tautomer of a ketone
 
 
Reaction 16.  Hydroboration of alkynes (formal addition of water).
Reagents and conditions Mechanistic details
  • BH3/THF gives mixture of regioisomers for disubstituted alkynes, double addition with terminal alkynes
  • R'2BH (R' = 1,2-dimethylpropyl) may be used for monoaddition to terminal alkynes
  • four - membered cyclic transition state for addition
  • syn addition
 
 
Reaction 17.  Hydrogenation of alkynes.
Reagents and conditions Mechanistic details
  • Lindlar catalyst used for cis product (Pd, CaCO3, Pb(OAc)2, quinoline)
  • lithium metal in ammonia for trans product
  • hydrogenation is a heterogeneous reaction
  • hydrogenation catalyst is poisoned (deactivated) to prevent further reduction of the double bond
  • Li reduction involves electron - transfer process and proceeds via an intermediate vinylic carbanion
 
 
Reaction 18.  Alkylation of acetylide anion.
Reagents and conditions Mechanistic details
  • KNH2 or NaNH2 used as a base (in NH3 or THF)
  • LDA in THF used as a base
  • primary electrophiles (alkylating agents) work well
  • the increased acidity of the sp hybridized carbon makes carbanion accessible (the lone electron pair in the conjugate base, acetylide anion, has large s character)
  • SN2 substitution mechanism followed (back-side attack on the electrophilic carbon)
 
 
Reaction 19.  Oxidative cleavage of alkynes.  
Reagents and conditions Mechanistic details
  • KMnO4 or ozone
  • often low yields
  • complicated oxidation mechanisms
  • more difficult to oxidize than alkenes
  • substituted "ends" yield the corresponding carboxylic acids, unsubstituted ones give CO2
 
 
Reaction 20.  Electrophilic addition of HX to conjugated dienes.  
Reagents and conditions Mechanistic details
  • HCl or HBr in ether
  • electrophilic addition leading to allyl (resonance stabilized) carbocations
  • the allyl cation can be attacked by the bromide anion at two positions
  • the 1,2-adduct (A) is kinetically favored (predominates at low temperatures)
  • the 1,4-adduct (B) is thermodynamically more stable and it predominates at higher temperatures
 
 
Reaction 21.  Electrophilic addition of halogens to conjugated dienes.  

 

Reagents and conditions Mechanistic details
  • Br2 or Cl2 in CCl4 or CH2Cl2
  • electrophilic addition leading to halonium ion intermediate
  • the 1,2-adduct is kinetically favored (predominates at low temperatures)
  • the 1,4-adduct is thermodynamically more stable and predominates at higher temperatures
 
 
Reaction 22.  Radical (chain) halogenation of alkanes.  
Reagents and conditions Mechanistic details
  • X2; the reaction is explosive for F2 and very sluggish for I2 (thermodynamic reasons)
  • heat or light used to generate radicals in the initiation steps
  • mixtures of products are obtained (mono- and poly-halogenated compounds, and different regioisomers)
  • NBS in CCl4 (with light or initiators) used for allylic or benzylic brominations
  • radical chain reactions
  • the initiation step generates X˙ radical
  • selectivity is established in the hydrogen-abstraction step by X˙
  • the more reactive X˙, the less selective it is
 
 
Reaction 23.  Conversion of alcohols into alkyl halides.  
Reagents and conditions Mechanistic details
  • HX in ether (works best for tertiary alcohols)
  • PBr3 in ether or CH2Cl2
  • SOCl2 in pyridine
  • TosCl/pyridine followed by X
  • SN1 mechanism for tertiary alcohols
  • SN2 mechanism for primary alcohols
  • hydroxyl group is converted to a better leaving group by reaction with the reagent of choice
 
 
Reaction 24.  Nucleophilic substitution reaction on sp3 hybridized carbons. 
Reagents and conditions Mechanistic details
  • variety of conditions and solvents usually polar and protic solvents for SN1 reactions
  • usually polar aprotic solvents for SN2 reactions
  • SN1 mechanism for tertiary substrates: the leaving group departs in a unimolecular rate-limiting step, generating the carbocation, which in the second step reacts with the nucleophile; ion pairs may be involved and carbocation rearrangements may compete
  • SN2 mechanism for primary substrates: the nucleophile displaces the leaving group in one-step bimolecular back-side attack leading to inversion of configuration on stereogenic centers
  • secondary, allylic or benzylic substrates may react by both mechanisms
  • competition with elimination reactions (E1 and E2) often observed  
 
 
Reaction 25.  Elimination reaction to form carbon-carbon double bonds.  
Reagents and conditions Mechanistic details
  • variety of conditions and solvents
  • usually strong bases favor E2 mechanism
  • E1 mechanism for tertiary or secondary allylic or benzylic substrates: the leaving group departs in a unimolecular rate-limiting step, generating the carbocation, which in the second step is deprotonated (with base) on the carbon adjacent to the cationc center,  yielding  the olefin; carbocation rearrangements may compete
  • E2 mechanism favored by strong bases: the base removes a proton from the carbon adjacent to one bearing the leaving group in a one-step bimolecular reaction that requires periplanar orientation of the hydrogen and the leaving group (anti-periplanar preferred)
  • competition with substitution reactions (SN1and SN2) often observed
  • Usually the most substituted olefin is the major product (Zaitsev's rule)
 
 
Reaction 26.  Aromatic electrophilic substitution.
Reagents and conditions Mechanistic details
  • Br2 and FeBr3 (or AlBr3) for bromination
  • Cl2 and FeCl3 (or AlCl3) for chlorination
  • I2 and H2O2 (or  CuCl2) for iodination
  • HNO3/H2SO4 for nitration
  • SO3/H2SO4 for sulfonation
  • RX and AlCl3 for alkylation
  • RCOX and AlCl3 for acylation
  • positively charged electrophile adds to the aromatic ring in the rate-limiting step; the resulting carbocation reverts to aromaticity by the loss of proton
  • the relative reactivity and regiochemistry of the reaction on substituted benzene derivatives is governed by the nature of the substituent: the substituents that are electron withdrawing by inductive and resonance effects are deactivating and meta-directing; the substituents that are electron withdrawing by inductive effects and electron donating by resonance are ortho- and para-directing and depending on the electron-density balance are deactivating (halides) or activating (O in ethers, N in amines or amides); the substituents that are electron donating by inductive and resonance (hyperconjugation) effects are activating and ortho- and para-directing
 
 
Reaction 27.  Oxidation of side chains in aromatic compounds.
Reagents and conditions Mechanistic details
  • KMnO4 or Na2Cr2O7
  • complex oxidation mechanism
  • requires at least one benzylic hydrogen
 
 
Reaction 28.   Hydrogenation of aromatic compounds.
Reagents and conditions Mechanistic details
  • H2 (several hundred atm) over Pd
  • H2 (1 atm) over Rh
  • heterogeneous catalysis with a complex mechanism
  • no partial reduction possible
 
 
Reaction 29.  Reduction of carbonyl compounds to alcohols.
Reagents and conditions Mechanistic details
  • NaBH4 (or LiAlH4) for aldehydes and ketones
  • LiAlH4 for carboxylic acids and esters
  • BH3-THF for carboxylic acids
  • the hydrides deliver H to the carbonyl-group carbon (nucleophilic addition to C-O double bond)
  • for carboxylic acids and their derivatives, the tetrahedral intermediate formed loses R'O group, and the newly formed carbonyl group is reduced again
 
 
Reaction 30.  Addition of Grignard reagents to carbonyl compounds to yield alcohols.
Reagents and conditions Mechanistic details
  • Grignard reagents are prepared by reacting organic halides with metallic magnesium in ether solvents
  • usually carried out in ether solvents (ether, THF)
  • organolithium compounds (RLi) can be used instead of Grignard reagents
  • nucleophilic addition of electron-rich (carbanion-like) carbon from the organometallic reagent to the electrophilic carbon of the carbonyl group
  • the addition to esters takes place twice; the initially formed tetrahedral intermediate expels RO, regenerating the carbonyl group which reacts with the second molecule of the organometallic reagent
 
 
Reaction 31.  Dehydration of alcohols.
Reagents and conditions Mechanistic details
  • acid with a non-nucleophilic counterion (H2SO4) for tertiary substrates
  • POCl3/pyridine for 2o and 1o alcohols
  • E1 mechanism for tertiary alcohols
  • E2 mechanism for POCl3/pyridine (POCl3 converts -OH into a good leaving group: -OPOCl2)
  • usually Zaitsev's rule followed (see Reaction 25)
 
 
Reaction 32.  Oxidation of alcohols.
Reagents and conditions Mechanistic details
  • PCC (pyridinium chlorochromate) or periodinane for oxidation of 1o alcohols to aldehydes (2o alcohols are oxidized to ketones)
  • Jones' reagent (CrO3/H2SO4/H2O/acetone) or dichromate (Na2Cr2O7) for oxidation of 1o alcohols to carboxylic acids and 2o alcohols to ketones
  • E2-like elimination on chromate  or periodinane intermediates
 
 
Reaction 33.  The Williamson ether synthesis.
Reagents and conditions Mechanistic details
  • alkoxides are prepared by reaction of alcohols with bases or alkali metals
  • reaction of alkoxides with primary alkyl halides
  • intramolecular reaction yields cyclic ethers
  • SN2 substitution reaction with oxygen serving as nucleophile
 
 
Reaction 34.  Acidic cleavage of ethers.
Reagents and conditions Mechanistic details
  • HI or HBr for 1o and 2o ethers
  • HI, HBr and HCl for 3o ethers
  • SN2 for primary ethers (after protonation on oxygen, attack by X on the least substituted of the two carbons)
  • SN1 for tertiary, benzylic or allylic ethers (after protonation on oxygen)
 
 
Reaction 35.  Synthesis of epoxides with peroxyacids.
Reagents and conditions Mechanistic details
  • peroxyacids (RCOOOH, for example m-chloroperoxybenzoic acid, MCPBA)
  • direct oxygen transfer from the peroxyacid to the alkene (syn stereochemistry)
 
 
Reaction 36. Ring-opening reactions of epoxides.
Reagents and conditions Mechanistic details
  • acid catalysis (H2O, Cl, Br, I as nucleophiles)
  • direct nucleophile addition (HO, RO, RNH2, R2N, RMgX)
  • under acid catalyzed conditions the protonated epoxide can be attacked by the nucleophile at the more (usually the major site of attack), or the less substituted site, depending on substitution patterns (anti stereochemistry results)
  • direct nucleophilic attack (SN2) takes place at the least substituted carbon (anti stereochemistry results)
 
Reactions Last updated 08/07/12 Copyright 1997-2013
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