Alkyl Halides
Classes of Halides 1) Alkyl halides- Halogen atom bonded to one of the sp3 carbon atom of an alkyl group CH3CH2CH2Br Propyl bromide 1-bromopropane(IUPAC) Cyclohexyl iodide Iodocyclohexane (IUPAC) t-butyl bromide 2-bromo-2-methylpropane
2. Vinyl halide - Halogen atom bonded to sp2 2. Vinyl halide - Halogen atom bonded to sp2 carbon atom of an alkyl group Vinyl chloride Chloroethene 1-chlorocyclobutene
3. Allyl halide- Halogen atom bonded to allylic carbon atom Allyl bromide 3-bromo-1-propene 2-cyclopentenylchloride 3-chlorocyclopentene
4. Benzyl halide- Halogen atom bonded to 4. Benzyl halide- Halogen atom bonded to benzyl carbon atom of an alkyl group Benzyl chloride Chlorophenyl methane Chloromethyl benzene Diphenylmethyl bromide Bromodiphenylmethane Note: allyl and benzyl equals in stability purposes.
5. Aryl halide -Halogen atom bonded to aryl carbon 5. Aryl halide -Halogen atom bonded to aryl carbon atom of an alkyl group Phenyl chloride (CN) Chlorobenzene (IUPAC) p-bromotoluene (CN) 1-bromo-4-methylbenzene
Dihalides Geminal dihalide: two halogen atoms are bonded to the same carbon Vicinal dihalide: two halogen atoms are bonded to adjacent carbons.
IUPAC Nomenclature Name as haloalkane. Choose the longest carbon chain, even if the halogen is not bonded to any of those C’s. Use lowest possible numbers for position of the halogen. 4-(2-bromoethyl)heptane 2-chlorobutane
Physical Properties Boiling point and melting point a. Alkyl halides have higher bp’s and mp’s than alkanes having the same number of carbons CH3CH3 CH3CH2Br bp = -89C bp = 39C b. Bp’s and mp’s increase as the size of R increases CH3CH2Cl CH3CH2CH2Cl bp = 12C bp = 47C Larger surface area ; higher mp and bp
F > Cl > Br >I Spherical shape decreases b.p (CH3)3CBr CH3(CH2)3Br 73C 102C c. Bp’s and mp’s increase as the size of X increases CH3CH2Cl CH3CH2Br bp = 12C bp=39C More polarizable halogen, higher mp and bp F > Cl > Br >I
Solubility Densities RX is soluble in organic solvents RX is insoluble in water Densities Alkyl fluorides and chlorides less dense than water. Alkyl dichlorides, bromides, and iodides more dense than water.
Preparation of Alkyl Halides
a. Free radical halogenation From Alkanes a. Free radical halogenation (remember stability of radical) and the mechanism
Free radical allylic halogenation Allylic radical is resonance stabilized. produces alkyl halide with double bond on the neighboring carbon, allylic carbon Allylic carbon – cabon atom next to a carbon-carbon double bond N-bromosuccinimide -Produce low concentration of bromine which will add to double bond
**Remember: Free radical chain mechanism initiation, propagation, termination
2. From Alkenes
3. From Alkynes
4. From Alcohols SN1 or SN2 depends on the steric effect of carbocation, R
Reactions of alkyl halides 1) Nucleophilic substitution (SN1 & SN2) 2) Elimination ( E1 & E2) 3) Formation of Organometallic Compounds
Nucleophilic Substitution or SN Reactions The overall process of SN reaction is - The halogen atom on the alkyl halide is replaced with another group. - Since the halogen is more electronegative than carbon, the C-X bond breaks heterolytically and X- leaves; halide is a good leaving group. - The group replacing X- is a nucleophile.
Nu- Has an unshared electron pair available for bonding and is basic in character
What are Nucleophiles? Species rich in electrons (in the form of -ve charge, lone pair of electrons, or ) Eg: a) Strong Nu : NaOH, NaBr, NaOCH3, NaNH2, HCN b) Weak Nu: NH3, H2O, ROH, RNH2 The –vely charge Nu in (a) have more electrons and therefore are stronger Nu- than neutral molecules in (b) with just lone pair of electrons, meaning (a) can react by donating its electrons much easier than (b). Also I > Br > Cl . Spesies in (a) can attack neutral R-X since it is a strong Nu but Species in (b) prefers attacking a charged R-X in order to react since it is less powerful Nu (since it itself is still a neutral molecule).
Second-Order Nucleophilic Substitution: The SN2 Reaction SN2 : substitution, nucleophilic, bimolecular - one step reaction - breaking and forming of bonds occur at the same time. SN2 Mechanism Bimolecular : the transition state of the rate-limiting step involves the collision of two molecules. Concerted reaction: new bond forming and old bond breaking at same time.
Facts about the SN2 reaction The SN2 reaction is a single, concerted process- new bond forming and old bond breaking at same time. The rate of an SN2 reaction depends on the concentration of both alkyl halide and nucleophile because these two molecules exist in the intermediate Rate = k [RX][Nu] Second order
3. Relative rates for SN2: CH3X > 1° > 2° Tertiary (3) halides do not react via the SN2 mechanism, due to steric hindrance.
All SN2 reaction proceed with complete inversion of configuration.
Summary of SN2 Reactions Substrate : CH3X > 1 RX > 2 RX (3 RX is not suitable) Nucleophile: Strong nucleophile. –ve charged molecule Solvent: Less polar solvent Kinetics: Second-order rate equation kr [RX][Nu] Stereochemistry: Complete inversion Rearrangement: Impossible (one step reaction)
First-Order Nucleophilic Substitution: The SN1 Reaction SN1 : substitution, nucleophilic, unimolecular SN1 Mechanism
Rearrangements of Carbocations Don’t Forget : Rearrangements of Carbocations Hydride shift: H- on adjacent carbon bonds with C+. Methyl shift: CH3- moves from adjacent carbon if no H’s are available.
Facts about the reaction The SN1 reaction is two step reaction with carbocation intermediate. The rate is first order in the alkyl halide, zero order in the nucleophile. Rate = k [RX] First order
3. The rate of SN1 reaction follow the order of stability of carbocation (opposite to SN2) Benzylic > allylic > 3° > 2° > 1° >> CH3 More stable ion requires less energy to form Note: aryl & vinyl will not react
4. Stereochemistry of SN1 Racemization: inversion and retention
Summary of SN1 Reactions Substrate : benzyl > allyl > ~3 RX > 2 RX (1 RX and CH3X are unlikely) Nucleophile: weak nucleophile, neutral molecule Solvent: polar protic solvent Kinetics: first-order rate equation, kr [RX] Stereochemistry: racemic; inversion & retention Rearrangement: common to form most stable carbocation
SN2 or SN1? CH3X > 1 RX > 2 RX (3 RX is not suitable) Strong nucleophile Rate = k[halide][Nuc] Inversion at chiral carbon No rearrangements; single step reaction benzyl > allyl > ~3 RX > 2 RX (1 RX and CH3X are unlikely) Weak nucleophile (may also be solvent) Rate = k[halide] Racemization of optically active compound Rearranged products; carbocation
Second-Order Elimination: The E2 Reaction Bimolecular elimination Requires a strong base One step reaction- Halide leaving and proton abstraction happens simultaneously - no intermediate. E2 Mechanism
Summary of E2 Reactions Substrate : benzyl > allyl > ~3 RX > 2 RX (1 RX and CH3X are unlikely) Nucleophile: strong base Solvent: polarity is not so important Kinetics: second-order rate equation, kr [RX][B:-] Stereochemistry: coplanar arrangement (anti) Rearrangement: none Product follows Saytzeff’s rule (alkene)
First-Order Elimination: The E1 Reaction Unimolecular elimination Two groups lost (usually X- and H+) Nucleophile acts as base (weak base) Also have SN1 products (mixture)
E1 Mechanism (Example) Halide ion leaves, forming carbocation. Base removes H+ from adjacent carbon. Pi bond forms.
Summary of E1 Reactions Substrate : benzyl > allyl > ~3 RX > 2 RX (1 RX and CH3X are unlikely) Nucleophile: weak base Solvent: polar protic solvent Kinetics: first-order rate equation, kr [RX] Stereochemistry: no particular geometry Rearrangement: common to form most stable carbocation Product follows Saytzeff’s rule (alkene)
E1 or E2 ? benzyl > allyl > ~3 RX > 2 RX (1 RX and CH3X are unlikely) Strong base required Solvent polarity not important Rate = k[halide][base] Saytzeff product No rearrangements benzyl > allyl > ~3 RX > 2 RX (1 RX and CH3X are unlikely) Weak base Good ionizing solvent Rate = k[halide] Saytzeff product Rearranged products
Predicting Substitutions and Eliminations To determine whether an alkyl halide reacts by an SN1, SN2, E1 or E2 1. Classify the alkyl halide as 1, 2 or 3 2. Classify the base or nucleophiles as strong, weak or bulky.
Some important facts Basicity is defined by the equilibrium constant for abstracting a proton. Nucleophilicity is defined by the rate of attack on an electrophilic carbon atom.
3 alkyl halides R3CX react by all mechanism except SN2 a. With strong bases Favors SN2 or E2 mechanism 3 halides are too sterically hindered to undergo an SN2 reaction, so only E2 elimination occurs. Example:
b. With weak nucleophiles or bases Favors SN1 and E1 mechanism and both occurs Example:
1 alkyl halides RCH2X react by SN2 and E2 mechanism a. Strong nucleophile Favors SN2 and E2, but 1 halides are the least reactive halide in elimination; therefore, only SN2 reaction occurs. Example:
Strong, sterically hindered bases for attack on carbon. - cannot as a nucleophile - but a stronger base - elimination occurs so the mechanism is E2 Example: E2
2 alkyl halides R2CHX react by all mechanisms a. With strong bases and nucleophiles A mixture of SN2 and E2 Example:
Strong, sterically hindered bases - cannot as a nucleophile - elimination occurs so the mechanism is E2 Example:
c. With weak nucleophile or base - Favours SN1 and E1 Example:
Summary chart on the four mechanisms: Alkyl Halide Conditions Mechanism 1RCH2X Strong nucleophile SN2 Strong bulky base E2 2R2CHX Strong base and nucleophile SN2 + E2 Strong bulky base and nucleophile Weak base and nucleophile SN1 + E1 3RX Strong base
Visual Tests of Alkyl Halides 1. With AgNO3 in ethanol solution (SN1 reaction) Halides Benzyl, allyl and 3 immediate precipitate 2 precipitate formed within 5 minutes 1 , aryl and vinyl no reaction (clear solution)
2. RBr with NaI in acetone (SN2 reaction) Bromides 1 immediate precipitate 2 precipitate formed within 5 minutes 3, aryl and vinyl no reaction (clear solution)