Chapter 7 Organohalides Alkyl halide: a compound containing a halogen atom covalently bonded to an sp 3 hybridized carbon atom –given the symbol RX

If the halogen is bonded to an sp 2 hybridized carbon, the compound is called a vinylic halide If the halogen is bonded to a benzene ring, it is called an aryl halide, given the symbol Ar-X A haloalkene (a vinylic halide) CC R R X R X A haloarene (an aryl halide)

Naming Alkyl Halides Step 1: Find the longest chain, and name it as the parent. Step 2: Number the carbons of the parent chain beginning at the end nearer the first substituent, regardless of whether it is alkyl or halo. Step 3: Write the name –halogen substituents are indicated by the prefixes fluoro-, chloro-, bromo-, and iodo- and listed in alphabetical order with other substituents

Preparing Alkyl Halides 1.Addition reactions of HX and X 2 with alkenes 2.The reaction of an alkane with Cl 2

3.The most general method for preparing alkyl halides is to make them from alcohol

Thionyl chloride Phosphorus tribromide Primary and secondary alcohols are best converted into alkyl halides by treatment with thiony chloride or phosphorus tribromide

Reactions of Alkyl Halides: Grignard Reagents Grignard Reagents: alkyl halides react with magnesium metal in ether solvent Organometallic compounds

A Grignard Reagents is formally the magnesium salt, R 3 C - + MgX, of a carbon acid, R 3 C-H, and is a carbon anion, or carbanion Carbon anions are very strong bases

Nucleophilic Substitution Reactions Alkyl halides react with nucleophiles/bases (such as hydroxide ion); either they undergo –Substitution of the X group by the neucleophile –Elimination of HX to yield an alkene

Walden’s cycle of reactions interconverting (+)- and (-)-malic acids. (1896)

Nucleophilic substitution reaction: a reaction in which one nucleophile is substituted for another Nucleophile: an atom or group of atom that can donate a pair of electrons to another atom or group of atom to form a new covalent bond; a Lewis base a nucleophile (Nu: or Nu: - ) reacts with substrate R-X and substitutes for a leaving group X: - to yield the product R-Nu Two major pathways: –S N 1 reaction –S N 2 reaction

If the nucleophile is negatively charged, the atom donating the pair of electrons in the substitution reaction becomes neutral in the product If the nucleophile is uncharged, the atom donating the pair of electrons in the substitution reaction becomes positively charged in the product

The S N 2 Reaction An S N 2 reaction takes place in a single step without intermediates when the entering nucleophile attacks the substrate from a direction 180 o away from the leaving group S = substitution N = nucleophilic 2 = bimolecular Bond breaking and bond forming occur simultaneously

Rate of S N 2 Reactions An S N 2 reaction takes place in a single step when substrate and nucleophile collide and react –If we double the concentration of OH -, the frequency of collision between the two reactants double and the reaction rate also double –If we double the concentration of CH 3 Br, the reaction rate doubles Bimolecular reaction S N 2 reactions are said to be Bimolecular reaction because the rate of the reaction depends on the concentrates of two substances – alkyl halide and nucleophile

Stereochemistry of S N 2 Reactions As the incoming nucleophile attacks the substrate and begins pushing out the leaving group on the opposite side, the configuration of the molecule inverts (S→R)

Steric effects in S N 2 Reactions Methyl halides (CH 3 -X) are the most reactive substrates, followed by primary alkyl halides (RCH 2 -X) Alkyl branching next to the leaving group slows the reaction greatly for secondary halides (R 2 CH-X) Branching effectively halts the reaction for tertiary halide (R 3 C-X)

Vinylic (R 2 C=CRX) and aryl (Ar-X) halides are completely unreactive toward S N 2 displacement This lack of reactivity is due to steric hindrance

The leaving groups in S N 2 Reactions The best leaving groups are those that give the most stable anions (anions of strong acids) A halide ion (I -, Br -, Cl - ) is the most common leaving groups F -, OH -, OR -, and NH 2 - are rarely found as leaving groups

The S N 1 Reaction Most nucleophilic substitutions take place by the S N 2 pathway The S N 1 reaction takes place only –on tertiary substrates –under neutral or acidic conditions in a hydroxylic solvent (water or alcohol) Loss of the leaving group before the incoming nucleophile approaches Loss of the leaving group gives a carbocation intermediate The reactivity order is 3 o >2 o >1 o >methyl

? R-OH + HBr → R-Br + H 2 O

Stereochemistry of S N 1 Reactions For an S N 1 reaction at a stereocenter, the product is a racemic mixture Rates of S N 1 Reactions The rate of an S N 1 reaction depends only on the concentration of the substrate

The leaving groups in S N 1 Reactions The S N 1 reactivity order of leaving groups is:

Eliminations: The E2 Reaction 1.The nucleophile/base can substitute for the leaving group in an S N 1 or S N 2 reaction 2.The nucleophile/base can also cause elimination of HX, leading to formation of an alkene

Zaitsev’s rule: in the elimination of HX from an alkyl halide, the more highly substituted alkene product predominates

Three different mechanisms

The mechanism of the E2 reaction

Eliminations: The E1 and E1cB Reactions E1 mechanism: breaking of the R-X bond is complete before reaction with base to break the C-H bond begins. Only R-X is involved in the rate-limiting step

The mechanism of the E1 reaction

The E1 and S N 1 reactions normally occur in competition whenever an alkyl halide is treated in a hydroxylic (protic) solvent with a nonbasic nucleophile

The E1cB reaction –Take place through a carbanion intermediate –Have a poor leaving group, such as –OH –Predominates in biological pathways

A Summary of Reactivity: S N 1, S N 2, E1, E1cB, and E2 Primary alkyl halide (RCH 2 X) reacts by an –S N 2 if a good nucleophile is used –E2 if a strong base is used (OH -, OR - ) –E1cB if the leaving group is two carbons away from a carbonyl group (HO-C-C-C=O) Secondary alkyl halide (R 2 CHX) reacts by –S N 2 if a weakly basic nucleophile is used –E2 if a strong base is used Tertiary alkyl halide (R 3 CX) reacts by an –E2 if a strong base is used –Mixture of S N 1 and E1 pathways under neutral or acidic condition