Organic Halides

Question 1

4 general types of organic halides

Answer 1

1. Alkyl Halide
   - halogen attached to alkyl group
2. Aryl Halide
   - halogen attached to aryl/aromatic group
3. Vinylic Halide
   - halogen attached to vinylic carbon
4. Acetylenic Halide
   - halogen attached to acetylenic carbon (carbon w/ triple bond mismo)

Question 2

ALKYL HALIDES

• HALOGEN bonded to WHAT hybridization of carbon?
• polar/nonpolar
• what bonds does it exhibit?
• 3 classifications?

Answer 2

Csp3 - X np
- polar (w polar bond)
- LDF and DDF

1. Primary
   - halogen attached to primary carbon
2. Secondary
   - halogen attached to secondary carbon
3. Tertiary
   - halogen attached to tertiary carbon

Question 3

NOMENCLATURE OF ALKYL HALIDES

1. Common Name
2. IUPAC Name

Answer 3

1. alkyl group + halide
   (methyl fluoride)
2. treat halogen as substituent + alkyl parent name

Question 4

DETERMINE THE common and IUPAC name of the ff:

CH2X2
CHX3
CX4

Answer 4

• CH2X2
  CN: methylene halide (methylene chloride)
  IUPAC: dihalomethane (dichloromethane)
• CHX3
  CN: haloform (chloroform)
  IUPAC: trihalomethane (trichloromethane)
• CX4
  CN: Carbon tetrahalide (carbon tetrachloride)
  IUPAC: tetrahalomethane (tetrachloromethane)

Question 5

PHYSICAL PROPERTIES - Polarity

Answer 5

slightly polar due to C-X bond

Question 6

PHYSICAL PROPERTIES - Physical State

• 4 examples of liquids at room temp?

Answer 6

CH3 I

CH3 CH2 Br

CH3 CH2 CH2 Cl

CH3 CH2 CH2 CH2 F

Question 7

PHYSICAL PROPERTIES - Boiling Point

• determine if the boiling point of the molecule will increase or decrease:

1. increase overall MW
2. increase branching
3. increase MW of X
4. increase # of X

Answer 7

1. increase BP
2. decrease BP
3. increase BP
4. increase BP

Question 8

PHYSICAL PROPERTIES - Boiling Point

is BP of alkyl halides HIGHER or LOWER than BP alkanes?

Answer 8

higher

Question 9

PHYSICAL PROPERTIES - Solubility

(2)

Answer 9

1. insoluble in polar (H2O)
2. soluble in non-polar (organic) solvents

Question 10

PHYSICAL PROPERTIES - Density

(2)

Answer 10

LESS DENSE than water
- Alkyl Fluorides (w/ 1 F atom)
- Alkyl Chlorides (w/ 1 Cl atom)

MORE DENSE than water
- Polychlorinated alkyl halides

Question 11

OCCURENCES OF ORGANIC HALIDES

undergoes free-radical reaction with ozone

Answer 11

chlorofluorocarbons

Question 12

OCCURENCES OF ORGANIC HALIDES

solvents (2)

Answer 12

carbon tetrachloride

dichloromethane

Question 13

OCCURENCES OF ORGANIC HALIDES

household cleaners (1)

Answer 13

dichloroethane

Question 14

OCCURENCES OF ORGANIC HALIDES

anaesthetics

Answer 14

halothane

Question 15

OCCURENCES OF ORGANIC HALIDES

topical cooling agent

Answer 15

chloroethane

Question 16

OCCURENCES OF ORGANIC HALIDES

medicine (2)

Answer 16

1. vancomycin
2. chlorphenamine maleate

Question 17

PREPARATIONS OF ORGANIC HALIDES

• 5 types + subtypes for each

Answer 17

1. From Alkanes
   - monohalogenation
   - halogenation of cyclopropane
2. From Alkenes
   - electrophilic addition of X2
   - electrophilic addition of HX
3. From Alkynes
   - electrophilic addition of X2
   - electrophilic addition of HX
4. From Aromatic Substitution
   - electrophilic aromatic substitution
5. From Alcohols
   - reaction with HX
   - reaction of primary and secondary OH w/ SOCl2 / PBr3

Question 18

beta-carbon vs alpha-carbon in organic halides?

Answer 18

beta-carbon = attached to alpha-carbon

alpha-carbon = attached to X atom

Question 19

REACTIONS OF ALKYL HALIDES

2 general steps?

Answer 19

1. Preparation of Grignard reagents
2. Nucleophilic Aliphatic Substitution (NAS)

OR

Elimination (Dehydrohalogenation)

Question 20

REACTIONS OF ALKYL HALIDES

• what are GRIGNARD REAGENTS?
• useful in ____?
• reagents (3)
• products (2)
• complete reaction (2-step) ?

Answer 20

• organometallic compounds
• organic synthesis

R-C-X (alkyl halide) + Mg -> R-C-MgX

-> R-C:- (carbanion)+ Mg+X

** dry ether or THF

Question 21

REACTIONS OF ALKYL HALIDES - NAS

• determine the properties of the ff:
  1. nucleophile (1)
  2. halogen (2)
• complete reaction?

Answer 21

1. has affinity for carbon atom
2. good leaving group & weak conjugate base of a strong acid

R-C-X + Nu- -> R-C-Nu + X-

R-C-X = alkyl halide
Nu- = nucleophile
R-C-Nu = product
X- = leaving group

Question 22

REACTIONS OF ALKYL HALIDES - NAS

SN2
- complete name?
- order of kinetics?
- dependent on what (2)?
- one-step or two-step reaction?
- essential feature (1)?

• 3 main steps?
• 2 possible products?

Answer 22

• substitution nucleophilic bimolecular
• second order of kinetics
• dependent on CONENTRATIONS OF RX & Nu
• one-step rxn
• transition state

1. backside attack of Nu to C in alkyl halide (slow rxn)
2. concerted bond breaking of the C-X and formation of C-Nu (fast rxn)
3. complete inversion of product configuration ONLY IN CHIRAL α-CARBONS

PRODUCTS:
1. NO chiral carbon
Nu-C + X-

2. W chiral carbon
   inverted Nu-C + X-

Question 23

REACTIONS OF ALKYL HALIDES - NAS

SN2

• what do you call the configuration inversion that takes place in PRODUCTS of chiral carbons?

Answer 23

Walden Inversion

Question 24

REACTIONS OF ALKYL HALIDES - NAS

SN1
- complete name?
- order of kinetics?
- dependent on what (1)?
- one-step or two-step reaction?
- essential feature (1)?

• 3 main steps?
• 2 possible products?

Answer 24

• substitution nucleophilic unimolecular
• first order of kinetics
• dependent ONLY in CONENTRATIONS OF RX
• two-step rxn
• formation of carbocation intermediate

STEP 1: slow rxn
1. formation of carbocation intermediate
R-C-X -> R-C+* + X-
*carbocation intermediate

STEP 2: fast rxn
2. attachment of Nu to carbocation intermediate (may be backside or frontside)
R-C+ + Nu- -> R-C-Nu

PRODUCTS: partial racemization ONLY IN CHIRAL α-CARBONS
1. (S)-product
2. (R)-product

Question 25

REACTIONS OF ALKYL HALIDES - NAS SN1 - percentage of partial racemic products IN CHIRAL CARBONS

Answer 25

60% inverted-product 40% retained-product inverted = inverted config based on original R-C-X retained = same config as original R-C-X

Question 26

REACTIONS OF ALKYL HALIDES - NAS SN2 vs SN1 in terms of: 1. number of steps 2. stereochemistry of products (CHIRAL CARBON) 3. dependence of rate-determining step 4. type of α-carbon involved 5. intermediate 6. transition state 7. solvent

Answer 26

SN2 1. one step (simultaneous dissociation of X & attachment of Nu) 2. inversion of original R-C-X 3. depends on concentrations of both RX and Nu 4. CH3X or primary or secondary carbon 5. no intermediate 6. with transition state 7. polar aprotic solvent --- SN1 1. two step (a. dissociation of X & b. attachment of Nu) 2. partial racemization (60% & 40%) 3. depends on concentrations of only RX 4. secondary or tertiary carbon 5. with intermediate 6. no transition state 7. polar protic solvent

Question 27

REACTIONS OF ALKYL HALIDES - ELIMINATION - general mechanism? - complete reaction? - follows the ______ orientation: _____ rule + description

Answer 27

nucleophile acts as base and abstracts a proton (H atom) from alkyl halide alkyl halide + B- -> alkene + BH + X- Nu- = B- NuH = BH --- positional orientation: Zaitsev's Rule - the more highly stable and substituted ALKENE PRODUCT predominates *disubstituted product - 30% *trisubstituted product - 70%

Question 28

REACTIONS OF ALKYL HALIDES - ELIMINATION E2 - complete name? - order of kinetics? - presence of intermediate or transition state - one-step or two-step rxn? - dependent on what (2)?

Answer 28

- elimination bimolecular - second--order kinetics - w/ transition state / no intermediate - one-step rxn - dependent CONENTRATIONS OF RX & BASE

Question 29

REACTIONS OF ALKYL HALIDES - ELIMINATION E2 - occurs in ____ geometry -> states that all 4 reacting atoms (which are?) are on the SAME PLANE - how will H be abstracted?

Answer 29

- periplanar 1. beta - H 2. beta - C 3. alpha - C 4. X - H must be "anti-planar" to departing X to be abstarcted

Question 30

REACTIONS OF ALKYL HALIDES - ELIMINATION E1 - complete name? - order of kinetics? - presence of intermediate or transition state - one-step or two-step rxn? - dependent on what (1)?

Answer 30

- elimination unimolecular - first order kinetics - w/ carbocation intermediate PRONE to rearrangement - two-step rxn - dependent ONLY in CONENTRATIONS OF RX

Question 31

REACTIONS OF ALKYL HALIDES - ELIMINATION which of the two type (E1 & E2) shows a special effect? - what effect is this? - wherein how much is the mass of the _____? - ^^ effect on speed of rxn

Answer 31

E2 - deuterium-isotope effect - mass of deuterium is twice that of H SLOWER E2 reaction when alkyl halide is deuterated at BETA-POSITION -- E1 doesnt show deuterium-isotope effect since base is not included in the rate-determining step SO the rate of E1 rxn is not dependent on whether the alkyl halide is deuterated or not

Question 32

REACTIONS OF ALKYL HALIDES - NAS 4 factors that affect substitution reactions

Answer 32

1. Nature of Substrate 2. Trends in Nucleophilicity 3. Leaving Group 4. Solvent

Question 33

REACTIONS OF ALKYL HALIDES - NAS AFFECTING FACTORS Nature of Substrate used for: 1. SN2 2. SN1

Answer 33

1. SN2 - bulky substrates attached to α-carbon = sterically hindered & unstable - so prefer ag PRIMARY and SECONDARY α-carbons 2. SN1 - reactivity depends on stability of carbocation intermediate - increasing stability of carbocation = highly substituted α-carbon - thats why tertiary carbons are preferred

Question 34

REACTIONS OF ALKYL HALIDES - NAS AFFECTING FACTORS Trends in Nucleophilicity - nucleophilicity parallels ____ (e-pair ____) - trend in periodic table? - which is stronger: charged vs neutral conjugate nucleophile? Preference of nucleophiles for: 1. SN2 2. SN1

Answer 34

- basicity (e-pair donor) - higher nucleophilicity = higher atomic mass (going down the periodic table) - charged nucleophile is stronger 1. SN2 - prefers stronger & increased concentration of nucleophile 2. SN1 - proceeds even when weak nucleophiles are used since Nu is not involved in rate-determining step

Question 35

REACTIONS OF ALKYL HALIDES - NAS AFFECTING FACTORS Trends in Nucleophilicity - determine the nucleophile examples under the ff categories: 1. strong Nu 2. moderate Nu 3. weak Nu

Answer 35

1. STRONG NU I- ; HS- ; RS- Br- ; HO- ; RO- ; -CN ; N3- Na+ ; Li+ ; K+ 2. MODERATE NU NH3 ; Cl- ; F- ; RCOO- 3. WEAK NU - water, alcohol - carboxylic acid

Question 36

REACTIONS OF ALKYL HALIDES - NAS AFFECTING FACTORS Leaving Groups - preference for SN1 and SN2? - examples of good and bad leaving groups for each

Answer 36

- both SN2 & SN1 prefers good leaving groups (weak base ; strong conjugate acid) GOOD LG: 1.) I- 2.) Br- 3.) Cl- BAD LG: 1.) F- (relatively better LG than others) 2.) others *HI is the strongest conjugate acid + weakest bond (easily broken)

Question 37

REACTIONS OF ALKYL HALIDES - NAS AFFECTING FACTORS Solvent Preference of solvent for: 1. SN2 2. SN1 + reason

Answer 37

1. SN2 (polar aprotic solvent) - does not SOLVATE ANIONS to any appreciable extent e.g. CH3COCH3 DMSO DMF CH3CN HMPA THF Acetone 2. SN1 (polar protic solvent) - SOLVATES CATIONS & ANIONS to increase rate of carbocation stability e.g. WATER ALCOHOLS CARBOXLYIC ACIDS AMMONIA

Question 38

REACTIONS OF ALKYL HALIDES - NAS SN2 or SN1 nucleophiles may be the solvent itself?

Answer 38

SN1 e.g. WATER ALCOHOLS CARBOXLYIC ACIDS AMMONIA

Question 39

REACTIONS OF ALKYL HALIDES - ELIMINATION which favours strong bulky bases? which favours weak bases?

Answer 39

E2: strong bulky base E1: weak base

Question 40

REACTIONS OF ALKYL HALIDES which is favoured in HIGH TEMPERATURES?

Answer 40

elimination

Question 41

REACTIONS OF ALKYL HALIDES 4 steps in determining if a rxn is SN1/SN2/E1/E2

Answer 41

1. determine if alkyl halide is 1°, 2°, or 3° 2. determine if Nu & Base is strong/weak 3. determine solvent (PAS or PPS) 4. check temperature

Question 42

REACTIONS OF ALKYL HALIDES determine examples of the fF: 1. strong Nu that are weak bases 2. borderline 3. strong Nu that are strong bases + determine if what type of rxn each will result to

Answer 42

1. strong Nu that are weak bases -> SN2 e.g. mga natitira 2. borderline -> SN2 or E2 e.g. -OR / -OH *note that ROH is NOT included 3. strong Nu that are strong bases -> E2 e.g. -C≡CR / -NH2 / H-

Question 43

ARALIN SUMMARY TABLE

Question 44

STEREOCHEM OF THE FF: 1. SN1 2. SN2 3. E1 4. E2

Answer 44

1. SN1 - if CHIRAL CARBON: partial racemization 2. SN2 - if CHIRAL CARBON: walden inversion 3. E1 - no stereochem but prefers trans 4. E2 - yung H na mawawala MUST BE antiplanar sa X atom (just follow zaitsev's rule)