Topic 15: Synthesis of Complex Aromatic Molecules Flashcards
Methods of adding carbon substituents to benzene
Gringard reagents (can make benzylic groups with alcohols + other alkyl groups
Carbonyl reduction reactions e.g. Freidel Crafts Acylation
Oxidation at benzylic position
Formation of the Gringard reagent C6H5MgBr (phenyl-magnesium bromide)
2 steps
Halogenation of benzene with Br2 and FeBr3
to form C6H5Br
This reacts with Mg, Et2O to form C6H5MgBr
C6H5MgBr reaction with epoxide
C-Mg bond attacks unsubstituted C
Reacts with acid (H3O^+) to form a benzyl alcohol
C6H5MgBr reaction with aldehyde
C-Mg bond attacks electrophilic C
curly arrow from C=O bond to O
Reacts with acid (H3O^+) to form a benzyl alcohol
C6H5MgBr reaction with R-C-X
Forms C6H5-C-R
A way to add alkyl groups without scrambling occuring like in Freidel Crafts alkylation
Reaction of ketone formed by … with H2HNH2 under presence of a … and … forms a … where 2 … replace the C=O. This is called a … . The same product can be formed from the same starting material via the … .It reacts with … under the presence of … . Or, by reacting it with a …, … and … .The C=O is replaced with … forming a … structure. This then reacts via … with … and a … catalyst. These methods have … than Freidel Crafts alkylation
acylation
base
heat
alkyl benzene
Hs
Wolf Kishner reduction
Clemmensen reduction
Zn/HG amalgam
HCl
dithiol (HS-R-HS)
BF3
OEt
2 C-S bonds
ring
reduction
H2
Raney-Nickel
Unusual reaction can occur on the benzylic carbon in the structure C6H5CH2R because … . e.g. … carried out by … using … as a solvent as … is a good oxidising agent. This forms a … .Oxidation to … can also occur using the starting material … where R = … .It reacts with … under … . Bromination to alkyl halide (C6H5CH3) can also occur using … under the conditions … or … to form … .The reagent … is … and forms a … which reacts with the starting material
reactive intermediates are stabilised by resonance around the ring
oxidation to aldehydes/ketones
IDX (2-iodoxybenzoic acid)
DMSO/Ph-F
iodine (v)
aldehyde or ketone
carboxylic acids
C6H5R
CH3, CH2R, CHR2
KMnO4 / Na2Cr2O4, H2SO4
heat
NBS
heat
hv
C6H5CH2Br
NBS
stabilised by resonance
Br radical
Aniline is a useful … as it acts as a precursor to … .It is formed by reacting … with … and … to form … .It was then … to … using either … or …
synthen
amides and diazo
benzene
H2SO4
HNO3
C6H5NO2 (nitrobenzene)
reduced
C6H5NH2 (aniline)
Sn, HCl
H2 , Pd/C catalyst
Aniline can react with either … or … to form amides
acetic anhydride (Me-C(=O)-O-C(=O)-Me)
acetyl chloride (Me-C(=O)-Cl)
The diazoisation of aniline occurs by reacting it with … under … conditions to form … .First, the … reacts with … to form … .2 of these molecules react together. A curly arrow goes from … to … and from … to … to form … and … under … . The … product reacts with aniline. A curly arrow goes from … to … and from … to … to form … .This can react under … to form … .A curly arrow goes from … to … and from … to … to form … under … to form … .A curly arrow goes from … to … and from … to … to form … which forms a salt with …
NaNO2, HCl
0-5 degrees celsius
benzenediazonium cation (C6H5-N^+(triple bond)N-Cl^-
NaNO2
HCl
H-O-N=O
lone pair on the O (double bonded to N, first molecule)
the H on the 2nd molecule
the H-O bond on the 2nd molecule
the O (bonded to H and N, second molecule)
H-O-N=O^+-H
O^–N=O
equilibrium
electrophilic (H-O-N=O^+-H)
N lone pair on aniline
N on H-O-N=O^+-H
The N=O^+ double bond
O^+
C6H5-NH2-N(OH)2
equilibrium (+/- H^+)
C6H5-NH-N(-OH)-H2O^+
lone pair on N (attached to C and H)
N-N bond
N-O^+ bond
H
C6H5-N^+(-H)=N-OH
equilibrium (-/+ H^+)
C6H5-N=N-O^+H2
Lone pair on N (attached to ring)
N=N bond
N-O^+ bond
H
C6H5-N6+(triple bond)N
Cl^-
C6H5-N6+(triple bond)N can react with … to form C6H5X, … to form C6H5I, … to form phenol (C6H5OH), … to form benzene or … to form C6H5CN
CuX
KI
water, heat
H3PO2 (hypo phosphorus acid)
CuCN, heat
OH, OR, SR, NHR, NR2, NHC(O)
framework
activating/deactivating
directing effect
pi
very activating (+M)
ortho/para (extra resonance structure)
alkyl, aromatic
framework
activating/deactivating
directing effect
sigma
activating (+I)
ortho/para (+I hyper conjugation)
NO2, SO3H, CHO, COR, CO2R, CONR2, CN
framework
activating/deactivating
directing effect
pi
very deactivating (-M)
meta
CF3, NR3^+, NH3^+
framework
activating/deactivating
directing effect
sigma
deactivating (-I)
meta
F, Cl, Br, I
framework
activating/deactivating
directing effect
pi (responsible for regioselectivity) and sigma (deactivating)
deactivating (-I)
ortho/para (extra resonance structure)
Expected ratio of ortho : para when adding electrophile to C6H5R
1:2
How to favour para over ortho
(2 methods)
Use larger group such as tertiary butyl as the steric block the ortho position .
Make a smaller group larger e.g. reacting Br2 with phenol at room temp would form COH-CBr-CH-CBr-CH-CBr ring (no catalyst as phenol very activating). Make OH group larger by reacting with acid anhydride/chloride to form ester which blocks ortho position + make less activating compound. React with Br2 at 0 degrees celsius to avoid polysubstitution. React with H2O, H^+ (equilibrium) to form alcohol from ester
How to favour ortho over para
Use sulfonation as its reversible
React phenol with oleum (H2SO4, SO3) at 100 degrees celsius (reversible reaction) to form phenol ring with SO3H at ortho and para position (1,3 substitution), makes less activating. Treat with NaOH to deprotonate SO3H groups then Br2 as both SO3^- groups direct meta. Can remove SO3 groups at 200 degrees celsius by steam distillation (reversible reaction) with H2O and H2SO4 to form 2-bromophenol
trend for halogens, NH2, NO2, alkyl, CF3 in terms of how activating they are to benzene ring
NH2 > alkyl > halogen > CF3 > NO2
What dictates the regioselectivity ?
Regioselectivity is a kinetic effect
Stability of Wheland intermediate
Hammond postulate
The TS structure will resemble the closest structure to it in energy
Groups with no lone pairs (e.g. alkyl groups) direct … due to … .The Wheland intermediate is a … with the initial … on the … and … double bonds. The … is stabilised by … and both variations of the intermediate (…) have … resonance forms
ortho and para (not meta)
the electron releasing affect on Wheland intermediate (+I)
carbocation
positive charge
C attached to the alkyl group
2
carbocation
hyper conjugation (+I)
ortho and para
3
Groups with lone pairs (e.g. OH groups) direct … .The Wheland intermediate is a … with the initial … on the … and … double bonds. The … is stabilised by having … resonance forms
ortho and para (not meta)
carbocation
positive charge
C next to the electrophile
2
carbocation
4
