Grignard reagents (13.6), oxidation of alcohols (13.10), retrosynthetic analysis (12.5)
do all practice probs and recommended problems in this section 13.6*****
*****
add 2 Cs by:
adding Na+ and C with pair of e- and - charge triple bonded to C, attached to an H
hydroboration-oxidation of an alkyne
-creates an aldehyde
grignard and carboxylic acid
-incompatible -grignard serves as base and deprotonates carboxylic acid
alkylation of a terminal alkyne
-installation of 2 additional carbon atoms
oxidation of alcohols
-involves increase in oxidation state -primary alc(2 protons, 1 R group): first oxidation forms aldehyde, second oxidation forms carboxylic acid. -secondary alc(2 R groups, 1 proton): can only be oxidized once to form a ketone -tertiary alc (no protons on alpha carbon): does not undergo oxidation
how to make a vicinal dihalide
-start with alkene -add X2 with CCl4 solventand it will ge(t added across the double bond
to form aldehyde as final product w/ primary alcohol:
-use more selective oxidizing agent to react w/ alcohol but not aldehyde -PCC (formed from reaction between pyridine, chromium trioxide, and HCl) when used as oxidizing agent---> aldehyde as major product -methylene chloride is usually solvent with PCC (CH2Cl2)
primary alcohol + chromic acid=
carboxylic acid
usually primary alc + chromic acid forms _______________ bc aldehyde is hard to isolate.
carboxylic acid
chromium trioxide + H3O+ + acetone =
chromic acid
chromium trioxide in acidic conditions (ex in H30+ and acetone) =
chromic acid
sodium dichromate +H2SO4 +H20 =
chromic acid
alkyne --> alkene
dissolving metal reduction -Na, NH3 (l)
alkene to alkane with halogen (Br) attached
1) HBr, ROOR
alkyne --> alkyne with additional c
1) NaNH2 2) MeI
oxidizing reagents
1) chromic acid(H2CrO4) - can be formed from CrO3 or Na2Cr2O7 (chromium trioxide or sodium trichromate) in aq acidic solution
alkene --> alkyne
1)Br2/Cl4 2)xs NaNH2 3) H2O
to remove OH substituent and add double bond
1)TsCl and pyridine - changes -OH to -OTS so it can be removed 2) t-BuOK (removes OTs and adds double bond)
secondary alcs are oxidized only once to form a ketone, which is stable under oxidizing conditions so secondary alc can be oxidized with:
1. chromic acid -Na2Cr2O7 (H2SO4 and H2O solvent) or 2. PCC (CH2Cl2 solvent) -PCC preferred if other sensitive functional groups in compound bc more gentle -sodium dichromate cheaper
2 steps of oxidation w/ chromic acid mechde + H3
1. formation of a chromate ester (how exactly is chromate ester formed mechanistically?) 2. E2 process to form carbon-oxygen pi bond (rather than C-C pi bond)
if grignard and water presented in one step (don't do this)
R + MgX + H2O---> R-H + HOMgX (R attacks H on H20, remaining OH attacks MgX). note that pka of h20 is 15.7 and RH is 50 ish so large pka difference makes reaction essentially irreversible. every water molecule in flask destroy 1 molecule grignard, and grignard even reacts w/ moisture in air.
terminal alkyne --> aldehyde
use 1) R2BH and 2) H2O2, NaOH
to make a geminal dihalide (w/halogens on same C)
must start w/ an alkyne
grignard and mildly acidic protons (like proton of hydroxyl group). make sure to know mechanism by which grignard attacks self to form alkoxide here?****
not compatible - cannot form grignard reagent -will attack itself to form alkoxide
ways to form triple bond - dihalides we could use:
Dihalide undergoes 2 successive E2 eliminations in the presence of NaNH2 (1. NaNH2 2. H2O) any of the following 3 dihalides could be used to form desired alkyne: 1)geminal dibromide (2 Br groups and 1 ch3 group) 2) vicinal dibromide(1 br group and 1 ch2br) 3) geminal dibromide (additional c and then 2 Br groups attached)
Grignard reagent
formed by reaction between alkyl halide and magnesium. R-X ---Mg---> R-Mg-X. useful in preparing alcohols. characterized by presence of C-Mg bond. C more electronegative than Mg, so carbon withdraws electron density from magnesium via induction which gives rise to partial neg charge on carbon. grignard reagents are carbon nucleophiles capable of attacking a wide range of electrophiles, including the carbonyl group of ketones of aldehydes by the following mech: grignard reagent acts as nucleophile and attacks the c of carbonyl group and e- push up onto oxygen. then proton transfer from water to O on carbonyl. product is an alcohol w/ new r group attached to C (grignard). steps: start w/ ketone or aldehyde 1) r-mg-x 2)H2O --> result = alcohol and extra r group attached. note, water cannot be presented along w/ grignard bc grignard is a strong base and will deprotonate water. after grignard has attacked ketone, water can be added to protonate alkoxide.
