14D alcohols and epoxides

Reaction type: synthesis of alcohols ROH from R-X

R-X → R-OH

LG: X

elec:R. (+)

nuc: OH-

reaction mech: Sn2 with primary haloalkane

• when sec or tert haloalkane elimination becomes a possibility

Reaction type: Reduction of aldehydes and ketones from NaBH4 (BH4) and LiAlH4(AlH4)

Step 1: the nucleophile attacks (hydrogen attachment to carbon)

Nuc: Hydride (neg H)

• elec: Carbon bound to O

Intermediate:

alkoxide→ oxygen with neg charge

Step 2: proton-transfer (proton attachment

• Nuc: Alkoxide

• elec: Proton from the solvent

Product: aldehyde and ketone with a H bound to the carbon and H bound to the oxygen

• characterized by the attachment of two hydrogens (unlike gringnard)

aldehyde and ketone

aldehyde→ at the end : R-CHO

keotne→ in the middle: R2-CO

what are the common reducing agents for alcohol generation from aldehyde and ketone

BH4 (-)

AlH4(-)

Reaction type: alcohols from organometallic reagents

Step1: Nucleophilic attack and carbon R group attachment

Nuc: carboanion on the R group

Elec: carbon attached to the oxygen

Intermediate: alkoxide with R group

Step2: Proton transfer from solvent

Nuc: alkoxide

elec: solvent proton

organometallic reagents types and associated solvents

-grignard: R-MgBr where R is (-) carboanion

-Organolithium: R-Li2Br where R is (-) carboanion

-essentially function as carbanions and strong base

Ether: polar aprotic solvent

primary, secondary and tertiary alchohols are produced from what when reacting with a organomettalic

primary→ formaldhyde

secondary→ aldehyde (any)

tertiary→ ketone

formaldehyde

simplist aldehyde,R group is a hydrogen CH2O

how to do retrosynthetic analysis

-goal: finding the starting species to produce the product

1. disconnect either side of the alcohol

2. the other group that is not attahced to the carbonyl group would be the R group on the organometallic (MgBr) (important, the cabron holdign Oh stays with the aldehyde piece)

3. the answer the original product would be the section you cut out that is attahced to the cabronyl group

4. 
   

carbonyl group

-on ketones and aldehydes, RCH=O

defintion of oxidation and reduction in alcohols

how to remember the reagents

oxidation-loss of hydrogen/gain of oxygens

reduction-gain of hydrogen

oxidizing agents are loaded with oxygens

reducing agents are loaded with hydrogens

Reaction type: Oxidation of the Alcohols

Reagent: K2Cr2O7/H2SO4 or CrO3/H2SO4 (JOnes) or KMnO4/OH-/heat

Removes hydrogens from the alchohol

-the more hydrogens on the alpha carbon, the more reactive

primary alc→ aldehyde→carboxylic acid

sec alc→ Ketone

tert alc (no hydrogen)→ no reaction

they turn an alcohol’s C–O single bond into a C=O double bond. The key is removing the O–H hydrogen and a hydrogen on the carbon bearing the OH

-the acids with the Cr and Mn species→creates acidic conditions that help the alcohol attach to the chromium oxidizing agent.

1. Generates the active oxidant: dichromate in acidic water forms chromic acid and related chromium(VI) species.

2. Makes chromium easier to attack: protonating an oxygen on the chromium reagent increases chromium’s electrophilicity. The alcohol oxygen can then donate a lone pair to chromium, forming the chromate ester

-do not need to know arrow pushing

carboxylic acid

R-COOH

reaction type; partial oxidation of alchohols

-use when you want to stop at aldehyde part when oxidating primary alchohols =→ to do so, use a weaker oxidizing agent/weaker version of cro3

oxidizing agents; PCC + aprotic olvent

primary alcohol + PCC → (in aprotic solvent) species that is the aldehyde version of the primary alcohol

secondary alcohol +PCC→ ketone

reaction type; coversion of alcohol into haloalkane (primary alchohol and methanol) sn2 mechanism

-requires STRONG BINARY ACID where the species bound to H is the halogen

-2 STEPS PT+ sn2

-sn2 can only do primary and meth

step1: PT (proton transfer)

Oxygen on alcohol donates electron to the proton, which the proton transfers the electron to hydrogen on h-x

h on h-x donates the electron to the x creating x- and h2o+-r

nucleophile: the oxygen on the alcohol

electrophile; the halogen

internediate: oxonium formation (oxygen with positive charge)

step 2: sn2

x- donates electron tot the bond connecting oxonium and r group, the bond donates electron to the oxonium creating free h2o (water) and x is bound to where oxonium was

nucleophile; halide (- charge)

electrophile; oxonoium

why conversion of alcohol into haloalkane

why?→ OH group on the alcohol is a bad LG since it is highly basic (wants to donate eleectrons rather than leave with it)(remember, the best LG’s are the weak bases) thus, we convert the LG into a halogen so that then we can undergo substitution to get rid of the group

reaction type; coversion of alcohol into haloalkane (sec and tert alchohol) sn1 mechanism

-requires STRONG BINARY ACID where the species bound to H is the halogen

-3 STEPS PT+ sn1

step1: PT (proton transfer)

Oxygen on alcohol donates electron to the proton, which the proton transfers the electron to hydrogen on h-x

h on h-x donates the electron to the x creating x- and h2o+-r

nucleophile: the oxygen on the alcohol

electrophile; the halogen

internediate1: oxonium formation (oxygen with positive charge)

step 2: sn1 LG leaves

the bond donates electron to the oxonium creating free h2o (water) and carbocation is formed

nucleophile; bond connecting c and oxonium

electrophile; oxonoium

intermediate2: carbocation

step 3: sn1 attack

x- attacks the carbocationm forming bond between carbon (preciously carbocation) and x-

nucleophile; halide (x-)

electrophile; carbocation

reaction type: Conversion of alchols to haloalkanes (WITHOUT BINARY ACID) (remember, the reactants are loaded with haloalkanes)

two reacting species/nucleophiles; PBr3, SOCl2

-sn2 reaction (DIRECT SUBSTITUTION)

-only effective in primary and secondary alcohols, NOT TERTIARY alchohols

remember, that all reactions that include sn2 have INVERSION possible for product

R becomes S, wedges becomes dashes. ‘

You actually don’t have to redraw it first. Here’s an easier way to show SN2 inversion when Br is on a straight bond:

1. Replace Br with the nucleophile, keeping that straight bond.

2. Switch the wedged and dashed groups on that same carbon.

Reaction type: conversion of a alcohol into aljyl sulfonates

-why? dont forget that sulfonates (ROSO2R’) are also good leaving groups

reagents: TsCl and pyridine base (pyr)

step 1: substitution of alc to sulfonate

R-OH + TsCl + Pyr → R-OTs

step 2: substitution of sulfonate to R-Nu

R-OTs + H-Nu → R-Nu

(can be bi or uni depending on R group classification)

good leaving groups

Halogens, OH2(+) (oxonium), sulfonates (ROSO2R’)

what is R-OTs

tosylate leaving group (ROSO2R’)

Reaction type Conversion of a PRIMARY alcohol to an alkene; ACID CATALYZED DEHYDRATION (what acid is used?)

acid→ oxoacid (not binary acid) h3, H2SO4, H3PO4

2 STEPS; PT + E2

REMEMBER< since this is E2, if the alcohol was on a ring structure then you would need to consider which beta hydrogen to DB (choose the one that is anti to the leaving group (which is h2o)

step 1: PT

oxygen donates electron to hydrogen on oxoacid, → oxygen becomes oxonium

hydrogen donates electron to the rest of the species, breaking bond between hydrogen and the acid

nucleophile; oxygen on alc

electrophile; hydrogen/part of the acid with pos formal charge

LG; none

transformations that occur; alcohol becomes oxonium, the acid becomes its conjugate base species

step 2: E2 reaction

beta hydrogen is attacked by base/nucelophilic atom on the base

attacked hydrogen leaves and joins conjugate base

extra electron attacks oxonium/LG → oxonium becomes water (ths dehydration)

product; db no alc alkene with acid that we started the reaction with

Nucleophile; conjugate base

electrophile; oxonium

LG: h2o

Reaction type Conversion of a SEC OR TERT alcohol to an alkene; ACID CATALYZED DEHYDRATION (what acid is used?)

E1 ACID-CATALYZED DEHYDRATION OF ALCOHOLS

Conditions: H₂SO₄ or H₃PO₄ + heat. H₃O⁺ may represent the acid in the mechanism.

Usually: secondary or tertiary alcohols, because they can form sufficiently stable carbocations.

3 STEPS: PT → WATER LEAVES → β-H REMOVAL
The last two steps make up the E1 elimination.

REMEMBER:

• The double bond forms between the carbocation carbon and an adjacent carbon that loses H.

• Usually favor the more substituted alkene: Zaitsev’s rule.

• No E2 anti-periplanar requirement, including no trans-diaxial requirement for cyclohexanes: the leaving group has already left before H is removed.

• Check for carbocation rearrangements before choosing the β-H. A hydride or alkyl shift may create a more stable carbocation.

Step 1: PT — proton transfer

The alcohol oxygen uses a lone pair to bond to a hydrogen on the acid.

Arrow pushing:

• Alcohol oxygen lone pair → H on the acid.

• Acid’s O–H bond → acid’s oxygen, breaking that bond.

The alcohol becomes R–OH₂⁺, a protonated alcohol or oxonium ion. Oxygen now has three bonds and a positive formal charge.

• Electron donor/base: oxygen on the alcohol.

• Electrophile: acidic H. It can be partially positive; it does not need a positive formal charge itself.

• Leaving group from the alcohol: none yet.

• Transformation: alcohol → oxonium; acid → its conjugate base.

Purpose: convert poor leaving group OH⁻ into a group that can leave as neutral H₂O.

Step 2: Water leaves — carbocation formation

The C–O bond breaks, and both bonding electrons go to oxygen.

Arrow pushing:

• C–O bond → oxygen of OH₂⁺.

Water separates from the carbon chain. Oxygen becomes neutral, and the carbon that lost water becomes a carbocation.

• Nucleophile/base: none involved in this step.

• Electrophilic center produced: the positively charged carbon.

• Leaving group: H₂O.

• Transformation: oxonium → carbocation + water.

This is usually the slow, rate-determining step.

CHECK NOW: can a hydride or alkyl shift produce a more stable carbocation?

Step 3: β-H removal — double-bond formation

A base, commonly water or the acid’s conjugate base, removes H from a carbon adjacent to the carbocation.

Arrow pushing:

• Base lone pair → β-H.

• β-C–H bond → bond between the β carbon and carbocation carbon, creating C=C.

The H transfers to the base. The C–H electron pair stays with the carbon skeleton and forms the π bond, giving the carbocation carbon a full octet.

• Base/electron donor: water or the acid’s conjugate base.

• Proton accepted by the base: β-H.

• Electron-deficient center receiving the new π bond: carbocation carbon.

• Leaving group: water already left in step 2.

• Transformation: carbocation → alkene; acid catalyst is regenerated.

Overall product: alkene + water, with the acid catalyst regenerated.

Memory sequence: protonate OH → lose water → remove neighboring H and form C=C.

conjugate base of h3o is..

h2o

Reaction type: conversion of alcohols into ethers (williamson ether synthesis)

step1: deprotonation of alc with a VERY STRONG BASE

strong base takes away hydrogen from alc to create alkoxide to formt he alkoxide nucleophile (o-)

step 2: sn2 subsitutition

alkoxide attacks a haloalkane, haloalkane leaves and joins with the strong base

the whole group with the alkoxide joins the alkane that was attched to the halogen, forming r-o-r

what is an ether look like

R-O-R

strong bases used for conversion of alcs into ethers

LDA, BuLi, KH, Li, Na, K, Cs

how to know that a reaction is going to be intramolecular

if you start with a chain and end with a cyclic molecule

intramolecular williamson ether synthesis forms epoxides

sn2 reaction within the molecule,

reagent; chain with both LG and OH + STRONG BASE

one step; base removes hydrogen from alc, forms alkoxide, alkoxide sttacked bonds leading to LG, LG leaves, the bond is mended by the LG side of the chain which is now pos to attach tot he negative alkoxide

converison of a ketone or aldehyde into a alcohol (reduction)

alcohols from organometallic reagents

acid retrosynthesis

oxidation of alcohol (oxygen added for carboxylic acid)

conversion of roh into haloalkane through sn2 reaction

conversion of roh into haloalkanes sn1 reaction

conversion of roh into alkenes; acid catalyzed dehydration

conversion of roh into ether

nucleophilic ring opening of oxiranes to produce alcohols

acid catalyzed ring opening (not a basic nucleophile for the ring opening like nucleophi;lic ring opening)

MgBr, Li2Br

grignard: R-MgBr where R is (-) carboanion

-Organolithium: R-Li2Br where R is (-) carboanion

-essentially function as carbanions and strong base

Ether: polar aprotic solvent

NaBH4 (BH4) and LiAlH4(AlH4)

K2Cr2O7/H2SO4

CrO3/H2SO4

KMnO4/OH-/heat

PCC + aprotic olvent

h-x strong binary acid

PBr3, SOCl2

conversion of alcohol to haloalkane without the use of a strong binary acid; direct susbtituion, with Sn2→ thus only occurs with primary or secondary

TsCl and pyridine base (pyr)

a VERY STRONG BASE LDA, BuLi, KH, Li, Na, K, Cs

primary alcohol into haloalkane, sec and tert alc into haloalkane

sn2, sn1

alcohol into tosylate

substitution

primary alcohol into an alkene, sec,tert alcohol into alkene

PT+E2, PT+E1

alcohol into an ether

pt + sn2

aldehyde/ketone into alchol

nucleophilic addition + PT

formaldehyde/other-carbonyl into alcohol using gringard

nucleophic addition + PT

nucleophilic chain opening

sn-2 like opening + PT

acid catalyzed chain opening

PT _+sn2 like opneing + PT

alkoxide is a good… and oxonium is a good…

nucleophile.base and oxonium is a good leaving group