Bromobutane

Nucleophilic Substitutions:Preparation of Alkyl Halides from Alcohols CH3-CH2-CH2-CH2-OH

CH3-CH2-CH2-CH2-Br
http://en.wikipedia.org/wiki/SN1_reaction http://ull.chemistry.uakron.edu/organic_lab/butyl/index.html http://www.cem.msu.edu/~reusch/VirtualText/intro1b.htm http://www2.chemistry.msu.edu/faculty/reusch/VirtTxtJml/alhalrx2.htm#hal4 http://www.colby.edu/chemistry/OChem/DEMOS/Substitution.html

Nucleophilic Substitution Reactions: SN1 and SN2

The replacement of an atom/group (leaving group) in a molecule by another atom/group (nucleophile).

Extremely important in organic synthesis!

Electrophile An electron deficient atom, ion or molecule that has an affinity for an electron pair, and will bond to a base or nucleophile. Nucleophile An atom, ion or molecule with an electron pair that may be donated to an electrophile (or Lewis acid) to form a covalent bond.

R = 1 , 2 or 3; the a-carbon could be a chiral center, (R) or (S) -X: Cl < Br < I (F is relatively unreactive)
Variable Nu: anion vs. neutral; change basicity; change polarizability

Solvent: polar vs. non-polar; protic vs. non-protic Mechanism: SN1 vs. SN2 Products: substitution, elimination, no reaction.
Results

Stereospecificity: for a chiral a-carbon,what happens to its configuration? Reaction Rate: is a function of reactant concentration

CH3Br + Cl ---> CH3Cl + Br

http://www.youtube.com/watch?v=ZtnAR3uOAbo SN1 http://www.youtube.com/watch?v=YGSiUZ443xY&fea ture=related

SN1

The C-Cl bond in the halogenoalkane starts to lengthen and weaken The HO- ion could attack from the left-hand side, leading to inversion of configuration of the carbon skeleton (flipped umbrella); or attack could come from the right, leading to retention of configuration. The use of a chiral halogenoalkane in this reaction leads to production of a racemic mixture if the amount of attack from each side is equal. However, hindrance caused by the departing Cl- gives about 40% attack from the right and 60% from the left. What favors SN1? How about the nature of the solvent?

http://www.youtube.com/watch?v=yJlSTWED8Iw

SN2

The HO- anion approaches the chloromethane along the path of lowest energy, colinear with the C-Cl axis As the C-O bond starts to form, the C-Cl bond starts to break The transition state has partial bonds between both C-O and the C-Cl C-O bond shortens/strengthens as the C-Cl lengthens and weakens In the final product the configuration of the carbon atoms has inverted; use of a chiral halogenoalkane leads to an inversion of configuration, called the Walden Inversion. What is the solvent effect?

SN2

SN2 Mechanism: Nucleophilic attack of HO- on CH3I

http://user.mc.net/~buckeroo/ANIM.html

SN1

racemization 2 steps, but unimolecular in the rate determining step Rate = kSN1[R3C-X]

SN2: Inversion of configuration, synchronous, bimolecular

one

step,

Rate = kSN2[R2CH-X][Nu-]

why no rxn?

why a polar solvent?

SN reaction may proceed in competition with eliminations: E2 (elimination to form a double bond)

In the lab: Mr. Butanol CH3-CH2-CH2-CH2-OH

Chemistry Start with 1-hydroxybutane and replace the -OH group with a -Br using a substitution reaction.

HBr is produced in-situ from NaBr and H2SO4

CH3CH2CH2CH2OH + HBr ------> CH3CH2CH2CH2Br + H2O

This is a nucleophilic substitution reaction.

Since the products are impure, purification is required.

Bimolecular Nucleophilic Substitution SN2

What does each reagent do? What is the stoichiometry, how are the amounts of reagents calculated?

How is the yield calculated?

Mechanism: protonation of the OH makes it a better leaving group (H2O), more easily displaced by Br-.

Possible Reactions
(1) HBR generation: NaBr + H2SO4 HBr + NaHSO4 (2) Sulfuric Acid oxidizes HBr to Br2 which dissociates into Br+ and Br 2HBr + H2SO4 Br2 + SO2 + 2H2O

(3) H2SO4 protonates the alcohol. The oxonium ion is a better leaving group than OH. The bromide ion nucleophilically displaces H2O. CH3CH2CH2CH2OH + H2SO4 CH3CH2CH2CH2-OH2+/HSO4-

(4) Sulfuric acid also catalyses the elimination (E2) of H2O a molecule of water intra- or intermolecularly to form a mixture of dibutyl ether and 1-butene. CH3CH2CH=CH2 + H2O + H2SO4 (intra) or CH3(CH2)3-O-(CH2)3CH3 + H2O + H2SO4 (inter)

Possible reactions bp = 118 oC

OH

1-bromobutane H2SO4

Br

substitution

bp = 101.6 C
intramolecular elimination

+
OH2

-H2O

1-butene

bp = -6 C
O

Brdibutylether

intermolecular elimination

How do you separate them? Rfs?

bp = 141 C

Procedure
Reaction (reflux 45 min) Distill at 115 C
Wash the distillate with water, NaHSO3 or Na2S2O3 Wash with sulfuric acid

Wash with NaOH

Dry the organic layer with anhydrous MgSO4 or CaCl2 Distill @99-103 C.

What is the purpose of each step? How do we calculate the yield?

Preparation of 1-Bromobutane

Synthesis of 1-Bromobutane from 1-Butanol Things to consider for the lab (macroscale, 16.2 ) 1.Write the mechanism for the reaction performed in this experiment. Point out the rate-determining step if the reaction is multi-stepped. 2.What are the roles of H2SO4 in this reaction? 3.What is the purpose of using a 10% sodium bicarbonate solution described in the procedure? 4.Why is it that the sodium bicarbonate solution is used after washing the organic phase with 10 mL of water? What if one used the sodium bicarbonate solution before washing the organic phase with water?

From the book procedure 13.3 g NaBr 10 mL butyl alcohol (r = 0.81) 11.5 mL sulfuric acid (r at 100% strength = 1.8305 g/mL say 1.22 at 30%) Determine the nr of moles of each reagent Verify the reaction stoichiometry (is anything used in excess and why?) Calculate the yield as = moles bromobutane/moles butanol.

Carrying out the Reaction Pour Butan-1-ol in a flask. Record the mass of the alcohol transferred. To that alcohol, add NaBr and water.

Add conc. Sulfuric Acid (30%) to the tap funnel over a period of about 5 minutes, under cooling with a cold water bath. The apparatus must also be swirled to prevent the acid from reacting too fast, (exothermic reaction) and splashing the acid.
The increased temperature may vaporize faster the Butan-1-ol, and decrease the yield.

Side reactions may happen at higher temperatures. The side arm in the apparatus (microscale) is needed for safety reasons, the air which the acid displaces can escape through that arm. The apparatus is heated under reflux using a condenser with a guard tube, after having removed the funnel, for approximately 45 minutes. Add boiling chips. Reflux to complete the rxn, but without loosing reactants through evaporation. The guard tube is necessary to absorb any acid fumes or SO2 gas. As the reaction progresses, the liquid becomes less opaque and a trace of yellow is observed. The reactants separate into two layers because there are in fact several reactions taking place at the same time and you have an organic and a water phase.

Separate the Products Due to the reactions mentioned earlier, there are several substances in the reaction mixture. To get 1-Bromobutane, the organic layer is sucked out carefully using a pipette.

Purify the Product HCl or H2SO4 (30%) is added to the organic layer in a funnel. The mixture is shaken vigorously, and the top is taken off from time to time to release the pressure. After the mixture has completely reacted (no more gas evolves), the organic layer is isolated and again placed in a funnel. 5% NaHCO3 is added to the organic solution, the solution is shaken, and the top is taken off from time to time to relieve pressure. The mixture is left standing for 5 minutes while the layers separate; the lower organic layer is carefully collected into a test tube. Anhydrous Na2SO4 is added to the test tube in small scoops to remove the traces of water and the test tube is shaken after each addition. When the liquid is totally clear it is ready for distillation.

Add NaBr and water to the butanol. With a clean syringe/pipet add concentrated sulfuric acid. The viscous acid moves slowly through the pipette; allow sufficient time for complete transfer.

Add a boiling chip, attach a condenser to the flask, and reflux the mixture vigorously for 45 minutes.

Add Sodium Sulfate to the distillate, and swirl the mixture. With a syringe/pipet transfer the bromobutane (which layer is it?) to a 4-inch test tube.

Replace the condenser with a small-scale distillation setup, and distil the bromobutane and water at a temperature below 110 into a 10-mL flask, cooled in an ice-water bath.

Using a clean syringe/pipette, add conc. sulfuric acid, and mix the two layers thoroughly. Set the test tube in an icewater bath and allow the layers to separate.

Draw off the sulfuric acid (bottom layer), and discard it into a beaker half- filled with ice.

Transfer the bromobutane to a clean 10-ml flask. Use clean adapters to set up the distillation apparatus as before.

Testing the purity of the product Fractional distillation of the organic liquid is carried out, and the fraction between 100 C and 104 C is collected into a weighed tube. The % yield is calculated. The reason why the % yield is not 100% is that there are many side reactions, and a lot of reagent is lost as other products. The steps and technique of purification will also allow some products to escape.

To Read
Bromobutane: 4th Ch 16: p 259 266; 5th Ch. 16 p 325-332, 6th 311-317

SN1,2
4th Ch 17: p 267-271; Ch. 17 p 333-340, 6th 318-325

Homework
4th Ch. 16: 2,4,7.; Ch. 17:2 5th, 6th Ch. 16: 2,4,7; Ch. 17:2

Next Time: Aspirin, 4th Ch 41, p 501-506. 5th Esters: Ch 40, p 554-568, Aspirin: Ch 41, p 569-574 6th, chap 40, 41