2 butanol sn1 or sn2

NUCLEOPHILIC ALIPHATIC SUBSTITUTION: SYNTHESIS OF 1- BROMOBUTANE

OBJECTIVES: To synthesize 1-bromobutane through a nucleophilic aliphatic substitution. To understand the use of distillation and extraction in the context of the synthesis. To characterize the desired product with GC-MS.

Background

A substitution reaction occurs when a suitable substrate undergoes a substitution by a nucleophile. In order for this to occur, the substrate must possess a good leaving group. Substitution reactions are classified as SN1 and SN2 depending on the mechanism of the reaction itself (unimolecular or bi-molecular). SN2 occurs via a concerted mechanism involving substrate and nucleophile while SN1 reactions take place with the formation of an intermediate carbocation. Therefore, the nature of substrate, nucleophile, electrophile and solvent have an impact on whether a reaction will occur via SN1 or SN2 mechanism. Methyl and primary substrate favor SN2 due to steric hyndrance of the transition state, whereas tertiary substrates favor SN1 due to the stability of the intermediate carbocation. Secondary substrate can proceed via SN1 or SN2, depending on the reaction conditions. Additionally, Sn2 reaction are stereospecific and characterized by inversion of configuration (If a chiral center is present) due to the fact that the nucleophile attacks from the backside and never from the frontside.

In this experiment you will synthesize 1-bromobutane from 1-butanol utilizing HBr (generated in situ by reacting NaBr and sulfuric acid).

Experimental

1) In the 10 mL round-bottomed flask, dissolve 3.0 g of NaBr in 3.4 mL of water, and 1.8 g of butanol. Add a boiling chip

2) While swirling, add 2.5 mL of concentrated sulfuric acid, dropwise.

3) Assemble the simple distillation apparatus and an ice-cooled receiver.

4) Reflux the reaction gently for 45 min (keep the Variac at a low setting - usually between 1 and 2).

5) Increase the temperature, and distill until all organic material has come over, up to about 115°C.

6) As soon as the distillation is over, clean the round-bottomed flask and rinse the distillation head with acetone. Set aside to dry.

7) Add 2 mL of H2O to the distillate, transfer it to the separatory funnel. Slowly, drain out the lower layer into a small Erlynmeyer flask, being careful not to collect any of the top layer. Add enough CaCl2 pellets to cover the bottom of the flask. Let it sit for about 2 minutes.

8) Pipet the dry bromobutane layer into your clean 10 mL round-bottom flask. Add a boiling chip, and distill the product without the condenser into a pre-weighed vial. (bp should be about 102˚C). Weight the distillate and report the percent yield.

9) Run a GC trace to obtain the percent of product and starting material in your distillate.

Note:

o H2SO4 is a very strong acid and it should be handled carefully.

One of the most common tasks in organic laboratory is the purification of desired compounds. The goal is to separate the target molecule from undesired byproducts and impurities. Several techniques are available and sometimes more than one is utilized in the same protocol (like in this case)

Extraction: involves the use of two immiscible solvents (S' and S"), one is generally water and the other one is an organic solvent. The solute partitions between the two phases, that forms two layers, with the denser phase at the bottom. Liquid-liquid extractions are characterized by a partition coefficient, D, that is defined as:

C"/C'=D

where C" is the concentration of solute in solvent S" and C' is the concentration of

Figure 1. Reaction scheme: synthesis of 1-bromobutane from 1-butanol

Figure 2 Inversion of configuration for an S

N 2 reaction

2

solute in solvent S'. the partition coefficient Is utilized to determine the number of successive extractions that have to be performed in order to extract the highest amount of solute. Extraction Is conducted using a separatory funnel.

How much solvent is enough to extract our desired compound? Multiple extraction with lower volume are more efficient than one extraction with a larger volume. If you want to have fun and practice on calculating the exact volume you need, you can use the following formula:

% compound in organic phase = DVaq / (DVorg +Vaq)

Distillation: Is the separation of a liquid mixtures in its components exploiting different boiling points. For this purpose, a distillation apparatus is utilized. A

phase change (from liquid to gas) occurs when a compound in the distilling flask, upon heating, reaches its

boiling point. When the gas vapors encounter the condenser of the distilling apparatus, the compound reverts back from gas to liquid and it is collected in the collecting flask. Remember to turn on the water for the condenser; the water hoses are connected with water

"in" at the bottom and water "out" at the top. Do not forget the thermometer! The system can be heated using a heating mantel, a sand bath or a water bath depending on the T that has to be reached.

Safety

▪ Sulfuric acid Is a very strong acid and has to be handled with care. It should be added dropwise to the water and not viceversa!! Use proper PPE

▪ Check the temperature of the heater and make sure you do not heat too fast or too much

▪ Make sure that electrical cords are in proper condition and far from the heating block. The same for the water hoses.

Real life example of an SN2 reaction.

Nitrogen mustards are utilized in medicine as cancer drugs, they belong to the class of "alkylating agents". Their mechanism of action involves an intramolecular SN2 reaction followed by an SN2 attack of an external nucleophile. They are extremely reactive and can react with some of the DNA bases, in particular deoxyguanosine. Because they possess two reactive sites, each molecule is capable of forming a "cross-link", that prevent the DNA replication and ultimately causing cell death.

Post lab assignment:

1) Complete the worksheet

2) Complete the writing assignment “Conclusions”

Figure 3. Distillation apparatus scheme