Experiment 5: Nucleophilic Substitution Reactions (SN1/SN2)

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SN1

SN2 (Williamson Ether Synthesis)

or

Due Dates:

Thursday, July 7 A/B

Chemical Safety Information:

SN1
2-methyl-2-butanol hydrochloric acid 2-chloro-2-methyl-butane
sodium chloride sodium bicarbonate magnesium sulfate
deuterated chloroform    
SN2
4-methoxyphenol 4-tert-butylphenol para-hydroxyacetophenone
4-nitrophenol 3-nitrophenol para-bromobenzyl bromide
KOH ethanol 1-bromobutane
1-bromopropane para-chlorobenzyl chloride 1-Bromo-4-((4-tert-Butylphenoxy)methyl)-benzene *
4'-​(4-​Bromobenzyloxy)​acetophenone * 1-​bromo-​4-​[(4-​nitrophenoxy)​methyl]​-benzene * 1-​[(4-​bromophenyl)​methoxy]​-​3-​nitro-benzene *
4-​bromobenzyl-​(4-​methoxyphenyl) ether * 4'-butoxyacetophenone * 4'-propoxyacetophenone *

* MSDS unavailable; treat with caution.

 

Experimental Spectra:

SN1

2-methyl-2-butanol 1H-NMR FID (FOR REFERENCE ONLY)

Sample NMR SN1 (not available for submission for credit)

Stock NMR SN1 (available for submission for credit, see laboratory manual for details)

Stock GC-MS SN1 (available for submission for credit, see laboratory manual for details)

 

SN2

4-bromobenzene bromide 1H-NMR FID (FOR REFERENCE ONLY)

4-chlorobenzene chloride 1H-NMR FID (FOR REFERENCE ONLY)

4-methoxyphenol 1H-NMR FID (FOR REFERENCE ONLY)

4-hydroxyacetophenone 1H-NMR FID (FOR REFERENCE ONLY)

4-tert-butylphenol 1H-NMR FID (FOR REFERENCE ONLY)

Sample 1H-NMR SN2 (Br) products a - e (not available for submission for credit)

Sample 1H-NMR SN2 product, 4-acetylphenyl-4-chlorobenzyl ether (not available for submission for credit)

Sample 1H-NMR SN2 product, 4-methoxyphenyl-4-chlorobenzyl ether (not available for submission for credit)

Sample 1H-NMR SN2 product, 4-tert-butylphenyl-4-chlorobenzyl ether (not available for submission for credit)

Sample 1H-NMR SN2 products from 1-bromopropane and 1-bromobutane (not available for submission for credit)

 

Stock FID 1H-NMR SN2 (Br) product - a (available for submission for credit, see laboratory manual for details)

Stock FID 1H-NMR SN2 (Br) product - b (available for submission for credit, see laboratory manual for details)

Stock FID 1H-NMR SN2 (Br) product - c (available for submission for credit, see laboratory manual for details)

Stock FID 1H-NMR SN2 (Br) product - d (available for submission for credit, see laboratory manual for details)

Stock FID 1H-NMR SN2 (Br) product - e (available for submission for credit, see laboratory manual for details)

Stock FID 1H-NMR SN2 (Cl) product - a (available for submission for credit, see laboratory manual for details)

Stock FID 1H-NMR SN2 (Cl) product - b (available for submission for credit, see laboratory manual for details)

Stock FID 1H-NMR SN2 (Cl) product - c (available for submission for credit, see laboratory manual for details)

Stock FID 1H-NMR SN2 product from 1-bromopropane and 1-bromobutane (available for submission for credit, see laboratory manual for details)

 

Additional Readings:

SN2 Mechanism: Otto, R.; Brox, J.; Trippel, S.; Stei, M.; Best, T.; Wester, R., Single solvent molecules can affect the dynamics of substitution reactions, Nature Chem., 2012, 4, 534538.

Summary of above aticle on the SN2 Mechanism: Orr-Ewing, A.J. Reaction Mechanisms: Stripping down SN2. Nature Chem., 2012, 4, 522-523.

Figure 1 from Orr-Ewing, A.J. Reaction Mechanisms: Stripping down SN2. Nature Chem., 2012, 4, 522-523.

Frequently Asked Questions:

Q1) What is a drying agent?  Why do we need them?  What do they do?

A1)  Drying agents dry things; it's that simple.  How they do so depends on the drying agent, but they remove water molecules from an organic solvent.  A brief summary of a few common drying agents is provided below.

Calcium chloride (CaCl2), sodium sulfate (Na2SO4) calcium sulfate (CaSO4, also known as Drierite) and magnesium sulfate (MgSO4) are the most common drying agents used in labs, The salts are used in their anhydrous (i.e. water-free) form.  Each salt readily forms hydrates as shown below – essentially, these drying agents trap water in their coordination sphere but do not react directly with the water.  (M = metal cation, X= anion)

 


Drying Agent Reaction

 

The capacity (n, the maximum number of water molecules that the drying agent can bind) and efficiency (e, the amount of water left in the organic solution after the drying process is completed) are important considerations in selecting a drying agent for an organic compound.  However, it is most important to select a drying agent that will not react with the molecule that you are drying!

1. Calcium chloride, CaCl2 (n=6, e=1.5 mg/L) is a good drying agent for a variety of solvents but is generally not compatible with molecules containing hydroxyl (alcohol, phenol), amino (amine, amide) and carbonyl (acid, ketone, ester) functional groups due to basic impurities such as Ca(OH)2 and CaCl(OH).

2. Calcium sulfate, CaSO4 (n=0.5, e=0.004 mg/L) is a neutral drying agent but suffers from low capacity.  The commercially available Drierite contains CoCl2 as an indicator (dry: blue, wet: pink). If the compound is wet, the water can be removed by heating to ~200 oC for 1 hr.

3. Magnesium sulfate, MgSO4 (n=7, e=2.8 mg/L) is a slightly acidic drying agent. It works well in solvents like diethyl ether, but not as well for ethyl acetate.  Mag sulfate works quickly because it exists as a fine powder with a large surface area.

4. Sodium sulfate NaSO4 (n=10, e=25 mg/L) has a very high capacity and is mainly used for very wet solutions.  It is very efficient for drying ether solutions but can absorb other polar compounds (alcohols etc.).  In addition, it is fairly slow compared to MgSO4.

5. Potassium hydroxide KOH (n= high, e=0.1 mg/L) and potassium carbonate (K2CO3, n=2, e=moderate) are often used to dry basic solutions containing amines (think about why KOH and K­2CO3 should not be used to dry acidic compounds).

Reactive drying agents such as calcium hydride (CaH2), sodium (Na) or potassium (K) metal, lithium aluminum hydride (LiAlH4), and phosphorus pentoxide (P4O10) are used when organic solvents, reagents etc. must be absolutely bone-dry (>99% anhydrous).  Such drying agents remove water by reacting with it.  We don’t need this level of dryness or purity in CHEM 344 so the non-reactive drying agents are sufficient – they are also safer and easier to handle than the reactive drying agents.