Analysis of a Substitution Reaction by Gas Chromatography PDF

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Synthesis and GC Analysis of Alkyl Halides by an SN2 Mechanism Introduction: Gas chromatography (GC) is an essential technique applied in organic chemistry labs with the intent of identifying compounds or testing the purity of a mixture by determining the relative amounts of each component present in the mixture. Upon injecting a sample into the GC, a carrier gas (such as helium) will push the different components through a column in the GC’s temperature-controlled oven. This carrier gas must be inert so that it does not react with the compounds being separated and alter the expected results. The most essential property in separation of compounds in the gas phase through a GC is the boiling points of each compound. As the boiling point increases, the speed at which a compound reaches the end of the column is reduced due to a lower vapor pressure 1. Basically, compounds that boil at higher temperatures will spend more time in the liquid phase than those with lower boiling points that will spend the majority of their time in the gas phase—vapors move through a column much faster than liquids. Compounds will shuffle through this equilibrium at different rates, resulting in different retention times observed at the end that can be used to identify a compound.

1 Padías, Anne B. Making the Connections: A How-To Guide for Organic Chemistry Lab Techniques. Plymouth: Hayden-McNeil, 2011. Print.

Image 1: illustration of the basic setup of a gas chromatograph 2. Nucleophilic substitution reactions depend on a variety of factors in determining whether they will proceed by a first-order mechanism or a second-order mechanism. S N2 reactions require a strong nucleophile (present as iodide and chloride in this experiment) while S N1 reactions can use any nucleophile due to the carbocation that is produced. S N2 reactions can only occur at a methyl, primary, or secondary positions due to the steric hindrance present where the backside attack would occur in a tertiary position; S N1 reactions are more common on tertiary groups, as well as secondary. All substitution reactions require a good leaving group, which is usually involved in the rate-determining step of a reaction. In this case, the bromine atom on 1-bromobutane (the electrophile in this experiment) will act as the leaving group due to its stability as a solvated ion in solution. Finally, the solvent used in a reaction plays a huge role in the outcome of the reaction, as well as which mechanism it will follow. In an SN2 reaction, an aprotic solvent, such as diethyl ether, is more effective because a protic solvent (e.g. water or ethanol) would stabilize the nucleophile through hydrogen bonding before it has a chance to locate and react with the electrophile. Conversely, polar protic

2 Snow, Nick. "Introduction to Capillary GC Injection Techniques." Chromedia Analytical Sciences. Chromedia, n.d. Web. 20 Nov. 2015. .

solvents favor SN1 reactions due to the stabilizing effect that polar solvents have on internal charges in solution3. In this experiment, lithium chloride and lithium iodide are to be used as the nucleophiles that will react with 1-bromobutane, the electrophile. The amount of each compound present after analysis will relate to the strongest nucleophile in the protic solvent used, ethanol. Due to the effect of hydrogen bonding from protic solvents on nucleophilic anions (iodide, bromide, and chloride), it is hypothesized that iodide will act as the strongest nucleophile due to its larger atomic size relative to bromide and chloride. Iodide is much larger than the preceding halides, resulting in more polarizability and weaker hydrogen bonding interactions than those seen in smaller halogens, such as fluoride (which is practically non-polarizable). Furthermore, smaller alkyl halides synthesized from this substitution reaction (1-chlorobutane in particular) are expected to proceed through the gas chromatograph more quickly due to a lower boiling point and molecular mass, both of which contribute to decreased retention time in the vapor phase. Alkyl Halide Molar Mass Boiling Point 1-bromobutane 137.02 g/mol 101.3° C 1-chlorobutane 92.57g/mol 78.5° C 1-iodobutane 184.02 g/mol 130.0° C Table 1: the molar masses and boiling points of the expected alkyl halides produced from this substitution reaction—values provided by PubChem database 4

Experimental:

3 Sharma, Ashiv. "Effects of Solvent, Leaving Group, and Nucleophile on Unimolecular Substitution." Chemwiki. MindTouch, 02 Oct. 2013. Web. 20 Nov. 2015. . 4 "PubChem Compounds." National Center for Biotechnology Information. U.S. National Library of Medicine, Web. 20 Nov. 2015. .

To initiate the substitution reaction, a reflux apparatus was set up with a 25 mL roundbottomed flask attached to it. Mixed into the flask was 1.0 mL of the nucleophile solution (containing LiI and LiCl), 1.0 mL of the electrophile solution (1-bromobutane), and 1.0 mL of ethanol. Several boiling chips were added before the mixture was allowed to reflux over a steam bath for approximately 90 minutes. Afterwards, the flask was cooled in a large beaker containing cold water—it is essential that the reflux condenser was not detached until the flask has been cooled down properly. 1.0 mL of the reaction mixture obtained from the reflux was mixed in a screw-cap vial containing 2.0 mL of pentane. The contents were swirled and washed three times with 1.0 mL of water each time. After each addition of water, the vial was shook to ensure equal distribution and then the aqueous layer was removed from the bottom (due to the fact that water is more dense than pentane) with a pipette. The remaining organic layer was dried once with 1.0 mL of brine—saturated sodium chloride solution—and subsequently with a portion of anhydrous magnesium sulfate. These two reagents absorbed excess aqueous material to further purify the organic sample. Finally, the organic layer was filtered into a screw-cap vial through a Pasteur pipette stuffed with glass wool and stored in a cabinet for one week. The organic layer acquired from the previous week was ran through a gas chromatograph for about ten minutes, and a corresponding chromatogram was printed out for further analysis of the alkyl halides integrated. Using these peaks, the approximate amounts of each product can be roughly determined (by percent).

Results:

Image 2: the gas chromatogram from the resulting analysis of the reaction. The peak at approximately 1.3-1.5 minutes corresponds to pentane, the solvent used to separate the organic and aqueous layers. Peak one corresponds to 1-chlorobutane (lowest boiling point/molar mass), peak two corresponds to 1-bromobutane, and peak three corresponds to 1iodobutane.

Alkyl Halide Time Elapsed Area Proportion 1-chlorobutane 1.80 minutes 8.78E+01 6.97% 1-bromobutane 2.23 minutes 8.06E+02 63.98% 1-iodobutane 2.95 minutes 3.66E+02 29.05% Table 2: the retention time, total area, and relative proportions of the corresponding peaks from image 2, which correspond to the alkyl halides synthesized.

Proportion of Alkyl Halides Versus Time 100.00% 90.00%

Relative Proportions

80.00% 70.00%

63.98%

60.00% 50.00% 40.00%

29.05%

30.00% 20.00% 10.00% 0.00% 1.5

6.97% 1.75

2

2.25

2.5

2.75

Time (in minutes)

Image 3: illustrates the relative proportion of each alkyl halide with respect to their retention times.

Ratio of Iodide Versus Chloride Following Reflux

Relative Proportions

29.05%

6.97%

Iodide Proportion

Chloride Proportion

Image 4: bar graph illustrating the relative concentrations of the iodide-containing alkane versus the chloride-containing alkane at the end of the reflux.

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Discussion: Based on the chromatogram acquired from gas chromatography, it is apparent that the dominant alkyl halide at the end of the nucleophilic reaction was the starting electrophile, 1bromobutane. This observation shows that a great majority of the electrophile either, 1) did not react with iodide and chloride nucleophiles or, 2) reacted with a nucleophile, and then reverted back to its original form through another substitution reaction between bromide and the alkyl halide produced. The latter option is more likely if the alkyl halide produced was 1chlorobutane because bromide is a stronger nucleophile in polar protic solvents than chloride and it is reasonable that the bromide ion that left as a leaving group would re-react with 1chlorobutane to produce 1-bromobutane once again. Iodide is presumably the strongest of these nucleophiles in protic solutions due to a decrease in hydrogen bonding interaction strength, and is therefore more likely to act as a nucleophile in ethanol than chloride. This relationship is reinforced by the chromatogram, as well as image 4 above, which displays the relative proportions of butyl iodides synthesized versus butyl chlorides synthesized. 1-iodobutane is present in more than four times the concentration of 1-chlorobutane, confirming the hypothesis that lithium iodide is a stronger, more effective nucleophile in protic solvents than lithium chloride. Because there are numerous protons present in the solution, chloride ions have a greater chance of being “blocked” from reacting with electrophiles by hydrogen interactions due to its small size. If this experiment were to be repeated with a different electrophile and used LiCl, LiBr, and LiI as nucleophiles, it is hypothesized that LiI would act as the strongest nucleophile while LiCl acts as a weaker nucleophile (assuming they are in a protic solvent such as water). LiBr will act as an adequate nucleophile, producing less alkyl halides than LiI but more than LiCl.

Several factors point to this reaction proceeding as an S N2 mechanism. First and foremost, the electrophile is primary (only attached to one other carbon member) at the leaving group. It is forbidden for SN1 reactions to occur at a methyl or primary position because a carbocation cannot be stabilized properly and therefore will not be formed. Also, the nucleophiles used (chloride and iodide) are very strong nucleophiles, making them more likely to perform a backside attack at the same time that the leaving group breaks off from the compound. Weak nucleophiles usually cannot do this and are more often observed in S N1 reactions. Although SN2 reactions proceed most efficiently in aprotic solvents that do not stabilize the charge of potential nucleophiles, they can and do continue to occur in protic solvents at a much slower rate. This may be the reason that so much 1-bromobutane remained unreacted—nucleophiles cannot react with electrophiles when they are solvated and their charges are stabilized in protic solutions. Changing the electrophile in this reaction would exhibit observable consequences on the outcome. For example, if 2-bromobutane were used instead of 1-bromobutane as the starting electrophile, then both SN2 and SN1 reactions would occur due to the secondary position of the leaving group. Carbocations could momentarily exist at this position, permitting a first-order mechanism. In fact, SN1 reactions could potentially be the dominant substitution reaction considering that the reaction occurs in a protic solvent, which is favorable for firstorder mechanisms. In this situation, significantly more 2-bromobutane would react with iodide and chloride since there are more mechanisms available for a reaction to occur. 2-iodobutane would once again take priority over 2-chlorobutane under the same conditions due to its increased nucleophilicity in protic solvents. Adding more groups to the electrophile (e.g. 1bromo-2-methylbutane) would further decrease the frequency of S N2 reactions due to an

increase in steric hindrance, ultimately making S N1 reactions the dominant substitution reaction that occurs.

Notebook/Observations:...