Alcohol - Alkyl Halide Unknown

Reading: McM sections 12.5, 12.6, 12.7, 13.5 and 13.7 with problems 13.11 and 13.12. Also review the Common Practices.. file (Table of Chemical Tests, Table of Candidates and Interpreting an IR Spectrum).

The purpose of this experiment is to identify a compound you will be given - an alkyl halide or an alcohol from the unknown's boiling point, infra-red and ¹H NMR spectra and its response to chemical tests. Make sure you have recorded the unknown number of the compound in your notebook.

In advance of this lab, set up a Table of Chemical Tests which you will use to organize the infrared and chemical test data and show your reasoning during the identification process (see Common Practices and Procedures for an example). Head columns "Test" then "Result" then "Inference" then "Comments" to span an entire page and expect the table to continue for several pages. In the "Test" column, list the following four preliminary tests that you will carry out no matter what kind of unknown you have: IR – 3200-3600 cm^-1, boiling point; ¹H NMR 2.5-4.5 ppm; Beilstein test. Other tests will be needed depending on the results of the preliminary ones.

Chemical tests and the spectra will complement each other to reveal which functional group, an -OH group (for an alcohol) or –X, a halogen (either -Cl, -Br or -I, for an alkyl halide). Chemical tests and the spectra will also often reveal details of the compound (whether it is 1^o, 2^o, or 3^o etc.).

From the lists of known alcohols and alkyl halides available in the file "Alcohol/Alkene/Alkyl Halide Unknown Candidates", the boiling point you measure will narrow the possibilities to 10 - 20 candidates. Based on the spectral properties, you should be able to select one compound that fits your data best.

Using a large drawing of your selected compound, you will need to point out how its structural features fit all the spectral data you have.

As mentioned in the "Common Practices…" file, the process of identifying an unknown compound often has inconsistencies and apparent contradictions. Do not allow the results of your first test to prejudice your inferences for later tests. Rather, base your decisions on the results of many initial, confirmatory and repeated tests. Repetition of tests is important since your first trials are not likely to be your best. Use your laboratory time to take measurements and carry out reactions. When you finish this lab, you may not have a final compound selected, but you should have evidence that you have confidence in and can base later decisions on to arrive at an identification. Looking up data, searching for spectra and planning reactions are best done outside of the laboratory period.

Procedures:

Boiling Point Determination. Your boiling point will be the reference point for the selection of candidates (see below): a small (10x75mm) test tube is clamped to a ring stand and loaded with 10-15 drops of the unknown liquid. A thermometer is also clamped so that its bulb is suspended within and 1mm above the bottom of the test tube. A capillary tube is broken 12-15mm from the bottom and is added to the tube, open end down. The test tube is suspended in a 30 mL beaker (also clamped to the ring stand) containing mineral oil. Heat the oil with a flame until the air trapped in the capillary bubbles out in a rapid stream (until you are unable to count them individually). Stop the heating and observe the capillary; record the temperature at which liquid just begins to enter the tube. If you have not done this measurement before, make a careful drawing of the apparatus for your records.

A Note on the Analysis of All Spectra. Mark these spectra liberally. Take measurements of peaks where appropriate, using your ruler, and mark the values on the paper. Indicate what these values mean. Also remember that the absence of a signal is often as useful as the presence of one. If this is the case, this too should be noted on the spectrum paper, for example "no OH absorption here – therefore not an alcohol."

Each finding, or absence of a peak, should be recorded in your Table of Chemical Tests. The entry you begin with, "IR – 3200-3600 cm^-1" should be reported with a result "large peak" or "no peak" and the inference and comments. Further tests as the presence or absence of other peaks should be reported and interpreted.

The IR Spectrum. If the IR spectrum is not provided to you use the same procedure as in the first laboratory. You may have to correct the peak measurements as a result of a calibration before making determinations from the spectrum. On the spectrum mark diagnostic absorptions with cm^-1 values.

a) a large, parabolic peak centered between 3200 and 3600 cm^-1 indicates the presence of an O-H bond, in other words, the unknown is an alcohol. Examples of this peak are found in McM p. 436 and 659 and Mayo, et al. fig 6.24.

b) Alkyl halides have a few IR absorptions characteristics that distinguish them from alkanes, but they are not reliable. Therefore the absence of alcohol peaks indicates that the unknown (in this experiment) is an alkyl halide.

Enter the results of this "test" using the appropriate section of the Common Practices…File as a guide.

A further test for alcohols: the C-O stretching bands between 1000 and 1200 cm^-1 are often helpful in determining whether the unknown is a 1^o, 2^o or 3^o alcohol, or at least in eliminating one of these possibilities. See Mayo, Table 6.12 for this information. OH groups attached to rings do not follow this pattern; for example, cyclohexanol’s C-O stretch is at 1060 cm^-1 (see McM p. 659) which suggests that it is a 1^o alcohol; in fact cyclohexanol is a 2^o alcohol.

There are far more IR absorption peaks in a spectrum than need be interpreted; only a few are necessary to determine the functional groups present. Always check the spectra in McM and Mayo for examples of diagnostic peaks.

¹H NMR Spectrum. With this instrument, every signal must be accounted for. All spectra will have a signal at 0 ppm for the internal standard, tetramethylsilane (TMS), which is used for calibration. In addition most spectra will have a small peak at 7.24 ppm for chloroform.

Recall that in ¹H NMR:

1. By counting the number of signals we can make deductions on the shapes of many simple molecules.

2. Each uniquely positioned hydrogen atom within the molecule will give a separate signal.

3. Relative peak areas are important in ¹H NMR because they are proportional to the number of H atoms in each group that is represented by a signal. For example, in a spectrum of propane, the areas of the two signals are in the ratio of 1:3, reflecting the 2 H atoms in one group and the 6 H atoms of the other group.

Other valuable information needs to be examined:

4. The location of signals in the spectrum – the chemical shift, measured in ppm – can be found in McM Table 13.3. While these chemical shift ranges are good for alkanes and alkenes, they must be adjusted if the H being observed is separated from a halogen or oxygen atom by 1 or 2 carbon atoms. In alcohols or alkyl halides, signals for H atoms separated from halogen (X) or oxygen atoms by only one carbon atom ( i.e. H-C-X or H-C-O) are typically in the 2.5-4.0 ppm region (Table 13.3). If two carbon atoms separate the observed H and either halogen or oxygen (i.e. H-C-C-X or H-C-C-O), the signal will range from 1.95 to 1.20 ppm. . When O or X is distanced by more than two carbon atoms from H, or when O or X is altogether absent from the molecule, the signal for H will be more dependent on whether the H is part of a methyl group ( - CH₃, 0.7-1.3 ppm) or a methylene group ( - CH₂- 1.2-1.4 ppm) or a methine group (>CH- 1.4-1.7 ppm). Thus a signal at 1.6 ppm may be either methine H remote from X or O, or any kind of H (methyl, methylene or methine) two carbons away from O or X or an allylic H.

H* = H at least 3 carbons removed from either O or X

5. Integration (determination of the area) of the peak, if any, in the 2.5-4.0 range gives important confirmatory information. A 1^o unknown R-CH₂-OH or R-CH₂-X, will integrate for 2 H atoms on the carbon that also bears O or X. The integral for a 2^o unknown will be 1 H in this range (R₂CH-OH or R₂CH-X.) A 3^o alcohol or alkyl halide will have no H atoms in this range, unless it is the oxygen bound H of an alcohol (RO-H).

6. ¹H NMR signals are often split into lines. The number of individual lines relates to the number of H atoms that are neighbors to the H that produces the signal. These lines are taller in the middle of the signal and diminish on the outside of the signal. For our purposes, "neighbor" H atoms are separated from the observed H by two carbon atoms. H atoms in the same group produce the same signal, are not neighbors, and therefore don’t split each other. For the present identification of the alcohol or alkyl halide, you need to note and interpret a few simple features of splitting, if they are apparent in your spectrum. Complex splitting is present in some unknowns, where neighbor hydrogens are very nearly identical, need not be interpreted, except for their chemical shifts and integrals. Examples of complex splitting are found in the 0.9-2.0 regions of McM Fig 13.5 a) and b) for cyclohexyl compounds. Long -CH₂- chains also give complex splitting.

• If a signal is not split, the observed H has no neighbor H atoms, or it is bonded directly to O (thus RO-H, alcohols)

  If a signal is split into a doublet, the observed H has one H neighbor. Examples would be BrCH₂CHBr₂ or (CH₃)₂CHCl. Note that when we examine the signal for the neighbor H it will be split by H in return, but not necessarily into a doublet.

  If a signal is split into a triplet, the observed H has two H neighbors. Examples would be CH₃CH₂CH₂CH₂OH and ClCH₂CH₂CH₂CH(CH₃)₂. Note that any H atoms distanced any more than carbon atoms from the observed H are not considered neighbors. Also note that actually two signals in the alcohol example are split into triplets.

  Signals can be split into quartets, pentets, etc. but these are often difficult to determine from the spectra you have without magnification. But, following the sequences started above, it is always true that if an observed H has n H neighbor atoms, it will be split into n+1 lines.

If your spectrum has singlet, doublet, and/or triplet, peaks you must interpret the reason(s) why. And this reason must fit the correct structure of your unknown.

Some spectra have:

1. impurities; a common one is acetone [ (CH₃)₂C=O ] which is used to clean the NMR sample tubes is found at 2.15 ppm.

2. peaks overlapped on another. The peak areas for the H atoms or groups represented in the overlapped region will be integrated together.

a. For alcohols, the H-OR peak is often overlapped with the signals for other H atoms in the molecule.

b. In other cases, H atoms technically different from one another but very similar in their positions in the compound will need to be lumped together; long sections of –CH₂- distant from oxygen or halogen atoms often have to be combined.

Whether your unknown is an alkyl halide or an alcohol will be best determined from the infrared spectrum, but this determination will be confirmed by the ¹H NMR spectrum.

1. Round off the integrals; remember that the actual numbers of hydrogens in each group may be a multiple of the integrals printed on your spectrum.

2. If an alcohol, locate (if possible) and mark the H-OR.

3. Locate the H-C-O or H-C-X signal (if it is present). Its integral may be the only sure way to determine if your alcohol or alkyl halide is primary, secondary or tertiary.

4. In the list of chemical tests ("Common Practices..") , treat each separable signal as a "test". Its position (ppm value) and integral should be reported as "results" in the table with suitable inferences and comments. Typically a "test" on an alcohol would be "¹H NMR 2.5-4.5 ppm" with the result "doublet at 3.4 ppm, area 2 H" and the inference would be "CH₂ attached to the OH also attached to another CH" with the comment "therefore this signal represents CH-CH₂-OH"

5. In the correct identification, every peak in the PMR must be accounted for.

Simple Chemical Tests. You need not run all the tests for all of the functional groups. Once you have determined the functional group from a preliminary examination of your spectra and preliminary tests, you should only run further tests for that group. Enter each test in the table. If you repeat the test, write a new entry. If you are unsure of what a positive test should be, run a compound from the reagent shelf known to have the functional group, and enter the data in the Table. Remember that a non-positive result is just as significant as a positive one. Be as detailed as possible and avoid writing results like "it came out negative". Instead, detail what was actually seen, then in the inference "negative for a …" would be appropriate.

Alkyl halides - the Beilstein test: Heat the end of a copper wire to redness in the oxidizing flame (inner cone) of a burner until the flame is no longer colored; let the wire cool slightly and dip it into a sample of the liquid and then reheat. A green flame indicates halogen present. Caution: Sometimes this test is difficult to interpret.

If the Beilstein test is positive, two tests are helpful - the S_N2 and S_N1 reactions.

For the S_N2 test , react 0.2 mL of the unknown in 2 mL of 15% NaI in acetone. Alkyl bromides will react more rapidly than chlorides, while iodides will not appear to react at all. The other effect, the nature of the substrate is also important (1^o > 2^o > 3^o). Compare the reactivity of your unknown with known alkyl halides (you may have notes on this from a previous experiment).

For the S_N1 test (McM sect.11.6), combine 0.2 mL of the unknown with 2 mL of 1% ethanolic AgNO₃ solution. Again compare with known reagents or refer to your notes. The rate of the production of silver halide (AgCl, white; AgBr, light yellow; AgI, yellow) is helpful. (Note the rate of the reaction and if necessary warm the solution on the steam bath until a precipitate is formed.) Carefully remove the liquid with a pipet and wash the precipitate in 5-10 drops of deionized water; again remove the water and add 5-10 drops of 3 M NH₃ (often labeled "NH₄OH"); if the precipitate dissolves, the alkyl halide is a chloride. If the solid does not dissolve, remove the aqueous part and add 5-10 drops of 15 M NH₃. If the solid dissolves, the unknown is a bromide; if it is insoluble, the substance is an iodide.

A combination of the results from the S_N1 and S_N2 tests should help you determine if your alkyl halide is primary, secondary or tertiary.

Alcohols - The ceric nitrate test can be run as confirmation as long as the alcohol has 10 carbons or less. Dilute 0.5 mL of the ceric nitrate reagent with 3 mL of deionized water and add 5 drops of the compound. A color change from yellow to red indicates an alcohol.

The Lucas test (McM sect. 10.7) distinguishes alcohols of 6 or fewer carbon atoms between primary, secondary and tertiary alcohols (higher alcohols do not dissolve in this reagent): add 3-4 drops of the compound to 2 mL of the Lucas reagent in a 10x75 mm test tube. Agitate well and allow the mixture to stand at room temperature. A reaction is indicated by a clouding of the solution due to the formation of a less soluble alkyl chloride. Tertiary alcohols react immediately; secondary alcohols react in 2-3 minutes and primary alcohols in 7 minutes or longer.

The chromic acid test: to a 10x75 mm test tube dissolve 1 drop of the compound in 1 mL of reagent acetone. Add one drop of the chromic acid reagent and agitate. Primary and secondary alcohols react within 10 seconds and give an opaque blue-green suspension. Tertiary alcohols do not react; other oxidizable compounds, phenols and aldehydes do react.

The iodoform test should be run if the above tests are positive for alcohols but it has limited usefulness since it will distinguish only certain secondary alcohols or ethanol. Dissolve 100 mg of the compound in 1 mL of dioxane (use water for water-soluble compounds); add 3 mL of 10% NaOH solution, and then add dropwise the reagent labeled: "10% I₂ with 20% KI" until a slight excess of brown color (due to I₂) appears. Warm the reaction in a 60 ^oC water bath and continue adding the I₂/KI reagent until the color persists for 2 minutes. Add drops of 10% NaOH until the color just disappears. Remove from the water bath and add 10 mL of water. A yellow precipitate of iodoform (m.p. 120 ^oC, antiseptic odor) indicates the presence of methyl secondary alcohols or ethanol. Ethanol can be used as a model positive test. The iodoform test is also positive for methyl ketones and acetaldehyde.

Before further analyzing the IR spectrum and the tests you have made, you should repeat tests and the boiling point measurement to ensure that your data can be depended on. It is common that data from various tests will be contradictory; repeating tests usually resolves these contradictions and running test with known compounds will help you know what to look for. With reliable information, the identification of your unknown can be done outside the lab.

If tests remain contradictory, you will have to base your best decision on the preponderance of the data.

Table of Candidates. A sample is provided on the WWW Server. For your unknown, select the entries that approximate the boiling point and functional group of your unknown. Supply structures for all candidates; the instructor will provide or check structures if they cannot be found.

It is unnecessary to interpret every peak on the infra red spectrum. On the other hand, if you intend to make a positive identification of a particular compound, your and the Aldrich Library spectrum should match for every peak.

• In the comparison of your spectrum with the spectra in the Aldrich library, you need to focus on the cm^-1 values and less on the amounts of the absorption (depth of the peaks).

  The spectrum you obtain is linear in cm^-1 values while the Aldrich Library spectra are linear in microns, so each major peak should be measured separately. There is a tendency for novices to compare their spectra with every one in the Aldrich IR Library; this is unnecessary. One should restrict the search to the compounds in the Table of Candidates.

  The Aldrich IR Library is organized by functional group. The first page of each section gives helpful information that, for the most part, repeats what is found here.

  Occasionally two spectra in the Aldrich that closely match the one for the unknown. If this is the case, refer to the appropriate section of the Common Practices.. file.

¹H NMR (and some IR) spectra can be found on a website:

• • http://www.aist.go.jp/RIODB/SDBS/menu-e.html

In your Conclusion give your best candidate: "based on the evidence gathered, unknown number ___ is _____ "

Make a full page drawing of the compound you have concluded to be your unknown, and include all the hydrogen atoms. Indicate where each H atom is located in the PMR spectrum.

References:

"Mayo et al:." Mayo, D.W., Pike, R.M., Butcher, S.S. and Trumper, P.K. Microscale Techniques for the Organic Laboratory; Wiley: New York, 1991

"McM": McMurry, J. Organic Chemistry, 5th ed., Brooks/Cole Publishing Company, Pacific Grove, CA. 1999

The "Handbook" recent editions of: Weast, R.D. Handbook of Chemistry and Physics; The Chemical Rubber Co.: Cleveland, OH, 1960-present.

The "Aldrich IR Library" refers to any edition of: Pouchert, C.J. The Aldrich Library of Infrared Spectra; Aldrich Chemical Co. Milwaukee WI 1970-present.

Rev. January, 2000