Writing an Experimental Procedure (For a synthetic preparation)

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Diane Walsh
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1 Writing an Experimental Procedure (For a synthetic preparation) The Experimental Section has a well defined, formal, almost cryptic, style that varies depending upon the exact type of experiment performed. Thus, it is essential to look at examples in the literature to get a feel for the accepted format. You should assume that your reader is familiar with standard laboratory procedures. The Experimental Section is where the details of the actual procedures are described. This is what you actually did, not a copy of the lab handout, nor recipes for someone else to follow. The level of detail necessary depends to some extent on the audience, but in general the experimental section should give all the information necessary for someone to actually repeat your experiments successfully. The experimental section is always in the past tense, with the passive voice. (So you should not use we or I in this section.) A couple examples of synthetic experimental procedures are presented below, followed by a detailed commentary to help you prepare your own. Example Experimental Sections 2,4-Dimethyl-3-pentanol-MOM 1f. To a solution of 2,4-dimethyl-3- pentanol (1.4 ml, 10.0 mmol) in dimethoxymethane (20 ml) was added LiBr (174 mg, 2.0 mmol) and para-toluenesulfonic acid monohydrate (p- TSA) (206 mg, 1.0 mmol) at 23 C. After stirring for 44 h, the reaction was quenched with sat. aq. NaHCO 3 (20 ml) and stirred for 15 min. The mixture was diluted with Et 2 O (100 ml), separated, washed with sat. aq. NaHCO 3 (10 ml), H 2 O (10 ml), sat. aq. NaCl (10 ml), and dried with Na 2 SO 4, filtered, and concentrated. Purification by flash column chromatography (hexanes:etoac 97:3) yielded 2,4-dimethyl-3-pentanol- MOM 1f (180 mg, 11%) as a colorless liquid: Rf = 0.50 (hexanes:etoac 90:10); IR (thin film) 1041 cm -1 ; 1 H NMR (500 MHz, CDCl 3 ) δ 0.92 (d, J = 6.5 Hz, 12H), (m, 2H), 2.93 (t, J = 5.0 Hz, 1H), 3.41 (s, 3H), 4.66 (s, 2H); 13 C NMR (125 MHz, CDCl 3 ) δ 17.9(2), 20.4(2), 30.5(2), 56.1, 90.2, 98.8; CI-HRMS calcd for C 9 H 21 O 2 [M + H] , found ((4-(Benzyloxy)-3-methoxyphenethylcarbamoyl)methyl)-3- (benzyloxy)-2-methoxybenzyl Acetate (11). To a solution of compound 10 (3.00 g, 5.54 mmol) in CH 2 Cl 2 (50 ml) was added Et 3 N (3.8 ml, 27.7

2 mmol). The mixture was cooled to 0 C, and acetic anhydride (1.6 ml, 16.6 mmol) was added dropwise. After being stirred overnight at room temperature, the reaction mixture was diluted with CH 2 Cl 2 (50 ml), washed with water and brine, dried over Na 2 SO 4, filtered, and concentrated. The residue was purified by recrystallization from toluene to afford a white solid 11 (2.37 g, 79%); Mp C. 1 H NMR (CDCl 3, 300 MHz): δ (m, 10 H), 6.90 (d, J = 8.3 Hz, 1 H), 6.84 (d, J = 8.3 Hz, 1 H), 6.73 (d, J = 8.2 Hz, 1 H), 6.64 (d, J = 1.9 Hz, 1 H), 6.46 (dd, J = 8.2, 1.9 Hz, 1 H), 5.46 (br, 1 H), 5.15 (s, 2 H), 5.12 (s, 2 H), 5.10 (s, 2 H), 3.88 (s, 3 H), 3.83 (s, 3 H), 3.53 (s, 2 H), 3.42 (q, J = 7.0 Hz, 2 H), 2.65 (t, J = 7.0 Hz, 2 H), 2.00 (s, 3 H); IR (cm 1, CCl 4 ) 3628, 3441, 2958, 2872; TLC Rf = 0.31 (4:1 hexane/ethyl acetate); GC-MS (EI) m/z (relative intensity) 182 (72) [M] +, 154 (63), 127 (100), 103 (53). [α] 23 D (c 1.0, CH 3OH). Comments on Writing Experimental Procedures Although the examples above are single-spaced to save space, remember that all manuscripts should be double-spaced when submitted for review. Notice that there are 3 main parts of a synthetic experimental procedure: Title, Procedure, and Analytical Data. These 3 parts are normally strung together in a single paragraph, but are distinct enough to warrant separate descriptions. Title The title is in bold, but in the same font and size as the rest of the experimental (12 pt Times is common.) The title for a synthetic procedure is normally the product s systematic name along with the structure number assigned to the compound elsewhere in the paper, usually as part of a scheme. Thus, of the two experimental examples given above, the second one s title is more correct since it has the full name, whereas the first has a simplified common name. Notice that when a structure number is used in conjunction with a complete systematic name it is put in parentheses, since it is not really necessary, just an aid to the reader. However, when a compound is referred to by a short nickname and then the structure number, the number is not in parentheses since it is essential for identifying the compound. Thus, in the second experimental procedure shown above, the number following the title is in parentheses, but later in the experimental it refers to compound 10 and white solid 11. As an aid to the reader, the adjective that precedes the structure number should usually describe some important functional group in the molecule. Thus, in example 2 above, it would be better to refer to compound 10 as alcohol 10 since it is the alcohol in this starting material that is participating in this reaction. Also note that compound numbers are in bold, even when not in the Title.

3 The title ends with a period, just like the end of a sentence. Then just switch back to the normal font (i.e., not bold), insert a space, and start in with the rest of the procedure. Do not put a return at the end of the title. Procedure The actual description of the procedure assumes that the reader is familiar with standard chemical techniques, and thus these techniques do not need to be described in detail. Ask yourself, could a competent chemist repeat this procedure with the information I am providing? If yes, then you are on the right track. Then ask yourself, could a competent chemist repeat this procedure with a more concise description? If yes, then you should probably shorten it. In general, if you are uncertain, look at some example procedures from the literature to get a feel for the level of detail normally provided. All reactants should have the amount actually used (mass or volume) listed along with the number of moles. The volume of all solvents used should also be listed, but NOT the number of moles. The number of moles should have the same number of significant figures as the amount used. The mass (or occasionally volume) of all products isolated should also be recorded along with the percent yield. (The moles of product is optional.) The experimental procedure should end with a phrase that lists the grams of product and the percent yield as well as the physical state and appearance of the product. For example, in the first example above, the procedure ended yielded 2,4-dimethyl-3- pentanol-mom 1f (180 mg, 11%) as a colorless liquid:. Always put a space between a number and its units. Do not start a sentence with a number. There are two general methods for transitioning from the procedural description to the analytical data. You may either end the experimental procedure section with a colon and then list the analytical data separated by semicolons (example 1 above), or you may end the experimental procedure with a period and then list the analytical data separated by periods (example 2 above). Analytical Data The analytical data obtained to characterize the product of the reaction are listed one after another, with the data from each of the techniques separated by either a period or a semicolon, depending on the style used for ending the procedural description. There is no set order for listing the different techniques. Each technique has its own particular style for listing the data, so find an example to model yours off of. TLC

4 R f = 0.50 (hexanes:etoac 90:10) R f = 0.33 (3:1 hexane/etoac) R f = 0.54 (20% Et 2 O/hexanes, black in PMA stain) The R f is typically listed with two decimal place accuracy and the eluent is listed in parentheses. The general section should list the type of TLC plates used and the visualization methods used. Melting Point mp C Mp C mp 314 C (dec) The M is capitalized if using the period separated style. The melting point should always be listed as a range. Tenth of a degree accuracy is not usually attainable, so melting points are normally listed to 1 degree precision. The last example indicates that the sample decomposed (e.g., turned black or bubbled) at the indicated temperature. Infrared (IR) Spectroscopy IR (thin film) 3112, 2985, 1715, 1620, 1599, 1512, 1480 cm -1 IR (KBr) (cm -1 ) 3506 (br), 1449, 751, 702 IR (nujol) 2980, 2180, 1620 cm -1 IR (cm -1, CCl 4 ) 3628, 3441, 2958, 2872 You should list the important absorptions that can be assigned to particular vibrations, or particularly strong absorptions. I prefer the method where the units are placed at the end, and are not in parentheses, although some authors now put it in the front parentheses. In the parentheses after the IR is the physical state of the sample. For our normal liquid samples, where the sample is squeezed between two salt plates, this is usually listed as thin film or film or neat. KBr is listed for solids ground with KBr and pressed into a pellet. With our diffuse reflectance setup, list this in the parentheses: (KBr, diffuse reflectance). When a solid sample is ground with nujol oil, the parentheses contains the word nujol. The last example above indicates that the sample was dissolved in carbon tetrachloride and the IR was then acquired in a solution cell. Parentheses after the numbers may be used to indicate the intensity of the signal (w=weak, m=median, s=strong, br=broad). Occasionally authors indicate the type of vibration assigned to the signal in parenthesis, for example: (C=O), (C=C), etc. Nuclear Magnetic Resonance (NMR) Spectroscopy

5 1 H NMR (500 MHz, CDCl 3 ) δ 0.92 (d, J = 6.5 Hz, 12H), (m, 2H), 2.93 (t, J = 5.0 Hz, 1H), 3.41 (s, 3H), 4.66 (s, 2H) 1 H NMR (CDCl3, 300 MHz): δ (m, 10 H), 6.90 (d, J = 8.3 Hz, 1 H), 6.84 (d, J = 8.3 Hz, 1 H), 6.73 (d, J = 8.2 Hz, 1 H), 6.64 (d, J = 1.9 Hz, 1 H), 6.46 (dd, J = 8.2, 1.9 Hz, 1 H), 5.46 (br, 1 H), 5.15 (s, 2 H), 5.12 (s, 2 H), 5.10 (s, 2 H), 3.88 (s, 3 H), 3.83 (s, 3 H), 3.53 (s, 2 H), 3.42 (q, J = 7.0 Hz, 2 H), 2.65 (t, J = 7.0 Hz, 2 H), 2.00 (s, 3 H) The solvent and the resonance frequency are listed in the initial parentheses. The listing of peaks starts with the greek letter delta (designating the ppm scale that is used universally now). Each peak is listed to two decimal place accuracy and is followed, in parentheses by the multiplicity (s=singlet, d=doublet, t=triplet, q=quartet, dd=doubledoublet, m=multiplet, etc.), the coupling constants in Hz (to 1 decimal place accuracy), and the relative number of protons from the integration. For a signal that is too complex to be analyzed, usually because multiple protons happen to have similar chemical shifts, the range of the signals is given and the multiplicity is listed as m. As you can tell from the examples above, some authors go from low to high chemical shift, and others go from high to low. Optical Rotation [α] 23 D (c 1.0, CH 3 OH) The specific rotation, not the observed rotation, should be calculated. Be sure and keep track of the sign. The temperature (in C) is superscripted, and the wavelength used is subscripted. In most cases this is the sodium D line, and so a D is used, but occasionally you will see a wavelength listed here. The optical rotation should be listed with the correct number of significant figures (depending upon the accuracy of the polarimeter). The concentration in parentheses is in grams per 100 ml, even though the concentration used in the calculation of specific rotation is g/ml! Chiral Gas Chromatography (GC) The ee of the recovered epoxide before recrystallization was determined to be 99.3% by chiral GC analysis (Cyclodex-B, 110 C, isothermal, t R (minor) = min, t R (major) = min) Some of the first couple things in parentheses could be in the general section if used repeatedly. Chiral High Performance Liquid Chromatography (HPLC) The ee of the product was determined to be 95% by chiral HPLC analysis (Chiralcel OD, 9:1 hexanes:i-proh, 1 ml / min, 214 nm, tr(minor) = min, tr(major) = min)

Supporting Information

Supporting Information Wiley-VCH 2006 69451 Weinheim, Germany A Highly Enantioselective Brønsted Acid Catalyst for the Strecker Reaction Magnus Rueping, * Erli Sugiono and Cengiz Azap General: Unless otherwise