Selected SOLID DERIVATIVES for various FUNCTIONAL GROUPS (protocols appear on subsequent pages)

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1 MAKE SOLID DERIVATIVES TO CONFIRM IDENTITY OF YOUR UNKNOWN(S) A solid derivative is a compound that arises by way of altering your parent unknown. Generally, derivatization occurs through the reactivity of a functional group in the unknown, transforming it into a new but related compound that has different physical and/or chemical properties. Solid derivatives can be very important for various situations. For example, you may narrow down the identification of your unknown to two isomers with similar boiling points, solubility properties, and IR spectra; however, the solid derivative of each isomer may differ enough to yield very different melting points, enabling you to identify your unknown with confidence. Decide on a single candidate and select an appropriate solid derivative to make. Obviously, we have to have the needed reagents available! As you choose, consider whether steric hindrance might make synthesis difficult, whether the derivative might be too water-soluble to recover given what you suspect your compound to be, or whether the mp of the derivative of your suspect is too close to the mp of the same derivative of another possible candidate. Make the derivative with about 1 g (but there are exceptions to this amount) of your unknown and 1 g of the authentic compound in parallel reactions. If you have two potential identities for your unknown, synthesize derivatives for your unknown and both of the authentic compounds in three parallel reactions. Protocols are found in Procedures for Synthesis of Solid Derivatives (web site). Follow the pertinent one carefully. Pay close attention to the proper method for recrystallization in the Procedural Goodies section of that document. Selected SOLID DERIVATIVES for various FUNCTIONAL GROUPS (protocols appear on subsequent pages) In your lab notebook be sure to include a reaction and reaction mechanism where possible for each derivative synthesized. CAUTION! Before committing to a given derivative, be sure you have its name exactly right. PAY ATTENTION TO SPELLING OF BOTH THE NAME OF YOUR COMPOUND AND THE DERIVATIVE!! Then check in the lab reference (at front desk) to see if the melting range for the derivative you have chosen will permit you to distinguish between candidates for your unknown. Avoid derivatives with low melting ranges and those with high solubility in water. Group Recommended Solid Derivatives Alcohol phenylurethane, p-nitrobenzoate or 3,5-dinitrobenzoate Aldehyde 2,4-DNP-hydrazone or semicarbazone Alkane No easy solid derivatives Alkyl Halide No easy solid derivatives Alkene ** oxidative cleavage to RCOOH and/or ketone Amine alkyl: benzamide or benzenesulfonamide aryl: those above, plus perbromo derivatives Arene nitro derivatives (only for some) Aryl Halide nitro derivatives (only for some) Carboxylic Acid amide, anilide, or p-toluidide; neutralization equivalent is also OK for ID-see p. 5 Ketone 2,4-DNP-hydrazone or semicarbazone Phenol perbromo derivative, phenylurethane, or 3,5-dinitrobenzoate ** Check with instructor before deciding how to proceed. See USEFUL PROCEDURAL GOODIES on the next page

2 USEFUL PROCEDURAL GOODIES Recrystallization Technique: Work in a beaker. Choose size so that it is ~1/2 to 3/4 full after all solvent has been added. Keep it covered with a watchglass unless you are actively working inside it. Put your crude solid into the beaker and dissolve in a suitable solvent as you heat the beaker. Often ethanol is a good choice, but consult the protocol you are using. Use the smallest volume of solvent that, when at its boiling point, is able to completely dissolve the solid (trial and error). The key to success is having a hot clear solution that you cool slowly (keeping it covered) so that crystals form slowly and, in so doing, exclude impurities. Sometimes there is insoluble matter (does not disappear if you add a little more solvent). Insoluble material needs to be removed by hot filtration see below. After you have a clear, hot solution, you can do a little quick and dirty work in a small test tube to speed things along. Pour about 1 ml of the hot solution into the tube. Swirl the tube vigorously to cool its contents fast (if no crystals form, cool in ice). If crystals do form in the tube, this solvent will work well. Swirl the tube contents, return them to the beaker, and cover it. Reheat if necessary to get a clear solution, then cool slowly, eventually on ice. If no crystals form in the tube, either you have used too much solvent, or this solvent won t work. If water is miscible in the solvent, add water slowly with mixing to see if the mixture becomes cloudy. If it becomes cloudy, stir and scratch gently to see if crystals will form. If they do, note the approximate percent incease in volume due to added water. Return the tube contents to the beaker, add the appropriate amount of water, cover, reheat as needed to get a clear solution, and cool as above. If adding water doesn t help, or if water is not compatible with the major solvent, you ll need to boil off at least half of the solvent. Return the contents of the tube to the beaker, boil it down, and then start again at the top of this paragraph. Instructors may be able to help in hard cases. Filter crystals on a Hirsch funnel and let air-dry for at least a day before taking a melting point. HOT FILTRATION (to remove insoluble material from a recrystallization in progress) Assemble the apparatus shown using a 400 ml beaker and stemless funnel. Fold the largest piece of filter paper you can find into a cone and put into funnel. Cover with watchglass. Bring beaker solvent to a slow boil and allow vapors to heat up all glassware. Heat suspension you wish to filter, then pour as much as possible into funnel. Cover and continue to boil very gently (don't let it go dry!). Desired material is in filtrate. Hot Plate Pour in hot suspension Keep covered with watch glass! Boiling solvent (thin layer) - 2 -

3 ALCOHOLS Phenylurethane work in a hood In a 20 ml beaker, mix 0.5 ml (4.60 mmols) phenylisocyanate (lachrymator!! USE HOOD!!) with 5.52 mmols of an alcohol (must be anhydrous). Mixture may spontaneously get hot. If not, warm it at a low setting until it does get hot (watch carefully only a little vapor steam - will be evident). You may need to feel it cautiously. Once hot, remove to desk top inside hood. While reaction mixture cools to room temperature, use a stirring rod to mix and loosen the solid as it forms. Vacuum filter the solid and recrystallize it from warm petroleum ether or hexanes (keep beaker covered!!). There will probably be a significant amount of white solid that does not dissolve even when solvent boils. This must be removed by hot filtration (or, it may settle so that you can just pour off the clear liquid). Allow the clear solution (covered!) to cool. Scratching may be necessary to get crystals. 3,5-dinitrobenzoate or 4-nitrobenzoate ester: work in hood; choose the one that gives the derivative with the highest m.p. Weigh approximately 0.5 g of 3,5-dinitrobenzoyl chloride [FW = 231] or 0.4 g of 4-nitrobenzoyl chloride [FW = 186] into a tiny beaker. Compute the moles of reagent based on its measured mass and multiply the result by 1.5. Compute the mass of your alcohol that corresponds to this number of moles and weigh at least this much into the beaker. Heat at a low setting until fumes evolve (hood!) but avoid heating so hot that color changes. Keep warm for ~10 min. Cool to room temperature. Add 10 ml of 0.2 M Na 2 CO 3 and mix well until everything is solid (this base destroys excess acyl chloride and ionizes resulting substituted benzoic acid so that it can be removed by the water wash). Crush any large chunks of solid to permit maximum contact with the base. Filter (Hirsch!) and wash the solid with water. Recrystallize from 10 ml of warm EtOH (covered!). If no crystals return on cooling, reheat and add water to the cloud point as you keep it warm, then allowing to cool slowly (covered). ALDEHYDES 2,4-dinitrophenylhydrazone Work in a small beaker. Follow instructions for the corresponding ID test (use the precipitate as your derivative). If this did not give enough precipitate, you can increase the amount of aldehyde a little (don t add too much because the aldehyde is a good solvent for the desired derivative, and you may not get any crystals). Mix thoroughly with a stirring rod. Filter the precipitate after letting the reaction go for about 3 min. Wash while on the filter with about a ml of icecold EtOH. Suspend the solid in 5 ml of 5 % NaHCO 3 and break up the crystals to ensure good mixing with the NaHCO 3 (this step removes DNP reagent and sulfuric acid from the solid and is essential to obtaining good crystals). Filter the solid and recrystallize from about 30 ml of EtOH. (When hot, the mixture will likely be very dark, which makes it hard to see whether all solids are in solution, so observe carefully. If difficult to dissolve, you can add up to 1 ml of ethyl acetate.) If crystals do not re-form when at room temperature, add water slowly with good mixing just until cloudy, cover, reheat until clear (but still colored!), and cool slowly. Semicarbazone work in a hood Dissolve 0.5 g of semicarbazide hydrochloride in 2 ml of water. In a separate tube that contains 2 ml of MeOH, dissolve 4 millimoles of the aldehyde. Pour the clear solution into the semicarbazide solution and add 0.5 ml of pyridine (STENCH!). Mix well. Warm gently for 5 minutes, then allow to cool. Crystals should form (scratch?). Cool on ice, recover crystals, and wash with water followed by a little ice-cold MeOH. Recrystallize from MeOH, EtOH, or EtOH/water. ALIPHATIC AND AROMATIC HYDROCARBONS AND HALIDES No easy solid derivatives of these classes are possible. For some aromatics, exhaustive nitration can work. Check with instructor. ALKENES These can be difficult. Certain alkenes can be oxidatively cleaved to make solid carboxylic acids. Consult with instructor

4 ALKYL HALIDES No easy solid derivatives of these classes are possible. Check with instructor. AMINES (1 and 2 only) If dark colored, try to decolorize with charcoal before making derivative see instructor. Benzamides (OK for all amines) work in a hood Work in a small Erlenmeyer flask that contains a small stir bar. Mix 0.5 g of benzoyl chloride (lachrymator; cautiously note its odor) with 0.5 g of amine. Stir vigorously while you add 2 ml of 3 M NaOH. Monitor ph with litmus paper. Add more portions of NaOH as needed to keep ph alkaline. Reaction is over when odor of benzoyl chloride is gone and no more oil is visible. Recover solid, wash with water. Recrystallize from water or ethanol/water. Acetamides (NOT suitable for small amines. See instructor if you have a weakly basic amine long reflux and pyridine are necessary.) Reflux 1 g of amine with 0.5 ml of acetic anhydride for 5 min. Cool, then dilute with 5 ml of water. Scratch if necessary to induce crystallization. (If any oily material is visible, some unreacted acetic anhydride is left, and this must be allowed to hydrolyze before you proceed. Crude product must be a free-flowing solid.) Recover crystals and wash with a little 1 M HCl to remove any unreacted amine. Recrystallize from water or ethanol/water. Benzenesulfonamides check to verify that the anticipated derivative melts above 60 C. If it does, use the procedure for the Hinsberg Test in the ID Tests document. Perbromo derivative: follow procedure under Phenols CARBOXYLIC ACIDS Amides (NOT suitable for small acids; check with instructor before choosing) Work in your hood this procedure releases HCl and SO 2 gases. Reflux 1 g of carboxylic acid with 2 ml of thionyl chloride for 30 min (the mole ratio of SOCl 2 :carbox. acid should be about 1.5:1). In the hood, in an Erlenmeyer flask on ice containing a stir bar, chill 20 ml of concentrated ammonia (ammonium hydroxide). When reflux is finished, cool the boiling flask without disassembling. Once cool, remove all glassware and use a Pasteur pipet to cautiously transfer the reaction mixture to the flask in ice that contains ammonia (stirring!). Each drop will hiss, spatter and produce lots of white smoke. When addition is complete, recover the solid and recrystallize from water (frequently a good choice!) or ethanol/water. Anilides or p-toluidides (OK for any acid, but generates a lot of waste and product is challenging to recover from reaction solvent) Work in your hood this procedure releases HCl and SO 2 gases. Reflux 1 g of carboxylic acid with 2 ml of thionyl chloride for 30 min (the mole ratio of SOCl 2 :carbox. acid should be about 1.5:1). While this is going on, prepare the amine that you chose, keeping in mind that it is toxic and easily absorbed through the skin. Working in a small Erlenmeyer flask that contains a stir bar, dissolve 2.5 g of aniline (avoid really dark stuff) or p-toluidine in 10 ml of toluene. Cool this on ice. After reflux is finished, lower the heating mantle and allow to cool before disassembling. When cool, remove glassware and use a Pasteur pipet to cautiously transfer the reaction mixture to the stirred flask in ice. Lots of heavy precipitate will form, but you do not want it. The product you want remains soluble in the toluene. Remove the solids by filtration, and wash them with a little clean toluene. Pour the combined toluene filtrates into a separatory funnel and shake in sequence with water, HCl (1 3 M), NaOH (1 3 M), and water. This treatment removes unreacted carboxylic acid and unreacted amine. Dry the washed toluene solution over CaCl 2, then remove solvent (distill without overheating the residue, or evaporate under vacuum). Recrystallize residue from ethanol/water or water. The waste solids filtered off earlier are toxic ask the instructor what you should do with them

5 Equivalent weight: How to estimate the equivalent weight of an unknown carboxylic acid by titration This is not a solid derivative, but for the purposes of this course is an acceptable alternate way to establish identity of a carboxylic acid. 1. Obtain (or make) 300 ml of approximately 0.1 M NaOH. This concentration will allow you to use about 30 ml for each titration. Titration can be done using a ph meter (recommended because you can see the end point coming; use a beaker) or an indicator like phenolphthalein (in which case, use Erlenmeyer flasks and do the titration on a white surface). A magnetic stirrer helps with either method. 2. Standardize the NaOH: Use potassium hydrogen phthalate (KHP; also called potassium biphthalate). The formula weight of KHP is g/mol. Weigh three samples of KHP, each containing about mole, into separate containers. Double check your calculation and record the actual masses used! Dissolve each in convenient amounts of water (the volume does not matter). Titrate each to ph ~8.5 using your NaOH. If any liquid splashes onto the side of the flask you must rinse it down using your wash bottle. Use the moles of KHP and the volume of NaOH consumed to calculate the (average) actual concentration of the NaOH. 3. Titrate unknown acid: You should have a pretty good idea of the identity of the acid. Calculate the mass of it that should contain about mole of H + (again, double-check your figures). Weigh three samples of the acid (even if a liquid), dissolve each in about 20 ml of water (or ethanol if not soluble in water), and titrate as above. From the volume of NaOH used and its known concentration you can calculate the number of "equivalents" of acid present in each sample (one equivalent = one mole of H + ). Use these and the corresponding masses of unknown to compute the average equivalent weight (the mass of acid that contains one mole of acidic H atoms). ESTERS These must be hydrolyzed into their constituent carboxylic acid and alcohol. The products must be separated and isolated, then individually characterized. If you were given an ester, you will not have a second component in your unknown. Hydrolysis: In a 50 ml boiling flask, add mol of NaOH pellets, 10 ml of the ester, and 15 ml water. Reflux this mixture with good mixing for 1 hr buried in a sand bath. The resulting reaction mixture will contain the neutral alcohol and the anion of the carboxylic acid. It is up to you to figure out how to physically separate, recover, and identify each of these compounds. Remember that either or both of the components of the ester may be water-soluble. KETONES: follow either procedure under ALDEHYDES PHENOLS if dark-colored, try to decolorize with charcoal before making derivative see instructor Perbromo derivative work in a hood Caution: chemical burn hazard! Have at hand a bottle of aq. sodium bisulfite (spelling!!), sodium thiosulfate, or glycerol. If you get any Br 2 on you, rub one of these substances into the affected area, then rinse with water. The chemicals will neutralize the Br 2. Find the bottle of Br 2 in water; make sure you can see some very dark elemental Br 2 at the bottom. If it is not full of water, open it in the hood (Br 2 vapor will escape) and add water, then cap tightly and shake for a minute to saturate the water with Br 2. Take this to your desk hood. Work in a 250 ml beaker that contains a stir bar. Dissolve about 0.25 g of phenol in a little methanol. As you stir, slowly add Br 2 /H 2 O at such a rate that the color disappears almost instantly. Make sure that you add only the clear redbrown water solution of Br 2, not the very dark elemental Br 2. Eventually a white solid will form. Keep adding Br 2 slowly until significant color persists for several minutes. Heat the covered mixture gently for a few minutes to insure that the Br 2 color persists. After you are sure that no more Br 2 is reacting, add an aqueous solution of sodium hydrogen sulfite (NaHSO 3 ; also called bisulfite; note spelling and formula) a little at a time until the color vanishes. Recover the solid, wash with water while on the funnel, and recrystallize from ethanol/water (if you don t know this technique, ask for help). Phenylurethane: follow procedure under ALCOHOLS - 5 -