INTRODUCTION TO MICROSCALE ORGANIC CHEMISTRY

INTRODUCTION TO MICROSCALE ORGANIC CHEMISTRY Welcome to the world of microscale organic chemistry. Most of the experiments you will perform this semester will be done on a small scale with specially designed microscale glassware and equipment. In combination with the experiments you performed the first semester using larger equipment and amounts of material, your experience with microscale experiments this semester will provide you with a wellrounded background doing various types of organic chemistry. Considerable scientific research in chemistry, biochemistry, biology and medically related areas is now done on a much smaller scale than years ago because of the current availability of computerbased instrumentation for doing analyses and structure determination on a few milligrams of material. This semester, you will routinely use less than a gram of starting material(s) and volumes less than 5 ml. Reaction vessels, called conical vials, hold no more than 5 ml of reactants. Weighing will be done on balances that are accurate to 0.1 mg. Liquids will be measured using syringes and pipettes. Extractions are often done using conical vials or sample vials rather than separatory funnels. Solids can be recrystallized in small Erlenmeyer flasks and isolated using small filter funnels (Hirsch funnels). All the equipment you will use is designed for doing reactions on, and purifying, small amounts of material. Hence, the term microscale organic chemistry applies. You will usually obtain less than 200 mg of solid product or a couple milliliters of liquid product. These quantities may seem unreasonably small, but they are more than enough material for melting or boiling point determinations and for spectral analysis. Do not expect to obtain large amounts of product as you did the first semester, and do not be frustrated when you get 100-200 mg of product. The microscale experiments you will perform involve the preparation of compounds. Most of these experiments have been completed successfully by previous classes. Join the students who have done microscale experiments in the past and claim they enjoyed them more than large-scale experiments. This introductory Chapter discusses some of the features of microscale organic chemistry and some of the experimental techniques and equipment that you will use routinely in the laboratory. 1

1. FEATURES OF MICROSCALE ORGANIC CHEMISTRY EXPERIMENTS You should be aware of the many features of microscale organic chemistry experiments. Most of them are advantageous, and they require you to exercise greater care and attention to detail in the manipulation of small quantities of material. Safety The chance of an accident is much less when using small amounts of reagents. Chemical exposure is lower so the risk from unknown toxicity and unexpected allergic reaction is greatly decreased. Cost of Chemicals By using small amounts of reagents, the cost of chemicals per student is much less. With the large number of students taking organic chemistry, reactions that would be too costly to perform on large scale can now be done on microscale. Equipment Cost and Breakage The initial investment to convert the laboratory to microscale organic chemistry was great. However, the microscale glassware is less fragile than the larger scale glassware so the amount of breakage is less, thus reducing the ongoing cost of operation. Waste Disposal The small quantities of chemicals used in microscale experiments result in less waste to dispose of and thus decreased cost of waste disposal. Ease of Using Apparatus The amount of time required to set up the apparatus for the microscale reactions is greatly decreased. It usually takes only a few minutes to do so, and it takes very little time to clean apparatus before and after using it. Equipment is no more than 6-10 high, and only one clamp is needed to support it. It is easy to swirl or shake reaction mixtures and in the event of overheating, it is simple to remove the apparatus from the heat source. Saving of Time With larger-scale reactions, a lot of time is spent waiting for reactions to heat or cool to the desired temperature. This time is greatly reduced with microscale reactions. The time required for a reaction to occur is also greatly decreased by using small quantities of starting material. Larger scale syntheses that might require two lab periods to complete can usually be done in several hours on microscale. Thus, repeating an experiment, if necessary, is much faster. Techniques and Attention to Detail You must concentrate on learning to be neat and to think about the work you are doing. Products must be handled with care to minimize loss, as must the transfer of reagents and products. Each time you transfer compounds, you lose a milligram or two. On this scale, losses greatly decrease the yield of the product. Some of the items used with microscale equipment are very small and easily misplaced, so you need to exercise care in using them. Microscale experiments require more manual dexterity and are unforgiving of carelessness. If you drop your product on the floor or bench, you are unlikely to recover it. Exercise care in storing products in your locker. If being left to dry, products will be left inside the funnel or beaker they 2

are isolated in to avoid their being dispersed throughout the drawer when it is opened and closed. 2. MICROSCALE EQUIPMENT a. Conical reaction vials of 5 ml capacity 1 will be used for reactions this semester. They have flat bottoms to allow them to sit on the bench, and they have conical (coneshaped) interiors to permit removal of small volumes of liquids. b. Standard taper joints are present on most of the glassware. No grease is used on these joints to avoid contamination. Instead, a seal is provided with an external O-ring that is held in place by a screw cap. Each standard taper joint already contains the O- ring and cap. Please do not remove either of them, as they are easily lost. The screw caps and O-rings hold the apparatus together so no joint clips (clamps) are needed. Only one clamp is needed to hold the assembled microscale apparatus. c. Screw caps with septa are used on occasion to close certain openings on microscale equipment. When the latter is not being used, please keep the caps on the equipment to avoid losing them. d. Magnetic stirring can be done with a tiny magnetic stir bar called a spin vane that is designed to fit the conical shape inside the conical reaction vials. Make sure it is inserted in the conical vial with the pointed end down. The spin vane has been forced into each conical vial so it does not come out. e. A syringe with a needle is used to accurately measure small volumes of liquids that are used in reactions. In some cases, the liquids are transferred directly to the reaction vessel. The needle can also be inserted through septa if it is desired to add reagents slowly to a reaction vial. If liquids cannot be drawn into the syringe, there are several possible reasons: (a) the needle is clogged (try cleaning it), or (b) the needle is not tightly connected to the syringe (make sure the connection is tight). If you cannot get the syringe to work, ask your instructor for help. Clean syringes when you are through using them. Immediately wash the syringe and needle with water and then with acetone to remove all inorganic and organic materials. Then, carefully remove the plunger from the syringe and pull air through the syringe barrel to remove the acetone. Be very careful when removing the plunger from the syringe and always replace it in the syringe when you are through cleaning it. Then, remove the needle from the syringe and wash the surfaces that held them together. When not being used, the needle should be stored in its plastic sheath and kept in one 1 Conical vials are also available in 1 ml, 2 ml, 3 ml and 4 ml capacity, but they will not be used this semester. 3

of the slots in the microscale lab kit. Place the clean syringe in the syringe slot in the microscale kit. 3. LOCKERS: PERSONAL AND COMMON The common cabinet/drawer contains equipment, including the microscale glassware kits that will be used by each section of the course. For a given section, each student is assigned a common cabinet/drawer for use during the lab period. Each student is also assigned a personal drawer that contains small, less expensive equipment and glassware (beakers, Erlenmeyer flasks, sample vials, etc). Each personal drawer has a divider in it, each half of which contains identical sets of glassware and equipment. In a given section, two students may be assigned to work out of the same drawer, with each student using the equipment in half of the drawer. Students in other sections will not be sharing the personal drawer, so safety goggles may be left in your personal drawer. The keys to the personal lockers are kept on the keyboard that is near the entrance to the lab. Take the key to your assigned locker and leave the key in the locker drawer while working in the lab. The last student using the personal drawer is responsible for locking the drawer and returning the key to the keyboard before leaving. 4. GLASSWARE: STORAGE, CARE AND CLEANING a. Storage Because students in other sections are using the equipment in the common drawer/cabinet, it is imperative that you clean, dry and return all the glassware belonging in the common drawer/cabinet at the end of the laboratory period. A list of equipment belonging in the common drawer/cabinet and of that belonging in your personal drawer is provided at the beginning of each semester and should be kept in your personal drawer to keep track of what equipment belongs where. Please do not leave equipment that belongs in the common cabinet/drawer in your personal locker. b. Care and Cleaning Be especially careful in handling the microscale glassware. To clean the glassware, first wash it with soap and then water. Then, rinse it with a minimum amount of acetone to remove any organic compounds and dry it using the laboratory hot-air dryer. Never, ever put glassware that contains acetone in the microscale glassware kit. Even acetone vapors will destroy the foam liners in the kit. c. Clean versus Clean and Dry An experimental procedure calling for the use of clean glassware means that it should be washed with water and soap, followed by rinsing with water. This glassware is normally used when a water-containing reagent is used in the experiment (i.e. trace amounts on water on the glassware will not dramatically affect the results because an aqueous solution is being added to the glassware). On the other hand, clean and dry glassware requires that the apparatus be washed and then dried; 4

this is conveniently done by rinsing the apparatus with acetone after washing it and then drying it. Clean, dry equipment is used when it is essential to have no moisture present. The experimental procedures in this booklet specify when the apparatus must be clean or clean and dry. 5. TRANSFERRING AND WEIGHING LIQUIDS Never transfer a liquid to a container that is sitting on the microbalance pan. Weigh the container (for example, conical vial or sample vial), remove it from the balance, transfer the required volume of liquid, and reweigh the container to determine the actual weight used. In computing theoretical yield, use the actual weight of liquid that you used. You are using small containers and vials; ensure they don t tip over, or don t get knocked over, by placing them in small beakers. When an experimental procedure requires the use of an accurate volume of liquid (for example, 0.3 ml or 0.55 ml), use a syringe to measure the volume. This is usually required for measuring starting materials. Syringes color-coded with tape corresponding to color-coded reagent bottles are provided with the containers of liquid starting materials. Be certain you use the correct syringe with the correct reagent bottle, and leave the syringe(s) by the reagent bottle(s) that are kept in the hoods. Never use the syringe from your kit for any reagent bottle in the hood! You risk contaminating the entire reagent bottle because you do not know if your syringe is 100% clean. When a procedure calls for the use of an approximate volume of liquid (for example, about 1 ml or about 2 ml), use a Pasteur pipette to measure the liquid. Approximate volumes are usually used in purification procedures when it is not essential to use an exact volume. Pipettes hold their contents with the vacuum created when the pipette bulb is squeezed and then released to draw liquid into the pipette. If the pipette is tilted, vacuum may be lost and the liquid in the pipette may be lost and squirt out onto the bench, your lab notebook or even your neighbor! A pipette tilted upsidedown will result in some of its contents running into and contaminating the inside of the pipette bulb. When you are through using them, the pipits can be washed and stored in your personal locker. Those that are too dirty to clean or are broken can be disposed of in the Glass Waste container. When larger volumes are required (for example, about 8 ml, etc), graduated cylinders may be used. These will also be color-coded to their respective reagent bottles if used in the reagent hoods. To avoid having sample vials or conical vials tipped or knocked over, it is convenient to put them in the aluminum heating block, which is the microscale analogue of a test tube rack for holding test tubes. However, do not forget to return the heating block to the common locker at the end of the lab period; do not leave the 5

heating block in your personal drawer. Sample vials containing products may be placed in small beakers in your locker to avoid their falling over if it is necessary to keep them until another period. 6. TRANSFERRING AND WEIGHING SOLIDS Never transfer a solid to a container that is sitting on the microbalance pan. If weighing a solid starting material, place a piece of weighing paper on the balance pan. Weighing paper is good for transferring solids because they don t stick to the paper. Carefully transfer the solid to the paper using a clean microspatula until the desired weight is obtained. Then, carefully transfer the solid directly to a conical reaction vial or to a clean dry, small sample vial if the solid is to be added to a reaction mixture (e. g. to a conical vial) in small quantities. It is highly unlikely you will be able to weigh exactly the amount of solid required for a reaction. It is quite satisfactory if you actually use a weight that is 5 mg of the required amount as long as you know the actual amount you used for purposes of calculating the theoretical yield. If determining the weight of a solid product, weigh the clean, dry sample vial, remove it from the balance, transfer solid to it and reweigh the container to determine the actual weight of the product (i.e. weighing by difference ). To avoid having sample vials or conical vials tipped or knocked over, it is convenient to put them in the aluminum heating block, which is the microscale analogue of a test tube rack for holding test tubes. However, do not forget to return the heating block to the common locker at the end of the lab period; do not leave the heating block in your personal drawer. Sample vials containing products may be placed in small beakers in your locker to avoid their falling over if it is necessary to keep them until another period. 7. EXTRACTIONS Many experimental procedures involving organic liquids require either washing the organic layer or extracting a desired compound from a reaction mixture. A useful and easy way to perform extractions or washings is to use a conical vial or a large sample vial, as described below. Depending on the experiment, the lower layer or the upper layer contains the desired compound and the experimental procedure will indicate the layer to keep. To avoid repeating an experiment, it is advisable to keep ALL layers until the desired product is obtained. Then, and only then, should all of the unwanted solutions be disposed of as directed in the Waste Disposal section of each experiment. a. Using Conical Vials Mix the organic and aqueous layers in a 5 ml conical vial by drawing some of the mixture into a Pasteur pipette and expelling it back in to the vial. Repeat this process several times. Alternatively, seal the vial with a cap containing a 6

septum, and shake the vial gently. Remember that pressure can build up inside the vial, so make sure the vial is upright and carefully remove the cap of a vial that has been shaken. When mixing is complete, allow the layers to separate, and use a Pasteur pipette to remove the lower layer first. Squeeze the bulb first, lower the pipette into the solution, through the top layer and into the bottom layer and slowly release the bulb to allow the pipette to suck up the liquid from the lower layer. Repeat this process, as necessary, until the entire bottom layer is removed. This process takes advantage of the taper of the conical vial and allows for better and more complete separation of the layers. Be careful not to draw the upper layer into the pipette. b. Using Large Sample Vials Mix the organic and aqueous layers in a large sample vial and cap it tightly, making sure the cap has a plastic insert in it and that the top rim of the sample vial is free of cracks, to avoid a vial that might leak. Shake the vial gently, and release the pressure by opening and retightening the cap periodically. Allow the layers to separate. Hold the vial at an angle and using a Pasteur pipette, remove the lower layer, using the technique described above for the conical vials. 7