First the Basics

ALWAYS Safety First Why? 1 Safety is important for you, as well as for your coworkers. There are inherent dangers in organic chemistry lab; the chemicals you will work with may be very flammable, and some are toxic. Safety is your number one priority. By working safely and in control of the situation, you not only protect yourself and your classmates, but you also protect the environment from the effect of harmful chemicals.

Which Safety Features Are Available in the Lab? A laboratory is always equipped with an alarm system and a sprinkler system, which will be activated either when an alarm is pulled or triggered by an occurrence in the building. Each laboratory room is equipped with safety showers, eyewashes, and fire extinguish- ers. The lab rooms have multiple exit doors to allow for quick evacuation. If anything goes wrong, your instructor must be alerted immediately. Most emergencies can be handled with available personnel. But if there is any doubt that help is needed, CALL 911. It is much better to err on the side of caution. When calling 911, it is advis- able to use a line phone, as most cell phones don’t tell the operator where you are located. 2 Chapter 1 • First the Basics of thefactthatgloves are alsocomposed ofchemicals, andtherefore kind theright inlabsafety.that gloves playanessentialpart However, you shouldbeconscious The remaining question is:Should gloves be worn ornot? There isnodenying Closed-toe shoesare alsoessential. orflip-flopsare notallowed. Sandals tank topswithoutalabcoat. apron orlabcoatshouldbeworn atalltimes. shouldbecovered, Shoulders sono ofyour bodyisvulnerabletocontaminationAny exposedpart by chemicals. An accident occursandyou are contacts, wearing remove themassoon aspossible. aware ofthefactthatyoubut you are have theselenses. tobevery wearing Ifan is notmore dangerous glassesinthelab, thanwearing aslonggoggles are worn, ofpeoplewear contactlenses.Lots Accident statisticsshow contacts thatwearing vent holesatthetopofthesegoggles donotallowanyliquidtoget inside. inthelab.goggles No exceptions. Your eyes ofyour are body. themostvulnerablepart What ShouldIWear? itself.benches are onthe equipped witheitheroverhead vent hoodsordowndrafts laboratory todispensereagentsratories inasafefashion. Frequently theworkbenches inthe space.fumes outofthegenerallaboratory usedinteachinglabo- Hoodsare often spacewithahigh continuous airflow,enclosed whichwillkeepnoxious andtoxic isequippedwithfumehoods. laboratory Each organicchemistry Ahoodisan is labeledas “ABC,” fires. ofmostchemical andisappropriate foruseintheevent of fire extinguishers. The mostcommonfire extinguisherinateachinglaboratory has beentrainedtouseafire extinguisher. Beaware thatthere are different kinds are notsure thatyou extinguishthefire, can don’t doit. Callyour instructor, who ofoxygen.lack Ifyou are notsure howtouseafire extinguisher, don’t doit. Ifyou or flask, much safertocover itis usually thecontainerandletfire diedue to The firecan beusedifthere extinguisher isafire inthelab. Ifthefire isinabeaker longtime,like avery buttakingthisprecautionisvitaltoyour safety! eye openwithyour fingers, your andirrigate eye for15minutes. This mayseem comesincontactwithyourIf anychemical the sink. Anycontamination withwaterfor15minutes. oftheskinmust berinsed ing. Ifthisisnotthecase, itismore efficienttouse thefaucetsandsprayheadsin hasbeenspilledonon fire your orifalargeamountofchemicals bodyandcloth- thatis, beusedifnecessary; shower should only The safety clothing is when your The goggles must be the resistant”; “chemical eye, usetheeyewash station. Holdyour At alltimes, you shouldwear of glove should be worn for specific chemicals. Manufacturers of gloves offer in- formation regarding the protection different gloves provide for certain chemicals. Also, it is more difficult to manipulate small items when wearing gloves, and the chances of spills increases with glove use. For most experiments in teaching labo- ratories, gloves are optional if the chemicals used are not toxic or caustic. Gloves should be worn if indicated in the procedure.

What Should I Pay Attention to? • No smoking, eating or drinking are allowed in the laboratory. Never taste anything in the lab. Safety First ALWAYS • Never leave an experiment in progress unattended, especially if heating is involved. Should you need to leave the lab while an experiment is in progress, get your instructor or a classmate to keep watch over your reaction while you are gone. • For most experiments, digital thermometers are the best choice. However, for certain experiments, mercury thermometers are irreplaceable. Special rules apply to mercury thermometers because of the highly toxic nature of mercury. 3 If you break a mercury thermometer, do not try to clean it up. You should notify your instructor immediately so that the problem will be taken care of. Make absolutely certain you do not walk through the mercury-contaminated area. You sure don’t want to track toxic mercury back to your apartment or dorm room. To avoid breaking a thermometer, secure it at all times with a clamp. • If there is a desk area in your lab room, there will be a very clear dividing line between the non-chemical area and the laboratory area. Classroom rules ap- ply to a desk area, while laboratory rules strictly apply once the line into the lab section is crossed. • Aisles must be kept free of obstructions, such as backpacks, coats, and other large items. • Never fill a pipet by mouth suction. Avoid contamination of reagents. Use clean and dry scooping and measuring equipment. • Do not use any glass containers, such as beakers or crystallizing dishes, to collect ice out of an ice machine. It is impossible to see the glass shards of a broken container in the ice, and fellow students could get seriously cut if they put their hand in. 4 Chapter 1 • First the Basics special wastestreams. We’ll discussalloftheseinorder. waste, regular garbage, glasswaste, liquidorganicwaste, waste, solidchemical and wastestreamsseveral ineachlaboratory, whetherteaching orresearch: aqueous fore, we are allresponsible formakingsure theyget where theybelong. There are isthattheydon’tOne thingtoremember aboutchemicals justgoaway. There- Chemical Waste berepaired. soitcan defective report equipmenttotheinstructor Immediately • waterare madeofplastic, thedeionized Ifthefaucetsfor treat themgently! •

Special wastestreams: Special waste: chemical Solid waste: Liquid organic Glass waste: Regular garbage: #1: Rule according toEPA (Enviro responsibly. capped atalltimeswhennotinuse,These containershave tobe identifiedatalltimeswithwastetags,has tobeclearly andwillbedisposedof your experiments, andalltheacetonewashingsofglassware. This waste liquid wastecontainer. theorganicsolutions generatedduring This includes objects, are inspecialcontainerstoavoid accidents. collected harmful bage cans. ofpapertowels enduphere. Lots the drain. and itistherefore godown whatsoever materials essentialthat nohazardous TIONS! joinsalltheothereffluentofcity The effluentofthelaboratories acidicoralkaline, slightly be very butthat’s where itstops. NOEXCEP- treatment orinherent properties. duetoeithertheirtoxicity chemical hydrogenation. usedincatalytic or thecatalyst These mixtures require special streams becreated. will from an oxidation reaction Crwaste This includes personnel inaresponsible fashion. agents, contaminatedfilterpaper, etc. Itwillbedisposedofby thelaboratory a designatedcontainer.from columns, gel silica drying This wasteincludes Only watergoesdownthedrain. Only Itcouldbesoapy water, oritcould Allglasswaste, Pasteur inparticular pipetsandothersharp All solid non-chemical non-glasswastegoesinthegar- Allsolidnon-chemical Solid organic chemical wasteshouldbeplacedinto organicchemical Solid Allorganicwaste, exceptthesolids, goesintothe For experiments, certain separatespecificwaste nmental Protection rules. Agency) The Why and How of a Laboratory Notebook

The Basics About Notebooks A laboratory notebook is the essential record of what happened in the laboratory. This is valid for teaching laboratories, synthetic research laboratory, or analytical chemistry laboratory. If you do an experiment, you need to write down exactly what you did and what happened. Fellow scientists should be able to read your notebook, and maybe come up with possible alternative explanations for what happened. If a chemist in a pharmaceutical company made the drug taxol for the first time, other scientists might want to repeat this synthesis and potentially improve upon it. To be able to publish experimental results, such as the synthesis of a drug, an official record of these experiments has to exist. There are some basic rules as far as notebooks are concerned: The Why and How of a Laboratory Notebook • The pages in a notebook are always numbered. • No pages are ever removed. • All entries are in ink, and are never deleted. If you change your mind about 5 something, you can always scratch out an entry, but never erase. • The entries should be dated.

What to Do Before Coming to Lab First and foremost, you should read and understand the experiment. Read through the description of the experiment, and ascertain that you understand all the under- lying chemical principles. If not, look up the chemistry background and study it. Once you completely understand the experiment, you can start making entries in the notebook. Here is what should appear in the notebook: • Date • Title of the experiment • Objective: What is the purpose of this experiment? It could be to learn a new technique, to examine a reaction mechanism, or to synthesize a compound, or to analyze a mixture, or a number of other possibilities. • Write the balanced chemical equation, if appropriate. In case of a synthesis reaction, write the starting materials and product. Use the space above and below the arrow to define the reaction conditions, such as temperature and solvent. 6 Chapter 1 • First the Basics H A complete balanced chemical equationshows allthereactants, Acompletebalancedchemical products, Inaddition, shouldbeinvestigated. ofthechemicals hazards thesafety In- constant sectionof shouldcontainanyphysical your report Theintroductory • Table 1-1. bp 102° 0.46 mol MW 88,d=0.806g/mL 50.0 mL 3 -ehl2btnl8 0 0.806 102 88 2-methyl-2-butanol CCH -ehl1btn 03 Flammable 31 70 2-methyl-1-butene -ehl2btn 03–8Flammable 35–38 70 2-methyl-2-butene Phosphoric acid opudMW Compound of molesused. For example: give themolecularweight ofeachreactant, theamountused, andthenumber catalysts, andreaction formulas. andsolvent conditionsusingstructural Also from themanufacturer used. ofthechemicals from willgive themostcompleteinformationandisobtained DataSheet) Safety booksoronlinesources; theMSDS(Materials befoundfrom formation can equation. inthechemical beincorporated constantscan these physical constants intableformat, asillustratedin Table 1-1. However, of quiteafew on theexperiment.bearing Itisconvenient andefficienttolistthephysical solubility, etc. Don’t listallconstantsyou find, can theonesthathave a only molecular weight, meltingpointsforsolids, boilingpointsforliquids, density, theexperiment. orinterpret that maybeneededtoperform For example: C CH OH 3 2 CH 3 H – H heat 3 PO 2 O 4 (°C) mp H 3 C+ bp 35–38° MW 70 C CH (°C) bp 3 HCH CH (g/mL) d 3 H Extremely corrosive, 2 CCH Considerations bp 31° MW 70 strong acid C CH Safety 3 CH 2 3 • Write the procedure. You should be able to run the experiment using only your outline of the procedure, without the lab manual or a literature article. Your outline should contain enough information to allow you to perform the experiment, but no more. Complete sentences are not needed; a bullet format is preferred. Quantities of materials are required. New procedures may re- quire a rather detailed description, but for familiar procedures only minimum information is needed. In fact, the name of the procedure may suffice; for ex- ample, “recrystallize from methanol.” Copying the procedure word for word from the original source is unacceptable; summarizing in your own words will be more helpful to you. Writing the procedure might seem like a waste of time, but doing so will ensure that you know and understand all the steps. Even researchers with de- cades of experience write out the procedure every time they do an experiment. It might be an abbreviated version with just quantities and keywords, but that The Why and How of a Laboratory Notebook is all the information needed to run the experiment. An easy format is to use the left half of a page to write out the procedure so that you can follow along during lab, and use the right half for recording observations and results on the right side. 7

What to Write During Lab When you begin the actual experiment, keep your notebook nearby so you are able to record the operations you perform. While you are working, the notebook serves as a place where a rough transcript of your experimental method is recorded. Data from actual weights, volume measurements, and determinations of physical con- stants are also noted. The purpose here is not to write a recipe, but rather to record what you did and what you observed. These observations will help you write re- ports without resorting to memory. They will also help you or other workers repeat the experiment. When your product has been prepared and purified, or isolated if it is an isolation experiment, you should record such pertinent data as the melting point or boiling point of the substance, its density, its index of refraction, spectral data and the conditions under which spectra were determined. Figure 1-1 shows a typical laboratory notebook. Note how much detail is given about what really happened during the experiment. The format can vary, and the important thing is to record information during the experiment. 8 Chapter 1 • First the Basics Figure 1-1. Figure Laboratory notebook. The Why and How of a Laboratory Notebook

9 10 Chapter 1 • First the Basics The Why and How of a Laboratory Notebook

11 12 Chapter 1 • First the Basics Finally, makesure you AND THOROUGH! BE THOUGHTFUL understandwhatyoureally didinthelab, andwhy, andwhereleadto, itcan etc. that istoconvince ofthe you your instructor report ofthis part The wholepurpose ortechniquebeappliedto? couldthischemistry What • Howcouldyour results have beenimproved? • didyou learnaboutthechemistry? What • didyou andlimitationsoftheequipment learnaboutthereliability What • didyou andlimitations learnaboutthereliability ofthetechniques What • explainthedifferences can between your expectations andthe actual What • Explainthelogicofwork-up procedure. Howdowe isolatetheproduct? • Explainthelogicofprocedure. The basicquestion is: why istheproce- • didithappen? Why • happened? actually What • didyou expecttohappen? What • contain discussion ofthefollowingtopics: posed mechanismforthereaction inquestion, ifappropriate. Your also can report youthe results can. you conclusions obtainedanddrawwhatever Give thepro- demonstrate your understandingofwhathappenedintheexperiment. You discuss You adiscussion. andwrite must alsodrawsome conclusions This iswhere you reading thespectra? from you ascertain spectra you recorded, ofthespectra. aswell asyour analysis information can What a as running ameltingpoint.TLC plateormeasuring You any shouldalsoinclude youIn your theresults performed, you report oftheanalyses shouldinclude such benecessary,tions willoften andrecovery. suchas%yield First your results. you your have toevaluate dataandanalyze basiccalcula- Some What toWrite AfterLab preting used? used? results? Why? dure thewayitis? your result. cite your data and observations while your data andobservations explaining and inter- Various formats for reporting the results of the laboratory experiments may be used. You may write the report directly in your notebook, or your instructor may require a more formal report that you write separately from your notebook. When you do original research, these reports should include a detailed description of all the experimental steps undertaken. Frequently, the style used in scientific periodi- cals, such as Journal of the American Chemical Society, is applied to writing labora- tory reports.

Important Calculations Laboratory results usually require you to perform some calculations. Here are some examples of calculations that are typically used.

Conversion of Volume to Mass and Number of Moles for a Pure Liquid Amounts of pure liquid reagents are specified in volume measure (mL or L). To The Why and How of a Laboratory Notebook convert volume to mass or to number of moles, use the following formulae: mass (g) volume (mL) density (g/mL) # of moles [volume (mL) density (g/mL)] / MW (g/mol) 13 Example: We start a reaction with 20 mL of 1-butanol. How many grams and moles does this represent? Solution: 1-butanol: d 0.810 g/mL, MW 74 g/mol mass (g) 20 mL 0.810 g/mL 16.2 g # of moles (20 mL 0.810 g/mL) / 74 g/mol 0.219 mol

Conversion of Concentration to Mass for a Solute The calculation for the amount of solute in a solvent depends on the type of solu- tion used. The concentration of the solute may be given in several different sets of units, such as weight/weight (w/w), weight/vol (w/v), and volume/volume (v/v). We shall only be dealing with w/v relationships, which can be expressed in terms of molar concentrations or as mass of solute per unit volume of solvent. a. Concentrations expressed in terms of molarity: If the molar concentration of the solute is known, then the following equation is applicable: Solute mass M V MW M solute molarity in mol/L V volume of solution in L MW molecular weight of solute in g/mol 14 Chapter 1 • First the Basics Solution: #ofmoles MeOH

b. Where Where M

V C c. Solution: Example: a specifiedvolume solution, ofalessconcentrated usethisequation: Dilution: 12 M mol/L Solution: Example: are thefinalconcentration andvolume. V Example: used: ofmasssolutepervolumeterms ofsolution. The followingequationis Weight/Volume solutions: volume inL concentrationofsoluteing/L To thevolume ofaconcentratedsolution calculate neededtomake

Mass NaOH Mass Use theequation

1 of MeOH Mass ofMeOH 1000 mLofsolution. 3.5 MsolutionofNaOH inwater. Calculate theamountofsodiumhydroxide present in100mL ofa with aconcentrationof240gmethanol(CH Calculate thenumberofmolespresent in250mLofasolution water tomake100mL1MHCl. We use8.3mLoftheconcentratedacidsolution andaddittothe HCl? 12MHCl, from howwould youStarting make100mLof1M and V 1 1

V 1 100mL/12

1 are theinitialconcentrationandvolume, andM M 2 V V Inthesesolutions, theconcentration isexpressed in Solute weight Solute 2 1

3.5mol/L 1mol/L M (240gofMeOH/1000mL) 8.3mL 1 V 1

60g/(32g/mol) M 0.100L 2 100mL C V 2 V 40g/mol 1.875mol 3 OH, MeOH)in 250mL 14g 2 and V 60 g 2

Percent Yield Several distinct types of yield calculations are used in organic chemistry lab, al- ways expressed in percentages. The simplest of these yield calculations is the % recovery; for example, in a recrystallization. In reactions, the quantity of material that can be obtained based only on stoichiometry is called the theoretical yield. Organic reactions, however, rarely proceed to completion as shown in the bal- anced equation. Competing reactions can consume some of the starting materials, thus reducing the amount of product obtained. In addition, many organic reac- tions involve equilibrium processes or can proceed rather slowly, and significant amounts of starting materials might still be present at the “end” of the reaction. The amount of material obtained is called yield. A measure of the efficiency of a particular reaction is the % yield. a. Determination of % recovery: In a purification procedure, such as a recrystalli-

zation, distillation, or sublimation, the amount of pure material recovered will The Why and How of a Laboratory Notebook necessarily be smaller than the amount of impure material you started with. The % recovery is calculated by the following formula: % recovery (g of pure material/g of impure material) 100 % 15 Example: Calculate the % recovery for the following: 2.5 g of anthracene were recovered after recrystallization of 4 g of an impure anthra- cene sample. Solution: % recovery (2.5 g/4 g) 100 % 62.5 % b. Determination of the theoretical yield: Several steps are necessary to calculate the theoretical yield of a reaction. As an example, we consider the acid-cata- lyzed esterification of 5 g of glutaric acid with 100 mL of ethanol. 1. First we have to balance the equation: 2 moles of ethanol are needed to convert each mol of diacid to the diester.

⎯→H HOOC–CH2CH2CH2–COOH 2 CH3CH2OH diacid

CH3CH2–OOC–CH2CH2CH2–COOCH2CH3 diester 16 Chapter 1 • First the Basics % Yield % Yield d. c. Calculate the number of moles of each starting material anddetermine material Calculatethenumberofmoleseach starting Theoretical 5.80g Yield yield / Third, MW yield based onthelimiting reagent calculate thetheoretical we 3. 188 . Next, we determinethelimitingreagent by examiningthestoichiometry 2. 100mL 1.706 :# d0.785g/mL MW46 mol :# 0.0379mol MW132 5g HOOC–CH Theoreticalyield ing equation: percentageDetermination of yield: weighing oftheproduct, inthiscase, 5.80g. yield theactual Determination of follows: the limitingreagent. can beaddedtotheequationas This information ratio: case, glutarate, acidleadstoonemolofdiethyl one molofglutaric a1/1 and themolarratiobetween the limitingreagent andtheproduct. Inthis acid isthelimitingreagent. be needed. The ethanolispresent inlarge excess, andthustheglutaric acid,taric therefore (0.0379mol of thereaction. Two molesofethanolare required foreachmolofglu- ing material) ing material) tao L0785 0 mL ethanol ltrcai oe g moles acid glutaric (5.80g/7.12g) (actual yield/theoretical yield) yield) (actualyield/theoretical oe mL g moles 2 CH MWproduct 2 CH == #moloflimitingreagent 0.0379mol 100 2 –COOH == 5 100% CH : # ## yield isdetermined The actual by thedirect The percentageyieldisgiven by thefollow- 132 3 CH 2CH (1/1) 81.5% gmol 1 2) 2 / –OOC–CH 3 CH 100% 0.0758molesofethanolwould 2 188g/mol OH 0379 0 . 46 2 (molproduct/mol start- CH gmol 1 / ⎯→ H mol 2 CH 2 7.12g –COOCH 706 1 . mol 2 CH 3 Basic Lab Techniques

Glassware In addition to the beakers and Erlenmeyer flasks that you used in your previous labs, organic chemists use a basic set of specialized glassware. This glassware ex- ists in different sizes. The amount of chemicals you use determines the size of the glassware you will use. Most organic chemistry lab students use a basic assembly of microscale glassware.

Why is it called microscale? The reactions are run on a much smaller scale in a Basic Lab Techniques teaching environment than in a research or industrial laboratory, where scientists are trying to make large quantities of material for commercial use. The quantities of starting material used in a teaching lab are usually on the 100–500 mg scale. The advantages of smaller-scale experiments are multifold: it is less dangerous when students are working with smaller amounts, running the lab is less expensive, less waste is generated, and it is more ecologically responsible. In research and indus- trial laboratories the size of the experiment can vary from <1 mg to several kilos.

Glassware used in organic labs has glass joints that fit together very tightly and are 17 used for efficient coupling of different pieces of glassware. You can even pull a high vacuum on an apparatus with glass joints once it is properly assembled. It is es- sential that both the male and female joints be of exactly the same size to achieve a tight fit and not break glassware. The size of a joint is defined by both the width and the length of the joint in mm, and is called Standard Taper TS (Figure 1-2). The first number refers to the diameter of the largest part of the ground joint, in millimeters, while the second number refers to the length of the ground joint. For microscale glassware, the TS is 7/10. Small-scale glassware (50–100 mL) is usually TS 14/20, while intermediate size glassware is TS 19/22 (250–500 mL). Really big glassware has really large joints, such as TS 45/50.

©Hayden-McNeil, LLC

Figure 1-2. Example of ground glass joints. The basic piece of glassware in an organic lab is the round-bottom flask. Its conve- nient shape allows for effective stirring and it can be placed under vacuum if nec- essary. A variation of the round-bottom flask is the conical vial found in many mi- croscale assemblies. Microscale glassware, used in many teaching laboratories, has an O-ring and a screw cap to simplify assembly of the small pieces of glassware. 18 Chapter 1 • First the Basics before storing. grease.amount ofstopcock Makesure you disassembletheground glassjoints (“frozen”),ing theexperiment small usingavery thejointsare tobelubricated all thisglassware withgreat care. To dur- gettingstuck prevent glassjointsfrom piecesofglasswareOther willbeintroduced techniquesare asnew discussed. Treat More aggressive beusedifneces- methodssuchasabaseoracidbathcan • used, are solvents often Organic glass- sincetheresidue remaining indirty • ofsoapsanddetergents are availableforwashing commercially Avariety • iteffectively. betoclean it will Here are options: various oftheglass.the surface clean glassware,The longer you waitto themore difficult getstuck, outandreally inacontainerdry als left orworse, theybegintoattack practice todoyour “dishwashing” away. right time, With materi- theorganictarry immediately. ifitiscleaned easily becleaned usually Glassware can Itisgood Clean Glassware available. Use extreme withanyoftheseoptions. caution acid.and sulfuric dangerous equivalentsof thelatterare commercially Less while an “acid bath” chromic isusually acid, amixture ofsodiumdichromate A bath”“base isa mixture ofKOH, somewater, andlotsofisopropyl alcohol, teaching laboratory. andtherefore caustic dangerous. Mostoftheseare very sary. These methodsare commonin research labs, usedina butare notoften through theglassware. Warning: flammable. acetoneisvery high volatility, soitiseasytoremove an used forthispurpose.solvent good, Acetone isavery with inexpensive solvent tobesolubleinanorganicsolvent.ware islikely Acetone isthemostcommon glassware. glassware. firstwhenwashingdirty can betried They Figure 1-3. Figure ©Ha©Hay Microscale connector. y den-McNeil, LLC Female glassjoint Male glassjoint O-ring Screw cap y lasttracesofacetone by blowingair Thermometers Temperature can be measured using different kinds of thermometers. • Digital thermometers are a rather novel addition to the organic lab, but are much safer than many of the other options. The temperature range of a digital thermometer is from –20 °C to 200 °C, but some thermometers can have a range up to 400 °C. The temperature range of the thermometer has to match the reaction conditions, and the temperature probe has to be resistant to the reaction conditions. For example, some probes might not be able to withstand

concentrated acid conditions. Basic Lab Techniques • Mercury thermometers were the mainstay of all laboratories for a very long time. They have a wide temperature range, up to 300 °C. Due to the fragility of these thermometers, coupled with the toxicity of mercury that is released upon breakage, many labs have minimized the use of these thermometers. In case of breakage, make sure you notify the appropriate personnel to clean up the mercury spill. • Alcohol thermometers can also be used, though they have a limited tem- perature range of up to 110 °C. They are also fragile, but the contents are 19 non-toxic.

Practical Tips • The temperature readings are only as accurate as the thermometer you use. It is good practice to occasionally calibrate a thermometer. The easiest calibra- tion method is to double-check the 0 °C reading by dipping the thermometer in an ice bath. • The thermometer can also be checked by measuring the melting point of known pure compounds. Examples are benzoic acid (mp 122.5 °C) and sali- cylic acid (mp 159 °C). • Mercury thermometers measure the temperature by measuring the expansion of the heated mercury in the thermometer; however, only the bottom part of the thermometer is subjected to this temperature, which can cause accuracy problems. Modern mercury thermometers are “corrected,” which means that the thermometer has been calibrated with part of the thermometer immersed in the liquid to be measured. If you look closely at the thermometer, you see an etched line ~7 cm from the bottom of the thermometer: this is the emer- gent stem line; the thermometer should be immersed in the liquid to this level to get an accurate temperature reading. • Some thermometers are calibrated for full immersion use, such as in heating baths. In this case there will not be an etched emergent stem line. 20 Chapter 1 • First the Basics • Place theround-bottom flaskthatyou flaskorErlenmeyer are Place going touse • Ifyou needanaccuratemeasurement, abalancethatreads atleasttothe • To weigh solids, thefollowingstepsare recommended: can beeitherliquidsorsolids.These For mostexperiments, and/orproducts materials have tobeweighed. starting Weighing Samples • Thermometers can alsohave ground Thermometers glassjoints(taperjoints), asshownin • for the experiment inasmallbeaker,for theexperiment andtakethesewithyou tothebalance. milligram (0.001g), tenthofamilligram (0.0001g), oreven are common. nearest (0.01g)isneeded. decigram Inorganiclabs, balancesaccurate tothe Figure 1-4, forusewithground glassequipment foreasyassembly. Figure 1-4. Figure

-80 -70 -60 -50 -40 -30 -20 -10 0 10 20 30 40 50 60 7080 90 100 110 120 130 ©Hayden-McNeil, LLC Different styles of thermometers. of styles Different Emergent stem line

-80 -70 -60 -50 -40 -30 -20 -10 0 10 20 30 40 50 60 7080 90 100 110 120 130 Taper glassjoint • Don’t weigh directly into the reaction flask. Instead, place on the balance pan a piece of weighing paper that has been folded once. The fold in the paper will assist you in pouring the solid into the flask without spilling. Tare the paper; that is, determine the paper’s weight or push the “zero” feature on the balance. • Use a spatula or scoopula to transfer the solid to the paper from the bottle, and weigh your solid on the paper. Don’t pour, dump, or shake a reagent from a bottle. • Weigh the solid and record the weight. Basic Lab Techniques • Transfer the solid from the paper to your flask before heading back to your bench. Having the flask in a beaker serves two purposes: it keeps the flask from toppling over, and the beaker acts as a trap for any spilled material. • It is often not necessary to weigh the exact amount specified in the experi- mental procedure. It is, however, very important to know exactly how much material you have. For example, if you obtain 1.520 g of a solid rather than the 1.500 g specified in the procedure, the actual amount weighed is recorded and the theoretical yield will be calculated using that amount. 21 To weigh liquids, the procedure is slightly different. • Weigh the empty reaction flask. • Calculate the volume of liquid needed based on the density. • Use a syringe or pipet to measure the liquid and transfer it to the reaction flask. It is essential to use a clean pipet or syringe to draw the liquid from the bottle. Don’t contaminate the bottle! Another option is to pour an approxi- mate amount of liquid into a beaker and transfer the reagent from the beaker to the reaction flask using the syringe or pipet. • Weigh the reaction flask again to determine the amount of reagent in the flask. Again, the most important thing is to know how much material you start with rather than matching the exact amount given in the procedure. The amount should be in the same range as the given procedure.

Measuring Volumes The method used to measure a volume largely depends on the accuracy needed. In the organic chemistry laboratory, some volumes are very important while others are not as crucial. An analogy is cooking spaghetti: when you cook the spaghetti, you don’t have to worry about measuring the exact amount of water used: the amount of water should be large enough so that the spaghetti doesn’t stick, but you 22 Chapter 1 • First the Basics measuring volumes. measuring volumes, accurateandconvenient. are very syringes Figure 1-5shows methodsfor cus. For more accuratemeasurements, usegraduatedpipetsorsyringes. For small has toberead theexactvolume correctly; corresponds tothebottom ofthemenis- are more usedtomeasure accurateandare ratherlargeamounts. often The volume as thevolume markers onthisglassware are notatallexact. Volumetric cylinders beusedtomeasure flasksshouldnever anaccuratevolume,Beakers orErlenmeyer long asyou are inthecorrect concentrationrange. usedinrefluxinglike theamountofsolvent (boiling)areaction mixture, donot, as someamounts have tobeexact, laboratory: in theorganicchemistry whileothers, surement ofthesaltyou add, ortheresults couldbedisastrous. The sameistrue it comestothespaghettisauce, however, tohave amore itisimportant exactmea- don’t wanttousetoomuch thenitwilltakeforever toboil. waterbecause When volumetric cylinder 20° C ml ml C

1 2 3 4 5 6 7 8 9 10

9

8

7

6

5

4 meniscus eye level 3

2

1 Figure 1-5. Figure reading 88.6mL Methods for measuring volumes. measuring Methods for 100 1100 60 70 80 80 90 90 0 0 0 0

©Hayden-McNeil, LLC graduated pipet

101 TD10IN1/10ml 20 C 9 8 7 6 5 4 3 2 1 0 0

1

2

3

4

5

6

7

8

9 syringe

10

5

10

15

20 Heating Methods Many organic reaction mixtures need to be heated in order to complete the reac- tion. In general chemistry, you might have used a Bunsen burner (open flame) for heating because you were dealing with non-flammable aqueous solutions. In an organic chemistry lab, however, you must heat non-aqueous solutions in highly flammable solvents. In general, you should never heat organic mixtures with a Bunsen burner. Many alternatives to Bunsen burners exist, such as:

• Heating mantles: These units are designed to heat round-bottom flasks of Basic Lab Techniques varying sizes. The inside is usually fabricated from a mesh material, and the heating controls are built into the unit. • Thermowells: They have a ceramic cavity designed for a specific size flask; a 250-mL thermowell is very common. The thermowell has to be connected to a rheovac, which controls the power and therefore the temperature of the flask. To adapt to smaller glassware, sand can be placed into the well. Just remember to use a minimum amount of sand, as sand is a bad conductor of heat (Figure 1-6). 23 • Hot plates with or without magnetic stirring: Hot plates can be used to heat flat-bottomed containers. NEVER heat a round-bottom flask directly on a hot plate: you are heating only one little part of the flask that way, creating a lot of stress on the glass leading to failure; the flask can break and not only do you have shattered glass, you have a shattered experiment, as well! Erlenmeyer flasks, beakers, and crystallizing dishes can be heated on hot plates. • Water baths with hot plate/stirrer: This heating method can be used if the required temperature is below 100 °C. Water baths are very convenient be- cause they are non-toxic and non-flammable, and the temperature is rather easily maintained. • Sand baths with hot plate/stirrer: This heating method can be used for high- er temperatures. Keep in mind that sand is a poor heat conductor; therefore, a minimal quantity of sand should be used. • Oil bath with hot plate/stirrer or heating coil: Different kinds of oil can be used, each with different heat stability. The more expensive silicone oils are more heat resistant. With cheaper Ucon oils, you have to keep in mind that they are flammable. • Aluminum block with hot plate/stirrer: An aluminum block is special- ized equipment often found in teaching labs that use microscale glassware (Figure 1-6). 24 Chapter 1 • First the Basics • Use caution when handling either dry iceandliquidnitrogen: eitherdry insulated whenhandling Use caution • flasksshouldbeusedforthelast two coolingmethods, Dewar these because • Liquidnitrogen isat–195.8°Cor77.3K. • icemixtures maintainatemperature iceorisopropyl alcohol/dry Acetone/dry • NaCl) reach can atemperature ice/1part Ice/salt mixtures of–20°C. (3parts • Ice/waterbathsare the simplest andare usedtomaintaintemperatures be- • Depending onthetemperature needed, different coolingmethodsare used: temperature foramuch thanasimplebeaker. longerperiod es. flasksare Dewar double-walledinsulatedcontainers, whichmaintainalow containers, beanyof various A coldbathcan dish- suchasbeakersorcrystallizing circumstances. orquickly,Cooling ofasolution mighthave tooccurslowly dependingon the inarecrystallization. alsoincreaseofcrystals Cooling solutions can theyield perature. tocontrol reaction products. temperatures mayalsobenecessary Low reactions exothermicandtherefore areSome atalowtem- highly shouldberun Cooling Methods • are a necessity when filling Dewar flasks with either dry iceorliquid nitrogen. flasks with eitherdry when fillingDewar are anecessity ice, ofdry gloves should beworn tograbablock glassesorgoggles and safety low temperatures are difficulttomaintain. of –78°C. water, asicealone isaninefficientheattransfermedium. tween 0and5°C. Finely-shaved iceis mosteffective, buthastobemixedwith Steam baths: Steam are much more convenient. equippedwithsteamlines. labswere often Older Hotplate

4 3 These have fallenintodisuse, ashotplatesandothermethods 5 2

6 1

7 0

1

0

9

8 Figure 1-6. Figure heating block Aluminum Heating methods. Thermowell

9 10 8

7

6

5

4

3

2

©Hayden-McNeil, LLC Generating a Vacuum In many instances, such as vacuum distillation or sublimation, lower pressures are necessary to run an experiment. How do we generate a vacuum? It depends how low the pressure has to be. To obtain low-pressure, vacuum conditions, one of the following methods can be used: • A water aspirator is cheap and effective, but limited by the vapor pressure of water at room temperature. Therefore, the maximum vacuum that can be obtained with a water aspirator is ~15 mmHg, depending on the temperature

of the water. Basic Lab Techniques Water aspirators connected to the city water supply have one major disad- vantage: as the water is washed down the sink, trace amounts of the solvent being evaporated are swept down the drain and into the sewage system. The use of water aspirators can lead to pollution, and in some jurisdictions, water aspirators are not allowed. Self-contained water aspirators are commercially available. These systems have their own water supply and minimize water waste. The advantage is that contaminated water is contained and can be disposed of properly as chemi- 25 cal waste. The other advantage is that the water bath can be cooled with ice, which results in a better vacuum and lower pressure (Figure 1-7). water in

connect to faucet

vacuum connection

water out ©Hayden-McNeil, LLC

Figure 1-7. A vacuum aspirator and a self-contained system. 26 Chapter 1 • First the Basics section on Recrystallization (Chapter3). section onRecrystallization For small amounts(<50mg), really useaCraigtube, in the whichisdescribed flask. The filterflaskisconnected tothevacuum source. with asmallfilterpaper. Aneoprene adapter isusedtoformthesealwithfilter product losses(Figure itminimizes cause 1-9). Itismadeofporcelain andfitted For microscale filtration (<20–300mg), aHirschfunnelismore appropriate, be- vacuum hose. source ofvacuum, likeawateraspiratororvacuumpump, withathick-walled nel andthefilterflask. The setupisconnectedtothehousevacuumoranyother stopperwithaholeisusedtoformthesealbetween thefun- adapter orarubber ithastowithstandvacuum,because itismadeofdurable, glass. thick Aneoprene funnels are made eitherofporcelain or plastic. Afilterflaskhasasidearmand, paper isusedinconjunctionwithafilterflask, asshowninFigure 1-9. Büchner amounts, filtration. anditisfasterthangravity ABüchnerfunnelwithafilter Vacuum powders filtrationisaneffective inlargeorsmall methodforfiltering slow. israther filtration fluted filterpaperresults and inalarger surface paper isplacedinthefunnel; beeitherfittedorfluted(seeFigure itcan 1-8). The tion flaskisequippedwithafunnel. anO-ring.by The funnelissupported Afilter filtrationisshowninF setup forgravity filtration. accomplished usinggravity 50mLofasolution iseasily agent from The rather granular, filtration works gravity dealwithroomLet’s temperature filtrationfirst. tobefiltered Ifthematerial is (hot filtration). atroom beperformed temperatureEither oneofthesecan orathightemperature There are two basicformsoffiltration: Filtration usingvacuum, When you installacoldtrap. must always The trapiscooled • For lower pressures, beused. vacuumpumpscan from littleme- These vary • chemical waste. chemical before theyreach thepump. The contentofthetrapshould bedisposedofas icemixture orliquidnitrogen,with eitheradry totrapunwantedvapors house vacuum. beobtainedwiththesevacuumpumps.can mighthave laboratories Some pumpstohighvacuumoilpumps.chanical Pressures ofas lowas0.01mmHg just fine. For example, removing adrying gravity filtration andvacuumfiltration. gravity igure 1-8. flaskorfiltra- AnErlenmeyer faster filtration. Overall, gravity Crease paper slightly Fold in Repeat quarters folding into sixteenths Fold in half Basic Lab Techniques

Open to Open to form form cone fluted cone

27

Erlenmeyer flask

©Hayden-McNeil, LLC

Figure 1-8. Gravity filtration. 28 Chapter 1 • First the Basics solution cools during filtration.solution coolsduring vacuum filtrationisfast, Because beusedto itcan outasthe crystallize factoristhatcompound Xwillmostprobably complicating room temperature filtration, vacuumandgravit hot, whilecompoundXisinsolution. above for Anyofthetechniques described not. Yistofilterthesolution The mostefficientwayof removing theimpurity athightemperature, issolubleinasolvent be purified Y is whilethe impurity (seeChapter3). acompoundby recrystallization purifying The compoundXto And nowlet’s discusshotfiltration. leaving thesolidbehind; it isalmostlikeareverse filtration. bulb. can alsobeusedtopipetliquidoutofasolid/liquidmixture,This filterpipet beforced pressure throughsolution can thecottonplugby usingapipet applying copper wire (Figure 1-10). ongravity,can beused This filterpipetrelying orthe a littlebitofcottonisforced ofthePasteur inthenarrow part pipetusingathin For smallervolumes even tobefiltered (<1mL), beusedinwhich afilterpipetcan thesolids.just enoughcottontoholdback glass wool, asitwillactaplugandslowdownfiltrationsignificantly. You want atthenarrowing ofthepipet. right isinserted ball Don’t usetoomuch cotton, or (Figureloss ofmaterial 1-10). The Pasteur pipetissuspendedandasmallcotton tion), Pasteur efficientandhelpminimize pipetsfittedwithcottonplugsare very To solutions microscale (<10 mLsolu- agentorothersolidsfrom remove drying fl filter flask paper at fil ter Figure 1-9. Figure ©Hayden-McNeil, LLC Büchner funnel Hot filtration is most commonly usedwhen Hot filtration ismostcommonly Vacuum filtration. y, beusedforhotfiltration. can The to vacuum flat filter Hirsch funnel paper avoid this problem. Another option is to keep the filter, and therefore the solution, warm; specialized equipment has been developed over the years to achieve this, but it can be as simple as insulating the filter with cotton wool.

Practical Tips • Use the appropriate size filter paper to exactly fit the Büchner or Hirsch funnel. • For vacuum filtration, first turn on the vacuum, then wet the filter paper with a minimum amount of solvent before pouring the solution on the filter: this

helps the paper to form a nice seal with the Büchner or Hirsch funnel. Basic Lab Techniques

Pasteur pipet with cotton plug

cotton plug 29

copper wire

Gravity pressure suction filtration applied

very small cotton plug ©Hayden-McNeil, LLC Filter pipet

Figure 1-10. Micro-filtration. 30 Chapter 1 • First the Basics significantly different from the macro- or miniscale setups. themacro- orminiscale different from significantly (Figurefor easyassembly 1-11). The microscale setupswillbediscussediftheyare compact, andtheground caps andscrew glass jointsare equippedwithO-rings arethe basicprinciples same. is The microscale glasswarevery inparticular or microscale(<1–2g)procedures, smallerversions ofthisglassware are used, but have (seeFigure ground glassjointsforeasyassembly 1-2). For (<50g) miniscale >50 gormL, “standard” glassware scale isused, andtheseglassware piecesusually oftheproceduredepend onthepurpose andalsoonthescale. For large quantities, from, ofbasic Therereaction are setupstochoose avariety andthesetups you use Basic ReactionSetup disconnect thefiltrationflaskbefore turningoffthevacuum. Always • you finishthefiltration; thevacuumonforawhileafter Leave thisway, you • Makesure thefiltrationflask. you clamp securely top- They tendtobe very • Use acoldtrapbetween avacuumpumpandthefilterflask. Ifusingawater • Use vacuumtubingforvacuum! Vacuum walls rubber thick tubinghasvery • pre-dry the crystals thankstothecontinuing airflow. thecrystals pre-dry easily.heavy andtipover very flask. aspirator, upintoyour backing filtration trapprevents waterfrom anempty collapse, andyou won’t anysuction. achieve tubing,tygon usedforcoolingwater, normally thetubingwillimmediately so thetubingwon’t collapse onitselfwhensubmittedtovacuum. Ifyou use Figure 1-11. Figure Microscale round-bottomMicroscale flask. ©Ha Screw cap Female glassjoint Male glassjoint O-ring y den-McNeil, LLC The setup for a reaction should be adapted to the specific circumstances. The size of the glassware used is determined by the size of the reaction. Will the reaction be cooled or heated? Will the reaction need protection from air? Is it moisture- sensitive? Is it oxygen-sensitive? Is the solvent volatile? Will reagents be added during the reaction? The answers to these questions will help you decide on the particular apparatus to use. We discuss a few simple setups here, which can be modified depending on the circumstances.

Reflux

Many reaction mixtures have to be heated for the reactions to proceed at a reason- Basic Lab Techniques able rate. The solvent is usually chosen so that its boiling point coincides with the ideal reaction temperature. If you heat the mixture to reflux, you are assured of a constant appropriate temperature. For example, if you want a reaction temperature of ~60 °C, tetrahydrofuran is a very appropriate solvent (bp 65 °C), but if you want slightly above 100 °C, toluene would be a great choice (bp 110 °C).

H O 2 31

H2O reflux condenser

H2O screw cap H O clamp 2

round-bottom flask with stirring bar microscale setup with Al heating block

Stirrer/Hot Plate hot plate/stirrer

4 3 0 2 1 10 5 2 1 9

6 3 power hot top

0

8

7

4

stir heat

5

6

7

©Hayden-McNeil, LLC

reflux setup with water bath

Figure 1-12. Refluxing. 32 Chapter 1 • First the Basics bubble rate ensures that no outside air can enterthereaction ensuresbubble rate setup. thatnooutsideaircan tive pressure by ismaintainedonthesystem theoilpresent inthebubbler. A slow reaction hasstarted, off withaseptum, thereflux condenseriscapped andposi- in through theClaisenheadandexhauststhrough thereflux condenser. Once the Before thereaction isstarted, thereaction gas: flaskisflushedwiththeinert itgoes viaa glass a gascylinder T joint. The third endofthe Tisconnectedtoabubbler. one endofwhichisequippedwithareflux condenser. The otherendislinkedto vent orreagent. As shown inFigure 1-13, beused, aClaisenheadcan inthiscase through thereaction results inexcessive ofany volatile evaporation material, sol- is advisabletomaintainapositive pressure. gas passingtheinert Continuously undernitrogen orargon.to berun gas, flushingthesetupwithinert After it If areaction more iseven beexposed toair, sensitive andcannot thereaction has usingalargeBunsenburner.flame-dried ofanhydrousIn case reactions, or toassembly theglassware prior isoven-dried Figure 1-13. agent,with drying withcottonplugsatbothends. examplesare shown Some in nected usingathermometeradapter. beassimpleaPasteur Itcan pipetfilled can takemanyforms: tube can have aglassjoint, it The drying can becon- orit placedontopofareflux condenser.is mostoften agent willprevent anymoisture from tube. bemaintained usingadrying ditions can Aglasstubefilledwithadrying sensitive tomoistureMany reactions oroxygen are orboth. very Anhydrous con- Controlled Atmosphere bubbleformation. point for leadtooverheating ofthesolution.can asanucleation also serve Astirbarcan glass round-bottom flaskisjusttoosmooth for effective bubbleformation, which ed, formingbubbles. edgesforthebubblestoform;The chipsalsoprovide sharp a inert. The boilingchipsare porous; liquidmigratesinsidethe pores andgetsheat- andsilicon), (compound ofcarbon carborundum are usually whichischemically solution. addtheboilingchipsbefore heating thesolution. Always Boilingchips To prevent bumping, beaddedtothe boilingchipsorstonesshouldalways andreagents. highboilingsolvent a very reaction. The reflux condenseriswater-cooled,can beair-cooledif or you are using The ofthetotal volume ofthe round-bottom flaskshouldbeatleasttwicethesize denser andthemixture isheated. The detailedsetupagaindependsonthesize. To reflux achieve (boiling), around-bottom flaskisequippedwithareflux con- contaminating thereaction. tube This drying Pasteur pipet drying tube filled with drying agent filled with drying agent

cotton plug at bottom thermometer adapter with O-ring

H2O out H2O out

H2O in H2O in Basic Lab Techniques

septum 33

adapter H2O out

glass T H2O in to gas cylinder

Claisen head

microscale reaction under ©Hayden-McNeil, LLC anhydrous conditions

Figure 1-13. Reactions run in anhydrous conditions. 34 Chapter 1 • First the Basics rate. The Claisen head rate. Claisen The accommodatesthesmallerquantitiesand syringe reflux. the isusedinsteadofanadditionfunnelbecause asyringe Inthiscase one neck. foraddition and Claisenadaptersprovide theaddedarmsnecessary theround-bottomcause flasksare sosmall, tohave more itisnotpractical than For setups, microscale (Figure thesituation isabitmore complicated 1-14). Be- mon setupisshown inFigure 1-14. stoppered,commonly ifnecessary. butcouldbeusedforotherpurposes Acom- pressure-equalizing bestoppered. tubesothatitcan The third ofthe flaskis neck oftheadditionfunnel.rate usingthestopcock hasa The additionfunneloften tion funnel. The reagent, orasolution ofthe reagent, slow can beaddedata very arm isequippedwithareflux condenser, beused foranaddi- whileanothercan For reactions, ratherlarge-scale used. commonly flaskisvery athree-neck One beusedtoaccomplishtheseadditions.(joints) orClaisenheadscan ofthereaction.the detailedsetupdependsonsize withmultiple necks Flasks rate. beaddedusingeitheranaddition funnelorasyringe. Liquidscan Again, times oneormore oftheingredients have tobeaddedataslowandcontrolled bemixedatthebeginningofareaction, allreagents can Sometimes butatother Addition ofReagentsDuringtheReaction on thecircumstances. can beeitherbelow orabove provides control oftheaddition thereflux condenser, depending addition funnel with pressure equalizer Basic Lab Techniques

reflux condenser

three-necked flask 35 20

15 drying tube

syringe 10 5

septum 20

syringe 15 Claisen head 10 5

septum

Claisen head

©Hayden-McNeil, LLC

Figure 1-14. Addition of reagents. 36 Chapter 1 • First the Basics can alleviate manyofthepollutionproblems alleviate inthelaboratory.can funnel mountedabove thereflux condenserandconnectedtoanin-housevacuum is limitedtodispensingofreagents andcollection ofwaste. Inthiscase, asmall theirreactionsis notpossibleforallstudentstorun inthosehoods; thehoods’ use environment,In ateachinglaboratory limitedand it thenumberofhoodsisoften (Figure 1-15). through aneutralizingsolution, flask bein a traporanErlenmeyer whichcan and notsentupthehood. To accomplish this, theoutgoing gasstream issent For example, areaction, ifHClisformedduring thisacidshouldbeneutralized in thehood. However, shouldnotbevented intotheatmosphere. somechemicals For reactions large-scale andinresearch laboratories, allreactions shouldbedone level,at atolerable thesereactions have tobevented inanefficientmanner. reactions result innoxiousOften fumes. To keeptheatmosphere inthelaboratory Dealing withNoxiousFumes neutralizing Figure 1-15. Figure trap with solution tubing Controlling noxious fumes. Controlling ©Hayden-McNeil, LLC inverted funnel house vacuum tubing to Solvents Solvents play several crucial roles in the organic chemistry laboratory. They are used to dilute the reagents in reactions, to control the reaction temperature (re- flux), to recrystallize compounds, and in chromatographic applications, just to name a few. It is essential to have a sound understanding of the role of the solvent, as well as of the interactions of the solvent with the reagents and solutes. The fol- lowing section aims to clarify these issues. Solvents

Melting and Dissolving What is the difference between melting and dissolving? Even though these two terms are often used interchangeably in common English, in a chemistry labo- ratory the two are fundamentally different. A candy that melts in your mouth doesn’t really melt; it actually dissolves in your saliva (water)—unless it is choco- late, of course! Melting is a phase transition a solid undergoes when heated. On a molecular level, the regular crystal structure of the solid is lost when the solid melts, but the inter- molecular distance between the molecules doesn’t really change a lot. 37 Dissolution of a solid, however, is very different. When a solid is dissolved in an appropriate solvent, the solvent molecules surround each individual molecule or ion. The same is the case when a liquid is dissolved in a solvent. The ability of a particular solvent to dissolve a particular solute depends on the intermolecular forces between the solvent and solute molecules. Melting

Heat

solid sample liquid sample (crystalline or amorphous)

Dissolving

Add solvent

solid sample dissolved sample ©Hayden-McNeil, LLC

Figure 1-16. Difference between melting and dissolving. 38 Chapter 1 • First the Basics • decreasing strengths (Figure 1-17): covalent bonds. Here are thedifferent kindsofintermolecularforces inorder of one substanceinanother. Intermolecularforces much are weaker generally than ist between moleculesinacompound, andtherefore of theyaffectthesolubility the watermolecules. Intermolecularforces are theforces ofattraction thatex- ofthehydrogen because sucrose mostly dissolves bondingbetween thesugarand forces between theNaandClanionswithdipolesofwater, cations while ferent intermolecular forces: ofion–dipoleattractive NaCl because willdissolve for tablesugar(sucrose), dif- thisisduetocompletely but onamolecularlevel of molecules. For example, forbothtablesalt(NaCl) waterisagoodsolvent and showsthatthere inasolvent aresolves interactive forces between thetwo kinds compound). aspecificsolute(thedissolved solve The factthatacompounddis- todis- ofaspecificsolvent influenceontheability hasasignificant The polarity Forces Polarity andIntermolecular A very goodexampleofhydrogen Avery bondingisH Hydrogen bondsare considered tobedipole–dipoleinteractions (seefol- • Electrostatic forces Hydrogen bonding: influencing the structure ofproteins.influencing thestructure molecules, ofbiological intheorganization important extremely in especially stronger thandipole–dipoleand/ordispersion forces. Hydrogen bondsare covalentbonds.~4–25 kJ/mol, sotheyare weaker thantypical Buttheyare an electronegative atom inanearby molecule. from Hydrogen bondsvary nakednucleus.virtually This positive charge isattractedtothelonepairsof electrons, thebondrepresents a sothesideofatom facing awayfrom lowing pages)andare quitepolar. The hydrogen atom hasnoinnercore of atom onanothermolecule). molecule orionthathasanunshared anOorN pairofelectrons (usually anattractive force electronegative experience withaneighboring H–N) can compounds andmetals. are responsible highmeltingandboilingpointsofionic fortheextremely –167.7 °C! There isno hydrogen bonding inmethane. ismethane;in size withamolecularweight of16g/mol, methaneboils at lecular weight of18g/molandaboiling pointof100°C. The alkanenearest the dramaticeffectofhydrogen bondingonboilingpoints. Water hasamo- of oxygen andonewitheachHatom. The boilingpointofwater illustrates infourhydrogenparticipate bonds, o to formanextensive hydrogen bonding network. Each watermoleculecan occurbetween chargedspecies, andanions, cations and ahydrogen atominapolarbond(e.g. H–F, H–Oor ne witheachnon-bondingelectron pair 2 O. Itisunusualinitsability CH3 Na+ Cl– Na+ Cl– CH2

Cl– Na+ Cl– Na+ O H

Na+ Cl– Na+ Cl– CH3 CH2 O Solvents H electrostatic forces in NaCl crystals CH3 CH2 O H hydrogen bonding b– in ethanol + + CH3 b O Na C I– O – CH3 b CH3 b+ b– + I– C b CO CH3 CH3 CH CH3 39 3 OC b– b+ CH b– b– 3 CH3 CH b+ + b+ 3 O Na O CH3 – + C C b OCb CH3 CH3 – CH3 O b CH3 CO b+ b– + CH3 C b CH 3 CH3 dipole–dipole forces in acetone ion–dipole forces in NaI/acetone solution

bb+ bb–

CH2 CH2

CH3 CH2 CH3

CH3 CH2 CH3

CH2 CH2 bb+ bb– London forces in pentane ©Hayden-McNeil, LLC

Figure 1-17. Intermolecular forces. 40 Chapter 1 • First the Basics • The chemi- hydrogen dissolve ofwaterallowsittoeffectively bondingability sodium iodide, aceticacid, benzene, andhexane. effective solvent. Acetone, for thesoluteandstillbean different from alsobevery can thatthesolvent clude Based onourknowledge ofthepossibleintermolecularforces, con- easily we can solubleinchloroform. is very tothesolute. ifithasasimilarstructure solvent For example, 1,3-dichlorobenzene alsooccur.situations can like” dissolves “Like iseffective impliesthat asolvent as “like dissolves The commonadage Solubility andSolventStrength • • Dipole–dipole forces: Ion–dipole forces previously. compoundswithhydrogencal bondingability, suchasthesucrose mentioned London forces: London ionic substancesinpolarsolvents, suchastablesaltinaqueous solution. to themidpointofdipole. Ion–dipoleforces insolutionsof are important dipole momentofthemolecule, thecenterofion andthedistancefrom dependsupo energy magnitude oftheinteraction end ofadipole, whileanionsare attractedtothepositive endofadipole. The molecule (awithadipole). Cations are attractedtothenegative tive regions inthemolecule. the electrons inthemolecule, positive andnega- whichgeneratestemporary non-polar covalentmoleculesexperience.from themovement of They result ofthemolecule. ofthesurface ability offorces that types These are theonly ment. area forces andthepolariz- dependentonthesurface are solely London result inatransientdipolemo- within anatomornon-polarmoleculecan interactions, butFritz (1930)suggested thatthemotion ofelectrons London forces. Non-polar moleculeswould notseemtohave anybasisforattractive the molecule. weaker thanion–dipoleforces of andincreasecally withincreasing polarity dipole–dipole forces tobesignificant. Dipole–dipoleforces are characteristi- on theothermolecule. close proximity forthe The polarmolecules must bein negative charge positive chargeononemoleculeisnearthepartial the partial tive endswhichattracteachother. Polar moleculesattractoneanotherwhen Polar covalentbondsactaslittle magnets; theyhave positive endsandnega- tones, toformdipole–dipoleattractions between have molecules. theability All molecules have the capability of generating London ofgeneratingLondon Allmoleculeshave thecapability involve aninteractionbet involve Polar covalentmolecules, suchasaldehydes andke- example, suchdisparate compoundsas dissolves like” isvalidinmanyinstances, but manyother ween achargedionandpolar n thechargeofion, the Many reactions are run in solution to bring the reactants together and to control the reaction conditions. Solvents are also used in purification and isolation tech- niques. For all these applications, it is essential to clearly understand the properties of the solvent used. A word of warning: Avoid contact with organic solvents as much as possible. Upon repeated or excessive exposure, some may be toxic or carcinogenic (cancer- causing), or both. It is also essential to remember that most organic solvents, with Solvents the exception of the chlorinated solvents, are flammable and ignite if they are exposed to an open flame or a match. The polarity is a crucial factor when a solvent has to be chosen for any application, be it as the solvent for a reaction, or for extraction, chromatography, or recrystal- lization. Table 1-2 lists the properties of many common solvents. The dielectric constant is a good measure for the polarity of the solvent. Other factors to be considered are the boiling point, melting point, and the density of the solvent. Also, is it flammable? Is it toxic? Is it inexpensive? Different compounds will have unique solubility behavior in various solvents (Fig- ure 1-18). As a rule, solubility will increase with temperature, but exceptions to 41 this rule are known: for example, the solubility of NaCl in water does not really increase with increasing temperature.

Cpd A

Cpd B Solubility (g/mL solvent) den-McNeil, LLC y ©Ha Temperature (°C)

Figure 1-18. Solubility curve. 42 Chapter 1 • First the Basics

Table 1-2. Properties of Common Solvents

Dielectric bp mp Density Solvent Constant Comments (ºC) (ºC) (g/mL) () • For very polar compounds Water H O 80 100 0 1.0 2 • Not miscible with most organic solvents

• Good recrystallization solvent for highly polar compounds

Methanol CH3OH 33 65 –98 0.81 • Crystals dry fast • Highly polar solvent for chromatography

• Very versatile solvent

Ethanol CH3CH2OH 24 78 –117 0.81 • Higher boiling than methanol • Less polar than methanol

• Very polar solvent • Dissolves almost any organic compound Acetone (CH ) CO 21 56 –95 0.79 3 2 • Highly polar solvent for chromatography • Very flammable

• Very good solvent for chromatography, extractions, and Dichloromethane recrystallization 9 40 –97 1.34 CH2Cl2 • More polar than chloroform • Not flammable

• Extremely versatile solvent Tetrahydrofuran • Medium polarity 7.6 66 –108 0.89 (CH2)4O • Reasonably chemically inert • Available in anhydrous form -hexane n Solvents lization, and chromatography recrystallization recrystallization 43 • versatile solvent for reactions, extractions, recrystal- Very • Semi-polar solvent for chromatography and recrystallization smell • Nice • Flammable • solvent for chromatography and recrystallization Versatile polarity • Medium flammable • Not • Non-polar solvent, very effective for chromatography and • low boiling and very flammable Very • in anhydrous form commercially Available polarity • Medium • Flammable • Isomer mixture of hexanes is cheaper than pure • non-polar solvent used for chromatography and Very • Flammable • Hydrocarbon mixture composed of mostly pentanes • non-polar solvent for recrystallization Very • Flammable 4 35 –116 0.71 6 775 –84 61 0.90 –63 1.49 2 110 –95 0.87 ~2 68–70 0.67 3 3 14 CH 2 3 H O 6 2 ) 2 –CH 5 CH 3 H 6 Toluene Toluene C -CO-OCH 3 (CH Diethyl ether Ethyl acetate Hexanes C Petroleum ether ~2 35–60 0.64 Chloroform CHCl CH 44 Chapter 1 • First the Basics 9. 8. 7. 6. 5. 4. 3. 2. 1. Problems forChapter1 What is the % recovery inthefollowingscenario: 1.63gof isthe%recovery student Apurifies What howtomake100mL0.01 MaqueousKI solution. Describe Calculatethefollowing: Assumingareaction between 0and100°C, isrun determinewhichphysical upthemolecular weight, Look boilingpoint, meltingpoint, of anddensity Discussthree issuesrelated totheuseofgloves inalaboratory. usingeitherbooksoron-line ofthefollowingchemicals Assessthehazards shouldshoesbeworn inalaboratory? Why fea- where andindicate thesafety classroom amapofyour laboratory Draw crude bromocyclohexane by distillation bromocyclohexane andobtains0.60gofpurecrude product. . Number ofmolesin30mL d. Volume inmLof0.01molelimonene c. Weight of0.01molepotassiumiodide b. Weight of100mLcyclohexane a. reaction. this 5willberelevant tothechemistrunning constants collectedforQuestion d. Limonene c. Potassium iodide b. a. Cyclohexane compounds: the following e. Tetrahydrofuran d. c. Toluene b. Sodium sulfate a. Methanol sources tofindthisinformation: tures are located. t n -Butyl bromide -Butyl -Butyl lithium -Butyl t -butyl bromide -butyl 13. 12. 11. 10. Consider the polarity of the following solutes (dissolved compounds)and ofthefollowingsolutes(dissolved Consider thepolarity pairs, Amongthefollowingsolvent whichlayer would would beontop?Or heatsource mightyou toreflux? usetoheatthefollowingsolvents Which For eachofthefollowingreactions, and%yield. thetheoretical yield calculate . 3-Ethylhexaneandwater f. 3-Ethylhexaneanddichloromethane e. Potassium bromide andtoluene d. 3-Pentanone acetate andethyl c. sulfateandacetone Sodium b. Acetic acidandwater a. proposed solvent: solvents, andpredict inthe whichcompoundswould have agoodsolubility Acetone andtoluene e. Water anddichloromethane d. Ethanolandchloroform c. Water andethanol b. Hexaneandwater a. they bemiscible? d. Diethyl ether c. Hexanes b. Toluene a. Methanol uptheboilingpointsfirst. Look c. b. a. Don’t forgettodeterminethelimitingreagent. ioeeH limonene .6 L1L124 mg 1L 0.162 mL .7 0.498g 0.274 g 1 mL Br Kl Br + KBr + 2 heat 0.184 mg 20 mg I + + HBr

45 Problems for Chapter 1 46 Chapter 1 • First the Basics 14. 15. H Arrange the following molecules in order of increasing polarity moleculesinorder thefollowing ofincreasing Arrange polarity Identifythemajorintermolecularforce inpure samplesofthefollowingmol- 3 ecules. Arrangeinorder ofincreasing polarity. CCH O 3 OH H 3 OCH C 3 CCH NC O OH 3