Organic Laboratory LABORATORY MANUAL - Moravian College ...

Organic Laboratory LABORATORY MANUAL - Moravian College ...

Assignment:Topic:5 I. IntroductionWeeks 9Laboratory Discussion(Tuesday, March 18)Retrosynthetic Approach to Alkene Synthesis: FGI dehydrationCGWW: pp. 482-484 & 487-490Lab Manual: Part V C sec. C. 1. Alkene Synthesis by Dehydration of Alcohols(pp. C5-6)Retrosynthetic Approach to Alkene Synthesis: FGI DehydrationLaboratory Periods(W-Th, March 19-20)Activity: Optional Open Lab for Final Data Analysis – No Lab Friday – Easter BreakExperiment 3: What Role Does Solvent Play in Nucleophilic Aliphatic SubstitutionReactions? (See Website)Assignment: Experiment 3: No PrelabAssignment:Topic:Week 10Laboratory Discussion(Tuesday, March 25)Lab Manual:Part V C sec. D. Oxidation of Alcohols to Ketones (pp. C7-C8)Lehman: Oper. 24 (pp. 126-127)Retrosynthetic “FGI oxidation” for Synthesis of KetonesLaboratory Periods(W-F, March 26-28)Activity: Experiment 4: How can a Complex Alkene be Synthesized?A multi-step synthesis of 2-methylheptenes. (See Website)Assignment: Experiment 4:Due: Report on Experiment 3Assignment:Topic:Lab Manual:Activity A - Prelab. 1 (See Website)Week 11Laboratory Discussion(Tuesday, April 1)Part V C sec. A->D. Retrosynthetic Analysis (pp. C1-C8)Alcohol SynthesisandMultiple Disconnections in Organic SynthesesLaboratory Periods(W-F April 2-4)Activity: Experiment 4: How can a Complex Alkene be Synthesized?A multi-step synthesis of 2-methylheptenes. (48-60)Assignment: Experiment 4:Activity A - Prelab. 2 (See Website)

I. Introduction 6Topic:Week 12Laboratory Discussion(Tuesday, April 8)No Lab DiscussionLaboratory Periods(W-F April 9-11)Activity: Experiment 4: How can a Complex Alkene be Synthesized?A multi-step synthesis of 2-methylheptenes. (See Website)Assignment: Exploration 4Topic:Assignment:Activity:Assignment:Topic:Lehman:Manual:Activity B - Prelab. (See Website)Week 13Laboratory Discussion(Tuesday, April 15)Alcohol SynthesisandMultiple Disconnections in Organic Synthesespp. 244-249 (Grignard Reaction)Part V C sec. A->D. Retrosynthetic Analysis (pp. C1-C9)Laboratory Periods(W-F April 16-18)Experiment 4:How can a Complex Alkene be Synthesized?A multi-step synthesis of 2-methylheptenes. (See Website)Week 14Laboratory Discussion(Tuesday, April 22)Current Class Group ActivityGeneral Class DiscussionLaboratory Periods(W-F April 23-25)Activity: Experiment 4:How can a Complex Alkene be Synthesized?A multi-step synthesis of 2-methylheptenes. (See Website)& Check OutAssignment: Complete Experiment 4: Activity B (See Website)Due:Lab report for Experiment 4 (See Website).Due by 5:00 PM on the day after your last lab period.Lab notebook & data binder (with all notebook checklists, data and returnedlab reports behind appropriate tabs) Due at the Final Exam

7 I. IntroductionPhilosophy(See also Lehman pp. 1-9)The laboratory part of Chemistry 211-212 is divided into two parts with different emphases.First semester, Chemistry 211 laboratory was an exploratory introduction to several major standardtechniques used by organic chemists. Second semester, Chemistry 212 laboratory utilizes thesetechniques and a few new ones to study organic isomerism, synthesize organic molecules andinvestigate both the outcomes and mechanisms of their reactions.This semester you will be exploring more complex problems than you did in CH 211, soagain, IT IS ABSOLUTELY ESSENTIAL THAT YOU PREPARE FOR EACH EXPERIMENTAHEAD OF TIME. Without a general understanding of the overall goals of each Experiment, anda plan for carrying out the procedure, you will have great difficulty in successfully completing thework presented to you.Administrative Details.Required Materials; (Same as for CHEM 211L)Lab Text: The Student’s Lab Companion, by John W. Lehman, Pearson Prentice Hall2004 (Lehman)Lab Notebook: must have a hard cover and be permanently bound (not spiral), must also fit inthe inside pocket of your data binder.Data Binder: A 1.5-inch three-ring loose-leaf binder with a hard cover and at least 9 tabdividers and an inside pocket that will accommodate your lab notebook.Grades:In general, satisfactory preparation for each lab period, completion of all work, laboratory notebookrecords and laboratory reports including answers to all prelab and postlab questions will earn a gradeof B for the lab. Higher grades will be given for demonstration of excellent understanding of theconcepts, preparation for the lab periods, performance in the lab, well organized and thorough labrecords and well-written lab reports.Your grade for the laboratory portion of the course will be calculated as indicated below:• 30% The quality and completeness of the laboratory notebook and data binder• 30% The quality and completeness of the laboratory reports• 20% Preparation for each laboratory period (Includes quality and completeness of the written prelabassignments, contributions to pre-lab discussions and initial awareness of experimentrequirements.)• 10% Attendance in the Tuesday discussion and laboratory periods• 10% Evidence of increasing skill and initiative in the laboratoryAttendanceStudents are required to attend all laboratory discussions (Tues. 9:10-10:00) and all scheduledlaboratory periods (See the Weekly Schedule on pp. 2-6) unless excused due to a valid medical excuse(verified by a physician, the Health Center or Dean of Students' office) or other accepted prior excuse. Makeupsor grade adjustments for excused absences will be arranged. Grades for work missed due tounexcused absences will be zero.Note: Neither trips scheduled for other courses nor travel schedules for weekends orbreaks are NOT acceptable excuses for missing lab discussions or lab periods.

I. Introduction 8Lab RecordsNotebookAs in CHEM 211L, all notebooks must be permanently bound hard cover record books not spiralbound books. Your records should be permanent; so all entries must be made in non-erasable ink.You may continue with the same notebook used in CHEM 211L, but you must be sure the laboratorysection designations on the front and bottom page edges are correct for this semester. Whether youuse your CHEM 211L notebook or not, you should have the material from CHEM 211L available forinformation on lab techniques.Data BindersAgain this semester, your data binder will provide you with a convenient place to keep the spectra,chromatographs and other sheets of data generated by your lab work. If it has sufficient space, youmay continue to use the your binder from CHEM 211L. Just add additional tabs for this semester'sExperiments. Whether you use your CHEM 211L binder or not, you should have the material fromCHEM 211L available for information on lab techniques.Laboratory ReportsOnce your laboratory work on each experiment is complete you will summarize and interpret yourresults in a formal laboratory report, which you will prepare using a word processing program. TheWeekly Schedule (pp. 2-6) lists specific due dates for your laboratory reports. The format for labreports is provided in Part II - E (pp. 19-20) and specific instructions for each report are provided ineach Experiment.

9PART II: Laboratory Rules and RegulationsWeekly Laboratory RoutineBecause of the increased complexity of this semester’s experiments, it is more essential than it waslast semester that you prepare for each experiment ahead of time. You have a limited amount oftime in the laboratory each week to collect data, so you need to be ready to work when you arrive.The lab is designed to begin at 12:45 PM and end at 3:45 PM. You are expected to be able tocomplete your assigned work in that time period. Only with a general understanding of theconcepts and techniques to be applied to a given problem will you be able to reach the goals of eachexperiment in the time provided. Again to help you prepare, there will be assigned backgroundreading to assist you in responding to the QOD for each experiment, an electronic pre-labassignment and a laboratory discussion on Tuesday mornings (See the CHEM 211L weekly schedulepp. 2-6). All of the assigned reading is to be done and the electronic pre-lab assignmentsubmitted by e-mail before 5:00 PM on Monday of the week the experiment begins. Then bringany questions to the Tuesday discussion so that we can solve problems before they arise. At the endof each lab period your laboratory notebook will be collected, it will be checked by your instructorand returned to you by the following morning. This check is designed to give you assistance inkeeping appropriate laboratory records.The listing of laboratory report due-dates in the laboratory schedule (See pp. 2-6) should provide youwith sufficient notice to complete required work, so the deadlines for laboratory reports are firm.Since you are now familiar with the major techniques, you should be able to work efficiently so thatyou should be able to keep several different procedures going at once. You have experience withrecognizing when your data are good enough to support conclusions and when you need to repeat aprocedure that did not yield data that are good enough to fulfill your needs. As you should havefound last semester, it is more efficient to work with care and produce good results than to rushthrough a procedure just to get it finished. Remember, the purpose of each experiment is to answer aspecific question. Be sure to ask for help if things seem confusing. You are here to learn; we do notexpect you to be able to do everything perfectly at once. Enjoy yourself as you learn.Safety RegulationsLaboratory Neatness.Neatness is essential for safety and for efficient work in the laboratory.• Keep the lab uncluttered by leaving book bags and all non-essential books in the front of thelaboratory. Outer-clothing should be hung on the pegs in the hall or the front or back of thelaboratory.• If you spill anything anywhere in the laboratory, clean it up immediately and leave a clean spacefor your neighbors. This applies particularly to the balances and melting point apparatuses.• If problems arise, then each week specific students will be given responsibility for seeing thatcertain areas are clean and orderly at the end of the period. Please cooperate.• If you spill acids, bases or other corrosive chemicals, inform the instructor and washcontaminated surfaces with copious amounts of water, and then neutralize as directed by theinstructor.• For reasons of safety and obtaining dependable results, all glassware must be thoroughly clean.After disposing of contents responsibly (see waste disposal instructions for each exploration), washglassware with hot soapy water and a test tube brush. In some cases, organic compounds aremost effectively removed by an acetone pre-rinse followed by a soap and water wash.Use of Reagents.• Most of the reagents used in this laboratory are irritants and/or toxic. Be careful handlingreagents. Gloves are available should you wish to use them, but remember that gloves do notgive you 100% protection from all lab reagents. If reagents come in contact with your skin orgloves, wash them off immediately with soap and water. It is also a good practice to wash yourhands periodically to remove any material that may have been left on your hands by incidentalcontact. Finally, be sure to wash your hands with soap and hot water before leaving thelaboratory.• Use reagent bottles only in the areas where they are provided. Solid reagents for this course willbe set out on benches at the side of the laboratory near the balances, and occasionally under thehood. Volatile or corrosive liquid reagents will be under the hood.• Try to take no more of the reagents than you need.

II Laboratory Rules and Regulations 10• If by accident you take an excess amount of a reagent, share it with a fellow student or dispose ofthe excess as instructed (see Table 1 below). Never pour anything back into a reagent bottle.• Always dispose of chemicals properly.In general, organic wastes are divided into two classes: "halogenated", compounds containingone or more atoms of F, Cl, Br, or I; and "non-halogenated", compounds containing no halogenatoms. For each exploration all reagents will be assigned to waste disposal categories.For disposal purposes we have five categories of chemical wastes:Table 1Laboratory Waste Disposal CategoriesCategory Compound Type Disposal1 Non-halogenated organic solids Labeled waste containers in waste hood2 Halogenated organic solids Labeled waste containers in waste hood3 Water-insoluble - halogenated organic liquids Labeled waste containers in waste hood4 Water-insoluble non-halogenated organic liquids Labeled waste containers in waste hood5 Acidic or Basic aqueous solutions Labeled waste containers in waste hood6 Water-soluble non-halogenated organic liquids Down drains with a flow of cold water7 Inorganic solids Varies with compoundAs indicated in Table 1, compounds in categories 1-5 go into appropriately labeled wastecontainers in the waste hood at the back of the lab while category 6 compounds go down labdrains with a flow of cold water. Category 7 disposal varies with compound and is specified ineach exploration.Use, Care and Replacement of Laboratory Equipment.• Keep all metal apparatus in a dry place. Water tends to rust equipment and cause drawers toswell so that they become difficult to open. Consequently, if you spill water in a drawer,immediately take time to dry it carefully.• At the end of each lab day equipment that is left around the lab will be placed in a bin at the backof the lab where it will be available for any student in the course. If you lose or break a piece ofequipment check the bin for a replacement. If none is available, ask your lab assistant for areplacement. There is no charge for replacement of broken equipment; however, materials usedin this laboratory are expensive so try to be careful. Also, excessive loss or breakage can be anindication of poor organization, technique or lack of preparation and can adversely affect yourlab grade.LabelingAll samples that are stored in your tote tray or turned in to your instructor must be labeledaccording to the following format:Name of SubstanceLab Notebook pageDateStudent NameLab Section DayPost-lab RoutineAt the end of each lab period:• Wipe off your personal bench-top area.• Clear any debris from your sink.• Check that the common drawer and sink items are in place (see equipment lists on the next page).• Wash your hands.• Submit your laboratory notebook to you instructor. It will be checked and left on the shelfoutside Dan Libby’s office for you to pick up.

11 II Laboratory Rules and RegulationsEQUIPMENT LISTPersonal Tote Tray Contents5 Beakers, 100, 250, 400, 600, 1000 ml1 Büchner or Hirsh funnel w/ rubber adapter1 Conical funnel5 Droppers8 Erlenmeyer flasks, 50, 3x125, 2x250, 2x500 ml1 Filter flask, 500 ml2 Graduated cylinders: 10, 50 ml1 Powder funnel1 Ruler, 6 in.1 Scupula1 Separatory 250 ml funnel w/ stopper & stopcock1 Spatula1 Stemless funnel1 Stirring rod1 Test tube clamp1 Test tube rack1 Test tube block10 Test tubes, 10x75 mm6 Test tubes, 13x100 mm6 Test tubes, 15x150 mm2 Test tubes, 25x175 mm3 Vials, w/ caps2 Watch glassesGoggles ($5 replacement fee if lost)Common Drawer Equipment3 Ring stands (bench top)1 Current regulator1 Heating well1 Iron ring1 Jar, glass w/ screw top1 Magnetic stirrer1 Mortar and pestle1 pH paper vial4 Rubber tubings, including 1 w/ thick wall1 Tongs4 Utility clamps w/ fasteners2 Wood blocks &/or cork rings1 Wire gauze1 Thermometer, -10 -> 250 oSink Area Equipment2 Cleaning brushes (large and small)1 H 2 O Wash bottle1 Soap Wash bottle1 Acetone Wash bottle, (shared with other sink)2 Water baths1 Roll of labeling tapeSee Lehman pp. 276, 279 for pictures of most of the equipment on this list.

II Laboratory Rules and Regulations 12Collaboration and Academic HonestyCollaboration among students in the laboratory and on analysis of data is generally encouragedand required for some Experiments. However, the final version of all written work (pre-labassignments and quizzes, and laboratory reports) submitted for evaluation must be individuallyprepared in your own words after consultation with other students. To be fair to all students inthe course and to assure maximum learning for each student, we follow all the guidelines foracademic honesty spelled out in the Moravian College Student Handbook 2005-2006 (pages 54-59). Particularly relevant passages are excerpted on the following page.Academic Honesty at Moravian CollegeAcademic integrity is the foundation on which learning at Moravian College isbuilt. Moravian College expects its students to perform their academic work honestlyand fairly. In addition, a Moravian student should neither hinder nor unfairly assistthe efforts of other students to complete their work successfully. The College'sexpectations and the consequences of failure to meet those expectations are outlinedbelow.In an academic community, students are encouraged to help one another learn. Infact, because no two students learn in exactly the same way or take exactly the samethings away from a lecture, the College encourages students to study together. Theboundaries on what is or is not acceptable work may not always be clear; thus, if atany point in academic work at Moravian the student is uncertain about his or herresponsibility as a scholar or about the propriety of a particular action, the instructorshould be consulted. The list below is not to be considered complete but rathercovers the most common areas of concern. In general, students should be guided bythe following principles.PlagiarismA major form of academic dishonesty is plagiarism, which the College defines asthe use, whether deliberate or not, of any outside source without properacknowledgement. While the work of others often constitutes a necessary resourcefor academic research, such work must be properly used and credited to the originalauthor. This principle applies to professional scholars as well as to students. An"outside source" is any work (published or unpublished) composed, written, orcreated by any person other than the student who submitted the work. . . . All workthat students submit or present as part of course assignments or requirements must betheir original work unless otherwise expressly permitted by the instructor. . . . Whenstudents use the specific thoughts, ideas, writings, or expressions of others, they mustaccompany each instance of use with some form of attribution to the source. Directquotes from any source (including the Internet) must be placed in quotation marks(or otherwise marked appropriately) and accompanied by proper citation, followingthe preferred bibliographic conventions of the department or instructor. . . . Studentignorance of bibliographic convention and citation procedures is not a valid excusefor having committed plagiarism. . . . A student may not present oral or writtenreports written by others as his or her own work. . . . You may not use writings orresearch obtained from any other student previously or currently enrolled atMoravian or elsewhere or from the files of any student organization (such asfraternity or sorority files) unless expressly permitted to do so by the instructor. . . .Students must keep all notes, drafts, and materials used in preparing assignmentsuntil a final course grade is given. . . . All such materials must be available forinspection by the instructor at any time.CheatingStudents may not submit homework, computer solutions, lab reports or any othercoursework prepared by, copied from, or dictated by others. If the student isemploying the services of a tutor (whether from the College community orelsewhere), the tutor may not prepare the student's work for class. . . .

False Testimony13 II Laboratory Rules and RegulationsStudents may not submit or present a falsified excuse for an absence from anexamination test, quiz, or other course requirement either directly or through anothersource.Students may not falsify laboratory results, research data, or results. They may notinvent bibliographical entries for research papers, websites, or handouts. They maynot falsify information about the date of submission for any coursework.

14Part III Laboratory Record & Report FormatNotebookGeneral Format and ProceduresOn the front cover and bottom outside page edges of your notebook, write your name and laboratoryday.Number all of the pages (both left- and right-hand) at the top of the page.Reserve the first four numbered pages of each book for the table of contents. As the semesterproceeds, enter the title of each experiment and designation of each activity (Part A, Part B, etc.)into your table of contents, along with the pages on which they are recorded. Note that the titles ofexperiments are required. The experiment and part designations are not sufficient.Dating Records:• As you work, insert the date at the top of each page used to record results obtained in thelaboratory.• At the end of each laboratory period date and initial your last data entry in each activitywith newly recorded data.• If you must insert data on an already dated page, initial and date the insertion.Laboratory Notebook RecordsDiagrams and descriptions are given below to illustrate where information must be entered into yourlaboratory notebook. Some experiments may not require all possible sections (See individual experimentdescriptions). In those cases, simply omit unnecessary parts, but keep the others in the order andposition (left- or right-hand page) as indicated below.First Set of Pages of an Experiment (Always starts on a clear set of left- and right-hand pages):Left-hand PageRight-hand Pagep. # p. #Title of the ExperimentName of Groupmate(s)Notes (Continued)Question of the DayPre-lab Discussion NotesContinue on the right-hand pageAlways go to next pair of clear facing pagesto start your Table of Compounds andWaste Disposal Instructions.Title of the ExperimentEach new experiment or part should always begin on a clean pair of facing left- and righthandpages. The title of the experiment should be at the top of the left-hand page. If anexperiment has more than one part (As with Experiment 1), the work for each part should bereported separately with the titles of both the experiment and the part at the beginning of eachnew part. Experiment numbers are not sufficient.Names of Partners or Groupmates:When you will be working with labmates, enter their full names below the title of theexperiment or activity.Question of the Day (QOD)Each experiment will start with a question that will be explored in the pre-lab discussion.The QOD will often be the title of the experiment.Pre-lab Discussion NotesYour notes from the pre-lab discussion are to be recorded on this first set of pages for theexperiment.

15 III. Laboratory Record & Report FormatSecond Set of Pages of an Experiment (always starts on next clear set of left- and right-hand pages):Left-hand PageRight-hand Pagep. # p. #Table of Compoundsmp bp densityWaste Disposal InstructionsChemical EquationsAlways go to next pair of clear facing pagesto start Procedures and Results pages.Table of Compounds:This is a list of names as well as important physical (mp or bp, density, solubility in acid, base andcommon organic compounds) and chemical properties (acidity, basicity or flammability) of the compoundsused in the experiment. When required for an experiment, this table should be located on theleft-hand page immediately following your pre-lab discussion notes. Unless otherwise directed,never put the Table of Compounds in your data binder; it must be in your notebook.Waste Disposal Instructions:Most of the compounds that you will encounter in this course are irritants or toxic. To avoidpolluting you, your classmates, and our environment, we must be careful to dispose of chemicalwaste properly. Thus, each experiment will provide instructions for disposal of excess reagents.These instructions should be written in your notebook, at the top of the right-hand page oppositethe table of compounds. Follow these instructions carefully.Chemical Equations:When experiments involve chemical reactions, chemical equations for the reactions should bewritten using structural formulas of the organic compounds. Equations should be on theright-hand page below the waste disposal instructions.Third Set of Pages of an Experiment (always starts on next clear set of left- and right-hand pages):Left-hand PageRight-hand Pagep. # date p. #Step #'s must be opposite correspondingprocedure steps.Procedure1. Obtain 2.2 g between steps2. Add A to 25 mL 2 M HCl.Results1. 2.351 g Aspace between steps2. White gas and fine pink ppt.form3. Etc.4.5.3. Etc.4.5.↓ Continues to the next left-hand page.↓ Continues to the next right-hand page.

III. Laboratory Record & Report Format 16Procedure (Always starts on next clear set of left- and right-hand pages):• Procedure consists of sequentially numbered steps (1, 2, 3, etc.) to be carried out in thelaboratory. These steps should represent your understanding of the procedure you followed incollecting your data. The steps should be separated by at least one line to allow for anymodifications that might be necessary as you work in the laboratory. Steps need not be writtenin complete sentences, but should be concise, complete and clear enough that someone elsecould repeat your work. This section should be organized to facilitate your work in the lab.Procedure should be written after the pre-lab discussion and before you start work in thelaboratory.NOTE: When using a procedure for the first time (e.g. distillation), include the completeprocedure in your notebook, including diagrams of apparatus. When yourepeat the same procedure in a later experiment, include a reference (withexperiment and notebook page number) to the original time you used the procedure.• Begin the Procedure at the top of the next available left-hand page after the Waste DisposalInstructions or Chemical Equations.Results (always starts on the right-hand page opposite the beginning of the Procedure):• Consist of observations that may be used as indications that an experiment is proceedingproperly or data collected as the result of a procedural step. Observations such as color changes,pH, evolution of gas and/or heat, violent reactions, dissolution of a solid, etc. and data such aswts., volumes, mp's, bp's, etc. should be recorded in your notebook Results section as the workproceeds.• Each entry in your Results section should be directly opposite the procedure step to which itrefers and be designated with the number of that step. (As illustrated in the diagram above) When datacannot be conveniently attached to the results section, it should be kept in the appropriate sectionof your data binder and a note to "see data binder - Experiment #" should be included at theappropriate position in your results section. (See the Data Binder section below).Data BinderGeneral DescriptionYour data binder needs to be a 1.5-inch, 3-ring, loose-leaf notebook binder with your name on thespine and front cover (lab label tape works for this). It must have a pocket sufficient toaccommodate your lab notebook on the inside of its front cover and contain at least 6 tab dividersthat separate the sections described below. Your data binder will be used to store data (e.g. thinlayerchromatography plates, infrared, mass and NMR spectra, etc.) that don't fit conveniently intoyour notebook. Also place returned lab reports in their appropriate section.Sections (Tab Dividers)• Lab Manual (Place 1 st tab after this.)• Weekly Post-lab Notebook Checklists: All checklists are to be kept in chronological order inthis section.• Experiment 1• Experiment 2• Experiment 3• Experiment 4Organization of SectionsEach section should be labeled as indicated above. Materials to be included in each section musthave 3-holes that match the rings of the binder or be permanently attached to a sheet that has theappropriate holes. Specific suggestions for certain types of items to be stored in the Experimentsections are:• The CHEM 212 Experiment sheets describing the experiment• Flow Diagram (see Appendix A, pp. A-1 – A2): Some laboratory procedures profit from beingpresented in a diagram that outlines the procedure followed. When such a “flow diagram” isappropriate, it should be prepared in the process of devising the procedure and included in theappropriate experiment section.

17 III. Laboratory Record & Report Format• Spectra collected from the experiment: They will be produced on punched paper or paper thatcan be punched.• Thin-layer plates produced in the experiment: Must be taped or stapled to 8.5 X 11 inchpunched paper, which will fit your data binder. Three-hole paper is available in the laboratory.Labeling and Cross Referencing Data:Each piece of data placed in your binder must be labeled with your name and a description of thedata and a reference to the page of your notebook and number of the procedure step thatproduced the item. Descriptions must be sufficient to identify the data without reference to thenotebook. (e.g. " A. B. Smith notebook page 36, step 4.-IR spectrum of Unknown X ")A. B. Smith notebook page 36, step 4.IR spectrum of Unknown XFREQUENCY (CM -1 )4000 3600 3200 2800 2400 2000 1800 1600 1400 1200 1000 800 600 40080Transmittance (%)OHCHAliphaticC604020OCO0In addition, your notebook results section should have an entry to indicate that the data from aprocedure step is in your data binder. (e.g. For the spectrum shown above, write next to step 4 onp. 37 of your notebook, which is a Results page, "Spectrum of X can be found in Experiment 3 ofmy data binder."36January. 28, 200837January. 28, 2008Procedure4. Obtain 2.2 g A . .5. Add A to 25 mL 2 M HCl.6. Etc.7. Obtain IR spectrum of XResults3. 2.351 g A4. White gas and fine pink ppt. form5. Etc.6. Spectrum of X can be found inExperiment 3 of my data binder.

III. Laboratory Record & Report Format 18Laboratory ReportGeneral DescriptionAfter completing all activities in an experiment you will compile your data and, when appropriate,those of your laboratory research group members, consider data from the whole class and write areport on your findings. Your analyses will usually be assisted by in-lab and post-lab questionsdistributed for most experiments. Each report will have it own specific issues that must be addressedand questions to answer as part of your report; however, all reports will follow the same generalformat that is outlined below.Required General FormatFonts and SpacingAll reports are to be produced with word processing software using the following parameters:Font:12 pointText Color: BlackMargins: 1 Inch (left, right, top & bottom)Spacing: Double SpaceHeaders on all pages except the title page including: your name, page numbers andExperiment # in this form:James Johnson 3 Experiment 4Required Sections:Title Page:Include the your lab day, your nameand the date the report is submitted.These items should be in a verticallist that is centered near the top of thepage. The title of the experiment iscentered both vertically andhorizontally on the page. Inexperiments involving researchgroups, groupmates’ names arecentered at the bottom of the page.(See the Figure 1 to the right.Figure 1: Title page TemplateCHEM 211L Tuesday- Section AJames JohnsonSeptember 4, 2007Experiment 1:How Can We Tell the DifferenceBetween Stereoisomers and Why is itImportant for NSAID Drugs?Groupmates:Cheryl Jackson, James Goodsalland Mary Wri ghtThe Question of the Day:In this section, state The Question of the Day and then provide a brief (100 words or less)description of the experimental plan that was developed to answer to it. There should also besome discussion of how the experimental plan was developed during the pre-lab discussion.

20Part IV. ExperimentsThe titles of the experiments to be used in CHEM 212L for the Spring Term of 2008 are listedbelow. The experiments themselves will be distributed at appropriate times throughout thesemester and posted on the course website.Experiment 1 How Can We Tell the Difference Between Stereoisomers and Why isit Important for NSAID Drugs?A. How can we isolate the drugs?B. How can we characterize their stereoisomers?C. How can stereoisomers be separated?Experiment 2 Do both Acid and Base Catalysis Work Equally Well in AcylSubstitution Reactions?Experiment 3 What Role Does Solvent Play in Nucleophilic Substitution Reactionsa Saturated Carbon?Experiment 4 How Can a Complex Alkene be Synthesized?A. How can a Grignard reaction be successfully accomplished?B. What is the Outcome of the Dehydration of an Alcohol?

A1Part IV: Techniques and TheoryA. Extraction (See also, Lehman pp. 70-77 and pp. 116-121)Sample Extraction Procedure for Separation of a Mixture of an Acid, a Base and a NeutralCompound by Chemically Active ExtractionThis procedure is designed to separate a ternary mixture of organic compounds using acid and baseextractions. This example is provided to give you some guidance for both acidic and basicextraction procedures.Procedure:Be sure to record all pH measurements, all weights, mp's and R f values of isolated products inyour Results Section. Be sure compounds are dry before weighing or taking m.p.'s.1. Dissolution of Sample.Weigh out, to the nearest thousandth of a gram, approximately 2 g of the mixture. Dissolvethe mixture in ~50 mL of dichloromethane (CH 2 Cl 2 ). If any solid doesn't dissolve, add anadditional 25 mL of CH 2 Cl 2 . If undissolved solid still remains, filter (by gravity) the solutiondirectly into a separatory funnel. Otherwise, pour the solution into the separatory funnel.2. Acid Extraction.Extract the CH 2 Cl 2 solution two times with 25 mL aliquots of 1.0 M HCl. Combine theaqueous layers from both extractions in a labeled 250 ml beaker and test the pH of theaqueous solution. It should be as acidic as the original 1.0 M HCl solution. If it is not,extract the CH 2 Cl 2 solution again with 25 mL of 1.0 M HCl.3. Basic Extraction.Extract the CH 2 Cl 2 solution resulting from step 2, two times with 25 mL aliquots of 1.0 MNaOH. Combine the aqueous layers in a labeled 250 mL beaker and test the pH of theaqueous solution. It should be as basic as the original 1.0 M NaOH solution. If it is not,extract the CH 2 Cl 2 solution again with 25 mL of 1.0 M NaOH.4. Recovery of the Compounds.CH 2 Cl 2 solution:Dry the CH 2 Cl 2 solution resulting from step (3.) with anhydrous Na 2 SO 4 . Let thismixture stand for about 5 min., swirling it frequently. Remove the drying agent bygravity filtering the solution into a 125 ml Erlenmeyer flask, add a boiling stone andevaporate the solvent in a hot water bath in a hood. Transfer the residue to a watch glassand allow it to dry.Acid Extracts:While the CH 2 Cl 2 is evaporating, cool the acid solution from step (2.) in an ice bath andthen make the solution basic by slowly adding 6 N NaOH until the solution tests stronglybasic with pH paper. A precipitate should form during the addition of NaOH. Collect thesolid by vacuum filtration and wash the solid on the filter with cold water. Transfer thecompound to a large filter paper and allow it to dry.Base Extracts:Cool the basic solution from step (3.) in an ice bath and then make the solution acidic byslowly adding 6 M HCl and stirring until it tests strongly acidic with pH paper. Collectthe precipitated solid by vacuum filtration and wash the solid on the filter with coldwater. Transfer the compound to a large filter paper and allow it to dry (see section [d.],below).

V A. StereoisomersDrying Procedures:The compound recovered from the CH 2 Cl 2 solution should be crushed to small particlesize and allowed to dry for a total of about 1 hour. It will dry quickly since it wasisolated from a low-boiling solvent.The compounds recovered from the acid and base extracts should be allowed to air dry inyour desk until the next period. These compounds were isolated from water and waterevaporates slowly from these polar compounds.5. Sample Characterization and Submission:Determine the mass of the compound recovered from the CH 2 Cl 2 solution. Verify theidentity of the recovered compound by TLC analysis vs. authentic samples of the originalcomponents using an appropriate developing solvent system. Finally, determine the mp ofeach recovered compound side-by-side with an authentic sample of the compound. Recordyour data in your Results Section, place your sample in an appropriately labeled vial (See LabManual Part II. p. 15), and seal it tightly. Submit your sample according to your instructor’sdirections.Next Lab Period:After the compounds you recovered from the aqueous solutions have had sufficient time todry completely, determine their masses and verify their identity by mp and TLC analysis vs.authentic samples, label, and submit the samples as with that recovered from CH 2 Cl 2 .Sample Flow DiagramFlow Diagram for Separation of the Mixture of an Acid, a Base and a Neutral Compounddescribed in the procedure on B-1. (See also, Lehman pp. 289-290)AbbreviationsA-H = acid N = neutral compoundB: = base DCM = dichloromethaneprecipitateB:-vacuum filter-wash w/ cold water-air dryB:A-HA-HOriginal Organic PhaseA-H, B:, N, DCMExtract w/ 1M HClaqueousorganic+A-H, NB-HDCM+ -H 3 O , ClH 2 O (trace)-coolExtract w/ 1M NaOH-basic w/ 6M NaOHorganicaqueousaqueousN- +DCMH 2 O , Na+ A , Na-H 2 O (trace)- - H 2 O , OHCl , OH-cool-acidic w/ 6N HClprecipitateA2-vacuum filter-wash w/ cold water-air dryaqueous+H 2 O , H 3 O- +Cl , Na-dry w/anhy. Na 2 SO 4organicsolidDCMN Na 2 SO 4 . H 2 Oevaporate solventN

V B. StereoisomersD. Explorations:HHOOHCOCH 3R-ConfigurationO O HCHCH 3O HS-ConfigurationB2HOOOHglyceraldehydeOHOOHOH4 carbonsFigure 3: Lactic Acid Configurational Isomers Figure 4: 3 & 4 Carbon Carbohydrates1. Recognizing Chiral Atomsa. Lactic Acid (See Eq. 1) has one chiral atom illustrated in Figure 4 with wedges and dashwedges.Thus it has two possible configurational isomers. Note that the three carboncarbohydrate in Figure 4, glyceraldehyde, also has one chiral carbon atom and can existas two configurational isomers. Put a checkmark (√) on the chiral atom in theglyceraldehyde structure in Figure 4 and draw wedge dash-wedge structures of its twoconfigurational isomers.b. The four carbon carbohydrate in Figure 4 also has configurational isomers. How manychiral carbon atoms does the four carbon carbohydrate have? Indicate each chiral carbonatom with a checkmark (√).c. How many configurational isomers are possible for the four carbon carbohydratestructure in Figure 4? Explain your reasoning. Draw wedge dash-wedge structures forall of the configurational isomers of the four carbon carbohydrate.

2. Drawing Fischer Projections: See also CGWW p. 395.As you may have noted in devising structures in 1., when a structure can have multiplestereoisomers, representing them on paper can be cumbersome. Fischer Projections arerelatively simple two-dimensional representations of three-dimensional structures and areparticularly useful for representing the configurations of atoms in molecules with multiplechiral atoms.Fischer Projections require that the molecule be oriented in a specific manner so that aflat representation (projection or shadow in two-dimensions) can give threedimensionalinformation.Figure 5: Wedge Dash-Wedge (left) with corresponding Fisher Projection Structures (right)HBrBrCH 3HHClCH 2ClCH 2 CH 3H ClClHCH 2 ClHCl HBr HCl CH 3CH Cl3HUsing the examples in Figure 5 as models, draw the Fischer Projection structure of:HOCH 3HHBrExplain the logic you used to determine your Fischer Projection.B3V B. StereoisomersHClHCH 3ClCH 3HBrb. Using Fischer Projections:Figure 6 provides the Fischer Projections of D-glucose, D-mannose, and D-galactose aswell as L-glucose.Figure 6: Fischer Projections of Some Six Carbon SugarsH 1 O H O H O H O2H OH HO H H OH HO H3HO H HO H HO H H OH4H OH H OH HO H HO HH5OH H OH H OH HO H6CH 2 OH CH 2 OH CH 2 OH CH 2 OHD-glucose D-mannose D-galactose L-glucose(1.) How many chiral atoms are there in each of these structures in Figure 6? Using thenumbering system illustrated for D-glucose, indicate which atoms are chiral. Howdid you recognize them?(2.) Using the numbering system illustrated for D-glucose, explain how the fourstructures differ.

V B. Stereoisomers3. Defining and Recognizing Relationships Among Configurational Stereoisomers:Explorations of terms that define relationships among configurational isomers:ENANTIOMERS, DIASTEREOMERS & EPIMERS See also CGWW pp. 382-396a. ENANTIOMERS:Figure 7: Examples of ENANTIOMERS (Enantiomeric Pairs of Compounds):These pairs of stereoisomers areENANTIOMERSH OH H OH1 2H CH 3CH 3HB4These pairs of stereoisomers are NOTENANTIOMERSH OH HO H9 10H CH H 3HCH 3 H CH 3CH 3 H H CH 33 4CH 3 CH 3CH 3Cl H H Cl&Cl HH Cl Cl H&H ClCH 3 CH 3 CH5 63CH 3 CH 3CH 3HO H&H OHHO HH OH&HO HH OH HOCH 2 CH 3 CH 2 CH 3CH 2 CH 37 815 16(1.) Place a checkmark (√) next to all chiral atoms in Figure 7.11 12CH 3Cl HCl HCH 313 14CH 3HO HHCH 2 CH 3CH 3(2.) How are the configurations of the chiral atoms of the enantiomeric stereoisomersin Figure 7 related to each other? Explain how you discerned the relationships.(3.) How are the configurations of the chiral atoms of non-enantiomericstereoisomers in Figure 7 related to each other? Explain how you discerned therelationships.(4.) Definition: On the basis of the structures in Figure 7, define, as specifically aspossible, the relationship between the members of a pair of enantiomers. Explainthe logic used to devise your definition.(a.)OHO(5.) Application: Identify all of the all pairs of compounds that are enantiomers.Briefly explain the logic of your classifications.Figure 8: Structures for enantiomer & diastereomer problems.(b.)(c.)H H OC C H OHH OHOOHCH 2 OHHOHCH 2 OHHOHHOHOCH 2 OHHHNH 3 NH 3OCH 2 OH

B5V B. Stereoisomersb. DIASTEREOMERS:Figure 9: Examples of DIASTEREOMERS: (Diastereomeric Sets of Compounds)These sets of stereoisomers are These sets of stereoisomers are NOTDIASTEREOMERSDIASTEREOMERSH CH H 3HH CH 3CH 3 HCH 3 H CH 3CH 3CH 3 H H CH 317 1826 27CH 3 CH 3CH 3 CH 3Cl H Cl HCl H H Cl&&H Cl Cl HH Cl Cl HCH 3 CH 3CH 3 CH 319 2028 29CH 3 CH CH 33 CH 3HO H&HO HH OH HO H&H OH HO HH OH HO HCH 2 CH 3 CH 2 CH CH 2 CH 3 CH 2 CH 3321 2230 31CH 3 CH 3 CH 3CH 3 CH 3HO H HO H HO HHO H H OHH OH & HO H & H OHH OH & HO HH OH HO H HO HH OH HO HCH 2 CH 3 CH 2 CH 3 CH 2 CH 3CH 2 CH 3 CH 2 CH 332 3323 24 25(1.) Place a checkmark (√) next to all chiral atoms in Figure 9.(2.) How are the configurations of the chiral atoms of the diastereomericstereoisomers in Figure 9 related to each other? Explain how you discerned therelationships.(3.) How are the configurations of the chiral atoms of the non-diastereomericstereoisomers in Figure 9 related to each other? Explain how you discerned therelationships.(4.) Definition: On the basis of the structures in Figure 9, define, as specifically aspossible, the relationship between stereoisomers that are diastereomers. Explainthe logic used to devise your definition.(5.) Application: Identify all of the all pairs of compounds in Figure 8 that arediastereomers. Briefly explain the logic of your classifications.

V B. Stereoisomersc. EPIMERS:Figure 10: Examples of EPIMERS (pairs of epimeric compounds)These pairs of stereoisomers are EPIMERS These pairs of stereoisomers are NOT EPIMERSHH CH 3HCH 3 H CH 3CH 334 35CH 3 CH 3Cl H Cl H&H Cl Cl HCH 3 CH 336 37CH 3 CH 3HO H&HO HH OH HO HCH 2 CH 3 CH 2 CH 338 39CH 3 CH 3HO H HO HHO H & H OHHO H HO HCH 2 CH 3CH 2 CH 3B6H CH 3CH 3CH 3 H H42 43CH 3CH 3 CH 3Cl H H Cl&H Cl Cl HCH 3 CH 344 45CH 3 CH 3H OH HO H&H OH HO HCH 2 CH 3 CH 2 CH 346 47CH 3HO HH OH &H OHCH 2 CH 340 41(1.) Place a checkmark (√) next to all chiral atoms in Figure 10.CH 3H OHOHHHHO48 49HCH 2 CH 3(2.) How are the configurations of the chiral atoms of the epimeric stereoisomers inFigure 10 related to each other? Explain how you discerned the relationships.(3.) How are the configurations of the chiral atoms of the non-epimeric stereoisomersin Figure 10 related to each other? Explain how you discerned the relationships.(4.) Definition: On the basis of the structures in Figure 10, define, as specifically aspossible, the relationship between stereoisomers that are epimers. Explain thelogic used to devise your definition.(5.) Application: Identify all of the all pairs of compounds in Figure 11 that areepimers. Briefly explain the logic of your classifications.Figure 11: Structures for epimer problems.(a.) (b.)(c.)CH3HO OHOHHOHCH 2 CH 3&HHCH 3OHOHCH 2 CH 3HOHHOClHHHOHHHOHClHO HHO HH OHH OHCH 2 OHCH 2 OHHO HH OHH OHH OHHOO

4. Defining and Recognizing Types of Stereoisomersa. CHIRAL COMPOUNDS:Figure 12: Examples of CHIRAL and ACHIRAL (not chiral) CompoundsThese compounds are CHIRAL These compounds are NOT CHIRAL(achiral)H OHHO HAECH 3 HH HBH CHF3CHCH 3CH 33CHCl H3CCl HH ClGCl HCH 3CH 3DCH 3HO HHOHCH 2 CH 3HCH 2 CH 3HO HHO(1.) Place a checkmark (√) next to all chiral atoms in Figure 12.(2.) Do all chiral molecules in Figure 12 contain chiral atoms?B7V B. StereoisomersHCH 2 CH 3(3.) Do any achiral molecules in Figure 12 contain chiral atoms? If so which ones?(4.) Definition: On the basis of the structures in Figure 12, define, as specifically aspossible, the characteristics required for a compound to be CHIRAL. Explainthe logic used to devise your definition.(5.) Application: Using the definition you derived in (4), identify all of the chiralcompounds in the Figure 13. Briefly explain the logic of your classifications.Figure 13: Structures for chiral and meso molecule problems.(a.)(b.)(c.)(d.)H OHO OCH OHCHH OH2 OHH OHHO H HO HCH 2 OHHO H HO HH OHCH 2 OHCH 2 OH

E. General Applications:B9V B. Stereoisomers1. Draw the required structure in each item below and briefly explain how your structurefulfills the requirements of the item:a.Enantiomer ofb.Diastereomer ofc.C3 epimer ofHO OH OHHO HHO HH OHCH 2 OHHOHOCH 3HHCH 2 CH 3HO OH OHHO HHO HH OHCH 2 OHd.Meso diastereomer ofd.Chiral diastereomer ofe.Enantiomer ofHOHHCH 3HOHOHCH 3HHOHOHCH 2 OHOHHHOHCH 2 OHHBrOHH2. Is it possible for a molecule to have more than one enantiomer? Explain using anexample.3. Is it possible for a molecule to have more than one diastereomer? Explain using anexample.4. Is it possible for a molecule to have more than one epimer? Explain using an example.5. Is it possible for a molecule to be chiral and meso? Explain using an example.6. Is it possible for a molecule with one chiral atom to be a meso compound? Explain usingan example.

V B. StereoisomersB10F. Nomenclature of Chiral compounds1. CGWW: pp. 387-3882. Tutorials:References: at Michigan State UniversityProvides naming rules and examples by Professor Dave Woodcock,Okanagan University College, British Columbia, CanadaSections:7. Stereochemistry (iii) Chirality(Contains many examples.)IV. Naming Enantiomers: R/S System(i) One Chirality Centre(ii) More than One Chirality CentreNote: Your browser must have the chemscape chime plug-in for these pages towork. Select "1. Introduction to these pages", then click on "Nomenclature Index -Chemscape Chime" and begin with the "How and Why". If you have problems, goto the and click on"chemscape chime" and follow directions to download the "chemscape chime plugin."If you have problems contact me.b. by Advanced Chemistry Development Laboratories(Gives detailed IUPAC rules for nomenclature.)Recommendations 1993R-7 Stereochemical SpecificationR-7.2 Chiral Compounds Specification of Absolute ConfigurationR-7.2.1 The R/S conventionc. Out of Class Applications of Nomenclature.HOBrO(1) Name the following:HH CH 3 H OHHCH 3ClHHOHHO CH 3(2) Draw structural formulas for the following compounds:R 2-iodobutaneS ethyl 2-hydroxypentanoate(2S,3R) 3-methyl-2-pentanolR 2-bromobutanoic acid

G. Out of Class Applications.a.e.i.m.1. Designate all chiral atoms in the compounds below as having either an R or Sconfiguration. Then classify each of the following compounds into ALL applicablecategories listed below:a. Compounds that have no stereoisomers.b. Chiral compounds.c. Meso compounds.d. Epimer of another compound in this group. Indicate the letter of the epimericcompound.Explain the logic of your choices.b.c.d.CH 2 OHH OCH 3HO OHO HHO HH ClH OHCH 3HO HH BrHO HOHCH 3HHHOHHOHOHCH 3OHHHCH 3NCCH 3BrCH 3HHOHCH 3f.j.n.HHHOHHOCH 2 OHCH 3CH 3HC 2 H 5OHCH 3CH 3HOHHCH 3B11g.k.o.h.CH 3 CH 3CH 3CH 3HHHOHOHOCH 3CH 3CH 3HHHCH 3l.p.V B. StereoisomersHHOHHHHOCH 3OHHOHCH 3CH 3CH 3OHCH 3H OHH OHHO HCH 32. Now look back at all of your classifications above.a. Do ALL CHIRAL compounds contain at least one chiral atom? Write the structures ofall chiral compounds that do not contain at least one chiral atom.b. Do ANY ACHIRAL molecules contain one or more chiral atoms? Write the structuresof all achiral compounds that contain one or more chiral atoms.c. Does the presence of a chiral atom allow you to identify chiral compounds dependably?If so, how? If not, can you devise a way to use the existence of chiral atoms to selectonly chiral compounds? If so, explain your method.

C1V C. General Structure Determination ProblemsDevise structures for the compounds that yielded the sets of data below. For each compound,indicate how your structure was determined and how it accounts for all of the spectral data.Data Set 1.1 H-NMR:Rel Areas 2.8 2.9 2.7 2.8 4.113 C-NMR

C2 V C. Gen. Structure Detn Prob.Data Set 1. (Continued)MS:Mass Tablem/e Intensity27.0 2.928.0 1.229.0 2.438.0 1.639.0 6.141.0 1.845.0 1.552.0 1.760.0 1.063.0 2.764.0 2.465.0 17.266.0 2.691.0 2.392.0 21.793.0 4.4108.0 1.5120.0 100.0121.0 11.4137.0 14.5138.0 1.2150.0 1.4165.0 42.8166.0 4.6IR:4000 3000 2000 1500 1000 500Frequency

V B. Gen. Structure Detn ProblemsB3Data Set 2.1 H-NMR:singletsingletdoubletmultipletdoubletRel Areas 4.3 2.8 1.4 8.313 C-NMR

C4 V C. Gen. Structure Detn Prob.Data Set 2. (Continued)MS:Mass Tablem/e Intensity15.0 1.518.0 1.427.0 2.428.0 3.029.0 1.730.0 3.739.0 2.741.0 4.142.0 4.343.0 2.344.0 100.045.0 2.755.0 1.756.0 1.757.0 1.868.0 1.069.0 1.170.0 1.871.0 1.172.0 2.586.0 1.187.0 7.0IR:4000 3000 2000 1500 1000 500Frequency

V B. Gen. Structure Detn ProblemsData Set 3.B51 H-NMR:2.2 Rel Areas 10.54.3 4.2 4.113 C-NMR

C6 V C. Gen. Structure Detn Prob.Data Set 3. (Continued)MS:Mass Tablem/e Intensity27.0 2.739.0 6.541.0 3.251.0 4.860.0 8.663.0 2.865.0 10.977.0 4.478.0 6.079.0 2.589.0 2.091.0 55.692.0 5.9103.0 4.4104.0 100.0105.0 40.1106.0 3.2115.0 2.3117.0 2.9146.0 9.2164.0 20.9165.0 2.4IR:4000 3000 2000 1500 1000 500Frequency

D1V D. The Retrosynthetic Analysis Approach to Designing Organic SynthesesA. Introduction:The retrosynthetic approach to organic synthesis starts from the product and attempts todetermine what reactant molecules might be used to synthesize the target molecule (The desiredproduct) in one reaction step. We will consider the synthetic utility of Grignard reactions forsynthesizing alcohols. Note that both of the following Grignard reactions form the same productbut use different starting materials.a.OH+CH 3 CH 2 Mg Cl1. Ether2. H 3 O + H 2 OOHHOb. +HMgBr1. Ether2. H 3 O + H 2 OOHH1. What bonds are made in reaction a? Mark them on the product structure.2. What bonds are made in reaction b? Mark them on the product structure.3. How are the bonds made in the two reactions similar? How are they different?4. What is the relationship between the C-C bond formed in each reaction and the OH group ofthe alcohol in the product?5. If the new C-C bonds were removed (disconnected), what additional changes would berequired to convert the product molecule back into the starting materials for each reaction?6. Considering your discoveries in 1->5, suggest structures for starting materials that wouldproduce the target alcohol given below. Explain the logic you used to devise your startingmaterialsOH3-ethyl-2-methyl-3-hexanol

V D: Retro Synthetic AnalysisD2B. Synthesis of Alcohols: C-C Disconnections1. Retrosynthetic AnalysisLook at the product molecule, find the alcohol OH and identify the bonds around the carbonholding the OH. These are the bonds that could have been made by a Grignard reaction.Disconnect each bond (C-C disconnections) in turn to reveal potential precursors for theproduct. Then identify the reaction that will reveal the precursors of the Grignard reagent.In the terminology of Retrosynthetic Analysis, a process such as the formation of theGrignard reagent is a Functional Group Interconversion (FGI) since it changes the nature ofthe functional group but does not change the carbon structure. So the retrosynthetic step forformation of an organometallic reagent is symbolized by FGI Grig, since it is the formationof a Grignard reagent.Full Retrosynthetic Analysis for the synthesis of 3-ethyl-2-methyl-3-hexanol(Starting materials in bold)b.OHa.a.Oc.c.C-CDisconnectionsb.C-CDisconnectionsC-CDisconnectionOsynthonOsynthonMg ClFGI GrigCl+Mg˚OsynthonOsynthonMg BrFGI GrigBr + Mg˚synthonCH 3 CH 2synthonOCH 3 CH 2 Mg ClFGI GrigCH 3 CH 2 Cl +Mg˚2. Synthesis based on retrosynthetic analysis b:OBr + Mg˚DryEtherMg Br1. Dry Ether2. H 2 SO 4 /H 2 OOH

D3 V D: Retro Synthetic Analysis3. An Additional C-C Disconnection Examplec.b.Oa.a.C-CDisconnectionOCH 3 Mg ClFGI GrigCH 3 Cl +Mg˚Hb. C-CDisconnectionsOc.C-CDisconnectionsOCH 3 CH 2 MgClFGI GrigCH 3 CH 2 Cl + Mg˚MgClFGI GrigCl+Mg˚4. Synthesis based on retrosynthetic analysis c:OCl+ Mg˚DryEther Mg Cl1. Dry Ether2. H 2 SO 4 /H 2 OOH5. Class Discussion Problem on Alcohol Synthesis:Use Retrosynthetic Analysis to devise a synthetic pathway for the following compound fromsmaller molecules.OHThen write a complete synthetic path, including reagents and reaction conditions based onyour retrosynthetic analysis.

V D: Retro Synthetic AnalysisD46. Out of Class Exercises on C-C disconnections in alcohol syntheses.For our next lab discussion period, use retrosynthetic analysis to devise at least twosyntheses for the following compounds.OHCH 3NCH 3Then write complete synthetic paths, including reagents and reaction conditions based onyour retrosynthetic analyses.Be prepared to discuss both the retroanalysis and the synthesis.OH

D5 V D: Retro Synthetic AnalysisC. Alkene Synthesis by Dehydration of Alcohols1. Dehydration of Alcohols:Dehydration of alcohols is induced by acidic conditions and (as we will see later) usuallyoccurs by a 2-step mechanism.O H H 2 SO 4a+borH 3 PO 4Major Producta. What bonds are made and broken in forming product a? Mark them on the productstructure.b. What bonds are made and broken in forming product b? Mark them on the productstructure.c. How do the bonds made and broken in the two reactions similar? How are theydifferent?d. What is the relationship between each bond made or broken and the OH group of thealcohol reactant?e. If the new bonds were removed (disconnected), what additional changes would berequired to convert each product molecule back into the starting material?f. Considering your discoveries in 1->5, suggest structures for starting materials that wouldproduce the target alkene given below. Explain the logic you used to devise your startingmaterials

V D: Retro Synthetic AnalysisD62. Retro Synthetic Step: FGI-DehydrationDehydration is another reaction that changes the functional group without altering thesequence of the carbon chain. The retrosynthetic step is designated as FGI dehydration.Usually FGI dehydrations can reveal two possible precursor compounds.HOFGIDehydrationORFGIDehydrationOHPotential precursor alcohols can be revealed by adding an OH to either end of the C=C. Thechoice of end will depend upon potential competing products.a.b.MgClOSample Retrosynthesis of an Alkenea.b. FGIDehydrationC-CFGIDehydrationHO HOC-CGrignardOCl-MgHFGI-MClMg oFGI-MGrignardClMg o2 other C-C'spossible3. Out of Class Application:For our next lab discussion period devise at least 2 different syntheses for each of thefollowing compounds from simple monosubstituted aromatic compounds and nonaromaticcompounds with four or fewer carbon atoms.Then write complete synthetic paths, including reagents and reaction conditions based onyour retrosynthetic analyses.Be prepared to discuss both the retroanalysis and the synthesis.

D7 V D: Retro Synthetic AnalysisD. Oxidation of Alcohols to Ketones1. Introduction:In the previous section we learned how to use C-C disconnections, FGI’s of Grignardreagents and FGI dehydrations to synthesize larger alkenes and alcohols from smallerketones or aldehydes and organic halides. This unit introduces methods for synthesizingketones from alcohols, another FGI, since these reactions change functional groups, but donot alter the carbon structure of the reactant. The addition of this reaction to our syntheticrepertoire greatly increases our abilities to build larger molecules from a number of smallermolecules.2. Oxidation of 2˚ Alcohols to Ketones:Chromium Trioxide (CrO 3 ) in acidic aqueous solution (H 2 SO 4 ) is a common reagent foroxidation of alcohols. This metal oxide reagent is a relatively strong oxidizing reagent. Itsmoothly converts 2˚ alcohols to ketones.HO HO+CrO 3H 2 SO 4HOH+CrO 3H 2 SO 4O3. FGI-oxidation:The following FGI Retrosynthetic step indicates that the ketone can be synthesized from thecorresponding alcohol by oxidation.OFGIHOHoxidationAlthough this is a simple addition to our reagent list, this oxidation increases our abilities tosynthesize complex molecules from relatively simple ones. Consider the potential synthesisof the complex molecule shown below. One Grignard C-C disconnection reveals that thetarget molecule can be synthesized from phenyl magnesium chloride and 2,5-dimethyl-4-heptanone.HOC-C disconnectionGrignardO+MgClWith only the Grignard C-C disconnection, we were able to disconnect the carbon structureof an alcohol only once.

V D: Retro Synthetic AnalysisD8However, we now see that the ketone precursor revealed by the above disconnection can besynthesized from a 2˚ alcohol as indicated on page 80 and reproduced below:OFGIHOHoxidationThis FGI reveals a compound that can be further disconnected with a Grignard C-C to revealeven simpler synthetic precursors.HOHC-C disconnectionGrignardHO+MgBrIf we recall that Grignard Reagents can be synthesized from alkyl halides, we can look at theentire synthetic pathway as a set of disconnections and FGI's. The starting materials areenclosed in rectangles.HOC-C disconnectionGrignardOFGIOxidation+MgClFGI-MOH+C-C disconnectionGrignardHOHCl+ Mg oMgBrFGI-MBr+ Mg o

D9 V D: Retro Synthetic Analysis4. Out of Class Application:For our next lab discussion period use retrosynthetic analysis to devise syntheses for thefollowing compounds from monosubstituted aromatic compounds and non-aromaticcompounds with four or fewer carbon atoms.OHOThen write complete synthetic paths, including reagents and reaction conditions based onyour retrosynthetic analyses.Be prepared to discuss both the retroanalysis and the synthesis.

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