Microscale Organic Laboratory: with Multistep and Multiscale Syntheses, 4th Edition

by Dana W. Mayo (Charles Weston Pickard, Bowdoin College); Ronald M. Pike (Emeritus, Merrimack College); Peter K. Trumper (Univ. of Maine School of Law)

• ISBN13: 9780471321859
• ISBN10: 0471321850
• Edition: 4th
• Format: Hardcover
• Copyright: 2000-01-01
• Publisher: Wiley

Summary

This is a laboratory text for the mainstream organic chemistry course taught at both two and four year schools, featuring both microscale experiments and options for scaling up appropriate experiments. It provides complete coverage of organic laboratory experiments and techniques with a strong emphasis on modern laboratory instrumentation, a sharp focus on safety in the lab, excellent pre- and post-lab exercises, and multi-step experiments. There is also another text available by the same authors titled Microscale Techniques for the Organic Lab, Second Edition which has more material on techniques and spectroscopy, but has no experiments.

Table of Contents

Introduction	1	(4)
General Rules for the Microscale Laboratory	3	(1)
The Organic Chemistry Laboratory	4	(1)
Safety	5	(11)
Making the Laboratory a Safer Place	5	(2)
Nature of Hazards	5	(1)
Reduction of Risks	6	(1)
Precautionary Measures	7	(1)
Thinking about the Risks in Using Chemicals	7	(9)
Disposal of Chemicals	8	(1)
Material Safety Data Sheets	8	(4)
Alternate Sources of Information	12	(1)
Estimating the Risks from Vapors	12	(1)
Concluding Thoughts	13	(3)
Introduction to Microscale Organic Laboratory Equipment and Techniques	16	(17)
Microglassware Equipment	17	(2)
Standard Taper Joints	17	(1)
Conical Vials	18	(1)
Condensers	18	(1)
Distillation Heads	18	(1)
Recrystallization Tubes	18	(1)
Miscellaneous Items	18	(1)
Gas Chromatographic Fraction Collection Items	19	(1)
Standard Experimental Apparatus	19	(6)
Heating and Stirring Arrangements	19	(1)
Sand Bath Technique/Hotplate Calibration	19	(1)
Metal Heat-Transfer Devices	20	(1)
Stirring	20	(1)
Reflux Apparatus	20	(2)
Distillation Apparatus	22	(1)
Moisture-Protected Reaction Apparatus	23	(1)
Specialized Pieces of Equipment	24	(1)
Microscale Laws	25	(4)
Rules of the Trade for Handling Organic Materials at the Microscale Level	25	(1)
Rules for Working with Liquids at the Microscale Level	26	(3)
Rules for Working with Solids at the Microscale Level	29	(1)
The Laboratory Notebook	29	(1)
Example of a Laboratory Notebook Entry	30	(2)
Calculation of Yields	32	(1)
Determination of Physical Properties	33	(11)
Liquids	34	(1)
Ultramicro-Boiling Point	34	(2)
Density	36	(2)
Refractive Index	38	(2)
Solids	40	(1)
Melting Points	40	(1)
Simple Capillary Melting Point	40	(1)
Evacuated Melting Points	40	(2)
Mixture Melting Points	42	(2)
Microscale Laboratory Techniques	44	(55)
Microscale Separation of Liquid Mixtures by Preparative Gas Chromatography	44	(1)
GC Instrumentation	45	(5)
Procedure for Preparative Collection	49	(1)
Distillation	50	(1)
Distillation	50	(1)
Simple Distillation at the Semimicroscale Level	50	(3)
Fractional Semimicroscale Distillation	53	(2)
Solvent Extraction	55	(1)
Solubility	55	(3)
Partition Coefficient	58	(2)
Extraction	60	(6)
Liquid-Liquid Extraction	60	(1)
Microscale Extraction	61	(2)
Separatory Funnel---Semimicroscale, Macroscale Extraction	63	(1)
Continuous Liquid-Liquid Extraction	64	(1)
Separation of Acids and Bases	65	(1)
Salting Out	66	(1)
Solid-Liquid Extraction	67	(1)
Drying Agents	67	(2)
Solid-Phase Extraction	69	(2)
Crystallization	71	(1)
General Crystallization Procedure	71	(2)
Simple Crystallization	73	(1)
Filtration Techniques	74	(3)
Use of the Hirsch Funnel	74	(1)
A Hirsch Funnel Alternative---Nail-filter Funnel	75	(1)
Craig Tube Crystallizations	75	(2)
Chromatography	77	(1)
Technique 6A Column, Flash, High-Performance Liquid, Paper, and Thin-Layer Chromatography	77	(1)
Column Chromatography	78	(4)
Packing the Column	79	(1)
Sample Application	79	(1)
Elution of the Column	80	(1)
Fraction Collection	80	(1)
Flash Chromatography	81	(1)
Thin-Layer Chromatography	82	(3)
Paper Chromatography	85	(1)
High-Performance Liquid Chromatography	85	(1)
Technique 6B Concentration of Solutions	86	(1)
Distillation	86	(1)
Evaporation with Nitrogen Gas	87	(1)
Removal of Solvent Under Reduced Pressure	87	(3)
Collection and Control of Gaseous Products	90	(1)
Water Insoluble Gases	90	(1)
Trapping By-product Gases	91	(1)
Measurement of Specific Rotation	92	(1)
Theory	92	(1)
The Polarimeter	93	(2)
High Performance Polarimeters and Optical Rotary Dispersion	95	(1)
Applications to Structure Determination in Natural Products	95	(1)
Inaccurate Measurements	95	(1)
Sublimation	96	(1)
Sublimation Theory	96	(1)
Experimental Set-up	97	(1)
Precautions	97	(2)
Microscale Organic Laboratory Experiments	99	(280)
Introduction	99	(1)
Measurement of Physical Properties	100	(6)
The Separation of a 25-L Mixture of Heptanol (bp 153 C and Cyclohexanol (bp 160 C) by Gas Chromatography	106	(6)
Distillation	112	(11)
Simple Distillation at the Semimicroscale Level: Separation of Ethyl Acetate from trans-1,2-Dibenzoylethylene	112	(3)
Fractional Semimicroscale Distillation: Separation of Hexane and Toluene	115	(2)
Fractional Semimicroscale Distillation: Separation of 2-Methylpentane and Cyclohexane Using a Spinning Band Column	117	(3)
Fractional Semimicroscale Distillation: The Separation of 2-Methylpentane and Cyclohexane Using a Spinning Band in a Hickman-Hinkle Still	120	(3)
Solvent Extraction	123	(10)
Determination of a Partition Coefficient for the System Benzoic Acid, Methylene Chloride, and Water	123	(5)
Solvent Extraction I: The System; Benzoic Acid, Methylene Chloride, and 10% Sodium Bicarbonate Solution; An Example of Acid-Base Extraction Techniques	128	(1)
Solvent Extraction II: A Three Component Mixture; An Example of the Separation of an Acid, a Base, and a Neutral Substance	129	(4)
Reduction of Ketones Using a Metal Hydride Reagent: Cyclohexanol and cis- and trans-4-tert-Butylcyclohexanol	133	(12)
Cyclohexanol	135	(4)
cis- and trans-4-tert-Butylcyclohexanol	139	(6)
Photochemical Isomerization of an Alkene: cis-1,2-Dibenzoylethylene	145	(10)
Purification of trans-1,2-Dibenzoylethylene	148	(1)
Isomerization of an Alkene: Thin-Layer Chromatographic Analysis	149	(5)
Isomerization of an Alkene: Nuclear Magnetic Resonance Analysis	154	(1)
The Cannizzaro Reaction with 4-Chlorobenzaldehyde: 4-Chlorobenzoic Acid and 4-Chlorobenzyl Alcohol	155	(10)
The Esterification Reaction: Ethyl Laurate, Isopentyl Acetate, and the Use of Acidic Resins	165	(19)
Ethyl Laurate	176	(2)
Isopentyl Acetate, Semimicroscale Preparation	178	(1)
Esterification by Acidic Resins	179	(5)
Semimicroscale Preparations
The E1 Elimination Reaction: Dehydration of 2-Butanol to Yield 1-Butene, trans-2-Butene, and cis-2-Butene	184	(8)
The E2 Elimination Reaction: Dehydrohalogenation of 2-Bromobutane to Yield 1-Butene, trans-2-Butene, and cis-2-Butene	192	(7)
The Isolation of Natural Products	199	(19)
Isolation and Characterization of an Optically Active Natural Product: Usnic Acid	199	(5)
Isolation and Characterization of a Natural Product: Caffeine and Caffeine 5-Nitrosalicylate	204	(9)
Isolation of a Natural Product by Steam Distillation: Cinnamaldehyde from Cinnamon	213	(5)
Reductive Catalytic Hydrogenation of an Alkene: Octane	218	(5)
Hydroboration-Oxidation of an Alkene: Octanol	223	(7)
Diels-Alder Reaction: 4-Cyclohexene-cis-1,2-dicarboxylic Acid Anhydride	230	(11)
Optional Semimicroscale Preparation
Diels-Alder Reaction: 9, 10-Dihydroanthracene-9, 10-,-succinic Acid Anhydride	241	(5)
Optional Semimicroscale and Macroscale Preparations
Grignard Reaction with a Ketone: Triphenylmethanol	246	(8)
Grignard Reaction with an Aldehyde: 4-Methyl-3-heptanol	254	(5)
The Perkin Reaction: Condensation of Rhodanine with an Aromatic Aldehyde to Yield o-Chlorobenzylidene Rhodanine	259	(5)
Optional Semimicroscale Preparation
Alkene Preparation by the Wittig Reaction: (E)-Stilbene; 1-Methylene-4-tert-butylcyclohexane; and trans-9-(2-Phenylethenyl)anthracene	264	(15)
(E)-Stilbene by the ``Instant Ylide'' Method	269	(2)
(E)-Stilbene by the Horner-Wadsworth-Emmons Reaction	271	(2)
Methylene-4-tert-butylcyclohexane	273	(2)
trans-9-(2-Phenylethenyl)anthracene	275	(4)
Aldol Reaction: Dibenzalacetone	279	(7)
Optional Semimicroscale Preparation
Quantitative Analysis of Grignard Reagents: 1-Methylbutylmagnesium Bromide and Phenylmagnesium Bromide	286	(4)
1-Methylbutylmagnesium Bromide	288	(1)
Phenylmagnesium Bromide	288	(2)
Williamson Synthesis of Ethers: Propyl p-Tolyl Ether and Methyl p-Ethylphenyl Ether	290	(12)
Propyl p-Tolyl Ether, Optional Macroscale Preparation	291	(4)
Methyl p-Ethylphenyl Ether	295	(7)
Optional Semimicroscale and Macroscale Preparations
Amide Synthesis: Acetanilide and N,N'-Diacetyl-1,4-phenylenediamine	302	(7)
Acetanilide, Optional Semimicroscale Preparation	304	(2)
N,N'-Diacetyl-1,4-phenylenediamine	306	(3)
Imide Synthesis: N-Phenylmaleimide	309	(5)
Maleanilic Acid	311	(1)
N-Phenylmaleimide	312	(2)
Synthesis of Cyclic Carboxylic Acid Anhydrides: Succinic Anhydride and Phthalic Anhydride	314	(5)
Succinic Anhydride	316	(1)
Phthalic Anhydride	317	(2)
Diazonium Coupling Reaction: Methyl Red	319	(5)
Friedel-Crafts Acylation: Acetylferrocene and Diacetylferrocene	324	(6)
Halogenation: Electrophilic Aromatic Substitution to Yield 4-Bromoacetanilide	330	(5)
Nitration: 2,5-Dichloronitrobenzene; N,N'-Diacetyl-2,3-dinitro-1,4-phenylenediamine; 5-Nitrosalicylic Acid; and 2- and 4-Nitrophenol	335	(10)
Semimicroscale Preparation of Anhydrous Nitric Acid
2,5-Dichloronitro-benzene	338	(1)
N,N'-Diacetyl-2,3-dinitro-1,4-phenylenediamine	339	(1)
5-Nitrosalicylic Acid	340	(2)
2- and 4-Nitrophenol	342	(3)
Nucleophilic Aromatic Substitution: 2,4-Dinitrophenylthiocyanate	345	(4)
Halogenation Using N-Bromosuccinimide: 9-Bromoanthracene	349	(4)
Hypochlorite Oxidation of an Alcohol: Cyclohexanone	353	(3)
Chromium Trioxide---Resin or Hypochlorite Oxidation of an Alcohol: 9-Fluorenone	356	(6)
9-Fluorenone: CrO3 Oxidation of 9-Fluorenol	357	(2)
9-Fluorenone: NaOCI Oxidation of 9-Fluorenol	359	(3)
Hypochlorite Oxidation of Methyl Ketones by the Haloform Reaction: Benzoic Acid and p-Methoxybenzoic Acid	362	(5)
Benzoic Acid	363	(2)
p-Methoxybenzoic Acid	365	(2)
Optional Semimicroscale Preparation
Conversion of Cyclohexyl Bromide to Cyclohexene---an E2 Elimination Reaction: Factors Affecting the Rate of a Chemical Reaction	367	(12)
Advanced Microscale Organic Laboratory Experiments	379	(40)
Introduction	379	(1)
Diborane Reductions: Thioxanthene and Xanthene	380	(8)
Thioxanthene	382	(2)
Xanthene	384	(4)
Heterocyclic Ring Synthesis: Benzimidazole	388	(3)
Heterocyclic Ring Synthesis: 4-Hydroxycoumarin and Dicoumarol	391	(6)
4-Hydroxycoumarin	394	(1)
Dicoumarol	395	(2)
Grignard and Aryl Halide Cross-Coupling Reaction: 1-Methyl-2-(methyl-d3)-benzene	397	(6)
Oxidative Coupling of 2-Naphthol: 1,1'-Bi-2-Naphthol	403	(5)
Beckmann Rearrangement: Benzanilide	408	(6)
Preparation of an Enol Acetate: Cholesta-3,5-dien-3-ol Acetate	414	(5)
Sequential Syntheses: The Transition from Macro to Micro	419	(113)
Introduction	419	(2)
The Synthesis of Hexaphenylbenzene	421	(32)
Experiment [A1a] The Benzoin Condensation of Benzaldehyde: Benzoin	426	(5)
Semimicroscale Preparation and Optional Microscale Preparations
Copper(II) Ion Oxidation of Benzoin: Benzil	431	(4)
Semimicroscale Preparation and Optional Microscale Preparation
Tetraphenylcyclopentadienone
Optional Microscale Preparation	435	(4)
(E)-Stilbene
Semimicroscale Preparation	439	(2)
Bromination of (E)-Stilbene: meso-Stilbene Dibromide
Semimicroscale Preparation and Optional Macroscale and Microscale Preparations	441	(5)
Dehydrohalogenation of meso-Stilbene Dibromide: Diphenylacetylene
Semimicroscale Preparation and Optional Macroscale and Microscale Preparations	446	(3)
Hexaphenylbenzene	449	(4)
The Stepwise Synthesis of Nylon-6,6	453	(8)
Oxidation of Cyclohexanol: Adipic Acid
Macroscale Preparation	454	(3)
Preparation of an Acid Chloride: Adipoyl Chloride
Semimicroscale Preparation	457	(3)
Preparation of a Polyamide: Nylon-6,6	460	(1)
The Synthesis of Sulfanilamide	461	(10)
Acetylation of Aniline: 2,2,2-Trifluoroacetanilide
Semimicroscale Preparation	463	(3)
Chlorosulfonation of 2,2,2-Trifluoroacetanilide: p-(Trifluoroacetamido) benzenesulfonyl Chloride
Semimicroscale Preparation	466	(2)
Preparation of an Arene Sulfonamide: Sulfanilamide
Semimicroscale Preparation	468	(3)
The Synthesis of 2'-Bromostyrene	471	(17)
The Verley-Doebner Modification of the Knoevenagel Reaction: trans-Cinnamic Acid
Semimicroscale Preparation	474	(4)
Bromination of trans-Cinnamic Acid: erythro-2,3-Dibromo-3-phenylpropanoic Acid
Semimicroscale Preparation	478	(4)
An Elimination Reaction with erythro-2,3-Dibromo-3-phenylpropanoic Acid: 2'-Bromostyrene
Semimicroscale Preparation	482	(6)
The Synthesis of Piperonylonitrile from Piperonyl Alcohol	488	(15)
Piperonal
Macroscale Preparation and Optional Microscale Preparations	489	(6)
Piperonal O-(2,4-Dinitrophenyl)-oxime
Semimicroscale Preparation and Optional Microscale Preparation	495	(4)
Piperonylonitrile	499	(4)
Introduction of Photochromism: The Synthesis of a Photochromic Imine	503	(29)
An Aldol Reaction: trans-4-Nitrochalcone
Semimicroscale Preparation	507	(5)
erythro-2,3-Dibromo-3-(4-nitrophenyl)propiophenone
Semimicroscale Preparation	512	(5)
trans-2-(4-Nitrophenyl)-3-benzoylaziridine
Semimicroscale Preparation	517	(8)
A Photochromic Imine: 2-exo-6-exo-2,4-Diphenyl-6-(4-nitrophenyl)-1,3-diazabicyclo[3.1.0]hex-3-ene	525	(7)
Spectroscopic Identification of Organic Compounds	532	(86)
Introduction to Infrared Spectroscopy	532	(1)
Introduction to Group Frequencies	533	(1)
Interpretation of Infrared Spectra	533	(1)
Strategies for Interpreting Infrared Spectra	534	(2)
A Survey of Group Frequencies Identified in Organic Molecules	536	(8)
Group Frequencies of the Hydrocarbons are Listed as Follows: Alkanes	536	(1)
Alkenes C=C Stretching	536	(1)
Alkene C---H	536	(2)
Alkynes	538	(1)
Arenes	538	(1)
Group Frequencies of Carbonyl Groups C=O	538	(1)
The major factors perturbing carbonyl frequencies	539	(1)
Group frequencies of the heteroatom functional groups
Alcohols	539	(1)
Aldehydes	540	(1)
Ketones	540	(1)
Esters	540	(1)
Acyl Halides	540	(1)
Carboxylic Acids	541	(1)
Anhydrides	541	(1)
Ethers	541	(1)
Primary Amines	542	(1)
Nitriles	542	(1)
Primary amides	542	(1)
Secondary amides	542	(1)
Isocyanates	543	(1)
Thiols	543	(1)
Alkyl halides	543	(1)
Aryl halides (Chlorobenzene)	544	(1)
Infrared Spectroscopy: Instrumentation and Sample Handling	544	(10)
Instrumentation	544	(1)
Sample Handling in the Infrared	545	(1)
Liquid Samples	545	(1)
Solution Spectra and Spectra of Materials Boiling Below 100, C	545	(1)
Solid Samples	545	(9)
Nuclear Magnetic Resonance Spectroscopy: Introduction to Nuclear Magnetic Resonance	554	(9)
Nuclear Spin	554	(1)
Instrumentation	555	(2)
Chemical Shift	557	(1)
Spin-Spin Coupling	558	(3)
Intensities	561	(1)
Second-Order Effects	561	(2)
Interpretation of 1H NMR Spectra	563	(10)
1H Chemical Shifts	565	(1)
Spin-Spin Coupling	566	(1)
Geminal Coupling	566	(1)
Vicinal Coupling	567	(1)
Long-Range Coupling	568	(1)
Examples of Complex, Yet First-Order, Coupling	568	(1)
Ethyl Vinyl Ether	568	(2)
Allyl Acetate	570	(3)
13C NMR Spectroscopy	573	(6)
Two-Dimensional Nuclear Magnetic Resonance Spectroscopy	579	(2)
Nuclear Magnetic Resonance Spectroscopy Sampling	581	(4)
Ultraviolet-Visible Spectroscopy: Introduction to Absorption Spectroscopy	585	(15)
UV-Vis Spectroscopy	586	(2)
Applications to Organic Molecules	588	(7)
Instrumentation	595	(3)
Sample Preparation	598	(2)
Mass Spectrometry	600	(2)
Instrumentation	602	(6)
Ion Source	602	(1)
Mass Analyzer	603	(2)
Detector	605	(1)
Tuning the Mass Spectrometer	605	(1)
Sample Introduction	605	(1)
Gas Chromatography/Mass Spectrometry	606	(1)
Capillary Columns	606	(2)
Split Injection	608	(1)
Split/Splitless Injection	608	(1)
Features of the Mass Spectrum	608	(5)
Terms	609	(1)
Isotope Peaks	609	(2)
Recognizing the Molecular Ion	611	(1)
Mass Spectral Interpretation	612	(1)
Case Study: Synthesis of Methyl Benzoate	613	(5)
Qualitative Identification of Organic Compounds	618	(34)
Organic Qualitative Analysis	618	(23)
Preliminary Tests	619	(3)
Separation of Impurities	622	(1)
Detection of Elements Other Than Carbon, Hydrogen, and Oxygen	622	(4)
Solubility Characteristics	626	(2)
The Classification Tests	628	(13)
Preparation of Derivatives	641	(11)
Carboxylic Acids	642	(1)
Alcohols	643	(1)
Aldehydes and Ketones	644	(1)
Amines	645	(1)
Acid Chlorides and Anhydrides	646	(1)
Aromatic Hydrocarbons	647	(1)
Nitriles	647	(1)
Phenols	647	(1)
Aliphatic Hydrocarbons, Halogenated Hydrocarbons, Amides, Nitro Compounds, Ethers, and Esters	648	(4)
Glossary	652	(3)
Index	655