ORGANIC CHEMISTRY - CHAPTER 14: DELOCALIZED Pi SYSTEMS

Important Concepts

1. The 2-propenyl (allyl) system is stabilized by resonance. Its molecular-orbital description shows the presence of three pmolecular levels: one bonding, one nonbonding, and one antibonding. Its structure is symmetric, any charges or odd electrons being equally distributed between the two 

end carbons.

2. The chemistry of the 2-propenyl (allyl) cation is subject to both thermodynamic and kinetic control. Nucleophilic trapping may occur more rapidly at an internal carbon that bears relatively more positive charge, giving the thermodynamically less stable product. The kinetic product 

may rearrange to its thermodynamic isomer by dissociation followed by eventual thermodynamic trapping.

3. The stability of allylic radicals allows radical halogenations of alkenes at the allylic position.

4. The S_N2 reaction of allylic halides is accelerated by orbital overlap in the transition state.

5. The special stability of allylic anions allows allylic deprotonation by a strong base, such as butyllithium – TMEDA.

6. 1,3-Dienes reveal the effects of conjugation by their relative stability (compared to nonconjugated systems) and a relatively short internal bond (1.47 Å).

7. Electrophilic attack on 1,3-dienes leads to the preferential formation of allylic cations.

8. Extended conjugated systems are reactive because they have many sites for attack and the resulting intermediates are stabilized by resonance.

9. Benzene has special stability because of cyclic delocalization.

10. The Diels-Alder reaction is a concerted stereospecific cycloaddition reaction of an s-cis diene to a dienophile; it leads to cyclohexene derivatives. It follows the endo rule.

11. Conjugated dienes and trienes equilibrate with their respective cyclic isomers by concerted and stereospecific electrocyclic reactions.

12. Polymerization of 1,3-dienes results in 1,2- or 1,4-additions to give polymers that are capable of further cross-linking. Synthetic rubbers can be synthesized in this way. Natural rubber is made by electrophilic carbon – carbon bond formation involving biosynthetic five-carbon cations derived 

from 3-methyl-3-butenyl pyrophosphate.

13. Ultraviolet and visible spectroscopy gives a way of estimating the extent of conjugation in a molecule. Peaks in electronic spectra are usually broad and are reported as λ_max (nm). Their relative intensities are given by the molar absorptivity (extinction coefficient) ɛ.

From "Organic Chemistry" Textbook of VOLLHARDT & SCHORE

ORGANIC CHEMISTRY - CHAPTER 13: ALKYNES

Important Concepts

1. The rules for naming alkynes are essentially the same as those formulated for alkenes. Molecules with both double and triple bonds are called alkenynes, the double bond receiving the lower number if both are at equivalent positions. Hydroxy groups are given precedence in numbering alkynyl alcohols (alkynols).

2. The electronic structure of the triple bond reveals two π bonds, perpendicular to each other, and a σ bond, formed by two overlapping sp hybrid orbitals. The strength of the triple bond is about 229 kcal mol^-1; that of the alkynyl C – H bond is 131 kcal mol^-1. Triple bonds form linear 

structures with respect to other attached atoms, with short C – C (1.20 Å) and C – H (1.06 Å) bonds.

3. The high s character at C1 of a terminal alkyne makes the bound hydrogen relatively acidic (pKa <25 o:p="">

4. The chemical shift of the alkynyl hydrogen is low (δ = 51.7 – 3.1 ppm) compared with that of alkenyl hydrogens because of the shielding effect of an induced electron current around the molecular axis caused by the external magnetic field. The triple bond allows for long-range coupling. IR spectroscopy indicates the presence of the C≡C and ≡C – H bonds in terminal alkynes through bands at 2100 – 2260 cm^-1 and 3260 – 3330 cm^-1, respectively.

5. The elimination reaction with vicinal dihaloalkanes proceeds regioselectively and stereospecifically to give alkenyl halides.

6. Selective syn dihydrogenation of alkynes is possible with Lindlar catalyst, the surface of which is less active than palladium on carbon and therefore not capable of hydrogenating alkenes. Selective anti hydrogenation is possible with sodium metal dissolved in liquid ammonia because simple alkenes cannot be reduced by one-electron transfer. The stereochemistry is set by the greater stability of a trans disubstituted alkenyl radical intermediate.

7. Alkynes generally undergo the same addition reactions as alkenes; these reactions may take place twice in succession. Hydration of alkynes is unusual. It requires an Hg(II) catalyst, and the initial product, an enol, rearranges to a ketone by tautomerism.

8. To stop the hydroborationof terminal alkynes at the alkenylboron intermediate stage, modified dialkylboranes — particularly dicyclohexylborane — are used. Oxidation of the resulting alkenylboranes produces enols that tautomerize to aldehydes.

9. The Heck reaction links alkenes to alkenyl halides in a metal-catalyzed process.

From "Organic Chemistry" Textbook of VOLLHARDT & SCHORE

ORGANIC CHEMISTRY - CHAPTER 12: REACTIONS OF ALKENES

Important Concepts

1. The reactivity of the double bond manifests itself in exothermic addition reactions leading to saturated products.

2. The hydrogenation of alkenes is immeasurably slow unless a catalyst capable of splitting the strong H – H bond is used. Possible catalysts are palladium on carbon, platinum (as PtO₂), and Raney nickel. Addition of hydrogen is subject to steric control, the least hindered face of the least substituted double bond frequently being attacked preferentially. 

3. As a Lewis base, the π bond is subject to attack by acid and electrophiles, such as H⁺, X₂, and Hg²⁺. If the initial intermediate is a free carbocation, the more highly substituted carbocation is formed. Alternatively, a cyclic onium ionis generated subject to nucleophilic ring opening at the more substituted carbon. Carbocation formation leads to control of regiochemistry (Markovnikov rule);onium ion formation leads to control of both regio- and stereochemistry.

4. Mechanistically, hydroboration lies between hydrogenation and electrophilic addition. The first step is π complexation to the electron-deficient boron, whereas the second is a concerted transfer of the hydrogen to carbon. Hydroboration – oxidation results in the anti-Markovnikov hydration of alkenes.

5. Carbenes and carbenoids are useful for the synthesis of cyclopropanes from alkenes.

6. Peroxycarboxylic acids may be thought of as containing an electrophilic oxygen atom, transferable to alkenes to give oxacyclopropanes. The process is often called epoxidation.

7. Osmium tetroxide acts as an electrophilic oxidant of alkenes; in the course of the reaction, the oxidation state of the metal is reduced by two units. Addition takes place in a concerted syn manner through cyclic six-electron transition states to give vicinal diols.

8. Ozonolysis followed by reduction yields carbonyl compounds derived by cleavage of the double bond.

9. In radical chain additions to alkenes, the chain carrier adds to the π bond to create the more highly substituted radical. This method allows for the anti-Markovnikov hydrobromination of alkenes, as well as the addition of thiols and some halomethanes.

10. Alkenes react with themselves through initiation by charged species, radicals, or some transition metals to give polymers. The initial attack at the double bond yields a reactive intermediate that perpetuates carbon – carbon bond formation.

From "Organic Chemistry" Textbook of VOLLHARDT & SCHORE

ORGANIC CHEMISTRY - CHAPTER 11: ALKENES; INFRARED SPECTROSCOPY AND MASS SPECTROMETRY

Important Concepts

1. Alkenes are unsaturated molecules. Their IUPAC names are derived from alkanes, the longest chain incorporating the double bond serving as the stem. Double-bond isomers include terminal, internal, cis, and trans arrangements. Tri- and tetra substituted alkenes are named according to the E, Z system, in which the R, S priority rules apply.

2. The double bond is composed of a σ bond and a π bond. The σ bond is obtained by overlap of the two sp² hybrid lobes on carbon, the π bond by interaction of the two remaining p orbitals. The π bond is weaker (~65 kcal mol^-1) than its σ counterpart (~108 kcal mol^-1) but strong enough to allow for the existence of stable cis and trans isomers.

3. The functional group in the alkenes is flat, sp² hybridization being responsible for the possibility of creating dipoles and for the relatively high acidity of the alkenyl hydrogen.

4. Alkenyl hydrogens and carbons appear at low field in ¹H NMR (δ = 4.6– 5.7 ppm) and ¹³C NMR (δ = 100– 140 ppm) experiments, respectively. J_trans is larger than J_cis, J_geminal is very small, and J_allylic is variable but small.

5. The relative stability of isomeric alkenes can be established by comparing heats of hydrogenation. It decreases with decreasing substitution; trans isomers are more stable than cis.

6. Elimination of haloalkanes (and other alkyl derivatives) may follow the Saytzev rule (nonbulky base, internal alkene formation) or the Hofmann rule (bulky base, terminal alkene formation). Trans alkenes as products predominate over cis alkenes. Elimination is stereospecific, as dictated by the anti transition state.

7. Dehydration of alcohols in the presence of strong acid usually leads to a mixture of products, with the most stable alkene being the major constituent.

8. Infrared spectroscopy measures vibrational excitation.The energy of the incident radiation ranges from about 1 to 10 kcal mol^-1 (λ ~ 2.5 - 16.7 μm; ʋ ~ 600 – 4000 cm^-1). Characteristic peaks are observed for certain functional groups, a consequence of  tretching, bending, and other modes of vibration, and their combination. Moreover, each molecule exhibits a characteristic infrared spectral pattern in the fingerprint region below 1500 cm^-1.

9. Alkanes show IR bands characteristic of C – H bonds in the range from 2840 to 3000 cm^-1. The C=C stretching absorption for alkenes is in the range from 1620 to 1680 cm^-1, that for the alkenyl C – H bond is about 3100 cm^-1. Bending modes sometimes give useful peaks below 1500 cm^-1. Alcohols are usually characterized by a broad peak for the O – H stretch between 3200 and 3650 cm^-1.

10. Mass spectrometry is a technique for ionizing molecules and separating the resulting ions magnetically by molecular mass. Because the ionizing beam has high energy, the ionized molecules also fragment into smaller particles, all of which are separated and recorded as the mass spectrum of a compound. High-resolution mass spectral dataallow determination of molecular formulas from exact mass values. The presence of certain elements (such as Cl, Br) can be detected by their isotopic patterns. The presence of fragment-ion signals in mass spectra can be used to deduce the structure of a molecule.

11. Degree of unsaturation (number of rings 1 number of p bonds) is calculated from the molecular formula by using the equation

          Degree of unsaturation = (H_sat - H_actual)/2

where H_sat = 2n_C + 2 - n_X + n_N (disregard oxygen and sulfur).

From "Organic Chemistry" Textbook of VOLLHARDT & SCHORE

ORGANIC CHEMISTRY - CHAPTER 10: USING NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY TO DEDUCE STRUCTURE

Important Concepts

1. NMR is the most important spectroscopic tool in the elucidation of the structuresof organic molecules.

2. Spectroscopy is possible because molecules exist in various energetic forms, those at lower energy being convertible into states of higher energy by absorption of discrete quanta of electromagnetic radiation.

3. NMR is possible because certain nuclei, especially ¹H and ¹³C, when exposed to a strong magnetic field, align with it (α) or against it (β).The α-to- β transition can be effected by radiofrequency radiation, leading to resonance and a spectrum with characteristic absorptions. The higher the external field strength, the higher the resonance frequency. For example, a magnetic field of 7.05 T causes hydrogen to absorb at 300 MHz, a magnetic field of 14.1 T causes it to absorb at 600 MHz.

4. High-resolution NMR allows for the differentiation of hydrogen and carbon nuclei in different chemical environments. Their characteristic positions in the spectrum are measured as the chemical shift, δ, in ppm from an internal standard, tetramethylsilane.

5. The chemical shift is highly dependent on the presence (causing shielding) or absence (causing deshielding) of electron density. Shielding results in relatively high-field peaks [to the right, toward (CH₃)₄Si], deshielding in low-field ones. Therefore, electron-donor substituents shield, and electron-withdrawing components deshield. The protons on the heteroatoms of alcohols, thiols, and amines show variable chemical shifts and often appear as broad peaks because of hydrogen bonding and exchange.

6. Chemically equivalent hydrogens and carbons have the same chemical shift. Equivalence is best stablished by the application of symmetry operations, such as those using mirror planes and rotations.

7. The number of hydrogens giving rise to a peak is measured by integration.

8. The number of hydrogen neighbors of a nucleus is given by the spin – spin  splitting pattern of its NMR resonance, following the N + 1 rule. Equivalent hydrogens show no mutual spin – spin splitting.

9. When the chemical-shift difference between coupled hydrogens is comparable to their coupling constant, non-first-order spectra with complicated patterns are observed.

10. When the constants for coupling to nonequivalent types of neighboring hydrogens are different, the N +1 rule is applied sequentially.

11. Carbon NMR utilizes the low-abundance ¹³C isotope. Carbon – carbon coupling is not observed in ordinary ¹³C spectra. Carbon – hydrogen coupling can be removed by proton decoupling, thereby simplifying most ¹³C spectra to a collection of single peaks.

12. DEPT ¹³C NMR allows the assignment of absorptions to CH₃, CH₂, CH, and quaternary carbons, respectively.

From "Organic Chemistry" Textbook of VOLLHARDT & SCHORE

ORGANIC CHEMISTRY - CHAPTER 9: FURTHER REACTIONS OF ALCOHOLS AND THE CHEMISTRY OF ETHERS

Important Concepts

1. The reactivity of ROH with alkali metals to give alkoxides and hydrogen follows the order R = CH3 > primary > secondary > tertiary.
2. In the presence of acid and a nucleophilic counterion, primary alcohols undergo SN2 reactions. Secondary and tertiary alcohols tend to form carbocations in the presence of acid, capable of E1 and SN1 product formation, before and after rearrangement.
3.  Carbocation rearrangements take place by hydride and alkyl group shifts. They usually result in interconversion of secondary carbocations or conversion of a secondary into a tertiary carbocation. Primary alkyl oxoniumions can rearrange by a concerted process consisting of loss of water and simultaneous hydride or alkyl shift to give secondary or tertiary carbocations.
4. Synthesis of primary and secondary haloalkanes can be achieved with less risk of rearrangement by methods using inorganic esters.
5. Ethers are prepared by either the Williamson ether synthesisor by reaction of alcohols with strong nonnucleophilic acids. The first method is best when SN2 reactivity is high. In the latter case, elimination (dehydration) is a competing process at higher temperatures.
6.  Crown ethersand cryptandsare examples of ionophores,polyethers that coordinate around metal ions, thus rendering them soluble in hydrophobic media.
7. Whereas nucleophilic ring opening of oxacyclopropanesby anions is at the less substituted ring carbon according to the rules of the SN2 reaction, acid-catalyzed opening favors the more substituted carbon, because of charge control of nucleophilic attack.
8. Sulfur has more diffuse orbitals than does oxygen. In thiols,the S – H bond is less polarized than the O – H bond in alcohols, thus leading to diminished hydrogen bonding.Because the S – H bond is also weaker than the O – H bond, the acidityof thiols is greaterthan that of alcohols.
9.  Note on color use: Throughout the main parts of the text, beginning in Chapter 6, reacting species in mechanisms and most examples of new transformations are color coded red for nucleophiles, blue for electrophiles, and green for leaving groups. Color coding is notused in exercises, summaries of new reactions, or chapter-end problems

From "Organic Chemistry" Textbook of VOLLHARDT & SCHORE

ORGANIC CHEMISTRY - CHAPTER 8: HYDROXY FUNCTIONAL GROUP: ALCOHOLS

Important Concepts

1. Alcohols are alkanols in IUPAC nomenclature. The stem containing the functional group gives

the alcohol its name. Alkyl and halo substituents are added as prefixes.

2. Like water, alcohols have a polarized and short O – H bond. The hydroxy group is hydrophilic

and enters into hydrogen bonding. Consequently, alcohols have unusually high boiling points

and, in many cases, appreciable water solubility. The alkyl part of the molecule is hydrophobic.

3. Again like water, alcohols are amphoteric: They are both acidic and basic. Complete deprotonation to an alkoxide takes place with bases whose conjugate acids are considerably weaker than the alcohol. Protonation gives an alkyloxonium ion. In solution, the order of acidity is primary .secondary .tertiary alcohol. Electron-withdrawing substituents increase the acidity (and reduce the basicity).

4. The conversion of the electrophilic alkyl group in a haloalkane, C^δ+ − X^δ-, into its nucleophilic analog in an organometallic compound, C^δ- − M^δ+, is an example of reverse polarization.

5. The carbon atom in the carbonyl group, C = O, of an aldehyde or a ketone is electrophilic and therefore subject to attack by nucleophiles, such as hydride in hydride reagentsor alkyl in organometallic compounds. Subsequent to aqueous work-up, the products of such transformations are alcohols.

6. The oxidation of alcohols to aldehydes and ketones by chromium(VI) reagents opens up important

synthetic possibilities based on further reactions with organometallic reagents.

7.  Retrosynthetic analysis aids in planning the synthesis of complex organic molecules by identifying

strategic bonds that may be constructed in an efficient sequence of reactions.

From "Organic Chemistry" Textbook of VOLLHARDT & SCHORE

ORGANIC CHEMISTRY - CHAPTER 7: FURTHER REACTIONS OF HALOALKANES

Important Concepts

1.  Secondary haloalkanes undergo slow and tertiary haloalkanes undergo fast unimolecular substitution in polar media. When the solvent serves as the nucleophile, the process is called solvolysis.
2. The slowest, or rate-determining, step in unimolecular substitution is dissociation of the C – X bond to form a carbocation intermediate. Added strong nucleophile changes the product but not the reaction rate.
3. Carbocations are stabilized by hyperconjugation: Tertiary are the most stable, followed by secondary. Primary and methyl cations are too unstable to form in solution.
4.  Racemization often results when unimolecular substitution takes place at a chiral carbon.
5.  Unimolecular elimination to form an alkene accompanies substitution in secondary and tertiary systems.
6. High concentrations of strong base may bring about bimolecular elimination. Expulsion of the leaving group accompanies removal of a hydrogen from the neighboring carbon by the base. The stereo chemistry indicates an anti conformational arrangement of the hydrogen and the leaving group.
7. Substitution is favored by unhindered substrates and small, less basic nucleophiles.
8. Elimination is favored by hindered substrates and bulky, more basic nucleophiles

From "Organic Chemistry" Textbook of VOLLHARDT & SCHORE

ORGANIC CHEMISTRY - CHAPTER 6: PROPERTIES AND REACTIONS OF HALOALKANES

Important Concepts

1. A haloalkane,commonly termed an alkyl halide, consists of an alkyl group and a halogen.

2. The physical properties of the haloalkanes are strongly affected by the polarization of the C – X 

bond and the polarizability of X.

3. Reagents bearing lone electron pairs are called nucleophilic when they attack positively polarized centers (other than protons). The latter are called electrophilic.When such a reaction leads to displacement of a substituent, it is a nucleophilic substitution.The group being displaced by the nucleophile is the leaving group.

4. The kinetics of the reaction of nucleophiles with primary (and most secondary) haloalkanes are second order, indicative of a bimolecular mechanism. This process is called bimolecular nucleophilic substitution (SN2 reaction).It is a concerted reaction, one in which bonds are simultaneously broken and formed. Curved arrows are typically used to depict the flow of electrons as the reaction proceeds.

5. The SN2 reaction is stereo specificand proceeds by backside displacement, thereby producing 

inversion of configuration at the reacting center.

6. An orbital description of the SN2 transition stateincludes an sp2-hybridized carbon center, partial bond making between the nucleophile and the electrophilic carbon, and simultaneous partial bond breaking between that carbon and the leaving group. Both the nucleophile and the leaving group bear partial charges.

7. Leaving-group ability, a measure of the ease of displacement, is roughly proportional to the strength of the conjugate acid. Especially good leaving groups are weak bases such as chloride, bromide, iodide, and the sulfonates.

8. Nucleophilicity increases (a) with negative charge, (b) for elements farther to the left and down the periodic table, and (c) in polar aprotic solvents.

9. Polar aprotic solvents accelerate SN2 reactions because the nucleophiles are well separated from their counterions but are not tightly solvated.

10. Branching at the reacting carbon or at the carbon next to it in the substrate leads to steric hindrance in the SN2 transition state and decreases the rate of bimolecular substitution.

From "Organic Chemistry" Textbook of VOLLHARDT & SCHORE

ORGANIC CHEMISTRY - CHAPTER 5: STEREOISOMERS

Important Concepts

1. Isomers have the same molecular formula but are different compounds. Constitutional (structural) isomers differ in the order in which the individual atoms are connected. Stereoisomers have the same connectivity but differ in the three-dimensional arrangement of the atoms. Mirror-image stereoisomers are related to each other as object and mirror image.

2. An object that is not superimposable on its mirror image is chiral.

3. A carbon atom bearing four different substituents (asymmetric carbon)is an example of a stereocenter.

4. Two stereoisomers that are related to each other as image – nonsuperimposable mirror image are called enantiomers.

5. A compound containing one stereocenter is chiral and exists as a pair of enantiomers. A 1:1 mixture of enantiomers is a racemate (racemic mixture).

6. Chiral molecules cannot have a plane of symmetry (mirror plane). If a molecule has a mirror plane,then it is achiral.

7. Diastereomers are stereoisomers that are not related to each other as object to mirror image. Cis and trans isomers of cyclic compounds are examples of diastereomers.

8. Two stereocenters in a molecule result in as many as four stereoisomers — two diastereomerically related pairs of enantiomers. The maximum number of stereoisomers that a compound with n stereocenters can have is 2ⁿ. This number is reduced when equivalently substituted stereocenters give rise to a plane of symmetry. A molecule containing stereocenters anda mirror plane is identical with its mirror image (achiral) and is called a meso compound. The presence of a mirror plane in any energetically accessible conformation of a molecule is sufficient to make it achiral.

9. Most of the physical properties of enantiomers are the same. A major exception is their interaction with plane-polarized light: One enantiomer will rotate the polarization plane clockwise (dextrorotatory),the other counterclockwise (levorotatory).This phenomenon is called optical activity.The extent of the rotation is measured in degrees and is expressed by the specific rotation,  [α]. Racemates and meso compounds show zero rotation. The enantiomer excessor optical purity of an unequal mixture of enantiomers is given by
                           % optical purity = ([α]_observed/[α]) x 100

10. The “handedness” of a stereocenter (its absolute configuration) is revealed by X-ray diffraction and can be assigned as R or S by using the sequence rules of Cahn, Ingold, and Prelog.
11. Fischer projections provide stencils for the quick drawing of molecules with stereocenters.
12. Chirality can be introduced into an achiral compound by radical halogenation. When the transition states are enantiomeric (related as object and mirror image), the result is a racemate because the faces of the planar radical react at equal rates.
13. Radical halogenation of a chiral molecule containing one stereocenter will give a racemate if the reaction takes place at the stereocenter. When reaction elsewhere leads to two diastereomers, they will be formed in unequal amounts.
14. The preference for the formation of one stereoisomer, when several are possible, is called
stereoselectivity.
15.The separation of enantiomers is called resolution. It is achieved by the reaction of the racemate with the pure enantiomer of a chiral compound to yield separable diastereomers. Chemical removal of the chiral reagent frees both enantiomers of the original racemate. Another way of separating enantiomers is by chiral chromatography on an optically active support.

From "Organic Chemistry" Textbook of VOLLHARDT & SCHORE

Textbooks for Chemistry Students

1. Principles of Chemical Science

• Chemical Principles: The Quest for Insight, Peter Atkins.
• Chemistry the molecular nature of matter and change, Martin Silberberg.  
• Principles of moder chemistry, David W. Oxtoby.
• Chemical bonds, Harry B. Gray.

2. Principles of Inorganic Chemistry

• Chemical Structure and Bonding, Roger L. DeKock.
• Inorganic Chemistry, Gary L. Miessler.
• Inorganic Chemistry, Peter Atkins.
• Inorganic Chemistry, Catherine E. Housecroft, A. G. Sharpe.
• Chemical Application of Group Theory, Frank A. Cotton.
• Chemistry of the Elements. N. N. Greenwood and A. Earnshaw.
• Orbital Interactions in Chemistry, Thomas A. Albright.
• Symmetry and Spectroscopy: An Introduction to Vibrational and Electronic Spectroscopy, Daniel C. Harris.
• Advanced Inorganric Chemistry, Frank A. Cotton.

3. Organic Chemistry

• Organic Chemistry, John McMurry.
• Organic Chemistry, Vollhardt.
• Organic Chemistry, Loudon.

4. Advanced Inorganic Chemistry

• Physical Methods in Bioinorganic Chemistry, Lawrence Que, Jr.
• Chemistry of Elements, Greenwood, Norman.
• Advanced Inorganric Chemistry, Frank A. Cotton.

5. Advanced Organic Chemistry

• Advanced Organic Chemistry, Part A, B, F. A. Carey.
• March's Advanced Organic Chemistry, Michael B. Smith.
• Heterocyclic Chemistry, J. A. Joule.

6. Physical Chemistry

• Quantum Chemistry, Donald A. McQuarrie.
• An Introduction to Statistical Thermodynamics, Terrill L. Hill.
• Physical Chemistry, Peter Atkins.

7. Organometallic Chemistry

• Principles and Applications of Organotransition Metal Chemistry, James P. Collman.
• Organometallics, A concise Introduction, Ch. Elschenbroich.
• March's Advanced Organic Chemistry, Michael B. Smith.
• Advanced Inorganric Chemistry, Frank A. Cotton.

8. Polymer Chemistry

• Hiemenz, P. C.; Lodge, T. P. Polymer Chemistry, 2nd Edition.

9. Nanomedicine

• Jain, Kewal K. The Handbook of Nanomedicine.
• Nanomedicine Design of Particles, Sensors, Motors, Implants, Robots, and Devices. Ed. Mark J. Schulz, Vesselin N. Shanov, and Yeoheung Yun. Artech House, 2009. 
• Nanotechnology: Volume 5: Nanomedicine. Ed. Viola Vogel. Weinheim: Wiley-VCH 
• Nanotechnology in Biology and Medicine: Methods, devices, and applications. Ed. Tuan Vo-Dinh. Boca Raton, FL: CRC Press, Taylor & Francis Group, 2007.
• Tibbals, Harry F. Perspectives in Nanotechnology: Medical Nanotechnology and Nanomedicine. Ed. Gabor L. Hornyak. Boca Raton, FL: CRC Press, 2011. 

10. Green Chemistry

• Green Chemistry: An Introductory Text, 2nd Edition" Mike Lancaster; RSC Paperbacks

11. Quantum Chemistry

•  Nitzan, Abraham. Chemical Dynamics in Condensed Phases
• Schatz, George C., and Mark A. Ratner. Quantum Mechanics in Chemistry
• McHale, J. L. Molecular Spectroscopy. 
• Merzbacher, E. Quantum Mechanics. 
• Quantum Chemistry, Donald A. McQuarrie.

12. Crystal Structure Refinement

• Müller, P. Crystal Structure Refinement.

13. Crystal Structure Analysis

• Massa, Werner. Crystal Structure Determination
• Giacovazzo, C., ed. Fundamentals of Crystallography

14. Organic Structure Determination

• Silverstein, R. M., F. X. Webster, and D. J. Kiemle. Spectrometric Identification of Organic Compounds. 
• Pretsch, E., P. Bühlmann, and C. Affolter. Structure Determination of Organic Compounds: Tables of Spectral Data. 
• Organic Structural Spectroscopy, Joseph B. Lambert, Herbert F. Shurvell, David A. Lightner, R. Graham Cooks.
• Organic Structure Analysis, Phillip Crews, Jaime Rodriguez, Marcel Jaspars.
• Organic Structures from Spectra, L. D. Field, S. Sternhell, J. R. Kalman.
• Understanding NMR Spectroscopy, James Keeler.

15. Introduction to Experimental Chemistry

• Introduction to Organic Laboratory Techniques, Pavia, D. L., et. al.

Tips for Growing X-ray Quality Crystals

Some Crystal Growing Tips

By Dr. Maarten Dinger

"In theory, every soluble pure solid compound can be crystallized to give single crystals suitable for X-ray diffraction studies, this still being by far the least ambiguous and most complete characterization method available to synthetic chemists."

A few general points should be noted:

- Do not disturb crystallizations! Bumping them, swirling, etc can completely mess them up.

- If using solvents, make sure everything is fully dissolved. If everything won't dissolve, then these are likely to be impurities, so filter them off.

- The purer the compound, the better your chance of growing single crystals. At least 75% pure or better is probably a minimum if you want your chances to be good.

- Don't give up too quickly! Solvent choice is critical, and sometimes multiple solvents are needed for the molecules to pack. Just try everything and you'll find that you can almost always get a crystal.

Five main methods present themselves for crystallization of compounds, all are valid for organic and inorganic materials:

1. Cooling

The simplest, but nonetheless very successful, method for crystal growth is the cooling of a saturated solution of the compound to be crystallized. Any solvent is fair game for this method (with the exception of water and benzene in the freezer). Simply make a saturated solution of the compound and allow it to cool, usually by placing the solution in the freezer. Also a hot solution can be slowly cooled to room temperature, although this really only works for known compounds in undergraduate laboratories.

2. Evaporation

This is the most common methodolgy for crystal growth, and involves simply evaporating solvent from the solution of the compound until saturation is reached and crystals form. This method is not the best and often leads to ugly crystals since the crystals tend to grow on the surface of the vessel . Also make sure you stopper it in time or solvate loss can occur, along with crystallinity.

An extension on this technique involves the use of two solvents, one in which the material to be crystallized is soluble and a second in which it is insoluble. What's important is that the first solvent is more volatile than the second, so that as 'solvent one' evaporates, 'solvent two' remains, eventually reaching a point where solubilty of the compound can no longer be sustained. Typical solvents used are ether, methylene chloride or pentane as 'solvent one' choices, and acetonitrile, methanol, ethanol, heptane, toluene as 'solvent two' choices.

To slow down crystal growth, and minimize solvate loss, the refrigerator or freezer can be used.

3. Vapor Diffusion

This is probably the most successful method to grow a crystal. Two vials are needed where one can fit inside the other. In the inner vial the compound to be crystallized is dissolved in a small quantity of a moderately non-volatile solvent, such as THF, benzene, chloroform, toluene, acetonitrile, methanol, and even methylene chloride. Then in the second vial, a volatile solvent in which the compound is insoluble is added - suitable solvents for this are pentane, diethyl ether or hexane, and the this vial is then capped. The second solvent then slowly diffuses into the first, precipitating the product and, hopefully, depositing crystals.

Again the refrigerator or freezer can be used to slow the diffusion process.

4. Liquid/liquid diffusion

This is similar to the vapor diffusion and involves simply carefully layering a low density solvent on top of higher one in a thin tube (NMR tube). Solvents of choice for the bottom layer (n which the compound is dissolved) are methylene chloride or chloroform, while typical top layer solvents are hydrocarbons or ether.

5. Sublimation

If you're very fortunate, your compound may be sufficiently volatile for this technique. Simply heat the compound (generally under vacuum), and collect crystals on a cooled cold-finger. Often the collected material is highly crystalline, and, best of all, by the very nature of the method free of all solvent impurities.

Good luck!!!

Dr. Maarten Dinger is a post-doc for the Scott research group

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Crystal Growing Tips

By Dr. Jerzy Klosin

General Thoughts

• Growing crystals is a skill, which can only be mastered well after attempting numerous crystallizations. 
• Be persistent - do not give up if the first, or second crystallization attempt fails. There is a lot of conditions at your disposal that you can change such as solvent ratio, solvent volume, temperature, add second or even third solvent to your crystallization mixture. The bottom line is experimentation - the more you play with crystallizations the more successful you get.
• Be observant! Pay close attention to the compound's behavior during its preparation and work-up - how soluble it is in a given solvent, what happens when a drop of solution is left to evaporate? This might give you important clues regarding what solvents to use in your crystallization.
• The purer compound you start with the better your chance of growing good crystals. I usually do not start growing crystals until the compound is at least 90 % pure.
• Crystallization solution must be homogenous! When a compound is dissolved in any solvent the resulted solution should be filtered (syringe filter works well for this purpose) to remove any floater before it is put aside - in my opinion this is probably the most important step in setting-up crystallization!

Practical Aspects

• All of my crystallizations were performed using five different solvents or their mixtures: toluene, hexane, THF, diethyl ether and methylene chloride. So far I did not have to resort to other solvents in my work but this does not mean that these five solvents will always work very well for your crystallization. All of the crystals I have obtained were either grown by cooling (drybox freezer set at -25 °C) or evaporating solution containing dissolved compound. Most of the compounds I crystallized were organometallic complexes (MW = 300 - 1000) although I also obtained crystals of several organic molecules.
• In my experience, salts are somewhat more difficult to crystallize than neutral compounds - some of them tend to oil out. Solvent mixtures for salt crystallization that I successfully used were methylene chloride/hexane and THF/hexane.
• Choice of crystallization solvent or solvent mixture depends, of course, on the compound's solubility. In any crystallization technique the idea is to exceed saturation level of the solution and force the solute to come out hopefully in the form of beautiful crystals. If the compound is very soluble even in hydrocarbons then solvent evaporation is a technique of choice. Slow evaporation (1-7 days) is usually recommended but at times good crystals can be obtained within 1 hr. by simply leaving the solution vessel wide open.

A Few Example Crystallizations from My Work

1. Organic compound (~ 30 mg) was dissolved in a mixture of 0.5 mL of methylene chloride and 2 mL of hexane (compound was very soluble in methylene chloride but much less soluble in hexane). Solution was filtered and put aside at room temp. Since methylene chloride evaporates faster then hexane after a few days solution reached saturation level and crystals formed.
2. Two reactants (~ 35 mg each) were dissolved in 0.6 mL of C6D6 in the NMR tube. The product of this reaction was a salt, which had much lower solubility in benzene that the starting materials. Good quality crystals were obtained within an hour in the NMR tube.
3. Organic salt (~150 mg) was dissolved in 1 mL of either followed by 2 mL of hexane (hexane was added until solution became slightly cloudy). Solution was filtered and put aside on the shelf in the dry box (room temp.). After 14 hr. colorless crystals formed.
4. Organometallic complex (50 mg) (highly soluble even in hydrocarbons) was dissolved in 1 mL of hexane and the vial was left opened in the drybox. After 8 hr. hexane evaporated leaving nice crystals. One way to slow down evaporation is to leave a closed NMR tube for a couple of weeks. Although this is a very slow process it quite often gives very nice crystals.
5. Organometallic complex (~ 300 mg) was dissolved in 1 mL of toluene followed by 4 mL of hexane. Solution was mixed, filtered and put into freezer (-25 °C). Next day crystals were formed.
6. Organometallic complex (~ 300 mg) was dissolved in 3 mL hexane. Solution was filtered and put into freezer (-25 °C). Next day crystals were formed.
7. Introduction of some solvents might change the interaction between cation and anion and help with crystallization. In one case, small amount of THF was added to crystallization mixture (ether/hexane). Obtained crystals contained THF molecule that formed hydrogen bond with ammonium cation of my compound. THF helped in crystallization by changing the composition of the compound.
8. Many solvents get incorporated into crystal lattice. This is an extremely common phenomenon. Aromatic solvents (toluene, benzene), for example, are among the most common solvents found in crystal lattices. If you have difficulty growing crystals from one set of solvents (even though you did everything right) you might want to introduce small amount of second or third solvent with the hope it will be used by Nature as a building block of the crystal lattice thus allowing good crystal formation.

Happy crystal growing!

Besides, you can see more at the link: http://www.xray.ncsu.edu/GrowXtal.html

ORGANIC CHEMISTRY - CHAPTER 4: CYCLOALKANES

IMPORTANT CONCEPTS

1. Cycloalkane nomenclature is derived from that of the straight-chain alkanes.

2. All but the 1,1-disubstituted cycloalkanes exist as two isomers: If both substituents are on the same face of the molecule, they are cis; if they are on opposite faces, they are trans. Cis and trans isomers are stereoisomers—compounds that have identical connectivities but differ in the arrangement of their atoms in space.

3. Some cycloalkanes are strained. Distortion of the bonds about tetrahedral carbon introduces bond-angle strain. Eclipsing (torsional) strain results from the inability of a structure to adopt staggered conformations about C – C bonds. Steric repulsion between atoms across a ring leads to transannular strain.

4. Bond-angle strain in the small cycloalkanes is largely accommodated by the formation of bent bonds.

5. Bond-angle, eclipsing, and other strain in the cycloalkanes larger than cyclopropane (which is by necessity flat) can be accommodated by deviations from planarity.

6. Ring strain in the small cycloalkanes gives rise to reactions that result in opening of the ring.

7. Deviations from planarity lead to conformationally mobile structures, such as chair, boat, and twist-boat cyclohexane. Chair cyclohexane is almost strain free.

8. Chair cyclohexane contains two types of hydrogens: axial and equatorial. These interconvert rapidly at room temperature by a conformational chair–chair (“flip”) interconversion, with an activation energy of 10.8 kcal mol^-1 (45.2 kJ mol^-1).

9. In monosubstituted cyclohexanes, the ΔG^o of equilibration between the two chair conformations is substituent dependent. Axial substituents are exposed to 1,3-diaxial interactions.

10. In more highly substituted cyclohexanes, substituent effects are often additive, the bulkiest substituents being the most likely to be equatorial.

11. Completely strain-free cycloalkanes are those that can readily adopt an all-anticonformation and lack transannular interactions.

12. Bicyclic ring systems may be fused or bridged. Fusion can be cis or trans.

13. Natural products are generally classified according to structure, physiological activity, taxonomy, and biochemical origin. Examples of the last class are the terpenes, of the first the steroids.

14. Terpenes are made up of isoprene units of five carbons.

15. Steroids contain three angularly fused cyclohexanes (A, B, C rings) attached to the cyclopentane D ring. Beta substituents are above the molecular plane, alpha substituents below.

16. An important class of steroids are the sex hormones, which have a number of physiological functions, including the control of fertility.

From "Organic Chemistry" Textbook of VOLLHARDT & SCHORE

ORGANIC CHEMISTRY - CHAPTER 3: REACTIONS OF ALKANES

IMPORTANT CONCEPTS

1. The ΔH^o of bond homolysis is defined as the bond-dissociation energy, DH^o. Bond homolysis gives radicals or free atoms.

2. The C–H bond strengths in the alkanes decrease in the order

3. Catalysts speed up the establishment of an equilibrium between starting materials and products.

4. Alkanes react with halogens (except iodine) by a radical chain mechanism to give haloalkanes. The mechanism consists of initiation to create a halogen atom, two propagation steps, and various termination steps.

5. In the first propagation step, the slower of the two, a hydrogen atom is abstracted from the alkane chain, a reaction resulting in an alkyl radical and HX. Hence, reactivity increases from I₂ to F₂. Selectivity decreases along the same series, as well as with increasing temperature.

6. The Hammond postulate states that fast, exothermic reactions are typically characterized by early transition states, which are similar in structure to the starting materials. On the other hand, slow, endothermic processes usually have late (productlike) transition states.

7. The ΔH^o for a reaction may be calculated from the DH^o values of the bonds affected in the process as follows:

               ΔH^o = ∑DH^o_{bonds broken} - ∑DH^o_{bonds formed}

8. The ΔH^o for a radical halogenation process equals the sum of the ΔH^o values for the propagation steps.

9. The relative reactivities of the various types of alkane C – H bonds in halogenations can be estimated by factoring out statistical contributions. They are roughly constant under identical conditions and follow the order

The reactivity differences between these types of CH bonds are greatest for bromination, making it the most selective radical halogenation process. Chlorination is much less selective, and fluorination shows very little selectivity.

10. The ΔH^o of the combustion of an alkane is called the heat of combustion, ΔH^o_comb. The heats of combustion of isomeric compounds provide an experimental measure of their relative stabilities.

From "Organic Chemistry" Textbook of VOLLHARDT & SCHORE

ORGANIC CHEMISTRY - CHAPTER 2: STRUCTURE AND REACTIVITY

IMPORTANT CONCEPTS

1. Chemical reactions can be described as equilibria controlled by thermodynamic and kinetic parameters. The change in the Gibbs free energy, ΔG^o, is related to the equilibrium constant by ΔG^o = - RT ln K = - 1.36 log K (at 25^oC). The free energy has contributions from changes in enthalpy, ΔH^O, and entropy, ΔS^o: ΔG^o = ΔH^o – TΔS^o. Changes in enthalpy are due mainly to differences between the strengths of the bonds made and those of the bonds broken. A reaction is exothermic when the former is larger than the latter. It is endothermic when there is a net loss in combined bond strengths. Changes in entropy are controlled by the relative degree of energy dispersal in starting materials compared with that in products. The greater the increase in energy dispersal, the larger a positive ΔS^o.

2. The rate of a chemical reaction depends mainly on the concentrations of starting material(s), the activation energy, and temperature. These correlations are expressed in the Arrhenius equation: rate constant k = Ae^-Ea/RT.

3. If the rate depends on the concentration of only one starting material, the reaction is said to be of first order. If the rate depends on the concentrations of two reagents, the reaction is of second order.

4. Brønsted acids are proton donors; bases are proton acceptors. Acid strength is measured by the acidity constant K_a; pK_a = - log K_a. Acids and their deprotonated forms have a conjugate relation. Lewis acids and bases are electron pair acceptors and donors, respectively.

5. Electron-deficient atoms attack electron rich atoms and are called electrophiles. Conversely, electron-rich atoms attack electron-poor atoms and are called nucleophiles. When a nucleophile, which may be either negatively charged or neutral, attacks an electrophile, it donates a lone electron pair to form a new bond with the electrophile.

6. An organic molecule may be viewed as being composed of a carbon skeleton with attached functional groups.

7. Hydrocarbons are made up of carbon and hydrogen only. Hydrocarbons possessing only single bonds are also called alkanes. They do not contain functional groups. An alkane may exist as a single continuous chain or it may be branched or cyclic. The empirical formula for the straight-chain and branched alkanes is C_nH_2n+2.

8. Molecules that differ only in the number of methylene groups, CH₂, in the chain are called homologs and are said to belong to a homologous series.

9. An sp³carbon attached directly to only one other carbon is labeled primary. A secondary carbon is attached to two and a tertiary to three other carbon atoms. The hydrogen atoms bound to such carbon atoms are likewise designated primary, secondary, or tertiary.

10. The IUPAC rules for naming saturated hydrocarbons are (a) find the longest continuous chain in the molecule and name it; (b) name all groups attached to the longest chain as alkyl substituents; (c) number the carbon atoms of the longest chain; (d) write the name of the alkane, citing all substituents as prefixes arranged in alphabetical order and preceded by numbers designating their positions.

11. Alkanes attract each other through weak London forces, polar molecules through stronger dipole – dipole interactions, and salts mainly through very strong ionic interactions.

12. Rotation about carbon – carbon single bonds is relatively easy and gives rise to conformations (conformers). Substituents on adjacent carbon atoms may be staggered or eclipsed. The eclipsed conformation is a transition state between staggered conformers. The energy required to reach the eclipsed state is called the activation energy for rotation. When both carbons bear alkyl or other groups, there may be additional conformers: Those in which the groups are in close proximity (60^o) are gauche; those in which the groups are directly opposite (180^o) each other are anti. Molecules tend to adopt conformations in which steric hindrance, as in gaucheconformations, is minimized.

From "Organic Chemistry" Textbook of VOLLHARDT & SCHORE

ORGANIC CHEMISTRY - CHAPTER 1: STRUCTURE AND BONDING IN ORGANIC MOLECULES

IMPORTANT CONCEPTS

1. Organic chemistry is the chemistry of carbon and its compounds.

2. Coulomb’s law relates the attractive force between particles of opposite electrical charge to the distance between them.

3. Ionic bonds result from coulombic attraction of oppositely charged ions. These ions are formed by the complete transfer of electrons from one atom to another, typically to achieve a noble-gas configuration.

4. Covalent bonds result from electron sharing between two atoms. Electrons are shared to allow the atoms to attain noble-gas configurations.

5. Bond length is the average distance between two covalently bonded atoms. Bond formation releases energy; bond breaking requires energy.

6. Polar bonds are formed between atoms of differing electronegativity (a measure of an atom’s ability to attract electrons).

7. The shape of molecules is strongly influenced by electron repulsion.

8. Lewis structures describe bonding by the use of valence electron dots. They are drawn so as to give hydrogen an electron duet and the other atoms electron octets (octet rule). Formal charge separation should be minimized but may be enforced by the octet rule.

9. When two or more Lewis structures differing only in the positions of the electrons are needed to describe a molecule, they are called resonance forms. None correctly describes the molecule, its true representation being an average (hybrid) of all its Lewis structures. If the resonance forms of a molecule are unequal, those which best satisfy the rules for writing Lewis structures and the electronegativity requirements of the atoms are more important.

10. The motion of electrons around the nucleus can be described by wave equations. The solutions to these equations are atomic orbitals,which roughly delineate regions in space in which there is a high probability of finding electrons.

11. An s orbital is spherical; a p orbital looks like two touching teardrops or a “spherical figure eight.” The mathematical sign of the orbital at any point can be positive, negative, or zero (node). With increasing energy, the number of nodes increases. Each orbital can be occupied by a maximum of two electrons of opposite spin (Pauli exclusion principle, Hund’s rule).

12. The process of adding electrons one by one to the atomic orbitals, starting with those of lowest energy, is called the Aufbau principle.

13. A molecular orbital is formed when two atomic orbitals overlap to generate a bond. Atomic orbitals of the same sign overlap to give a bonding molecular orbital of lower energy. Atomic orbitals of opposite sign give rise to an antibonding molecular orbitalof higher energy and containing a node. The number of molecular orbitals equals the number of atomic orbitals from which they derive.

14. Bonds made by overlap along the internuclear axis are called σ bonds; those made by overlap of p orbitals perpendicular to the internuclear axis are called π bonds.

15. The mixing of orbitals on the same atom results in new hybrid orbitals of different shape. One s and one p orbital mix to give two linear sp hybrids, used, for example, in the bonding of BeH₂. One s and two p orbitals result in three trigonal sp² hybrids, used, for example, in BH₃. One s and three p orbitals furnish four tetrahedral sp³ hybrids, used, for example, in CH₄. The orbitals that are not hybridized stay unchanged. Hybrid orbitals may overlap with each other. Overlapping sp³ hybrid orbitals on different carbon atoms form the carbon – carbon bonds in ethane and other organic molecules. Hybrid orbitals may also be occupied by lone electron pairs, as in NH₃.

16. The composition (i.e., ratios of types of atoms) of organic molecules is revealed by elemental analysis. The molecular formula gives the number of atoms of each kind.

17. Molecules that have the same molecular formula but different connectivity order of their atoms are called constitutional or structural isomers.They have different properties.

18. Condensed and bond-line formulas are abbreviated representations of molecules. Dashed-wedged line drawings illustrate molecular structures in three dimensions.

From "Organic Chemistry" Textbook of VOLLHARDT & SCHORE