JEE Chemistry Organic Chemistry Some Basic Principles And Techniques Notes Set 24

Solvents in Organic Reactions

Solvents are grouped by polarity and by their ability to donate a proton. Non-polar solvents (hexane, benzene, toluene, \( \ce{CCl4} \)) are always aprotic. Polar protic solvents have an acidic hydrogen (on O or N) and can hydrogen-bond: water, alcohols, carboxylic acids, ammonia. Polar aprotic solvents are polar but have no acidic hydrogen: acetone, DMSO, DMF, DMA, acetonitrile and ethers (weakly polar). Protic solvents solvate anions strongly through hydrogen bonding, so they favour ionisation (SN1, E1) and slow down small, charge-dense nucleophiles. Aprotic solvents solvate cations but leave anions 'naked', so they accelerate SN2 reactions.

Nucleophiles and Nucleophilicity

A nucleophile is an electron-rich species with a lone pair (or a pi bond) that attacks an electron-deficient carbon; it is a Lewis base. Examples: \( \ce{CN^-} \), \( \ce{OH^-} \), halides, \( \ce{NH3} \), \( \ce{H2O} \), alkenes. Ambident nucleophiles have two reactive sites, e.g. cyanide (C or N), nitrite (N or O) and the enolate ion (C or O).

Nucleophilicity is a kinetic property (how fast the species attacks carbon), while basicity is thermodynamic (how strongly it holds a proton, measured by the pKa of its conjugate acid). Trends: (1) Across a period both fall from left to right, \( \ce{CH3^- > NH2^- > OH^- > F^-} \). (2) Down a group basicity falls but nucleophilicity rises in protic solvents, because larger ions are more polarisable and less strongly solvated: \( \ce{I^- > Br^- > Cl^- > F^-} \). In polar aprotic solvents there is little solvation and the order reverses to follow basicity, \( \ce{F^- > Cl^- > Br^- > I^-} \). (3) For the same donor atom, the more basic species is the better nucleophile, so an anion is a better nucleophile than its neutral conjugate acid (\( \ce{HO^- > H2O} \)) and an alkoxide is better than a carboxylate. (4) Steric crowding lowers nucleophilicity much more than basicity: tert-butoxide, LDA and triethylamine are strong bases but poor nucleophiles; iodide and bromide are good nucleophiles but weak bases; \( \ce{HS^-} \) and hydrazine are strong nucleophiles with moderate basicity.

Electrophiles and How They Are Generated

An electrophile is electron-deficient, with a positive charge or a vacant orbital: \( \ce{H+} \), \( \ce{NO2+} \), \( \ce{NO+} \), carbocations, \( \ce{AlCl3} \), \( \ce{BF3} \), \( \ce{SO3} \), carbenes, carbonyl carbon. Many electrophiles are made in situ from a reagent and a catalyst:

alkene or alcohol + \( \ce{H+} \) gives a carbocation (alcohols after loss of water); alkyl halide + Lewis acid (\( \ce{AlCl3} \)) gives \( \ce{R+} \); acid halide or anhydride + \( \ce{AlCl3} \) gives the acylium ion \( \ce{RC+=O} \); halogen + \( \ce{FeBr3} \) or \( \ce{AlCl3} \) polarises X-X to give \( \ce{X+} \); conc. \( \ce{HNO3} \) + conc. \( \ce{H2SO4} \) gives the nitronium ion \( \ce{NO2+} \); conc. \( \ce{H2SO4} \) (oleum) gives \( \ce{SO3} \); \( \ce{HNO2} \) + acid gives \( \ce{NO+} \) (nitrosation); CO + HCl + \( \ce{AlCl3} \) gives the formyl cation \( \ce{HC+=O} \) (Gattermann-Koch); HCN + HCl + \( \ce{AlCl3} \) gives \( \ce{HC+=NH} \) (Gattermann). A carbonyl compound is protonated by acid to make the carbon more electrophilic.

Leaving Groups

A good leaving group departs with the bonding pair and is stable as an anion or neutral molecule. A weaker base is a better leaving group, because its conjugate acid is stronger. Order for halides: \( \ce{I^- > Br^- > Cl^- > F^-} \). Excellent leaving groups: tosylate, mesylate, triflate and neutral molecules such as \( \ce{H2O} \) (after protonation of an alcohol) and \( \ce{N2} \). Poor leaving groups: \( \ce{OH^-} \), \( \ce{OR^-} \), \( \ce{NH2^-} \) and \( \ce{R^-} \); that is why alcohols must be activated with acid. Better leaving ability stabilises the transition state, lowers the activation energy and speeds up substitution and elimination.

Types of Organic Reactions

By the change in the substrate: addition (two molecules combine, e.g. HBr to an alkene or HCN to a carbonyl), substitution (one group replaced by another: free radical, SN1, SN2, SNi, electrophilic aromatic substitution), elimination (loss of two groups to give a pi bond, e.g. alcoholic KOH on an alkyl halide), rearrangement. By the attacking reagent in the first step: nucleophilic, electrophilic or free radical reactions. Examples: \( \ce{CH3CH2Br ->[NaOH(aq)] CH3CH2OH} \) is nucleophilic substitution; \( \ce{CH3CHBrCH3 ->[alc. KOH] CH3CH=CH2} \) is elimination; benzene + \( \ce{Br2} \)/Fe is electrophilic aromatic substitution; propene + HBr with peroxide is free radical addition; methane + \( \ce{Cl2} \)/light is free radical substitution.

Chemical Kinetics Applied to Organic Reactions

Rate of reaction is the change of concentration per unit time. For \( \ce{aA + bB -> cC + dD} \), \( \text{rate}=-\tfrac1a\tfrac{d[A]}{dt}=-\tfrac1b\tfrac{d[B]}{dt}=\tfrac1c\tfrac{d[C]}{dt}=\tfrac1d\tfrac{d[D]}{dt} \). The rate law is \( \text{rate}=k[A]^p[B]^q \), where the order \( p+q \) is found experimentally and may be zero, fractional or negative. Molecularity is the number of species colliding in an elementary step; it is always a whole number (1, 2 or at most 3) and has no meaning for a complex reaction. For an elementary reaction the order equals the molecularity, but for a multi-step reaction the order is determined by the rate-determining step (the slowest step), and the rate law is written from it.

The transition state is the highest-energy point on the reaction coordinate; it cannot be isolated, unlike an intermediate, which lies in an energy valley. The activation energy is the energy difference between transition state and reactants; a higher barrier means a slower reaction. A catalyst provides a path of lower activation energy without changing the overall enthalpy change. For a reversible step, \( \Delta H=E_{a(forward)}-E_{a(backward)} \). Rate increases with concentration, temperature and catalyst, and depends strongly on the nature of the reactants, which is the main subject of organic mechanism.

Organometallic Compounds and the Grignard Reagent

Organometallic compounds have a carbon-metal bond (RMgX, RLi, \( \ce{R2CuLi} \), \( \ce{R2Zn} \)). Sodium alkoxides, sodium acetate, silver acetate and lead tetraacetate are not organometallic, because the metal is bonded to O (or S, N) and not to carbon; tetramethylsilane is excluded since silicon is a non-metal. A Grignard reagent is made from an alkyl or aryl halide and magnesium turnings in dry ether: \( \ce{RX + Mg ->[dry ether] RMgX} \). The C-Mg bond is strongly polar (about 35 percent ionic), so the carbon behaves as a carbanion, a strong nucleophile and strong base. Because it is destroyed by any compound with an acidic hydrogen (water, alcohols, acids, terminal alkynes, amines), moisture must be excluded: \( \ce{RMgX + H2O -> RH + Mg(OH)X} \). It adds to carbonyl compounds to give alcohols (formaldehyde gives primary, other aldehydes secondary, ketones tertiary) and to carbon dioxide to give carboxylic acids.