Alkyl Halides Part 3.pdf

Alkyl Halides Organic chemistry Alkyl Halides Substrate Reactivity in SN1 Reactions The rate of an SN1 reaction is affected by the type of alkyl halide involved. This trend is exactly opposite to that observed in SN2 reactions Alkyl Halides Carbocation Stability The effect of the type of alkyl halid...

Alkyl Halides Organic chemistry Alkyl Halides Substrate Reactivity in SN1 Reactions The rate of an SN1 reaction is affected by the type of alkyl halide involved. This trend is exactly opposite to that observed in SN2 reactions Alkyl Halides Carbocation Stability The effect of the type of alkyl halide on SN1 reaction rates can be explained by considering carbocation stability. Carbocations are classified as primary (1°), secondary (2°), or tertiary (3°), based on the number of R groups bonded to the charged carbon atom. As the number of R groups increases, carbocation stability increases. Alkyl Halides Carbocation Stability Alkyl Halides Carbocation Stability Alkyl groups are electron donor groups that stabilize a positive charge because they contain several σ bonds, each containing electron density. As a result, alkyl groups are more polarizable than a hydrogen atom, and better able to donate electron density. In general, the more alkyl groups attached to a carbon with a positive charge, the more stable the cation will be. Alkyl Halides Characteristics of the SN1 Mechanism Alkyl Halides Predicting the Mechanism of Nucleophilic Substitutions Reactions Four factors are relevant in predicting whether a given reaction is likely to proceed by an SN1 or an SN2 mechanism: 1.The alkyl halide—CH3X, RCH2X, R2CHX or R3CX 2.The nucleophile—strong or weak 3.The leaving group—good or poor 4.The solvent—protic or aprotic Alkyl Halides 1. Nature of the Alkyl Halide The most important is the identity of the alkyl halide. Alkyl Halides 2. The nature of the nucleophile is another factor. Strong nucleophiles (which usually bear a negative charge) present in high concentrations favor SN2 reactions. Weak nucleophiles, such as H2O and ROH favor SN1 reactions by decreasing the rate of any competing SN2 reaction. Let us compare the substitution products formed when the 2° alkyl halide A is treated with either the strong nucleophile HO¯ or the weak nucleophile H2O. Because a 2° alkyl halide can react by either mechanism, the strength of the nucleophile determines which mechanism takes place. Alkyl Halides 2. The nature of the nucleophile is another factor. Alkyl Halides Alkyl Halides 3. Effect of Leaving Groups A better leaving group increases the rate of both SN1 and SN2 react Alkyl Halides 4.Effect of Solvent 1. Polar protic solvents like H2O and ROH favor SN1 reactions because the ionic intermediates (both cations and anions) are stabilized by solvation. Polar protic solvents have acidic hydrogens (O—H or N—H) that can solvate the nucleophile, reducing their nucleophilicity. Alkyl Halides 4.Effect of Solvent 2. Polar aprotic solvents do not have acidic protons and therefore cannot hydrogen bond. Some aprotic solvents are acetonitrile, DMF, acetone, and DMSO. SN2 reactions proceed faster in aprotic solvents. Alkyl Halides Alkyl Halides Alkyl Halides Thinking Backwards in Organic Synthesis To carry out the synthesis of a particular compound, we must think backwards, and ask ourselves the question: “What starting material and reagents are needed to make it?” If a nucleophilic substitution is being used, determine what alkyl halide and what nucleophile can be used to form a specific product. Alkyl Halides Alkyl Halides Approaches Used in Organic Synthesis To determine the two components needed for synthesis, remember that the carbon atoms come from the organic starting material, in this case, a 1° alkyl halide. The functional group comes from the nucleophile, HO¯ in this case. With these two components, we can “fill in the boxes” to complete the synthesis. Alkyl Halides Approaches Used in Organic Synthesis Alkyl Halides The SN2 Reaction in the Synthesis of Drugs Alkyl Halides Elimination Reactions General Features of Elimination Elimination reactions involve the loss of elements from the starting material to form a new π bond in the product. Alkyl Halides Elimination Reactions Equations and illustrate examples of elimination reactions. In both reactions a base removes the elements of an acid, HX, from the organic starting material. Alkyl Halides Elimination Reactions Removal of the elements HX is called dehydrohalogenation. Dehydrohalogenation is an example of β elimination. The curved arrow formalism shown below illustrates how four bonds are broken or formed in the process. Alkyl Halides Elimination Reactions The most common bases used in elimination reactions are negatively charged oxygen compounds, such as HO¯ and its alkyl derivatives, RO¯, called alkoxides. Alkyl Halides Elimination Reactions To draw any product of dehydrohalogenation—Find the α carbon. Identify all β carbons with H atoms. Remove the elements of H and X from the α and β carbons and form a π bond. Alkyl Halides Mechanisms of Elimination There are two mechanisms of elimination—E2 and E1, just as there are two mechanisms of substitution, SN2 and SN1. E2 mechanism—bimolecular elimination E1 mechanism—unimolecular elimination The E2 and E1 mechanisms differ in the timing of bond cleavage and bond formation, analogous to the SN2 and SN1 mechanisms. E2 and SN2 reactions have some features in common, as do E1 and SN1 reactions.