I. Qualitatively Predicting Favorable Direction of Hydrate EquilibriumII. HemiacetalsI. Glucose: Finding the Hemiacetal CarbonII. Equilibrium Differences in Inter vs. Intra-molecular Hemiacetal ReactionsIII. You cannot make a full acetal under acidic conditionsIV. Acetal Protecting GroupsI. Glucose: Making the Hemiacetal Carbona. To find the hemiacetal carbon on glucose, s tart counting the carbons starting at the aldehyde carbon, which is 1.b. To form the preferred ring structure of glucose:i. The oxygen that attacks is the sixth atom counting from the aldehyde carbon (carbonyl carbon)ii. The attacking oxygen is part of a hydroxyl group, and is a poor nucleophile (it’s really an alcohol, R-OH).iii. In adding a source of proton (acidic conditions), the carbonyl oxygen attacks and deprotonates an acid, making it positively charged. Now the weak nucleophile can do intramolecular attack on that oxygen, forming a ring. Conjugate base deprotonates H on protonated aldehyde O, making the hemiacetal.II. Equilibrium Differences in Inter vs. Intra-molecular Hemiacetal Reactionsa. Entropy drives favorability towards a given side of an equilibrium reaction involving formation of hemiacetalsi. Recall from the equilibrium equation: Kc = [products] n/[reactants] n1. With more molecules on the right side of the reaction, the product factor is greater, raising the value of equilibrium constant. Thus, a larger Kc, the more negative ∆G (we know this from the ∆G = ∆H – T∆S equation)2. More negative the Gibbs free energy, the more favorable the reaction will be.III. You cannot make a full acetal under basic conditionsa. Only under acidic conditions is this reaction possibleb. Why?i. When you generate an alkoxide ion, it is very destabilizingIV. Acetal Protecting Groupsa. Protecting the ketone from attack of nucleophiles (such as acetylide anion)b. For example:i. Acetylide anion can attack methyl iodide and a ketone/aldehyde.1. This anion is a very good nucleophile for SN2 or addition to the aldehyde or ketoneii. The acetylide anion also attacks the partial positive carbonyl c of a ketone (or aldehyde), making a new C-C bond.And that same addition that was made can also be a nucleophile that will attack other ketones or aldehydes.iii. For synthesis, the anion can attack other ketones instead of a methyliodide. So you need a protecting group to prevent this from happening.1. You need a temporary identity change: protecting group. An example of a protecting group is ethylene glycol, which means you are temporarily turning the ketone or aldehyde into an acetal.CHEM 0320 1st Edition Lecture 18Outline of Last Lecture I. Qualitatively Predicting Favorable Direction of Hydrate Equilibrium II. Hemiacetals Outline of Current Lecture I. Glucose: Finding the Hemiacetal Carbon II. Equilibrium Differences in Inter vs. Intra-molecular Hemiacetal Reactions III. You cannot make a full acetal under acidic conditionsIV. Acetal Protecting Groups Current LectureThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.I. Glucose: Making the Hemiacetal Carbon a. To find the hemiacetal carbon on glucose, s tart counting the carbons starting at the aldehyde carbon, which is 1. b. To form the preferred ring structure of glucose:i. The oxygen that attacks is the sixth atom counting from the aldehyde carbon (carbonyl carbon)ii. The attacking oxygen is part of a hydroxyl group, and is a poor nucleophile(it’s really an alcohol, R-OH).iii. In adding a source of proton (acidic conditions), the carbonyl oxygen attacks and deprotonates an acid, making it positively charged. Now the weak nucleophile can do intramolecular attack on that oxygen, forming a ring. Conjugate base deprotonates H on protonated aldehyde O, making the hemiacetal.II. Equilibrium Differences in Inter vs. Intra-molecular Hemiacetal Reactions a. Entropy drives favorability towards a given side of an equilibrium reaction involving formation of hemiacetalsi. Recall from the equilibrium equation: Kc = [products] n/[reactants] n1. With more molecules on the right side of the reaction, the product factor is greater, raising the value of equilibrium constant. Thus, a larger Kc, the more negative ∆G (we know this from the ∆G = ∆H – T∆S equation)2. More negative the Gibbs free energy, the more favorable the reaction will be.III. You cannot make a full acetal under basic conditionsa. Only under acidic conditions is this reaction possibleb. Why? i. When you generate an alkoxide ion, it is very destabilizingIV. Acetal Protecting Groups a. Protecting the ketone from attack of nucleophiles (such as acetylide anion)b. For example: i. Acetylide anion can attack methyl iodide and a ketone/aldehyde. 1. This anion is a very good nucleophile for SN2 or addition to the aldehyde or ketoneii. The acetylide anion also attacks the partial positive carbonyl c of a ketone(or aldehyde), making a new C-C bond.And that same addition that was made can also be a nucleophile that will attack other ketones or aldehydes.iii. For synthesis, the anion can attack other ketones instead of a methyliodide. So you need a protecting group to prevent this from happening.1. You need a temporary identity change: protecting group. An example of a protecting group is ethylene glycol, which means youare temporarily turning the ketone or aldehyde into an