Arrows In dealing with various aspects of organic chemistry we use a various arrows, each with a unique, specific meaning. The list below contains all the arrows that cost many 307 students valuable points. Be familiar with them and specific in their use. 1. The reaction arrow is placed between starting material(s) and product(s); we use this arrow when we want to emphasize the chemical conversion without attention to the mechanism. Typically we place reagents above the arrow and solvents and conditions below. 2. “Reversible” or Equilibrium arrows or are used to signify that a conversion is reversible or in equilibrium. 3. The resonance arrow is used to signify the fact that several structures are contributing to the overall structure of a compound or intermediate. 4. The retrosynthetic arrow is used to signify that a target molecule (on the left) can be synthesized from the precursor (on the right). The precursor is chosen by a “strategic disconnection”. 5. Curved arrows or are used to describe the movements of electrons in a reaction or between resonance contributors in a compound or intermediate. A double-­‐hooked arrow indicates the movement of an electron pair (always from nucleophile to electrophile) whereas single-­‐hooked arrows denote the movements of single electrons (typically in free radicals). Bond-­‐breaking (e.g., in Br–Br) is indicated by two curved arrows pointing away from each other, bond-­‐making is shown by two such arrows “meeting”. Arrows Applied We use the pinacol rearrangement to illustrate several of these arrows. The pinacol rearrangement is an acid catalyzed dehydration converting a 1,2-­‐diol to a ketone. O H3O+ HO OH The reaction arrow simply indicates that the starting material is converted to the product; stoichiometry is not a consideration. We could also identify the H+ source (e.g., H2SO4) and the reaction temperature (e.g., 100°). Mechanism H HO 1) + OH HO + HO 2) + OH2 OH2 OH2 + HO + H2O + H2O HO HO 3) H2O 4) + HO + + O H O + + + H3O When we discuss the mechanism, we begin by protonating one of the OH groups (step 1). We show this by a double-­‐hooked arrow originating at an oxygen lone pair and pointing to the H; a second similar arrow “moves” the two electrons of the O–H bond to the O, creating a lone pair. NOTE that the positive charge does not “move”: the existing charge (on H3O+) is neutralized by the moving electron pair and a new positive charge is generated on the OH group, because its lone pair captures an H+. The protonation is reversible; hence the “reversible” arrows. In step 2 the good leaving group, H2O, is lost generating a tertiary carbocation. We signify this by a two-­‐spiked curved arrow, “moving” the electron pair to the O. Because carbocations are electrophiles (and H2O is a sufficiently good nucleophile) the reaction is reversible. In step 3 one of the adjacent methyl groups moves to the cationic site. We signify this by a curved two-­‐spiked arrow pointing to the carbon bearing the positive charge. Is this reaction reversible? In principle, alkyl shifts can be reversible. In the special case discussed here, there are two factors working against reversibility: 1) the rearranged carbocation is resonance stabilized (indicated by the resonance arrow), giving it added stability; 2) the hydroxyl proton is highly acidic because of the partial positive charge on O. Accordingly the rearranged carbocation is deprotonated rapidly (step 4, curved arrow from base, H2O). These facts justify the use of a reaction arrow for step 3. NOTE that resonance is not a separate reaction step; the reaction forms the resonance hybrid, not a resonance contributor. The deprotonation (step 4) is, of course, reversible, just as the protonation (step 1); it requires the use of “reversible” arrows. Further Examples Curved arrows are suitable to signify the “electron flow” in concerted reactions, such as the Diels-­‐Alder reaction, CHO CHO or to signify the electron movement converting two resonance contributors, as in the allyl cation (Chapter 15). + + We will use these arrows extensiveely when discussing resonance in aromatic compounds (Chapter 16). [Please, get used to the notion that resonance contributors do not exist – they are used only to represent resonance hybrids which we cannot depict properly by a single line structure.] Single-­‐hook curved arrows are used to account for electron movement in free-­‐radical reactions. For example, the initiation step of a free-­‐radical bromination can be shown as follows: Br• + Br–Br Br• a termination reaction (in the chlorination of methane) is shown below. H3C• •CH 3 H3C CH3 The retrosynthetic arrow (⇒) signifies that “the compound on the left should be accessible from the compound on the right”. For example, to synthesize a ketone you would recall that, in general, ketones can be prepared by oxidation of an alcohol O OH You then recall that secondary alcohols can be prepared from an aldehyde by reaction with an organometallic reagent. The key is the electrophilic nature of the carbonyl carbon and the nucleophilic nature of the organometallic reagent. For the compound shown above we can choose two different approaches depending on which fragment carries the carbonyl group and which is attached to the organometallic reagent. We call this choice a strategic disconnection. H Met O OH H Met O As synthesis becomes more prominent in the course, you need to do more retrosynthetic thinking.