The Wittig Reaction-Synthesis of Alkenes, Lab Reports of Organic Chemistry

Download The Wittig Reaction-Synthesis of Alkenes and more Lab Reports Organic Chemistry in PDF only on Docsity! Wittig Reaction 53 The Wittig Reaction: Synthesis of Alkenes Intro The “Wittig Reaction” is one of the premier methods for the synthesis of alkenes. It uses a carbonyl compound as an electrophile, which is attacked by a “phosphorus ylide” (the “Wittig reagent”.) While many other routes to alkenes can proceed via elimination reactions (E1 or E2 reactions from alcohols or alkyl halides, for example), in elimination reactions the carbon skeleton is already pre-assembled. In the Wittig reaction, however, two smaller carbon units are conjoined to make the alkene double bond. Thus molecules of increasing size and complexity can be quickly assembled. In addition, there is no ambiguity regarding the site of the double bond. (In contrast to elimination reactions, which often give mixtures of “more substituted” and “less substituted” structural isomers.) The Wittig reaction is nicely complementary to the aldol condensation, in which carbonyl compounds are attacked not by a phosphorus ylide but by an enolate. Aldol condensations always result in “enones”, alkenes with a carbonyl attached. Wittig reactions are more general in that the product carbonyl does not need to have an attached carbonyl. The alkene product 4 that you make today is the one that was used a few weeks ago as the colorizer for the chemiluminscence experiment (it gave the green solution.) Mechanism The general mechanism of the Wittig reaction is shown above. The phosphonium ion is deprotonated by base. The positively charged phosphorus atom is a strong electron-withdrawing group, which activates the neighboring carbon atom as a weak acid. For many phosphonium ions, a very strong base (commonly butyl lithium) is required in order to do the deprotonation. The use of such strong base requires moisture-free conditions such as were required for doing the Grignard reaction. In today’s experiment, however, very concentrated sodium hydroxide is OH Ph3P H H H H + Benzyltriphenyl- phophonium chloride mw = 389 g/mol 1 2 4 9-Anthraldehyde mw = 206 g/mol 9-(2-Phenylethenyl)anthracene mw = 280 mp = 100-150º NaOH CH2Cl2, H2O Ph3P H 3 The "Wittig Reagent" an "ylide" Cl R3 R R3 OR2 Ph3P R1 H R2 R1 R Br R1 H R PPh3 SN2 Phosphonium Salt Aldehyde or Ketone Alkene General Wittig Reaction: Synthesis of Alkenes R Ph3P R1 The "Wittig Reagent" an "ylide" Base (usually BuLi) Br + Ph3P=0 Wittig Reaction 54 strong enough to do the deprotonation. This is because the carbanion 3 that is produced is stabilized not only by the positive phosphorus, but also by conjugation with the benzene ring. Notice that carbanion 3 has a resonance structure, 3’, in which it is unnecessary to draw any formal charges. Either resonance structure is reasonable; 3’ has the advantage that it involves no formal charge, and has a double bond to carbon in exactly the same place where the final alkene C=C double bond ends. But 3’ has the disadvantage that it doesn’t illustrate why the carbon should be so nucleophilic. In addition, it involves a phosphorus with five bonds. Resonance structure 3 is useful in that it shows why the carbon should be so nucleophilic, and also is consistent with the popular octet rule. Once the carbanion/ylide 3 is formed, it is strongly nucleophilic, and attacks carbonyls just like other strong nucleophiles (for example, Grignard reagents…), producing an alkoxide 5. Alkoxide 5 rapidly closes onto the phosphorus to form the 4-membered ring 6, which is not very stable. The “betaine” 6, with its 4-membered ring, rapidly fragments to give the desired alkene 4 and triphenylphosphine oxide 7 as a side product. Wittig Reactions and the Phosphine Oxide Side Product 7: This side product is non- trivial to remove. It’s too “organic” to wash out into a water layer, and it’s too heavy to boil away. In today’s experiment, we will remove it based on its polarity and H-bonding ability, in contrast to the non-polar alkene 4. This separation will be accomplished by recrystallization from a somewhat polar hydrogen-bonding alcohol solvent, but it needs to be done carefully to selectively remove phosphine oxide 7 without losing too much of alkene 4. The Diagnostic Color Changes of Wittig Reactions: One interesting aspect of Wittig reactions that is not well illustrated today is that normally the carbanion/ylides 3 are colored, often intensely so. (Many are a deep, blood red or sometimes grape-juice purple). The product alkene and phosphine oxides are normally not colored, as is normally true of the phosphonium salt and the carbonyl electrophile. Thus you can often monitor Wittig reactions by color: formation of color shows you’ve made the ylide; disappearance of the color shows that the ylide has reacted and gone on to final products. While you will see some meaningful color changes today, they won’t be as intense or diagnostic, for a couple of reasons. 1) In today’s case, the extended conjugation of both the starting anthraldehyde 2 and the product alkene 4 make both of them colored. So whereas H H Ph3P H H 1 OH Ph3P H Ph3P H 3 OH O Ph3P O Ph3 P O PPh3 + Triphenylphosphine Oxide 2 4 5 6 7 3' Wittig Mechanism