Cmpund Structure Carbnyl Fundamentals (All infrmatin and examples brrwed frm Chem. 14D Thinkbk fr Fall 2006, Dr. Hardinger s Lecture Recrdings and Paula Yurkanis Bruce s Organic Chemistry 4 th editin, unless therwise indicated) Carbnyl- the functinal grup is cmprised f a carbn atm duble-bnded t an xygen atm (C=O). The varius types f carbnyl cntaining functinal grups are listed in the table n the right. Carbnyls can functin as bth a nuclephile and an electrphile. The plarity f the carbn-xygen bnd causes there t be a partial psitive charge n the carbn atm and a partial negative charge n the xygen atm. This electrn-deficient carbn atm acts as an electrphile. The carbnyl grup can als act as a nuclephile. The xygen f this functinal grup is electrn rich because f its lne pairs and the pi bnd. Nuclephilic attack n anther mlecule by the lne pairs n xygen r by the pi bnd give the same result because the prducts are resnance structures and thus identical. Aldehyde Ketne Carbxylic Acid Ester Amide Primary, Secndary, Tertiary (shwn) Enne Three C=O Fates Accept nuclephile at carbn Occurs in ALL Carbnyl additin mechanisms Prduces tetrahedral adduct which ccurs when the carbnyl carbn ges frm sp 2 t sp 3 hybridizatin. Depending n if there is a leaving grup attached t the carbnyl carbn there are tw pssibilities fr the prduct f a nuclephilic attack n the carbnyl carbn. Acetyl Chlride Acetic Anhydride Table Nte: Imines are nt included in this table hwever they have similar chemistry t aldehydes because the functinal grups share many similarities. Bth cntain a pi bnd between a carbn and heteratm. In additin bth can underg the three fates: nucelphilic attach, electrphilic attach, and enlate frmatin. Table Diagrams: www.wikipedia.rg Additin: n leaving grup (LG) present. Occurs with aldehydes and ketnes since alkenes and hydrgen are nt LGs. The first step invlves nuclephilic attack n the partially psitive carbn atm t create the tetrahedral adduct resulting in an xygen with a frmal psitive charge. The xygen is then prtnated t create an alchl. Diagram Taken Frm: http://www.chemhelper.cm/nucadd.html
Nuclephilic Carbnyl Substitutin: LG is present. Occurs with ester, amide, anhydride, and acid chlride functinal grups. Diagram Taken Frm: http://chemistry2.csudh.edu/rpendarvis/carbxder.html Accept electrphile (usually H+) at xygen There are tw pssible sites fr nuclephilic attack f the carbnyl n an electrphile: the lne pairs and the pi bnd. Is there a preference fr the electrphile (usually H+) t be accepted by the lne pair r the pi bnd? N. Bth sites are nuclephilic and bth lead t the same prduct thrugh resnance. Frm Enlate Assisted by resnance stabilizatin f cnjugate base Initiated by a base deprtnating the carbn adjacent t the C=O carbn. Diagram Frm: http://www.chem.leeds.ac.uk/peple/cmr/labstuff/litreviews/carbnylchemistry.dc Hw d we determine the rate f a C=O reactin? The rate determining step (rds) is the slwest step f the reactin, the step with the highest energy f activatin. This is the step that cntrls the rate f the reactin. In rder t determine the rate determining step f the C=O, we must use its mechanism. Prtn transfers are usually nt the rate-determining step s we can ignre them fr ur analysis. Nuclephilic attack n the C=O is usually the RDS. What factrs cntrl the rate f nuclephilic attack n C=O? (in rder f imprtance) 1) Magnitude f δ+ n the carbnyl carbn: A larger δ+ makes the carbnyl grup mre electrphilic, nucelphilic attack will ccur faster as a result. 2) Resnance: Resnance can increase r decrease the δ+ n the carbnyl carbn. Resnance may als be lst when the tetrahedral adduct is frmed. Resnance adds extra stability t the mlecule. As Dr. H put it, Resnance is like mney. Mlecules
that have it want t keep it and mlecules that dn t have it want t get it. Therefre, if resnance is lst the energy f the transitin state is higher since the mlecule is less stable. This will make the mlecule mre resistant t nuclephilic attack. As a general rule, resnance between atms in the same rw f the peridic table is strnger than resnance between atms that are in different rws. 3) Leaving grup: The presence f a gd leaving grup cntrls whether additin r substitutin ccurs. (Study the mechanisms fr additin and substitutin t better visualize this cncept). 4) Steric effects: If there are large grups attached t the carbnyl carbn the nuclephile may be sterically hindered frm attacking the carbnyl carbn and thus nuclephilic attack will be slwed because the carbn is blcked. What t think abut when asked t identify the fastest reactin relative t ther reactins: Lk fr differences between the reactins, cnsidering similarities will nt help in yur analysis. Analyze each f the fur factrs Examining nuclephilic additin and nuclephilic substitutin in the varius carbnyl cntaining functinal grups As mentined befre, the presence f a gd leaving grup determines if nuclephilic additin r nuclephilic substitutin will ccur. With that in mind, when bserving the varius carbnyl cntaining functinal grups, aldehydes and ketnes will underg nuclephilic additin since alkenes and hydrgen are nt gd leaving grups. By the same lgic, thilester (R-C-O-S-R), ester, amides, and carbxylate in (R-C-O-O - ) can underg nuclephilic substitutin since they cntain gd leaving grups. Nucelphilic additin reactivity fr aldehydes vs. ketnes Cnsidering the fur factrs mentined in the previus sectin: We will cnsider the differences between aldehydes and ketnes. Nte that neither have a leaving grup and that resnance is the same. Therefre, these tw factrs d nt affect the relative reactivity f the functinal grup in this case. δ+ C=O: The δ+ n the aldehyde carbnyl carbn is greater than that f the ketne carbnyl carbn because the ketne cntains tw alkyl grups that dnate electrn density t the carbnyl carbn whereas the aldehyde nly has ne alkyl grup. The mre the magnitude f the δ+ is reduced the mre resistant the carbnyl carbn is t nuclephilic attack. If the δ+ is reduced, the mlecule will be mre stable initially and there will be less f a need t get rid f the partial psitive charge.
Diagram Frm: http://www.chem.leeds.ac.uk/peple/cmr/la bstuff/litreviews/carb nylchemistry.dc ROHROR Sterics: The ketne has tw large alkyl grups attached t the carbnyl carbn, whereas the aldehyde nly has ne large alkyl grup attached. Therefere, the ketne has mre steric hinderance which inhibits the nuclephile frm attacking the carbnyl carbn mre than in the aldehyde case. As a result, ketnes are less reactive than aldehydes. Cnclusin: The rate f additin f aldehydes is faster than that f ketnes. Nuclephilic substitutin in thilesters, esters, amides, and carbxylate in. (Adapted frm Chem 14D Thinkbk CFQ #9, Carbnyl Chemistry-Fundamentals) Cnsidering the fur factrs that affect reactin rate: Carbnyl carbn δ+ and Resnance: cntrlled by the magnitude f resnance between the carbnyl carbn and its attachments. We must cnsider the resnance lst as a result f substitutin in additin t the affects f resnance n the magnitude f the δ+ n the carbnyl carbn (described abve). The magnitude f resnance lst will affect the rate nuclephilic attack n the carbnyl carbn. Let s cnsider the resnance f each functin grup in questin individually. Thilester: Resnance is between carbn and sulfur. Resnance is best between atms in the same rw f the peridic table. This is nt the case here as carbn is in the secnd rw and sulfur is in the third rw. Ester: Resnance between carbn and xygen. Strnger resnance because carbn and xygen are within the same rw f the peridic table. Amide: Better resnance than ester case because C and N are n the same rw f the peridic table and N is less electrnegative than O, meaning it is mre willing t share its lne pair electrns. Carbxylate in: Resnance with a negative xygen in the carbxylate case results in much mre significant resnance cntributrs than with neutral nitrgen in the amide case. Thus we cnclude based n carbnyl carbn δ+ and resnance that the rder f increasing resnance stabilizatin is thilester < ester < amide < carbxylate in. Steric effects: Difficult t determine. SR, OR, and NR2 are larger than O -, hwever it is difficult t distinguish between the thers. Overall, resnance
plays a mre crucial rle in determining the rate f nuclephilic attack. In this analysis, steric effects can be ignred because its effect n the reactin rate is minimal. Leaving grup: Thilester: SR is a gd leaving grup because f its high plarizability Ester: -OR is a prer leaving grup than SR because it is less plarizable than S, hwever, its higher electrnegativity makes it a better leaving grup than NH2. Amide: -NH2 a prer leaving grup than OR because N is less electrnegative and less willing t accept electrns. Carbylate: -O2 is a hrrible leaving grup. It has a frmal charge f 2- and lw plarizability. Cnclusin: In rder f nucelphilic carbnyl substitutin reactivity: thilester > ester > amide > carbxylate in. Recgnizing Mechanism Patterns The flwchart belw can help yu recgnize the mechanistic patterns present in carbnyl chemistry and help yu lgically reasn ut what cmes next when thinking abut mechanisms. 1. C=O 2. Nuclephilic attack at carbnyl carbn 3. Prtnate carbnyl xygen 4. Enlate frmatin 5. Tetrahedral Intermediate 6. Frm Enl 7. _-carbn acts as nuclephile 8. Eject a Leaving Grup 9. O acts as a nuclephile (This flwchart was derived frm OWLS-Survey f Carbnyl Reactins and Mechanisms Prblem #1) *Nte: At every tetrahedral intermediate step (5), yu shuld ask yurself Is there a leaving grup? in rder t knw if nuclephilic carbnyl substitutin r nuclephilic carbnyl additin will ccur.
Examples f the Varius Mechanism Steps The numbers at the varius mechanism steps crrespnd t the numbers in the flwchart. Lk at the flwchart while fllwing the mechanisms t reinfrce the cncepts learned and help guide yu thrugh the pssibilities f what can cme next. Mechanism #1 1) Start with C=O 2) Nuclephilic attack 3)Tetrahedral intermediate (n LG present) Deprtnate H2O+ 9) O acts as a nuclephile Prduct Mechanism #2 1) Start with C=O 2) Nuclephilic attack Mechanism #3 3)Tetrahedral intermediate (LG present) Deprtnate H2O+ 8) Eject a Leaving Grup 1) Re-frm C=O Prduct 1) Start with C=O 4) Enlate Frmatin Draw Resnance structure 7) _-carbn acts as nuclephile Prduct
Mechanism #4 1) Start with C=O 4) Enlate Frmatin 6) Frm Enl Prduct Mechanism #5- Fischer Esterificatin Even thugh we have nt explicitly learned this mechanism yet, using the flwchart f pssible mechanism steps as well as ur knwledge f carbnyl chemistry, we can predict the mechanism. We will learn the intricacies f this reactin in ur Carbnyl Survey f Reactins in the next tpic we will cver. But fr nw, let s analyze the mechanism steps with respect t ur flwchart. Sme Ntes abut Fischer Esterificatin: In Fischer Esterificatin we begin with a carbxylic acid in the presence f strng acid and a large excess f alchl. The reactin results in the frmatin f an ester. The carbxylic acid carbnyl must be prtnated first because the carbnyl carbn is a pr electrphile due t significant resnance with the hydrxyl grup. Als, methanl is a pr nuclephile due t the high electrnegativity f xygen. Putting a frmal negative charge n the methanl by deprtnating it in the presence f strng acid makes the methanl a better nuclephile. With this infrmatin, we can nw analyze the mechanism (see next page).
(A) 3. Prtnatin f the Carbnyl Oxygen (B) 2. Nuclephilic attack at carbnyl carbn (C) Deprtnatin (D) Prtnatin t create a leaving grup (E) 8. Eject a Leaving grup (F) Mre significant resnance structure (G) Deprtnatin