صدى الصوت مشرفـة عـامـة
كيف تعرفت علينا : من صديق الكــلــيــة : العلوم القسم ( التخصص ) : ميكروبيولوجي السنة الدراسية (المستوى الدراسي) : دراسات عليا الجنس : عدد الرسائل : 10196 العمر : 45 الدوله : اليمن العمل/الترفيه : . المزاج : متقلب نقاط : 13687 تاريخ التسجيل : 27/12/2010 : :قائمة الأوسمة : :
بطاقة الشخصية التقييم: 10
| موضوع: The Aldol Reaction الإثنين يوليو 25, 2011 4:20 pm | |
|
The AldolReactionIntroduction-Near the end of the discussion ofenolization there was an analysisof the reactivity of hydroxide ion towards the carbonyl carboncompared to the hydrogen ato the carbonyl carbon in acetaldehyde. That analysis concludedthat addition to the carbonyl group was approximately 10,000 timesmore likely than abstraction of an a-hydrogen.But because addition of hydroxide ion to the carbonyl group isreadily reversible, it is a non-productive reaction. While the abstraction of ana-hydrogen isalso a reversible reaction, the enolate ion that is formed has analternative reaction pathway available to it- addition to thecarbonyl carbon of another acetaldehyde molecule. This is calledthe aldolreaction.Figure 1 summarizes the process.Figure1The Aldol Reactionof AcetaldehydeNote that the net effect of the aldolreaction is to add the "components of" one molecule ofacetaldehyde to the carbonyl group of a second molecule ofacetaldehyde, the "components of" acetaldehyde being H andHCOCH2.The aldol reaction of two aldehydes is oflimited synthetic utility. However, there are many "aldol-like"reactions which involve the essential features described in Figure1. Figure 2 highlights these features.Figure2General Features ofthe Aldol ReactionThe aldol reaction requires an aldehyde orketone that contains at least one a-hydrogen. Thea-carbonbecomes nucleophilic when it is deprotonated by a base. Thecarbonylcarbon is electrophilic. Coulomb's Lawbrings these two oppositely charged species together to form a C-Cbond.The R groups may be H, alkyl, or aryl. Whenthe R groups in one molecule are different than those in theother, the reaction is called a crossed-aldolreaction. Theability to join different aldehydes and ketones together is whatgive this process its synthetic value.The word aldol is a common name for theproduct of the reaction shown in Figure 1. It is a type ofcompound called a b-hydroxyaldehyde.Generally the word aldol is used to refer to anyb-hydroxyaldehydeor b-hydroxyketone.Exercise 1Enter the letter of any compoundthat does not meet the structural requirements for the aldolcondensation: Exercise2 Enter the letter of anyb-hydroxyaldehydeor b-hydroxyketoneinto the text field: Exercise3 Draw the structure of the aldolthat would be formed from the aldol condensation of each of thefollowing aldehydes and ketones.Like other alcohols, b-hydroxyaldehydesand b-hydroxyketonesundergo dehydration to produce alkenes. In fact, it is difficultto isolate b-hydroxyaldehydesand b-hydroxyketonesbecause they are very prone to dehydration. Dehydration ofb-hydroxyaldehydesand b-hydroxyketonesIn order to isolate the product shown inFigure 1, the reaction conditions must be mild; the temperaturemust be kept low and the amount of acid used to protonate thealkoxide ion intermediate must be carefully controlled. If toomuch acid is added, or if the temperature is too high, the aldolwill dehydrate to form a conjugatedalkene as demonstrated in Figure 3.Figure3Dehydration of ab-hydroxyaldehydeThe conjugated alkene shown in Figure 3 isalso called an a,b-unsaturatedaldehyde. This means that the double bond is between the carbonatoms a andb to thecarbonyl carbon. In this position the p orbitals of the doublebond may interact with those of the carbonyl group to form anextended, i.e. delocalized, pi system. The delocalization of theelectrons in this pi system results in greater stabilization sincethe electrons experience greater nuclear attraction. Figure 4offers two perspectives of the orbital geometry that affords thisextra stabilization. The trans isomer was chosenarbitrarily.Figure4Orbital Alignmentin a,b-unsaturatedSystemsExercise4 Draw the structure of thea,b-unsaturatedaldehyde or ketone that would be formed by dehydration of each ofthe aldol products you drew in Exercise 3.RetrosyntheticAnalysisFor synthetic organic chemists it'simportant to develop the ability to mentally "deconstruct" atarget structure into simpler molecules from which that target maybe made. The process of intellectual deconstruction is calledretrosyntheticanalysis. The focal point of suchendeavors is inevitably the functional group(s) within the targetmolecule. In the case of a,b-unsaturatedaldehydes or ketones the functional group of interest is the C-Cdouble bond. Disconnecting these two carbons as animated in Figure5 reveals the structures of the two components from which thetarget molecule was prepared.Figure5Take One StepBackExercise5 Each of the following compoundswas prepared by an aldol condensation followed by dehydration. Ineach case, select the structure of the starting material from thelist of choices in the box below. Enter the appropriate letterinto the text field.Exercise6 Each of the following compoundswas prepared by a crossed aldol condensation followed bydehydration. In each case, select the structures of the startingmaterials from the list of choices in the box above. Enter theletter of the compound that serves as the nucleophilic componentfollowed by that of the electrophilic component. For example, thenucleophilic component used to prepare the first compound is A,while the electrophilic component is F.ExamplesTreatment of acetone with base results inthe aldol reaction shown in Equation 1.Experimentally reaction 1 is tricky toperform. However, if the product is separated from the reactionmixture as it is formed, it is possible to isolate the product inover 70% yield.Acetone participates in a crossed-aldolreaction with furfural, an aldehyde produced from corn stalks, asdescribed by Equation 2, where the carbon-carbon bond that isformed is highlighted in red.An amazing aldol-type reaction was involvedin the total synthesis of ginkolide B, one of the activecomponents in extracts from the Ginko biloba tree. Equation3 outlines this key step.In this reaction the potentiallynucleophilic carbon is ato the carbonyl group of an ester rather than a ketone oraldehyde. Lithium diisopropylamide (LDA) was used to deprotonatethis carbon. The resulting enolate ion added to the carbonylcarbon of the complex pentacyclic ketone to form the C-C bondshown in red.Equation 4 depicts an intramolecularcrossed-aldol reaction that constitutedthe last step in a total synthesis of racemic progesterone.Even though the reaction conditions were very mild, theintermediateb-hydroxyketoneunderwent spontaneous dehydration to produce thea,b-unsaturatedketone.O=CHemDirectory
_________________ | |
|