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CHEM 2120 Experiment 5
Crossed-Aldol Condensation Objectives i. To synthesize dibenzalacetone from benzaldehyde and acetone acetone using the important
“Aldol condensation” reaction (carbon-carbon coupling) on the microscale: CHO
"
!-
+
benzaldehyde
dibenzalacetone
ii. To purify the microscale product by recrystallization#
Introduction The most characteristic reaction of the carbonyl group is the addition of nucleophiles at the electron-deficient carbon# $f the nucleophile is a carbanion (or at least an electronrich carbon atom) %e ha&e one of the most con&enient %ays of ma'ing CC bonds for the synthesis of comple carbon s'eletons# $n the aldol condensation* condensation* an aldehyde or 'etone is able to pro&ide both components for such an addition* since the -hydrogens are acidic* and in a sodium hydroide solution a small amount of the nucleophilic enolate ion is formed# The aldol reaction in&ol&es se&eral steps (see figure " belo%): i# base-catalysed generation of an enolate anion ii# nucleophilic attac' of this anion on a carbonyl carbon iii# protonation of the resulting anion to yield the initial aldol product
,
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ote that each step in the se.uence is in e.uilibrium and the entire reaction is therefore re&ersible# Treatment of the β-hydroy carbonyl compound %ith base causes the re&erse aldol (retro-aldol) reaction to occur#
O R1
C
CH 3
+
O
OH
R1
C
O CH 2
R1
C
CH 2
an /enolate/ anion
O R2
C
O R3
+
H2C
C
O
O R1
R2
C
C
CH 2
R1
R3
nucleophilic attac'
H
O
OH R2
C
CH 2
C
R1
R3
aldol product (a beta-hydroy carbonyl compound)
!i"ure 2# 0eneralized Aldol reaction mechanism#
+
H 2O
"
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Aldols readily lose %ater (dehydration) to complete the condensation process (of %hich the abo&e addition is the first stage)#
O
OH R2
C R3
CH 2
C
O
R2 R1
C
CH 2
C
R1
+
H2O
R3
ote that the C1C bond and the C1 bond are con2ugated* this resonance stabilization pro&ides the dri&ing force for the dehydration# The dehydration is usually acid catalysed but it can also occur in neutral or e&en basic conditions especially %hen the ne%ly forming C1C bond is con2ugated (for eample* in the product of this eperiment)# $n a “self condensation” there is only one type of carbonyl compound (e#g# acetaldehyde (%here 3,* 3" 1 ! and 3 4 1 C!4 in figure ") that reacts %ith itself# $n “crossed” or “mied” aldol condensations* t%o different reacting carbonyl compounds (aldehydes or 'etones) are used# Crossed aldols are usually synthetically poor reactions since they yield product mitures (%hy a miture5)# !o%e&er* they can be useful synthetically if one component has no -hydrogens (and hence cannot generate an enolate ion)# $n addition* the aldehyde carbonyl is more reacti&e to%ards nucleophiles than is the 'etone and this fact may be used to ad&antage# $n this eperiment* propanone (acetone) condenses %ith " moles of benzaldehyde (in " separate condensations) gi&ing ,*6-diphenyl-,*7-pentadien-4-one (“dibenzalacetone”) &ia a crossed aldol reaction (8igure , abo&e)# ote that the intermediate alcohols lose %ater spontaneously to gi&e the unsaturated product# This reaction is one of many &ariations* 'no%n collecti&ely as 9A;-CATA<=;> C>;AT$#
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#re$%b #rep%r%tion 1. 3eading# 3ead
and p# "@7-"@6 on 'etone and aldehyde C1 stretches# As per the %rite up .uestions belo%* refer to the posted $3 spectra of pure dibenzalacetone and identify the C1 and C1C stretching bands of dibenzalacetone (gi&e the fre.uencies)# Bie% the follo%ing =ouTube &ideos on the Aldol mechanism and laboratory method: http:%%%#youtube#com%atch5&14Di!rsEE'o (acti&e ",7) http:%%%#youtube#com%atch5&1=&zciFiao (acti&e ",7)
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2. Grite the $ntroduction for the lab report before the lab and submit a copy to the TA at the
beginning of the labH only this &ersion %ill be mar'ed by the TA and included in the report mar'* ie# any changes made to the $ntroduction after the lab %ill not be mar'ed# >etails on %hat to include in the $ntroduction are gi&en in the
Ia'e up a complete 3eagent >ata table in your lab noteboo' before the lab and submit a copy to the TA at the beginning of the labH this &ersion %ill be mar'ed by the TA as part of the report mar'# 8or your report* edit the table to gi&e the “actual” amounts used for the labH no other changes from the originally submitted &ersion %ill be mar'ed (e#g# changing the IG of a compound)# ote that you can either (i) hand %rite the data table into the lab noteboo' and submit a photocopy to the TA or (ii) ma'e up the table in ;cel (or G3>) and print t%o copies* one to submit to the TA and one to staple into the lab noteboo'# 3ecord the follo%ing data in your hardcover labbook for each reagent and additi&e in the reaction: • chemical name H structure H molar mass H amount to be used (grams and mol) H density (of li.uids) H m#p# b#p# H hazards and re.uired safety precautions •
stoichiometry of the reagents and theoretical yield of product
•
dra% the reaction e.uation
•
The reagent data and safety info can be found in the I>:
M&'& ben(%$de)*de +,$dric) eb site/
http:%%%#sigmaaldrich#comcatalogJroduct>etail#do5719,447K $AMN;=L81J;C M&'& %cetone +,$dric) eb p%"e/
http:%%%#sigmaaldrich#comcatalogJroduct>etail#do571,OP,"7K $AMN;=L81J;C M&'& diben(%$%cetone +,$dric) eb p%"e/
http:%%%#sigmaaldrich#comcatalogJroduct>etail#do571"7Q7"6K A<>3$C!L61;A3C!MCCATMJK93A>MN;=L81J;C
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#rocedure &%et* ote/ sodium hydroide in ethanol solutions are highly corrosi&e - e%r "$oves %nd s%et* "o""$es # ($f you get sodium hydroide on your hands* %ash them %ith
%ater until the “soapy” feeling has gone* including around your fingernails)# &*nt)esis
Jipette "7 µ< of benzaldehyde and then P µ< of acetone into a " m< sample &ial containing a magnetic spin &ane# Neep the &ial capped to a&oid e&aporation of the acetone# et add 4 m< of the a! catalyst solution (pre-prepared for you)# note: the a! catalyst solution is prepared by dissol&ing #7 g of a! in 7# m< of %ater then adding 4# m< of P6R ethanol#
tir the reaction at room temperature for 4 minutes# >uring this time* solid yello% product should precipitate from solution# note: good stirring is necessary in order to a&oid the formation of large clumps of product containing partially condensed materials and Strapped” a ! solution#
Collect the crude dibenzalacetone precipitate by suction filtration using a !irsch funnel (material coated on the spin &ane should be scraped off and included to a&oid product loss)# Gash the filter ca'e %ith three portions ( " m< each) of distilled %ater to remo&e a! (the filtrate should be neutral by the time of the last %ash)# note: it is essential to remo&e the a! completely# $f it is not remo&ed %ell* the recrystallization %ill be difficult#
Air-dry the product by maintaining the suction on the !irsch funnel for approimately , min# 3emo&e the product from the suction funnel and* if there is enough material* gently press the solid on a small clean dry piece of filter paper (clean spatula) to dry it as %ell as possible# et aside a small portion ( 6 mg) of the crude to be spotted on the T
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(&,!E/ > T use the centrifuge %ithout first sho%ing your instructor that the tubes are correctly balanced)#
Recr*st%$$i(%tion
3ecrystallize the crude product from hot P6R ethanol (up to " m< is usually needed but it depends on your yield so you must add the hot sol&ent in portionsH if there are solids that do not dissol&e e&en after adding " m<* use the pipette filter plug techni.ue to remo&e them)# 9ring the ethanol to boiling to dissol&e the product* then cool to room temp* then use an ice bath to cool further# The crystalline product should form fairly .uic'ly from the P6R ;t! upon cooling# After crystallization is complete* decant or filter the solution and allo% the crystals to dry then record the yield# ho% your recrystallized product to your instructor# ,n%$*sis o Recr*st%$$i(ed #roduct 1. 4C %n%$*sis. 3un T
product and (i&) pure dibenzalacetone standard using "R ethyl acetate in pentane as the mobile phase# note: dissol&e small amounts of each of the compounds in , m< or less of acetone# $t is &ery important to dissol&e the li.uid benzaldehyde sample in acetone because a neat sample of a li.uid is much too concentrated to gi&e a good Tissol&e about a half a drop or a drop of the benzaldehyde in , - ,#6 m< of sol&ent#
2. Me$tin" #oint. 3ecord the melting point of the dry recrystallized product and
compare to the literature &alue# 3. Inr%red &pectr%. There %ill be time to run $3 spectroscopy of se&eral
representati&e student samplesH your instructor %ill di&ide the class into three groups of fi&e students# ote that "nd year students are not per!itted to use the $3 instrument due to ris' of damage to the V,6 0e crystalH instead* your instructor %ill run the samples and demonstrate the instrument to you# An eample $nfrared spectrum of the benzaldehyde reagent and a genuine dibenzalacetone sample %ill be posted on 9lac'board for analysis#
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RIE-6# 8ull report as the /o only the followin for your introduction: ;plain %hat an Aldol reaction is# >ra% and describe each step of the mechanism for the " benzaldehyde + acetone reaction to gi&e the initial bi"-(β-hydroy)carbonyl product: !
Jh
!
Jh
Ia'e sure you use the proper terminology ie# nucleophilic attac'* deprotonation* etc#* and use the correct arro% con&entions for electron mo&ements (reproduce the same steps sho%n in the generalized mechanism abo&e in the introductory material* but gi&e the specific case of this product* ie# eplicitly identifying the 3 groups etc)# Ghat is function of the a! in this reaction (dra% the reaction step)5 Jropose and dra% a reasonable mechanism for ho% the initial bi"-(β-hydroy)carbonyl product forms the final product dibenzalacetone# Ghy is benzaldehyde + acetone synthetically useful %hereas acetaldehyde + acetone %ould gi&e a complicated miture5 Ghat apparatus and conditions (sol&ent* temp#* reaction time* etc) %ill be used for the reaction5 !o% %ill the dibenzalacetone product be isolated from the reaction miture and ho% %ill it then be further purified5 !o% %ill the product be characterized5 Jrocedure: as per the /ata and 3esults: as per the /iscussion: as per the /oes the T
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Compare the melting point of the recrystallized product %ith the literature melting point for dibenzalacetone (to get the m#p#* go to the Aldrich chemical company %eblin' listed in the prelab prep I> section abo&e)5 A concluding statement concerning %hether or not your data sho%s that dibenzalacetone %as produced in your eperiment# Fuestions on $3 spectra (4 mar's allotted* , mar' per .uestion) i# 3efer to the posted $3 spectra of pure dibenzalacetone and identify the C1 and C1C stretching bands of dibenzalacetone (gi&e the fre.uencies)H refer to IcIurry lecture tetboo' chap," and
7uestions on MR ,n%$*sis - 3 8O6& M,R9&
9elo% are $bonu" #ue"tion"% on the interpretation of the I3 spectra for the dibenzalacetone product# $t is not re.uired to do these for the lab report but the mar's indicated belo% %ill be a%arded as bonus mar's if they are done and ans%ered correctly# At most uni&ersities* "nd year che!i"try students are epected to be able to do this le&el of interpretation* therefore it is recommended that the chemists go through these .uestions to gain &aluable eperience and to prepare for the structure elucidation course* C!;I 4""X# 3efer to the IcIurry (@th ed) chapter ,4 and
! and ,4C-I3 I3 spectra posted to 9lac'board: • pure dibenzalacetone (Aldrich) • student dibenzalacetone product G,4 (pure) • a selected student dibenzalacetone product made this term
, !-I3# note: do not attempt to interpret the splitting patterns of the aromatic ,!-I3 pea's (O#Q and O#7 ppm) because they &iolate the “n+, rule” (due to long range coupling
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bet%een !Ws meta to each other) and there is an o&erlap of t%o multiplets at O#7 ppm# i# $dentify the chemically ine.ui&alent and e.ui&alent !Ws in the dibenzalacetone structure and ho% many ,!-I3 pea's are epected# ;plain %hat symmetry features cause %hat !Ws to be e.ui&alent# :1 bonus m%r;<
ii# >oes the student benzalacetone product ,!-I3 spectrum posted to 9lac'board (from this year) sho% pure product or are there significant impurity or side product pea's5 >oes the I3 spectrum sho% any unreacted reactants5 :0.5 bonus m%r;s<
,4C-I3# note: the three closely spaced pea's at OO# ppm in the ,4C-I3 spectrum are caused by the C>Cl4 sol&ent that the sample is dissol&ed in* thus they ha&e nothing to do %ith the product and should be ignored# i# $dentify the chemically ine.ui&alent and e.ui&alent CWs in the dibenzalacetone structure and ho% many ,4C-I3 pea's are epected# ;plain %hat symmetry features cause %hat CWs to be e.ui&alent# >oes the ,4C-I3 of pure benzalacetone gi&e the number of pea's epected5 :1 bonus m%r;<
ii# >oes the posted student benzalacetone product ,4C-I3 spectrum sho% the epected pea's5 $s the product pure or are there significant impurity or side product pea's5 >oes the I3 spectrum sho% any unreacted reactants5 :0.5 bonus m%r;s<
