Lab SYNT 718

7/24/2019 Lab SYNT 718

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Nucleophilic Addition to Carbonyl:

Grignard Reaction with an Aldehyde.

Instructor : Dilusha Harischandra ,PhD

Student: Betty Weiss

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ab !"N# $%&: Nucleophilic Addition to Carbonyl: Grignard Reaction

with an Aldehyde.

by : 'etty (eiss

Date of experiment:

)anuary *+, *%-

IN#RD/C#IN

#H0 GRIGNARD R0AC#IN

In 1912 the Nobel Prize in Chemistry was awarded to Victor ri!nard for his wor"#

In$esti!ation into the reactions of or!anic halides with ma!nesi%m# &his reaction is $al%able for its

ability to form carbon'carbon bonds# &he ri!nard rea!ents are formed from the reaction of an al"yl

halide with ma!nesi%m metal in anhydro%s ether# &he carbon of the ri!nard rea!ent can f%nction as

both as stron! base and a stron! n%cleophile# (owe$er) d%e to the hi!h reacti$ity of these ri!nard

rea!ents) !reat care m%st be ta"en to "eep the reaction as free from air and water as possible#

')0C#I10

&o perform and prepare the ri!nard rea!ent*isopropyl'ma!nesi%m bromide from 2'bromopropane#

&he ri!nard rea!ent reacts with +'methoxybenzaldehyde to form a secondary alcohol)1'

,+methoxyphenyl-'2'methylpropa'1'ol# &he ri!nard prod%ct sho%ld be p%rified by recrystallization

and characterized by &.C) I/ and N0/#

CH02ICA R0AC#IN

Br

+ Mgether

MgBr

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CH3CHCH2CH3

Clether

+ Mg CH3CHCH2CH3

MgCl

2A#0RIA!

ml bea"er

1 ml bea"er

2 ml bea"er

3rlenmeyer flas" ,2) 4 2 ml-

5%nsen b%rner

capillary t%bes

condenser with t%bin! cotton

filter f%nnel

fl%ted filter paper

2 ml !rad%ated cylinder

p( paper

Paste%r pipet)w6latex b%lb

hot plate

12 ml separatory f%nnel

silica !el &.C plate

R0AG0N#! AND PRP0R#I0!

1#

*3bro4opropane

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C3(75r ,Isopropyl 5romide-

00: 122#99 !6mol

5P: 97C

(azard: (i!hly flammable li8%id and $apor may dama!e fertility of %nborn child#

2#

CaCl2 Calciu4 chloride, anhydrous

00: 11#99 !6mol

(azard: (armf%l if swallowed) may ca%se respiratory irritation) can ca%se se$ere s"in b%rns and eye

dama!e#

#

,C2(5)2O Diethyl ether, anhydrous

dried ≥ 99# ,C- ); #< water

00: <+#12 !6mol

5P : +#=7C

(azard: Colorless) hi!hly $olatile flammable li8%id) it has narcotic properties) can ca%se temporary

dependence#

Pre$io%sly %sed as a !eneral anesthetic in early 1>+?s#

+#

,C2(5)2O Diethyl ether, solvent grade (ASC grade 5& 6, contains 7 *6 0#H8

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00: <+#12 !6mol

5P: +#=7C

(azard: Is sensiti$e to li!ht and air) tendin! to form explosi$e peroxide) $apor is hea$ier than air#

Diethyl ether inhibits the metabolic oxidation of 3&@() can ca%se false positi$e res%lts on Dr%!

Acreens#

Bhen sha"en %nder absol%tely dry conditions ether can !enerate eno%!h static electricity to start a fire#

#

I ,tomic n%mber -) the name is from ree" meanin! $iolet) p%rple d%e to the color of elemental

iodine $apor#

00: 2#> !6mol

0P: 117C

5P: 1>+7C

(i!hly sol%ble Iodine ion I) as other halo!ens free iodine occ%rs mainly as diatomic molec%le I2# (as

low toxicity and easy attachment to or!anic compo%nds) %sed in ray contrast#

Iofl%pane 12 I ,Da&scan- p%rification by (P.C) contrast a!ent %sed with AP3C&

for detectin! dopamine transporters in Par"inson?s diseases ,3'(ealthcare) ,mersham-# I wor"ed on

the proEect from Aept#21'pril#211# (i!hly radioacti$e materialF

ppro$ed by GD in Han#211) prod%ction in .ondon) ,mersham-) p%rification performed in

rlin!ton (ei!hts) proEect f%nded by 0#H# Gox#

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=#

2g ,0a!nesi%m- solid)atomic n%mber 12

00: 2+# !6mol

5P: 1917C

0a!nesi%m is the ele$enth most ab%ndant element by mass in the h%man body)ions are essential to all

cells # &hey interact with polyphosphate co%mponds s%ch as) &P)DN and /N#

<#

2agnesiu4 sul9ate, anhydrous

00: 12#< !6mol

Colorless crystal %sed as an anticon$%lsant) treatin! low ma!nesi%m le$els and maintainin! the proper

amo%nt of ma!nesi%m in the body when %sed as part of intra$eno%s feedin!s# It is also %sed in

pre!nant women to control seiz%res d%e to certain complications of pre!nancy) se$ere toxemia) pre'

clamsia and to control hi!h blood press%re) encephalopathy and seiz%res in children who ha$e s%dden)

ac%te nephritis#

0a!nesi%m s%lfate is a mineral# It wor"s by replacin! ma!nesi%m in patients who ha$e low

ma!nesi%m le$els in the body d%e to illness or treatment with certain medicines# 0a!nesi%m s%lfate

may also be %sed to treat seiz%res by decreasin! certain ner$e imp%lses to m%scles.

>#

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34etho;yben<aldehyde =3Anisaldehyde8

C>(>@2

00: 1=#1 !6mol

5P: 2+>7C

0P: '17C

Very sol%ble in alcohol) benzene and ether) insol%ble in water) acetone and chloroform #C60A top

pea"s 1)1=)<< m6z# @r!anic compo%nd that is commonly enco%ntered in the fra!rances both

synthetic and nat%ral# Clear li8%id with stron! aroma#

9#

%3=34etho;yphenyl83 * 4ethylpropan3%3ol =product8

C%%H%-*

22: %&.*%g>4ol

5P: 2=+ 7C

1#

% 2 Phosphoric Acid

0P: 7C

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5P: 17C

(azard: Nonflammable) corrosi$e) may ca%se irritation) redness) pain) b%rns to the s"in# Inhalation

may ca%se respiratory problems#

11#

NaCl =!odiu4 Chloride8

00: >#++ !6mol

0P: >17C

5P: 1+17 C

(azard: Irritant

12#

+6 NaH

00: 9#99 !6mol

5P: 1>>7C

0P: 1>7C

(azard: Corrosi$e) toxic) can ca%se b%rns6corrosion to the s"in#

20#HD! AND CAC/A#IN!

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Prepare the refl%x apparat%s and dry the !lassware in the o$en

Bei!ht #=2 ! 0! t%rnin!s

dd '+ crystals of iodine to the flas"

(eat the refl%x apparat%s to flood with iodine $apor ,my obser$ation dar" p%rple $apor

becomes clear-

Bei!ht 1#+>=! ,1#1ml- of 2'bromopropane and dissol$e in 1 ml of anhydro%s diethyl ether

dd 2'bromopropane sol%tion to the ma!nesi%m t%rnin!s 4 refl%x to ma"e the ri!nard

rea!ent

Poor the sol%tion thro%!h the condenser into a flas" and stir at medi%m speed while boilin!

Prepare hot water bath) immerse the flas" %ntil the water le$el is e$en with the reaction

mixt%re le$el in the flas") warm it for 1'1 min to complete the formation of ri!nard rea!ent

• llow sol%tion to cool to room temperat%re

• Bei!ht #=9=2 ! of +'methoxybenzaldehyde, p'anisaldehyde- into dry 2 ml 3rlenmeyer flas"

and add 1 ml of anhydro%s diethyl ether directly po%rin! from the container

• dd the sol%tion to the condenser o$er 1'1 min inter$als in a # ml portions and stir !ently

• Barm the sol%tion for 1 min and allow to cool to room temperat%re

• Isolate the prod%ct by po%rin! the mixt%re into ice water and acidify with 10 (P@+ %ntil

mixt%re is acid to p( paper ,p( 2# $erified by instr%ctor-

• Aeparate the layers by li8%id6li8%id extraction

• 3xtract the prod%ct into ether 4 wash it with Na@( 4 1 ml of sat%rated NaCl sol%tion

• Dry the ether layer with 2# ! of anhydro%s 0!A@+) !rad%ally %ntil sol%tion is not clo%dy

• se the hot water bath to distill the ether from the prod%ct

• Bei!ht the prod%ct and label it as ri!nard Prod%ct

• Characterize the prod%ct by %sin! &.C)I/ and N0/ method

R0!/#! AND CNC/!IN!

3mpty $ial: =#1>9!

Vial with a prod%ct: =#<!

Grignard Product: .+ g

#C =#HIN ?A"0R CHR2A#GRAPH"8

&hin'layer chromato!raphy) also "nown as &.C is a simple and inexpensi$e analytical

techni8%e %sef%l in identifyin! the p%rity of a compo%nd) and also can help identify the 8%antity of

compo%nds in a mixt%re of less than ten micro!rams# &his is performed by testin! the same mixt%re in

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a n%mber of different sol%tions and comparin! the / f $al%es ,distance compo%nd tra$eled6distance

el%ent tra$eled-# &.C is comprised of two different phases) the first is a stationary phase in which

s%itable absorbent ta"es in the compo%nd mixt%re and is %s%ally polar#

&he second is a mobile phase in which an el%ent ,a !as or a li8%id- mi!rates %p the &.C silica

!el plate) and is %s%ally nonpolar# If the compo%nd is more attracted to the non'polar el%ent then the

compo%nds will mi!rate farther %p the &.C plate) and if the compo%nd is less attracted to the polar

adsorbent than it will not mi!rate far# &he farther the compo%nd mi!rates with the el%ent) the lar!er

the / f $al%e will be# &he / f $al%e of a compo%nd in one el%ent may not be eno%!h to identify one

%n"nown compo%nd) it %s%ally will need to be tested in m%ltiple el%ents to be properly identified s%ch

as benzene or methylene chloride sol$ent#

&he principle of &.C method is "nown for more than 1 years# &he real brea"'thro%!h of &.C

as an analytical method ,(P&.C- "nown as hi!h performance thin layer chromato!raphy) also "nown

as planar chromato!raphy came abo%t years a!o as a conse8%ence of the pioneerin! wor" of 3!on

Atahl# &.C method has !ained increasin! importance as an analytical separation techni8%e) which is

probably d%e the effects of instr%mentation and a%tomation#

• Place #1ml of prod%ct into 2# ml $ial and add 1#9 ml of anhydro%s diethyl ether and cap it

• Apot the standard +'methoxybenzaldehyde one time and the %n"nown sample two times on

&.C silica !el plate and let the spot to air dry) mar" yo%r sample with pencil

• Prepare de$elopin! chamber) obtain ml of dichloromethane) c%t a piece of filter paper and

place it inside the chamber wall

• Poor ml of el%ent into chamber and moisten the filter paper 4 form a layer '+ mm deep at

the bottom

• Place the spotted silica &.C plate into the dichloromethane de$elopin! chamber and seal with a

clampin! chamber lid

• &he sol$ent mi!rates %p the silica !el plate) carryin! with it components at different rates

• fter de$elopin! the plate) remo$e it from the chamber and immediately mar" the el%ent front

with a pencil line

• Vis%alize %nder V li!ht) mar" the spots and calc%late the /f ,/etention factor-

/f J distance mi!rate by s%bstance6 distance mi!rate by sol$ent

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@igure %: Displayin! prod%ct spotted twiceK in the

middle is the standard) mi!ration by polarity %nder

V li!ht 2+ nm

Aol$ent: Dichloromethane

R9 std: +.>-.+ .$-5

R9 product: .&>-.+ .$B&

IR =IN@RAR0D !P0C#R!CP"8

Infrared ,I/- spectroscopy is an excellent method of the identification of or!anic f%nctional !ro%ps#

It?s often %sed to confirm presence or absence of a specific f%nctional !ro%p in a compo%nd) as well as

compo%nd p%rity# dditionally it can be also %sed as a preliminary indicator of types of f%nctional

!ro%ps that are present in the %n"nown sample L 1

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@igure *: n"nown L 1

Displayin! I/ spectr%m of maEor pea" @( !ro%p at cm'1) ,('bonded- broad spectr%m with

stron! intensity) stretchin! $ibration

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@igure B: Displayin! a prod%ct a secondary alcohol) 1',+'methoxyphenyl-'2'methylpropan'1'ol

I/ spectr%m at ++ cm'1 @( !ro%p) at 29< cm'1 showin! stron! intensity with 2) bands

C()C(24C( !ro%p ,al"enes-

Aince most or!anic compo%nds ha$e C'( bonds absorption in the ran!e of 2>' cm'1 is d%e to

sp C'( stretchin!K absorption abo$e cm'1 is from sp2 C'( stretchin! or sp C'( is near

cm'1# Apectr%m from 1'1+=2 cm'1 showin! bendin! $ibrations) medi%m intensity C(24C(

deformation# bsorption from 111'1=1 cm'1) showin! medi%m'stron! intensity) bendin! $ibrations

N(2 scissorin! 17 amines#

@igure : Displayin! I/ Apectr%m of p'anisaldehyde ,+'0ethoxybenzaldehyde-)the noticeable spectra

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broadens in

the cm

'1 re!ion)

with

medi%m

intensity

which

indicates a

benzaldehyde

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@igure +: 34etho;yben<aldehyde =p3anisaldehyde8

@r!anic compo%nd) consist of benzene rin! with an aldehyde and methoxy !ro%p# It?s a clear li8%id

with stron! aroma) widely %sed in pharmace%tical ind%stry#

N2R =N/C0AR 2AGN0#IC R0!NANC08

N0/ is one of the most important dia!nostic tools a$ailable to or!anic chemist# &his method pro$ides

information as to the relati$e positions and n%mbers of spin acti$e n%clei in a compo%nd )this tool can

be %sed to identify the str%ct%ral feat%res of a molec%le# N0/ can be %sed a s analytical tool to define

prod%ct ratios) p%rity complete chemical str%ct%re in a short period of time# Determination of pea"

inte!ration is performed by meas%rin! the line hei!ht of each inte!ral plot of the spectr%m and di$ided

by lowest $al%e to !et relati$e pea" intensities# Next step is to determine the chemical shift of each

resonance in the spectr%m# Important is also to determine the splittin! of each resonance in the

spectr%m#

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@igure -: Displayin! N0/ of p' anisaldehyde ) first si!nal is ( of C() second is a do%blet

of two ( of aromatic rin! ortho to @ atom) third is a do%blet of two ( of aromatic rin! ortho

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to *C(@ !ro%p) last is a lone ( of C(@#

&his lab and its techni8%e seemed to me to be the easiest to %nderstand I ha$e performed it

se$eral years and I fo%nd it a bit easier# &he only error made in this lab with my lab partner Aa%l

was by spottin! the &.C standard) please see fi!%re 1)it sho%ld ha$e been dil%ted##he percent yield o9 the product is: .+>.5 % - 6

&he p%rpose of addin! anhydro%s 0!A@+ is to ma"e ri!nard /ea!ent ,electron transfer from

ma!nesi%m to bromobenzene) carbonation occ%rs-#If the steps are omitted in the proced%re no

reaction will occ%r# &he first side prod%ct is biphenyl ,Ph'Ph-) the second is benzene ,Ph'

(-)res%ltin! from protonation of carbonation) so if there is any water in the sol$ent or

!lassware or if moist air is allowed to enter the reaction mixt%re) some of the carbonation will

be pronated# &he last problem co%ld be %nreacted startin! material, Ph'5r)0! or ester- )which

didn?t happen in o%r case# @$erall the proced%re and res%lts were s%ccess#

R0@0R0NC0

Atahl) 3!on# Thin layer chromatography, 2nd edition. Aprin!er'Verla! 5erlin) /eprint# 19>>#

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Lab SYNT 718

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