ORGANIC ANALYSIS BY FUNCTIONAL GROUP Prof' Guilbault Lecture 3 13th October 2006

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ORGANIC ANALYSIS BY FUNCTIONAL GROUPProf.
Guilbault Lecture 313th October 2006
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1 N,N,N,NTETRAMETHYLUREA 2 N,N
DIMETHYLFORMAMIDE 3 ACETAMIDE 4 N,N DIETHYL
ACETOACETATE
5 n-DODECYLAMIDE 2
. SAPONIFICATION REACTION WORKS FOR PRIMARY
AMIDES NOT SECONDARY OR TERTIARY 3.
REDUCTION TO AMINE SIGGIA (Anal. Chem.
27,550,1955) R-CONR1 LiAlH4 RCH2NR1
LiAlH2 STEAM DISTILL OUT AMINE AND TITRATE WITH
ACID NOT USED ANY LONGER PRIMARY
AMIDESREACT WITH 3,5 DINITRO BENZOYL CHLORIDE
2. TRACES OF AMIDES FERRIC HYDROXAMATE
METHOD CARBOXYLIC ACID CHLORIDES (CONTAIN
TRACES OF HCl OR ACIDS) l. TITRATE HCl in
CHLOROBENZENE-ETHER WITH n-TRIPROPYLAMINE
THEN 2. TITRATE FREE CARBOXYLIC ACID WITH NaOH
AFTER ACID CHLORIDE IS CONVERTED TO AMINE-HCl
WITH CHLOROANILINE GET 2 BREAKS ONE FOR ACID
CHLORIDE (AMINE-HCl FORMED),2nd FOR CARBOXYLIC
ACID
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• OR REACT ANHYDRIDE WITH ANILINE
• (SIGGIA, Anal Chem, 23,1717,1951)
• ANHYDRIDE ANILINE(EXCESS) RCONHPhenyl
  RCOOH
• EXCESS ANILINE TITRATED WITH ACID
• MIXTURE OF ACID AND ANHYDRIDE
• (SIGGIA, Anal Chem. 25,797,1953)
• TITRATE ACID DIRECTLY WITH TRI-n-PROPYL AMINE OR
  n-ETHYLPIPERIDINE (NO REACTION WITH ANHYDRIDE)
• THEN DO ANHYDRIDE AS ABOVE.
• 4. CARBOXYLIC ACID ANYDRIDE
• JOHNSON AND CRITCHFIELD (Anal Chem 28,430,1956)
• ANYDRIDE MORPHOLINE(EXCESS) ACID AMIDE
• THEN TITRATE TOTAL OF FREE CARBOXYLIC ACID ACID
  FORMED ABOVE AS ONE WITH NaOH.

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THEN ADD CS2 TO REACT WITH MORPHOLINE TO GIVE
THIOCARBAMIC ACID(TITRATE WITH NaOH)
1st END POINT TOTAL ACID ANHYDRIDE 2nd END
POINT IS ANHYDRIDE DIFFERENCE
ACID ALKOXYL AND OXYALKYLENE GROUPS
H
R O - AND O- C (CH2)n-O-
R A
ALKOXYL GROUPS R- 0 R1 HI
RI R1I H2O CUNDIFF AND
MARKUNAS (Anal. Chem. 33,1098, 1961) Titrate
excess HI with tetrabuylammonium hydroxoide in
Non-Aqueous Solution
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IF ANY ESTER PRESENT

• 2nd minus 1st - Alkoxyl Content
• 1st break use azoviolet orange to red
• 2nd break - red to
  violet
• Use visual or potentiometric
• 2. METHOXYL AND ETHOXYL ETHERS USE IODOMETRIC
  APPROACH
• R-O-R HI ? RI RI
• RI Br2 ? RBr IBr
• IBr 3 H2O 2 Br2 ? HIO3
  5 HBr
• HIO3 5 HI ? 3 I2 3
  H2O
• TITRATE IODINE WITH THIOSULFATE
• OXYALKYLENE GROUP.
• -O- CHR (CH2)n-O- Excess HI ?
  xI-CH2(CH2)nI xH2O
• 
  (decomposes to CH2CH2- I2)

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EPOXIDE GROUPS R-C-C-R HCl
(Excess) ? R COH CCl-R Titrate Excess
HCl with NaOH VARIOUS REAGENTS HAVE BEEN
PROPOSED MgCl2-HCl HCl EthylEther
HCl-cellosolve HCl-Dioxane Pyridine Cl
Pyridine OF THESE MgCl2-HCl IS GENERALLY USED
DIELDRIN IS ONE OF MOST COMMONLY ASSAYED EPOXIDES
A PESTICIDE
ONLY REACTS WITH HBr-DIOXANE REAGENT FOR EPOXY
RESINS HCl DIOXANE METHOD BEST INTERFERENCES
Alpha, Beta UNSATURATED ALDEHYDES AND
KETONES-SERIOUS INTERFERENCE AMINES SLIGHT
BENZOYL PEROXIDES D. ORGANIC PEROXIDES THEY
ARE VERY GOOD OXIDIZING AGENTSSTRENGTH VARIES SO
MUST KNOW WHAT YOU HAVE IN SOLUTION USE
REDUCING AGENTS AS I-, Fe,Sn, As3,
Ti3,Leucomethylene blue
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(a) IODOMETRIC METHODS WAGNER ET AL(Anal.Chem.
19,976,1947) RCOOOH 2 I- ? I2
RCOOH Titrate I2 with Thiosulfate
INTERFERENCES I2 WHICH REACTS WITH
UNSATURATED COMPOUNDS I2 R-CHCHR
? RCHICHIR (b) FERROUS Fe3
RCOOOH ? Fe SCN - ? FeSCN(Red)
(c) LEUCOMETHYLENE BLUE

• Zr4 ACCELERATES REACTION GOOD CATALYST
• TRACE METHOD USING N,N-DIMETHYL-p-PHENYLENE
  DIAMINE(NNDPD)
• RCOOOH NNDPD ? OXIDIZED NNDPD (560nm)
• ppm CONCENTRATIONS DETERMINABLE
• SCHOENEMAN REACTION
• RCOOH o-DIANISIDINE NO DYE FORMED
• RCOOH ORGANOPHOSHOROUS COMPOUND
  (PENTAVALENT)
• o-DIANISIDINE
  DEEP RED COLOR

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ORGANIC ANALYSIS BY FUNCTIONAL GROUPProf.
Guilbault Lecture 420th October 2006
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E. UNSATURATION R-C H CH R FOUR
APPROACHES (a) BROMINATION SIMPLE, RAPID
INTERFERENCE BROMINE CAN SUBSTITUTE FOR
HALOGENS ON ORGANIC MOLECULES, ALSO ADD TO
BENZENE RING (b) ADDITION OF IODINE
MONOHALIDES(CALLED IODINE NUMBER) MORE
SELECTIVE CAUTION THESE ARE OXIDIZING
AGENTS (c) HYDROGENATION VERY SPECIFIC BUT TIME
CONSUMING , NOT AS EASY TO RUN AND SPECIAL
EQUIPMENT NEEDED. NOT USED MUCH ANYMORE (EXCEPT
COULOMETRICALLY) (d) ADDITION OF Hg
GOOD LETS LOOK AT EACH ONE SEPARATELY (a) BROM
INATION Br2 RCHCHR ?
R-CHBR-CHBr-R FREE BROMINE ADDED IN SOLVENT OR
GENERATED COULOMETRICALLY FROM BrO3-, FROM Br-
H OR PYRIDINE SULFATE DIBROMIDE USUALLY
GENERATE Br2 COULOMETRICALLY UPON USE TO AVOID
INSTABILITY OF REAGENT COULOMETRIC GENERATION.
CALCULATE COULOMBS USED. (b) IODINE NUMBER ICl
and IBr USED RCHCHR IX(EXCESS) ?
R-CH- CH-R
I X IX
I- I2(Titrate with Thiosulfate) IODINE
NUMBER ((mL Thiosulfate for Blank)
(mLThiosulfate for Blank))N X 12.69 / Grams of
sample used (c) HYDROGENATION H2
catalyst(Rainey Nickel Used)
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Special Apparatus Coulometrically Generrated
Hydrogen (Miller and Ford, Anal. Cem. 30,
295,1958) Number of coulombs consumed amount
of unsaturation Use of coulometry has revived
hydrogenation. Very specific MERCURIC ACETATE
- C C - Hg(OAc)2(EXCESS) ROH ?
-COR-CHgOAc- TITRATE EXCESS Hg(OAc)2 BY ADDING
NaOH, THEN KI KOH LIBERATED IS TITRATED WITH ACID
TO PHENOLPHTHALEIN END POINT OR TITRATE HOAc or
IODINE ACETONE WILL INTERFERE 3 Hg(OAc)2
2 CH3CO 6 NaOH? COMPLEX E Alpha,Beta
UNSATURATION l. BISULFITE
ADDITION NaHSO3 CH2CH-X ?
NaSO3-CH2CH2-X WHERE X STRONG ELECTRON
ATTRACTING GROUP TITRATE EXCESS NaHSO3
IODOMETRICALLY INTERFERENCE ALDEHYDES 2.
MORPHOLINE REACTION
NOTES 1st ADDITION FAST BUT SECOND GENERALLY
SLOW WITH HALOGEN OR WITH HYDROGENATION F.
ACETYLENIC HYDROGEN a. HYDRATION METHOD
(SIGGIA, Anal. Chem. 28, 1481,1956) R-C CR
2 MeOH ? R-C(OMe)2CH2R H2O
R-CO-CH2-R NH2OH-HCl ? R-CNOH-CH2-R
HCl TITRATE HCl or ASSAY HYDROXAMATE
COLORIMETRICALLY b. USE OF SILVER(I) OR Cu(II)
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• SILVER NITRATE Ag HCCR ? AgCCR
  HNO3
• a. Add EXCESS AMMONIACAL SILVER NITRATE
• TITRATE EXCESS BY VOLHARD METHOD
• b. USE NEUTRAL SILVER NITRATE TITRATE ACID
  PRODUCED
• 2. Cu2Cl2
• Cu2Cl2 2 HCC-R ? 2 CuCC-R 2
  HCl
• TITRATE HCl WITH NaOH
• G. MIXTURES
• DO KINETICALLY BY REACTION WITH HYDROGEN OR
  BROMINE COULOMETRICALLY
• H. ACTIVE HYDROGEN
• THIS IS A HYDROGEN ATTACHED TO ANY ATOM EXCEPT
  CARBON(eg. ALCOHOLS, AMIDES,MERCAPTANS, SULFONIC
  ACID
• a. GRIGNARD REAGENT

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• (A) HYDROXYAMINE HYDROCHLORIDE
• OR
• R-C-H H2O NH2OH ? R-CNOH
  R1OH H
• OR
  H
• OR
• R-O-CHCH2 NH2OH H2O ? CH3-CNOH
  R-OH H
• 
  H
• WORKS WITH ALL
• HYDROLYSIS CATALYZED BY HYDROXYLAMINE
• (SAME REAGENT USED FOR KETONES AND ALDEHYDES)
• (B) OTHER METHODS
• l. DETERMINE ACETALS, ALDEHYDES AND VINYL
  ETHERS WITH BISULFITE

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• NITROGEN COMPOUNDS
• AMINO GROUPS
• l. TITRATIONS MOST AMINES ARE BASIC ENOUGH TO
  BE DIRECTLY TITRATED WITH ACID
• - ALL UNSUBSTITUTED ALIPHATIC AMINES HAVE THE
  SAME pKb ABOUT 5. CAN BE TITRATED IN
  NONAQUEOUS SOLUTION.
• UNSUBSTITUTED AROMATIC AMINES pKb ABOUT
  4.5.USE NONAQUEOUS. SUBSTITUENTS CAN AFFECT
  BASICITY
• 
  pKb
• SUBSTITUENT 2Position 3
  Position 4 Position
• None(Pyridine)
  pKb 5.2
• CH3- 6.0
  5.7 6.0
• C2H5- 5.8
  5.7 6.0
• t-Butyl- 5.8
  5.8 5.8
• F-
  -0.4 2.0
• Cl- 0.7
  2.8
• Br- 0.9
  2.8
• I-
  l.8 3.3
• OH- 0.8
  4.7 3.1

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OTHER METHODS FOR AMINES l. ANHYDRIDE R-NH2

R-CO-NHR RCOOH Or
Acetic Anhydride ? R2 NH

R-CONR2 RCOOH FAST, GOOD FOR PRIMARY
AND SECONDARY AMINES IN PRESENCE OF TERTIARY
AMINES INTERFERENCE HYDROXY GROUPS 2.
DIAZOTIZATION AROMATICS AND ALIPHATICS
BENZENE NH2-HCl HNO2 ? BENZENE-
NN-Cl ?
AZO DYE
(CHROMOGENIC) IF ALIPHATIC VAN SLYKE METHOD
R-CH2NH2 HNO2 ? RCH2OH
N2(Measure)
AROMATIC PRIMARY AND SECONDARY ONLY MIXTURES l.
ACETYLATE PRIMARY AND SECONDARY ONLY TITRATE
TERTIARY AS BASE IN GLYCOL-HYDROCARBON
SOLVENT 2. PRIMARY AMINE - REACT WITH
BENZALDEHYDE ? WATER USE KARL FISCHER
TITRATION (SULFUR DIOXIDE IODINE IN PYRIDINE)
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B. IMINO GROUPS R -C NR2
R1 l. COMPOUNDS ARE VERY BASIC, BUT LESS THAN
CORRESPONDING AMINES. CAN BE TITRATED IN
NON- AQUEOUS WITH PERCHLORIC ACID SOLVENTSACETIC
ACID AND DIOXANE 2. HYDROLYSIS R C NR2
WATER ? R CO R2NH2 R1

R1 DETERMINE KETONE WITH 2,4 DINITOPHENYLHYDRAZIN
E?RED COLOR C. USE OF TITANOUS AND CHROMOUS IONS
AS REDUCTANT OBJECTIVE- DETERMINE ANY ORGANIC
COMPOUND PRESENT IN A REDUCIBLESTATE. THESE ARE
VERY STRONG REDUCTANTS GENERATED
COULOMETRICALLY COMPOUNDS DETERMINABLE -NN-
-NO2 -NO -NHNH-
NN REAGENTS ARE Ti3 OR Cr2 EXAMPLES
R-NNR1 4 (H) ? RNH2 R1NH2
R-NO2 6 (H) ? RNH2 2H2O
R-NO 4(H) ? RHN2
H2O R-NHNHR1 2(H) ? RNH2
R1NH2 PROCEDURE DETERMINE EXCESS WITH Fe3 OR
COULOMETRICALLY D. HYDRAZINES DETERMINED BY
OXIDATION WITH IODATE, IODINE, OR Cu(II)
NH2NH2-H2SO4 2 I2 6 NaHCO3 ?
4NaI Na2SO4 6 CO2 N2 E. HYDRAZIDES
R- CO- NHNHR1 H2O H ? RCOOH
RNHNH2 DETERMINE HYRAZINE BY OXIDATION AS ABOVE

F. DIAZONIUM SALTS
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• BENZENE-NNCl- Cu2Cl2 HCl ?
• PHENOL N2
• MEASURE PHENOL FORMED
• G. QUATERNARY NITROGEN TITRATE AS BASE WITH
  ACID
• H. ISOCYANATES RCCO
• REACT WITH PRIMARY AMINE
• R-NCO R1NH2 ? R-NH-CO-NHR1
• (A) SULFUR COMPOUNDS
• ISOTHIOCYANATES
• R-NCS
• REACT WITH PRIMARY AMINE

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• ALSO OXIDATION
• 2 Cu 4 RSH ? 2 CuSR R-S-S-R
  H
• I2 2 RSH ? R-S-S-R 2 HI
• LATTER BETTER SINCE CAN TITRATE EXCESS I2 WITH
  THIOSULFATE

• IF ELEMENTAL FREE SULFUR PRESENT
• 2 Ago 2 RSNa ?? 2 RSSNa 2 Ag
  Ag2S R2S
• DISULFIDES R-S-S-R
• l. REDUCTION WITH SODIUM BOROHYDRIDE
• R-S-S-R H2 ? 2 R-S-H
• TITRATE MERCAPTAN FORMED AS ABOVE
• 2. OXIDATION TO SULFONIC ACID WITH Br2
• R-S-S-R 5 Br2 ? 2 RSO2Br 8
  HBr
• C. ALKYL SULFIDES
• R2S BrO3- ? R2SO ? R2SO2
• 
  Sulfoxide Sulfone
• TITRATE EXCESS BrO3- IODOMETRICALLY
• D. SULFOXIDES
• TITRATE AS BASES IN ACETIC ANHYDRIDE WITH
  PERCHLORIC ACID