081006 Benzocaine III
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Transcript of 081006 Benzocaine III
Synthesis of benzocaine – 3rd step 1
Synthesis of Benzocaine – 3rd step
☞ Deprotection of p-acetamidobenzoic acid 08. 10. 6. 月
담당 조교 : 문현영 (21-224, ☎ 9174)
▣ Scheme & Reagents
HN
O
CO2H
NH3
CO2H
NH2
CO2H
H3O
reflux
NaOAc
1. p-Acetamidobenzoic acid 179.17 250 mg mmol 1 eq.
2. 5% Hydrochloric acid ml mmol 6ml / g
▨ Procedure & Conditions of Reaction
bar in 10ml RBF with reflux condenser +1 +2 reflux
▣ Checking the Progress
TLC; Benzene:THF:Formic acid = 15:5:1, ref. 1, UV & develop with PMA
♨ Quenching & Work-up
Cool down to room temperature add same volume of water add sodium acetate trihydrate to pH 5
0oC solidify filtrate under reduced pressure dry
▽ References 실험유기의약품화학, 실험유기의약품화학 편찬위원회, 청문각, 2000
Synthesis of benzocaine – 3rd step 2
HAZARD DATA˙ ˙ ˙ ˙ ˙ ˙ ˙ ˙ ˙ ˙ READ THIS BEFORE GOING ANY FURTHER!˙ ˙ ˙ ˙ ˙ ˙ ˙ ˙ ˙ ˙ ˙ ˙ ˙ ˙ ˙ ˙ ˙ ˙ ˙ ˙ ˙ ˙ ˙ ˙ ˙ ˙ ˙ ˙ ˙ ˙
- p-acetoamidobenzoic acid (redirected from p-toluidine)
Poison. May be fatal if inhaled, ingested or absorbed through the skin. Suspected human carcinogen. Readily
absorbed through the skin. May cause cyanosis. Severe irritant.
- hydrochloric acid (less than 10%)
DANGER! CORROSIVE. LIQUID AND MIST CAUSE SEVERE BURNS TO ALL BODY TISSUE. MAY BE FATAL IF
SWALLOWED OR INHALED.
- sodium acetate trihydrate
CAUTION! MAY CAUSE IRRITATION TO SKIN, EYES, AND RESPIRATORY TRACT..
Synthesis of benzocaine – 3rd step 3
Valuation Report – 3rd report
조 ____ 학번 ___________
이름 ___________ 담당 조교 ___________
☞ Discussion of “Oxidation of p-toluidine”
Synthesis of benzocaine – 3rd step 4
Valuation Report – 3rd report
조 ____ 학번 ___________
이름 ___________ 담당 조교 ___________
☞ Deprotection of p-acetamidobenzoic acid
Q. p-acetamidobenzoic acid의 deprotection 후 생성되는 부산물은?
☞ Stereochemistry
Q. Ketone에 존재하는 carbonyl group의 α-position이 metal-base에 의해 deprotonation 되면 다음과 같은
두 가지의 가능한 enolate가 생성된다.
반응 기전은 다음과 같은 electron pushing으로 나타 낼 수 있고, chair transition state 를 거친다.
1) 이 enolate 들의 (E)-/(Z)- form 을 결정하고
2) aldehyde를 넣어주었을 때 가능한 4가지 transition state와
3) 이를 거쳐 생성되는 4가지 diastereomers 를 그려라.
Synthesis of benzocaine – 3rd step 5
Valuation Report – 3rd report
조 ____ 학번 ___________
이름 ___________ 담당 조교 ___________
☞ Metathesis
Q. (-)-Griseoviridin은 Streptomyces속에 속하는 Streptogramin antibiotics의 일종으로 vancomycin-resistant
bacteria에 활성이 있다고 알려져 있다. 2000년에 A.I. Meyers와 그의 co-workers들에 의해 처음으로 전합
성이 보고되었고, 다음과 같은 조건에 의해 성공적으로 합성을 마무리 지었다. (-)-Griseoviridin 전 단계
물질의 예상되는 구조를 그려라. 단, 보통의 화학 반응은 0.2∼0.5M에서 진행하는데 반해 이 반응은
0.001M 농도에서 수행되었다.
ref. Dvorak, C.A., Schmitz, W.D., Meyers, A.I. Angew. Chem., Int. Ed. Eng. 2000, 39, 1664-1666
Synthesis of benzocaine – 3rd step 6
Purification – 3rd Lecture
☞ 입체화학 (Stereochemistry) 08. 10. 6. 月
1. Isomer
a) constitutional isomer
b) stereroiomer
- chirality - asymmetric carbon(point) or plane
- enantiomer
- diastereomer - configurational diastereomers cis/trans diastereomers E/Z
- geometrical isomer
- conformational isomer
- epimer, anomer
2. How can we determine absolute configuration?
a) Polarimeter : d/l(+/-), optical activity
[α]D25 =α observed/l×c
b) X-ray crystallography : three dimensional structure
c) NMR : can discriminate diastereomer
but can't enantiomer
NOE(nuclear Overhauser enhancement)
d) Chiral HPLC or GLC : detect predominent ratio
3. Stereochemistry of Reactions & Stereoselectivity
a) determination of (R/S)-configuration
b) asymmetric synthesis
c) stereoselectivity