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

Synthesis of benzocaine – 3rd step 7

Instant Report – 3rd report

조 ____ 학번 ___________

이름 ___________ 담당 조교 ___________

☞ Introduction

☞ Procedure and who did it

☞ What did you see

☞ Mechanism