Selective transformations of substituted aryl compounds to fluorenes and phosphoramidates [Elektronische Ressource] : synthetic and spectroscopic studies / presented by Reda Haggam

Chemiker

Sujets

• Biologie

Informations

• Publié par: universitat_hohenheim
• Publié le: 01 janvier 2010
• Nombre de lectures: 21
• Langue: English
• Poids de l'ouvrage: 2 Mo

Extrait

Selective Transformations of Substituted Aryl
Compounds to Fluorenes and Phosphoramidates:
Synthetic and Spectroscopic Studies





Thesis presented in fulfilment of
the thesis requirement for the degree of
Doctor of Philosophy in Natural Sciences (Dr. rer. nat.)




Faculty of Natural Sciences
Universität Hohenheim


Institute of Chemistry




presented by

Reda Haggam


from Zagazig
(Egypt)



2010







Dean: Prof. Dr. Heinz Breer

1. Supervisor and Reviewer: Prof. Dr. Uwe Beifuss
2. Co-reviewer: Prof. Dr. Henry Strasdeit
3. Additional examiner: Prof. Dr. Walter Vetter

Submitted: 05.08.2010

Oral defence (viva voce): 30.09.2010



This submission was accepted on 30.09.2010 by the Faculty for Natural Sciences at the
Universität Hohenheim as “Thesis presented in fulfilment of the thesis requirement for the
degree of Doctor of Philosophy in Natural Sciences (Dr. rer. nat.)”











Die vorliegende Arbeit wurde unter der Leitung von Herrn Prof. Dr. Uwe Beifuss am Institut
für Chemie der Universität Hohenheim in der Zeit von August 2006 bis Oktober 2009
durchgeführt.

























I wish to express my cordial endless thanks and sincere
gratitude to Prof. Dr. Uwe Beifuss for his supervision,
valuable support and constructive encouragement that
were the solid pillars for the achievement of this
research. Without his advice and endless interest, this
study could not have been carried out and completed.
















TO MY PARENTS
MY WIFE & MY CHILDREN
MY BROTHER & MY SISTERS!




















PRELMINARY REMARKS

The work presented in this thesis was carried out under the supervision of Prof. Dr. Uwe
Beifuss at the Institute of Chemistry, University of Hohenheim, from August 2006 to October
2009. Parts of the results have already been published in an international peer reviewed
journal:


1 REDA HAGGAM, JÜRGEN CONRAD and UWE BEIFUSS
“Pactical and reliable synthesis of dialkyl N-arylphosphoramidates with nitroarenes as
substrates”
Tetrahedron Lett. 2009, 50, 6627–6630.


Concerning the co-authors:

Prof. Dr. Uwe Beifuss was the supervisor of this work. He was always available for scientific
discussions and valuable suggestions. He was involved in preparing the manuscript
throughout the whole process of publication and was responsible for all aspects of
publication. He is also the corresponding author of the publication.

Dr. Jürgen Conrad advised on all analytical processes and assisted in the interpretation of
NMR data. He was always available for scientific discussions. Also, he measured all of the
UnityNMR samples on the 500 MHz Varian Inova spectrometer.










TABLE OF CONTENTS

A GENERAL PART
1 INTRODUCTION…………………………………………………………………….1
2 HIPPOSUDORIC ACID AND NORHIPPOSUDORIC ACID……………………6
3 SYNTHESIS OF FLUORENES……………………………………………………10
3.1 Electrophilic aromatic cyclizations…………………………………………………...10
3.2 Radical cyclizations…………………………………………………………………..11
3.3 Palladium-mediated cyclizations for the synthesis of fluorenes and
related skeletons………………………………………………………………………14
3.4 Modifications of the fluorene skeleton……………………………………………….24
4 NATURAL PRODUCTS WITH A BENZO[b]FLUORENE SKELETON……...28
4.1 Isolation…………………………………………………………………………….…28
4.2 Structure elucidation of the kinamycins…………………………………....................30
4.3 Biological activity…………………………………………………………………….31
4.4 Synthesis of natural products with a benzo[b]fluorene skeleton……………………..31
5 DEOXYGENATION OF NITROAROMATICS………………………………….35
5.1 Early stage intramolecular cyclizations of nitroaromatics……………………………35
5.2 Cyclization of nitroaromatics with tervalent phosphorous reagents………….............36
5.3 Synthetic approaches to phosphoramidates…………………………………………..40
6 AIM OF THE WORK……………………………………………………………….47
7 RESULTS AND DISCUSSION…………………………………………………….53
7.1 Synthesis of fluoren-9-ones by Pschorr cyclization..………………………………....53
7.1.1 starting materials………………………………………………...............53
’ ’ ’ ’ ’7.1.2 Synthesis of the (2,5-dialkoxyphenyl)(2 ,3 ,4 ,5 -tetraalkoxy-6 -nitrophenyl)
methanols 233a-e……………………………………………………………………..54
’ ’ ’ ’7.1.2.1 Discussion of the spectral data of the (2,5-dialkoxyphenyl)(2 ,3 ,4 ,5 -tetraalkoxy
’-6 -nitrophenyl)methanols 233a-e…………………………………………………….56
’ ’ ’ ’ ’7.1.3 Synthesis of the (2,5-dialkoxyphenyl)(2 ,3 ,4 ,5 -tetraalkoxy-6 -
nitrophenyl)methanones 234a-e………………………………………………………60
’ ’ ’ ’ ’7.1.3.1 Discussion of the spectral data of (2,5-dialkoxyphenyl)(2 ,3 ,4 ,5 -tetraalkoxy-6 -
nitrophenyl)methanones 234a-e………………………………………………………62
’ ’7.1.4 Synthesis of the (2-amino-3,4,5,6-tetraalkoxyphenyl)(2 ,5 -
dialkoxyphenyl)methanones 235a-e…………………………………………………..67
’ ’7.1.4.1 Discussion of the spectral data of the (2-amino-3,4,5,6-tetraalkoxyphenyl)(2 ,5 -
dialkoxyphenyl)methanones 235a-e…………………………………………………..69
7.1.5 Synthesis of the methoxy-substituted fluoren-9-ones 236a-e by Pschorr
cyclization…………………………………………………………………………….73
7.1.5.1 Discussion of the spectral data of the methoxy-substituted fluoren-9-ones 236a-e….76
7.2 Synthesis of the hydroxy-sustituted fluoren-9-ones 242a-e…………………………..80
7.2.1 the hydroxy-substituted fluoren-9-ones 242a-e…..83
7.3 Synthesis of methoxy-substituted fluoren-9-ones by intramolecular
palladium-mediated arylation…………………………………………………………88
’ ’ ’ ’ ’7.3.1 Synthesis of the (2,5-dialkoxyphenyl)(2 -iodo-3 ,4 -5 ,6 -
tetraalkoxyphenyl)methanones 243a-e………………………………………………..89
’ ’ ’ ’ ’7.3.1.1 Discussion of the spectral data of the (2,5-dialkoxyphenyl)(2 -iodo-3 ,4 -5 ,6 -ethanones 243a-e………………………………………………..90
’7.3.2 Synthesis of the (2,5-dimethoxyphenyl)(2 -iodophenyl)methanone 243f…………….94
7.3.3 Palladium-mediated arylations of the 2-iodobenzophenones 243a-f…………………95
7.4 Cyclization studies of 2-nitrobenzophenones with triethyl phosphite……………....100
’ ’7.4.1 Discussion of the spectral data of the diethyl N-2-(2 ,5 -dialkylbenzoyl)-3,4,5,6-
tetraalkylphenylphosphoramidates 251b,c…………………………………………..101
7.5 Synthesis of dialkyl N-arylphosphoramidates using nitroarenes
as starting materials………………………………………………………………….103
7.5.1 Discussion of the spectral data for the diethyl N-arylphosphoramidates 256a-o……111
8 SUMMARY…………………………………………………………………………116
9 ZUSAMMENFASSUNG…………………………………………………………..125

B EXPERIMENTAL PART…………………………………………………………135
1. General Methods…………………………………………………………………….135
2. Synthesis of starting materials……………………………………………………….136
2.1 2-Bromo-1,4-dimethoxybenzene (229)…….………………………………………..136
2.2 3,6-Dimethoxy-2-nitrobenzaldehyde (231)……….…………………………………137
2.3 2,5-Dimethoxy-4-nitrobenzoic acid (232)………...…………………………………138
’ ’ ’ ’ ’3. Synthesis of the (2,5-dialkoxyphenyl)(2 ,3 ,4 ,5 -tetraalkoxy-6 -nitrophenyl)
methanols 233a-e……………………………………………………………………138
’ ’ ’ ’3.1 General procedure for the synthesis of the (2,5-dialkoxyphenyl)(2 ,3 ,4 ,5 -
’tetraalkoxy-6 -nitrophenyl)methanols 233…….…………………………………….138
’ ’3.2 (3,6-Dimethoxy-2-nitrophenyl)(2 ,5 -dimethoxyphenyl)methanol (233a)………….139
’3.3 (2,5-Dimethoxyphenyl)(2 -nitrophenyl)methanol (233b)…………………………...140
’ ’3.4 (4,5-Dime ,5 -dimethoxyphenyl)methanol (233c)…………..141
’3.5 (2-Methoxyphenyl)(2 -nitrophenyl)methanol (233d)……….………………………142
’3.6 (4,5-Dimethoxy-2-nitrophenyl)(2 -methoxyphenyl)methanol (233e)……………….143
’ ’ ’ ’ ’4. Synthesis of the (2,5-dialkoxyphenyl)(2 ,3 ,4 ,5 -tetraalkoxy-6 -
nitrophenyl)methanones 234a-e……………………………………………………..144
’ ’ ’ ’4.1 General procedure for the synthesis of the (2,5-dialkoxyphenyl)(2 ,3 ,4 ,5 -
’tetraalkoxy-6 -nitrophenyl)methanones 234…………………………………………144
’ ’4.2 (3,6-Dimethoxy-2-nitrophenyl)(2 ,5 -dimethoxyphenyl)methanone (234a)………...144
’4.3 (2,5-Dimethoxyphenyl)(2 -nitrophenyl)methanone (234b)…………………………145
’ ’4.4 (4,5-Dime ,5 -dimethoxyphenyl)methanone (234c)………...146
’4.5 (2-Methoxyphenyl)(2 -nitrophenyl)methanone (234d)…………..………………….147
’4.6 (4,5-Dimethoxy-2-nitrophenyl)(2 -methoxyphenyl)methanone (234e)……………..148
’5. Synthesis of the (2-amino-3,4,5,6-tetralkoxyphenyl)(2 ,5’-dialkoxyphenyl)
methanones 235a-e…………………………………………………………………..149
5.1 General procedure for the synthesis of the (2-amino-3,4,5,6-tetraalkoxyphenyl)
’ ’(2 ,5 -dialkoxyphenyl)methanones 235………….…………………………………..149
’ ’5.2 (2-Amino-3,6-dimethoxyphenyl)(2 ,5 -dimethoxyphenyl)methanone (235a)………150
’ ’5.3 (2-Aminophenyl)(2 ,5 -dimethoxyphenyl)methanone (235b)………..……………...151
’ ’5.4 (2-A