Synthesis and Thermolysis of Some Aromatic and Heterocyclic Amidoxime Derivatives

285 Pages·2013·2.29 MB·English

Kingdom of Saudi Arabia
Ministry of Higher Education
Umm Al-Qura University
Faculty of Applied Science
Chemistry Department

Synthesis and Thermolysis of Some Aromatic
and Heterocyclic Amidoxime Derivatives

By
Layla Ahmad Taib
M.Sc. in Chemistry

A thesis
Submitted in Partial Fulfillment of the Requirements for the Doctor
Degree Philosophy of Sciences in Chemistry (Ph.D)
( Organic Chemistry)

Supervised by

Prof. Dr. Abdel-Aal M. Gaber Prof. Dr. Hussni A. Muathen
Professor of Organic Chemistry Professor of Organic Chemistry
Department of Chemistry Department of Chemistry
Faculty of Applied Science Faculty of Applied Science
Umm Al-Qura University Umm Al-Qura University
Makkah Al-Mukkaramah Makkah Al-Mukkaramah

1433H- 2012G

ﻢﯿﺣﺮﻟا ﻦﻤﺣﺮﻟا ﷲا ﻢﺴﺑ

مﻮﻠﻌﻠﻟ ﺰﯾﺰﻌﻟاﺪﺒﻋ ﻚﻠﻤﻟا ﺔﻨﯾﺪﻤﻟ ﺮﯾﺪﻘﺘﻟاو ﺮﻜﺸﻟا ﻞﯾﺰﺠﺑ مﺪﻘﺗأ
ﻢﻗر ﻢﻋﺪﻟا ﻰﻠﻋ (ﺔﯿﺜﺤﺒﻟا ﺢﻨﻤﻟا ﺞﻣاﺮﺒﻟ ﺔﻣﺎﻌﻟا ةرادﻹا) ﺔﯿﻨﻘﺘﻟاو
(ﺚﺤﺒﻟا) ﺔﻟﺎﺳﺮﻟا هﺬھ مﺎﻤﺗ ﻷ مﺪﻘﻤﻟاو (٠٥٧٧- ١١-ط-ت)

ﺔﺜﺣﺎﺒﻟا
ﺐﯿﻃ ﺪﻤﺣأ ﻰﻠﯿﻟ
ACKNOWLEDGEMENT

Praise and gratitude be to ALLAH, almighty, without whose
gracious help it would have been impossible to accomplish this work.
Working with this thesis has been a very interesting and valuable
experience to me and I have learned a lot.
First and foremost, I would like to thank my supervisors Prof. Dr.
Abdel-Aal Mohamed Gaber and Prof. Dr. Hussni Ahmad Muathen, for
their guidance, encouragement, advice and constructive comments have
greatly improved this work. I would like to specially thank them for all the
discussions that we undertook, which improved my understanding of the
work tremendously. They taught me to realize the importance of
fundamental research and its broad impact. Their patience in handling
situations, generous support and confidence in my abilities motivated me to
give my best in studies. It was a great pleasure for me to conduct this
thesis under their supervision.
I am especially thankful and grateful to Prof. Dr. Khalid S. Khairou
Head of Chemistry Department, Umm Al-Qura University for his
continuous encouragement and for the facilities provided during the work.
In addition, I would like to express gratitude to all my colleagues and my
friends for useful discussions and prayers
I would like to show my greatest appreciation to Mr. Mohamed M,
Ekhwan I can't say thank you enough for his tremendous support and help.
Finally yet importantly, I would like to thank King Abdulaziz
University and labs at King Fahd Center for Medical Research.
Layla Tiab
CONTENTS
CONTENTS

Page
LIST OF FIGURES……………………………………………. i
AIM OF THE WORK….……………………………………….. vii
ENGLISH SUMMARY…………………………………………. ix
ABBREVIATIONS……………………………………………… xvi
INTRODUCTION……………………………………………….. 1
Chemistry of Amidoxime Derivatives………………………….. 1
1. Synthesis of Amidine Derivatives……………………… 2
1.1. Preparation of Amidines from Cyanides…………………… 2
1.2. Prepration of Amidines from Cyanides, Alumininum
Chloride, and Ammonia or Amines……………………… 2
1.3. Preparation of Substituted Amidines from Ketoxime
Sulphonates and Ammonia or Amines……………………. 2
1.4. Preparation of Amidines from Cyanides, Ammonia or an
Amine, and an Ammonium or Substituted ammonium Salt. 3
1.5. Preparation of Amidines from Substituted Amides, a
Sulphonyl Chloride and an Amine………………………. 4
1.6. Preparation of Substituted Amidines from Ammonium or
Substituted Ammonium Salts and N-Acylbenzene
sulphonalkyl amides or Acyl benzenesulphonanilides…… 4
1.7. Preparation of N-Arylbenzamidines from Benzonitriles and
Anilines in the Presence of AlCl 5
3………………………………………….
1.8. Preparation of Amidines by Photolysis……………………. 5
2. Synthesis of Amidoximes……………………………………. 6
2.1. Action of Hydroxylamine on Nitriles…………………….. 6
2.2. Action of Hydroxylamine on Amides or Thioamides……. 6
2.3. Reduction of Nitrosolic and Nitrolic Acids 7
2.4. Action of Ammonia on Hydroximic Acid Chlorides 8
2.5. Reduction of Oxyamidoximes………………………… 8
2.6. Action of Hydroxylamine on Iminoethers 9
2.7. Action of Hydroxylamine on Amidine Hydrochlorides 9
2.8. Action of Ammonia on Oximinoethers…………………… 9
2.9. Action of Formamidoxime on Aromatic Aldehydes 10
2.10. Action of Ammonia on Glyoxime Peroxides………….... 10
2.11. Rearrangement of α-Hydroxylamino Oximes to Cyclic
Amidoximes by the Action of Sodium Borohydride……. 11
2.12. Synthesis of Arylamidoximes from Arylnitriles and
Hydroxylamine……………………………………………. 11
2.13. Reactions of Monothiooxamides with О-Methylhydroxyl
amine………………………………………………………. 11
2.14. Synthesis of O-Vinylamidoximes 12
2.15. Synthesis of Heterocyclic Amidoximes 12
3. Properties and Chemical Reactivities of Amidoximes 16
3.1. Organic Complexes……………………………………… 16
3.2. Thermal Decomposition………………………………… 16
3.3. Thermal Fragmentation of N-Arylbenzamidoxime and O-
Phenylsulfonyloxime Derivatives (STP)………………….. 18
3.4. Flash Vacuum Pyrolysis of N-Phenylbenzamide Oxime
and Related Compounds (FVP)…………………………… 19
3.5. Thermal Transformation of Arylamidoximes in the
presence of Phosphorous Ylides………………………….. 20
3.6. Hydrolysis 21
3.7. Reduction 22
3.8. Oxidation 23
3.8.1. Oxidation of Arylamidoximes by Hydrogen Peroxide and
Horseradish Peroxidase in Water………………………….. 23
3.8.2. Oxidation of Arylamidoximes by Various Chemical and
Biomimetic Systems……………………………………….. 24
3.9. Cyclization………………………………………………….. 26
3.9.1. Synthesis of New Thiophene, Furan and Pyridine
Substituted 1,2,4,5-Oxadiazaboroles……………………… 26
3.9.2.Synthesis of 3-aryl-5-(n-propyl)-4,5-dihydro-1,2,4-
Oxadiazoles……………………………………………….. 27
3.9.3. Synthesis of 4,5-dihydro-1,2,4-oxadiazolines from N-
unsubstituted amidoximes………………………………… 27
3.9.4. Synthesis of 3-Aryl-1,2,4-Oxadiazines………………….. 28
3.9.5. Synthesis of 1,2,4-Oxadiazoles 29
3.9.6. Synthesis of 1,2,4-Thiadiazoles 32
3.9.7. Synthesis of 1,2,3,5-Oxathiadiazoles 33
3.9.8. Cyclization and Rearrangement of N-Arylbenzamid-
oximes by Reaction with Nitrile Oxides……………. 34
3.9.9. Cycloaddition of Nitrile Oxides to Amidoximes 34
3.9.10. Synthesis of Benzimidazoles from N’-Aryl-N-Hyroxy
Amidines………………………………………………. 35
3.9.11. Beckmann Transformation of Amidoximes 35
4. Application of Amidoximes……………………………. 37
4.1. Chemotherapeutic Properties of Amidoximes 37
4.2. Antimalarial Activity of Amidoximes…………………….. 37
4.3. Anti-pneumocystis Activities of Aromatic Diamidoximes
Prodrugs………………………………………………….. 38
4.4. Miscellaneous uses of Amidoximes………………….. 39
EXPERIMENTAL…………………………………………….. 40
1. Preparation of N-p-Substituted Phenylbenzamide Oxime I-III 42
1.1. Preparation of N-p-Chlorophenylbenzamide Oxime I………. 42
-Thermal fragmentation of N-p-chlorophenylbenzamide oxime I 44
-Thermal fragmentation of N-p-Chlorophenylbenzamide Oxime I
in the Presence of Naphthalene…………………………………… 47
-Thermal Fragmentation of N-p-Chlorophenylbenzamide Oxime I
in the Presence of Tetralin……………………………………… 48
1.2. Preparation of N-p-Nitrophenylbenzamide Oxime II 49
-Thermal Fragmentation of N-p-Nitrophenylbenzamide Oxime II 51
1.3. Preparation of N-p-Methoxyphenylbenzamide Oxime III 54
-Thermal Fragmentation of N-p-Methoxyphenylbenzamide
Oxime II………………………………………………………… 58
2. Preparation of N-p-Substitutedphenyl Nicotinamide Oxime
IV-VI………………………………………………………. 58
2.1. Preparation of N-Phenylnicotinamide Oxime IV…………. 58
-Thermal Fragmentation of N-Phenylnicotinamide Oxime IV 60
2.2. Preparation of N-p-Methylphenylnicotinamide Oxime V 63
-Thermal Fragmentation of N-p-Methylphenylnicotinamide
Oxime V………………………………………………………… 65
2.3. Preparation of N-p-chlorophenylnicotinamide Oxime VI 67
-Thermal Fragmentation of N-p-Chlorophenylnicotinamide
Oxime VI…………………………………………………… 69
3. Preparation of N-p-Substituted Phenyl-2-Furamide Oxime VII
– IX…………………………………………………………….. 71
3.1. Preparation of N-phenyl-2-furamide oxime VII…………… 71
-Thermal Fragmentation of N-Phenyl-2-furamide Oxime VII 73
3.2. Preparation of N-p-methylphenyl-2-furamide oxime VIII 75
-Thermal Fragmentation of N-p-Methylphenyl-2-furamide Oxime
VIII……………………………………………………………… 77
3.3. Preparation of N-p-chlorophenyl-2-furamide oxime IX……. 79
-Thermal Fragmentation of N-p-Chlorophenyl-2-Furamide
Oxime IX………………………………………………………… 81
4. Preparation of N-(pyridin-2-yl)benzamide oxime X 83
-Thermal Fragmentation of N-2-Pyridylbenzamide Oxime X 85
5. Preparation of N-α-Naphthyl heteroarylamide Oxime XI-XIII 88
5.1. Preparation of N-α-Naphthylbenzamide Oxime XI……….. 88
-Thermal Fragmentation of N-α-Naphthylbenzamide Oxime XI 90
5.2. Preparation of N-α-Naphthylnicotinamide Oxime XII 92
5.3. Preparation of N-α-Naphthyl-2-Furamide Oxime XIII 94
RESULTS AND DISCUSSION……………………………… 96
REFERENCES COMPOUNDS………………………………. 151
REFERENCES…………………………………………………. 173
FIGURES……………………………………………………….. 184
ARABIC SUMMARY…………………………………………..
LIST OF FIGURES