CONCERNING THE STRUCTURE OF (ALPHA,BETA,GAMMA,SIGMA)OCTAMETHYLPORPHINOGEN(ACETONEPYRROLE)

105 Pages·03.502 MB·English

by  GAGE, CLARKE LYMAN

CONCERNING THE STRUCTURE OF
a,P,r#fi-OCTAr-ETHyiiPORPHINOGEN
( "ACETONEFYRROLE")
DISSERTATION
Presented in P a rtia l F u lfillm en t of the Requirements
fo r the Degree Doctor of Philosophy in the
Graduate School of the Ohio S tate
U n iv ersity
by
Clarke Lyman Gage, B .S .,
The Ohio S ta te U n iversity
1951
Approved by:
t " y .
• -I :C - , i .. / J,, . i &
A dviser
- i-
AC KUOWLEDGEMENT
The author wishes to express h is ap preciation
fo r the kind cooperation of Dr. Edward H'ack, J r . and other
members or the Department of Chemistry a t the Ohio S tate
U n iv ersity , He wishes to thank the K ettering Foundation,
in whose la b o ra to ries at antioch C ollege the work on th is
d isse r ta tio n was ; erformed, fo r the Fellow ship which made
th is study p o ssib le . The enerous loan of hydrogenation
and fra ctio n a tio n equipment, bp the Chemistry Department
of Antioch C o lleg e, is g r a te fu lly acknowledged, The author
e sp e c ia lly wishes to express h is gratitu d e to Dr. Paul
Rothemund of the K ettering Foundation for h is guidance.
892503
-11-
TABLK OF COMTENTS
Page
Part I* H is to r ic a l Review 1
Condensation or Pyrrole and Acetone 1
E arly H istory 1
Structu re of "Acetonepyrrole" 2
Nomenclature
6
Condensation of Pyrrole w ith Other A liphatic
Ketones
8
Condensation of Pyrrole w ith A r o m a tic Ketones 9
Condensation of Pyrrole w ith Ketone Mixtures 10
Condensation of S u b stitu ted Pyrroles with Ketones 10
Formation of Porphyrino, ons by tho Reduction
of Porphyrins 15
Formation of a Porphyrinogen from a Pyrro-
methene 15
Formation of a Porphyrinogen Interm ediate in
the S yn th esis of a Porphyrin 18
Part I I . D iscu ssio n 19
In trod u ction 19
Purpose of th is D isse r ta tio n 20
Preparation and P u r ific a tio n of "Acetone-
pyrrole"
2 1
Condensation of M eaityl Oxide w ith Pyrrole 25
Condensation of I.'othyl-Isobutyl Ketone with
P yrrole 27
R eaction of 'Vicetonenvrrole" w ith S u lfu ryl
C hloride 27
Zinc Dust P y ro ly tic Degradation of "Acetono-
p y r r o le ” v 30
-111-
Page
S yn th esis of Some Isonropyl Pyrroles 158
Hydrorenation of Several Isopropyl Pyrroles 45
Hydroronolysis of "A cetonepyrrole” 46
Low-pressure Experiments 47
High-prcssuro Experiments 47
Is o la tio n of a C ry sta llin e Hydro-
g en o ly sis Product 48
H ydrogenolysis with N ickel UOP
c a ta ly s t 51
Is o la tio n of a CaeHa„N Compound 53
4 ,0
Reaction Product of Pyrrole and ulkane
S u lfon ic acid 54
Part I I I . Experim ental 57
Apparatus 57
P hysical Measurements 58
Preparation of C atalysts 59
Pyrrole 60
Preparation and P u rifica tio n of "tcotone-
pyrrole 60
R eaction of Pyrrole with L'esityl Oxide 62
a,p ,Y > 0-T etra(h eth yl-Isob u tyl)-P orp h in o *en 64
R eaction of "A cetonepyrrolerf with S u lfu ryl
C hloride 65
Zinc Dust P yrolytic Degradation of 'Vvcotone-
p y r r o le "
6 8
D eriv ativ es of the C0HnN Compound 70
S yn th esis of Isopropyl S u b stitu ted Pyrroles 71
D eriv a tiv es of 2-Isopronylpyrrole 77
S ynthesis of Isopropyl S u b stitu ted
P yrrolid in es 77
V
- 1 V-
Page
H ydrogenolysis of "Acetonepyrrole" w ith
CuCrO C a ta ly st 81
Hydrogonolysis of "A cetonepyrrole" w ith
N ickel UOP C atalyst 84
I so la tio n of a C*eH <lN Compound 87
3 4 .0
Reaction Product of Pyrrole and Alkane
S u lfon ic Acid
8 8
Part IV* Summary 91
B ibliography 94
Autobiography 99
V
• V -
LIST OF ILLUSTRATIONS
Figure Page
I* wa c ©tonepyrrole", Liebermann and Krause 4
II* "Acetonejiyrrole , F ischer and ZImmermann 4
I I I . wT etrapyrrole-T etracetone" and*Tetra-
p yrrole-T ri ace tone*, C helintzev and Tronov 4
IV. Numbering System , F ischer 7
V. Numbering System, I.U .C . 7
V I, Diphenyl-Pyrromothane 11
V II. "DIpyrrole-DIcyclohexanone" LI
V III. R eaction Product, P yrrole, Acetone and
Cyclohexanon© LI
IX. S u b stitu ted Diphenyl-Pyrromethane, R=H 12
X. S u b stitu ted Di phenyl-Pyrrome thane, R=<3Ha 12
X I, S u b stitu ted D I-isobutylene-Pyrrom ethane,
R«CaH*
1 2
X II, S u b stitu ted D i-isobutylene-Pyrrom ethane,
R«H
X III. S u b stitu ted [3,p -Pyrromethane
1
XIV. R eaction Product, 2 #5-Dim ethylpyrrole and
Acetone :.2
XV* Mesoporphyrinogen IX :.4
XVI* Mesoporphyrino-en I Octamethyl E ster :.6
XVII * Oc tae thylporphyrInogen 16
XVIII* Etioporphyrinogen I 17
XIX. Porphinogen Ring System 22
XX• he thy - 1s obu ty le n e - Pyrromethane 22
1
XXI* D iehlorom aleic Imide SS
8
%
XXII, D ennstedt's Structure fo r C i Hx®N
0 £!8
- wl-
Fi cure Page
XXIII, D ennstedt's Structure For Ci »Hi tN 28
XXIV, P o ssib le Structures For CBHnN 33
XXV, P o ssib le Structures For Ca. Hj. N 36
5 7
XXVI, D en nstedt's Structure For D i­
isopropyl -D ipyrrole 42
XXVII, A lle n 's Structure For D ipyrrole 42
XXVIII, Formation of an Indole From the D ipyrrole 42
XXIX, P o ssib le S tructu res For C i Ha Na 49
4 4
list of tables
TABUS Page
I# P o ssib le R eaction Products of Pyrrole
and M esltyl Oxide 24
II# P hysical Data of Some Isopropyl Pyrroles 37
III# P hysical Data of Some Isopropyl
P yrrolid in es 43
V
- 1-
HI3T0KICAL REVIEW
C ondensation o£ Pyrrole w ith Aoatone
Early H istory
In 1886, Adolf Baayor (1) reported the Iso la tio n
of a w hite c r y s ta llin e product from the rea ctio n of pyrrole
w ith excess a ceto n e, usin g a small amount of hydrochloric
acid as c a ta ly s t. This exothermic rea ctio n p rec ip ita ted
c o lo r le s s c r y sta ls from the h o t, red-colored mother
liq u ors in poor y ie ld , a considerable amount of resinous
m aterial a lso being formed. The c r y s ta llin e m aterial
m elted a t 291*., was in so lu b le in w ater, potassium hydrox­
id e , and cold hydrochloric a cid , d if f ic u lt y solu b le in
a lcoh ol and e a s ily soluble in eth er, chloroform and
a ceton e, Baeyer assumed for the r e su ltin g compound the
formula C ^H ie Ha , obtained in the follo w in g manner:
2CSH,0 + 2GaH|N ■ C i Hi|Na + 2H*0 + Ha
4
The In v estig a tio n of th is compound, termed
"acetonepyrrole", was sh o rtly taken up by LI, Dennstedt
and Zimmerman ( 2 ), vftio m odified Baeyer's procedure by
u sin g ethanol as the so lv e n t, r e su ltin g in a b e tte r
y ie ld and a purer product* Dennstedt ( ) , however, was
2
convinced that no evolu tion of hydrogen took place during
the rea ctio n and from h is a n a ly tic a l data proposed the
formula Cx*HiaNa, which he la t e r (3) revised to CaaHoeH
4
from m olecular w eight data obtained from the freezin g
point degression in a c e tic a c id . The determination was
d if f ic u lt because of the Blight so lu b ility of the com­
pound,
C helintzev and Tronov (4) made an exam ination
of the condensation products o f pyrrole prepared by a
number of methods. According to these in v estig a to rs
Baoyorfs method gave the c r y s ta llin e compound CaaHaaN .
4
(m,p, 296° C »), which they renamed " tetra p y rro le-tetra co -
tone", together with an amorphous substance CaeHaaNtO,
which fu rth er oxidized during p u r ific a tio n , Dennstedt*s
method gave, at higher tem peratures, alm ost e x c lu siv ely
" tetra p y rro le-te trace ton e,r, w hile in the cold both of
the above products were obtained. Using aqueous acetone
the condensation in the cold y ield ed a b righ t yellow
s o lid , CgnHaaN*, which C helintzev and Tronov named
tetra p y rro le-tria ceto n e" , and a sm all amount of
11
" tetra p y rro le-tetra ceto n e". From hot so lu tio n s , about
30j£ of the la t te r was formed, " T otrap yrrole-triaceton e",
when heated w ith acetone and hydrochloric acid changed
alm ost q u a n tita tiv ely to " to tra p y rro le-to traceto n e? ,
Struoture of "Ace tone p y rro le
11
In the f i r s t in v e stig a tio n s on the c o n stitu tio n
of "acetonepyrrole" such reaction s were used which caused
considerable changes in the m olecule. Thus, Dennstedt
( ) obtained from the dry d i s t illa t io n of "acetonepyrrole"
2
p y rrole, -isop rop yl pyrrole (a t f i r s t , erroneously
2
•3«
a
thought to be the 3-isom er) and another p y rro le, C i H10N
0
(b .p . 275-285*)•
A high b o ilin g o il (300-305*) was a lso obtained,
which upon reduction w ith zinc and a lc o h o lic hydrochloric
acid gave a p y rro lin e, C i Ha,0N (b*p. 274*) • No attempt
0
was made to co rrela te these degradation products w ith a
structure fo r l,aceton ep yrrole,,.
The e a r lie s t proposal for the stru ctu re of the
p y rro le-a cet ne condensation product was that of L ieber-
6
mann and Krause (5) in 1907* Hoy/ever, th is stru ctu re
(Figure I) was based on the ea rly m olecular formula of
Dennstedt and Zimmermann (2 ). A somewhat sim ila r
stru ctu re (Figure IX) was suggested by H. F ischer and
W, Zirnmemann ( ) in 1914*
6
C helintzev and Tronov (4) used m ilder rea ction
conditions in th e ir in v estig a tio n s* Treatment of " tetra-
p y rro le-tetraceton e" and " tetra p y rr o le-tria c eto n eM w ith
propyl-magnesium iodide gave a quantity of gas as to
in d ica te the presence of four groups. The presence
of free ^NII groups was fu rth er corroborated by the fa c t
that the organo-^nagnesium compounds absorbed carbon d iox­
id e . Upon decom position carbon dioxide was a>ain given
o ff w ith regen eration of the sta r tin g m a teria l. That the
condensation of pyrrole w ith acetone did not in volve the
/NH grouping was &ls o sliown hy the fa c t th a t I]™ino thyl*
pyrrole with acetone yave the corresponding: homologous