Table Of Content70-292
HUBER, Richard deVere, n.d.
AN IMPROVED SYNTHESIS OF ALPHA-
CARBETHOXYLACTONES.
University of Delaware, Ph.D., 1950
Chemistry, organic
University Microfilms, Inc., Ann Arbor, Michigan
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An Improved Synthesis
of
alpha-Garbethoxylactonas
by
Richard deVere Huber
A thesis submitted to the Faculty
of the University of Delaware in p a rtial
fulfillm ent of the requirements for the
degree of Dootor of Philosophy.
June, 1950
*
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Approved!
ssor in'Charge or Theali
Approve
Head of department
Approved: „ • t J. f •
Ar* J ft * - i »
Dean of the School oF^frts and SS<cience
Approved:
Chairman .d iv isio n of Graduate Study
/a ( 7 7 7
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1 Acknowledgement
The author wiahee to express his appreciation to
Dr. Glenn S. Skinner for his advice and assistance.
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Table of Contents
a rtic le Page
A* Summary 1
B. Object 3
C. H istorical Section 5
(1) 5-Sthyl*5-(l-chloro-3-propenyI)- 5
barbiturio acid
(2) Preparation and D istillation of 6
Ethyl.(3-chloro-2-butenyl)-
carbethoxyacetic Acid
(3) The Formation of Lactones from 7
Some T</“Uneaturated Acids
(A) Equilibrium Between (1,1-Dimethyl- 10
3-propenyl)acetic Acid and Ieo-
heptolactone
(5) Preparation of cf-chloro- OC- 12
carbethoxy- ‘/••n-valerolactone
(6) Preparation of Lactone Acids 15
(7) Diethyl Ethyl(3-propenyl)malonate 19
and Diethyr Ethyl(2-methyl-3-
propenyl)malonate
(8) Reactions of Lactones with Sodium 21
Alkoxides
D. Theoretical Section 29
(1) Introductory Statement 29
<*) Preparation of the Cis and Trans 29
Isomers of 5-Ethyl-5-(l-chloro-
3-propenyl)barbituric Acid
(3) Preparation of the Acid Ester Derlva 30
tlves of llalonic Esters
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article page
(4) Synthesis of the Lactone Esters from 33
the Acid Esters
(5) The Condensation of the Laotone Esters 45
with Urea
E* Experimental Section 54
(1) Starting m aterials 54
(2) Preparation of the Isomers of Diethyl 55
Ethy1(l-chloro-3-propeny1)malonate
(3) Ethyl(3-propenyl)carbethoxyaeetic 66
Add
(4) Lactonlzatlon of Ethyl(3-propenyl)- 72
carbethoxyacetic Acid
(5) Preparation and Properties of Diethyl 87
Ethyl(2-methyl-3-propenyl)malonate
(6) Ethyl(2-methyl-3-propenyl)carbethoxy- 89
acetic Acid
(7) Comparison of Yields and Physical 96
Properties of the Lactone Esters
(8) A cidification of the Sodium Salt 104
Intermediate of 5-Isoamyl-5-/3-
hydroxyethylbarbituric Acid
(9) 5-£thyl-5- jQ -hydroxypropylbarbituric 105
Acid
(10) 5-Ethyl-5- (>©-hydro xy-jQ-methyl- 108
propylJbarbiturlc Acid
P > Bibliography 113
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A. Summary
The preparation of the els and trane isomers of
diethyl ethyl(l-ohloro-3-propenyl)malonate and their
respective barbituric acid derivatives has been
accomplished.
A new method for the synthesis of alpha-alkyl-
alpha-carbethoxy-gamma-lactones from alpha-alkyl-
alpha-carbethoxy-gamma, delta-unsaturated acids has
been developed by employing 95-or 100 per cent
sulfuric acid as the lactonizatlon reagent. By this
method, OC-ethyl- 0C-carbethoxy- y-n-valerolactone
and OC-ethyl- OC-carbethoxy-'y-methyl-'T’-n-valerolactone
have been prepared from ethyl(3-propenyl)carbethoxy
acetic acid and ethyl (2-methyl-3-propenyl )carbethoxy-
acetlc acid, respectively. The physical constants
and Infrared absorption spectra of these lactone esters
also have been obtained and compared.
No lactone ester has been prepared by treating
ethyl(3-propenyl)carbethoxyacetic acid with boiling,
dilute sulfuric acid. Instead, varying yields of
diethyl ethyl (3-propenyl )malonate have been obtained
depending upon the time of heating or the concentration
of the sulfuric acid. The presence of ethyl alcohol
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2
aa a solvent also has given the same malonlc ester
derivative In yields that depended upon the concentration
of the inorganic acid. D istillatio n of CC-alkyl-OC-
carbethoxy- yy-unsaturated acids under diminished
pressure likewise has produced no lacto.nlzatlon.
OC-Ethyl- OC-carbethoxy- “y-n-valerolactone
and OC-ethyl- ©C-carbethoxy- y^-methyl- -n-valero-
lactone have been condensed with urea to give 5-
eth y l-5-^-hydroxypropylbarbituric acid and 5-ethyl-
-hydroxy-^ - me thylpropyl) barbituric acid. The
Intermediate sodium salt of the 5- /Q -hydroxypropyl
derivative has been isolated while that of the 5-
0 3 -hydroxy-^ -methylpropyl)derlvative has not.
5-Ethyl-5-( jQ -hydroxy- JQ -methylpropyl)barblturlc
acid has been treated with fuming hydrochloric acid
to give a chloride which, when treated with Bodium
ethoxide, gave a chemically saturated product.
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3
B« Object
14
In a recent Investigation , os-alky 1-fiC-carbethoxy-
Y^-butyrolactonee were condensed with urea In an alcoholic
solution of sodium ethoxide at temperatures less than 55°C
‘to give 5-alky 1-5-/3 -hydroxyethylbarbituric acids* During
the course of this work**, a sodium salt Intermediate,
whose composition corresponded to two atoms of sodium per
molecule, was isolated during the preparation of 5-isoamyl-
Y
T A
5-|9-hydroxyethylbarbituric acid • The molecular con
stitu tio n of th is intermediate was not certain, although
14
structures were tentatively assigned for It .
In order to study th is problem of structure further,
pC-«thyl-OC-carbethoxy- ^-alkyl- ^bu ty rolacton es were to
be condensed with urea by employing sim ilar reagents and
conditions of reaction since it was believed that the pre
sence of secondary and tertiary ^ c a rb o n atoms in the
lactone esters would tend to have some effect on the struct
ure of the desired sodium salt intermediates and their
barbituric acid derivatives. For th is purpose, oc-ethyl-
oC- carbethoxy- Y'-n-valerolactone and OC-ethyl-0C-carbethoxy-
Y'-me thy l-^jf-n-valerolac tone were to be prepared from their
isomeric, unsaturated acid esters by employing sulfuric acid
as the reagent of lactonizatlon.
In addition to the work Just described, the cis and
trans Isomers of diethyl ethyl(l-chloro-3-propenyl)malonate
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4
were to be prepared and condensed with urea In an alcoholic
solution of sodium ethoxide In order to obtain tnelr re
spective cis and trane barbituric acid derivatives.
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