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NAME AND ADDRESS DATE
NORTHWESTERN UNIVERSITY
THE REACTION BETWEEN PHENYL MAGNESIUM BROMIDE AND
CYCLIC ACETALS
A DISSERTATION
SUBMITTED TO THE GRADUATE SCHOOL
IN PARTIAL FULFILLMENT OF THE REQUIREMENTS
for "the degree
DOCTOR OF PHILOSOPHY
DEPARTMENT OF CHEMISTRY
BERNARD ANDREW NELSON
EVANSTON, ILLINOIS
AUGUST, 1942
ProQuest Number: 10101787
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ACKNOWLEDGEMENT
The author wishes to express his most
sincere appreciation to Dr* R. K. Summerbell
for his encouragement, supervision and many
suggestions during the course of this work.
TABLE OF CONTENTS
Page
INTRODUCTION ................................................ 1
HISTORICAL
1. Acyclic Acetals....................... 2
2. Acyclic Ketlas ....................................... 4
3. Cyclic Acetals 4
4. Cyclic Ketals . . . . . . . . . . . . . . ......... 10
5. Uses For Cyclic Acetals and Ketals.......... 11
6. Heterocyclic Acetals Containing A Dioxane
Nucleus......................... 11
7. The Reaction Between Acyclic Acetals and Ketals
And Grignard Reagents ........................... 13
8. Conclusion............... 15
DISCUSSION OF RESULTS
1; The Isomeric Naphthodioxanes ...................... 16
2* The Reaction Between Glycol Acetal And
Phenyl Magnesium Bromide ............ 20
3. Reactivity Of Compounds Having A Vicinal
Aldehyde Structure Toward Phenyl Magnesium
Bromide ........................................... 22
a. 1,4,5,8-Naphthodioxane ................ 22
h. 2,3-Diethoxy-l, 4-Dioxane................... 23
c. Tetraethyl Acetal Of Glyoxal .................. 26
4. The Development Of A New Problem For
Investigation . . . . . ............................ 29
5. Compounds Having An Alcohol And An Aldehyde
Oxidation State On Vicinal Carbon Atoms........... 30
a. 2,5-Diethoxy-l, 4-Dioxane....................... 30
b. Mono ethoxy-1,4-Dioxane.......................... 35
c. 1,1,2-Trie thoxy-Ethane.......................... 37
d. 2-Ethoxymethyl-l, 3-Dioxalane.................... 38
6. A Study Of The Reaction Between 2-Methyl-1,3-
Dioxane And Phenyl Magnesium Bromide . . . . . . . . 41
7. Concluding Remarks................. 43
EXPERIMENTAL
1. Preparation Of Glycol Acetal ........................ 47
2. Preparation Of Phenyl Magnesium Bromide.
A General Prodedure............ 47
3. Reaction Between Glycol Acetal And Phenyl
Magnesium Bromide ............... . . . . . . . . . . 48
4. Preparation Of The p-Nitro-Benzoate Derivative Of
4-Phenyl-3-Oxapentano1-1 . . . . . 49
Page
5. Preparation Of 1,4,5,8-Naphthodioxane (m.p. 136°) 50
6. Attempted Separation Of The Lower Melting Isomer. 50
7* Reaction Between 1, 4, 5,8-Naphthodioxane And Phenyl
Magnesium Bromide ................. . . . . . . . 52
8. Preparation Of 2,3-Diethoxy-l,4-Dioxane ......... 52
9. Hydrolysis Of 2,3-Diethoxy-l,4-Dioxane.. 53
10. Reaction Of 2,3-Diethoxy-l,4-Dioxane With Phenyl
Magnesium Bromide.......................... 54
11. Synthesis Of Glyoxal Tetraethyl Acetal.
a. Preparation Of Glyoxal Sulfate........... 55
b. Preparation Of Glyoxal Tetraethyl Acetal. . . 56
12. Reaction Between Glyoxal Tetraethyl Acetal And
Phenyl Magnesium Bromide................. 56
13. The Refractive Index-Percentage Composition
Curve For Glyoxal Tetraethyl Acetal And Biphenyl. 57
14. Preparation Of 2,5-Diethoxy-l,4-Dioxane ......... 58
15. Reaction Between 2,5-Diethoxy-l,4-Dioxane And
Phenyl Magnesium Bromide ........................ 59
16. Oxidation Of 2-Phenyl-3-0xapentanol-l.... 60
17. Synthesis Of Monoethoxy-1,4-Dioxane...... 61
a. Preparation Of p-Dioxene................ 61
b. Preparation Of Crude Monochloro-1,4-Dioxane . 62
c. Preparation Of Monoethoxy-1,4-Dioxane . . . 62
18. Hydrolysis Of Monoethoxy-1,4-Dioxane............. 63
19. Reaction Between Monoethoxy-1,4-Dioxane And
Phenyl Magnesium Bromide.......................... 63
20. Synthesis Of 1,1,2-Triethoxy-Ethane ............. 64
a. Preparation of Ethyl Bromoacetal ............. 64
b. Preparation Of 1,1,2-Triethoxy-Ethane . . . . 64
21. Reaction Between 1,1,2-Triethoxy-Ethane and
Phenyl Magnesium Bromide .......................... 65
22. Synthesis Of 2-Ethoxymethyl-l,3-Dioxalane . . . . 66
a. Preparation Of Crude Bromoacetaldehyde . . . . 66
b. Preparation Of 2-Bromomethyl-1,3-Dioxalane . . 66
c. Preparation Of 2-Ethoxymethyl-l,3-Dioxalane. . 67
23. Reaction Between 2-Ethoxymethyl-l,3-Dioxalane And
Phenyl Magnesium Bromide.........* .............. 68
24. Preparation Of 2-Methyl-1,3-Dioxane.......... 68
25. Reaction Between 2-Methyl-1,3-Dioxane And Phenyl
Magnesium Bromide................... .............. 69
26. Preparation Of The p-Nitro Benzoate Derivative
of 5-Phenyl-4-0xa-Hexanol-l ........................ 70
27. Relationship Between Molar Ratios Of Acetals To
Grignard Reagent and Percentage Yield of Products . 70a
SUMMARY.................................................... 71
BIBLIOGRAPHY
VITA
INTRODUCTION
The formation of acetals, both acyclic and cyclic, has been
reported by such early workers as Wurtz1 and Geuther,3 Since their
time, a large number of compounds belonging to this class have been
prepared and their properties studied.
A property that has received considerable investigation has
been the displacing of an alkoxy group with an alkyl or aryl group
by reacting an acetal with a Grignard reagent. This displacement
of alkoxy groups has provided a method to synthesize ethers which
have been difficult to prepare by the ordinary procedures. It might
be anticipated that a reaction between a cyclic acetal and a Grignard
reagent would be advantageous in producing a series of ether-alcohol
compounds.
The purpose of this investigation has been to determine whether
or not cyclic acetals with varying structures could be differentiated
by a study of their reaction with a Grignard reagent. The study
included simple cyclic acetals, naphthodioxane, the ethoxy-dioxanes
and certain acyclic acetals, which were employed for comparative
purposes. As a result of this investigation, several new compounds
were prepared and a new synthesis of cellosolves (ether-alcohols)
was developed.
(1) Wurtz, Ann., 108, 226 (1857); 120, 328 (1861)
(2) Geuther, Ibid., 126, 63 (1863)
HISTORICAL
1. Aoyolio Acetals.
When an aldehyde and an alcohol have been allowed to react
together upon standing, an equilibrium results with the formation
of an ether-like substance, called an acetal. In the presence of
a small quantity of some condensing agent, usually an inorganic acid,
the reaction time can be materially decreased. The general reaction
can be expressed by the equation:
RCHO + 2RiOH ' RCH(OR1)3 + H20
It was Geuther® who first effected a direct condensation, when
he treated acetaldehyde with ethyl alcohol at 100° C* in the volume
ratio of one to three in the presence of glacial acetic acid. The
same product was previously obtained by Wurtz1 through two steps
when he first prepared the <*-chloro-ethyl ether from acetaldehyde,
ethyl alcohol and hydrogen chloride and then treated this ether with
sodium ethoxide.
Fischer and Giebe,3 by using one per cent dry hydrogen chloride,
were able to obtain good yields of acetal in eighteen hours at room
temperatures* Murat and Cathala,4 also using one per cent dry hydro
gen chloride, condensed formaldehyde with ortho-, meta- and para-
met hy Icy cl ohexanol to yield the corresponding formals. More recently,
Zaganiaris6 prepared a series of acetals in which he used naphthalene
stearosulfonic acid, known as Twitchell*s reagent,6 as the condensing
agent.
(3) Fischer and Giebe, Ber., 50, 3055 (1897)
(4) Murat and Cathala, J. Pharm. Chim., 6, 289;
Chem. Abstr., 7, 2381 (1913)
(5) Zaganiaris, Ber., 71B, 2002 (1938*5"
(6) Twitchell, J. Am. Chem. Soc., 29, 506 (1907)
An interesting study was made by Adkins, Semb and Bolander7 of*
the effeot of the ratio of the reactants upon the equilibrium constant
for acetal formation. The reactants were benzaldehyde, furfural,
ethyl alcohol, butyl alcohol and iso-propyl alcohol. Dry hydrogen
chloride was the catalyst. The ratid of the aldehyde to the alcohol
was varied from one mole of aldehyde and two moles of alcohol to
one mole of aldehyde and ten moles of alcohol. Their results showed
that although the equilibrium constant decreased slightly in value
as the ratio increased, the yield of the acetal was substantially
increased. As an example of their investigation, these values were
obtained for the reaction between benzaldehyde and ethyl alcohol:
Aldehyde-Alcohol Equilibrium Per Cent
Ratio Constant Acetal
1 to Z 0.091 25
1 to 5 0.085 39
1 to 10 0.081 53
Adkins and Minne6 made a study regarding the factor of steric
hindrance in acetal formation* After investigating eighty-five acetals
these conclusions were formed:
a) Acetal formation was decreased slightly and then increased
materially as the length of the carbon chain of the alcohol
was increased.
b) Acetal formation was decreased if either the alcohol of
the aldehyde contained an alkene group. The effect was
greater if the aldehyde was unsaturated.
c) Acetal formation was decreased by the presence of a cyclic
group.
d) Acetal formation reached a maximum using primary alcohols.
With the advent of preparing acetaldehyde from acetylene and
(7) Adkins, Semb and Bolander, J. Am. Chem. Soc., 53, 1853 (1931)
(8) Adkins and Minne, Ibid., 55, 299 (1933)
