A Study of Some Five-Membered

Home , Hofmann elimination

A STUDY OF SOME FIVE-MEMBERED

OXYGEN HETEROCYCLES

DISSERTATION

Presented in Partial Fulfillment of the Requirements

for the Degree Doctor of Philosophy in the

Graduate School of The Ohio State

U n iv e rsity

CARL HENRY SNYDER, B.S. in Chem.

The Ohio S ta te U n iv e rsity 1958

Approved by

r 1 .

A dviser1 a v» ! Department of Chemistry ACKNOWLEDGMENT

I wish to thank Professor Melvin S. Newman for his suggestion of this problem and for his guidance throughout the work presented in this dissertation. My thanks are also givaa to the other members of the Chemistry Department and to my fellow graduate students for allowing me free use of their time, chemicals, and equipment. I wish to express my gratitude to the Kettering Foundation for fellowships granted during the years 1954-1957- Finally, I wish to thank my wife,

Jean, for her sympathy and understanding throughout this work.

i i TABLE CSP CONTENTS

INTRODUCTION...... 1 HISTORICAL...... 7 Investigations Involving Vinylene Carbonate. . . . 7 3”dioxolane (V) ...... 8 PROPOSED PLAN OP RESEARCH...... 11 Investigations Involving Vinylene Carbonate. . . . 11 4.5-Dimethylene-l,3-dioxolane (V) ...... 12 NOMENCLATURE...... 15 STRUCTURE ...... 15 RESULTS AND DISCUSSION ...... 16 Investigations Involving Vinylene Carbonate. . . . 16 4.5-Dimethlene-1,3-dioxolane (V) ...... 23 EXPERIMENTAL...... 52 Investigations Involving Vinylene Carbonate. . . . 53 4.5-Dime thylene-1, 3-dioxolane ...... 57 SUMMARY...... 93 AUTOBIOGRAPHY...... 95

i i i LIST OF TABLES

Table 1 Results of Diels-Alder Additions of Vinylene Carbonate and F u ran ...... 17 2 Reduction of XXI to XXII with Lithium Aluminum Hydride in Tetrahydrofuran ...... 35 3 Fractionation of XVI ...... 39 4 Fractionation of XXII ...... 71 5 Fractionation of XXV ...... 85

iv LIST OF FIGURES

F ig u re 1 Synthetic Approaches and Structure Proof for 4,5-Dimethylene-1,3-dioxolane ...... 25

2 4>5-DImethylene-l,3-dioxolane ...... 76

3 Hydrocarbon-soluble Portion of Bis- (amine oxide) (XXIII) Pyrolysate ...... 80

4 Slower-moving Chromatographic Band ...... 80

5 Faster-moving Chromatographic Band ...... 81

6 Material Extracted from Column below Lower B a n d ...... 8l

7 Compound XXIX ( U ltr a v io le t S p ectru m ) ...... 84

8 Product Obtained from Pyrolysis of d- 4,5-Bis-(hydroxymethyl)-1,3-^ioxolane Diacetate . . . 89

9 N-Phenylmaleimide (Ultraviolet Spectrum) ...... 9°

1 0 Compound XXIX (in f r a r e d S p e c tr u m ) ...... 91

11 N-Phenylmaleimide (infrared Spectrum) ...... 91

12 Compound XXVT ...... 92

13 4 ,5 -D im e th y l-l, 3-d io x o la n e ...... 92

v INTRODUCTION

Inositols are naturally occurring 1,23 33k,5,6- hexahydroxycyclohexanes, which are capable of existence in nine stereoisomeric forms as follows (the substituent -OH is indicated by a vertical line):

1 2 3 4

5 6 7 8

The ninth configuration is the optical antipode of struc tu re 7 • One of the most interesting of these is mesolnositol

(structure 5)* a growth stimulant for yeast. The original objective of this research was to synthesize mesolnositol.

An interesting starting material for this synthesis was the

DIels-Alder adduct (i) of furan and vinylene carbonate (l).

(1) M. S. Newman and R. Addor.* J. Am. Chem. Soc.* 77j 3792(1955).

1 It was felt that since synthesis might involve several steps, the yield of I, reported as 3 should be improved.

Furthermore, because of interest in syntheses involving vinylene carbonate, attempts were directed toward preparation of IV, an Interesting heterocyclic compound. The path chosen involved protection of the double bond of vinylene carbonate by Diels-Alder addition to anthracene, hydrolysis of the car bonate moiety, formal formation and pyrolytic reversal of the

Diels-Alder reaction: Because of a continuing interest in Diels-Alder reactions, thought was also given toward design of a diene which might prove the most reactive Diels-Alder diene known.

To satisfy conditions necessary for diene reactivity (l) the

(l)M.C. Kloetzel, "Organic Reactions," Vol. 4, John Wiley and Sons, New York, 1948, p. 1. proposed diene should:

1. contain electron-donating groups adjacent to the diene moiety,

2. contain els-fused, conjugated, terminal methylene groups, and

3» be planar.

The simplest structure satisfying these three criteria is 4,5-dimethylene-l,3-dloxolane (v ):

CH V

This planar structure contains a 1,3-butadiene moiety, cis-

fused by a 5-membered ring and vinylic to the electron-

donating heterocyclic oxygens.

If the synthesis of V were successful, addition of the

diene to di-t-butylaeetylene might prove an important step

leading toward a synthesis of 3*4-di-t-butylphenol (Vi) (R

represents -c(CH ) ): v 3 3 a c a cill -h

R ft V

Hz °

✓ ~~

'OH

VI A study of the equilibrium between VI and Its quinoidal form

(VII) : a

f t f t H VI VII should prove interesting since the equilibrium might favor

VII for relief of steric strain caused by eclipsing of the two t-butyl groups In VI. 5 The diene (V) contains several desirable features for the synthetic route described. First, the 1,3-dioxolane moiety is actually a formal and should be hydrolyzed easily.

Also, the cis-fused butadiene moiety is held in the configur ation necessary for Diels-Alder addition. Finally, V should offer very little steric resistance to addition. The planarity of the molecule should allow intimate approach to the dienophile for formation of an intermediate ionic com plex (l) , and the terminal methylene groups should be

( 1 )I b i d . sterically free to add. That steric factors are operative in the Diels-Alder reaction is borne out by the fact that perchlorocyclopentadiene, a very reactive diene, does not undergo addition with di-t-butylacetylene or a 1:1 mixture of cis- and trans-dl- 1-butylethylene ( 2) although it adds to k-

(2)W. H. Puterbaugh, Thiele College, Greenville, Pa.; private communication. methyl-2-pentene and 3,3-dlmethyl-l-butene ( 3) . T his i s

(_3)H. E. Ungnade and E. T. McBee, Chem. Rev., £ 8, 2^9 (1958)j C. Berger and 0. Becker, Z. Naturforsch, 9b, 584 U954). probably due to extreme steric oppositions between the two t- butyl groups and a chlorine atom of the ^CClg bridge -

Since the present research involves two general areas of interest--investigations involving vinylene carbonate, and synthesis of 4, 5~dimethylene-l, 3~dioxo.lane--future dis cussions of this research will be in the order:

1. investigations involving vinylene car bonate., and 2. 4,5-dimethylene-l, 3-dioxolane. HISTORICAL

Investigations Involying Vinylene Carbonate

The only reported Investigation of vinylene carbonate pertinent to the present work Involves a synthesis of alioinositol (structure 3* P* l) In 20$ overall yield from vinylene carbonate and trans,trans-diacetoxybutadlene (l):

(l)R. Criegee and P. Becher, Ber., 9°> 2516 (1957)*

CH C Ox P., CCH

CCH3

OsO, PH Bo. (OH) "L V/

alloinosltol H

A reported yield of 31$ In the Diels-Alder reaction compares well with the yield reported by Newman and Addor (2) for the

(2)M. S. Newman and R. Addor, loc. c it.

Diels-Alder addition of vinylene carbonate and furan.

Although many substituted dioxole derivatives have been reported, the parent heterocycle itself is unknown

4,5-Plmethylene-lj3-dioxolane (v)

The synthesis of V by the route shown below has been r e p o r te d ( 1):

(l)M. R. Radcliffe and W. G. Mayes (to Firestone Tire & Rubber Company), U. S. patent 2,445,733, July 20, 1948.

CH, C| CH-OH l * CH-OH Cm Cl

VIII IX V

Very little evidence for the proposed structure (v) was given in the patent. Aside from a boiling point (115-116°) and a brief report of polymerization studies, the most important information supporting the structure assigned to the product was a description of reaction conditions. It was later learned (2) that the yields of reactions VIII—> IX and IX—»V

(2)F. W. Stavely, The Firestone Tire and Rubber Company Akron, Ohio; private communication. were, respectively, 70$ and 25$; that the density of final product was about 1.15; refractive index, 1.4833* This is hardly scientific confirmation of the proposed structure (V).

The work of Radcliffe and Mayes was based on a preparation of

4-methylene-1, 3-dioxolane (l):

(l)H. Pischer et al., Ber., 63B, 1738 (1930).

Two dienes very similar to V have been reported to

polymerize readily and undergo Diels-Alder reactions vigor

ously. The synthesis of 2 , 3 -dimethylene-1,4-dioxane (X) in

volves ( 2 ) :

(2)R. K. Summerbell and G. J. Lestina, J. Am. Chem. Soc., 79, 3878 (1957)-

A second related diene, 1,2-dlmethylenecyclopentane 10

(XI) has been prepared by vapor-phase pyrolysis of a diacetate (XII) (1, 2):

( 1) W. J . B ailey and W. R. Sorenson, J . Am. Chem. Soc., 76, 5^21 (195^)- (2)A. T. Blomquist et al., ibid., 78, 6057 (1956).

XII XI

Bailey reported a 26% yield for X II—* XI; Blomquist, 13$*

Blomquist found, moreover, a Hofmann elimination superior:

The knowledge that X and XI can be prepared readily and react vigorously In Diels-Alder reactions indicated a good chance of success for the related part of our proposed

plan of research. PROPOSED PLAN OF RESEARCH

Investigations Involving Vinylene Carbonate

Investigations involving vinylene carbonate followed two lines. First, It was hoped that mesoinositol (structure

5, p. l) could be synthesized from the Diels-Alder adduct (I) of furan and vinylene carbonate:

HO OH

OH I mesoinositol Since the synthesis might Involve several steps, the initial objective in this line of research was the improvement of the yield of I. It was felt that if I could be obtained in satisfactory yield, then epoxidation of the double bond of I, followed by general hydrolysis would give mesolnositol.

The second line of research Involving vinylene carbonate was directed toward preparation of dioxole (IV) by the gen

eral scheme outlined on p. 2s

11 12

:c=o +

4^5-Plmethylene-lj 3 ~dloxolane (v)

The second general area of research involved synthesis and reactions of 4,5-dimethylene-l,3-dioxolane (V). Since patent data given by Hadcliffe and Mayes (l) was quite meager

(l)M. R. Radcliffe and W. G. Mayes, loc. cit. and since no product characterization was given, it was felt that the reported synthesis probably gave traces of product.

Rather than repeat or attempt to improve the synthesis used by Radcliffe and Mayes, an alternate route was sought.

Thus, the object of this area of research was to pre pare and characterize V by a synthesis utilizing readily available starting materials and involving reactions likely to proceed in good yield. As was previously stated, no attempt would be made to improve the method of Radcliffe and

Mayes. Nor would the method of Summerbell and Lestina (2)

(2 )R. K. Summerbell and G. J. Lestina, loc. c it. be attempted since it involved formation of a slx-membered ring and was similar to the method of Radcliffe and Mayes in generation of the diene.

Since a structure such as V should result from elimination of 2HX from CHlX

CHZX (X is a generalized functional group), appropriate starting materials might be d_-tartaric acid and formaldehyde. d_-Tar- taric acid was chosen because of its availability and superi ority to raeso-tartaric acid in that once a cyclic system were formed, manipulations upon functional groups should not be subject to steric or electrical interactions of the functional groups themselves:

C O-<9 C •<> , MH r H

H diethyl meso diethyl d- or me t hy 1 ene ta rtra te JL-methylene Tartrate H

The formaldehyde would, of course, be used to form the cyclic

s y s te m .

The elimination reactions considered were the Hofmann

elimination, acetate pyrolysis, and amine oxide 1^ pyrolysis (1). Acetate pyrolysis and amine oxide pyrolysis

(l)A . C. Cope and E. M. A ction, J . Am. Chem. S o c . 3 80, 355 ( 1 9 5 8 ), is the most recent paper in a series on amine oxide studies. were attempted, hut since amine oxide pyrolysis gave the de sired product, the Hofmann elimination was not investigated. NOMENCLATURE

Compounds of the general structure GOX H--cx H -o COX can be considered derivatives of methylenetartaric acid

or as 4,5-disubstituted 1,3-dioxolanes. (Methylenetartaric- acid Is 1,3-dloxolane-4,5 dicarboxyllc acid.) Since the

"dioxolane" system Is used by Chemical Abstracts it will be given preference here. To avoid confusion, however, com pounds will also be named (in parentheses) as derivatives of methylenetartaric acid wherever possible.

STRUCTURE

All optically active compounds discussed will be of the d-configuration unless noted otherwise, and their general structures will be drawn as X H H—n

X for convenience

15 RESULTS AND DISCUSSION

Investigations Involving Vinylene Carbonate

Diels-Alder Additions of

Vinylene Carbonate and Furan As was mentioned in the Introduction, the first objec tive in this research was the determination of conditions necessary for a satisfactory yield of adduct (I). An ex haustive survey of reaction conditions was not intended nor was rigorous and selective control of reaction conditions a tte m p te d .

In these experiments, mixtures of vinylene carbonate

and furan were heated under nitrogen in a Carius tube for

varying lengths of time and at various temperatures. The

tubes were opened and products determined by distillation.

The results of 21 similar additions are summarized in

Table 1. Improvement of the reported yield (l) was not

(l)M. S. Newman and R. Addor, loc. c it.

achieved, although conversion (based on unrecovered starting

material) could be improved at the expense of yield. 16 TABLE I RESULTS OF DIELS-ALDER ADDITION-3 OF VINYLENE CARBONATE AND FURAN Moles Introduced Run Vinyl- Furih- Mole Moles Time Temper Yield Conversion Remarks ene Ratio Vinylene (Hours) ature Based On Based On Carbon V.C./ Carbonate Furan Unrecovered ate Furan Reoovered V.C.

1 .140 .032 4.4 — 20 125 25 — 0.5 ml.6# copper nuocide;0.2g.benzyltriethylammonium chloride; 2.5 ml.dry benzene;considerable gas gener ated. 2 .191 .0147 13.0 — 20 122-6 15 — l.Og. dry benzene; o.iog,hydroquinone.

3 .522 .116 5.0 — 117 125 l 4 — 50ml, dry benzene; rocked, stainless steel autoclave

11 .145 .032 4.6 — 65 room — 0.5 ml. 6$ copper nuocide;0.1g. benzyltriethylammoni 73 40-45 trace um chloride; 3 ®1» dry benzene.

5 .14 .034 4.1 — 42 room — 1 ml. 6# copper nuocide; l.Og. benzyltriethylammoni 22 125-30 0 um chloride 2 ml. dry benzene.

6 .305 .069 4.4 5 165-9 0 — refluxed in mesitylene

7 .617 .122 5-1 .609 20 110-30 6 gg ,015g. sodium hydroxide; tube flushed with steam; vinylene carbonate not freshly distilled.

g .514 .052 9.6 .496 22 120-40 16 53

9 .546 .055 10.0 .531 43 120-35 10 34 vinylene carbonate not freshly distilled.

10 .6og .119 5-1 .553 21 120-50 16 34 ------n .577 .120 4.g .552 10 120-40 5 30 vinylene carbonate not freshly distilled.

12 .606 .121 5.0 .520 20 120-5 5 22 .015-.020 g. diphenylamine; tube flushed with steam

13 .523 .117 4.6 .514 47 125 11 19 vinylene carbonate not freshly distilled

14 .611 .121 5.1 • 54i 42 120-5 9 16 .010 - .020 g, sodium hydroxide; tube flushed with steam; vinylene carbonate not freshly d istilled .

15 • 6ig .119 5.2 • 573 21 110-30 6 14 tube flushed with steam.

16 •571 s„ .116 4.6 .41 30 125 9 7 100 ml. dry benzene; gently rocked 450 ml. stainless steel autoclave.

17 .663 .130 5-1 .476 30 125-30 10 6 furan not freshly d istilled ; 10ml. dry benzene; gently rocked stainless steel autoclave. lg • 552 .119 5.1 .543 4g 65 0.1 0.7 run in tightly stoppered seltzer-water bottle

19 1.75 .359 4.9 1.32 20-22 125 o.3 0.3 700 psi nitrogen; 33 ml. dry benzene; gently rocked 300 ml. stainless steel autoclave.

20 .542 .109 5.0 .437 g 220-50 0 0

21 .574 .123 4.7 ? 12 120-40 * 1 2 ml. 6# copper nuocide; 1 g. benzyltriethylammonium chloride 10 ml. dry benzene; vinylene carbonate, not freshly d istilled ; exploded. « .29 .059 4.9 .25 20 123-7 34 54

V s . Newman and R. Addon, J. Am. Chem. Soc.., ]]_, 3792 (1955). All runs were carried out In nitrogen-flushed containers and, unless otherwise noted, were made with freshly distilled reagents In sealed earius tubes. Runs 1-6 are listed in order of decreasing yield — recovered vinylene carbonate was not measured. Runs 7-21 sre listed in order of decreasing conversion. Carius tubes flushed with steam were flushed 45 minutes, then rinsed with distilled water and dried with acetone. Any solids distilled from the reaction mixture in the range 120-160° at 1-2 mm, were considered as product. 18

The results summarized in Table 1 were obtained from reactions carried out over a period of several months. Since different samples of reagents , solvents, and catalysts were used, variations in yields may have been due to variations in reagents rather than in conditions. However, since this is only a possibility, and since in many reactions the degree of variation in reagents was probably much less than the degree of variation in reaction conditions, the following conclusions are based on Table 1 (numbers in parentheses refer to specific runs).

A. Time.--Optimum reaction time for maximum conversion is probably not greater than 20 hours ( 7 , 1*0 •

B. Temperature.--Optimum reaction temperature is prob ably in the 120-150° range (10). With a reaction time of

47-48 hours, a higher yield was obtained at 125° (13) than at

65° (18). With a reaction time of 8-10 hours, a higher yield was obtained at 120-140° (ll) than at 220-250° ( 2 0 ).

C. Reaction vessel.—Use of a stainless steel auto clave rather than a Pyrex glass Carius tube resulted in de creased yield and conversion (16, 17, cf. 10). The optimum reaction time in a stainless steel autoclave may be somewhat longer than in a Carius tube (3)•

D. Mole-ratio.—Increasing the mole-ratio of vinylene carbonate to furan tended to increase both yield and conver sion (9, cf. 11). The increase in conversion was greater with freshly distilled vinylene carbonate ( 8 , c f . 1 0 ). E* Catalysts and Inhibitors . - - A combination of copper

Nuocide and benzyltriethylammonium chloride was effective (1) but dangerous (21). Surprisingly, no adduct was obtained when this mixture was used in a run which was stored at room temperature almost two days before it was heated ( 5 )* although relatively long reaction times at low and moderate temperatures did not result in excessive loss of vinylene carbonate (16, 17* 18). Neither simply flushing the Carius tube with steam ( 1 5 ), use of diphenylamine in a steam-flushed tube (12), nor use of hydroquinone seemed promising (2). As was mentioned, a trace of sodium hydroxide in a steam-flushed tube ( 7 ) increased conversion remarkably, but at the expense o f y ie ld .

Precision.—Almost identical results were obtained from the only two runs made under almost identical conditions

(16, 17)* These two runs were made two weeks apart and in volved use of different samples of vinylene carbonate and different samples of furan. Indeed, furan used in run 16 was freshly distilled while furan used in run 17 was n o t.

In conjunction with the work of Newman and Addor (l) and

(1)M. S. Newman and R. Addor, lo c . c i t .

Criegee and Becher ( 2 ), the results just discussed Indicate

(2 )R. Criegee and P. Becher, lo c . c i t . little possibility of obtaining very high yields of I. They do suggest further studies in three lines. First, use of a mixture of copper Nuocide and benzyltriethylammonium chloride

under various conditions may lead to improved yields since

use of this mixture produced the best yield obtained in this

series. Also, since the optimum reaction time for additions

in Pyrex Carius tubes was not the optimum time in stainless

steel autoclaves, further study of conditions Involving these

autoclaves might be profitable. Finally, studies of addi

tions in the presence of traces of alkali may result in

reduced losses of vinylene carbonate due to side reactions.

Possibly the ratio of vinylene carbonate to furan could be

reduced since alkali may inhibit further Diels-Alder addition

of furan to I (l).

(l)Newman and Addor, loc. cit., showed that this type of addition becomes important as the vinylene carbonate-furan ratio approaches unity.

Because of a lack of success in obtaining satisfactory

yields of I, attempts at synthesis of mesoinositol were

abandoned.

Attempted Preparation of

Dioxole (IV) 9 ,lO-Dihydro-9,10-ethano-11,12-methylenedioxyanthracene

(III), which may be considered the Diels-Alder adduct of IV

and anthracene, 21

IV was prepared in 92 $ yield by hydrolysis of the anthracene - vinylene carbonate adduct and reaction of the resulting glycol (l) with paraformaldehyde in the presence of

(1)Newman and Addor, lo c. ci t . p-toluenesulfonic acid. Several partially successful attempts were made at generation of IV by pyrolytic reversal of the Diels-Alder reaction (2).

(2)Milton C. Kloetzel, Organic Reactions, John Wiley and Sons, Inc., 19^8, Vol. IV, p. 9*

Two methods of pyrolysis were attempted. In the first method, a solution of III in diphenyl ether was refluxed

(2 5 9 °) for periods ranging from two and one-half to nine days

Into a short fractionating column so that low boiling material would be isolable. In one attempt, pyrolytic reversal of the

Diels-Alder reaction was confirmed by isolation of 22 anthracene. In another, in which about 20 mg. of powdered

glass was added to the reaction mixture,a very small quantity of what may have been impure IV was recovered. The material

decolorized bromine and potassium permanganate but attempted

purification produced a material which was not analytically

pure IV. In attempts at pyrolysis In lower-boiling solvents

(80-140°), only starting material was recovered.

In the second pyrolytic approach, an attempt was made

to pyrolyze III by passing it through a furnace at 400°.

While attempted sublimation at atmospheric pressure proved

much too slow, attempted sublimation at 1 mm. failed because

the pyrolysate passed through traps cooled with Dry Ice.

Finally, III was introduced into the furnace by a combination

of sublimation and fusion at atmospheric pressure. The

pyrolysate, however, condensed In a hard plug just below the

furnace and had to be dug out. Although no trace of IV could

be detected, strong Indications of the presence of anthracene

were observed in the pyrolysate.

The results indicate that IV might be prepared by con

tinued reflux of III In a high boiling (250-30°°) solvent. Pyrolysis in a furnace has inherent difficulties which might

be overcome by use of a pressure intermediate between 1 mm.

and atmospheric, or by use of a dispersion of solid III in a

carrier such as mineral oil. 2 3 4,5-Dimethylene-lj 3-dloxolane (v)

Introduction

(Reference to Figure 1 may be helpful in the following discussion.) The discussion of results obtained In the

preparation, proof of structure, and reactions of V is

divided into three major portions:

1. Preparation of N,N,N 1,N’-tetramethyl- d_-l, 3-dioxolane-4,5-dicarboxamide (N, N,N ',N'-tetramethyl-d-methylenetar- tramide) (XXI).

2. P re p a ra tio n o f V from XXI.

3- Attempted conversion of diethyl d-1,3- dloxolane-4,5-dlcarboxylate (diethyl d- m e th y le n e ta r tr a te ) (XVI) to V by pyrolysis of an Intermediate diacetate (XXV).

Preparation of N,N,N 1,N 1-Tetramethyl-d-1,3-dioxolane-

4,5-dicarboxamide (N,N,N 1 ,N 1-Tetramethyl-d-methylene-

ta rtra m id e ) (XXI)

A. Via diethyl d-1,3-dioxolane-4,5~dicarboxylate

(diethyl d-methylenetartrate) (XVT).—Two approaches to XVI

were considered: one involving cycllzation of d-tartarlc

acid (XIIl) with paraformaldehyde to d-l,3-dioxolane-4,5-

dicarboxylic acid (d-methylenetartaric acid) (XV), followed

by esterlfication to XVT; the other involving, first, esteri-

flcation of XIII to diethyl d-tartrate (XIV)i* then a similar

cycllzation to XVT.

Since conversion of XIII to XV by addition of fuming

sulfuric acid to a warm, fused mixture of XIII and 2 4

F ig u re 1

Synthetic Approaches and Structure Proof for

4 , 5 -DImethylene- 1 , 3 -d io x o la n e

Reactions not attempted are Indicated b y ^ ,

Unsuccessful reactions are indicated by ^ „

Structures in brackets represent previously unreported compounds for which no analyses were obtained.

Structures in boldface (XVIII, XXI, XXII, XXVII, and XXVIII) represent previously unreported compounds for which analyses are reported. CHzN(CH3)2 - H0C6H2(N02)3 c o 2c4 h 9 xxvit H--OH - 0 HO--H C H ^ (CH3)2* H 0C6 H2(N02)3 C 0 2C4H9 22HL CON (CH3 )2 TST XVTT H +O H \ CON(CH3) 2 CH2N (CH 3)2 HO - - H CON(CH3)2 CP2C2H5 H OH & c o n

s CH20 2CC6 H3 (N02)2 CHgOgC C H 2 c°2h C H 2OH XXVL XWTTT X5T •°) - 0 |—0L 0> -0 CH202CC6 H3 (N 02)2 c h 2o 2c c h 3 c h 2o h XXV xxnr_ fC \J1 26 paraformaldehyde (l) gave only 37$ of XV as the barium salt,

(l)H. G. Rule and J. P. Cunningham, J. Chem. Soc., 1935, 101*2 . esterification of XV was not attempted.

Other methods of preparation of XV include use of concentrated rather than fuming sulfuric acid ( 2 , 3 ), heating a

(2 )P. C. A ustin and V. A. C a rp en ter, J . Chem. S o c ., 125, 1939 (1921*). (3)C. A. L. de Bruyn and W. A. van Ekenstein, Rec. t r a v . chlm ., 2 1 , 313 ( 1 9 0 2 ). mixture of XIII, formalin, and hydrochloric acid in a sealed tube (4, 5 , 6 ), and repeated evaporation of a solution of

(4)K. Weber and B. Tollens, Ann., 299, 335 ( 1 8 9 8 ).

(5)lbid., Ber., 3 0 , 2513 (1897)- (6 )W. Henneberg and B. Tollens, Ann., 2 9 2 , 53 ( 1 8 9 6 ).

XIII and formalin ( 7 )*

(7)C. A. L. de Bruyn and W. A. van Ekenstein, Rec. trav. chlm. ,, 20, 336 (1901).

Before the second approach to XVI was Investigated, attempts were made to convert XV to cl-4,5-bis-(hydroxymethyl)-

1,3-dioxolane dlacetate (XXV) by reduction of XV with lithium

aluminum hydride to the diol (XXIV) and treatment of XXIV with acetic anhydride. Because of the extreme Insolubility of the barium salt of XV in tetrahydrofuran (10.1 g. was 27 recovered after 65 hours of continuous extraction of 1 1 .1 g.

in a Soxhlet extractor), the salt was converted to the free acid by quantitative treatment with sulfuric acid.

Reduction of the crude free acid (XV) in tetrahydro-

furan and treatment of XXIV with acetic anhydride gave 20$ of very impure XXV. No further work was done with XV.

In the second approach to XVI, diethyl jd-tartrate

(XIV) was p rep ared in 88 $ yield by esterification of XIII in

the presence of p-toluenesulfonic acid. Cyclization to XVI

was attempted with formaldehyde and with methylal (dimethoxy-

methane)• It was hoped that what could be designated a

transformalification could be carried out between XIV and

methylal In the presence of acid.

Reaction of XIV with formaldehyde was investigated

under four different sets of reaction conditions. Nearly

equal quantities (50.0-52.4 g.) of XIV were:

1 . refluxed with paraformaldehyde and benzene In the presence of p-toluenesulfonic acid,

2. refluxed In a similar mixture containing formalin (40$ aqueous formaldehyde) In place of paraformaldehyde,

3* refluxed In a mixture of benzene and acid, into which formaldehyde vapor was bubbled, and

4. heated on a steam bath with toluene, p-toluenesulfonic acid, paraformaldehyde, and magnesium sulfate.

No benzene-water azeotrope could be detected In the

distillate of the first three runs after six hours reflux. 28 The fourth was heated 36 hours. All four were worked-up s i m i l a r l y .

The procedure involving passing vaporized formaldehyde into the reaction mixture was eliminated immediately because of the tendency of the formaldehyde vapor to form a plug by condensation to paraformaldehyde when it came into contact with the reaction mixture. The mouth of the tube could not be raised above the surface of the reaction mixture because of the low solubility of formaldehyde in benzene (l) .

(1)J. P. Walker, "Formaldehyde," Reinhold Publishing Corporation, New York, 1953* P* 36.

Examination of the infrared spectra of products of the other three runs revealed that the strength of the hydroxyl band (about 3 p.) relative to carbonyl band (about 6 p.) was least in the product obtained from the first run. Since the only difficulty encountered in this run was a tendency for paraformaldehyde to leave the reaction mixture and coat the condenser, this method was used in the synthetic scheme.

Another reported preparation of XVT (in 22$ yield) (2)

(2)Y. Tsuzuki, Bull. Chem. Soc. Japan, 11, 362 (1 9 3 6 ). involved treatment of XIV with paraformaldehyde in the presence of zinc chloride.

Actual preparation of a large quantity of XVI was accomplished by esterlficatlon of XIII and treatment of unisolated XIV with paraformaldehyde In the presence of sulfuric acid. This reaction was carried out twice, In yields of 37$ crude and 25$ pure (2° boiling range) XVI. A mixture of XIII, ethanol, benzene and concentrated sulfuric acid was refluxed for a week as water was removed from the reaction mixture by azeotropic distillation. When the forma tion of azeotrope slowed noticeably and the reflux tempera ture began Increasing above 64°, esterification was con sidered complete and excess ethanol removed. Small portions of paraformaldehyde were added over another week to complete the reaction. Addition of paraformaldehyde In small por tions decreased the rate at which the condenser was coated.

Although the work-up of the dark reaction mixture Involved neutralization of the acid catalyst, distillation of product

(XVI) always resulted In formation of rather large quantities of residual tars, no matter how pure the undlstilled XVI ap p ea re d .

p-Toluenesulfonic acid is probably superior to sulfuric acid as a catalyst In formal formation. Throughout this work it was generally found that darkening of reaction mixtures and tar-formation were associated with reactions involving

sulfuric acid catalysis rather than p-toluenesulfonic acid

catalysis. Sufficient p-toiuenesulfonlc acid must be used to

Insure a satisfactory reaction rate.

No useful products could be obtained from two attempts

at transformalifIcation by refluxing solutions of XIV, methylal, and p-toluenesulfonic acid. Although an Increase 30 of 4° in reflux temperature was noted in one case, the re fractive indices and infrared spectra of the product indicated mostly unreacted starting material was obtained. It is possible that insufficient acid catalyst was used in these investigations. Further investigations of this reaction with relatively large amounts of catalyst (perhaps 1-3 g. o f p- toluenesulfonic acid per 20-30 g. of XIV) , or use of sulfuric acid, might be profitable.

Two ro u te s were used f o r conversion of XVI to XXI. The first, and most direct, involved treatment of XVI with an excess of dimethylamine. A mixture of absolute ethanol and a

6:1 molar ratio of anhydrous dimethylamine and XVI gave 72$ crude XXI after 3 days In a Carlus tube at room temperature.

While yields of crude XXI were as high as 80$, the average yield of recrystallized (from benzene-Skellysolve C or from tetrahydrofuran) product from 12 runs was about 50$*

A brief study of reaction conditions showed that heating the Carius tubes 12 hours at 150° affected yields only slightly. At 200°, however, only 18$ of recrystallized

XXI was obtained. Use of a stainless steel autoclave re

sulted in considerable tar formation. Finally the reaction was found to proceed satisfactorily but much more slowly.at atmospheric pressure (in an unsealed container). It was also found that a well stoppered seltzer-water bottle could be

satisfactorily substituted for the sealed Carius tube. The stopper had to be wired or taped to the bottle. 31 The second, more circuitous route, involved saponifi cation of XVI to the disodlum salt of XV (XIX), conversion of

XIX to d-l,3-dioxolane-4,5-bis-(carbonyl chloride) (d- methylenetartaryl chloride) (XX), and treatment of XX with dimethylamine. Saponifications, accomplished In 10$ alcoholic sodium hydroxide, were rapid and clean and yielded from 91 $ to 106$ of XIX (washed thoroughly with ethanol and dried to constant weight) in five saponifications. Yields in excess of 100$ were probably due to occluded alkali.

Conversion of XIX to XX was attempted with thionyl chloride and phosphorous pentachloride. Reflux of XIX with thionyl chloride and distillation of product from the reac tion mixture gave 68 $ XX after one and three-quarters hours r e f lu x , 72$ after eight hours.

Treatment of dry XIX with solid phosphorous penta chloride at room temperature resulted in a vigorous reaction and extensive carbonization. Although no product could be obtained by heating the dark solids under reduced pressure,

24 hours reflux of these solids with thionyl chloride gave

26$ XX. In a second attempt, no product could be obtained after nine hours reflux of a mixture of XIX, phosphorous

pentachloride and benzene. Nine hours reflux of the residual

solids with thionyl chloride gave 33$ XX* While these

results indicate that thionyl chloride is superior to phos

phorous pentachloride for the conversion of XIX to XX, 3 2 thorough mixing of dry, solid XIX and phosphorous penta chloride, each diluted with sand, may be worthwhile.

The final step, treatment of XX with dimethylamine by addition of an ethereal solution of XX to a cold ethereal solution of an excess of dimethylamine, gave 35$ of XXI. A very vigorous reaction occurred in a preliminary attempt to add undiluted XX dropwise to an excess of undiluted dimethylamine cooled to 0°. No product was isolated.

Two attempts were made to convert XIX to XXI without isolation of XX. In the first attempt, XX was prepared with thionyl chloride as described previously. After excess thionyl chloride had been removed from the reaction mixture, benzene was added to the residual solids and, after a short period of reflux, the mixture filtered and the filtrate treated with dimethylamine, as described, to yield 52$ o f very Impure -product recrystallized to 42$ XXI. The second attempt was similar to the first except that the dimethyl amine solution was added to a solution of pyridine and filtrate containing XX. Only tar was obtained.

The route omitting Isolation of XX resulted in a 42$ yield, while Isolation of XX led to an overall yield (from

XIX) of only 25$. The lower yield may have resulted from

Incomplete continuous ether-extraction of XXI. In the route involving isolation of XX, the reaction mixture containing crude XXI was washed with water to remove dimethylamine hydrochloride. The product Itself is so water-soluble, 33 however, that It was necessary to extract the aqueous washings continuously with ether. In the path omitting isolation of

XX, dimethylamine hydrochloride was removed by filtration and

XXI recovered from the ethereal filtrate by evaporation.

B. From N,N7N1,N1-tetramethyl-d-tartramlde (XVIIl)

(attempted).--Preparation of XVIII from diethyl d-tartrate

(XIV) was similar to the direct preparation of XXI from XVI.

A fter 69 hours in a Carius tube at room temperature, a solu

tion of ethanol, dimethylamine, and XIV gave 58 $ crude

(recrystallized to 43$) XVIII. Substitution of di-n-butyl-

tartrate (XVII) for XIV gave yields of 64-72$ crude XVIII in four ru n s .

Although XVIII was obtained easily, no usable product was obtained on treatment of XVIII with paraformaldehyde In benzene and benzene-alcohol solvent systems. Use of both

sulfuric acid and p-toluenesulfonic acid In each solvent

system led to recovery of starting material and uncrystalli-

zable oils. The Infrared spectrum of one sample of oil indi

cated mostly starting material with no trace of XXI.

This completes the discussion of methods considered for

p re p a ra tio n of XXI.

Conversion of N,N,N * ,N1 -Tetramethyl-d-1,3-Diox:olane-

4,5-Dicarboxamide (N,W,N 'Jf1-Tetramethyl-d-methylene-

tartramide) (XXI) to 4,5-Dimethylene-1,3-Dioxolane (V)

A. Reduction of N,N,N',N1-Tetramethyl-d-1,3-Dioxolane- 34

4,5-Dlcarboxamlde (N,N,N 1 ,N 1 -Tetramethyl-d-me thylenetar,r tram ide) (XXl) to d - 4 , 5 - b i 3 -(dlmethylaminomethyl)-1,3- djoxolane (XXIl).—Satisfactory reduction of XXI to XXII was accomplished with lithium aluminum hydride in tetrahydro- fu ra n .

The r e s u lts of seven red u c tio n s o f XXI to XXII are

listed in Table 2. Major variations from the procedure described on page 70 are listed under "Comments." Values under "Yield" represent XXII recovered by distillation of residues remaining after solvent removal. Since boiling ranges of yields averaged 1 0 - 15° a t 20 mm., a sample of crude

XXII (product of run No. 2) was fra c tio n a te d through a 10 cm.

h elix es-p ack ed column. From 13*85 g* o f crude XXII was obtained 12.33 g* of XXII In three fractions which varied by

0 .0 0 0 2 in their refractive indices and O. 50 in total boiling

range* Specific results of this fractionation are tabulated

on page 7 1 .

Yields obtained in runs 1-4 vary from 55-69$ with

variations of 3 * 3 - 5*1 in the ratio of moles of hydride to

moles of diamide * The corresponding values for runs 5-7 are

26-33$ and 1.2-1.4 mole-ratio. Since, in theory, 0 .5 mole

of lithium aluminum hydride will reduce one mole of an N,N-

dialkyl amide to a tertiary amine, one mole of lithium

aluminum hydride is equivalent to one mole of XXI. It seems,

then, that the hydride hydrogens do not remain equally effec

tive throughout the course of this reduction. 33

TABLE I

REDUCTION OP XXI TO XXII UITH LITHIUM ALUMINUM HYDRIDE IN TETRAHYDRQFURAN

Moles Amide Mole Ratio Addition Run Yield Used Hydride/Amide Temperature Time Remarks

I 69 $ .0690 Kl refluxed during addition 5 min. described on p, 70 and 5 hr. afterward

2 a .166 3.3 not heated; heat of re action caused reflux 15 rain. reaction mixture stood overnight at room temperature 3 59 .065^ 5.1 refluxed 5-10 rain. refluxed 5.5 hr* aq. phase continuously extracted with CHC1-, 20 hr.

55 . 23^ U not heated; heat of re 10 min. stirred additional 30 rain.,stood 12 hr. room tem action caused reflux perature, 3*3 g* residue after distillation.

5 33 .130 1 .2 refluxed 1 hr. reaction mixture filtered before and after hydroly sis; solids not treated with base

6 29 .137 U 0-10° 2 hr. reaction mixture stood 15 hr. room temp,; solids not treated with base; triturated with ether-benzene

7 26 . 1^3 1 .2 not heated; heat of re 10 min, inverse addition; stirred 6 hr. room temperature. action caused reflux

* 36

To determine the effect of variations in solvent, an eighth reduction was attempted in diethyl ether. Because of the insolubility of both the diamide and an intermediate formed in the reaction, the reduction was completely unsuc c e s s f u l.

The conclusion drawn from these reductions is that the major requirement for a good yield of XXII Is use of a large excess of lithium aluminum hydride. Tetrahydrofuran was found a more satisfactory solvent than diethyl ether since use of tetrahydrofuran resulted In a homogeneous reaction mixture. If further investigation of diethyl ether is de sired, It is recommended that XXI be Introduced into the hydride solution via a Soxhlet extractor. Vigorous refluxing of the reaction mixture should be expected.

B. Oxidation of d-4,5-bis-(dlmethylamlnomethyl)-1,3- dloxolane (XXII) to d-4,5-bis-(dlmethyloxyaminomethyl)-1,3- dloxolane (XXIII).--After the liquid amine (XXIl) had been characterized by Its picrate (XXVIl), XXII was converted to

N,N,N’,N 1 -d-^,5-bis-(dimethyloxyaminomethyl)-1,3-dioxolane

(XXIIl) by treatment in the cold with 30$ hydrogen peroxide (l) .

(l)A. Cope, R. Pike, and C. Spenser, J. Am. Chem. Soc.,"71 3212 (1953)-

A cold aqueous solution of XXII was treated with cold

30$ hydrogen peroxide and, when the reaction mixture was acidic to phenolphthalein, excess hydrogen peroxide 37 destroyed with platinum black. Water was removed under re duced pressure and the syrupy XXIII dried under reduced pressure over phosphorous pentoxide to give 97$ XXIII.

Characterization of XXIII presented a problem not satisfactorily solved. Direct elemental analyses could not be accomplished because the extremely hygroscopic XXIII could not be crystallized from any common organic solvent or solvent-pair. The amorphous solids obtained on drying XXIII were almost completely soluble or insoluble In the solvents investigated, and formed oils with every solvent pair inves tig a te d .

The next approach, picrate formation, was completely unsuccessful since every attempt at picrate formation re sulted in uncrystallizable yellow oils. However, a yellow crystalline chloroaurate (RNR 2 *HAuCl^) was prepared by t r e a t ment of XXIII with chlorauric acid. Repeated recrystalliza tion from water gave a material which, when dried to constant melting point, analyzed for an elemental ratio corresponding

to XXIII* 2HAuCl4 *H20 *-|HCl.

Although XXIII was never formally characterized, two pieces of evidence (aside from further reactions of XXIIl)

tend to verify the assigned structure. The major uncertainty

In assigning a structure to XXIII is whether one or both tertiary amine moieties were oxidized. The first indication

that a bis-(amine oxide) structure should be assigned to

XXIII was the observation that aqueous solutions of XXIII 38 were acidic to phenolphthalein but tested very slightly basic to Fisher Alkacid Test Ribbon. This, in conjunction with the facts that aqueous solutions of the diamine (XXII) were basic

to phenolphthalein and that the pKA of trimethylaraine oxide

is about 4 x 1 0 ( l) (XXIII should have about the same pK^

(1)T. D. Stewart and S. Maeser, J. Am. Chem. Soc., 46, 2583 (1924). and thus be acidic to phenolphthalein), indicates that both dimethylaminomethyl moieties have been oxidized to dimethyloxyaminomethyl moieties ( 2 ). The other evidence for

(2 )The only objection to this reasoning would be that presence of a dimethyloxyaminomethyl function on a molecule might interfere with the phenolphthalein test for a di me thylaminomethy1 function on the same molecule. This appears unlikely, especially since the functional groups of d - 4 , 5 -disubstituted dioxolanes are fused in a trans-configur a t i o n .

the structure assigned to XXIII is that 2 5 .6 g. (Q.136 mole)

of XXII was oxidized to 2 9 .0 g . (O .I32 mole; 97$) of XXIII.

Oxidation of only one of the functions would have given

2 7 * 7 g* o f p ro d u c t. Discussion of the pyrolytic conversion of XXIII to V

and dimethylhydroxylamine, hereafter referred to as DMHA, is

divided into four sections: pyrolysis of XXIII, attempted

purification of V, quantitative treatment of the pyrolysate,

and r e a c tio n s o f V.

C. Pyrolysis of d-4,5-bis-(dimethyloxyaminomethyl)-1,

3-dioxolane (XXIIl).—The results of 16 pyrolyses of XXIII, carried out under varying conditions, indicate that the most satisfactory pyrolysis can be obtained by heating XXIII slowly, under nitrogen, in an all glass, one-piece distilla tion apparatus to about 140° at about 1 mm. Pyrolysate, con sisting of V and DMHA, was trapped in a receiver cooled in a

Dry Ice-chloroform-carbon tetrachloride bath. For conveni ence in repeated runs, a 10 ml. Claisen-like flask fitted with a 'rubber stopper and connected by a ground glass joint to a 10 ml. so lids-receiver was found satisfactory. Although under these conditions slow pyrolysis (at 140°) seemed to give a slightly cleaner product than rapid pyrolysis (at

190 °), the major factor determining pyrolysate cleanliness seemed to be purity of XXIII. Specifically if XXIII were not

completely free of hydrogen peroxide, tarry product was obtained. In the preparation of XXIII, excess peroxide

should be destroyed with freshly prepared platinum black.

D. Attempted purification of 4,5-dimethylene-1,3-dioxo-

lane (V).--Pyrolysates generally consisted of a two-phase

light-yellow liquid: the less dense phase apparently V con

taminated with base; the heavier phase, DMHA containing some

V. Although analytically pure V was never obtained, investi

gations of V were carried out by physical separation of the

two phases with a capillary pipette, or by extraction of the

pyrolysate with purified Skellysolve F.

The unresolved problem in purification of V was removal

of DMHA. The first attempt, fractional distillation through 40 a 30 cm., helixes-packed column, was unsuccessful because of formation of a two-phase azeotrope, b.p. 8 0 -81 ° at atmospheric pressure. Each phase of the azeotrope was basic, decolorized bromine and aqueous potassium permanganate, and reacted exothermically with maleic anhydride and N-phenylmaleimide to give tars. It was assumed that the composition of the azeotrope was similar to the composition of the pyrolysate itself. Because of sensitivity of V to heat, as evidenced by extensive polymerization observed during the distillation, gas chromatography was eliminated as a possible method of purification.

In a second attempted method of purification, base was removed from the pyrolysate by neutralization. Since aqueous solutions of DMHA hydrochloride are acidic (l), the

(1)H. Hepworth, J. Chem. Soc. 119, 256 (1921). base itself must be weak and require a strong acid for neu

tralization. It was hoped that if the pyrolytic system were

kept completely anhydrous, V might survive treatment of the

pyrolysate with an acid strong enough to remove DMHA. This

proved incorrect.

Since removal of DMHA by neutralization with p-toluene-

sulfonlc acid ( 2 ) proved much less than quantitative because

(2 )Preparation of anhydrous p-toluenesulfonic acid is described on p. 7 ^« 41 of salt-formation on the surface of the crystalline acid., neutralization of DMHA was attempted with methanesulfonic a c id ( 1 ), a strong acid, liquid at room temperature.

(l)Purified by distillation at 138-140° and 1 mm.

Treatment of pyrolysate and of a benzene-extract of the pyrolysate with methanesulfonic acid resulted in rapid, exothermic carbonization.

No further attempts were made at removal of DMHA by neutralization with a strong acid.

In a final attempt at purification, pyrolysate was ex tracted with purified Skellysolve F and the yellow hydro carbon extract, which had an amine odor, passed through a short column of carboxylic acid ion-exchange resin. Although no carbonization was observed, the yellow eluent still had an amine odor and was basic to Fisher Alkacid Test Ribbon.

Chromatography of this eluent on 10^ Celite in silicic acid resulted in separation of two yellow bands. The ultraviolet spectra of ethanol-extracts of these two bands and of a por tion of the column below the faster-moving band are given In

Figures 4, 5, and 6 . Comparison of these spectra with the spectrum of the original hydrocarbon extract of the pyrolysate

(Figure 3) suggests that the column may have effected changes

In the pyrolysate. Interestingly, the spectrum of the higher band contains a shoulder at 2 3 O-2 7 O my^, and the spectrum of the lower band a maximum at 247 my/. This suggests that the 42 lower band may be primarily V (1), while the higher band may

(l)The ultraviolet spectrum of V will be discussed in the next section. still contain some V. Since the column apparently effected changes in the pyrolysate, chromatographic purification of the pyrolysate was not investigated further.

Because attempts at isolation of V or removal of base were unsuccessful, physical separation of pyrolysate phases or extraction of the pyrolysate with purified Skellysolve F was used in practice. Skellysolve P was chosen for solvent

extraction because of its low polarity. It was hoped that

the relatively polar DMHA would not be as soluble as V in a low moleeular-weight hydrocarbon. Actually, all Skellysolve

F extracts of the pyrolysate had an amine-odor, certainly due

to solution or emulsification of the base in the hydrocarbon

p h a se.

E. Quantitative treatment of the pyrolysate.—Although

this section deals with quantitative treatment of the

pyrolysate itself, it is noted that residues remaining after

16 pyrolyses of the bis-(amine oxide) (XXIIl) were 3% to 22$

of the starting weight of XXIII. Excluding the 22$ residue,

which was obtained In the only pyrolysis carried out at

atmospheric pressure, the average residue was 5$ of XXIII.

Quantitative investigations of pyrolysates fell into

three categories:

1. titrations of base generated In the pyrolysis, 2. investigation of the ultraviolet a b so rp tio n spectrum o f V, and

3 . quantitative hydrogenation of V.

1. Since two moles of base are generated for every mole of V produced in a pyrolysis, electrometric titration of the pyrolysate offers a convenient, but indirect, measure of the yield of V. A total of five titrations were carried out, each on freshly generated pyrolysate. Two of these five titrations involved treatment of the pyrolysate with a measured excess of methanesulfonic acid and titration of the acidic mixture with 1 N sodium hydroxide. Two other titra tions involved direct titrations with 1 N hydrochloric acid of aqueous solutions of pyrolysate. The fifth titration in volved 1 N hydrochloric acid and an aqueous solution of the hydrocarbon-insoluble portion of the pyrolysate. Since aqueous solutions of salts of DMHA and strong acids are, as previously mentioned, acidic, titrations of these salts in volved points of inflection below pH 7* Each of the five titration curves contained a point of inflection ranging from pH 2.5 to 2.8.

Y ields o f 69 $ and 72$ of V were calculated in the two pyrolyses involving titration with sodium hydroxide (l);

(l)Moles of V generated were calculated from the differ ence between the total amount of acid used in treatment of the pyrolysate, and the amount of base required to neutralize excess acid remaining after neutralization of pyrolysate. 1 * in the two pyrolyses involving direct titration with hydrochloric acid, yields of 77$ and 79$ of V were calculated

(l). The remaining titration involved hydrochloric acid and

(1)Based on the total amount of acid required to reach a point of inflection at about pH3. residual pyrolysate after extraction with Skellysolve F. A

calculated yield of 41$ of V from this pyrolysis indicates

that DMHA is fairly soluble in Skellysolve F.

Interestingly, each of the titration curves obtained from hydrochloric acid titrations contained an additional,

unexplained point of inflection at about pH 6.5. Each of the

curves obtained from sodium hydroxide titrations contained an expected point of inflection at about pH 6.5 (probably from

neutralization of DMHA'C^SOjjH) and an additional unexplained point of inflection at about pH 10.

2. In a more direct determination, the yield of V was calculated from a value of e 5l90 at A max. 247 mf^ 95$ ethanol) obtained from the ultraviolet spectrum of a portion

of the less dense phase of a relatively clean pyrolysate (2).

(2) A comparison was desired between the measured value of A max. of v and a calculated value of X max. B* Wood ward, J. Am. Chem. Soc., 6k, 72 (1914-2); L. F. Fieser, "Natural Products Related to Phenanthrene," Reinhold Publishing Corp., New York, 1949* p. l84.^> or between the X max. of V and the X max. °f some closely related compound. The validity of a calculation of X max. of V by application of Woodward's rule to V was questioned since appropriate paramaters were not known for calculating the effect on X max. of vinylic oxygens or double bonds exo to five-membered rings. kS While comparison of the X max. of V to the X max. of a compound containing an identically substituted diene moiety was desired, no such compound could readily be found. Finally, an attempt was made to compare the measured )\ max. of V with that of a similar compound and to estimate the effect on X max. of structural differences between V and the compound used for comparison. Although the X max. of X, a closely related enol ether, has not been reported, X !s max. of 21^.8 m^

e cu ^ e a. e

IT XI (in isooctane) £ “&• B lom quist at, a l . , J . Am. Chem. S o c ., 78. 6057 (1958)^/ and just under 220 m^ Ts’olvent not reported) /w . J. Bailey and W. R. Sorensen, J. Am. Chem. Soc., £1+21 Tl951+)_7 h-av© been reported for XI. With X max. 21+8 m^ assumed for XI (for reasons given by Blomquist e_t al. ), it was desired to estimate the effect on this X max. produced by substitution of two oxygen atoms for the two vinylic methylene groups (positions e and f) in XI. An attempt was made to find two compounds containing diene moieties related to each other exactly as the diene moiety of V is related to the diene moiety o f XI. Although two compounds .bearing th is relationship could not be found readily, evidence that X max. of V should be similar to the X max. of XI has been found by comparison of the reported V s max. °£ t1*10 following two steroids:

C z CL cu 3 - ethoxy - 16, 17 - oxido- 3 - m e th y lc h o le s ta 3,5 - pregnadien - 21 - 3,5 - diene ol - 20 - one acetate 3 XI I ij.6 The max. of V1' is 21*1 hir (In methanol) /~P. L. Julian et al., J. Am. Chem. Soc., 22., 1982 (1951) JJ while the A max. of XI* is 239 m^. (in cyclohexane) ^f”o. C. Musgrave, J. Chem. Soc., 1951. 3 1 2 1 J. The diene ays tern of V* is identical with the diene system of XIA except that an oxygen atom (e in Vi) has been substituted for a methyl groups (e in XlA). Similarly the diene system of V Is identical with the diene system of XI except that oxygen atoms (e and f in V) have been substituted for methylene groups (e and f in XI).Thus while systems V-XI and vA-Xll are not strictly comparable to each other (e.g. the d^ene system of V-XI is cis-fused while the diene system of Vl-XlA is trans fused), the difference between Vl and XI -1 is roughly analogous to the difference between V and XI.

Thus a A max. of 2J4.7 (An ethanol) observed for V seems reasonable in view of the reported X max. °f 2i|.8m^u (in isodc- tane) for XI and the reported sim ilarity of A*s max. ^or V in methanol) and XI* (239m^ in cyclohexane). Although this is only an approximate value of € , its use in

conjunction with the absorbance at 2J+7 of a known volume of pyrolysate-extract led to a calculated %Q% yield of V,

This agrees well with a yield of \\$% calculated from catalytic hydrogenation of pyrolysate-extract.

3 . An ethanolic solution of pyrolysate-extract was

hydrogenated, in the presence of freshly prepared platinum

oxide, at about 50 psi. hydrogen and at room temperature.

The previously mentioned value of 1|5$> yield of diene was

calculated from hydrogen absorption, corrected by a similar

blank hydrogenation, and based on the assumption that V was

converted quantitatively to 1|,5-dimethyl-1,3-dioxolane (XXVI).

The discrepancy between yields calculated from titrations of

base, and yields calculated from spectral data and catalytic

hydrogenation may be due to polymerisation of V.

F . R e a c tio n s o f iu 5-Dime th y l e n e - l .3 -d io x o lan e (V) and

Proof of Structure.--The most successful reaction of V was 47 hydrogenation to 4,5-dimethyl-1,3-dioxolane (XXVI). The yellow hydrogenate obtained from the previously described reduction was filtered to remove platinum black and an attempt made to reduce the volume of the filtrate by dis tillation. Since this gave a very dark concentrate with an amine-odor, yellow filtrate obtained from another hydro genation was passed through a gas chromatography column.

Eluent which corresponded to a peak at about 11 minutes was diluted with a small amount of carbon disulfide with appear

ance of a trace of second phase. Since the infrared spectrum of this mixture contained a strong band at 3p, which disap

peared on removal of this second phase, it was assumed that

this impurity was DMHA.

The larger phase (mostly carbon disulfide) was

rechromatographed and again eluent at 11 minutes diluted with

carbon disulfide, this time without separation of phases.

The infrared spectrum of this solution (Figure 32) was almost

identical with that of a sample of 4,5-dimethyl-1,3-dioxolane

prepared from butane-2,3-diol and formaldehyde (Figure 13) *

Since the configurations for these two samples are unknown,

minor differences in spectra may have been due to differences

in configuration (the methyl groups may be els or trans)*

Correspondence of infrared spectra and elution times

of XXVT and the authentic sample of 4,5-dimethylene-1,3-

dioxolane is considered confirmation of the structure

assigned to XXVI and thus, indirectly, of the structure a ssig n e d to V. As additional evidence for the structure of V, hydrolysis of the pyrolysate and treatment with Dimedon

(Methone; 1,1-dimethylcyclohexane-3,5-dione) readily gave a compound identical (by mixed melting point) with that ob tained on treatment of formalin with Dimedon.

Although attempts at formation of a 2,4-dinitrophenyl- hydrazone derivative of the hydro lysate were unsuccessful, presence of biacetyl (butane-2,3-dione) was indicated by a positive iodoform test and appearance of a trace of red color on treatment of the hydrolysate with hydroxylamine and nickel chloride (l)• While this red color is not considered proof

(l)Compounds of the type

N N l i I f give red precipitates with nickel [F. Feigl, "Spot Tests," Elsevier Publishing Company, New York, 1954, P« 141] . Appearance of a red color in the work described indicates t h a t

r / was present before treatment of the hydro lysate with hydro xylamine. A positive iodoform test indicates that at least one -R is methyl. of the presence of biacetyl, results described in this para graph, along with proof of the presence of formaldehyde in the hydrolysate, are considered additional evidence supporting the structure assigned to V.

Difficulties encountered in detection of biacetyl can be explained if a greater rate of polymerization than 49 hydrolysis is assumed for V in the presence of water. Ease of detection of formaldehyde should not be affected by such polymerization. Indeed, V polymerized readily. A tacky layer was formed within 3° minutes, and a soft film within

6 hours of exposure of V to air at room temperature. A hard, dry film was never formed, probably because of presence of

DMHA.

In preliminary attempts at Diels-Alder reactions, V reacted vigorously at room temperature with solid maleic anhydride and with quinone to give dark, tarry products. A yellow-green, crystalline compound of unknown structure

(XXIX), m.p. 139*3-139*7° or 144.8-145.6°, depending on which of two isomorphic forms was present, was obtained from an attempted addition of V to N-phenylmaleimide. While ele mental analysis of XXIX indicated an empirical formula

CgHgNO, Insufficient material was available for a molecular weight determination or other further study. If the mole cular formula of XXIX were C22K12N2°2> X^IX might have arisen from reaction of N-phenylmaleimide with DMHA, rather than with V, to give a structure such as

CHa The ultraviolet spectra of XXIX and N-phenylmaleimide are 5 0 given in Figures 7 and 9 * respectively; the infrared spectra

in Figures 10 and 11.

Attempted Conversion of Diethyl d-l,3~

&ioxolane-4,5-dicarboxylate (Diethyl d-

Met h y l e n e t a r t r a t e) (XVI) to 4 , 5 -D im eth y len e-

1,3-dioxolane (v) via Pyrolysis of d-4,5-Bis-

(hydroxymethyl)-1,3-dioxolane Diacetate (XXV)

Reduction of XVI to d-4,5-bis-(hydroxymethyl)-I,3-

dioxolane (XXIV) with lithium aluminum hydride in ether at

0-5°, and addition of acetic anhydride to the reaction mix

ture, gave 36% XXV. Results of six reductions under various

conditions indicate that ether is a much better solvent than

tetrahydrofuran for the reduction of XVI. Hydrolysis of

reduction mixtures containing tetrahydrofuran led to un-

filterable gels which were destroyed by treatment with

hydrochloric acid. However, easily filterable solids were

obtained from hydrolysis of ethereal reaction mixtures. In

deed, these solids were merely washed with ether and discarded

in the two reductions which gave the highest yields (36# and

31#) of XXV.

Yields obtained In these reductions were apparently

insensitive to the molar ratio of hydride to XVI. Use of

molar ratios of 4.1 and 1.3 led to the two highest yields, previously mentioned. 51

Product (XXV) was characterized by conversion to the bIs-3,5-dinltrobenzoate of XXIV (XXVIIl).

Pyrolysis of XXV at 470°-5°°° in a Pyrex tube partially packed with glass helixes gave a brown oil. Codistillation of the volatile fraction of this oil with purified ethanol gave an ethanolic solution which did not react with vlnylene carbonate, N-phenylmaleimide or hexyne-3* Presence of V in the distillate in suggestedty a shoulder at 240-255 in the ultraviolet absorption spectrum of the ethanolic solution

(F igure 8 ). A yield of 1$ V was calculated with the approxi mate value o f € previously discussed and on the assumption that this shoulder Is due to the presence of V. Association of a strong, olefinic odor with the distillate and the presence of an absorption maximum at 2 2 3 m|JL(F igure 8 ) i n d i cate that another, unidentified product was generated in the pyrolysis. The odor strongly suggests a low-molecular-weight o l e f i n . EXPERIMENTAL

Melting points of analytical samples were taken in a

Hershberg melting point apparatus with total Immersion ther mometers calibrated by the National Bureau of Standards and are corrected. All other melting points and all boiling points are uncorrected.

All analyses were performed by Galbraith Microanaly- tical Laboratories, Knoxville, Tennessee.

All Infrared absorption spectra were measured on a

Baird Associates, Inc., Infrared Recording Spectropho tometer, Model B; ultraviolet absorption spectra, on a Beck mann Model D-U S pectrophotom eter.

Skellysolve P, Skellysolve B, and Skellysolve C are petroleum fractions with boiling ranges of 3 5 - 55° , 65- 69° , and 9 0 - 97 °, respectively.

The term "purified Skellysolve" refers to Skellysolve which had been washed with concentrated sulfuric acid until washings were barely colored, then washed with 2 0 -30$ aqueous sodium hydroxide, filtered through magnesium sulfate, and d i s t i l l e d .

The term "purified ethanol" refers to 95$ ethanol which had been refluxed for one-half hour in a nitrogen 52 5 3 atmosphere with, and then distilled from, sodium hydroxide or potassium hydroxide pellets.

"Purified tetrahydrofuran" refers to tetrahydrofuran which had been stored several days over potassium hydroxide or sodium hydroxide pellets, then distilled from lithium aluminum hydride.

Unless noted otherwise, optical rotations were mea

sured in 0.1 to 0.3 M aqueous solutions.

Investigations Involving Vinylene Carbonate

Diels-Alder Additions of Furan and Vinylene Carbonate

Generally, freshly distilled samples of vinylene car bonate and furan were heated, under nitrogen, In Carius

tubes. The procedure reported here, however, utilized

vinylene carbonate which had not been freshly distilled.

In the experiment which gave the highest conversion

of vinylene carbonate to adduct (I), 8 .2 7 g. (0 .1 2 2 mole)

of freshly distilled furan, 5 3 *° g. ( 0 .6 1 7 mole) of viny

lene carbonate, which had been distilled a week earlier and

refrigerated, and 1 5 . mg. of finely ground 9 9 . 1$ sodium hydroxide were sealed under nitrogen in a Carius. tube which 54 had been flushed with steam 45 min., rinsed with distilled water and dried with acetone. The reaction mixture was kept at 110-130° for 20 hours and distilled from a modified Claisen flask to yield 5 2 .4 g . (0 .6 0 9 mole) of vinylene carbonate and 1 .0 6 g. (O.OO6 8 9 mole; 6$ based on furan; approximately 88 $ based on unrecovered vinylene carbonate) of tan, amorphous solids, I (a mixture of exo- and endo-isomers of the Diels-Alder adduct of vinylene carbonate and furan)>

Preparation of 9,10-Pihydro-9.>l0-ethano-ll,12- methylenedioxyanthracene (III) A mixture of 1.20 g. (0.00504 mole) of cis-9,10-dihydro -9,10-ethanoanthracene-ll,12-diol (l), O. 7 O g. (0.023 mole)

(l)M. S. Newman and R. W. Addor, J. Am. Chem. Soc.,77 j 3793 (1955). of paraformaldehyde, 0 .1 7 g. of p-toluenesulfonic acid mono hydrate and 2 5 0 ml. of dry, thiophene-free benzene was placed in a 5 0 0 ml. one-neck flask equipped with a phase-separating condenser. Water was removed from the reaction mixture by azeotropic distillation with benzene. After six hours of re flux, the reaction mixture was allowed to cool and was washed with three 100 ml. portions of 25$ sodium carbonate solution. The basic washings were extracted with two 60 ml. portions of dry, thiophene-free benzene, which were combined with the reaction mixture. The combined organic phases were washed once w ith 50 ml. of saturated sodium chloride solution and dried by filtration through anhydrous magnesium sulfate. Solvent was removed under vacuum on a steam-bath and the residue recrystallized from benzene-Skellysolve B. Two crops of colorless needles (combined yield, 1 .1 6 g .; 92 $)* 55 m.p. 240,5-243.0°, were obtained. A portion of the first crop, recrystfj.llized from benzene-Skellysolve C and sublimed (150- 2 0 0 ° at 4 mm.), gave an analytical sample, m.p. 241.3- 2 4 3 .4 °. A n a l. C alcd. f o r CjL^HjAOg: C, 8 l . 6 ; H, 5*6. Pound: C, 8 1 . 6 ; H, 5 . 6 .

Pyrolysis of Q,10-dlhydro-9,10- ethano-11,12-methylenedioxyanthracene (III) A* By reflux.—A mixture of 3.9 g. of III and 50 m l. of diphenyl ether (b.p. 2 5 9 °) was refluxed for nine days in a one-piece apparatus consisting of a 100 ml. flask sealed to a 2 0 cm. helixes-packed column topped by a condenser. Within two hours the originally colorless mixture had turned yellow, and at the end of reflux had deepened to reddish- brown. The moxt volatile fraction obtained from the reaction mixture was diphenyl ether, as indicated by its infrared spectrum . The cooled reaction mixture was filtered and the solids heated for ten minutes on a steam bath with 50 ml. of ben zene. Filtration yielded a few milligrams of colorless cry stals of starting material, m.p. 242-244°. From the filtrate were recovered two crops of a mixture of starting material and anthracene: 1 .0 g . , m .p. 2 0 0 - 2 2 5 °, and 0 . 8 g . , m.p. 195-214°. Treatment of these two crops of crystals and of the filtrate with trinitrofluorenone gave three portions of red needles of anthracene-trinitrofluorenone complex (l):

(l)M. Orchin and E, 0. Woolfoik, J. Am. Chem. Soc., 6 8 , 1727 (1 9 4 6 ), report this as a 1 :1 complex, m.p. 1 9 3 .8 - 1 9 ^ . 0^

1 . 3 g.* m.p. 185-194 0 (mixed m.p. with authentic complex, 184-190°); 0 . 6 g ., m .p. 1 8 7 - 1 9 3 °; 0 . 6 g., m.p. 192-194°. 56 This represents a 30# yield of anthracene. Chromatography on alumina of a benzene solution of a portion of this red complex gave colorless plates of anthracene, m.p. 1 1 5 . 9 - 1 1 7 . 6 °, mixed m.p. with authentic anthracene, 1 1 5 .9 - 1 1 6 .5 °. In a similar pyrolysis, dry nitrogen was bubbled tnrough a refluxing mixture of 16.4 g. (O.O 6 5 6 mole) of III, 1 5 0 ml. diphenyl ether, and about 2 0 mg. of powdered glass in a 2 5 0 ml. one-neck flask connected to a reflux condenser. The emerging vapors were passed through a trap cooled in a Dry Ice-acetone mixture. After 60 hours of reflux, the trap was emptied and an attempt made to purify its contents (about 1 ml. of a two- phase liquid). Analysis indicated that any dioxole present was contaminated with water. Unfortunately the infrared spectrophotometer was not functioning properly at this time. However, the material was apparently olefinic since it de colorized bromine and potassium permanganate.

B. In furnace.—In another attempted pyrolysis, 29.5 g. of III was placed In a small (approximately 2 5 m l.) flask sealed to the inside portion of a standard taper joint. This was inverted and connected to the top of a 75 x 2.5 cm., nitrogen-flushed Pyrex tube containing a 5 2 cm. section of glass beads. About 70 cm. of the tube was heated to 400° in dn electric furnace. The flask containing III was flamed and III entered the heated zone by a combination of sublimation and fusion. A Dry Ice trap connected to the bottom of the column was unnec essary, for the pyrolysate condensed in a solid, brown, amorphous plug just below the furnace. The plug was removed with considerable difficulty and refluxed for one-half hour 5 7 in xylene. The infrared spectrum of the first 25 d ro p s of distillate, b.p. 138-139°, was identical with that of sol vent. Filtration of the cooled residue yielded 13. g. of tan solids. Treatment of the filtrate with trinitrofluor enone gave a few milligrams of deep red needles which, when chromatographed in benzene through a short column of alumina gave an eluent which fluoresced brightly in ultraviolet light, indicating presence of anthracene in the pyrolysate.

4,5-Dimethylene-l,3-dioxolane

The barium salt of XV was prepared in 37# yield by addition of fuming sulfuric acid to a mixture of parafor maldehyde and d-tartaric acid (XIII) at 60 to 75°* and neu tralization of the reaction mixture with barium carbonate (l)•

(l)H. G. Rule and J* P. Cunningham, J. Chem. Soc., 1935, 1042.

Quantitative addition of sulfuric acid to an aqueous solu tion of the salt, filtration, and solvent removal gave the free acid (XV).

Preparation of l)iexhy"l d'-'ta‘rTrate (XIV) . A mixture of 119. g. (0.793 mole) of Pfizer ji-tartaric acid (XIII), 200 ml. (4.35 moles) of 95 # ethanol, 450 ml. of benzene and about 0.1 g. of p-toluenesulfonic acid mono hydrate was refluxed for about 6 hours in a one 1. one-neck flask fitted with a phase-separating condenser. Reflux was continued until benzene-water azeotrope was no longer removed from the reaction mixture. Solvent was removed under 5 8 reduced pressure and the residue distilled directly to give oQ 143. g . (8856 ) of XXV ,b.p. IIO. 5 - 1 2 6 . 5 0 a t 1 ram., n£° 1 .4 4 3 3 .

Preparation of Diethyl d-l,3-Dloxolane- 4.5-di ca rboxylate (Diethyl d-Methylene- tartrate) (XVI) from Diethyl d-Tartrate XIV A. With paraformaldehyde.—A mixture of 3.99 kg. (2 6 .6 moles) of d^tartaric acid (XIII), 3.5 1. (60 moles) of ethanol, 2 . 5 1 . of b en zen e,an d 15 m l. of 96 ^ sulfuric acid was placed in a 12 1., three-neck flask. Two of the necks were plugged, and the flask was fitted with a heatlng- mantle and attached to a 7 0 cm. helixes-packed column equipped with a phase-separating condenser. The mixture was refluxed for a week with removal of the lower phase of condensed benzene-water-ethanol azeotrope. During this period about 2 1. of a lsl benzene-ethanol mix ture was added to the reaction mixture to maintain the liquid-level. As soon as the reflux temperature began to increase above 64°, at the end of the week, excess ethanol was dis tilled and replaced by benzene. Formal-formation was begun by the addition, in small portions and over a period of five days, of a slurry of 864. g. ( 2 8 . 8 moles) of paraformalde hyde in sufficient benzene to make the mixture fluid. After addition of paraformaldehyde had been completed, d istilla tion of the benzene-water azeotrope slowed noticably and the reflux temperature began increasing again. Solvent wa 3 distilled until the volume of the reaction mixture was about 6 1 ., and the cooled reaction mixture was separated into three nearly equal portions, each of which was washed with one 1 . of 10 96 sodium carbonate solution. Each aqueous wash was extracted once with 600. ml. of a lsl ether-benzene mix ture and discarded. 59 All organic phases were combined, washed similarly w ith IO 56 sodium bisulfite and saturated sodium chloride solutions, and dried by filtration through anhydrous mag nesium sulfate. Removal of solvent under reduced pressure and distillation of the residue from a modified Glaisen flask yielded two fractions: 1 . 8 l kg. (31#) of viscous, colorless liquid &VI), n§° 1.4420, b.p. 120-135°t lit. ( 1 ), 153-4° at

(l)Y. Tsuzuki, Bull. Chem. Soc. Japan, _11, 362 (1936).

19 mm. ] a t 1 -2 mm., and 3 7 3 . g* ( 6#) of yellow, turbid 20 liquid, nD 1.4490* b.p. 135-180° at 1-2 mm. A tarry residue of 1 .2 6 kg. (22#) remained. Since the infrared spectrum of each fraction of distil- . late contained a medium-strong band at 2 . 8 j* (indicating the presence of free hydroxyl groups, probably due to incomplete formal formation), 2 9 6 . g. of the lower boiling fraction was fractionated through a 6 0 cm. helixes-paeked column:

TABLE 3 FRACTIONATION OF XVI Tem- P re s nD Fraction perature su re Weight 1 1 1 0 - 1 1 5 ° 25 mm 1.4443/* 3.2 g .

2 1 5 5 -1 5 6 25 1.4409 20 1 2 1 .6 24 1.4399 3 1 5 5 -1 5 4 25 1.4391 2 3 5 5 .5 4 148-153 22 1.4394 2 3 7 .3 5 153-154 22 1.4399 2 3 4 9 .0

Of) Since Tsuzuki ( 2 ) r e p o r ts np 1.4400 f o r XVI, f r a c t io n s

(2 ) I b id . 6 0 2-5 were considered pure XVI. The residue consisted of 60. g. of tar. Indeed, whenever this ester was distilled, a large portion (20-40$) remained as tar.

B. With methylal fdimethoxymethane) (attempted).—In a one-neck, 1 0 0 ml. flask were placed 3 2 .3 g . (0 .1 5 7 mole) of f r e s h l y d i s t i l l e d $CIV), b .p . 9 8 -IOO0 a t O .5 -I mm., 50 ml. (0.60 mole) of Eastman Kodak White Label methylal, and 0 . 1 - 0 . 5 g. of technical grade p-toluenesulfonic acid mono hydrate . The flask was equipped with a heating mantle and a reflux condenser through which was suspended a thermome ter. At the beginning of gentle reflux, the temperature of condensing vapor was 40.5°. Reflux was maintained for five days as the reflux temperature rose steadily to 44.5°. The cooled reaction mixture was washed with 300 ml. of a concentrated potassium carbonate solution, the aqueous phase separated, washed once with 1 0 0 ml. of a 60:40 ether- benzene mixture and discarded. Organic phases were combined and dried by filtration through magnesium sulfate, solvent was removed under vacuum, and the residue distilled from a modified Claisen flask to give 1 7 .5 g* (54$ recovery) of mostly unreacted XIV, b.p. 122-130° at 1 mm., n ^ 3 1.4450 (l).

( l ) n ^ 3 XIV is 1.4452; n | 3 XVI, 1.4395.

The Infrared spectrum of this distillate was very similar to that of XIV. In a second attempted preparation by this method, a mixture of 1 9 .6 6 g . (O.O9 5 5 mole) of diethyl d-tartrate PO (ng 1.4465, b.p. 146.0-147.0 at 1 1 - 1 2 mm.), 1 5 0 m l. (1 . 7 O mole) of Eastman Kodak White Label methylal and 0.1-0.2 g. of p-toluenesulfonic acid monohydrate was placed In a 250 ml. 61 one-neck flask equipped with a heating mantle and a reflux condenser loosely plugged with glass-wool and containing a thermometer. After eight days, reflux was discontinued and excess methylal distilled under vacuum from the clear, colorless reaction mixture. D istillation of the residue gave 17*84 g. PO (91#) of clear, colorless XIV, n£ 1.4461, b.p. 118-128 at 1-2 mm. The infrared spectrum of this distillate was nearly identical with that of starting material.

Preparation of N,N.KMiP-Tetramethyl- d -1 .3-dioxolane-4,5-dicarboxamide (N.N. N 1.N1-Te trame thyl-d-me thylenetartram lde) t e i ) A. By treatment of XVI with dimethylamine.—A solu tio n of 1 5 .8 g . (O.O7 2 7 mole) of XVI, nj*° 1.4409, 16.0 g. (0 .3 5 6 mole) of Eastman Kodak anhydrous dimethylamine, and 5 ml. of purified ethanol, was kept in a 40 . x 2 .5 cm. Carius tube at room temperature for 6 9 h o u rs. Filtration of the colorless, partly crystalline reac tion mixture gave 11.4 g. (72#) o f colorless crystals of XXI, m.p. 86-94°. Recrystallization from tetrahydrofuran yielded 8.0 g. (51#)* m*P« 90.5-96.0° and 0.9 g., m.p. 73-90° of colorless needles of XXI (combined yield after re crystallization, 8 . 9 g . ) . Repeated recrystallization from purified tetrahydro furan and sublimation gave an analytical sample of XXI, m.p. 93.7-94.3 (sintering about 9 2 °), [ cC ] (as a 5M aqueous solution). A nal. C alcd. f o r 0 9 Hl6 N O^s C, 50.0s H, 7 .5 ; N, 1 3 .0 . Found: C. 4 9 . 8 ; H, 7.3; N,13.0. 62 B. By treatment of d-l,3-dioxolane-4,5-bis-(;arbonyl chloride) (d-methylenetartaryl chloride) (XX) with dimethylamine.—Discussion of this procedure ia divided into four p a r t s :

1. Saponification of X V I to the disodium s a l t of X V ( X I X ) , 2 . P re p a ra tio n of XX from XIX, 3. Preparation of XXI from XX, and

4. Preparation of X X I from X I X w ithout isolation of XX, 1 . To a filtered solution of 50• g. (1.25 moles) of sodium hydroxide in 5 00 ml, of warm ethanol was added 1 0 1 . 20 g, (0.542 mole) of XVI n^ 1,4404, in 100. ml, of ethanol. White amorphous solids, which formed immediately, were allowed to stand for 0 .5 hour, filtered, washed with two 1 0 0 ml. portions of ethanol, and dried at 9 0 ° to a constant w eight of 1 0 2 . g . (91 $) of disodium d-l,3-dioxolane-4,5- dicarboxylate (disodium cl-me thylene tartrate) (XIX). 2. In a 250, ml., one-neck flask equipped with a Y- adaptor containing a pressure-equalizing dropping funnel and a reflux condenser fitted with a calcium chloride drying tube, was placed all the disodium d-methylenetartrate (XIX) prepared from 59*2 g. (O. 2 7 O mole) of XVI. Over a 15 minute period, 73.9 g. (0.621 mole) of Eastman Kodak thionyl chlor ide was added. Two more portions, 15. g. (0.13 mole) and 1 0 6 . g. (O.8 8 5 m ole )tJ were added after reflux periods of 15 minutes and one hour. Reflux was continued for eight hours and the cooled reaction mixture allowed to stand overnight. Excess thionyl chloride was removed by codistillation with benzene at atomspheric pressure, and 3 8 .5 g . (7 *$) of> pale yellow XX, b.p. 75-80° at 4 mm., was distilled from 63 the residual solids under reduced pressure. A tan, solid residue of 3 7 • S* ( 120# based on sodium chloride) remained. The infrared spectrum of XX contained a strong band at 5.55-5.63|i(-coci). In an attempted preparation of XX with phosphorous pentachloride, 254. g. (1.23 moles) of powdered XIX, dried to constant weight at 108°, was added to 1 7 1 . g . (0 .8 2 2 mole) of phosphorous pentachloride in a one 1 ., one-neck flask. Since no reaction was observed, the reaction vessel was shaken to mix the solids. An immediate, vigorous reac tion ensued. The flask became very hot and cooled to room temperature only after 20-30 minutes in an ice-bath. After the charred reaction mixture had been heated ten minutes on a steam bath without further reaction, it was kept 14 hours a t 17O-18 O0. Although the reaction mixture was then heated to 220° at 2-3 mm., no distillate could be obtained. Addi tion of 624. g. (5.24 moles) of thionyl chloride to the dark reaction solids and reflux for 24 hours, followed by distillation of excess thionyl chloride, gave 6 3 . g. (26#) of XX, b.p. 75-80° at 3-4 mm. In another attempt at use of phosphorous penta chloride, a mixture of 20.5 g. (O.O 985 mole) of phosphorous pentachloride and 2 0 0 ml. of dry, thiophene-free benzene was placed In a 500 ml. three-neck flask equipped with a reflux condenser, mechanically driven Hershberg stirrer, and a rubber stopper fitted with a thermometer. The mixture, cooled to 5-10° by an Ice-water bath, was stirred as 30.4 g. (0.148 mole) of XIX was added over a ten minute period. After addition had been completed, the reaction mix ture was refluxed seven hours and benzene distilled over an additional two hours. Although the residual solids were 64 h e ated to 2 0 0 ° a t 5 mm., only a few drops of distillate were obtained near 80°. After the residue had stood overnight at room temperature, six hours reflux with 115. g. (O .9 6 5 mole) of thionyl chloride yielded 9.76 g. (32$) of XX, b.£. 88-93° a t 5 mm. 3. In the preparation of XXI, a solution of 65 m l. (O.9 8 mole) of anhydrous dimethylamine and 2 5 0 ml. of dry ether was placed in a one 1 . three-neck flask equipped with a dropping funnel, a motor driven Hershberg stirrer, and a condenser through which a thermometer was suspended. S tir ring was initiated and the mixture cooled to 0 ° in a salt- ice-water mixture. Over a period of 1 .5 hours, 3 8 .5 g. (0.194 mole) of XX (b .p . 7 5 - 8 0 ° a t 3 -5 mm.), diluted to 1 0 0 ml. with dry ether, was added. Although an attempt was made to keep the reaction temperature 0 to 5°, reaction vapors and solid 3 obscured the o thermometer; reaction temperature was probably 5 to 15 . After addition had been completed, the dropping funnel was washed with two 25 ml. portions of dry ether. The reaction mixture, which had warmed slowly to room temperature, was washed with water to remove solid dimethylamine hydrochloride. While removal of solvent from the organic phase produced a small amount of oil, the major por tion of product was recovered, as an oil, by continuous ether-extraction of the aqueous phase. No distillate could be obtained from the combined oils although they were heated to 250° at 5 mm. On cooling, the residue solidified. Crys tallization from benzene-Skellysolve C yielded the following crops of product: 6 .5 O g .^ m .p . 98.8-99.4°;3.38 g.^m.p. 93.0-94.0°;2.38 g . , m .p. 90.0-95.0°;2.70 g., m.p. 8a-97.°. The total crude yield was 15.0 g. (36$) of colorless 6 5 -6 6 orthorhombic crystals of XXI. Repeated recrystallization of the highest-melting fraction from benzene-Skellysolve C and sublimation at 9 5 ° and 1 mm. gave a white powder, m.p. 9 9.6-1 0 0 .1 °. A n a l. C a lc d . f o r C C ,5 0 .0 ; H, 7 . 5 ; N, 1 3 .0 . Found: C, 50.2; H, 7.3; N, 13.0 (l).

(l)Chronologically, the preparation of XXI just des cribed was performed before the preparation of XXI by treat ment of XVI with dime thy lamine. All XXI prepared from XX, including, inadvertently, the analytical sample, was used in reactions of XXI and could not be used to establish the identity of samples of XXI produced by treatment of XVI with dimethylamine. Identity of the products of the two methods established by: 1 * elemental analyses, 2 . identity of spectra, and 3 . identity of amine obtained on reduction with lithium aluminum hydride. The slight diserepency in melting points of analytical samples is undoubtedly related to the fact that XXI can ex ist in two crystalline forms: needles are obtained from tetrahydrofuran, orthorhombic crystals from benzene-Skelly so lv e C.

4. In a preparation of XXI from XIX without isolation o f XX, 3 2 8 . g. (2.8 moles) of Eastman Kodak thionyl chloride was added over 35 minutes to a stirred, refluxing mixture of 102* g. (0.491 mole) of XIX and one 1. of dry ether in a 3 1 ., three-neck flask equipped with heating mantle, reflux condenser, mechanical stirrer, and dropping funnel. After addition had been completed, 6 5 0 ml. of ether was distilled o v e r a 35 minute period and replaced by 5 0 0 ml. of dry ben zene. In the next one and one-half hours, 500 ml. of solvent was distilled. The cooled reaction mixture was filtered and the solids washed with two 1 0 0 ml. portions of dry ether and discarded. The combined organic phases, refrigerated overnight and re duced to about 5 0 0 ml., were added, over two and one-half 6 7 -6 8 hours* to a stirred* cooled solution of one 1 . of dry e t h e r and 2 9 5 . g . (6 .5 6 moles) of dimethylamine, as previ ously described. The resulting slurry was filtered and the solids washed with ether and discarded. The dark filtrate was re duced to about one 1 0 and treated with activated charcoal with little effect. About 200 ml. of benzene was added and the reaction mixture dried by azeotropic distillation of water. Removal of solvent under reduced pressure on a steam bath and refrigeration of the residue gave 55.4 S* o f dark solids* recrystallized from benzene-Skellysolve C to £4. g. (4<#) of XXI, m.p. 9^.5-96.0°.

C. Prom N* N* N1»N *-tetramethyl d-tartramlde fcVIIl) (attempted).—Treatment of diethyl and di-n-butyl d-tartrates with dimethylamine gave XVIII. A solution of 3.57 S« (0*0174 mole) of diethyl d-tartrate (Eastman Kodak)* 4.1 g. (0.091 mole) of anhydrous dimethylamine and 2 ml. of absolute ethanol was kept at room temperature JO hours in a 40. x 2. cm. Carius tube. After crystallization had been induced by scraping the inner wall of the cold, opened tube* filtra tion gave 2 *05 g. (58^) of colorless crystals of XVIII* m.p. 179 -185°. Repeated recrystallization from ethanol-tetrahydrofuran (ethanol-Skellysolve B was also effective) and subli m ation a t 1 mm. and 140° gave an analytical sample* m.p. I 8 6 . 4 - 1 8 7 . 30 , [

(l)A . N. Campbell, J . Chem. Soc., 1929, 1111. anhydrous dimethylamlne and 5 ml. of absolute ethanol was kept at room temperature 5 0 hours in a sealed tube and gave 11.0 g. (72$) of colorless crystals of crude XVIII,m.p. 18 O-I9 O0. Several recrystallizations from ethanol-Skelly solve B gave crystals, m.p. 186.3-188.0°, mixed m.p. with the analytical sample described above, 1 8 5 . 9 - 1 8 8 .0 ° . In an attempted conversion of XVIII to XXI, a mixture of 43. g. (0.21 mole) of XVIII, 400 ml. of Isopropyl a lc o h o l, 300 ml. of benzene, 1 6 . g . (0 .5 3 mole) of parafor maldehyde, and 5 . ml. of concentrated sulfuric acid was refluxed in a one 1 ., one-neck flask connected to a 1 0 . cm. beads-packed column topped with a phase-separating condenser. After 3.5 ml. of aqueous phase had been collected in one hour, sulfuric acid was neutralized by addition of solid potassium carbonate and the warm reaction mixture filtered. Removal of solvent under reduced pressure on a steam bath, trituration of the colorless residue with hot tetrahydro furan and filtration gave 2 0 .2 g. (47# recovery) of crude, colorless starting material, m.p. 172-179°. Removal of sol vent from the filtrate gave a partially crystalline material from which was obtained 4.15 6 * (24.4 g. combined recovery) of crude starting material, m.p. 147-176°, 3 quantity of yellow oil. Although the infrared spectra of both por tions of crystals were nearly Identical with the spectrum of the starting material, presence of a band at 9*3 j#_(-C-0-C-) in the infrared spectrum of the yellow oil suggests the presence of a small amount of XXI. No further work was done with this oil. 70 Reduction of N.N.N 1 »N1-Tetram ethyl-d-1.S-dloxolane-^^-dicarboxamide (N.N, N 1 .Nt-Tetramethyl-d-methylenetartramlde) (XXI) totd-4.5-Bis(dimethylamlnomethyl)-l,3-dioxolane (XXII) In the best of seven reductions, a faintly turbid mix t u r e o f 1 0 .6 g . (0 .2 8 0 mole) of lithium aluminum hydride and 5 0 0 ml. of purified tetrahydrofuran in a one 1 ., three-neck flask equipped with a reflux condenser, air-driven stirrer, dropping funnel and heating mantle, was stirred and refluxed gently. A warm solution of 14.9 g. (O.O 6 9 O mole) of XXI (m .p . 9 2 - 9 7 °; recrystallized from purified tetrahydrofuran) i n 1 0 0 ml. of purified tetrahydrofuran was added over five minutes. Stirring and refluxing were maintained for five h o u r s . After heating had been discontinued and excess lithium aluminum hydride destroyed by addition of 37 ml. of ethyl acetate, water was added until separation of solids ceased. The slurry was filtered with Celite and the solids triturated with about 5 0 0 ml. of concentrated potassium hydroxide solu tion. Extraction of the basic,*aqueous slurry with five 200 ml. portions of ether, combination of organic phases, and solvent removal at reduced pressure on a steam bath, gave a residue which was distilled twice from a modified Claisen flask to yield 8.21 g. of XXII, b.p. 112-116° at 21-22 mm.(l).

(l)j. P. Porneau and S, Chantalou, Bull* soc. chim., 1 2 , 8 4 5 -6 4 ( 1 9 4 5 ), report 2,4-bis(dimethylaminomethyl)-l,3- 3Toxolane, b.p. 1 2 0 a t 2 0 mm.

The forerun of the first distillation was redistilled and yielded 0.82 g. of product, b.p. 1 1 2 - 1 1 6 ° a t 2 0 mm. (co m b in ed y i e l d , 69 ^ ) . Crude product obtained from a sim ilar preparation was fractionated at 2 0 ’ mm.: 71 TABUS 4

FRACTIONATION OP XX II 2 6 .4 W eight Temperature of distillate nD 2 .4 6 g IO7 . 5 -IO 8 .O0 1 .4 4 5 7 7 .7 5 1 0 8 .0 1 .4 4 5 7 2 .1 2 1 0 8 .0 1 .4 4 5 9

The 7*75 S* portion [c£3 31-85° was refractionated for a n a l y s i s . Anal. Calcd. for C H^N 0 : C, 57.4; H, 10.7; N, 14.9. Pound: C, 5 7 -4 ; H, 1 0 .9 ; N, 1 4 .7 . The dipicrate of XXII was prepared according to Pro cedure 23 A of Shriner and Puson (l). Since attempted re-

(l)R. L. Shriner and R. C . Puson, ‘'The Systematic Iden tification of Organic Compounds, John Wiley and Sons, Inc., New York, (1948), p. 180. crystallization resulted in decomposition, the analytical sample of dipicrate, m.p. 132.6-133-4°, consisted of orange crystals of crude dipicrate, dried at 5 6 ° an d 1 mm. Anal. Calcd. for c 2 1 H2 5 N3 ° l 6 : c > 3 9 -°* H> 4 .1 ; N, 1 7 .3 . F ound: C, 3 8 . 9 ; H, 4 .0 ; N, 1 7 . 8 .

Oxidation of d-4,5-bis-(dimethylaminomethyl)-l,3- dioxola'ne fXXII) t o d-4,5-bis- (dimethyloxyaminome thyl) - 1 ,3-dioxolane (XXIII) (2)

(2)By the method of A. Cope, R. Pike, and C. Spenser, J. Am. Chem. Soc., 3212 (1953).

Over a period of about 3 minutes, 70 ml. (O .7 1 m ole) of 30^ hydrogen peroxide wa3 added to a cold solution of 25.6 g. (0.136 mole) of XXII, n | 5 1.4453, in 25 ml. of 7 2 distilled water. Since the temperature of the solution began rising rapidly when the reaction mixture was removed from the ice-water bath (5-10 min. after addition had been completed)j the solution was kept at 0-5° an additional one and one-quarter hours, after which it warmed slowly to room tem perature. After the reaction mixture had remained at room tem perature 100 hours [ a phenolphthalein test (l) was negative

(l)The phenolphthalein test for the presence of amine is considered negative only when the solution of phenolph thalein and reaction mixture remains colorless after addi tion of several drops of distilled water. Cope, loc. c it., reports that this test w ill detect 0.1$ of an a 1 kylcTimethy 1 - amine in the presence of 1$ hydrogen peroxide and 10$ of the amine oxide. The sensitivity of the test may be differ ent here, however, because of the possible existance of an intermediate containing amine and amine oxide functions on the same molecule. after 24 hours ] , excess hydrogen peroxide was destroyed by the addition of platinum black (2). The suspension was

(2)Prepared by the method of B. Feulgen, Ber., 54., 3 6 0 (1 9 2 1 ). stirred overnight, filtered, and solvent removed at 1-2 mm. (the residue was heated Interm ittently to 80°) until a viscous syrup was obtained. On treatment at room tempera ture of the syrup, which tested "pH 8, weakly basic" to Pisher Alkacid Test Ribbon, with JO ml. of cold 3C$ hydro gen peroxide, apparent partial decomposition of hydrogen peroxide occurred with effervescence and a rise in tempera ture (3)* The mixture was cooled 10 minutes in an ice-water

(3)Although the evolution of heat might be interpreted as evidence of continued amine oxide formation, appearance of a myriad of small bubbles indicated hydrogen peroxide de composition due to traces of unremoved colloidal platinum. 73 bath and allowed to come to room temperature with no further evidence of exothermic reaction. Excess hydrogen peroxide was destroyed (l) and solvent

(l)Degree of destruction of hydrogen peroxide was de termined by the lead sulfide test described by Cope, loc. c it. It was found, moreover, that 0.3$ hydrogen peroxide reacted rapidly with 0.1 N potassium permanganate with a color change from violet to brown (manganese dioxide) and a slight evolution of oxygen. A negative lead sulfide test and lack of reaction with permanganate solution were taken as indications of complete destruction of peroxide. removed as described previously and the resulting syrup dried over phosphorous pentoxide under reduced pressure to a constant weight of 2 9 .0 g . (97 $) of colorless, amorphous XXIII. Although the product was extremely hygroscopic and could not be crystallized satisfactorily, a crystalline derivative was prepared with chloroauric acid (HAUCI 4 ) and recrystallized from water to a constant melting point of 188.4-190.0°. Anal. Calcd. for C^H^AUgClgJ^O^ (corresponding to CgHgQNgO^.aHAuCl^): C, 12.0; H, 2.5; Au, 43.8; Cl 31-5. Pound: C, 11.55 H, 2.75 Au, 42.1; Cl, 32.0. Required for Cl 8 H4 9 Au4 C1 1 7 N4 ° 1 0 (corresponding to C^QNgO^HAuCl^.HgO. •g-HCl): C, 11.55 H, 2 . 6 ; Au 4 2 .1 ; C l, 3 2 .2 . All attempts at formation of the dipicrate of XXIII resulted In formation of yellow, uncrystallizable oils.

P y r o l y s i 3 of d-4,5-bis- (dimethyloxyaminomethyl)- 1,3-dloxolane (XXIII) to . „ 4 ,b-"Dimethylene^T ; 3-dToxolane (v) Of 16 pyrolyses carried out under various conditions, two are described: the first because evidence for the for mation of V was obtained by spectroscopic analysis of the hydrocarbon-extract of the pyrolysate; the second because 7 4 the hydrocarbonj^soluble portion of the pyrolysate was sub sequently hydrogenated to 4, 5 -dim ethyl-l,3-dioxolane (XXVI). A. Spectroscopic analysis.—A 15. x 2. cm. Carius tube (Tube l) containing 3.22 g. (0.0146 mole) of XXIII was connected by a short piece of glass tubing to a trap con sisting of a sim ilar tube (Tube 2) containing 2.23 g. of barium oxide and cooled in a Dry Ice-acetone bath. The ap paratus was flushed with dry nitrogen and evacuated to 1-2 mm. Rapid pyrolysis began when Tube 1 was heated to 1 6 0 ° and continued, for about ten minutes, at 1 5 0 t o 1 6 7 ° . At completion of pyrolysis, Tube 1 was flamed until the carbonized residue (0.11 g.) began foaming. A new trap was then prepared from a sim ilar Carius tube (Tube 3 ) c o n t a i n in g 6 .1 8 g. anhydrous p-toluenesulfonic acid (l), and the

(l)Anhydrous p-toluenesulfonic acid was prepared by heating the pure commercial monohydrate to 1 0 0 - 1 2 0 ° a n d 1 mm. in a modified Clalsen flask until complete fusion had oc curred and water was no longer collected in the condenser. This method gave almost colorless crystalline residues with equivalent weights of 1 7 3 -1 7 5 ( c a l c d . , 1 7 2 ).

volatile contents of Tube 2 distilled into Tube 3* In this distillation, Tube 2 was heated ten minutes at 6 5 0 a n d 1 mm., then flamed gingerly for about 30 seconds. Similarly, the volatile contents of Tube 3 were distilled into Tube 4, an empty Carius tube. Tube & was allowed to come to room tem perature and its contents, O .6 3 1 g. of a two-phase, yellow liquid, removed and refrigerated overnight. The water-soluble residue (nearly colorless crystal line solids and a brown syrup) of Tube 3 was titrated elec- troraetrically with 0.5000 N sodium hydroxide and gave a curve containing points of Inflection at pH 3.4 (54.7 ml.) and pH 7.0 (64.0 m l.). 75 The refrigerated distillate was allowed to come to -4 room temperature and 0.0409 g. (4.17 x 10 mole, assuming pure V) of the less dense phase diluted to 10.0 ml. with 95# ethanol. The ultraviolet spectrum (Figure 2 ) of t h i s solution (diluted 1 : 500) c o n ta in s X m ax. 247 mjjLjfc 5 1 9 0 log € 3.71. Since addition of purified Skellysolve F to another portion of the previously mentioned lighter phase caused separation of a very small amount of denser second phase, the value given for (: must be considered only as an approximation. B. Hydrogenation.—A 10 ml. Claisen-like flask con t a i n i n g 2 .9 8 g. (0.0136 mole) of XXIII and fitted with a rubber stopper, was connected by a ground glass joint to a 10 ml. receiver-condenser and the apparatus, evacuated to 1 mm., allowed to stand 15 minutes at room temperature. A Dry Ice-chloroform-carbon tetrachloride bath was placed around the receiver-condenser and the distilling flask Im mersed as far as possible In an oil bath. With the portions of the flask outside the bath heated with an infrared lamp, the bath was heated to 1 3 5 - 145° for one hour and forty-five minutes. A residue of 0 . 2 9 g. of black, water-soluble resin remained in the dis tilling flask at the end of this period. The receiver-condenser was placed in an ice-water bath and the pyrolysate washed with two 1 ml. portions of purified Skellysolve F. Structure Proof of 4,5-Dlmethylene- rr^-dToxoTane' TVT ------A. Hydrogenation to 4,5-dlmethyl-l,3-dloxolane (XXVI) .—The previously described pyrolysate extract was combined with a mixture of three ml. of purified ethanol 76

3 .8

3.6

3.4

3.2 LOG €

3.0

4 , 5 - DIMETHYLENE - 1,3 - DIOXOLANE

2.8 .CH

H2C 2.6 SOLVENT: 9 5 % ETHANOL

230 245 260 275 WAVELENGTH (m \ i )

FIGURE 2 7 7 a n d 0 .0 5 0 g. of freshly prepared platinum oxide catalyst. Hydrogenation of the mixture at room temperature and under an Initial pressure of 50 psi. of hydrogen In a Parr Hydrogenation Apparatus, resulted In absorption of 0.0122 mole (including blank correction; of theoretical, neglecting residue after pyrolysis) of hydrogen within two h o u r s . Platinum was removed from the hydrogenate by filtra tion through diatomaceous earth and 1 . 5 ml. of the pale yellow filtrate passed through a six foot gas-chromatography column packed with (Johns-Mansville C-22) firebrick (30/60 mesh, 100 parts) Impregnated with a mixture of Dow Corning Silicones No. 550 (33 parts) and triethylene glycol (8 parts) (l). A carrier-gas pressure of 5.0 psi. of

(l)A more complete description of this column Is given by A. Arkell, Ph.D. dissertation, The Ohio State University, 1 9 5 8 . helium, an Inlet temperature of 137°, and a column temperature of 103° were used. After ethanol had been eluted (about two minutes) a plateau was recorded at about 9.5-10.0 minutes Since eluent corresponding to this plateau was insufficient for effective handling, it was diluted with reagent grade carbon disulfide, with separation of a small portion of a second phase. This mixture was refrigerated overnight and 0.1 ml. of the major phase rechromatographed as described. The eluent corresponding to a plateau at 10.8-11.1 minutes was diluted with carbon disulfide without formation of a second phase. The infrared spectrum (Figure 12) of this solution was nearly Identical with that obtained from a simi lar solution of carbon disulfide and an authentic sample of 78 4,5-dimethyl-l,3-dloxolane (l), elution time, under the

(l)Prepared from formaldehyde and 2 , 3 -butanediol with a polystyrene ^ulfonic acid catalyst. The author is grate ful to Professor M. J. Astle of Case Institute of Tech nology for supplying this sample. The configuration of this m aterial Is unknown. same chromatographic conditions, 1 1 .1 m in.

B. Hydrolysis of 4,5-dimethylene-1,3-dioxolane (V).— A solution of 3.68 g. of Dimedon (Methone; 1,1-dimethylcyclo- hexanedione-3,5) In 20 ml. of ethanol was added to a sample of pyrolysate, previously titrated with hydrochloric acid but subsequently adjusted to pH 5.0 with sodium hydroxide solution. The mixture was refrigerated one hour, filtered, and the solids recrystallized from ethanol-water to give 0.41 g. of methylene bis-DIraedon, m.p. I 9 O-I9 I 0 , m ixed w ith an authentic sample prepared from formalin, I 9 O-I9 2 0 (2 ).

(2)J. P. Walker, formaldehyde," Reinhold Publishing Corp., New York, 1953 j p . 390.

An aqueous solution of nickel chloride was added to another portion of pyrolysate treated with hydroxylamine hydrochloride (3). The blue-green mixture was made nearly

(3)R. L. Shriner and R. C. Puson, The Systematic Identification of Organic Compounds, John Wiley and Sons, Inc., New York, 1948, Procedure 42 B, p. 202. neutral and an additional few drops of nickel chloride solu tion added. Appearance of a slight streak of red indicated the presence of nickel dimethylglyoxime (4), the precursor

(4)F. Peigl, ^Spot Tests," Elsevier Publishing Com pany, New York, 1954, p. 141. of which would have been biacetyl 7$ A positive iodoform test (l) on this same portion of

(l)R. L. Shriner and R. C. Fuson, The Systematic Identification of Organic Compounds, John Wiley and Sons, Inc., New York, 1948, p. 1 3 8 . pyrolysate was additional evidence for the presence of b i a c e t y l . Unsuccessful attempts were made at preparation of derivatives of biacetyl with 2 ,4-dinitrophenylhydrazine and o-phenylenediamine.

Attempted Chromatographic Purification of 4,5-Dimethylene-l,3-dloxolane (V) The Skellysolve F-extract ( A max. 247 mp; ultravio let absorption spectrum given in Figure 3) of pyrolysate o b ta in e d from 1 .7 1 g- (O.OO 778 mole) of XXIII was passed through a 5 cm. column of (Amberlite XE- 9 7 ) c a r b o x y lic acid ion-exchange resin and gave an eluent (3 0 ml.), basic to Fisher Alkacid Test Ribbon and possessing an amine-like odor. This eluent was chromatographed with purified Skellysolve F on a 5 x 1 cm. column of 1C$ Celite in silicic acid. Twenty ml. of eluent, which contained no V as evidenced by lack of significant absorption in the re g io n 2 2 0 -5 0 0 mp., was collected, and the column extruded. Two yellow bands, which appeared within 2 cm. of the top of the column, and a portion of the column below the lower band, were extracted with purified ethanol. The ultraviolet absorption spectrum (Figure 4) of the extract of the slower-moving band, which was basic to Fisher Alkacid Test Ribbon, contained a maximum below 2 2 0 m p, a shoulder at 2 3 0 -2 7 0 mp. and a small peak at 329 m p. The ultraviolet spectrum (Figure 5) of the extract ;jO

HYDROCARBON - SOLUBLE PORTION OF BIS - (AMINE OXIDE) ( 2X PYROLYSATE

SOLVENT^ PURIFIED SKELLYSOLVE F

220 2603 0 0 340 380 WAVELENGTH (mu)

FIGURE 3

SLOWER-MOVING CHROMATOGRAPHIC BAND

SOLVENT : 95% ETHANOL

220 260 300 340 380 WAVELENGTH (mu)

FIGURE 4 8 l

FASTER-MOVING CHROMATOGRAPHIC BAND

SOLVENT: 9 5% ETHANOL

220 260 300 3 4 0 380 WAVELENGTH (mu) FIGURE 5

MATERIAL EXTRACTED FROM COLUMN BELOW LOWER BAND a

SOLVENT: 95% ETHANOL

220 260 300 340 380 WAVELENGTH (mu)

FIGURE 6 82 of the lower band, which was weakly basic (pH about 8) to Fisher Alkacid Test Ribbon, was nearly identical with that of the diene (V). Finally, the ultraviolet spectrum (Figure 6) of the neutral extract of the column Just below the lower band contained a broad maximum at about 2 2 5 mjji and a smaller peak at about 252 m jd L .

Attempted Preparation of the Diels-Alder Adduct of 4,5-Dlmethylene-l,3-dioxolane (V) arid N-rnenyImaielmlde The benzene-extract (about 10 ml.) of pyrolysate ob tained from 3*32 g. (0.0151 mole) of XXIII was added to a solution of 2.84 g. (0.0164 mole) of N-phenylmaleimide in 15-20 ml. benzene. Because the reaction mixture warmed slightly, it was cooled immediately in an ice-bath and re frigerated overnight with formation of a few rag. of dark, viscous oil which was removed and discarded. Since the absorption spectrum of the oil contained a broad, strong band at 3.0j* , the oil was probably largely dimethylhydrox- ylamlne. Solvent was removed from the more fluid phase and the residue crystallized from benzene-Skellysolve F and chromatographed on a column of nearly neutral grade I alumina with 1556 ether in benzene. A single yellow band was observed on the column. Removal of solvent from eluent preceding this band gave no residues; after the band had been removed, the column was washed with ether, then ethyl acetate, without recovery of residues. The yellow band was removed in seven fractions which were assumed Identical because of an undepressed mixed melting point of the solutes of the first and last frac t i o n s . 83 Combination of fractions and repeated recrystalli zation from benzene-Skellysolve F gave an analytical sample of a compound of unknown structure, XXIX, yellow crystals, m.p. 139.3-139*7° (an isomorphic form, m.p. 144.8-145.6°, was observed during recrystallization). Anal. Found: C, 67.0; H, 5 . 5 ; N, 1 3 . 3 . R e q u ire d for the empirical formula C 5 H5 NO: C, 6 6 . 7 ; H, 5*6; N, 1 3 .0 . The ultraviolet spectrum of the analytical sample o f XXIX (F ig u re 7 ) contains maxima at 237* 2 6 9 , and 385 m |jl . Extinction coefficients could not be calculated because insufficient XXIX was available for a molecular weight determination. Only tar or raaleic acid was recovered from attempted Diels-Alder additions of V and maleic anhydride.

Preparation of 4,5-Plmethylene-1,3-dioxolane (V) via Pyrolysis of d-4,5-BI 3 -(hydroxyme thyl)- 1,3-dioxolane Dlacetate (XXV) A. Preparation of d-4,5-bis-(hydroxymethyl)-1,3- dioxolane diacetate (XXV) from diethyl d-1,3-dioxolane- 4,5-dicarboxylate (diethyl d-m ethylenetartrate)(XVI).—To 1 .2 1 . of dry ether in a 3 1 . three-neck flask equipped with a drying tube (calcium chloride), air-driven mechani cal stirrer, and a rubber stopper containing a -5 0 t o 1 0 0 ° thermometer was added 35*7 g« (0.943 mole) of lithium aluminum hydride. After the mixture had been stirred at room tempera ture overnight, the drying tube was replaced by a dropping funnel and the slightly turbid solution cooled to 0 ° i n a salt-ice-w ater bath. A reaction temperature of 0-5° was maintained while a solution of 49.9 S* (0.229 mole) of 9 0 XVI, nj 1.4412, in 100 ml. of dry ether was added over a 0.5

0.4 COMPOUND 3XEX: CONCENTRATION: ,0 0 8 0 g/l. SOLVENT: 95% ETHANOL

0.3

0.2

220 3 0 0 340260 3 80 WAVELENGTH (mp.) FIGURE 7 ^ 85 period of two hours with continuous stirring. After an additional three-quarters of an hour of stirring, a solu tion of 275. ml, ( 2 .9 2 mole) of (Carbon and Carbide) acetic anhydride in 2 2 5 . ml. of dry ether was added over a two and one-half hour period to the cold, stirred reac tion mixture. After the reaction mixture had remained at room temperature three hours, the addition of 8 0 m l. o f distilled water caused the copious formation of solids. Stirring wa 3 discontinued, the reaction mixture filtered, and the solids washed twice with approximately their own volumes of ether and discarded. The filtrate was refrigerated overnight and dried by filtration through anhydrous magnesium sulfate. The residue remaining after solvent removal was distilled from a modified Claisen flask to give two fractions: 2 2 :1 8 g. of a colorless liquid, b.p. room temperature to 130.5° at 3-4 mm., and 1 8 .3 0 g . ( 36$) of a colorless vis cous liquid (XXV), b.p. 130.5-132.5° at 3-4 mm. A residue o f 1 . 3 g. of dark solids remained. Refractionation of the combined fractions through a 15 cm. beads-packed column gave a large amount of low boiling liquid (not Investigated) and two fractions:

TABLE 5

FRACTIONATION OP XXV ...... n'20------F r a c t i o n b . p . P r e s s u r e D We ig h t 1 1 3 0 -1 3 5 ° 3 -4 mm 1 .4 5 5 0 1 1 .2 8 g . 2 1 3 5 -1 3 6 3 -4 1 .4 5 4 1 4 .8 9 8 6 These fractions were combined and a portion saponified with 20$ aqueous sodium hydroxide to give a single phase after six hours on a steam bath. After the saponification mixture had been continuously extracted with fcther for two weeks, the organic phase was dried by filtratio n through anhydrous magnesium sulfate, solvent was removed on a steam bath, and the colorless, viscous residue (XXXV) converted to the bis-(3>5-

(1)R. L. Shriner and R. C. Fuson, "The Systematic Identification of Organic Compounds, John Wiley and Sons, Inc., New York', 1948, Procedure 9j» p. 1 6 5 . acetate-ethanol gave an analytical sample, m.p. 1 7 5 * 3 - 1 7 7 .1 ° .

Anal. Calcd. for C-^H-^Nj^O^: C, 43.7; H, 2 . 7 ; N,

IO. 7 . Founds C, 4 4 .1 ; H, 2 . 7 ; N, 1 0 .8 . A saponification equivalent ( 2 ) o f 1 1 6 (calcd., IO 9 )

(2 )Ibid., p. 1 3 3 . was found for a fraction of XXV, b.p. 128-130° at 1 - 2 mm.

B. Preparation of d-4,5-bis-(hydroxymethyl)-l,3- dioxolane diacetate (XXV) from d-1.3-dioxolane-4.5- dicarboxvllc acid fd-methylenetartaric acid) (XV) .—A solu tion of 10.2 g. (O .2 6 9 mole, 15$ excess) of lithium alumi num hydride in 400 ml. of purified tetrahydrofuran, in a one 1 . three-neck flask equipped with a dropping funnel, motor driven Hershberg stirrer, and rubber stopper contain ing a thermometer, was cooled to 0 ° in a salt-ice-water bath. A warm slurry of 25.2 g. (O .1 5 6 mole) of crude XV 8 7 in 200 ml. of purified tetrahydrofuran was added, with stirring, over a four and one-half hour period. The re action mixture, which had been kept at 5-10° during addition, was refluxed for one hour. Just over 40 g. (about 0.4 mole) of acetic anhydride was added to the cooled reaction mixture and reflux continued for an addi t i o n a l 15 m i n u t e s . After the reaction mixture had remained at room tem perature for 36 hours, the slurry was filtered and the residue extracted for three hours with 600 ml. of refluxing acetone and filtered. Organic phases were combined, solvent and excess acetic anhydride removed, and the resi due distilled from a modified Claisen flask to give 6 .6 5 g . (20$) of very crude XXV, b.p. 50-150° at 3 mm.

C. Pyrolysis of 4,5-bis-(hydroxymethyl)-1,3-dioxo lane diacetate (XXV).—An 87 x 2.5 cm. Pyrex tube contain in g a 5 0 . cm. section of glass helixes was capped with a dropping funnel. The bottom of the tube was connected to a trap containing 47. g. finely ground 97 $ sodium hydroxide and cooled in a Dry Ice-chloroform-carbon tetrachloride bath. A second trap, sim ilarly cooled but containing no base, was connected in series with the first trap. The Pyrex tube was heated to 470-500° in an electric furnace, and the entire apparatus flushed thoroughly with dry nitro g e n . While the portion of the tube extending from the top of the furnace to the dropping funnel was heated with an infrared lamp, 51«9 6 * (0.23& mole) of XXV was passed through the furnace over a period of two and one-quarter hours with an addition rate of approximately one drop every seven seconds. 8 8 After all the diacetate had passed through the furnace, the first trap, which consisted of a 2 5 0 m l. o n e - neck flask connected to a Y-adaptor, was dismantled and allowed to warm slowly to room temperature until rapid heating of the pyrolysate was observed. The flask wa3 then replaced in the cooling bath. The second trap, which contained 2-3 ml. of pyrolysate, was washed with two 25 ml. portions of purified ethanol, which were added to the cooled flask. The process of removal from the bath and reimmersion was repeated until rapid heating of the flask was no longer d e t e c t e d . The pyrolysate (a brown oils considerable carboniza tion had occurred during pyrolysis), base, and ethanol were mixed as well as possible and the mixture heated at room temperature to 40° for five hours at 40 mm., then three hours at 2-3 mm. The distillate (30-40 m l.), con taining ethanol and volatile reaction products, was diluted to 50. ml. with purified ethanol. No reactions were observed between 4 ml. aliquots of the ethanolic solu tion and 1.12 g. of vinylene carbonate, 0.04 g. of N- phenylmaleimide, or 2 ml. of hexyne-3. The ultraviolet absorption spectrum of a 1 ml. aliquot diluted 1:2500 with 95# ethanol is given in Fig ure 8. A yield of about 1# V was calculated on the assumption that the shoulder at 240-255 m|t represents absorption due to the diene (V), and € ■ 5 .1 9 x 10 ^ a t 247 m|x. fo r V. .24

PRODUCT OBTAINED FROM PYROLYSIS OF

—Q

SOLVENT : 95% ETHANOL

.06

220 2 6 0 0 3 4 0 3 8 030 WAVELENGTH (m|i) ^ VO FIGURE 8 0.8 r

0.6

0.4 N - Phenylmaleimide

0.2 Concentration^ 0.0076 9/ Solvent: 95% ethanol

200 240 280 320 360 400 VO Wavelength (nryi) O FIGURE 9 Percent transmittance o-ioo 100 80 20 40 40 60 IUE 0 II 10, FIGURE opud i Compound FIGURE 10 FIGURE IUE II FIGURE in KBr a oe length in microns Wove Percent transmittance 0-100 100 60 80 60 - 60 40 20 IUE 2 13 12, FIGURE i n CS2 in CS2 inCS2 FIGURE 12 FIGURE h c IUE 13 FIGURE 3

aeegh in micronsWavelength SUMMARY

A brief study has been made of the effect of reaction conditions on the yield of the Diels-Alder adduct of furan and vlnylene carbonate. A good conversion of vinylene car bonate to adduct has been obtained at the expense of yield.

9,10-Dihydro-9* 10-ethano-11,12-methylenedioxyanthracene

(ill) has been prepared in 92 % yield by reaction of 9 >1° - d i h y d r o - 9 , 1 0 -athanoanthracene-cis-ll, 1 2 -diol with parafor maldehyde in refluxing benzene. Anthracene and a small amount of olefinic m aterial have been obtained from an attempted preparation of dioxole by pyrolysis of III.

Evidence has been obtained for the formation of 4,5- dimethylene-1,3~dioxolane (V) by pyrolysis of ci-4,5-bis-

(dimethyloxyaminomethyl)-1,3-dioxolane (XXIII). Compound

XXIII has been prepared by the following sequence of reac

tions. Reaction of diethyl d-tartrate with paraformaldehyde

in refluxing benzene has given diethyl d- 1 , 3 -dioxolane-4,5-

dicarboxylate (XVI) in 25$ yield. N,N,N1,N 1-Tetramethyl-

d-1,3-dioxolane-4,5-dicarboxamide (XXI) has been prepared

from XVI by two routes. After three days at room tempera

ture, a mixture of XVI and dimethylamine has given 57$ of

XXI. Also, saponification of XVI to disodium d-1,3-

dloxolane-4,5-dlcarboxylate (XIX), preparation of d-1,3-

dioxolane-4,5-bis-(carbonyl chloride) (XX) by refluxing a

mixture of XIX and thionyl chloride, and addition of XX to an

93 9 4 ethereal solution of dimethylamine has given XXI in 42$ overall yield, d-4,5-Bis-(dimethylaminomethyl)-1,3-dioxolane

(XXIl) has been prepared in 69 $ yield by reduction of XXI with lithium aluminum hydride in tetrahydrofuran. Oxidation of XXII with hydrogen peroxide has given XXIII in 97$ yield.

Pyrolysis of XXIII has given V in a calculated yield of 5°$*

Although isolation of V has not been achieved because of difficulties encountered in the removal of dimethylhydroxylamine from the pyrolysate, the structure of V has been con firmed by hydrogenation of the hydrocarbon-soluble portion of the pyrolysate to 4,5-dimethyl-1,3-dioxolane. Additional evidence for the presence of V in the pyrolysate has been obtained from spectroscopic analysis of the hydrocarbon- soluble portion of the pyrolysate and from reactions of products obtained on hydrolysis of the pyrolysate.

Attempts to purify V and to obtain a Diels-Alder adduct of V with N-phenylmaleimide have been described.

The preparation of N,N,N‘ '-tetraraethyl-d-tartramide

(XVIII) and the attempted preparation of XXI from XVIII have been described. Finally, the preparation of d-4,5-bis-

(hydroxymethyl)-1, 3 -dioxolane diacetate (XXV) and the attempted preparation of V by pyrolysis of XXV have been d e s c r i b e d . AUTOBIOGRAPHY

I, Carl Henry Snyder, was born in Pittsburgh, Pennsylvania, September 18, 1931. I received my elemen tary school education in the public schools of Pittsburgh and Penn Township, Pennsylvania, and my secondary school education from the public schools of Penn Township. In 1953 I received the Bachelor of Science degree in Chemistry from the University of Pittsburgh and was ap pointed Assistant in the Department of Chemistry at The Ohio State University. I held this position during the years 1953-54 and 1957“58* £ was also appointed Ketter ing Fellow In 1954 and held this position for three years while completing the requirements for the Doctor of Philosophy degree.