ON CONDENSATION PRODUCTS OF PROPYLENE OXIDE AND OF GLYCIDOL.

BY P. A. LEVENE AND A. WALTI.

(From the Laboratories of The Rockefeller Institute for Medical Research, New York.)

(Received for publication, July 29, 1927.)

One of the problems of organic chemistry which engages the attention of the workers of today is that of the structure of natur- ally occurring substances of high molecular weight such as poly- saccharides, proteins, etc. Whereas classical organic chemistry viewed the formation of the complex from the simple molecules as a process of condensation through the well recognized forces of primary valence, present day chemists are inclined to the view that the simpler components are linked to each other by the forces of residual valence due to incomplete saturation of groups or elements within the simpler molecules. In the polysacchtirides, such resid- ual affinities are attributed principally to the oxidic ring. Con- siderable evidence has been advanced in favor of this view by Bergmann,l Karrer,2 Pictet,3 Pringsheim,4 and others. Still the problem as yet cannot be regarded as definitely settled.

From this view-point it seems important to investigate the simple cyclic compounds with respect to their tendency to poly- merize or to condense with one another. Taking for example ethylene oxide, the simplest substance of this group, it is evident that it may polymerize or give an ether of the composition

CH2-0-CHI

I I CH,--0-CH2

1 Bergmann, M., and Ludewig, S., Ann. Chem., 1924, cdxxxvi, 173. Bergmann, M., and Kann, E., Ann. Chem., 1924, cdxxxviii, 278.

2 Karrer, P., Polymere Kohlenhydrate, Leipsic, 1925. 3 Pi&et, A., and Ross, J. H., Compt. rend. Acad., 1922, clxxiv, 1113;

Helv. Chim. Acta, 1922, v, 876.

’ Pringsheim, H., Die Polysaccharide, Berlin, 1923; Naturwissenschaften, 1925, xiii, 1084.

325

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Propylene Oxide and Glycidol

or more complex ones as

CHz-CHr-O-CHz-CH2

/ \ 0

\ /” CHe-CHr-O-CHs-CHs

The ethers do not differ in their elementary composition from the polymers.

Which are the factors that determine the direction of the reac- tion towards polymerization or towards condensation? The pres- ent work is undertaken to obtain some light towards the solution of this problem.

The substances taken for the present investigation were propy- lene oxide and glycidol. These two substances differ from each other only in that the first contains in position (3) a methyl group, the second, in the same place, a hydroxymethyl group.

It was desired to study first those reactions which would take place under the influence of higher temperature and pressure only. In the case of propylene oxide, however, there was tested also the tendency towards condensation of propylene oxide with propylene glycol and also the condensation under the influence of a minimal quantity of a 50 per cent solution of alkali.

Experiments on condensation of propylene oxide with propylene glycol were made in the absence of catalysts and also in the pres- ence of a trace of concentrated sulfuric acid.

In the case of the glycidol, the condensations were brought about without the action of catalysts. It must be added here that the property of glycidol to condense with itself has been observed before. The product of condensation, however, was never studied.

Experiments with Propylene Oxide.--On heating the oxide in a sealed tube at 165-167°C. for 4 weeks only a small part of the substance reacted; the greater part, about two-thirds, remained unchanged. The product which boiled at a higher temperature, namely at 122-135”C., had the odor and other properties of the diether of propylene glycol.

CHa-O-CH,

I I CHrCH-0-CH.CHs

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P. A. Levene and A. Walti 327

For identification the ether was prepared by distillation of pro- pylene glycol with sulfuric acid. The substance obtained under such conditions was definitely the diether and not a polymer of propylene oxide for the reason that it was prepared on distillation of the di(hydroxypropy1) ether,

CHz-O-CHz

I I CH, CHOH CHOHCH,

The di(hydroxypropy1) ether was obtained from propylene oxide on heating with very little alkali (0.5 cc. of a 50 per cent solution to 8.5 gm. of the oxide). Undoubtedly, part of the oxide was hydrolyzed to the glycol and the reaction proceeded in the follow- ing way.

HOCHz

o+ +

CHe-0-CHI

I I CH,CH ’ CHOHCHB CH~CHOH CHOHCHi

Indeed, the same substance 6vas obtained on condensation of pro- pylene oxide with propylene glycol in the absence of catalysts, or in the presence of a trace of sulfuric acid.

As regards the condensation of propylene oxide in the presence of a little alkali, it may be added that the reaction does not stop at the dimolecular ether, inasmuch as alongside with the di- hydroxy ether, substances were obtained which analyzed well for the trimolecular and for the tetramolecular complexes.

Thus, under the conditions thus far employed, propylene oxide showed great reactivity towards the formation of condensation products. Polymerization in the true sense, has as yet not been observed. This, however, does not mean that conditions for polymerization will not be found in the future. Efforts to accom- plish this end will be continued in this laboratory.

Experiments with Glyc doL5-On heating anhydrous glycidol for 42 hours, at the temperature of the boiling steam bath, a prod- uct was obtained which distilled at 128-130°C. at 1.5 mm. and had the same elementary composition as glycidol. The sub-

6 Cj. Bresslauer, M., J. prakt. Chem., 1879, xx, 188.

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328 Propylene Oxide and Glycidol

stance, thus, could be either a product of polymerization of the glycidol or a condensation product of the following composition.

In order to decide between the two structures, the substance was hydrolyzed with dilute sulfuric acid and the product obtained in this manner analyzed not for glycerol, as it should have in case of simple polymerization, but for the following substance.

CH,OHCHOHCHz \o

CHzOHCHOHCH/

Thus the condensation undoubtedly proceeded in the following way.

On heating at 125°C. for several days, a higher condensation product was obtained.

The elementary composition of the substance was identical with that of glycidol but it was a heavy, viscous substance, non-distill- able and possessing the molecular weight of a 6-molecular glycidol. On hydrolysis with dilute sulfuric acid a distillable substance could not be obtained from it. On treatment with ammonia a substance was obtained which contained only a small quantity of amino nitrogen. On account of these properties and because of the re- sults of the condensation experiment at lower temperature, it is assumed that the substance consists of one or several condensation products of the general formula

/“\ CHsOHCHOHCH, 1 0 CH, CHOH CHt 1 n-OCHz-CH- CHt

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P. A. Levene and A. Walti 329

EXPERIMENTAL.

Distillation of Propylene Glycol in the Presence of Sulfuric Acid- To 40 gm. of propylene glycol were added 1.1 cc. of concentrated sulfuric acid (sp. gr. = 1.84). The solution was distilled. The distillate consisted of two layers; the bottom layer weighed 15 gm. and was colorless; the top layer weighed 21.5 gm. and had a greenish color.

The top layer was taken up in ether, washed, with dilute sodium carbonate until it was free from acid, and then with water until the solution gave only a faint test for aldehyde with fuchsin and sulfurous acid, as well as with sodium nitroprusside and piperidine. To remove the traces of the aldehydes the solution was allowed to stand overnight with Tollens’ reagent. The reaction product was extracted with ether. The ethereal solution was washed, dried over sodium sulfate, and distilled. The presence of traces of alde- hydes even after a repeated treatment with Tollens’ reagent suggests that some aldehyde is continually produced by hydrolysis of the propionic aldehyde propylene glycol acetal which very probably formed from the diether of propylene glycol.

The residue after removing the et.her was

I. 114-117” about 8.5 cc. II. 127-170’ “ 2 “ at 771 mm. pressure.

The first fraction was refractionated in a small distilling flask with a column into the following parts.

I. 112-114’, 2 cc 11. 11&117°, 4.5 “

III. 117-125’, 1 “

Residue 0.3 cc.

The analysis of the third fraction corresponds to the propylene glycol diether

CHr-CH-CHz

I I

!H PH-CH 2- s

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330 Propylene Oxide and Glycidol

CHs CH - CHn

I / 0 0

I/ CH-CHz-CH,

0.0934 gm. substance: 0.2125 gm. COz and 0.0881 gm. HaO. CBHISOS. Calculated. C 62.07, H 10.34.

Found. “ 62.04, “ 10.55.

On distilling 2.9 gm. of di(hydroxypropy1) ether (preparation described later in this paper) in the presense of 0.06 cc. of con- centrated sulfuric acid between 80-115”C., 2 cc. of a mixture were obtained consisting of 1.5 cc. of a yellow top layer and 0.5 cc. of an aqueous bottom layer. In the distilling flask remained a black residue. The aqueous part gave an aldehyde reaction with a sulfurous fuchsin solution. The top layer was taken up in ether to which a little ice was added. The mixture was neutralized with sodium carbonate solution and washed until neutral (the aqueous wash water still gave the aldehyde reaction). The ether solution was dried over sodium sulfate, then a little sodium was added to remove traces of water, and the ether was removed by distillation with a long column. From the residue a fraction was received boiling from llO-119“C. at ordinary pressure. This substance represents dimethyldioxane.

2.633 mg. substance: 6.110 mg. CO2 and 2.604 mg. HzO.

GH1202. Calculated. C 62.07, H 10.34. Found. “ 62.10, “ 10.77.

Condensation of Propylene Oxide.-8 gm. of propylene oxide (not entirely anhydrous) were kept in a sealed tube at 165167°C. for 4 weeks. Two-thirds of the reaction mixture distilled over at the temperature of unchanged propylene oxide. 1 cc. of substance distilled between 122-135”. The odor of the latter fraction was similar to that obtained on distilling propylene glycol or isohydroxypropyl ether in the presence of sulfuric acid. It represents very probably impure dimethyldioxane. A small amount of higher boiling liquids was obtained boiling from 11Q 140°C. and 14&17O”C. at 5 mm. pressure. These two liquids

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P. A. Levene and A. Walti 331

represent a mixture of various polyethers which are described below.

Action of Potassium Hydroxide on Propylene Oxids.--8.5 gm. of optically active propylene oxide ([a]: = f10.3”) to which 0.5 cc. of a 50 per cent potassium hydroxide solution had been added, were heated at 117-118°C. for 12 days. The reaction product was subjected to fractional distillation. A small fraction, 1.5 cc., dis- tilled at 128-130°C. and 2.4 mm. pressure. The temperature of the bath was 167-170°C.

A second fraction (about 2 cc.) was obtained at 130-140°C. and 2.4 mm. pressure, the temperature of the bath being 175- 185°C. This liquid showed a slight turbidity. The greater part could not be distilled. In the distilling flask remained 3.5 gm. of a brownish viscous liquid.

The analysis of the first fraction corresponds to a propylene glycol triether. It is as follows:

5.386 mg. substance: 11.071 mg. COZ and 5.155 mg. HzO. ChH~004. Calculated. C 56.19, H 10.50.

Found. “ 56.05, “ 10.72.

The rotation of the substance in water was

Lx = - 5.46" X 100 = _ 430”

1 X 12.69 . .

The second fraction analyzed for a tetramolecular condensation product.

4.154 mg. substance: 8.834 mg. CO, and 3.987 mg. HLO. GIHsOS. Calculated. C 57.55, H 10.47.

Found. “ 57.99, “ 10.74.

The rotation of the substance in water was

14: = - 6.05' X 100

1 X 12.30 = - 49.19”.

Action of Propylene Glycol on Propylene Oxide.-5 gm. of pro- pylene glycol and 8 gm. of propylene oxide were heated at a temperature of J17-118°C. for 12 days. The following frac- tions were obtained.

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332 Propylene Oxide and Glycidol

I. Fraction boiling from 90-103°C. at 5 mm. pressure, yielding about 2 cc.

II. Fraction boiling from 99-100°C. at 2 mm. pressure, yielding about 2 cc.

III. Fraction boiling from 93-103°C. at 0.8 mm. pressure, yielding about 4 cc.

The residue was further separated into two fractions.

IV. Fraction boiling from 120-125°C. at 1.6 mm. pressure. V. “ “ “ 126131°C. “ 1.6 “ “

The temperature of the bath during the last fractionation was 162-168°C.

The analysis for the second and third fraction was as follows:

5.895 mg. substance: 11.586 mg. CO2 and 5.553 mg. H20. 2,483 ” “ : 4.935 “ “ “ 2.433 “ “ CBHr403. Isohydroxypropyl ether. Calculated. C 53.69, H 10.52.

Found. II. “ 53.59, “ 10.54. III. “ 54.09, “ 10.94.

The analysis of the first fraction indicates that it also consists mostly of the di(hydroxypropy1) ether contaminated with a little unchanged propylene glycol.

The analyses of the fourth and fifth fractions correspond to a substance of the following composition.

CHt-0-CHp I I

CH(OH)CH,-0-CH CHOH I I I

CHE CHa CHs

The formation of this compound is very probably due to the in- terreaction of 1 molecule of propylene oxide with 1 molecule of the di(hydroxypropy1) ether. This substance analyzed as follows:

3.109 mg. substance: 6.420 mg. CO2 and 3.001 mg. H,O. 5.887 “ “ : 12.146 “ “ “ 5.441 $‘ “

&HzoOd. Calculated. C 56.19, H 10.50. Found. IV. “ 56.26, “ 10.31.

V. “ 56.31. “ 10.80.

In the following experiment 4 pm. of optically active propylene oxide ([cy]:’ = + 10.3”) and 2.6 gm. of optically active propylene

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P. A. Levene and A. Walti 333

glycol were heated at 117-119°C. for 8 days. About 1 gm. of unchanged propylene oxide and 2.5 gm. of propylene glycol were recovered. The fraction boiling from 95-100°C. at 4 mm. pres- sure was redistilled and a fraction received at 129-132°C. at 30 mm. pressure. This fraction represents optically active di(hy- droxypropyl) ether.

The analysis was as follows:

3.944 mg. substanbe: 7.630 mg. CO2 and 3.743 mg. HtO.

C&L403. Calculated. C 53.69, H 10.52. Found. “ 52.75, “ 10.61.

The rotation of the substance in water was

Lx = - 3.00” x loo

1 X 8.24 = - 36.4”.

Condensation in Presence of Sulfuric A cid.-To 3.8 gm. of optically active propylene glycol([01]~~ = - 14”) were added 2.9 gm. of inactive propylene oxide and 0.02 cc. of concentrated sulfuric acid. A reaction took place immediately and spontaneously. After the initial reaction subsided, the mixture was heated for 6 hours on a steam bath under a retlux. After 15 hours standing, 12 cc. of water were added and the mixture was neutralized with a barium hydroxide solution. After heating with a little char- coal and filtering, the solvent was removed by distillation under reduced pressure. Some unchanged propylene glycol was re- covered. The fraction boiling from 115130°C. at 19 mm. pres- sure was redistilled at ordinary pressure (765 mm.) boiling from 226235°C. (uncorrected). It represents di(hydroxypropy1) ether. The analysis was as follows:

3.404 mg. substance: 6.687 mg. CO, and 3.229 mg. H20.

C6H140~. Calculated. C 53.69, H 10.52. Found. “ 53.59, “ 10 61.

The rotation in water was

[a]z,o = - 1.9i-T x loo

1 x 10.02 = - 19.76”.

The higher boiling fractions were not analyzed. Condensation of GlycidoL-The condensation of glycidol pro-

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334 Propylene Oxide and Glycidol

ceeds at ordinary temperature very slowly if at all, at 100°C. moderately, and at 16O”C., glycidol turns, within a few hours, very viscous and difficultly soluble in ether.

30 gm. of glycidol were heated for 42 hours on a steam bath under a reflux condenser with a calcium chloride tube. The unchanged glycidol was recovered by distillation under reduced pressure boiling from 42-44°C. at 2.6 mm. Then a fraction of 3.5 gm. was obtained which boiled at 135°C. and 1.6 mm., the temperature of the bath being 170-185°C. This substance analyzed for a dimeric glycidol.

3.844 mg. substance: 6.768 mg. COz and 2.941 mg. H20.

C&Oz. Calculated. C 48.61, H 8.10. Found. “ 48.01, “ 8.56.

In order to test the structure of this substance, two experiments were performed.

1. It was hydrolyzed with dilute sulfuric acid. If the substance were a dimeric glycidol, the product of hydrolysis should be glycerol; otherwise it should be an ether.

2. The addition of ammonia was tested. The proportion of amino nitrogen should permit the conclusion as to the number of oxidic rings that were in the molecule.

1. 2.5 gm. of this substance were. dissolved in 50 cc. of a 5per cent sulfuric acid solution and refluxed for 5 hours. The solution was neutralized with a saturated barium hydroxide solution and a little barium carbonate. After heating with a little char- coal and filtering, the water was removed under diminished pres- sure, and the residue repeatedly dissolved in a little absolute alco- hol and evaporated. Then the residue was distilled at 1.7 to 2 mm. pressure and a fraction received boiling from 199-202°C. The temperature of the bath was 235250°C. The substance weighed 1.5 gm. The boiling point as well as the analysis indi- cates that the substance is diglycerol,

CHzOHCHOHCHz-0-CH&HOHCH20H

The analysis was as follows:

4.239 mg. substance: 6.755 mg. CO2 and 3.286 mg. HtO. C6H1,06. Calculated. C 43.35, H 8.49.

Found. “ 43.45, “ 8.67.

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P. A. Levene and A. Walti 335

2. 1 gm. of the substance was dissolved in 200 cc. of concentrated ammonia and allowed to stand for 15 hours at 12°C. On evapora- tion under reduced pressure a residue was obtained which con- tained a considerable amount of ammo nitrogen but not quite enough even for 1 nitrogen atom in the molecule. Thus, the composition of the original substance may be expressed by the following structural formula.

/“\ CHzOHCHOHCHz-0-CHz-CH - CHa

Higher Condensation Product of GlycidoL-On heating glycidol for 7 days at 125°C. in a sealed tube, a yellow non-distillable sub- stance was obtained. The analysis agreed with a polymeric glycidol and was as follows:

0.0832 gm. substance: 0.1472 gm. CO2 and 0.0616 gm. HzO. C3H602. Calculated. C 48.61, H 8.10.

Found. “ 48.24, “ 8.28.

5 gm. of this substance were dissolved in 25 cc. of a 2 per cent sul- furic acid solution and refluxed for 74 hours. The solution was neutralized with barium carbonate, filtered, and the water removed under reduced pressure. The residue could not be distilled at 3 mm. pressure.

That the original substance still contained an cr-oxidic ring sys- tem could be shown by dissolving 1 gm. of the substance in 200 cc. of concentrated ammonia. After 15 hours standing, the ammonia with the water was removed under reduced pressure. The residue showed some amino nitrogen, but very little. The molecular weight determination shows that 6 molecules of glycidol had combined.

The Molecular Weight Determination by the Freezing Method. 18.9700 gm. HzO, 0.4981 gm. substance, O.ll’C. difference in

freezing temperature.

M _ 100 X 0.4981 X 18.5 ___ = 441.6.

0.11” X 18.970

6 x CsHsOs. Calculated 444. This estimation is given in a preliminary way and will be repeated.

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336 Propylene Oxide and Glycidol

SUMMARY.

1. On distillation of propylene glycol in the presence of sulfuric acid the following substance was obtained.

CHa-CH-CHz

I I 0 0

I I CHaCH-CHz

2. On condensation of propylene oxide in the absence of cat.alysts, the same substance is formed.

3. On condensation of propylene oxide in the presence of alkali, di(hydroxypropy1) ether is obtained, which can then be converted into the above diether.

4. Under the same conditions higher condensation products also are obtained of the type

CH, CHOH CHr-0-CHz CH-0-CH, CHOH CHs

I CHa

6. On condensation of propylene glycol with propylene oxide in the presence of sulfuric acid the same products are obtained as in (3) and (4).

6. Glycidol on warming at about 100°C. condenses into the substance

/O\ CHzOH CHOH CHr-OCHs-CH- CHa

7. Glycidol on condensation at higher temperat,ure gives higher condensation products.

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P. A. Levene and A. WaltiGLYCIDOL

PROPYLENE OXIDE AND OF ON CONDENSATION PRODUCTS OF

1927, 75:325-336.J. Biol. Chem. 

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