AU623023B2

AU623023B2 - Process for the preparation of derivatives of 1,3-dioxolane and of 1,3-dioxane

Info

Publication number: AU623023B2
Application number: AU57909/90A
Authority: AU
Inventors: Peter Dr. Lappe; Helmut Springer; Jurgen Dr. Weber
Original assignee: Hoechst AG
Current assignee: Hoechst AG
Priority date: 1989-06-29
Filing date: 1990-06-28
Publication date: 1992-04-30
Anticipated expiration: 2010-06-28
Also published as: DE3921280A1; EP0405271A1; AU5790990A; CA2019929A1; JPH0338585A

Description

COMMONWEALTH OF A N PATENTS ACT 1951i fa 3 r COMPLETE SPECIFICATION

(ORIGINAL)

Class In Application Number: Lodged: Form t. Class Complete Specification Lodged: Accepted: Published: Priority Related Art Name of Applicant Address of Applicant Actual Inventor Address for Service HOECHST AKTIENGESELLSCHAFT Bruningstrasse, D-6230 Frankfurt/Main of Germany 80, Federal Republic JURGEN WEBER, PETER LAPPE and HELMUT SPRINGER WATERMARK PATENT TRADEMARK ATTORNEYS.

LOCKED BAG NO. 5, HAWTHORN, VICTORIA 3122, AUSTRALIA Complete Specification for the invention entitled: PROCESS FOR THE PREPARATION OF DERIVATIVES OF 1,3-DIOXOLANE AND OF 1,3-DIOXANE The following statement is a full description of this invention, including the best method of performing it known to us 1.

_L

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2 Process for the preparation of derivatives of 1,3dioxolane and of 1,3-dioxane The present invention relates to a novel process for the preparation of 2-[(1,l-dialkyl-2-hydroxy)ethyl]-l,3dioxolanes and 2-[(1,l-dialkyl-2-hydroxy)ethyl]-1,3dioxanes of the gneral formula O C(R 3

R

4 HOCH C(R R (CR7R 0 C(R R 6 Dioxolanes and dioxanes which conform to the above formula may be summarized as cyclic hydroxyacetals.

Accordingly, a common method for their preparation is the condensation of aldehydes with 1,2- or 1,3-diols. The fsubstituted dioxalanes and dioxanes of the invention are extremely important as intermediates for the preparation of plastics and pharmaceuticals as well as plasticizers for cellulose acetates as raw materials for paints and as a component of printing inks.

Various orocedures are known for the preparation of dioxolane and dioxane derivatives from aldehydes and diols, differing in the reaction conditions and, in S."0 particular, in the catalyst employed.

Thus, according to Japanese Patent Application 16,867 (1966), cited in C.A. 66, 10943 d (1967), 2-substituted 5,5-dimethyl-l,3-dioxanes are obtained from 2,2-dimethylpropane-1,3-diol and an aldehyde at elevated temperature in the presence of a highly acidic cation exchanger. If, for example, 2,2-dimethyl-3-hydroxypropanal is employed, 2-[(l,l-dimethyl-2-hydroxy)ethyl]-5,5-dimethyl-l,3dioxane is produced in a yield of 64.1% at a reaction temperature of 50 to 60 0

C.

In J. Org. Chem. 29, 3424 ff (1964), Galiano et al.

L d 3 describe the formation of cyclic dioxanes in water as the reaction medium. When 2,2-dimethylpropane-1,3-diol is used as the alcohol and 2,2-dimethyl-3-hydroxypropanal as the aldehyde, the starting materials obviously being employed in pure form, the corresponding rclic acetal 2- [(l,l-dimethyl-2-hydroxy)ethyl]-5,5-dimethyl-1,3-dioxane is produced in a yield of 88% at 75 0 C and in the presence of p-toluenesulfonic acid as the catalyst. This procedure is unusual, since it is customary to shift the equilibrium established in the reaction of aldehyde and diol in the direction of the cyclic acetal by removing the water of reaction azeotropically. This process is not suitable for industrial use since it requires long reaction times, for example 16 hours for the reaction described.

According to Spath et al., Ber. 75, 949 ff (1943), 2,2dimethylpropane-1,3-diol and 2,2-dimethyl-3-hydroxypropanal are reacted at 100 c in the presence of dry, gaseous hydrogen chloride. After 14 hours, the desired condensation product is obtained in 56% yield. However, this procedure again fails to meet the requirements for industrial use.

t t The reaction of 2,2-dimethyl-3-hydroxypropanal with various 1,2-diols such as ethylene glycol or 2,3-butane- 25 diol, and 1,3-diols, such as 1,3-butanediol or 1,3propanediol, to give cyclic acetals is subject-matter of German Offenlegungsschrift 1,957,621. In this process, ptoluenesulfonic acid or a mineral acid is used as the 4.

catalyst, and the water of reaction is removed by distillation. The cyclic acetals are obtained in a yield of 63 to The cyclic acetal obtainable from 2,2-dimethylpropane- 1,3-diol and 2,2-dimtthyl-3-hydroxypropanal can also be obtained directly from 2,2-dimethylpropane-l,3-diol by heating the diol to 190 C with a Pt/carbon catalyst.

After a reaction time of 5.5 hours, the yield of cyclic

Y

4 acetal is 41.1%. If the same reaction is carried out in the presence of a Pd/carbon catalyst, the cyclic acetal is obtained, after a reaction time of 8 hours, in a yield of 26% (British Patent 1,046,608).

As can be seen from the outlining of the prior art, the known processes for the preparation of substituted dioxolanes and dioxanes still have a number of disadvantages. Thus, Lhe reaction times required or the yields obtained are not always satisfactory; in some cases, both criteria fail to meet the requirements made of industrial processes. In addition, the published data generally do not indicate the degree of purity required for the starting materials. Only in German Offenlegungsschrift 1,957,521 is the indication found, in Example 9, that a crude product having a purity of 79% is used as the aldehyde component for the reaction. The use of such an impure starting material obviously adversely affects the yield, which is only 49% of theory. In this connection, it should be taken into account that the aldehyde can only be obtained in pure form using great equipment complexity and in poor yield.

There is therefore interest in a process for the ,preparation of cyclic acetals which ensures high yields in short reaction times, even when starting materials of "25 technical-grade purity are employed.

The invention relates to a process for the preparation of derivatives of 1,3-dioxolane and of 1,3-dioxane of the general formula 0 C(R3R 4 HOCH2-C(R 1

R

2 CI (CR 7

R

8 0 C(R 5

R

6 IL I 5 in which R 1 and R 2 are identical or different and are straight-chain or branched alkyl radicals having 1 to 4 carbon atoms, R 3

R

4

R

5

R

6

R

7 and R" are identical or different and are hydrogen or straight-chain or branched alkyl radicals having 1 to 4 carbon atoms, and n is 0 or 1, by condensation of 2,2-dialkyl-3-hydroxypropanals of the general formula

HOCH

2

-CR'R-CHO

in which R 1 and R 2 are as defined above, with diols of the general formula

HOCR

3 "R (CR78) CR5R60H in which R 3 R R R 6

R

7 R and n are likewise as defined above. The process comprises employing the 2,2dialkyl-3-hydroxypropanals in the form of the crude product obtained on addition reaction of formaldehyde with 2-alkylalkanals in the presence of a tertiary amine.

Surprisingly, the process according to the invention makes it possible, starting from starting materials which are readily available in technical-grade purity, to *20 prepare substituted 1,3-dioxolanes and substituted 1,3dioxanes in high yields and short reaction times.

oThe 2,2-dialkyl-3-hydroxypropanals used as one component Sof the reaction, for example 2,2-dimethyl-3-hydroxypropanal (formisobutyraldol, hydroxypivaldehyde) are obtained in a known manner by aldol addition from formaldehyde and 2-alkylalkanals in the presence of tertiary amines (cf. for example, German Auslegeschrift 1,793,572). Examples of suitable 2-alkylalkanals are 2methylpropanal, 2-methylbutanal, 2-ethylbutanal and 2ethylhexanal. The reaction is generally carried out at between 20 and 100°C, preferably between 60 and 95"C, to 1.5 moles, preferably 1 to 1.1 moles, of formaldehyde, L I 6 expediently as aqueous solution, being employed per mole of 2-alkylalkanal. The tertiary amines used as catalysts are generally used in an amount of from 0.5 to advantageously 2 to 10, mole relative to the 2-alkylalkanals. In particular, aliphatic tertiary amines are suitable, although cycloaliphatic, araliphatic, aromatic or heterocyclic amines have also proven successful as catalysts. Triethylamine, methyldiethylamine, tributylamine, cyclohexyldimethylamine, triethanolamine and, in particular, tripropylamine, for example, are used successfully.

In practice, 2-alkylalkanal, formaldehyde and amine are mixed at room temperature, and the exothermic reaction is Iaccelerated, if necessary, by heating. Water and amine are subsequently removed from the mixture by distillation. The crude product obtained in this way contains between 80 and 90% by weight of 2,2-dialkyl-3hydroxypropanal and between 2 and 4% by weight of amine.

It can be fed to the process according to the irD';ntion without further purification.

The suitability of a crude 2,2-dialkyl-3-hydroxypropanal for the preparation of cyclic acetals in high yield was not to be expected. It should be taken into ac., here that the crude products may contain 10 to 20% b_ weight 25 of impurities besides amine. In the case of the 2,2dimethyl-3-hydroxypropanal, obtained from 2-methylpropanal (isobutyraldehyde) and formaldehyde, these impurities are, in particular, isobutanol, 2,2-dimethyl- 1,3-propanediol and the neopentyl glycol ester of hydroxypivalic acid, as well as unreacted starting aldehydes.

Suitable glycols are, inter alia, ethylene glycol, 1,2and 1,3-propylene glycol, 1,3-butanediol, 2,3-butanediol, 2,2-dimethyl-1,3-propanediol (neopentyl glycol), 2methyl-2-ethyl-1,3-propanediol, 2,2-diethyl-1,3-propanediol, 2-ethyl-2-isopropyl-1,3-propanediol, 2,2,4- -1 1 7 trimethyl-1,3-pentanediol, 2-ethyl-1,3-hexanediol and 2ethyl-2-n-butyl-l,3-propanediol. The glycols may also be employed in the commercially available form.

The reaction of the reactants can be carried out in a manner known per se. In general, they are employed in the molar ratio 1:1. However, it is of course also possible to use either the hydroxyaldehyde or the diol in excess.

In this case, it has proven successful to employ 0.7 to 1.3, in particular 0.8 to 1.1, moles of the diol per mole of aldehyde. The reaction takes place in the presence of acidic catalysts. Strong acids, such as sulfuric acid, hydrochloric acid, sulfonic acid and, preferably, phosphoric acid are suitable. The amount of catalyst, relative to the starting materials, may vary within a 15 broad range. It has proven successful to use 0.1 to by weight, and preferably 0.5 to 6% by weight, of cataoo lyst, relative to the aldehyde, where care should be a.o taken that the amine present in the reaction mixture has 0, previously been neutralized. In principle, however, larger amounts of mineral acid can also be used.

The reaction temperature may be varied within broad limits. In general, temperatures of from 50 to 180 0 C, in particular 90 to 140 0 C, are maintained.

It is possible to carry out the reaction in the presence of a solvent. Expediently, the solvent simultaneously serves as an entrainer for the water produced during the reaction. Benzene, toluene and xylene are suitable, and in addition also chlorinated hydrocarbons, such as chloroform, 1,2-dichloroethane, trichloroethylene or perchloroethylene. The solvents are employed in amounts of from 20 to 80% by weight, -elative to aldehyde.

Under the conditions described, the reaction requires reaction times of between 1 and 4 hours, in particular and 3 hours.

I 1- 8 For work-up, the reaction mixture is treated with an alkaline reagent, for example sodium hydroxide, potassium hydroxide or sodium carbonate, in an amount such that a pH of about 7.0 is produced. Water and organic phase are separated from one another, and the organic phase is subjected to fractional distillation. After the readily volatile components of the mixture, in particular organic solvents and the amine as well as low-boiling byproducts, have been removed, the residue containing the acetal is subjected to fractional distillation. Depending on the starting materials, the yield is generally greater than of theory.

The invention is explained in the examples below. It is of course not intended to limit the invention to these specific working examples.

Example 1: Preparation of 2-[(1,l-dimethyl-2hydroxy)ethyl]-1,3-dioxane 271.0 g of 2,2-dimethyl-3-hydroxypropanal (85.6% purity, amine nitrogen content: 0.33%) (2.27 mol) are dissolved at about 70 0 C in 300 g of toluene in a 2 1 round-bottom flask. 23.0 g of 85% strength phosphoric acid (200 mmol) and 174,4 g of 1,3-propanediol (96% purity) (2.20 mol) are added, the mixture is warmed to the reflux S^o temperature and the water of reaction produced (49.2 g) is removed via a water separator. The reaction time is 2 hours. When the reaction is complete, the mixture is allowed to cool and is neutralized to pH 7.03 using 111.8 g of 10% strength sodium hydroxide solution; 119.0 g of water phase and, as the organic phase, 712.0 g of crude acetal are produced, and the latter is subjected to fractional distillation. Yield; 308.5 g (87.5% of theory).

Example 2: (1,-dimethyl-2-hydroxy)ethyl]-4methyl-1,3-dioxane J_ A

I

S9 271.0 g of 2,2-dimethyl-3-hydroxypropanal (85.6% purity, i amine nitrogen content: 0.33%) (2.27 mol) are dissolved i at about 70°C in 300 g of toluene in a 2 1 round-bottom flask. 23.0 g of 85% strength phosphoric acid (200 mmol) and 208.8 g of 1,3-butanediol (94.9% purity) (2.20 mol) are added, the mixture is warmed to the reflux temperature and the water of reaction produced (51.7 g) is removed via a water separator; the reaction time is 2 hours. When the reaction is complete, the mixture is allowed to cool and is neutralized to pH 7.11 using 123.2 g of 10% strength sodium hydroxide solution; 127.9 g of water phase and, as the organic phase, 746.4 g of crude acetal are produced, and the latter is subjected to fractional distillation. Yield: 337.8 g (88.2% of theory).

Example 3: Preparation of 2-[(1,1-dimethyl-2hydroxy) ethyl]-1, 3-dioxolane 271.0 g of 2,2-dimethyl-3-hydroxypropanal (85.6% purity, amine nitrogen content: 0.33%) (2.27 mol) are dissolved at about 70"C in 300 g of toluene in a 2 1 round-bottom flask. 23.0 g of 85% strength phosphoric acid (200 mmol) 1: and 136.6 g of ethylene glycol (99.9% purity) (2.20 mol) are added, the mixture is warmed to the reflux temperature and the water of reaction produced (51.4 g) 0. 25 is removed via a water separator; the reaction time is 2.5 hours. When the reaction is complete, the mixture is allowed to cool and is neutralized to pH 7.10 using 132.5 g of 10% strength sodium hydroxide solution; 137.9 g ca water phase and, as the organic phase, 673.8 g of crude acetal are produced, and the latter is subjected to fractional distillation. Yield: 277.8 g (86.5% of theory).

Example 4: Preparation of 2-[(1-methyl-1-ethyl-.2hydroxy)ethyl] -4-methyl-l,3-dioxane 258.2 g of 2-hydroxymethyl-2-methylbutanal (89.9% purity,

I~

;i I r i:! i i i i 10 o i i 00 i 0 0 o0 0 0 C o o D oa amine nitrogen content: 0.21%) (2.0 mol) are dissolved at about 70°C in 300 g of toluene in a 2 1 round-bottom flask. 16.1 g of 85% strength phosphoric acid (140 mmol) and 189.2 g of 1,3-butanediol (94.9% purity) (2.0 mol) are added, the mixture is warmed to the reflux temperature and the water of reaction produced (45.1 g) is removed via a water separator; the reaction time is 3 hours. When the reaction is complete, the mixture is allowed to cool and is neutralized to pH 7.08 using 100.1 g of 10% strength sodium hydroxide solution; 109.5 g of water phase and, as the organic phase, 709.0 g of crude acetal are produced, and the latter is subjected to fractional distillation. Yield: 321.6 g (85.5% of theory).

15 Example 5: Preparation of 2-[(1-methyl-l-ethyl-2hydroxy)ethyl]-5,5-dimethyl-1,3-dioxane 258.2 g of 2-hydroxymethyl-2-methylbutanal (89.9% purity, amine nitrogen content: 0.21%) (2.0 mol) are dissolved at about 70 0 C in 300 g of toluene in a 2 1 round-bottom flask. 16.1 g of 85% strength phosphoric acid (140 mmol) and 218.4 g of neopentyl glycol (99.5% purity; 2.09 mol) are added, the mixture is warmed to the reflux temperature and the water of reaction produced (41.7 g) is removed via a water separator; the reaction time is 3 hours. When the reaction is complete, the mixture is allowed to cool and is neutralized to pH 7.11 using 72.7 g of 10% strength sodium hydroxide solution; 82.8 g of water phase and, as the organic phase, 740.9 g of crude acetal are produced, and the latter is subjected to fractional distillation. Yield: 362.3 g (89.7% of theory).

Example 6: Preparation of 2-[(1,l-diethyl-2-hydroxy)ethyl]-5,5-dimethyl-l,3-d.oxane 357.4 g of 2-ethyl-2-hydroxymethylbutanal (80.09% purity, amine nitrogen content: 0.44%) (2.20 mol) are dissolved 11 at about 70°C in 300 g of toluene in a 2 1 round-bottom flask. 23.1 g of 85% strength phosphoric acid (200 mmol) and 230.2 g of neopentyl glycol (99.52% purity; 2.20 mol) are added, the mixture is warmed to the reflux temperature and the water of reaction produced (43.8 g) is removed via a water separator; the reaction time is 3 hours. When the reaction is complete, the mixture is allowed to cool and is neutralized to pH 7.09 using 149.6 g of 10% strength sodium hydroxide solution; 161.1 g of water phase and, as the organic phase, 855.4 g of crude acetal are produced, and the latter is subjected to fractional distillation. Yield: 410.0 g (86.3% of theory).

Example 7: Preparation of 2- i-diethyl-2-hydroxy) ethyl] 3-dioxane 357.4 g of 2-ethyl-2-hydroxymethylbutanal (80.09% purity, amine nitrogen content: 0.44%) (2.20 mol) are dissolved at about 70 0 C in 300 g of toluene in a 2 1 round-bottom flask. 23.1 g of 85% strength phosphoric acid (200 mmol) and 174.4 g of 1,3-propanediol (96.0% purity; 2.20 mol) are added, the mixture is warmed to the reflux temperature and the water of reaction produced (54.9 g) is removed via a water separator; the reaction time is 3 hours. When the reaction is complete, the mixture is 25 allowed to cool and is neutralized to pH 7.15 using o 163.0 g of 10% strength sodium hydroxide solution; 202.8 g of water phase and, as the organic phase, 760.2 g of crude acetal are produced, and the latter is subjected to fractional distillation. Yield: 349.5 g (84.5% of theory).

Example 8: Preparation of 2-[(1,l-dimethyl-2hydroxy) ethyl]-5,5-diLethyl-1, 3-dioxane 392.0 g of 2,2-dimethyl-3-hydroxypropanal purity, amine nitrogen content: 0.36%) (3.40 mol) are dissolved at about 70°C in 463.6 g of toluene in a 2 1 round-bottom c 12 flask. 35.6 g of 85% strength phosphoric acid (309 mmol) and 321.3 g of neopentyl glycol (99.52% purity; 3.08 mol) are added, the mixture is warmed to the reflux temperature and the water of reaction produced (67.2 g) is removed via a water separator; the reaction time is hours. When the reaction is complete, the mixture is allowed to cool and is neutralized to pH 7.1k using 227.2 g of 10% strength sodium hydroxide solution; 243.3 g o' water phase and, as the organic phase, 1129.2 g of crude acetal are produced, and the latter is subjected to fractional distillation. Yield: 508.4 g (87.8% of theory).

Claims

3- 13 THIE CLAIMS DEFINING THE INVENTION ARE AS FOLLOWS: A process for the preparation of derivatives of 1,3-dioxolane and of 1,3-dioxane of the general formula j i 1 :i i i 0 C(R 3 R 4 HOCH 2 -C(R 1 R 2 CH (CR 7 R 8 0 C(R5R6) 1 to 3, present preferab the aide 1 to 4 temperat 140"C.
6.) 1 to pres enc entrain
7.) entrain hydroca
8.) the sol weight, in which R' and R 2 are identical or different and are straight-chain or branched alkyl radica1s having 1 to 4 carbon atoms, R 3 R 5 R 6 R 7 and R' are identical or different and are hydrogen or straight-chain or branched alkcyl radicals ha-viing 1 to 4 carbon atoms, and n is 0 or 1, by condensation of 2,2-dialkyl-3-hydroxypropanals of the general formula HOCH 2 -CR 1 R 2 -CHO I in which R 1 and R 2 are as defined above, with diols of the general formula II 6 1 £6 I 6 gI 66 6 @646 P6 66 6 66 DATE HOCR 3 R 4 5 6 7 HOCRR' -(CRi R I)n CR R Oi in which R 3 R 5 R 6 R7 R' and n are likewise as defined above, wbich comprises employing the 2,2-dialkyl- 3-hydroxypropanals in the form of the crude product obtained nn addition reaction of formaldehyde with 2- alkylal.kanals in the presence of a tertiary amine. The process as claimed in claim 1, wherein 0.7 to 1.3, in particular 0.8 to 1.1, molc's of diol are employed per mole of aldehyde. The process as claimed in claim 1 or 2, wherein the aci%2P catalyst ;nployed is phosphoric acid. HOEC 1C- I- I i- 14 The process as claimed in one or more of claims 1 to 3, wherein, after neutralization of the amine present in the reaction mixture, 0.1 to 10% by weight, preferably 0.5 to 6% by weight, of catalyst, relative to the aldehyde, are employed. The process as claimed in one or more of claims 1 to 4, wherein the reaction is carried out at temperatures of from 50 to 180, in particular 90 to 140"C. The process as claimed in one or more of claims 1 to 5, wherein the reaction is carried out in the presence of a solvent which simultaneously serves as an entrainer for the water produced during the reaction. The process as claimed in claim 6, wherein the entrainer is an aromatic hydrocarbon or a chlorinated hydrocarbon. The process as claimed in claim 6 or 7, wherein the solvent is employed in an amount of from 20 to 80% by 1 weight, relative to aldehyde. DATED this 27th day of June 1990. HOECHST AKTIENGESELLSCHAFT WATERMARK PATENT TRADEMARK ATTORNEYS "THE ATRIUM" 210 BURWOOD ROAD HAWTHORN. VIC. 3122.