CZ28898A3 - Alkoxylated compounds reducing estrogenicity and process for preparing thereof - Google Patents

Abstract

Compounds of the formula A-D-(OC2H4)x-(O-Alk)y-(OC2H4)z-OR, wherein A denotes a straight-chained or branched alkyl or alkenyl group containing 1 to 18 carbon atoms, a phenyl group, a phenyl-alkenyl group wherein the alkenyl moiety contains 1 to 4 carbon atoms, a polycyclic group containing 9 to 14 carbon atoms, a polyol, alkoxy group, or hydrogen; B denotes phenoxy, oxy, phenyl, a linear or branched alkyl or alkenyl group, an amino group, or a carbonyl group; x is 0 - 10; y is 1 - 10; z is 0 - 100; each (O-Alk) denotes straight-chained or branched propoxy, butoxy or substituted oxirane; and R is hydrogen, sulfate, sulfonate, monophosphate, diphosphate, carboxylate, monosulfosuccinate, disulfosuccinate, or a salt thereof, are useful as surfactants per se and in any application in which the corresponding purely ethoxylated surfactants are useful, and have been found to exhibit reduced or no estrogenicity in themselves and their degradation products.

Description

Alkoxylated estrogen-reducing compounds and processes for their preparation

Technical field

The present invention relates to alkoxylates, including alkoxylates of phenolic compounds such as straight or branched chain alkylphenols, naphthol and naphthol derivatives, biphenols, straight or branched chain dialkylphenols, benzenediols, benzentriols, phenolic resins, stilbene and derivatives thereof, and phenylphenol on which however, the list is not limited. The invention further relates to alcohol alkoxylates, polyhydric alcohol alkoxylates, fatty acid alkoxylates, amine alkoxylates, carboxylic acid alkoxylates, and any other potentially alkoxylated species. In particular, the invention relates to certain derivatives of precisely such alkoxylates, for example useful as surfactants in many different industrial applications, and as intermediates from which other related compounds having various industrial and commercial uses can be prepared.

BACKGROUND OF THE INVENTION

Alkylphenol alkoxylates, and especially alkylphenol ethoxylates, have found widespread use in a variety of applications. These applications rely generally on the surfactant properties of these compounds. The surfactant properties can in turn be matched by the appropriate choice of the alkyl substituent on the phenol group and the number of repeating ethoxy groups forming the (ethoxy) chain attached at the oxygen atom that is bound to the phenyl group. For example, nonylphenol ethoxylates are well known surfactants having a variety of uses;

• ΒΒΒΒ · * · * 4 4 4 4 ·

Β · · Β »» »β β Β Β β β ·

ΒΒ Β ·· ΒΒΒ

Β Β «· ΒΒ Β <Β Β Β

These compounds are commonly known as nonoxynol compounds and contain from about 1 to 100 (or optionally more) repeating ethoxy groups. Alkylphenol ethoxylates have found widespread use in cosmetics, toilet products, and in various industrial applications such as oil slippery dispersants, de-inking agents, metal finishing, textile treatment, emulsion formulations, emulsion polymerization, detergents and related cleaners and the like.

Recently, there has been an interest in the scientific community as to whether a number of commonly used compounds, including nonylphenol and phenolic derivatives, such as nonylphenol ethoxylates, may exhibit estrogenicity [references:

S. Jobling et al., Detergent Components in Sewage Effluent Are Weakly Oestrogenic to Fish: An In-vitro Study Using Rainbow Throut (Oncorthynchus mykiss) Hepatocytes,

Detergent compounds in liquid effluents are weakly estrogenic to fish: In vitro study using rainbow trout hepatocytes (Oncorhynchus mykiss), Aqatic Toxicology, Vol. 27, pp. 361-372 (1993), AM Soto et al., P- Nonyl-Phenol: An Estrogenic Xenobiotic Released from Modified Polystyrene - p-Nonylphenol: Estrogenic xenobiotics released from modified polystyrene, Env. Health Perspectives, Vol. 92, pp. 167-173 (1991)].

The possibility that many phenolic compounds, their derivatives and derived biodegradation products may be associated with such an undesirable side effect is therefore of interest to all who manufacture and use these materials. Now, cautious and responsible behavior as a possible source of these substances in the environment, many of which have been shown to be estrogenic, must be approached in accessing ethoxylates and their derivatives, various nonionic, anionic, cationic and amphoteric surfactants.

· 9

98 ·· 999 «

9 9 9 9 9 9 9 9 9 9 9 9

9999 9 · 9 9

It is therefore desirable to recognize substances from which end-products having a wide variety of useful properties can be synthesized, such as those presently available with alkoxylated substances which do not present a risk of estrogens in use and which do not produce estrogenic substances during biodegradation.

Given the widespread use and wide variety of uses of alkylphenol ethoxylates coupled with the possibility that such ethoxylates can be decomposed, in particular by biodegradation, into the corresponding alkylphenol compounds or derivatives thereof, which may prove to be estrogenic, to find acceptable alternatives that might not appear as precursors of possible estrogenic materials, of course, extends widely beyond the alkylphenol alkoxylate range.

SUMMARY OF THE INVENTION

Despite the reasonable assumption that alkoxylated alkylphenol alkoxylate analogues may be expected to exhibit degradability to possible estrogenic alkylphenols and derivatives thereof, it has been determined that compounds having a hydrophobic moiety and a hydrophilic moiety in which the hydrophilic moiety consists of a polyethoxy chain, such as have alkoxylates and alkylphenols, characterized by that

(1) a short block of propoxy and / or butoxy group (s) stretches from the hydrophobic portion and precedes the ethoxy chain; or

2) a short block of propoxy and / or butoxy group (s) is inserted into the ethoxy chain, or

4

- 4 • 44 «• · 4 4 · * 4 4 4 · 944« * 9 · 9999 * 4 4 · 4 · 4 99 99 «944

4450 49 4 99 9 »

3) the propoxy and / or butoxy group (s) are randomly inserted into the ethoxy chain; or

4) the propoxy and / or butoxy group (s) are added to the end of the ethoxy chain; or

5) the propoxy and / or butoxy group (s) are replaced by an ethoxy chain, exhibiting highly desirable properties, exhibiting reduced or no estrogenicity of themselves and their degradation products.

In one aspect, the present invention includes compounds of formula

A ₁ _ ₄ -D- (OC ₂ H ₄ ) _X - (O-Alk) _y - (OC ₂ H ₄ ) _Z -OR (1), where

A denotes a straight or branched chain alkyl or alkenyl group containing 1 to 18 carbon atoms, a phenyl group, a phenylalkenyl group wherein the alkenyl moiety contains 1 to 4 carbon atoms, a polycyclic group containing 8 to 14 carbon atoms, a polyol, alkoxy or hydrogen atom ,

D is a phenoxy, oxy, phenyl, alkyl or alkenyl group formed by a straight or branched chain, amino or carboxy group, is 0 to 10,

I clay »« *

- 5 y is 1 to 10, z is 0 to 100, each (O-Alk) denotes a propoxy group or a straight or branched butoxy group or a substituted oxirane, and

R is hydrogen, the remainder of the sulfate, sulfonate, mono / or diphosphate, carboxylate, mono- and / or disulfosuccinate, or a salt thereof.

Yet another feature of the present invention are compounds of formula

A-D- (O-Alk) -OH wherein

A, D, (O-Alk) and y are as defined above, and their use as starting materials for the synthesis of compounds of Formula 1.

The compounds of the above formulas and methods as defined above are characterized by the formation of alkoxylated compounds which retain all the desired properties as surfactants, and also exhibit highly desirable properties exhibiting reduced or no estrogenicity of themselves and their degradation products.

• · «* * * * *

A detailed description of the invention will now be given.

Compounds corresponding to the above general formula

AD- (OC ₂ H ₄ ) _X - (O-Alk) _y - (OC ₂ H ₄ ) ₂ -OR (1) are useful in many commercial applications involving the use of surfactants. The present invention encompasses such compounds as such, as well as any final consumer compositions of a large number thereof, which may contain at least one compound of the formula. Without intending to limit the scope of the invention, such compositions include, but are not limited to, oilfield emulsifiers and demulsifiers, oil slip dispersants, de-inking surfactants, metal-treating surfactants, textile-surfactants, paper-gluing compositions, emulsion polymerizing surfactants, surfactants and emulsifiers for cosmetics, toilet preparations and other personal care preparations, hard surface cleaners, low foaming detergents, emulsifiers and dispersing agents, wetting agents, emulsifiers for agriculture, paint surfactants and the like.

Referring to the above general formula 1, the moiety N 4 - D - represents more generally the hydrophobic portion of the compound in which D is substituted with 1 to 4 groups designated as A. Thus, A _{4 -} D - may represent a wide variety of possible structures. For example, A can be:

a straight or branched alkyl or alkenyl group containing 1 to 18 carbon atoms, such as methyl, or preferably

• · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ·

- Ί containing 4 to 10 carbon atoms such as nonyl,

- phenyl,

- phenylalkenyl wherein the alkenyl moiety contains 1 to 4 carbon atoms, an example of which is benzyl,

a C 8 -C 14 polycyclic group which may be fully saturated, fully unsaturated or partially saturated and partially unsaturated, such as indanyl, naphthalene, dihydronaphthalene, tetrahydronaphthalene and their analogues containing cyclohexyl, cyclohexenyl, cyclopentyl, or cyclopentenyl in place phenyl ring,

a hydroxyl or polyol, preferably having 2 to 6 carbon atoms and 2 to 6 hydroxy groups, or

an alkoxy group, preferably straight or branched, containing from 1 to 20 carbon atoms.

For example, D can be a phenoxy, oxy (i.e. -O-), phenyl, straight or branched chain alkyl or alkenyl group containing from 1 to 18 carbon atoms, an amino group or a carbonyl group [i.e.

-What)-].

Preferred A ₁ _ ₄ ~ D groups include hydroxybenzylfenyl, i.e. residue derived from Bisphenol A. Another preferred embodiment of the molecule there depicted is a phenyl ring which is substituted with one, two or three alkyl and / or alkenyl groups having straight or branched chain, containing 1 to 18 carbon atoms, or may be any of the other groups described herein. Preferably A comprises 4 to 12 atoms

Φ Φ * 4

4 «4

Φ Φ Φ Φ

- 8 carbon.

It will, of course, be appreciated that the present invention also encompasses mixtures comprising two or more different compounds of Formula I, as mixtures containing more than one structural isomer of a compound having a given number of carbon atoms, as well as mixtures containing compounds corresponding to two or more different versions of Formula A compound of formula 1 also contains a chain of ε 1 to 10 alkoxy groups, represented by formula (O-Alk), wherein each (O-Alk) denotes a straight or branched propyl or butyl moiety, or a substituted oxirane moiety. Preferably, in any given molecule corresponding to the general formula 1, each (O-Alk) unit will be the same, although segments containing short blocks poles (propoxy) and / or poles (butoxy) moieties or random sequences of propoxy and / or butoxy groups are contemplated of the invention.

In Formula 1, a chain composed of repeating units (O-Alk) may be terminated by a segment of 1 to 100 ethoxy groups which is optionally substituted, as in the case of nonylphenol ethoxylates known generally as nonoxynols, wherein the number of repeating ethoxy groups may be selected in in agreement with the number of carbon atoms in segment A to provide the desired degree of solubility in the specified medium and to provide the desired HLB [hydrophilic-lipophilic equilibrium, reference: WC Griffin, J. Soc. Cosmetic Chemists, Vol. X str., 311 (1949)], as is well known in the art of surfactants. Random mixtures as well as blocks of ethoxy and propoxy and / or butoxy groups are also contemplated within the scope of this invention.

As indicated in formula (1), the (ethoxy) rim of the poles are:

- 0 0 0 * 0 0 0

0

0 * 0

The closed alkylphenol alkoxylate can be terminated simply by a -H group to provide a suitable nonionic surfactant. Alternatively, the compound of Formula 1 may be anionically sealed, such as a sulfate, sulfonate, carboxylate, phosphate, or sulfosuccinate moiety and salts thereof to form useful series of anionic surfactants.

The anionic group can be charged in charge by a cation M, such as, but not limited to, a sodium, potassium, lithium, ammonium, or amine salt, or left in the form of its acid. The particular choice of nonionic surfactant and anionic surfactant groups is entirely within the capabilities of the creator. The nonionic surfactants of formula 1 and the anionic surfactants of this formula all have a wide variety of uses adapted to the use of these surfactants known for conventional alkylphenol ethoxylates, as well as the carboxylates, sulfates, sulfonates, phosphates, and sulfosuccinates of alkylphenol ethoxylates.

An important feature of the present invention is the Applicant's discovery of methods by which the alkoxylates of the alkylphenols of formula 1 can be synthesized, which indeed exhibit reduced or no estrogenicity of themselves and their degradation products.

As already mentioned, the methods of synthesis involve incorporating propoxy and / or butoxy groups into the poly (ethoxy) segment. Of course, it is recognized that there are several different synthesis paths through which the desired insertion can be achieved. For example, in one preferred embodiment, a precursor of the general formula is prepared

A-D- (O-Alk) y-OH, «» · · · · · · OH OH OH OH OH OH OH ««

Β Β · Β Β Β «« «« «· · · ·

- 10 where

A, D, (O-Alk) and y are as defined above and then ethoxylated to the desired degree, after which the alkoxylate can be further reacted to obtain the desired sulfate, carboxylate, sulfonate, phosphate or sulfosuccinate. In other preferred embodiments, the starting material of formula AD-OH is reacted with an already formed segment of formula H (OAlk) y (OC ₂ H ₄ ) ₂ OH, or sequentially with H (OAlk) yOH and then with H (OC _2). H ₄ ) ₂ OH, to form the final product.

In this aspect and in other aspects, which will be readily apparent to those skilled in the art, the result is a synthesis process that has been shown to be successful in producing surfactant compounds showing very reduced or no estrogenicity of themselves and their degradation products.

The synthesis of any individual desired compound of formula (1) is quite straightforward and uses conventional synthetic techniques that are adopted from known methods for forming alkoxylates. Obtaining precursors and determining appropriate reaction conditions can be readily determined by one of ordinary skill in the art. As generally indicated, the alkylphenol of the desired composition and positional substitution is alkoxylated in a manner that introduces propoxy and / or butoxy groups into the ethoxy chain to produce a product with the desired properties. The alkoxylate is then obtained or, if appropriate, further processed to obtain the sulfonate, phosphate, sulfate, sulfosuccinate, or carboxylate in accordance with known techniques. Usually, the use of a stoichiometric is desirable.

Β Β · ΒΒΒΒ ΒΒΒΒ · · · · · · · · · · · · · · · · · · · · · · * *

ΒΒΒΒ · Β Β ·

- an excess of propylene oxide and / or butylene oxide to ensure complete alkoxylation of the alkyl phenol. A general excess of up to about 5: 1 (mole alkylene oxide: mole alkylphenol) or higher will be found to be sufficient.

DETAILED DESCRIPTION OF THE INVENTION

The invention will now be described in the following examples, which are given for illustrative purposes and should not be construed as limiting the scope of the present invention.

Example 1 (p-Nonyphenol + 2 EO)

2.558 kg of nonylphenol and 10.8 g of a 50% aqueous sodium hydroxide solution were charged to the reactor, which was then purged and heated to 125 ° C. The mixture was dehydrated at this temperature for two hours, then 1.026 kg of ethylene oxide (EO) was added to the reactor and allowed to react at 125 ° C for one hour. The resulting mixture was neutralized and removed from the reactor. The results of a standard test procedure obtained in this field, as well as testing the stimulation of the expression of the vitamin I gene in trout hepatocytes [literary reference: Jobling et al., Detergent Components in Sewage Effectiveness Are Weakly Oestrogemc to Fish: An In-vitro Study Using Rainbow Throut (Oncorthynchus mykiss) Hepatocytes, - Detergent compounds in liquid effluents are poorly estrogenic to fish: In vitro study using rainbow trout hepatocytes (Oncorhynchus mykiss), Aqatic Toxicology, Vol. 27, pp. 361-372 (1993) and R. White et al. Enviromentally persistent Alkylphenolic Compounds Are Estrogenic

· • • • φ φ φ · φ φ φ φ φ φ φ φ φ φ

- 12 - Environmentally persistent alkylphenolic compounds are estrogenic ¹¹ , Endocrinology, Vol. 135, No. 1, pp. 175-182] showed that the substance is estrogenic.

Example 2 (p-Nonyphenol + 4 EO)

1.989 kg of nonylphenol and 10.8 g of a 50% aqueous sodium hydroxide solution were charged to the reactor, which was then purged and heated to 125 ° C. The resulting mixture was dehydrated at this temperature for two hours, then 1.595 kg of ethylene oxide (EO) was added to the reactor and allowed to react at 125 ° C for one hour. The resulting mixture was neutralized and removed from the reactor. The results of the above standard test procedure showed that this substance is estrogenic, although higher concentrations are likely to be required to achieve the same estrogenic effects as in Example 1.

Example 3 (p-Nonyphenol + 2 PO)

2.455 kg of nonylphenol and 10.8 g of 50% aqueous sodium hydroxide solution were charged to the reactor, which was then purged and heated to 125 ° C. The resulting mixture was dehydrated at this temperature for two hours, then 1.239 kg propylene oxide (PO) was added to the reactor, and the mixture was allowed to react at 125 ° C for one hour. The resulting mixture was neutralized and removed from the reactor. This product, nonylphenol propoxylate, was found to be non-estrogenic using the above standard test procedure.

- 13 • 0 0 00 00 • * «000 • 0 0 0 * 0 0 0 0 0 00 000000 0000 0 0 0 · 0 * 00 • ·· 0 · <· ♦

Example 4 (p-Nonyphenol + 2 PO + 4 EO)

2.455 kg of nonylphenol and 10.8 g of 50% aqueous sodium hydroxide solution were charged to the reactor, which was then purged and heated to 125 ° C. The resulting mixture was dehydrated at this temperature for two hours, then 812.5 g propylene oxide was added to the reactor and allowed to react at 125 ° C for one hour. After completion of the propylene oxide reaction, the reactor was degassed and 1.233 kg of ethylene oxide was added thereto, and the mixture was allowed to react for 1 hour. The resulting mixture was neutralized and removed from the reactor. This product, nonylphenol alkoxylate, was tested for estrogenicity using the above standard test procedure and found non-estrogenic. Degradation studies have also shown that this substance does not degrade to estrogenically active material.

Example 5 (p-octylphenol + 4 EO)

1.932 kg of nonylphenol and 10.8 g of a 50% aqueous sodium hydroxide solution were charged to the reactor, which was then purged and heated to 125 ° C. The resulting mixture was dehydrated at this temperature for two hours, then 1.652 kg of ethylene oxide was added to the reactor and allowed to react at 125 ° C for one hour. The resulting mixture was neutralized and removed from the reactor. The results of the above standard test procedure showed that the substance was estrogenic.

- 14 «000

Example 6 (p-octylphenol + 2 PO + 4 EO)

1.41 kg of octylphenol and 10.8 g of a 50% aqueous sodium hydroxide solution were charged to the reactor, which was then purged and heated to 125 ° C. The resulting mixture was dehydrated at this temperature for two hours, then 836 g propylene oxide was added to the reactor and the mixture was allowed to react at 125 ° C for one hour. After the propylene oxide reaction was complete, the reactor was degassed and 1.266 kg of ethylene oxide was added thereto, and the mixture was allowed to react for 1 hour. The resulting mixture was neutralized and removed from the reactor. The results of the above standard test procedure show that this substance is substantially less estrogenic than its ethoxylated counterpart.

Example 7 (o-Nonyphenol + 4 EO)

1.989 kg of o-nonylphenol and 10.8 g of a 50% aqueous sodium hydroxide solution were charged to the reactor, which was then purged and heated to 125 ° C. The resulting mixture was dehydrated at this temperature for two hours, then 1.5959 kg of ethylene oxide was added to the reactor and allowed to react at 125 ° C for one hour. The resulting mixture was neutralized and removed from the reactor. The results of the above standard test procedure show that the substance is estrogenic.

Example 8 v v · v · v · v v · v v · v · v · v · v · v · v · v

V V V V * 1 · · · · ·

- 15 (2-Methyl-4-nonylphenol + 4 EO)

2.043 kg of 2-methyl-4-nonylphenols and 10.8 g of a 50% aqueous sodium hydroxide solution were charged to the reactor, which was then purged and heated to 125 ° C. The resulting mixture was dehydrated at this temperature for two hours, then 1.5409 kg of ethylene oxide (EO) was added to the reactor and allowed to react at 125 ° C for one hour. The resulting mixture was neutralized and removed from the reactor. The results of the above standard test procedure show that the substance is estrogenic.

Examples 9 to 12 describe the synthesis of other compounds that exhibit reduced estrogenicity and reduced tendency to degrade to estrogenic products.

Example 9 (2-Methyl-4-nonylphenol + 2 PO + 4 EO)

1.592 kg of 2-methyl-4-nonylphenols and 10.8 g of a 50% aqueous solution of sodium hydroxide were charged to a reactor, which was then purged and heated to 125 ° C. The resulting mixture was dehydrated at this temperature for two hours. 790.9 g propylene oxide was added to the reactor and the mixture was allowed to react at 125 ° C for one hour. After the propylene oxide reaction was complete, the reactor was degassed and 1.201 kg ethylene oxide was added and allowed to react for one hour. The resulting mixture was neutralized and removed from the reactor.

Example 10 • 99 9 · 9 9 · 9 9 * 99

9 9 · 9 · 99 ··

9,999,999,999,999 9 «99 · 9 9

9 9 99 99 99 99

- 16 (p-Nonylphenol + 1 EO + 2 PO)

2.073 kg of p-nonylphenol and 10.8 g of 50¾ aqueous sodium hydroxide solution were charged to the reactor, which was then purged and heated to 125 ° C. The resulting mixture was dehydrated at this temperature for two hours, then 416 g of ethylene oxide was added to the reactor and the mixture was allowed to react at 125 ° C for one hour. After completion of the ethylene oxide reaction, the reactor was degassed and 1.201 kg propylene oxide was added thereto and allowed to react for 1 hour. The resulting mixture was neutralized and removed from the reactor.

Example 11 (p-Nonylphenol + 1 EO + 2 PO + 3 EO)

1.538 kg of p-nonylphenol and 10.8 g of 50¾ aqueous sodium hydroxide solution were charged to the reactor, which was then purged and heated to 125 ° C. The resulting mixture was dehydrated at this temperature for two hours, then 308 g of ethylene oxide was added to the reactor and the reaction mixture was allowed to react at 125 ° C for one hour. After the ethylene oxide reaction was carried out quantitatively, the reactor was degassed and 812 g of propylene oxide were added to the reactor. The resulting mixture was allowed to react for one hour. After the propylene oxide reaction was complete, the reactor was degassed and 925 g of ethylene oxide was added to the reactor and allowed to react for one hour. The resulting mixture was neutralized and removed from the reactor.

Example 12 «« ··

(p-Nonylphenol + 2 PO / 4 EO)

2.455 kg of p-nonylphenol and 10.8 g of a 50% aqueous sodium hydroxide solution were charged to the reactor, which was then purged and heated to 125 ° C. The resulting mixture was dehydrated at this temperature for two hours, then 812.5 g propylene oxide and 1.233 kg ethylene oxide as a mixed oxide were added to the reactor and allowed to react at 125 ° C for one hour, the resulting mixture was neutralized and removed from the reactor. reactor.

Examples 13 and 14 were made to allow a comparative estimate to be made.

Example 13 (p-Nonylphenol + 10 EO)

1.193 kg of p-nonylphenol and 10.8 g of a 50% aqueous sodium hydroxide solution were charged to the reactor, which was then purged and heated to 125 ° C. The resulting mixture was dehydrated at this temperature for two hours, then 2.391 kg was added to the reactor and allowed to react at 125 ° C for one hour. The resulting mixture was neutralized and removed from the reactor.

Example 14 (p-Nonylphenol + 2 PO + 10 EO)

1.014 kg of p-nonylphenol and 10.8 g of 50% aqueous sodium hydroxide solution were charged to a reactor which was then

- 18 fl fl fl fl fl flush and heat to 125 ° fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl Fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl Deň: 32 ° C. The resulting mixture was dehydrated at this temperature for two hours, then 536 g propylene oxide was added to the reactor and the reaction mixture was allowed to react at 125 ° C for one hour. After the propylene oxide reaction was carried out quantitatively, the reactor was degassed, and 2.034 kg of ethylene oxide was added to the reactor and allowed to react for one hour. The resulting mixture was neutralized and removed from the reactor.

A degradation study comparing the compounds of Examples 13 and 14 shows that the procedure described for the preparation of the above compounds also reduces the estrogenicity of their degradation products.

An evaluation of the functional and physical properties of nonoxynol-4 with its non-estrogenic counterpart shows that modifications prepared to obtain non-estrogenic analogs do not adversely affect other functional properties, such as the tidal function of these materials.

• ·· 9

- 19 • 99 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 99 99 99

Claims (11)

PATENT CLAIMS i. A compound of the formula Ia _{1 - 4 -} d - (α ₂ h ₄ ) _x - (o-Al) _y - (α ₂ H ₄ ) ₂ -OR (1), where AND denotes an alkyl or alkenyl group formed by a straight or branched chain of 1 to 18 carbon atoms, a phenyl group, a phenylalkenyl group wherein the alkenyl moiety contains 1 to 4 carbon atoms, a polycyclic group containing 8 to 14 carbon atoms, a polyol, an alkoxy group containing 1 to 20 carbon atoms or a hydrogen atom; D denotes a straight or branched chain phenoxy, oxy, phenyl, alkyl or alkenyl group containing from 1 to 18 carbon atoms, amino or carbonyl, X is 0 to 10, y is 1 to 10, of is 0 to 100, each (O-Alk) ) denotes a propoxy group or a butoxy group formed straight or branched chain or substituted oxirane a > · · To · - 20 • R is a hydrogen atom, a sulfate, sulfonate, monophosphate, diphosphate, carboxylate, monosulfosuccinate or disulfosuccinate residue, or a salt thereof with hydrogen, ammonia or an alkali metal cation, exhibiting reduced or no estrogenicity per se and its degradation products related to its analogs where y is 0. A compound according to claim 1, wherein A is a straight or branched chain alkyl or alkenyl group containing 1 to 18 carbon atoms, and D is phenyl. The compound of claim 1, wherein x is 0. A compound according to claim 3, wherein A is a straight or branched chain alkyl or alkenyl group containing 1 to 18 carbon atoms, and D is phenyl. A compound according to claim 4, wherein A is nonyl. 6. A method of improved synthesis of a compound comprising a hydrophobic moiety and a hydrophilic moiety, wherein the hydrophobic moiety comprises a polyethoxy chain, wherein the improvement comprises imparting to the compound both reduced estrogenicity and reduced propensity to biodegradate to estrogenic by-products by including between such hydrophilic and hydrophilic moieties. a segment of formula (O-Alk) y wherein y is 1 to 10 and each of the Alk units is propyl or butyl. Method according to claim 6, characterized in that the flfflfl flfflfl flfflfl flfflfl flfflfl flfflfl flfflfl flfflfl flfflfl flfflfl flfflfl flfflfl · ·· ·· - 21, wherein the compound has the general formula 1 AD- (OC ₂ H ₄ ) _χ - (O-Alk) - (OC ₂ H ₄ ) _from -OR (1), where A denotes a straight or branched chain alkyl or alkenyl group containing 1 to 18 carbon atoms, a phenyl group, a phenylalkenyl group wherein the alkenyl moiety contains 1 to 4 carbon atoms, a polycyclic group containing 8 to 14 carbon atoms, a polyol, an alkoxy group containing 1 to 18 20 carbon atoms or hydrogen atoms, D is a straight or branched chain phenoxy, oxy, phenyl, alkyl or alkenyl group having 1 to 18 carbon atoms, amino or carbonyl, x is 0 to 10, y is 1 to 10, z is 0 to 100, each ( O-Alk) denotes a straight or branched chain propoxy or butoxy group or a substituted oxirane and is a hydrogen atom, a sulphate, a sulphonate, a monophosphate, a diphosphate, a carboxylate, a monosulphosuccinate or a disulphosuccinate. 4 4 4 44 · 4 4 4 4 4 · · · · · · · · 4 4 4 44444 4444 4 4 4 4 4 4 4444 44 - 22 or a salt thereof with hydrogen, ammonia or an alkali metal cation. 8. The method according to claim 7, characterized in that the alkyl phenol compound of the formula c ₆ H ₄ -OH, wherein A denotes a straight or branched chain alkyl group having 1 to 18 carbon atoms, reacted with at least one compound selected from the group consisting of propylene oxide, butylene oxide, and substituted oxiranes to form an intermediate of formula AC ₆ H ₄ - (O-Alk) y OH where y is 1 to 10 and each of the y units Alk is propyl or butyl, and this intermediate is reacted with ethylene oxide to give a compound of formula AC ₆ H ₄ - (O-Alk) _y - (OC ₂ H ₄ ) _Z OH, where - 23 φ φ φ φ φ φ φ φ φ φ φ φ φ φ · · · V V V V V V V V V V V φ φ φ φ φ The process of claim 8, wherein A is nonyl. 10. The method according to claim 7, characterized in that the alkyl phenol compound of the formula c ₆ H ₄ -OH, wherein A is a straight or branched chain alkyl group containing from 1 to 18 carbon atoms and reacted with a compound of formula H- (O-Alk) _y - (OC ₂ H ₄ ) _Z OH, where y is 1 to 10 and z is 1 to 100, to form a compound of formula AC ₆ H ₄ - (O-Alk) _y - (OC ₂ H ₄ ) _Z OH. The process of claim 10, wherein A is nonyl.