WO1997006125A1

WO1997006125A1 - Reducing estrogenicity of alkoxylated compounds and products thereof

Info

Publication number: WO1997006125A1
Application number: PCT/US1996/012673
Authority: WO
Inventors: M. Wayne Meadows; Christie Berger; Paul Berger; Rodney Cravey; Charles Davis; Kim Friloux; Charles Green; Ying Dau-Lu; Giao Nguyen
Original assignee: Witco Corporation
Priority date: 1995-08-04
Filing date: 1996-08-02
Publication date: 1997-02-20
Also published as: CN1197449A; AR003190A1; CZ28898A3; KR19990036176A; EP0848694A4; CA2228133A1; AU6950996A; ZA966604B; TW340110B; MX9800979A; EP0848694A1; NO980462D0; BR9610073A; NO980462L; JPH11510189A

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

REDUCING ESTROGENICITY OF ALKOXYLATED COMPOUNDS AND PRODUCTS THEREOF

FIELD OF THE INVENTION

The present invention relates to alkoxylates, including but not limited to alkoxylates of phenolic compounds, such as, branched and linear alkylphenols, napthtol and napthtol derivatives, bisphenols, branched and linear dialkyl phenols, benzene diols, benzene triols, phenolic resins, stilbene and its derivatives, and phenylphenol. The present invention further relates to alkoxylates of alcohols, polyols, fatty acids, amines, carboxylic acids, and any other potentially alkoxylated material and relates more particularly to certain derivatives of such alkoxylates useful as, for instance, surfactants in many varied industrial applications, and as intermediates from which can be prepared other related compounds having a variety of uses in the industrial and commercial arena.

Alkylphenol alkoxylates, and particularly alkylphenol ethoxylates, have found widespread use in a number of applications. These applications rely generally on the surfactant properties of such compounds. The surfactant properties can, in turn, be tailored by appropriate selection of the alkyl substituent on the phenol group, and of the number of repeating ethoxy units

forming the poly(ethoxy) chain pendant from the oxygen atom which is bonded to the phenyl group. For instance, nonyl phenol ethoxylates are well known surfactants having a wide variety of uses; such compounds are known generically as "nonoxynol" compounds, and contain anywhere from 1 to 100 (or optionally more) repeating ethoxy units. The alkylphenol ethoxylates find widespread use in cosmetics, toiletries, and in such diverse industrial applications as oil slick dispersants, deinking surfactants, metal treating, textile treatment, emulsion formation, emulsion polymerization, detergents and related cleaners, and the like.

Recently, concern has developed in the scientific community that a number of commonly used compounds including nonylphenol, and phenolic derivatives, like the nonylphenol ethoxylates, may exhibit estrogenicity (References: Jobling, S. et al., "Detergent Components in Sewage Effluent Are Weakly Oestrogenic to Fish: An In-vitro Study Using Rainbow Trout (Oncorhynchus mykiss) Hepatocytes," Aquatic Toxicology, Vol. 27 (1993), pp. 361- 372; Soto, A.M. et al., "p-Nonyl-Phenol: An Estrogenic Xenobiotic Released from "Modified Polystyrene", Env. Health Perspectives, Vol. 92 (1991), pp.167-173.) The possibility that many phenolic compounds, their derivatives, and the derivatives¹ biodegradation products may be associated with such an undesirable side effect therefore presents a concern to all who manufacture and use

these materials. At present, ethoxylates, and their derivatives, the various nonionic, anionic, cationic, and amphoteric surfactants, must out of prudence and responsible conduct be treated as possible sources of these materials in the environment, many of which have been demonstrated to be estrogenic.

Accordingly, it is desirable to identify materials from which one can synthesize end-products having the variety of useful properties presently exhibited by the presently available alkoxylated materials, yet which do not pose a risk of being estrogenic in use, and which do not upon biodegradation generate estrogenic materials.

In view of the widespread use and wide variety of uses of alkyl phenol ethoxylates, coupled with the possibility that such ethoxylates may degrade, particularly biodegrade, into the corresponding alkyl phenol compounds or derivatives thereof which may prove to be estrogenic, the search for acceptable alternatives which would prove not to be precursors of possibly estrogenic materials has understandably led far afield of alkyl phenol alkoxylates.

BRIEF SUMMARY OF THE INVENTION

Notwithstanding the quite reasonable expectation that alkoxylated analogs of alkyl phenol alkoxylates would be expected to exhibit degradability to possibly estrogenic alkyl phenol and derivatives thereof, it has been

determined that compounds having a hydrophobic moiety and a hydrophilic moiety in which the hydrophilic moiety is a polyethoxy chain, such as alkyl phenol alkoxylates, but characterized in that 1) a short block of propoxy and/or butoxy unit(s) extends from the hydrophobic moiety and precedes the ethoxy chain, or 2) a short block of propoxy and/or butoxy unit(s) have been inserted into the ethoxy chain or 3) propoxy and/or butoxy unit(s) have been randomly inserted into the ethoxy chain, or 4) propoxy and/or butoxy unit(s) have been added to the end of the ethoxy chain, or 5) propoxy and/or butoxy unit(s) are substituted for the ethoxy chain, exhibit the highly desirable properties of reduced or no estrogenicity in themselves and their products of degradation.

Thus, the present invention comprises in one aspect compounds of the formula

A..₄-D-(OC₂H _χ-(0-Alk)_y-(OC₂H₄)_z-OR (1)

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 8 to 14 carbon atoms, a polyol, an alkoxy group, or hydrogen; D denotes phenoxy, oxy, phenyl, a linear or branched alkyl or alkenyl group, an amino group., or a carboxy 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, mono and/or diphosphate, carboxylate, mono and/or disulfosuccinate, or a salt thereof.

Yet another aspect of the present invention is in compounds of the formula A-D-(0-Alk)_y-OH, wherein A,D, (O- Alk) and y are as defined herein, and in their use as starting materials for synthesis of compounds of formula

(1).

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

DETAILED DESCRIPTION OF THE INVENTION

The compounds in accordance with the foregoing formula (1) A-D-(OC₂H₄)_χ-(0-Alk)_y-(OC₂H.)₂-OR are useful in many commercial applications including surfactants. Thus, the present invention extends to such compounds per se as well as to any of the large number of end-use formulations which can contain one or more compounds of the formula. Without intending to limit the scope of the invention, such formulations include oil field emuisifiers and

demulsifiers, oil slick dispersants, deinking surfactants, metal treating surfactants, textile treating surfactants, paper debonding compositions, emulsion polymerization surfactants, surfactants and emuisifiers for cosmetics, toiletries, and other personal care products, hard surface cleaning formulations, low-foaming detergent formulations, emuisifiers and dispersing agents, wetting agents, agricultural emuisifiers, paint surfactants, and the like. Returning to the aforementioned formula (1), the moiety A-^-D- represents more generally the hydrophobic portion of the compound in which D is substituted with 1 to 4 groups denoted as A. Thus, A₁.₄-D- can represent a wide variety of possible structures. For instance, A can be:

- straight-chained or branched alkyl or alkenyl containing 1 to 18 carbon atoms, such as methyl, or preferably 4 to 10 carbon atoms, such as nonyl;

- phenyl;

- phenyl-alkenyl, wherein the alkenyl portion contains 1 to 4 carbon atoms, an example of which is benzyl;

-a polycyclic group containing 8 to 14 carbon atoms, which can be wholly saturated, fully unsaturated, or partially saturated and partially unsaturated, such as indanyl, naphthalene, dihydronaphthalene, tetrahydronaphthalene, and analogs thereof containing cyclohexyl, cyclohexenyl, cyclopentyl or cyclopentenyl in place of the phenyl ring;

- hydroxyl or polyol, preferably containing 2 to 6 carbon atoms and 2 to 6 hydroxyl groups; or alkoxy, preferably straight-chained or branched and containing 1 to 20 carbon atoms.

For instance, D can be phenoxy, oxy (that is, -0-), phenyl, a straight-chained or branched alkyl or alkenyl group containing 1 to 18 carbon atoms, an amino group, or carbonyl (that is, -C(O)-).

Preferred A_1-4-D- groups include hydroxy benzylphenyl, i.e. a residue from Bisphenol A. Another preferred embodiment of the molecule there depicted is a phenyl ring which is substituted with one, two or three straight-chain or branched-chain alkyl and/or alkenyl groups containing 1 to 18 carbon atoms, or can be any of the other groups described herein. Preferably,- A contains 4 to 12 carbon atoms.

It will of course be recognized that the present invention also extends to compositions containing two or more different compounds of formula (1)/ such as compositions containing more than one structural isomer of a compound having a given number of carbon atoms, as well as compositions containing compounds corresponding to two or more different versions of formula (1). The compound of formula (1) also contains a chain of 1 to 10 alkoxy units exhibiting the formula (O-Alk), wherein each (O-Alk) denotes a straight-chained or branched propyl, butyl or substituted oxirane moiety. Preferably, within any given

molecule corresponding to formula (1), each (O-Alk) unit will be the same, although segments containing short blocks of poly (propoxy) and/or poly (butoxy) portions or random sequences of propoxy and/or butoxy groups are contemplated in the scope of this invention.

In formula (1), the chain composed of repeating (O-Alk) units can be terminated with a segment of 1-100 ethoxy units which is itself optionally substituted. As is the case with the nonyl phenol ethoxylates known generically as "nonoxynols", the number of repeating ethoxy units can be chosen in conjunction with the number of carbon atoms in the segment A so as to afford the desired degree of solubility in the intended medium, and to afford the desired HLB (hydrophilic-lipophilic balance (reference: Griffin, W.C, J. Soc. Cosmetic Chemists, vol. 1 (1949), p. 311), as is well known in the surfactant art. Random mixtures as well as blocks of ethoxy and propoxy and/or butoxy units are also contemplated in the scope of this invention.

As indicated in formula (1), the poly(ethoxy) capped alkyl phenol alkoxylate can be capped simply with a -H group, thereby affording a useful nonionic surfactant. Alternatively, the compound of formula (1) can be capped with an anion such as a sulfate, sulfonate, carboxylate, phosphate group or sulfosuccinate, and salts thereof, thereby forming a useful series of anionic surfactants.

The anionic group can be balanced in charge by a cation M such as sodium, potassium, lithium, ammonium, or amine salt among others or left in its acid form. The particular choice of nonionic surfactant and anionic surfactant groups is well within the ability of the formulator. The nonionic surfactants according to formula (1), and the anionic surfactants according to that formula, all have a wide variety of uses conforming to those uses known for conventional alkyl phenol ethoxylates, as well as alkyl phenol ethoxylate carboxylates, sulfates, sulfonates, phosphates, and sulfosuccinates.

A significant aspect of the present invention is the applicants' discovery of methods by which alkyl phenol alkoxylates of formula (1) can be synthesized which in fact exhibit reduced or no estrogenicity in themselves and their products of degradation.

As stated, the synthetic method resides in incorporating propoxy and/or butoxy units into the poly(ethoxy) segment. It will be recognized of course that there are several different synthetic pathways by which a desired insertion can be accomplished. For instance, in one preferred embodiment, a precursor of the formula

A-D-(0-Alk)_y-0H

where A, D, (O-Alk), and y are as previously defined.

is prepared, and thereafter ethoxylated to the desired degree, whereupon the alkoxylate can be further reacted to give the desired sulfate, carboxylate, sulfonate, phosphate or sulfosuccinate. In other preferred embodiments, the starting material A-D-OH is reacted with an already formed segment H(OAlk)_y(OC₂H₄)_zOH, or in sequence with H(OAlk)_yOH and then with H(OC₂H₄)₂OH, to form the final product.

In this aspect, and in others that will be readily apparent to those who are experienced in this art, the result is a synthetic process which has been shown to successfully create surfactant compounds exhibiting greatly reduced or no estrogenicity in themselves and their degradation products.

Synthesis of any particular desired compound in accordance with formula (1) is quite straightforward and employs quite conventional synthetic techniques adapted from the known methods for forming alkoxylates. The sourcing of the precursor materials, and the identification of suitable reaction conditions, can readily be determined by those of ordinary skill in this field. As indicated, in general, an alkyl phenol of the desired composition and positional substitution is alkoxylated in a manner which incorporates propoxy and/or butoxy units into the ethoxy chain producing a product with the desired properties. Thereafter, the alkoxylate is recovered or, if desired, further processed to produce the sulfonate, phosphate, sulfate, sulfosuccinate, or carboxylate in accordance with

known techniques. It is usually desirable to employ a stoichiometric excess of propylene oxide and/or butylene oxide in order to insure complete alkoxylation of the alkyl phenol. Generally, excesses of up to about 5:1 (moles of alkylene oxide:moles of alkyl phenol) or higher will be found sufficient.

The invention will now be described in the following examples which are provided for purposes of illustration and should not be interpreted as intending to limit the scope of the present invention.

EXAMPLE 1

(p-nonylphenol + 2 EO) 2.558 kg of nonyl phenol and 10.8g of a 50% aqueous solution of sodium hydroxide were charged to a reactor, which was then purged, and heated to 125°C. This mixture was dehydrated at this temperature for two hours, following which 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. Results from a standard test procedure recognized in this field, as well as testing for stimulation of vitellogenin gene expression in trout hepatocytes (reference: Jobling et al., "Detergent Components in Sewage Effluent ..." (see above); and White, R. et al., "Environmentally Persistent Alkylphenolic Compounds Are Estrogenic", Endocrinology, Vol. 135, No. 1, pp. 175-182) demonstrated that this material is estrogenic.

EXAMPLE 2

(para-nonylphenol + 4 EO)

1.989 kg of p-nonyl phenol and 10.8g of a 50% aqueous solution of sodium hydroxide were charged to a reactor, which was then purged, and heated to 125°C. This mixture was dehydrated at this temperature for two hours, following which 1.595 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. Results from the aforementioned standard test indicated that this material is estrogenic, although higher concentrations are probably needed to elicit the same estrogenic effects as the materidx in Example 1.

EXAMPLE 3

(p-nonylphenol + 2 PO) 2.345 kg of nonyl phenol and 10.8g of a 50% aqueous solution of sodium hydroxide were charged to a reactor, which was then purged, and heated to 125°C. This mixture was dehydrated at this temperature for two hours, following which 1.239 kg of propylene oxide (PO) 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. This product, a nonyl phenol propoxylate, was shown to be non-estrogenic using the aforementioned standard test procedure.

EXAMPLE 4 (p-nonylphenol + 2 PO + 4 EO)

2.345 kg of nonyl phenol and 10.8g of a 50% aqueous solution of sodium hydroxide were charged to a reactor, which was then purged, and heated to 125°C. This mixture was dehydrated at this temperature for two hours, following which 812.5 g of propylene oxide was added to the reactor and allowed to react at 125°C for one hour. After reaction of propylene oxide was complete, the reactor was vented and 1.233 kg of ethylene oxide was added to the reactor and reacted for one hour. The resulting mixture was neutralized and removed from the reactor. This product, a nonyl phenol alkoxylate, was tested for estrogenicity employing the aforementioned test procedure, and was found not to be estrogenic. It was also shown, via degradation studies, that upon degradation this material did not degrade into an estrogenically active material.

EXAMPLE 5 (p-octylphenol + 4 EO) 1.932 kg of octyi phenol and 10.8g of a 50% aqueous solution of sodium hydroxide were charged to a reactor, which was then purged, and heated to 125°C. This mixture was dehydrated at this temperature for two hours, following which 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. Results from the aforementioned standard test procedure indicated that this material is estrogenic.

EXAMPLE 6

(p-octylphenol + 2 PO + 4 EO)

1.481 kg of octyi phenol and 10.8g of a 50% aqueous solution of sodium hydroxide were charged to a reactor, which was then purged, and heated to 125°C. This mixture was dehydrated at this temperature for two hours, following which 836 g of propylene oxide was added to the reactor and allowed to react at 125°C for one hour. After reaction of propylene oxide was complete, the reactor was vented and 1.266 kg of ethylene oxide was added to the reactor and reacted in for one hour. The resulting mixture was neutralized and removed from the reactor. Results from the aforementioned standard test procedure indicated that this material is substantially less estrogenic than its ethoxylated counterpart.

EXAMPLE 7 (ortho-nonylphenol + 4 EO) 1.989 kg of o-nonyl phenol and 10.8g of a 50% aqueous solution of sodium hydroxide were charged to a reactor, which was then purged, and heated to 125° C. This mixture was dehydrated at this temperature for two hours, following which 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. Results from the aforementioned standard test procedure indicated that this material is estrogenic.

EXAMPLE 8

(2-methyl, 4-nonylphenol + 4 EO) 2.043 kg of 2-methyl, 4-nonyl phenol and 10.8g of a 50% aqueous solution of sodium hydroxide were charged to a reactor, which was then purged, and heated to 125°C. This mixture was dehydrated at this temperature for two hours, following which 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. Results from the aforementioned standard test procedure indicated that this material is estrogenic.

Examples 9-12 describe synthesis of additional compounds to 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-nonyl phenol and 10.8g of a 50% aqueous solution of sodium hydroxide were charged to a reactor, which was then purged, and heated to 125°C. This mixture was dehydrated at this temperature for two hours, following which 790.9 g of propylene oxide was added to the reactor and allowed to react at 125°C for one hour. After reaction of propylene oxide was complete, the reactor was vented and 1.201 kg of ethylene oxide was added to the reactor and reacted in for one hour. The resulting mixture was neutralized and removed from the reactor.

EXAMPLE 10 (p-nonylphenol + 1 EO + 2 PO)

2.073 kg of p-nonyl phenol and 10.8g of a 50% aqueous solution of sodium hydroxide were charged to a reactor, which was then purged, and heated to 125°C. This mixture was dehydrated at this temperature for two hours, following which 416 g of ethylene oxide was added to the reactor and allowed to react at 125°C for one hour. After reaction of ethylene oxide was complete, the reactor was vented and 1.201 kg of propylene oxide was added to the reactor and reacted in for one hour. The resulting mixture was neutralized and removed from the reactor.

EXAMPLE 11

(p-nonylphenol + 1 EO + 2 PO + 3EO) 1.538 kg of p-nonyl phenol and 10.8g of a 50% aqueous solution of sodium hydroxide were charged to a reactor, which was then purged, and heated to 125°C. This mixture was dehydrated at this temperature for two hours, following which 308 g of ethylene oxide was added to the reactor and allowed to react at 125°C for one hour. After reaction of ethylene oxide was complete, the reactor was vented and 812 g of propylene oxide was added to the reactor and reacted in for one hour. After reaction of propylene oxide was complete, the reactor was vented and 925 g of ethylene oxide was added to the reactor and reacted in for one hour. The resulting mixture was neutralized and removed from the reactor.

EXAMPLE 12 (p-nonylphenol + 2 PO/4 EO)

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

Examples 13 and 14 were carried out to enable a comparative assessment of estrogenicity to be made.

EXAMPLE 13 (para-nonylphenol + 10 EO)

1.193 kg of p-nonyl phenol and 10.8g of a 50% aqueous solution of sodium hydroxide were charged to a reactor, which was then purged, and heated to 125°C. This mixture was dehydrated at this temperature for two hours, following which 2.391 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.

EXAMPLE 14 (p-nonylphenol + 2 PO + 10 EO)

1.014 kg of nonyl phenol and 10.8g of a 50% aqueous solution of sodium hydroxide were charged to a reactor, which was then purged, and heated to 125°C. This mixture was dehydrated at this temperature for two hours, following which 536 g of propylene oxide was added to the

reactor and allowed to react at 125°C for one hour. After reaction of propylene oxide was complete, the reactor was vented and 2.034 kg of ethylene oxide was added to the reactor and reacted in for one hour. The resulting mixture was neutralized and removed from the reactor. Degradation studies comparing the materials prepared in Examples 13 and 14 indicated that the process described for preparing the aforementioned materials does also reduce the estrogenicity of their degradation products.

Functional and physical property evaluations of nonoxynol-4 with its non-estrogenic counterpart, indicate that the modifications made to produce the non-estrogenic analogs do not adversely effect the other functional properties, such as surfactancy, of these materials.

Claims

WHAT IS CLAIMED IS:

1. A compound of the formula (1)

A₁.₄-D-(OC₂H₄)_χ-(0-Alk)_y-(OC₂H₄)₂-OR (1)

exhibiting reduced or no estrogenicity in itself and its products of degradation relative to its analog wherein y is zero; 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 8 to 14 carbon atoms, a polyol, an alkoxy group containing 1 to 20 carbon atoms, or hydrogen; D denotes phenoxy, oxy, phenyl, a linear or branched alkyl or alkenyl group containing 1 to 18 carbon atoms, 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 with hydrogen, ammonium or an alkali metal cation.

2. A compound according to claim 1 wherein A is a straight-chained or branched alkyl or alkenyl group containing 1 to 18 carbon atoms, and D is phenyl.

3. A compound according to claim 1 wherein X is zero,

4. A compound according to claim 3 wherein A is a straight-chained or branched alkyl or alkenyl group containing 1 to 18 carbon atoms, and D is phenyl.

5. A compound according to claim 4 wherein A is nonyl

6. An improved method of synthesis of a compound having a hydrophobic moiety and a hydrophilic moiety, wherein the hydrophilic moiety comprises a polyethoxy chain, the improvement comprising imparting to said compound both reduced estrogenicity and a reduced tendency to biodegrade to an estrogenic byproduct by including between said hydrophobic and hydrophilic moieties a segment of the formula (0-Alk)_y wherein y is 1 to 10 and each of the y Alk units is propyl or butyl.

7. The method of claim 6 wherein said compound has the formula (1)

A-D-(OC₂H₄)_χ-(O-Alk)_y-(0-C₂H₄)_Z~0R (1)

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 8 to 14 carbon atoms, a polyol, an alkoxy group containing 1 to 20 carbon atoms, or hydrogen; D denotes phenoxy, oxy, phenyl, a linear or branched alkyl or alkenyl group containing 1 to 18 carbon atoms, 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 with hydrogen, ammonium or an alkali metal cation.

8. The method of claim 7 wherein an alkyl phenol compound of the formula A-C₆H₄-0H wherein A is a straight- chained or branched alkyl group containing 1 to 18 carbon atoms is reacted with one or more compounds selected from the group consisting of propylene oxide, butylene oxide, and substituted oxiranes to form an intermediate of the formula A-C₆H₄-(O-Alk)_y0H wherein y is 1 to 10 and each of the y Alk units is propyl or butyl, and wherein said intermediate is reacted with ethylene oxide to form a product of the formula A-C₆H₄-(O-Alk)_y-(0C₂H₄)_z OH wherein Z is 1 to 100.

9. The method of claim 8 wherein A is nonyl.

10. The method of claim 7 wherein an alkyl phenol compound of the formula A-C₆H₄-OH wherein A is a straight- chained or branched alkyl group containing 1 to 18 carbon atoms is reacted with a compound of the formula H-(O-Alk) - (OC₂H₄)_zOH wherein y is 1 to 10 and z is 1 to 100, to form a compound of the formula A-C₆H₄-(0-Alk)_y-(0-C₂H₄)_zOH.

11. The method of claim 10 wherein A is nonyl.