CA1169875A - Chelating agents for non-aqueous systems - Google Patents

Abstract

ABSTRACT

Alkyl-substituted hydroxy benzyl amino acid oligomers are effective metal chelating agents in a broad range of non-aqueous systems. The products claimed display surprisingly high solubil-ities in a broad range of substituted and unsubstituted aliphatic and aromatic solvents.

Description

BACKGROUND OF THB INVENTION
, This invention is in the field of metal chelating agents.

Metal chelating agents are well known to be useful for sup-plying trace elements to plants suffering from metal de~i-ciencies, for inclusion in metal plating baths, for removing "rust" stains from various types of surfaces, for removing impurities from liquid systems, and for analytical chemical titrations. However, many of the known chelating agents are useful only in aqueous systems. 5ee, e.g., Kroll U.S. Patent No. 2,967,196; Rubin U.S. Patent No. 3,11Q,679. It is he purpose of this invention to provide a new class of metal chelating agents which is soluble in a wide range of non-aqueous systems. Such chelating agents are useful for the extraction or deactivation of metals in non-aqueous systems, for the introduction of metals into non-aqueous systems, for pro-viding oil-borne micronutrients to plants, and for many other applications.
Sl~MMARY O~ THE I~7ENTION
It is an object of this invention to provide a new class of metal chelating agents which are soluble in a wide range of non-aqueous systems.
The compounds claimed coxrespond to the general formula t D 69875 OH OH OH

~CH - - CH2 - R COOM -wherein R is an alkyl sr~up having from 1 to 15 c~rb~n htams; R' is ~
or the residual group of an ~-amino acid of natural ~ccurrence; M is sele~ted from the group H+, an alkali meta- ion, NH4+, or an aminium ion; and n is an integer from 1 to 6.
The compoun~s o~ the invention are prepared by a two-step reaction between formaldehyde, an amino ~cid of the ~ormula NH2CHR'COOM, and a phen~l of the formula ~H

Various other objects and advantages cf this invention will become apparent from the following detailed description thereof.

DETAILED DESCRIPTION OF THE INVENTION
The invention is directed to comp~unds useful as metal chelating agents in a wide range of non-aqueous systems. The compounds are of the ~eneral formula:
OH I OH OH

~HR' [ ~ C~IR
~OOM ~ COOM n wherein R is an alkyl group having fro~ 1 to 15 carbon atoms;
R' is H or the residual ~r~up of an ~-amino acid of natural occurrence;
M is selected ~rom the group con~istin~ o H~, an alkali metal ion, NH4+, or sn ~minium ion; and n is an integer ~rom 1 to 6.
The claimed compounds are prepared in a two~tep reaction.

I 1 69~75 In the first step, formaldehyde is reacted with an amino acid of the general formula NH2CHR'COOM in an aqueous solution whose pH is maintained at 7.5-8.0 with sodium or potassium hydroxide. A co-solvent such as methanol is then added. In the second step, while still maintaining the pH at 7.5-8.0, a methanol solution of a phenol of the ~eneral formula is slowly added to the reaction mixture, which is then heated to a temperature of approximately 30-60CC. On cooling and standing, the desired product can be separated out as an oily layer while the water/methanol layer is decanted. The product is then dried and ground to a powder. Vacuum drying has been used for laboratory scale preparations, but other types of drying could obviously be employed for commercial purposes.
It has been found that when lower alkyl substituents are used (R = 1-3 carbons), compounds are obtained with a commercially significant solubility in methanol. However, as one moves to higher alkyl substituents, the compounds of the present invention are found to display high solubilities in a much wider array of non-aqueous systems while the aqueous solubility of such compounds becomes negligible.
The fomaldehyde may be supplied in any of its commercially available forms, such as formalin, paraformaldehyde, formcel~, and trioxane.
In a preferred embodiment of this invention, R is a nonyl group, R' is H, M is Na+, and n = 1.
The following Examples illustrate, without limitation, various additional embodiments of the invention.

R = nonyl, n = 6, M = Na In a ~00 ml beaker, a mixture of glycine, 52.5 g/0.7 mole; water, 64 mls; and 50% NaOH, 28 g/0.35 mole was prepared and adjusted to pH = 8 with hydrochloric acid. To th-is was added 134 g ~1.47 mole) of 30% formaldehyde solution over a 30 minute period, causing the tempexature to rise to 36C.
During the addition, the pH was held at 7.5-8.0 by concurrent addition of 28 g of 50% NaOH. This first solution was then added to 300 ml of methano~ in a 2 liter three neck flask; and I .1 ~9~5 the pH, which fell t~ 6.2, was readjuste~ to 7.5. T~ this was then added a solution of p-nonylphenol, 176 g/0.8 mole, in 15~ ml of methanol over a 45 minute period. During the addition, the mixture was heated to 6~C and then to reflux. The mixture remained turbid throughout the addition in spite of additional solvent. Refluxing was continued for 5 hours after the addition ended. Vpon cooling, two liquid layers were obtained. The upper, solvent, layer was decanted off, and the lower, product, layer was dried in a vacuum desiccator and ground to a fine powder. The product weighed 233 g or 89.3% of theory. A toluene solution of this product was shakPn with aqueous solutions of iron, copper, cobalt, and nickel salts. In each case metal chelation was indicated by strong coloration of the toluene layer.

R = nonyl, n = 6, M = Na A solution of 52.5 g glycine, 64 ml water, and 28.2 g of 50~ NaOH
was prepared and adjusted to pH = 8 with dilute HCl. To this was added 134 g of 30% formaldehyde over a 40 minute period, then 28.3 g of 50~ NaOH was added dropwise. This solution was mixed with 600 ml of methanol, and the pH was readjusted,to 7~5. Over a 2 hour period, a solution of 177.8 g of nonyl phenol in 200 ml of methanol was added.
Thirty minutes into the addition, heating was begun, raising the temperature to 56C by the end of the addition. The mixture was refluxed at 72-73 for about 3 1~2 hours after the addition, then allowed to cool and settle. The upper layer was decanted, and the lower layer was dried. Obtained 197.5 g of dried powder for a 75.7% yield.

EXAMP~E 3 R = nonyl, n = 1, M = K
The general procedure of Example 2 was repeated except that potassium hydxoxide was used in place of sodium hydroxide and the charges used were as follows:
p-nonyl phenol 65.4 gms. (O.3 mole) glycine 15 (0.2 mole) KOH 11.2 (0.45 "

The product recovered was 84.6 ~ms. of a yellow s,olid.

- 1~6g875 R = nonyl, n = 4, M = Na The general procedure of Example 2 was repeated except that the reactant charges were changed to give a 6:5 phenol to glycine ratio. The dried product weighed 136.6 g, or 70.8%
of theory.

R = nonyl, n = 2, M = Na The general procedure of Example 2 was repeated except that the reactant charges were chànged to give a 4:3 phenol to glycine ratio. The dried product weighed 30.4 g, or 24.4% theory.

R - t-butylj n = 6, M = Na The general procedure of Example 2 was repeated except that .8 mole of p=tert-butylphenol was substituted for the nonyl-phenol. The dried product weighed 145.5 g, or 71% sf theory.

R = dodecyl, n = 6, M = Na The general procedure of Example 2 was repeated using p-dodecyl phenol. The dried product weighed 255.8 g, or 86.8% of theory.

R = t-amyl, n = 6, M = Na The yeneral procedure of Example 2 was repeated using p-tert-amylphenol. The dried product weighed 129.7 g, or 59.4% of theory.

R = nonyl, Rl = ~H3-, n = 6, M = Na The general procedure of Example 2 was repeated except that alanine was used in place of glycine. An equimolar solution I of 15.6 gms. of alanine and 7 gms. of 50% NaOH was prepared.
¦ To this was added ll.l gms of formaldehyde. Finally, a I methanol solution of 43.6 gms. of para-nonyl phenol was added.
I 37 gms. of a sold yellow product were recovered.

,:,~,"j 1 1 69~75 R = nonyl, ~' = (CH3~2 CH-, n = 6, M = Na The general procedure of Example 2 was repeated except that valine was used in place of glycine. ~n equimolar solution of 20.5 gms. of valine and 7 gms. of 50% NaOH was prepared.
To this was added 11.1 gms. of formaldehyde. Finally, a methanol solution of 43.6 gms. of para-nonyl phenol was added. 33.6 gms. of a solid yellow product were recovered.

R = nonyl, R' = CH3S-CH2-CH~-, n = 6, M = Na The general procedure of Example 2 was repeated except that methionine was used in place of glycine. An equimolar solu-tion of 26.1 gms. of methionine and 7 gms. of 50% NaOH was prepared. To this was added 11.1 gms. of formaldehyde.
Finally, a methanol solution of 43.6 gms. of para-nonyl phenol was added. 44.9 gms. of a solid yellow product were recovered.

R = nonyl, n = 1, ~ = Na The general procedure of Example 2 was used except that the following charges were used in order to give a product in which n = 1:
p-nonyl phenol 65.4 gms. (0.3 mole) glycine 15 (0.2 mole) NaOH 8 (0.2 mole) HCHO 13.5 (0.45 mole) The product recovered was 81.A gms. of an off-white solid.
The following structure was assigned to the product recovered on the basis of method of syntheses, elemental analysis, and copper chelation value:

~E~ OEI ~I

t:g~9 ~ ~9~319 ~a t~ g After extraction with acetonitrile to give a purified product for analysis, aata from elemental analysis (see D. Pasto &
C. Johnson's "Organic Structure Determination, Prentice-Hall ~ ~1 69~7S

1969 p. 321) confirmed a formula of C53H80N2O7Na2, consistent with the foregoing structure. The following data were obtained:
N C H
Theory (%) 3.1 70.5 8.9 Found (%) 2.9 69.64 9.6 In addition, the chelation value of the purified product (as found by the methods hereinafter specified) for copper (l:l)was 70.6 mgs/gr., the exact value that would be expected for this structure in theory.

R = methyl, n = 1, M = Na The general procedure of Example 2 was repeated using para-cresol. The product was isolated by removal of solvents on the Rotovap followed by precipitation with acetonitrile and vacuum drying. The following charges were used:
p-cresol 97.2 gms. 0.9 mole glycine 45 0.6 NaOH 24 0.6 HCHO 40.5 1.35 130 gms. of a yellow solid product were recovered.

I R = isopropyl, n = 1, M = Na The general procedure of Example 2 was repeated using para-isopropyl phenol. The following charges were used:
p-isopropyl phenol 61.3 gms. 0.45 mole glycine 22.5 0.3 -I NaOH 12 0.3 HCHO 20 0.65 77 gms. of a yellow solid product were recovered.
The products of the foregoing examples were evaluated for their chelating ability. In a test for copper chelating `ability, a 0.350-0.400 gxam sample of the chelating agent is weighed accurately into a 4 oz. bottle, 25 ml of reagent toluene is added, and the bottle is shaken until a solution is obtained. To this is then added hy pipet exactly 25 ml of 0.04 M CuC12 aqueous solution. The bottle is then mechan-ically shaken for one hour, after which the two layers are given time to separate completely. A 5 ml portion of the lower, aqueous, layer is withdrawn by pipet and the residual Cu is determined by titration with 0.01 M EDTA to a PAN endpoint as describea in EDTA Titrations, H.A. Flaschka, Pergamon Press, 1 ~ 69875 New York (1959), pg. ~1. In a test for iron chelating ability the extraction procedure above is followed except that 0.05 M FeC13 is used and 0.5 g of crystalline NaCl may be added to aid in layer separation. A 10 ml portion of the lower, aqueous, layer is withdrawn by pipet and the residual Fe is determined by titration with 0.05 M EDTA
to a Chromazurol S endpoint as described in Complexometric Titrations, G. Schwarzenback (H. Irving, Trans.), Interscience Publishers, New York ~;(1957), pg. 77. The results are summarized below:
Product Copper CV (mg/g) Iron CV (mg/g) Ex.2 83.00 50.12 EX.3 72.50 36.30 Ex.4 77.16 72.41 Ex.5 69.61 69.28 Ex.6 92.68 ppt Ex.7 70O42 38.60 Ex.8 99.56 90.69 Ex.9 74.93 not obtained Ex.10 63.09 17.29 Ex.ll 62.68 10.95 Ex.12 79.80 29.40 Ex.13 not obtained; water not obtained; water layers too highly layers too highly colored colore~
Ex.14 not obtained; water not obtained; water layers too hiyhly layers too highly colored colored l'hese high results demonstrate that the compounds of the present invention are highly effective chelating agents.
Moreover, although the chelated metals used in this demon-stration were Cu (II) and Fe (III), it should be obvious to those skilled in the art that the compounds of the present invention could also be used with other commonly chelated metals.
The products of the present invention display sur-prisingly high solubilities in a broad range of substituted and unsubstituted aliphatic and aromatic solvents. For pur-poses of illustration, and without limitation, the products of the foregoing examples were evaluated for approximate solu-bility in a number of common solvents. In determining solu-bility, the following procedure was employed: The sample was first weighed into a vial and enough solvent was added to give the desired weight percent. The vial was then capped and left at room temperature overnightO Finally, the vial was checked for the presence or absnce of solid. The results a~re summarized ~69~7~

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SUPPLE~NTARY DISCLOSURE

In accordance with the teachings of the Principal Disclosure compounds useful as metal chelating agents ha~e been outlined. The compounds have the general formula:

OH OH OH
~ o~ tR loc~

wherein R is an alkyl group having frol~ 1 to 15 carbon atoms;
R' is H or the residual group of an a-amino acid of natural occurrence;
M is selected from the group consisting of H~, an alkali metal ion, NH4~, or an aminium ion, and n is an integer from 1 to 6.
Also disclosed is the process for the preparation of these compounds.
No~, and in accordance with this Supplementary Disclosure there i3 provided additional speciic compounds within the scope of the Principal Disclosure.
l'he compounds have the general formula OH O~ OH
[~CH2 ~1--CH2t ~ H2 ~ CH2 - ~OOM ~ loo~

.~ -SD10-wherein R is an alkyl group having from l to 15 carbon atoms;
R' is H-, a lower alkyl group, HO~CH2-, CH3CH(OH)-, HSC~12' CH3-SCH2C~2-' H2NCCH2 ' H2NC 2 2 HOOCCH2-, HOOCCH2CEI2--, or < ~ CH2-;
M is selected from the group consisting of H+, an alkali metal ion, NH4+, or an aminium ion; and n is an integer from l to 6 The corpounds of the present invention are prepared by a two-step reaction in which an aqueous solution of formaldehyde is first added to an aqueous solut1on of an amino acid having the general formula WH2CHR'C00~1, and a methanol ~olution of a pheno1 having the f~rmula ~ i5 chen added to the resulting mixture~
; 210re specifically, in the first step, formalde11yde is reacted with an amino acid of the general fox~ula NH2CHR'COOM in the aqueous solution whose p~I is maintained at 7.5-8.0 with sodium or potassium hydroxide. A co-solvent such as methanol is then added. In the second step, while still maintaining th~ pH at 7.5-8.0~ a methanol solution of a phenol of the general formula OH is slowly added to the : R
reaction mixture, which is then heated at reflux. On cooling and standing, the desired product can be separated out as on oily layer while the water/methanol layer is decanted. The product is then dried and ground to a powder. Vacuum drying has been used for laboratory scale preparationsl but other typres of drying -SDll-~ , . .
,~ O . , I 1 6987$

could obviously be em~loyed for commercial purposes.
It has been found that whPn lower alkyl substituents are used (R - 1-3 carbons), compounds are obtained with a commercially significant solubility in metllanol. However, as one moves to higher alkyl substituents, the compounds of the present invention are found to display high solubilities in a much wider array of non aqueous systems while the aqueous solubility of such compounds becomes neglibible.
R' is the residue of an ~-amino acid of natural occurrence. For example, if the amino acid used is glycine, R'=H; if alanine, R'=CH3-, etc. The invention is not limited to cases where R' iS a lower alkyl residue, but also includes residues consisting of hydroxyalkyl, thioalkyl~ phenylalkyl, and other groups. By way of illustration, the following list contains various values of R' which are deemed to be within the scope of the present invention, as well as the name of the a~ino acid from which that residue is obtained:

R' = H- glycine CH3- alanine (CH3)2 CH valine ~CH3)2-C~c~I2 CH3cH2cH(cH3)-HO-CH2- serine CH3CH (OH)- thrionine HSCH2- cysteine CH 3- S- OEI2 CH 2 ` methionine H2~COCH2- asparagine H2NCOCH2CH2- glutamine HOOCCH2 aspartic acid HOOCCH2CH2- gluta~ic acid ~ H2- phenylalanine The following additional example is provided for purposes of further illustrating, without limitation, embodiments of the invention, I 1 ~9~75 - EX~IPLE 15 R = nonyl, R' = ~IOOCCH2-, n=6, ~ a The general proc~dure of Ex~nple 2 was repeated using aspartic acid in place of glycine. The following charges were used:
p-nonyl phenol 179 gms. 0.~ moles aspartic acid 93.1 0.7 HCHO 42 1.4 NaOH 28 0.7 152 grams of a fin~ yellow solid product were obtained.
These results may be summarized:
~roduct Copper CV (mg/g) Iron CV (mg/g) Ex. 15 105 not obtained; no layer separation For the purpose of illustration, and without limitation, the product of the foregoing example was evaluated for approximate solubility in a number of common solvents. In determining solubility, the following pro-cedure was employed: The sample was first weighed into a vial and enough solvent was added to give the desired weight nercent. The vial was then capped and left at room temperature overnight. Finally, the vial was checked for the presence or absence of solid. The results are summarized below (values are in weight percent):

-SDl3-. ' '~, .

`- I 1 69~375 Ex. 15 water ... <1 methanol ...
ethanol ... <1 i-PrOH ... <1 butanol ... <1

2-ethylhexanol ....................... <1 acetone ... <1 4-methyl-2-pentanone ... <1 toluene ... <1 ethylbenzene ... <1 ethyl acetate ...
acetonitrile ...
tetrahydrofuran ...
hexanes ... <1 cyclohexane ... 20 octane ... <1 iso-octane ... <1 decane ... <1 CH Cl ...
ch~oroform ... 30 i

Claims (30)

We claim:

1. A compound having the formula wherein R is an alkyl group having from 1 to 15 carbon atoms;
R' is H or the residual group of an .alpha.-amino acid of natural occurrence;
M is selected from the group consisting of H+, an alkali metal ion, NH4+, or an aminium ion, and n is an integer from 1 to 6.

2. A compound according to claim 1 in which R is an alkyl group having from 4 to 15 carbon atoms.

3. A compound according to claim 1 in which R is selected from the group t-butyl, t-amyl, nonyl, and dodecyl.

4. A compound according to claim 1 in which R' is selected from from the group H, CH3-, (CH3)2CH-, and CH3S-CH2CH2-.

5. A compound according to claim 1 in which R is a nonyl group.

6. A compound according to claim 1 in which R' is H.

7. A compound according to claim 1 in which M is Na+.

8. A compound according to claim 1 in which n is 1.

9. A compound according to claim 1 in which R is a nonyl group, R' is H, M is Na+, and n is 1.

10. A methanol solution of a compound according to claim 1 wherein R is an alkyl group having from 1 to 3 carbon atoms.

11. A process for preparing a compound having the formula:

wherein R is an alkyl group having from 1 to 15 carbon atoms;
R' is H or the residual group of an .alpha.-amino acid of natural occurrence;
M is selected from the group consisting of H+, an alkali metal ion, NH4+, or an aminium ion; and n is an integer from 1 to 6;
said process comprising i) forming a first resulting mixture by admixing in an aqueous solution whose pH is maintained at 7.5-8.0, a) formaldehyde, and b) an amino acid of the general formula NH2CHR'COOM;
ii) forming a second resulting mixture whose pH is maintained at 7.5-8.0 by admixing with said first resulting mixture a methanol solution of a phenol of the general formula ;

iii) heating said second resulting mixture for a time and to a temperature effective for forming the desired compound:
iv) allowing said second resulting mixture to stand and cool so as to permit recovery of the desired product.

12. The process according to claim 11 in which R is an alkyl group having from 4 to 15 carbon atoms.

13. The process according to claim 11 in which R is selected from the group t-butyl, t-amyl, nonyl, and dodecyl.

14. The process according to claim 11 in which R' is selected from the group H, CH3-(CH3)2CH-, and CH3SCH2CH2-.

15. The process according to claim 11 wherein R is a nonyl group.

16. The process according to claim 11 in which R' is H.

17. The process according to claim 11 in which M is Na+

18. The process according to claim 11 in which n is 1.

19. The process according to claim 11 in which R is a nonyl group, R' is H, M is Na+, and n is 1,

20. The process according to claim 11 in which R is an alkyl group having from 1 to 3 carbon atoms and in which the desired product is soluble in methanol.

CLAIMS SUPPORTED BY THE SUPPLEMENTARY DISCLOSURE

21, A compound having the formula wherein R is an alkyl group having from 1 to 15 carbon atoms;

R' is H-, a lower alkyl group, HO-CH2-, CH3CH(OH)-HSCH2-, CH3-SCH2CH2 - H2NCOCH2, H2NCOCH2CH2, HOOCCH2-, HOOCCH2CH2-, or M is selected from the group consisting of H+, an alkali metal ion, NH4+, or an aminium ion, and n is an integer from 1 to 6.

22. A compound according to claim 21 in which R
is an alkyl group having from 4 to 15 carbon atoms.

23. A compound according to claim 21 in which R is selected from the group T-butyl, t-amyl, nonyl, and dodecyl.

24. A compound according to claim 21 in which R' is selected from the group H-, CH3-, (CH3)2CH-, CH3S-CH2CH2-, and HOOCCH2-.

25. A compound according to claim 21 in which R is a nonyl group.

26. A compound according to claim 21 in which M is Na+.

27. A process for preparing a compound having the formula:

wherein R is an alkyl group having from 1 to 15 carbon atoms;
R' is H-, a lower alkyl group, HO-CH2-, CH3CH(OH)-, HSCH2- CH3-SCH2CH2, H2NCOCH2-, H2NCOCH2CH2-HOOCCH2 , HOOCCH2CH2-, or ;
M is selected from the group consisting of H+, an alkali metal ion, NH4+, or an aminium ion; and n is an integer from 1 to 6;
said process comprising:
i) forming a first mixture by adding about 2 molar equivalents of an aqueous solution of formaldehyde to about 1 molar equivalent of an aqueous solution of an amino acid having the general formula NH2CHR'COOM over a time period of 0.5-2 hours and at a temperature of 20-50°C while maintaining the mixture at a pH of 7.5-8;
ii) forming a second mixture by admixing the first mixture with a sufficient amount of methanol to permit dissolution of a phenol of the general formula while maintaining the pH of the second mixture at 7.5-8;
iii) forming a third mixture by adding to the second 1.1 to 1.5 molar equivalents of a methanol solution of a phenol of the general formula over a period of 0.5-2 hours at a temperature of 30-80°C while maintaining the pH at 7.5-8.0;
iv) heating the third mixture at reflux for a period of 5-7 hours; and v) allowing the third mixture to cool, followed by separation and recovery of said compound.

28. The process according to claim 27 in which R
is an alkyl group having from 4 to 15 carbon atoms.

29. The process according to claim 27 in which R
is selected from the group t-butyl, t-amyl, nonyl, and dodecyl.

30. The process according to claim 27 in which R' is selected from the group H-, CH3-, (CH3)2CH-, CH3S-CH2CH2-, and HOOCCH2-.