CA1088069A - Preparation of n,n'-dicarboxymethyl-1,3- propanediamines - Google Patents

Abstract

PREPARATION OF N,N'-DICARBOXYMETHYL-1,3-PROPANEDIAMINES
ABSTRACT OF THE INVENTION
N,N'-Dicarboxymethyl-1,3-propanediamine (designated PDDA) is prepared by reacting 1,3-propanediamine with formaldehyde and HCN to form hexahydroprimidine-1,3-diacetonitrile, which is hydrolyzed with an aqueous alkali metal hydroxide to form dialkali metal hexahydropyrimidine-1,3-diacetate which, in turn, is reacted with mineral acid to form the desired PDDA and formaldehyde.
N,N'-Dicarboxymethyl-2-hydroxy-1,3-propanediamine (designated HYDROXY-PDDA) is prepared by reacting 1,3-diamino-2-propanol with formaldehyde and HCN to form 5-hydroxyhexa-hydropyrimidine-1,3-diacetonitrile, which is hydrolyzed with an aqueous alkali metal hydroxide to form dialkali in turn, is reacted with acid to form the desired HYDROXY-PDDA and formaldehyde.

Description

BACXGROUND OF THE INVENTION
This invention is in the field of; (a) N,N'-dicar-boxymethyl-1,3-propanediamine, which has the formula CH2 NC~2CH
¦ H
fH2 H
C~2 NCH2COOH, which is sometimes called 1,3-propanediamine-N,N'-diacetic acid and which is designated PDDA; and (b) N,N'-dicarboxymethy~-2-hydroxy-1,3-propanediamine which has the formula HO-CH H
¦ H
C~2-NCH2COOH, which is sometimes called 2-hydroxy-1,3-propanediamine-N,N'-diacetic acid and which is designated HYDROXY-PDDA.
~ ~ore partlcularly, this invention is directed to L0 an improved process for preparing PDDA of high ~uality by an improved route involving the following sequential re2ctions:

H2N(CH2)3N~2 + 3 C~20 + 2 HCN ~ ~ + 3~2 C~ 2CN
(hexahydropyrimidine-1,3-diacetonitrile) ~ ?D.~N) ~088V69 CH2CN CH2COONa ~--N /~-N
> + 2 NaOH +2H2o~ + 2 NH3 CH2CN H2COONa (disodium hexahydropyrimidine-1,3-diacetate) (HYPDANa2) CH2cooNa CH2COOH fH2COOH

2 ~ HNcH2cH2cH2NH + CH20 + 2 Na+.
CH2COONa (PDDA) This invention is also directed to HYDROXY-PDDA and to a process for preparing HYDROXY-PDDA of high quality by the following sequential reactions:

~ N
H2NCH2CHCH2NH2 + 3 CH20 + 2 HCN >HO ~ ) + 3 H20 I

(5-hydroxyhexahydropyrimidine-1,3-diacetonitrile)(HYDROXY-HYPDAN) CH2CN fH2COONa + 2 NaOH + 2 H20 ~ HO C ) + 2 NH3 CH2CN CH2COONa (disodium 5-hydroxy-hexahydro-pyrimidine-1,3-diacetate) (HYDROXY-HYPDANa2) fH2COONa CH2COOH CH2COOH

{ N H2O
¦ 21 CH2 NH + CH20 + 2 Na .
CH COONa OH
2 (HYDROXY-PDDA) Prior art methods of preparing PDDA are taught by Johnson et al., J. Org. Chem. 1962, 27, 2077-2080. See the second column on page 2079 and the first column on page 2080.
The preparation of H

is taught by Titherly et al, J. Chem. Soc., 1913, 103, 330-340 (at 334).
The preparation of H2I C~CH2 H2C ~ C~7 - CH2 C - N H2C\ ~ H2 H Z C FC ~N C H 2 H2C`C'CH2 which, elsewhere in this specification, is referred to as r N~N-CH

from formaldehyde and 1,3-propanediamine is tausht by Krassig, I

Makromol. Chem., 1956, 17, 77-130 (at 87-88).

The process of the instant invention constitutes a decided improvement over prior art. routes to PDDA. Among the advantages of the process of the instant invention are; (a) the fact that PDDA
formed by the method of this invention is free of side products;
(b) the by-products (NH3, formaldehyde, and an alkali metal salt, e.g., sodium or potassium chloride or sulfate) are readily separated from the respective intermediate or final product with which the by-product i9 formed; (c) the use of objectional or inconvenient materials such as anhydrous HCl and hydrogenation catalysts is avoided; and (d) the final product is substantially pure PDDA which is obtained without resorting to the expensive and inconvenient repeated decantations and crystallizations of the prior art.
SUNMARY OF THE INVENTION
In accordance with the present teachings, a compound is prepared having the formula HQ____-CH CIH2 C 2 ~ N-H
In accordance with a further teaching, a process is provided for preparing the compound of the formula above which comprises admixing in an aqueous medium 1, 3-diamino-2-propanol and an amount of formaldehyde effective for forming the compound, maintaining the resulting admixture at a temperature effective for forming the com-pound and for a period of time to form the compound.
DESCRIPTION OF PREFERRED EMBODIMENTS
In one preferred embodiment ("Embodiment A") this invention is directed to a process for preparing the nitrile of the above Summary, said process comprising admixing in an aqueous medium:
(a) 1,3-propanediamine or 1,3-diamino-2-propanol; and (b) formaldehyde and HCN or formaldehyde and glycolonitrile in amounts effective for forming said nitrile.
Preferred mole ratios of amine to formaldehyde to HCN are 1:3-3.5:2-2.5 or 1:3-3.1:2:2.1, preferred mole ratios of glycolonitrile to formaldehyde are 2:1 or 2:0.9-1.1, and preferred mole ratios of HCN or glycolonitrile to 1,3-?ro-panediamine or 1,3-diamino-2-?ro?anol are 2:1 or 2:0.9-1.1.
It is generally ?referred that the mixture formed by admixing the amine, formaldehyde, and HCN or glycolonitrile be prepared at 45-70C (or 50-60C) and maintained at said temperature to form the nitrile. ~owever, excellent results have been obtained where said mixture was prepared at 20-80C
!0 and maintained at 40-60C to form the nitrile. It is generally preferred to maintain said mixture at 50-60C (or 55-60C) for l-S hours (or 2-4 hours) to form the nitrile.
In another preferred embodiment ("Embodiment B") this invention is directed to a salt having the formula CH2COOM fH2COOM

lH2 ICH2 orHO _ CH2 1CH2 in which M is an alkali metal cation le.g., sodium or potassium) or 1/2 of an alkaline earth metal cation (i.e., barium, stront-ium, or calcium), or an ammonium ion having the formula Rl N R3 where Rl, R2, R3 and R4 is each inde~endently selected from a 0 group consisting of hydrogen, lower alkyl, or hydroxy lower alkyl.

In another embodiment ("Embodiment C") _his invention is directed to a process for preparing the alkali metal and alkaline earth metal salts of ~mbodiment B, said process com-?rising hydrolyzing the nitrile of the above Summary in an aqueous medium with an amount of an alkali metal hydroxide (e.g., sodium or potassium hydroxide) or an alkaline earth metal hydroxide effective for hydrolyzing the nitrile.
Generally a mole ratio of nitrile to alkali metal hydroxide of 1:2.2-2.4 or 1:2.02-2.20 is preferred (where using an alkaline Q e~rth metal hydroxide the mole ratio of nitrile to alkaline earth metal hydroxide would be 1:1.1-1.2 or 1:1.01-1.1). The hydrolysis has been conducted with excellent resu~ts at about 95-110C. Where using temperatures above the normal boiling point of the reaction mIxture in which the hydrolysis occurs, an apparatus designed to conduct the hydrolysis under super-at~ospheric pressure can be used. However, this is not necessary because excellent results have been obtained where conducting ~he hydrolysis at the normal boiling point of the mixture in which the nitrile is being hydrolyzed. Residence ~` time in the hydrolysis zone has been varied from 1-3 hours with excellent results, but a residence time of 1.5-2 hours is gene-ally preferred. It is preferred to boil the mix'.ure in which the hydrolysis occurs until said mixture is free of by-product ammonia.
In another preferred embodiment (n~mbodiment D n ) ~his invention is directed to a process for forming an acid selected from 2 first group consisting o lH2 NCH2COOH C~2NCH2COOH
CH2 and ~o _ CH

C~2 NC~i2COCH t H;~H2COOH
Com?risins:

(a) forming a nit~ile selected '-om a second group consisting of CH CN
1 2 C~2CN
CH N

lH2 ~2 ~ lc~2 INH2 CH I I

C~2C~
C~2C~
by admixing, in an aqueous medium formaldehyde; (i) a m~mber selected from a third group consisting of HCN and glycolo-nitrile; and (ii) a member selected from a fourth group con-sisting of 1,3-propanediamine and 1,3-di~mino-2-propanol, to form a resulting admixture and maintaining the resulting ad-m~xture at a temperature effective for forming the second group member for a time effective for forming the second group mem-ber, the formaldehyde, the third group mem~er, and the fourth group member being admixed in amounts effective for forming the second group member;
(b) hydrolyzing said nitrile in an aqueous medium 'O with an amount of an alkali metal hydroxide or alkaline ear'~h metal hydroxide effective for hydrolyzing the nitrile to form a salt selected from a fifth group consisting of CH2 N C~2 ICH2 ICH2 or ~o CH fH2 CH2 N C~2 C~2COOM CH2COOM

n which M is an al~all metal ion or 1/2 o. an alkaline ea-_h o metal cation (e.g., 1/2 Ba , 1/2 Sr , or 1/2 Ca ); and (c) converting said sal- -o _he acid having a ,o~ula 101~3069 1 2 ICH2COOH lx2 1 2COOH

CH2 or ~o CH

CH2 NC82CH CH2--NC~2C~
by treating said salt in an aqueous medium with an amount or a mineral acid or an acidic ion exchange resin effective for forming said first group member.
The mixture formed by admixing 'ormaldehyde, ~CN, and the fourth group member (or formaldehyde, g-l-ycolonitrile and fourth group member) is preferably prepared at 45-70C (or 50-60C) and maintained at said temperature (or at ;5-60C) for 1-5 hours (or 2-4 hours) to form the second group member.
Sodium hydroxide is a preferred alkali metal hydroxide for use in the process of this embodiment. ~n-alkaline earth metal hydroxide ~e.g., Ba(OH)2, Sr(OH)2, or Ca(OH)2) can be used in place of the alkali metal hydroxide. Obviously, where using an alkaline earth metal hydroxide, 1/2 mole is equivalent to 1 mole of an alkali metal hydroxide.
The hydrolysis of the nitrile is generally conducted at about the normal boiling point of the aqueous medium in which the hydrolysis is c~nducted. However, lower temperatures (e.g., 30-100C) have given excellent results, and excellent results can be obtained at higher temperatures (e.g., 110-120C) where using a pressurized system. It is generally prefer_ed to boil the aqueous medium in which the hydrolysis of the ni-rile is being (or has been) conducted until said medium is sub-stantially rree or by-product ammonia.
In general it is ?reCer~ed to use 2.0-2.5 (o_ 2.0-2.05) moles o' a monoprotic acid or 1-1.25 (or 1-1.02) moles o- a diprotic acid per mole o_ the 'i-_h grou? member to convert said -i-th sroup member (the a oresaid sal_) o -he i-st ~-oup memDer. ~vdrochloric acid is ~ ?_e~er-ed mineral ~cid. h'he_e 1~8069 using an acidic ion exchange resin to convert the fif.h sroup member (the salt) to the first group member, it is generally preferred to use 2-3 (or 2.2-2.6) equivalents of an acidic ion exchange resin per mole of the fifth grou? membe-.
Where treating the fifth group member (the afore-said salt) in an aqueous medium with hydrochloric acid to 'orm the first group member (the acid of this invention), it is often advantageous to use an excess of hydrochloric acid (pre-ferably added as concentrated (e.g.,-33-40% HCl) aqueous hydro-.0 chloric acid solution) to precipitate the product acid (first group member) as a dihydrochloride salt having the formula CH2 1 2COOH CH2 1 C~I2COOH
¦ H I E
CH2 .2HCl or HO - CH .2HCl I H i H
CH2-- 2COOEi CH2 NCH2COOH

In other words, the salt (the fifth group member) which is present as an aqueous solution is treated with an amount of hydrochloric acid effective for formi~g and precipitating a sixth group member (a hydrochloride having the formula CH .2HCl or HO - CH .2HCl 2 ~ I H

Excellent results have been obtained where provlding 4-8 (or 4-6) moles of hydrochloric acid ?er mole of -ifth srou? member (the aforesaid salt).
~ he above-mentioned sixth s_ou? member (said hvd_3-chloride) can be conve~ted to the fi-st sroup membe~ (a-. aci~
having the formula CH2 - NC~2COOH ! 2 ~C~2COOH ~
IC.2 . or iO - ,CH J

CH.~ ~C'i~COOH ~ C COOE

by treating the sixth group member (preferably in an aqueous medium) with a stoichiometric amount of sodium (or potassium) hydrogen carbonate. For this purpose a stoichiometric amount of the sodium (or potassium) hydrogen carbonate is two moles per mole of the sixth group member. Ammonium carbonate, am-monium hydrogen carbonate, or ammonium carbamate can also be used to convert the hydrochloride to the free acid.
Alternatively, the first group member (the acid having the formula CH2 or HO CH

CH2 . NCH2COOH CH2 NCH2COOH ~

can be precipitated from the aqueous medium in which it (the first group member) was formed by adding to said aqueous medium an amount of a water soluble alcohol (e.g., methyl alcohol, ethyl alcohol, or iso-propyl alcohol) effective for precip-itating the first group member. Excellent results were ob-tained where adding such amount of the alcohol that the alcohol 2~ constituted about 75-95% (or 90-95%) of the aqueous medium after the first group member had been precipitated therefrom.
The first group member of Embodiment D can be con- !
verted to the sixth group member - the above described hydro-chloride - by treating the first group member with hydrochloric acid (e.g., 4-8 or 4-6 moles of hydrochloric acid per mole of flrst group member.) In another preferred embodiment ~"Embodiment E") this invention is directed to an acid having the formula ICH2-N~CH2COOH
HO-CH

. C~2-NCH2COOH, ~)8~3069 ~nd to a hydrochloride of said acid, the hydrochloride having the formula OH- CH .2HCl CH 2 NCH 2 C OOH .

In another preferred embodiment of this invention ("kmbodiment F"), which is equivalent to the embodiment recited in theabove Embodiment A, the procedure of step "(a)" of Embodiment D, supra, was modified by:

l. Admixing in an aqueous medium 1,3-propanediamine or l,3-diamine-2-propanol and formaldehyde, the amine and the formaldehyde being admixed in an amount effective for forming a compound having the formula CH -N-H CH -N-H

IC~2 ICH2 or HO-CH FH2 CH -N-H CH2-N-H.

2. Admixing in an aqueous medium; (a) the compound 2~ having the formula C~2-N-H CH -N-H

CH2 CH2 or HO-CH CH2 CH -N-H CH2-N-H ; and (b) formzldehyde plus HCN the equivalent thereo_ (e.g., slycolonitrile which is eauivalent on a mole-for-mole bas s to 'ormaldehyde ?l~ls HCN), szid compound having the _ormula ~ 2 I H CH2-N-n ; ICH2 ICH2 or HO-CH ~:~2 CH -N-H CH2-N--., 10E~8V69 said formaldehyde, and said HCN beins admixed in amounts ef-fective for forming a nitrile havlng the formula IcH2cN f H2C~

N
ICH2 ICH2 or HO CH

CH2C~ C~2CN
.0 3. Substituting the thus prepared nitrile in step "b" of the procedure set forth in said Embodiment D to form the salt (fifth group member) formed in ste? "b" of Embodiment D. The thus formed salt can then be nsed in step "c" of said Embodiment D to form the first group member of said Embodiment D.
We have obtained excellent resul~s with this pro-cedure ~_he procedure of Embodiment F) by admixing the amine and formaldehyde in a mole ratio of 1:1-1.5 (or 1:1.0-1.05) and maintaining the resulting mixture at about 50-70C (or :0 5;-6SC) for about 0.25-16 hours (or O.S-1 hour).
We have also obtained excellent results with this procedure (that of Embodiment F) by admixing he compound having the formula CH2-N-H C~2_~_~
CH2 CH2 or HO-CX CH2 C~2-N-H C~i2~

the formaldehyde and the HCN-in 2 mole ~atio of 1:2.0-2.5:
2.0-2.5 (or 1:2.0-2.1:2.0-2.1) a. about 45-70C (o- ~0-50C~
0 and main-.aining the -esulting mixtu~e 2t ~O-oOC (O- 55-oOC) -or about 1-5 hours (or 2-' hours) _o -onm he ~-o_esai~
~it~iie. ~lterna~ivelv, the on~2ldehvde ~nc HCN can be re~laced with glycolonitrile which is equivalent to 'ormaldehyde plus HCN.
In another preferred embodiment ("Embodiment G") this invention is directed to a process for formins a ni~rile having the formula fH2CN

comprising mixing: (a) a tetramer of 1,3-prooanediamine and formaldehyde; (b) formaldehyde; and (c) HCN and main-taining the resulting mixture at a temperature effective for forming said nitrile for a time effective for forming said nitrile, the tetramer, formaldehyde, and HCN being admixed in amounts effective for forming said nitrile.
Preferred mole ratios of the tetramer to formalde-hyde to ~CN are 1:3.2-4.8:7.2-8.8. Glycolonitrile, (one mole o' which is equivalent to one mole of formaldehydr plus one mole of HCN) can be substituted on a mole-for-mole basis 'or HCN plus formaldehyde. A preferred reaction temoerature is about 45-70C and a preferred residence (reaction) time is about 20-90 minutes (or 25-40 minutes).
A nitrile having the formula ICH2C~
ca2 N

'~OCH ICH2 C~2 C'i2C.`~

can be formed by substituting a tetramer or 1,3-diamino-2-propanol for the tetramer of 1,3-propanediamine in ~odiment G. (See Procedure 17.) - In another preferred embodiment ("Embodiment H") a product salt having the formula ~CH2 N CIH2 N

ICH2 ICH2 or HO - CH ICH2 C~2 N CH2 N

in which M is an alkali metal cation, 1/2 of an alkaline earh metal cation, or an ammonium ion having the formula IR2 +
T
L R4 _ in which each or Rl, R2, R3, and R4 is selected from a group consisting of hydrogen, lower alkyl, or hydroxy lower alkyl can be prepared by admixing in an aqueous medium a reactant salt having the formula CH2 ' NCH2COOM CH2 NCH2COOM
¦ H ¦

CH2 or HO CH

and an amount of ~ormaldehyde ef ective ,or forming .he ?--duct salt.

l~W69 DETAILED DESCRIP~ION OF THE INVENTION
This invention is directed to the preparation of: -(a) PDDA; and (b) intermediates on a route to PDDA from 1,3-diaminopropane, formaldehyde and ~CN, and to said intermediates.
This invention is also directed to HYDROXY-PDDA, to intermediates on a route to HYDROXY-PDDA from 1,3-diamino-2-propanol, formaldehyde and HCN, to the preparation of HYDROXY-PDDA, and to the preparation of said intermediates.
PDDA and ~YDROXY PDDA are useful for for~ins chelates 0 of copper. Such copper chelates are useful to control the concentration of copper ions in metal plating baths and as a means for supplying copper to soil which is deficient in cop-per.
PDDA and HYDROXY-PDDA are also useful for preparing chelating compounds having the formula ~ c~2-1-c-c-c-1-CX2 0 in which Z is ~ or OH.
Chelating compounds having 'he above ~ormula are especially useful for chelating iron (i-ron(III) and iron (II)). These chelating agents, their preparation, the pre-paration and use of such iron chelates is taught in our copending Canadian Patent Application Seriai No. 259,664 - filed August 23, 1976 which is assigned to ~. R. Grace &
Co .
The instant invention will be better understood by referring to the following speci-ic but nonlimiting ex-0 amples and ~rocedures. It is unders~ood that said invention is not limited by said examples or by said ?rocesdu-es 211 _5 ~0813069 of which are orfered merely as illustrations; it ls also understood that modifications can be made without departing from the spirit and scope of the invention.
The examples were actually run.
The procedures, while not actually run, will illus-trate certain embodiments of our invention.
EXAM~LE 1 A 74.1g portion (1 mole) of 1,3-propanediamine was fed into 50 ml. of water in a reaction zone. 68.2g (1 mole) of 44% formaldehyde was fed into the aq~s ~P solution in said reaction zone over a period of 40 minutes while maintaining the temperature of the resulting mixture at 50 - 70C. The thus formed mixture was cooled to SO~C in the reaction ~one and 166.4g of 68.5% glycolonitrile was added thereto over a period of 50 minutes. The temperature of the mixture in the reaction zone increased during the first half of the glycolo-nitrile addition thereto;,cooling was applied to the reaction - zone followed by heating, said temperature being maintained at 45 to 55C. The clear, colorless solution was stirred an additional 1 3/4 hours and allowed to stand overnight.
When the straw-colored solution was agitated on the next day a mass of white crystals formed. The mass was broken up, added to water, stirred, and ~iltered. After re-slurrying twice in S00 ml portions of water, the collected product was dried at 4i-;0C. 63.6 g or ?roduct (nit~ile) cor_espondins to a conversion (one pass yield) or 38.3~ was obtained.
A small sample o_ the above prepared nitrile was taken for analysis. This aliquot was titrated with ?e-chlo~ic acid in glacial acetic acid. A monoperchlorate salt was fo~med during the titration. The results of this tit-ation ~0~8069 showed a molecular weight of 164 v. a theoretical value of 16~. The product was identlfied by gas chromatography and infrared spectroscopy as substantially pure hexahydro-pyrimidine-1,3-diacetonitrile (~YPDAN), C~2CN
I

C~2 CH2 A 370.5g portion (5 moles) of 1,3-propanediamine was fed into 250 ml of water in a reaction zone. 341.0g of 44~ formaldehyde was fed into the aqueous amine solution in said reaction zone over a period of 30 minutes while maintain-ing the temperature of the resulting mixture at 50 - 63C.
The thus formed mix.ure was ~tirred an additional 40 minutes and allowed to stand overnight.
2Q 832.0g (10 moles) of 68.5% glycolonitrile was added thereto over 40 minutes. The temperature rose from 21C to 54C during the glycolonitrile addition. ~alf way through sald addition, 275 ml of water was also fed into the reaction zone.
The resultant mixture was stirred at 50 - 57C for two hours, during which time crystals formed. An additional 250 ml of water was added to the mixture halfway through said 2-hour hold perlod. The reaction mixture was cooled over th_ee hours to 23C, filtered, and the produc' c~ystals were washed with 125 ml of water. The product W2S dried in ai- to g ve 691g of ~Y~DAN, corresponding to a conversion of 85~.

- i3 -A 74.lg portion (1 mole) of 1,3-propanediamine was fed into S0 ml of water in a reactlon zone. The resultins aqueous solution of the amine which became hot (reachlng a temperature of about 60C as it was formed), was cooled to 50C, and 68.2g (1 mole) of 44% formaldehyde solution was fed into the aqueous amine solution in said reaction zone over a period of 45 minutes while maintaining the temperature of the resulting mixture at 50 - 70C. The thus formed mixture was cooled to 47C in the reaction zone and a pre-mix of 136.4g (2 moles) of 44~ formaldehyde solution and 84 ml (2.1 moles) of ~CN (which had been stabilized with 0.4g of 85% ~3PO4) having a temperature of 15C was added thereto, over a period of 50 minutes. The temperature of the mixture in the reaction zone increased as the formaldehyde and HC~
were added thereto; said temperature reached a maximum of 65C. Within two minutes of the end of the premix feed, white crystals of the nitrile product precipitated. The mixture from which the crystals precipitated (with the cyrstals therein) was stirred two hours while maintaining it at S0 -55C. The mixture was then cooled to 25C, filtered, and the nitrile crystals were washed with cold water. The re-covered nitrile was dried at 50C. 138.5g of product (~YPDAN) corresponding to a conversion (one pass ~ield) of 85% was obtained.
E ~MPLE 4 A 148.2g portion (2 moles) of 1,3-propanediamine was fed into 100 ml of water in a -eactlon zone. The -esultin5 aqueous solution of the amine which became hot (-eachins a temperature of about 60C as it was fo~med), was cooled to 23C, and 136.4g (2 moles) of 44~ formaldehvde solution was 1 q 1~8~3C169 fed into the aqueous amine solution in said reaction zone over a period of 40 minutes. The temperature of the reaction mix-ture rose to 2 maximum of 69C by the end of the formaldehyde feed. After stirring for 20 minutes, 275g (4 moles) of 44%
formaldehyde and 168 ml (4.3 moles) of hydrogen cyanide were fed into the reaction zone simultaneously from separate reservoirs over a period of 65 minutes while maintaining the temperature of the resultant mixture at 52 - 69C. Cooling was required twice during the 65-minute feed period. The reaction mixture was stirred at 58 - 69C for two hours, al-though the reaction was essentially complete in 1 1/2 hours when analyzed. Product crystallized from the reaction mixture upon seeding with a small amount of HYPDAN during the 2-hour hold period. The slurry was cooled to 20C over 25 minutes and centrifuged and the collected product was washed with 65 ml of water from a spray nozzle. The product was allowed to dry. 277g (or 84% yield) of ~YPD~ crystals W25 obtained.

A 246y portion (1.5 moles) of the nitrile prepared in Example 2 was hydro}yzed by saponification with 5~2g (3.2 moles) of 22.8% sodium hydroxide at about 100 - 106C. The resulting hydrolyzed mixture was boiled at a~mospheric pres-sure until su~stantially all by-product ammonia had been vaporized therefrom to form an ammonla-free solution. This required about 1.25 hours. During the above mentioned hydrolysis and boiling periods water was added as necessary to maintain the volume of the system substantially constant.
The final weight of the very light straw-colored sodium salt solution was 851g.
A small portion of the above ?repared ammonia- ree -- solution was ta~en 'o- analysis leaving a major ?o_tion o-1~88069 said solution for furthe- processing. An attempt was made to titrate a small portion o~ ammonia-free solution wi'h copper (II) chloride at pH9 but the product did not chelate copper (II). However, at p~ 6.0, C~2O was released and the copper (II) ion was chelated. The sodium salt was disodium hexa-hydropyrimidine-1,3-diacetate (HYPDANa2), - CH2COONa iX2 N
l~2 lH2 C~2COONa .

Titration of a weighed portion of the ammonia-free sodium salt solution with copper (II) chloride at p~ 6 using a copper (II) selective electrode established that conversion (one pass yield) of ~YPDAN to ~YPDANa2 was 100%
of theory based on the nitrile charged. A gas chromatogram of the acidified, dried, and silylated product (~Y~DANa2) showed that the EYPD~Na2 was substantially free of impurities.

The ma~or portion of the ~YP~ANa2 solution prepared in Example 5 was diluted to 2 liters with water; the resulting aqueous system was acidified by passing it through a tube con-taining about 2.6 equivalents (17% deficiency) of Amberlite 200 ~ (a strongly acidic cation exchange resin). A 900 ml f-action of p~ 2.8 to 4.1 product solution was collected from the ~ottom of the column. Said product solution smelled stronglv Oc formaldehyde; such odor was not evident in l~e o-iginal sodium salt solution. ~e -action was ev2?0-2,ed in 2ir. ~hen ~e ~raction became sv-upv, i~ was mixed with me~hanol. A solic ?rocuc= ?r-ci-i-a_ed. m~e ?-eci-i:~-e was ~088069 filtered off, methanol washed, and dried at iOC. An aqueous solution of the dried solid ?roduct chelated co~per (II) at pH 9 (unlike the orisinal sodium salt solution) and at pH
6. Acid-base titra~ions, copper (II) titrations, gas chromato-grams, and an infrared spectogram showed the solid is 1,3-propanediamine-N,N'-diacetic acid (PDDA), CH2 - NCH2COOE~

lc~2 H
' C~2 - NC~2COOH

This pass yielded 106.8 g of PDDA, which is a 37.5% recovery.
The-re~aining alkaline fractions were eluted with 1.5 liter of H2O.
The above mentioned alkaline fractions were run through the same column after ~he resin was rege~erated. A
700 ml fraction of pH 3.0 to 4.0 was collected and evaporated - in air. PDDA was isolated by-using the methanol precipitation procedure described supra. This pass yielded 74.5 g ~f P~DA, or a total of 63.6~ recovery. A 1 liter ~raction having a pE of 6 to 11 which was eluted with the aid of a dilute ammonia solution was also collected.

The resin in the column of Example 6 was replaced by Amberlite IRC 84 (a wealky acidic ion exchange reslr.). The final 1~ al~alire f-action obtained in E ~MPT~ 6 was ?assed through the new resin. The Amberlite IRC 84 ~ did not abso-b - ~he PDDA zwitterions as tenaciously as the .~mberlite 200 ~.
PDDA was eluted with distilled wate-. An 850 ml -ac~ion o-pH 3.4 to 4.4 was collected and evaporated in ai-. ~DDA W2S

isolated as in Example 6.

810 ml of concentrated hydrochloric acid (37.5~ HCl) was add~d to 1,000 g of a 39.3% HYPDANa2 solution with stirring.
This resulted in the precipitation of white crystalline mate-rial which was identified as PDDA dihydrochloride, CH2 H .2HCl CH2 -'- NCH2COOH
.0 The PDDA dihydrochloride of Example 8 was dissolved in 600 ml water and treated with concentrated aqueous ammonia to pH 3.8. The resultant PDDA/ammonium chloride solution (1250 ml total) was mixed with 6Q of methanol. White solids precipitated. The mixture was stirred overnight. The pre-cipitate was filtered off and slurried with 4Q of methanol for three hours. The crystalline product was filtered, washed with methanol, and dried in air. The yield W2S 203 grams of 92.4% PDDA, or a 62% recovery.
o EXAMPLE 10 A 39.2g portion -`(0.2 mole) of 50% sulfuric acid followed by 5 ml of concentrated (95.7%) sulfuric acid was added to 62.6g (0.1 mole) of 39.3% HYPDANa2. The resultant solution was allowed to stand for a few days to slowly evaporate. Crystals formed during this standing period.
The crystalline product was filtered off, washed with a small amount of H2O, and dried at 50C. A 14.3g yield was obtained and was shown to be 97.3%. PDDA sulfate, i.e., PDDA H2SO4, having the formula ). CH2 NCH2COOH

: CH2 ~ NCH2COOH

Recovery was 50~ of theory.

An 18.0g (0.2 mole) porllon o 1,3-dlamino-2-pro?anol was added to a reaction zone and diluted to about 40 ml with water. 13.8g (0.2 mole) of 44~ .ormaldehyde solution was -'ed into the aqueous amine solution in-said reaction zone over a period of four minutes at 30 to 70C. The thus formed mixture was allowed to cool with stirring over 15 minutes to 47C
and was analyzed by gas chromatography. The gas'chromato~ram showed that the major component of the mixture was not 1,3-diamino-2-propanol but a formaldehyde adduct of it, namely, 5-hydroxyhexahydropyrimidine, H
, I
f ~IO C~I l H2 C~2--- -- W

EXA~PLE 12 The thus analyzed reaction mixture of EXAMPLE 11-above was further reacted with 34.0g (0.41 mole)' of 68.;%
-; glycolonitrile, fed into the reaction zone o~er 6 minutes at 47 to 58C. The resultant mixture was heated at 45 to 55C
for almost three hours and then cooled to 25C. ~he -inal reaction mixtu-e, a yellow solutlon, was analyzed by gas - chromatog_aphy. The major component was found to be the ~'' product 5-hydroxyhexahydropy~imidine-1,3-diacetonlt-i~
(EYPDANOL), 1~)88069 C~2 EXA~PT~ 13 The HYPDANOL obtained in Example 12 was saponified Q in 34.4 g (0.43 mole) of 50% NaO$ diluted with about 100 ml of water at 99-105C. Th~ ~YPDANOL solution was added portion-wise to the hot caustic solution over 15 minutes, and the re-sulting hydrolyzed mLxture was boiled at atmospheric pressure until substantially all by-product ammonia had been vaporized (about l_S hours). Water was added during the boil-o,f period to maintain volume. The fin21 weight of the yellow solution was 146.1 g.
A small portion of the above prepared ammonia-free solution was taken for analysis; the major portion of said solution left for further processing into a very stable, iron-specific chelating agent. An attempt was made to ti'rate - a small portion of the ammonia-'ree solution wi.h copper ~II) chloride at pH 9. Like HYPDANa2, this solution did not chelate copper (II). However, like HYPDANa2, CH2O was released at pH
6.0, and the solution chelated copper (II). The soai2m sal' was disoaium 5-hydroxyhexahydropyrimidine-1,3-diacetate . ~, (HYPDA-OLNa2), CH2COONa ) CH2 N

C~2 Ci~C~ONa.

1~198069 Titration of a weighed portion of this EYPDA-O~a2 with copper ~ chloride at p~ 6 using a copper ~ selective electrode established that conversion (one pass yield) of 1,3-diamino-2-propanol to ~YPDA-OLNa2 was 96.7% of theory based on the starting amine. A gas chromatogram of the acidified, dried, and silylated product showed that ~YPDA-OLNa2 is the principal component of the hydrolysis mixture.

A 74.1 g portion (1 mole) of 1,3-propanediamine can O be fed into 50 ml of water in a reaction zone. The resulting aqueous solution of the amine will become hot (reaching a temperature of about 60C as it is formed~. Said mixture can be cooled to 50C and a premix of 204.6 g (3 moles) of 44~ formaldehyde and 84 ml (2.1 moles) of ~CN (which has been stabilized with 0;4 g of 85% H3PO4) having a temperature of 15C can be added thereto over a period of 1 1/2 hours. The temperature of ~he mixture in the reaction zone increases as the formaldehyde and HCN are added thereto. Said temperature can be allowed to reach a maximum of 70C. Within a few

3 minutes of the end of the premix feed, white crystals of the nitrile prod~ct will crystallize exothermally. The mixture from which ~he crystals precipitate (with the crystals therein) can be stirred for 2 hours while maintaining it at 60-70C;
- then the mixture can be cooled to 25C, filtered, and he separated nitrile crystals can be washed with cold water.
The washed nitrile can be dried in air or at 50C. ~bout 138 g Oc product (HYPDAN) corresponding to a conversion (one pass yield) of 85% will be obtained.
~rom the above examples and procedure, it is readily seen that in the preparation of ~YPD~N, glycolonitrile is eauivalent on a mole-for-mole basis to 1 mole of fo~maldehvde plus 1 mole of ~CN.

~01g8069 The method of ~xample 5 can be used to prepare other alkali metal and al~aline earth metal hexahydro~yrimldine-1,3-diacetates by replacing sodium hydroxide with the same number of equivalents of potassium hydroxlde, lithium hydroxide, barium hydroxide, or calcium hydroxide, for example, in the saponification of ~YPDAN.

The p~ of the ammonia-f-ee EYPDANa2 solution pre-O pared in Example 5 can be adjusted to pH 3.8 by adding concen-trated hydrochloric ~Cl acid (ca. 37.5~ HCl) thereto.
The resultant solution can be concentrated by evapor-ation to yield a slurry of the major part of the sodium chloride in a PDDA/C~20 solution. The sodium chloride can be removed by filtration. Sodium chloride can be removed in this manner as many times as is practical by alternate concentrating and filtering. The final filtrate can be evaporated to near dryness and the residue recrystallized from hot water/methanol mixtures to yield the solid product on cooling. Said product can be O~ filtered off, washed with methanol, recovered and dried. The solid is PDDA (containing a minor amount of sodium chloride).

- PDDA can be precipitated from the p~ 3.8 solution of Procedure 3 by the addition of large amounts of methanol (10 times the volume of PDDA solution) to the PDDA/formaldehyde/-sodium chloride solution. The PDDA can be filtered off, washed with methanol/water mixtures, recovered, and dried.

The reaction o- a solution of 190 g (1 mole) of P3DA
with 80 g (2 moles) of sodium hydroxide can form a ~ s~ solu-tlon of disodlum 1,3-propanedlamine~ '-di~cet~.e. The add -tlon of 68.2 g (1 mole) o^ ~% o~n21dehvde .o szld f~-s_ solu-tion can form a second solution of 246 g (l~mole) of HYP3ANa2.

Various hexahydropyrimidine-1,3-diacetates of the formula given below can be prepared using the general me'hod of Procedure 5 by replacing sodium hydroxide with the same number of equivalents of another hydroxide:

. C~2 N

C~2 1~2 CH2COOM, where M is an alkali metal ion, 1/2 an alkaline earth metal ion, or an ammonium ion of the formula . . Rl-- N--R3 ` wherein Rl, R2, R3, and R4 is each independently hydrogen, lower ~ alkyl, or hydroxy lower alkyl.
- ~ PROCEDURE 7 - ~YPDANOL can be prepared from the 1,3-diamino-2-propanol/formaldehyde mixture (prepared according to the method of Example 11) by using the general method of Example 12 but replacing the glycolonitrile of ~xample 12 with an equivalent amount of formaldehyde and ~CN.

HYPDAN01 can be prepared directly from 1,3-diamino-2-propanol and a formaldehyde/HCN premix using the general me~hod described in ~rocedure 1, su?ra, wherein 1,3-diamino--- _3 10~ 69 2-propanol is substituted ror the 1,3-propanediamine of Procedure 1.
PROCEDURE g The method of Example 13 can be used to ?re?are other alkali metal and alkaline ea-th metal 5-hyd-oxyhexa-hydropyrimidine-1,3-diacetates by replacing sodium hydroxide with the same number of equivalents of potassium hydroxide, lithium hydroxide, barium hydroxide, or calcium hydroxide, or the like, in the saponification of HYPDP~OL.
L0 PROCED~RE 10 The method of Example 6 or 7 can be used to acidify .;
HYPDA-OLNa2 and to isblate 1,3-diamino-2-propanol-N,N'-di-acetic acid (HYDROXY-PDDA) therefrom, f H2 NCH2C
OOH
H
HO CH H

COOH.

:-'0 The method of Ex mple 8 can be used to form HYDROXY-PDDA dihydrochloride, HO C~ .2HCl H

C~2 NCH2COOH
HYDROXY-PDDA can be prepared therefrom using the methoc. o Example 8.
PROCED~RE 12 .0 The method O r Example 10 can be used to ?re?a_e .~YDROXY-PDDA sulfate, - 2~ -C~2 I CE~2C~
I H

~he reaction of a solutlon of 206 g (1 mole) of ~YDROXY-PDDA with 40 g (1 mole) of sodium hydroxide can be used to prepare a solution of the monosodium hydrogen HYDROXY-PDDA. Various other mono-salt hydrogen 1,3-diamino-2-propanol-N,N'-diacetates of the formula given below can be prepared by replacing the sodium hydroxide with the same number of equivalents of another hydroxide:

. 1~2 NCH2COOH
.;, HO _ C~
- I H

CH2--NCH2COOM~

wherein M is an alkali metal ion, 1/2 an al~aline earth metal, or an ammonium ion of ~he formula -- IR2 --+

Rl _ N - R3 in which Rl, R2, R3, and R4 is each independently hydrogen, lower alkyl, or hydroxy lower alkyl.

The reaction of a solution of 206 g (1 mole) o HYDROXY-PDDA with 80 g (2 moles) of sodium hvdroxide can be used to ?repare a solution of disodium HYDROXY-?DDA. The zddition of 68.2 g (1 mole) of 44~ for~aldehvde will ?rocuce a solution o- 262 g (1 mole~ o~ HYPD~-OENa~ -CH2COONa CH N
HO CH CH
CH N
I

CH2COONa Various 1,3-di~m;no-2-propanol-N,N'-diacetates and various 5-hydroxy-hexahydropyrimidine-1,3-diacetates of the Q formulas given below can be prepared using the method of Procedure 14 by replacing the sodium hydroxide with the same - number of equivalents of another hydroxide: -2 IC~2COOM and f~2COOM
I H fH - N
- ~O - CH HO CH CR

H CH2 - ~

C~2, N~2COOM CH2COOM, )^ where M is as defined in Procedure 13.

This procedure illustrates a method which can be used to prepare CH -- N
Cl H2 l H2 by t~ie reaction re?resented by tie equation ~1~88069 L~ 2 + 4C~2o + 8HCN ~ 2CN

_ (HYPDAN) wherein [ ~ -CH2 ~' a tetramer o~ 1,3-propanediamine and formaldehyde is used as starting amine:

98.0 g (0.24 mole) of said tetramer of 1,3-pro-pane-diamine and CH2O can be slurried in 125 ml of water.
42 ml (1.05 moles) of HCN can be fed in over 30 minutes from 25 to 55C. The resulting mixture is held at ;0-5;C
- for 30 minutes until most of the amine dissolves. A premix of 68.2 g (1.0 mole) of 44% CH2O and 42 ml (1.05 moles) of HCN stabilized with 0.2 g of 85% H3PO4 can be fed in over 30 minutes (65C maximum temperature). White crystals of the nitrile will precipitate within a few minutes of the end of the feed. The slurry can be stirred for 2 hours at 50-;5C
then cooled to 25C, filtered, washed with water, and dried at 50C. About 138 g (85% yield) of HYPDAN will be obtained.

- PROCED~RE 17 H ,~OH
H2C~ c ~ fH

2 ~ ~C i ~ CH2 H \~ / 2 H2 ~ OH

H~ ICH2 2 ~ ~ 2 HO~H
which elsewhere in this speci ication, is re~e~_ed ,o as - 3_ -~088069 r ~
HO 4 ~ .;
. n can be prepared by the general procedure of Krassig (Makromol. Chem., 1956, 17, 77-130 (at 87-88)) wherein said general procedure is modified by replacing the 1,3-,~10 propanediamine of Krassig with an equal molar amount of 1,3-diamino-2-propanol.

The general method of Procedure 16 can be used to prepared HYPDANOL wherein said general method is modified by replacing the [~N-CH 2 of Procedure 16 with N N-CH

H
_ _ 4 which can be prepared according to the method of Procedure 17.
As used herein, the term "ml n means milliliter or milliliters.
As used herein, the term "g" means gram or grams.
As used herein, the term "mole~ has its generally accepted meaning, a mole being that quantity-of a substance which contains the same number of molecules of the substances 10~3069 as there are atoms in 12 g of pure 12C.
As used herein, the term "~ercent (%)" means pa-ts per hundred, and the term "parts" means parts by weight un-less otherwise defined where used.
As used herein, t~e term "water solu~le alcohol n means an alcohol (including a diol or a polyol) whïch is miscible or substantially miscible with water in all proportio or in substantially all proportions.
As used herein, the term "equivalentn as applied to ! lo alkali metal or alkaline earth metal hydroxide means that quantity of hydroxide which will provide 17.007g of hydroxide ~ ' ions.
; I As used herein, the term "equivalent" as applied to an acidic ion exchange resin means that amount of the ion i exchange resin which will provide 1.008 g of hydrogen ions.
! A stoichiometric amount of sodium (or potassium) hydrogen carbonate based on PDDA dihydrochloride or HYDROXY-PDDA dihydrochloride is 2 moles of the sodium (or potassium) I hydrogen carbonate per mole o~ such dihydrochloride.
' 20 A lower alkyl group is an alkyl group having about 1-7 carbon atoms, and a hydroxy lower alkyl group is a lower alkyl group in which one of the hydrogens has been replaced by a hydroxy (-O~) group.
As used herein:
- nPDDA" means N,N'-dicarboxymethyl-1,3-propane2i~m;n~
diacetic acid.
"HYDROXY-PDDA" means N,N'-dicarboxvmethyl-2-hydroxy-1,3-propanediaminediacetic acid.
"~YPDANa2" means d sodium hexahydro?v-lmidir.e-1,3-- 30 diacetate.
"~YDROXY-h~ DANa2" and "hYPDA-OLNa2" mear.s d s~dil~m ~-hydroxvhexahydropvr~midine-1,3-diacet~te.

10~8069 "~YPDAN" means hexahydropyrimidine-1,3-diacetonitrile.
"HYPDANOL" means 5-hydroxyhexahydropyrimidine-1,3-diacetonitrile.
"HYPDA-OLNa2u means disodium 5-hydroxyhexahydropyr-Lmidine-1,3-diacetate.

','LO

Claims (2)

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

1. A compound having the formula:

2. A process for preparing the compound of Claim 1 comprising admixing in an aqueous medium: (a) 1,3-diamino-2-propanol; and (b) an amount of formaldehyde effective for forming said compound and maintaining the resulting admixture at a temperature effective for forming said compound for a period of time effective for forming said compound.