CA1097641A - 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 hexahydropyrimidine-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 metal 5-hydroxyhexahydropyrimidine-1,3-diacetate which, in turn, is reacted with acid to form the desired HYDROXY-PDDA and formaldehyde.

Description

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BACKGROUND OF THE INVENTION
This invention is in the field of; (a) N,N'-dicar-boxymethyl-1,3-propanediamine, which has the formula CH 2~NCH 2 COOH
H

CH2 ~NCH2COOH, which is sometimes called 1,3-propanediamine-N,N'-diacetic acid and which is designated PDDA; and (b) N,N'-dicarboxymethyl-2-hydroxy-1,3-propanediamine which has the formula HO-CH H
I H

CH2 -NCH 2 COOH, which is sometimes called 2~hydroxy-1,3-propanediamine-N,N'-diacetic acid and w~ich is designated HYDROXY-PD~A.
More particularly, thi~ invention is directed to 10 an improved process for preparing PDDA of high quality by an improved route involving the following sequential reactions:

.

H2N (CH2) 3NH2 ~ 3 C:H20 + 2 HS:~N ~ Q + 3H20 (hexahydropyrimidine-1,3-diacetonitrile) (HYPDAN) ,, ~ ,.

~76~1 CH2CN CIH COONa C N, ~ 2 NaOH + 2 H2O r~ + 2 NH3 CH 2 CH CH 2 COON a (disodium hexahydropyrimidine-1,3-d~acetate) (HYPDANa2) CH2COONa C N + 2H H2O ~ 2 /CH2CH
--~ HNCH2CH2CH2NH
CH2COONa (PDDA) + CH2O + 2 Na , This invention is also directed to HYDROXY-PDDA and to a process for preparing HYDROXY-PDDA of high quality by the follo~ing sequential reactions: i H2NCH2CHCH2NH2 ~ 3 CH2O + 2 HCN--~HO C ) + 3 ~2 (5-hydroxyhexahydropyrimi- ¦
dine-1,3-diacetonitrile) (HYDROXY-HYPDAN~ ¦
C 2C fH2COONa HO ~ ~ + 2 NaOH + 2 H20 ~ + 2 NH3 I N
C~I2CN CH2COONa (disodium 5-hydroxy-hexahydropyrimidine-1,3-diacetate) (HYDROXY-HYPDANa2 ) - CH2COONa CH2COOH CH2COOH

HO { ~
CH2COONa HNCH:21H ~H2NH + CH2O + 2 Na .
0~1 tHYDROXY-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.
Th~ preparation of fH2 - N

H

is taught by Titherly et al, J. Chem. Soc., 1913, 103, 330-340 (at 334).

The preparation of H
H2~ C`CH2 H2C ' ~ ~7 CH2 \C - N ~zC\ ~ ~z H2 N~ CH2 H2C~C H2 which, elsewhere in this specification, is referred to as ~ ~ N-C~ ¦

from formaldehyde and 1,3-propanediamine is taught by Krassi~, Makromol. Chem., 1956, 17, 77~130 (at 87-88).

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The process of the instant invention constitutes a decided improvement over prior art routes to PDDA. Amoung the advantages of the process cf the instant invention are;
(a) the fact that PDDA formed b~ the method of this inven-tion is free of side products; (b) the by-products (NH3, formaldehyde, and an alkali metal salt, e.g., sodium or potasslum chloride or sulfate) are readily separated from the respective intermediate or final product with which the by-product is formed; (c) the use of objectional or incon-`10 venient materials such as anhydrous HCl and hydrogenation catalysts is avoided; and (d) the final product is sub-stantially pure PDDA which is obtained without resorting to the expensive and inconvenient repeated decantations and crystallizations of the prior art.
SUMMARY OF THE INVENTION
In summary this invention is directed to a nitrile having the formula CH - N ~2-- N
1 2 1 ~ l CH2 lH2 orHO - f~ l H2 ~ C~2-- N CH2 N
CH 2 CN CH 2 C:N
.` ~
DESCRIPTION OF PREFERXED EMBODIMENTS
In one preferred embodiment ("Embodiment A") this '0 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 mo~e ratios of amine to formaldehyde to 76~

HCN are 1 r 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-pro-panediamine or 1,3-diamino-2-propanol are 2:1 or 2:0.9-1.1.
It is generally preferred that the mixture formed by admixing the amine, formaldehyde, and HCN or glycolonitrile be prepared at 45-70~C (or 50-60C) and maintained at said temperature to form the nitrile. However, excellent results have been obtained where said mixture was prepared at 20-80~C
and maintained at 40-60C to form the nitrile. It is generally preferred to maintain said mixture at 50-60C (or 55~60C) for 1-5 hours (or ~-4 hours) to form the nitrile.
In another preferred embodiment ("Embodiment B") this invention is directed to a salt havlng the formula CH2COO~ CH2COOM

N lCH2 N

lH2 lH2 orHG _ CH2 fH2 CH2 ~ N C~2 N

in which M is an alkali metal cation (e.g., sodium or potassium) or 1/2 of an alkaline earth me~al cation (i.e d I barium, stront-ium, or calcium), or an ammonium ion having the formula - l2 Rl - N R3 R~

where Rl, R2, R3 and R~ is each independently selected from a ~0 group consisting of hydrogen, lower alkyl, or hydroxy lower alkyl.

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In another embodiment ("Embodiment C") this lnvention is directed to a process for preparing the alkali metal and alkaline earth metal salts o~ Embodiment B, said process com-prising hydrolyzing the nitrile of the above Summary in an aqueous medium with an amount of an alkali metal hydroxide (e.g., sodium or potassium hydro~ide) 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 earth metal hydxoxide 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 results at about 95-110C. Where using temperatures above the normal boiling point of the reaction mlxture in which the hydrolysis occurs, an apparatus designed to conduct khe hydrolysis under super-atmospheric pressure can be used. However, this is not necessary because excellent results have been obtained where conducting the hydrolysis at the normal boiling point of th~
mixture in which the nitxile is being hydrolyzed. Residence 0 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 generally preferred. It is preferred to boil the mixture in which the hydrolysis occurs until said mixture is free of by-product ammonia.
In another preerred embodiment ("Embodiment D") this invention is directed to a process for forming an acid selected from a first group consisting of I H lH2 ~ NCH2COOH

F I and HO --CH

comprising:

64~

(a) forming a nitrile selected from a second grou?
consisting of CH CN

lH2 CH2 and HO - - CH CH2 by admixing, in an aqUeQus medium formaldehyde; (i) a member `10 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:amino-2-propanol, to form a resulting admixture and maintaining the resulting ad- -mixture at a temperature effe tive for forming the second group member for a time eff~ctive for forming the second group mem-ber, the formaldehyde, the third group member, and the fourth group member being admixed in amounts effective for forming the second group member;
(b) hydrolyzing said nitrile in an aqueous medium '0 with an amount of an alkali metal hydroxide or alkaline earth metal hydroxide effective for hydrolyzing the nitrile to ~orm a salt selected ~rom a fifth~group consisting of ;:
~ ~ CH~COOM : CH2COOM

: CH~ N CH - N
I ~ I 1 2 CH2 lH2 or HO ~- CH fH2 CX2 . - N CH2 - - N

in which M is an alkali metal ion or 1/2 of an alkaline earth o ~ metal cation (e.g., 1/2 Ba+ , 1j2 Sr~ , or 1/2 Ca+ ); and (c) converting said salt to the acid having a formula :

~L~Q76~

CH2 or ~ CH
I H I H

by treating said salt in an aqueous mediurn with an amount of a mineral acid or an acidic ion exchange resin effective for forming said first group member.
The ~ixture formed by admixing formaldehyde, HCN, and the fourth group member (or formaldehyde, s-l-ycolonitrile and ~10 fourth group member) is preferably prepared at 45-70C (or 50-60C) and malntained at said temperature (or at 55~60C) for 1-5 hours (or 2-~ hours) to form the second group member.
Sodium hydroxide is a preferred alkali ~etal hydroxide for use in the process of this embodiment. An 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 u~ing 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 ~0 at-about the normal boiling point of~the aqueous mediwn in which the hydrolysis is conducted. However, lower temperatures (e.g., 90-100C) ~have given excellent results, and excellent re~ults can be obtained~at higher temperatures (e.g., 110-120C) where using a pressurized system. It is generally preferred to boil the aqueous medium in which the hydrolysis of the nitrile i~ belng (or has been~ conducted until said mediurn is sub-stantially free of by-product ammonia.
In general it is preferred to use 2.0-2.5 (or 2.0-2.05) moles of a monoprotic acid or 1-1.25 (or 1-1.02) moles of a diprotic acid per mole of the fifth group mem~er to convert said fifth group rnember (the aforesaid salt) to the first group member. Hydrochloric acid is a preferred mineral acid. Where _ g _ using an acldic ion exchange resin to canvert the fi~th group member (the salt) to the flxst 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 group member.
Where treating the fifth group member (the afore-said salt) in an aqueous medium with hydrochloric acid to form the first group member (the acid of this invention), it is often advantageous to use an excess of hydrochloric acid (pre-fexably added as concentrated (e.g.,.33-40% HCl) aqueous hydro-LU chloric acid solution) to precipitate the product acid (first group member) as a dihydrochloride salt having the formula CH2 ---NCH2COOH 2 1C~2COOH
¦ H I H
CH2 .2HC1 or HO - CH .2HCl I H ¦ H
CH2 ` NCH2COO~ ' CH2 NCH2COOH

In other words, the salt (the fifth group member) which is present as an aqueous solution is treated with an amount of hydro~hloric acid effectlve for forming and precipitating a . sixth group mem~er (a hydrochloride having the formula ~ ~ fH2 - NC~2COOH I H
CH2 .2HCl :or HO - CH .2HC
J
: CH2 _ ~NC~2COOH CH~ - NCH2COO~ /

Excellent results have been obtained where pro~iding 4-8 (or 4-6) moles of hydrochloric acid per mole of fifth group member ~the aforesaid salt).
The above-mentioned sixth group member (said hydro-chloride) can be converted to the first group mem~er (an acid having the formula O CH2 NCH2COOH fH2 ' NCH2COO~ ~
CH or HO - CH

CH2-- ~CH2COOEI CH2 - - NCH2COOH
,~ -! ' ~a7~

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

1H2-- NCH2CH C~2 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 constituted about 75 95% (or 90-95~) of the aqueous medium after ~he first group member had been precipitated therefrom. I
The first group member of Embodiment D can be con~ ¦
I

verted to the sixth group member - ~he 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 first group member.) In another preferred embodiment ("Embodiment E") this invention is directed to an acid havlng the formula CH2-NCH25~H
I H

CH2-NCH~COOH

~L~97~

and to a hydrochloride of said acid, the hydrochloride having the formula OH - CH .2HCl ¦ H
C~2 NCH2COOH.
In another preferred embodiment of this invention ~"Embodiment F"), which is equivalent to the embodiment recited in theabove Embodiment A, the procedure of step "(a)" of Embodiment D, supra, was modified by:
1. Admixing in an aqueous medium 1,3-propanediamine or 1,3-diamine-2-propanol and formaldehyde, the amine and the formaldehyde beins admixed in an amount effective for forming a compound having the formula

2 CH -N-H
1 2 ICH2 or HO-CH CH2 CH2-N-H CH -N-H.
~ 2. Admixing in an aqueous medium; (aj the compound having the formula CH -N-H CH -N-H

CH CH or HO-CH CH
2 1 2 1 ~ 2 CH2-N~H CH2 N-H ; and (b) formaldehyde plus HCN the equivalent thereof (e.g., glycolonitrile which is equivalen~ on a mole~for-mole b~sis to formaldehyde plu5 HCN), said compound having the formula CH -N-H CH -N-H

30CH2 ~H2 or HO-CH CH2 C~2 ~ CH2-N H, : - 12 -,~

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said formaldehyde, a~d said HCN being admixed in amounts e~-fectlve ~or forming a nitrile ha~ing the formula IH2CN f~ 2CN

CH2 lH2 or HO _ - CH lH2

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 step "b" of Embodiment D. The thus formed salt can then be used in step "c" of said : Embodiment D to form the first group member of said Embodiment .
We have obtained excellent results with this pro-cedure (the procedure of Embodiment F) by admixing the amine and formaldehyde in a mole ratio o~ 1.5 ~or 1:1~0-1.05) and maintaining the resulting mixture at abou~ 50-70C (or 55-65C) for about 0.25-16 hours (or 0.5-1 hour).
We have also obtained excellent results with this proceduxe (that of Embodiment F) by admixing the compound ~ hav~ng the formula : CH -N-H CH~-N-H

2 C~2 or HO-CEI CH?
:.~ I I I I
CH2-M-H CH -N-H , the formaldehyde and the HCN in a mole ratio of 1:2.0-2.5:
2.0-2.5 (or 1:2.0-2.1:2.0-2.1) at about 45-70C (or 50-60C) ~,0 and maintaining the resulting mixture at 40-60C (or 55 60C) for about 1-5 hours (or 2-4 hours) to rorm the aforesaid nitrile. Alternatively, the formaldehyde and HC~ can be ~ - 13 -a7~

replaced with glycolonitrile which is equivalent to formaldehyde plus HCN.
In another preferred embodiment ("Embodiment G") this invention is directed to a process for forming a nitrile having the formula CH2~N

comprising mixing: (a) a tetramer of 1,3-propanediamine 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 HCN are 1:3.2-4.8:7.2-8.8. Glycolonitrile, (one : mole of which is equivalent to one mole:of formaldehydr plus one mole of HCN) can be substituted on a mole-for-mole basis for HC~ plus formaldehyde. A preferred reaction temperature is about 45-70'C and a preferred residence (reaction) time is about 20-90 minutes (or 25-40 minutes).
A nitrile ha~ing the formula 3~ HOCH ICH2 ~ 14 -, ~7~

can be formed by substituting a te~ramer or 1,3~diami~o-2-propanol for the tetramer of 1,3-propanediamine in Embodiment G. (See Procedure 17.) In another preferred embodimen~ ("Embodiment H") a product salt having ~he formula C~2COOM CH2COOM

~CH2 N CH - N

ICH2 ~H2 or HO ~H lH2 in which M is an alkali metal cation, 1~2 of an alkaline earth metal cation, or an ammonium ion having the formula 2 +

l ~ I R3 : in which each or Rl, R2, R3, and R4 is selected from a sroup 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 lH2 NCH2COOM
H ¦ H

CH2 or HO - CH
H ¦ H
CH2 NCH2COOM CH2 ~ NCH2COOM

and an amount of formaldehyde effective for forming the pro-duct salt.

:

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DETAILED DESCRIP~ION OF THE INVENTION
.
This invention is directed to the preparation OL:
ta) PDDA; and (b) intermediates on a route to PDDA from 1,3-diaminopropane, formaldehyde and HCN, 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, fo~maldehyde and HCN, tO the preparation or HYDROXY-PDDA, and to the preparation of said intermediates.
PDDA and HYDROXY-PDDA are useful for forming chelates 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 ¦ H H H ¦

~0 in which Z is H or OH~
Chelating compounds having the above formula are especially useful for chelating iron (Iron(III) and iron ~II)3. These chelating agents, their preparation, the pre-paration and- use of such iron chelates is taught in our copending Canadian Patent Application Serial No. 259,664 filed August 23, 1976 which ~is assigned to W. R. Grace Co .
The instant invention will be better understood by referring to the following specific but nonlimiting ex-0 amples and procedur~s. It is understood that said invention is not limited by said examples or by said procesdures all , ~7~

of which are offered merely as illustrations; it is also understood that modifications can be made without departins 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.
EXAMPL _ 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% ~ormaldehyde was fed into the aqueous amine sclution m 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 50~C in the reaction zone 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 ~emperature being maintained ~ at 45 to 55C. The clear, colorless solution was stirred Z0 an additional 1 3/4 hours and allowed to stand overnight.
When the straw-colored soluti~n was agitated on the next day a mass of white crystals formed. The mass was brokPn up, added to water, stirred, and filtered. After re-slurrying twice in 500 ml portions of water, the collected product was dried at 45-50C. 63.6 g of product (nitrile) corresponding to a conversion (one pass yield) of 38.3% was obtained.
A small sample of ~he above prepared nitrile was taken for analysis. This aliquot was titrated with perchloric acid in glacial acetic acid. A monoperchlorate salt was formed during the titration. The results of this titration ~ C37~

showed a molecular weight of 164 v. a theoretical value of 164. The product was identified by gas chromatography and infrared spectroscopy as substantially pure hexahydro-pyrimidine-1,3-diacetonitrile (HYPDAN), I

CH N

.1 1 .
CH N

'10 EXAMæLE ~
A 370.5g portion (5 moles) of 1~3-propanediamine was fed into.250 ml of water in a reaction zo~e. 341.0g of 44% formaldehyde was fed into the aqueous amine solution in said xeaction zone over a period of 30 minutes while maintain-ing the temperature of the.resulting mixture at 50 - 63C.
The thus formed mixture was stirred an additional 40 minutes and allowed to stand overnight.

832.0g (10 moles) of 68.5% gl~colonitrile was added - thereto over 40 minutes. The temperature rose from 21C to 54C during the glycolonitrile addition. Half way through said addition, 275 ml of water was also fed into the reaction zone.
The rPsultant mixture wa~ s~irred at 50 - 57C for two hours, .
during which time crystals formed. An additional 250 ml of water wa dded to the mixture halfway through said 2-hour hold period. The reaction mixture was cooled over three hours to 23CI filtered, and the product crystals were washed with 125 ml of water~ The product was dried in air to give 694g of HYPDAN, corresponding to a conversion of 85%.

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A 74.lg portion (1 mole) of 1,3-propanediamine was fed into 50 ml of water in a reaction zone. The resulting aqueous solution of the amine which became hot (reaching a temperature of about 60C as it was formed), was cooled to 50C, and 68.2g (1 mo~e) 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 47~C in the reaction zone and a pre-mix of 136.4g (2 moles) of 44% formaldehyde solution and 84 ml (2.1 moles) of HCN (which had be~n stabilized with 0.4g of 85~ H3PO4) having a temperature of 15C was added thereto, ovex a period of 50 minu~es. The temperature of the mixture in the reaction zone increased as the formaldehyde and HCN
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 (wlth the cyrstals therein3 was stirred two hours while maintaining it at 50 -55C. The mixture was then cooled to 25C, fil~ered, and the nitrlle crystals were washed with~cold water. The re-; covered nitrile was drled at 50C. 138.5g of product (~YPDAN) corresponding to a conversion (one pass yield) of ~5% was obtained.
EXAMPLE 4~
A 148.2g port1on (2 moles) of 1,3-propanediamine was fed into 100 ml of water in a reaction zone. The resulting aqueous solution of the amine which became hot (reaching a temperature of about 60C as it was formed), was cooled to 23C, and 136.4g (2 moles) of 44% formaldehyde solution was -~76~L

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 a 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 ~one simultaneously from separate reservoirs over a period of 65 minutes while maintaining the temperature of the resultant mixture a~ 52 - 69C. Cooling was required twice dl~ring the 65-minute feed period. The reaction mixture was stirred at 58 - 69C for two hours, al~
though the reaction was essentially complete in l l/2 hours when analyzed. Product crystallized from the reaction mixture upon seeding with a small amount of ~YPDAN during the 2-hour hold period. The slurry was cooled to 20~C over 25 minutes and centrifuged and the collected product was washed with 65 ml of water from a spray nozzleO The product was allowed to dry. 277g (or 84% yield) of H~PDA~ crystals was obtained.

A 246g portion (1. 5~ moles) of the nitrile prepared in Example 2 was hydrolyzed by saponification with 552g (3.2 moles) of 22.8~ sodium hydroxide at about 100 - 106C. The resu1ting hydrolyzed mixture was boiled at a~mospheric pres-sur~ until substantially all by-product ammonia had been vaporized therefrom to form an ammonia fxee 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 ].ight straw-colored sodium salt solution was 851g.
A small portion of the above prepared ammonia-fxPe solution was taken for analysis leaving a major portion of -- ~0 --., 6~

said solution for fu~ther processing. An attempt was ~ade to ~itrate a small portion o~ ammonia-free solution with copper (II) chloride at pH9 but the product did not chelate copper (II). However, at pH 6.0, CH2O was released and the copper (II) ion was chelated. The sodium salt was disodium hexa-hydropyrimi~ine-1,3-diacetate (HYPDANa2), CH2COONa l H2 l H2 CH2 ~ N
CH2COONa .

Titration of a weighed portion of the ammonia-free sodium salt solution with copper (~I) chloride at pH ~
using a copper (II) selective electrode established that conversion (one pass yield) of HYPDAN to HYPDANa2 was 100~
of theory based on the nitrile charged. A gas chromatogram of the acidiied, dried, and silylaked product (HYPDANa~) showed that the HYPD~Na2 was substantially free of impurities.

The major portion of the HYPDANa2 solution prepared in Example S was diluted to 2 liters with water; the resulting aqueous system was acidified by passing I~ through a tube con-taining about 2.6 equivalents (17% deficiency) of Amberlite ; 200 ~ (a stro~gly acidic cation exchange resin). A 900 ml fraction of pH 2.8 to 4.1 product solutlon was collected from the bottom of the column. Said product solution smelled strongly of formaldehyde; such odor was not evident in the original sodium salt solution. The fraction was evaporated in air. When ~he fraction became syrupy, it was mixed with methanol. A solid product precipitated. The precipita~e was 76~
filtered off, methanol washed, and dried at 50C. An aqueous solution of the dried solid product chelated copper (II) at pH 9 (unlike the original sodlum salt solution) and at pH
6. Acid-base titxations, copper (II) titrations, gas chromato-grams, and an infrared spectogram showed the solid is 1,3-propanediamine-N,N'-diacetic acid (PDDA), CH2 ' NCH2COOH

C~2~ NCH2COOH

This pass yielded 106.8 g of PDDA, which is a 37.5% recovery.
The-remaining alkaline fractions were eluted with 1.5 liter f H2O.
The above mentioned alkaline fractions were run through the same column after the resin was regen~rated. 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 of P~DA, or a total of 63.6% recovery. ~ 1 litex fraction having a pH of 6 to 11 which was eluted with the aid of a dilute ammonia solution was also col}ected.
EXAMæLE 7 The resin in the column of Example 6 was replaced by Amberlite IRC 84 (a wealky acidic ion exchange resin). The final lQ alkaline fraction obtained in EX~MPLE 6 was passed through the new resin. The Amberlite IRC 84 ~ did not absorb the PDDA zwitterions as t2naciously as the Amberlite 200 ~.
PDDA was eluted with distilled water. An 850 ml fraction of pH 3.4 to 4.4 was collected and evaporated in air. PDDA was isslated as in Example 6.

810 ml of concentrated hydrochloric acid (37.5~ HCl) was added to 1,000 g of a 3~3% HYPDANa2 solution with stirring.
This resulted in the precipitation of white crystalline mate-rial which was identified as PDDA dihydrochloride, CH2 '- - NCH2COOH
I H
CH2 .2HCl I H

EXP~LE 9 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) ~as mixed with 6Q of methanol. White solids precipitated. The mixture was s~ir~ed 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 was 203 grams of 92.4% PDDA, or a 62~ recovery.
o EX~MPLE 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) o~ 39 3~ HYPDANa2. The resultant solution was al~owed 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 E2O, and dried at 50C. A 14.8g yield was obtained and was shown to be 97.3%. PDDA sulfate, i.e., PDDA H2SO4, having the formula ) CH2 NC~2CH
CH2 .H SO

! 2 NCH2COOH

76~

Recovery was 50~ of theory.
E~MPLE 11 An 18.0g (0.2 mole) portion of 1,3-diamino-2-propanol was added to a reaction zone and diluted to about 40 ml with water. 13.8g (0.2 mole) of 44~ formaldehyde solution was fed into the aqueous amine solution in-said reaction zone over a period of fo~r minutes at 30 to 70C. The thus formed mixture was allowed to cool with stirring ovex 15 minutes to 47C
and was analyzed ~y gas chromatography. ThP gas chromatogram showed that the ma-jor component of the mixture was not 1,3-diamino-2~propanol but a formaldehyde adduct of it, namely, 5-hydroxyhexahydropyrimidine, H
I

CH N

HO - ~ IC~2 IH2 . I

H

The thus analyzed reaction mixture of EXAMoeLE 11-: -above was fur~her reacted wlth~34.0g (0.41 mole) of~ 58.5~
glycolonltrile, fed into ~he reactlon zone over 6 minutes at 47 to ;8C. The resulta~t mixture was heated at 45 to 55C
for almost three hours and then cooled to 25C. The final reaction mixtu~re, a yellow solutlon, was analyzed by gas chromatsgraphy. The major component was found to be the product 5-hydroxyhexahydropyrimidine-1,3-diacetonitril~
~ (HYPD~NOL~, - 2~ -', , 7~4~

HO ~ - CH lH2 CH - ----N

EX~MPI,E 13 The XYPDANOL obtalned in Example 12 was sapsnified 0 in 34.4 g (0.43 mole) of 50% NaOH diluted with a~out 100 ml of water at 99-105C. Th~ HYPDANOL solution was added portion-wise to the hot caustic solution over 15 minutes, and the re-sulting hydrolyzed mixture was boiled at atmospheric pressure until substantially all by-product ammonia had been vaporized tabout 1;5 hours). Water was added during the boil-off period to maintain volume. The final weight of the yellow so}ution : was 146.1 g.
; - A small portion ~f the:above prepared ammonia-free ~ solution was taken for analysis; the major:portion of.said Ø ~ ~ sol~tion left for further~processing into a very:stable, iron-: ~ ~ specific chel~ting agent. :An~attempt was:made to:titrate a small porti~n of the ammonia-free solution~with copper (II) ohlor1de~at pH 9. Like HYPDANa~, this~solution:did~not chelate copper (II).: .~owever, like;HYPDANa2,:~CH2O-~was released at pH
6.0, and the.aolution chela~ed copper~ (II):. ~The soaium salt was disoai~m 5-hydroxyhexahydropyrimldine-1,3-diacetate (HYPDA-OLNa2)~

CH~COONa :
~ C 2 HO - I 2 ~ I

: CH2COONa.

76~

Titration of a wei~hed portion of this HYPDA-OLNa2 ~ith copper (IIl chloride at p~ 6 using a copper ~II) selec~ive electrode established that conversion Cone pass yield) of 1,3-diamino-2-propanol to HYPDA-OLNa2 was 96.7% of theory based on the starting amine. A gas chromatogram of the acidified, dried, and silylated product showed that HYPDA-OLNa2 is the principal component of the hydrolysis mixture.

A 74.1 g portion (1 mole) of 1,3-propanediamine can 0 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 HCN (which has been stabilized with 0.4 g of 85% H3PO4) having a temperature of 15C can be added thereto over a period o 1 lf2 hours. The temperature of the 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 0 minutes of the end o the premix feed, white crystals of the nitrile prod~ct will crystallize exothermally. The mixture from which the crystals precipitate (wi~h the crystals therein) can be stirred ~or 2 hours while mainta~ning it at 60-70C
then the mixture can be coolsd to 25C, iltered, and the separated nitrile crystals can be washed with cold water.
The washed nitrile can be~dried in air or at 50C. About 138 g of product (HYPDAN) corresponding to a conversion (one pass yield) of 85% will be obtained.
From the above examples and procedure, it is readily ~0 seen that in the preparation of HYPDAN, glycolonitrile is equivalent on a mole-for-mole basis to 1 mole of formaldehyde plus 1 mole of HCN.

The method of Example 5 can be used to prepare other alkali metal and alkaline earth metal hexahydropyrimidine-1,3-diacetates by replacing sodium hydroxide with the same num~er of equivalents of potassium hydroxide, lithium hydroxide, barium hydroxide, or calcium hydroxide, for example, in the saponification of HYPDAN.

The pH of the ammonia-free HYPDANa2 solution pre-0 pared in Example 5 can be adjusted to pH 3.8 by adding concen-trated hydrochloric HCl 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/CH20 solution. The sodium ch~oride 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 ~ecrystallized from hot water/methanol mixtures to yield the solid product on cooling. Said product can be 0 filtered off; washed with methanol,~ recover~d and dried. The solid is PDDA (containing a mi~or amount of sodium chloride).

PDDA can be precipitated from the pH 3.8 solution of Procedure 3 by the addition of lar~e~amounts of methanol (10 times the volume of PDDA solution) to the PDDA/formaldehyde/-sod~um chloride solution. The PDDA can be filtered off, washed with methanol/water mixtures, recovered, and dried.
PROCEDURE S
The reaction of a solution of 190 g (1 mole) of PDDA
with 80 g (2 moles) of sodium hydroxide can form a fi~st solu-tion of disodium 1,3-propanediamine-N,N'-diacetate. The addi-tion of 68.2 g (1 mole) of 44% formaIdehyde to said first solu-- 27 ~

7~

tion can form a second solution of 246 g (l mole) of HYPDANa2.
PROCEDU~E 6 Varlous hexahydropyrimidine-1,3-diacetates of the formula given below can ~e prepared using the general method of Procedure S by replacing sodium hydroxide with the same number of equivalents of another hydroxide:

OOM

0 C~2 l H2 CH2COOM, where M is an alkali metal ion, 1/2 an alkaline earth metal ionj or an ammonium ion of the formula R2 +

Rl - N - R3 . : 4 :

wherein Rl, R2, R3, and R4:is each independently hydrogen, lower alkyl, or hydroxy lower alkyl.;

: - HYPDANOL can be prepared from~he 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 Example 12 with an equivalent amount of formaldehyde and ECN.

HYPDANOL can~be~ prepared directly from 1,3-diamino-2-propanol and a form~ldehyde/HCN premix using the general method described in Procedure 1, supra, wherein 1,3-diamino-- 2~ -, 7~

2-pxopanol is substituted for the 1,3-propanediamine of Procedure l.

The method of Example 13 can be used to prepare other alkall metal and alkaline earth metal S-hydroxyhexa-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 HYPDANOL.

The method of Example 6 or 7 can be used to acidify HYPDA-OLNa2 and to isola~e 1,3-diamino 2-propanol-N,N'-di-acetic acid (HYDROXY-PDDA) therefrom, CH2 ~ NCH2COOH
H
HO ~ CH
I H
CH2-- N~H2COOH .

PROCEDURE ll:
20The method of Example 8:can be used to form HYDROXY-PDDA dihydrochloride, H
~O CH . .2HC1 l H
I

HYDROXY-PDDA can be pxepared therefrom using the method of Example 8.

30The-method of Example 10 can be used to prepare HYDROXY-PDDA sulfate, -- 2g --:. .
' 6~

CH2 ~ -- NCH COOH
I H
HO _ CH H 2 4 I
CH2 '- NCH2COOH

The reaction of a solution of 206 g (l mole) of HYDROXY-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 replaciny the sodium hydroxide with the same number of equivalents of another hydroxide:

¦ H
HO - CH
H
CH2 _ NcH2cooMl wherein M is an alkali metal ion, l/2 an alkaline earth metal, or an ammonium ion o~ the formula : R2 +

l - N - R3 in which R1, R2, R3,-and R4 is each independently hydrogen, lower alkyl, or hydroxy~lower alkyl.
PROCED~ Æ-14 : The reactlon of a solution of 206 g (l mole) of HYDROXY-PDDA with 80 g (2 moles) of sodium hydroxide can be used to prepare a solution of disodium HYDROXY-PDDA. The addition of 68.2 g (l mole) of 44~ formaldehyde will produce a solution of 262 g ~l mole) of HYPDA-OLNa~ -~7~

fH2COONa fH2 - I

CH N
CH2COONa PROCEDU~E 15 Various 1,3-diamino-2-propanol-N,N'-diacetates and . various S-hydroxy-hexahydropyrimidine 1,3 diacetates of the 0 formulas given below can be prepared uslng the method of Procedure 14 by replacing the sodium hydroxide with the same number of equivalents of another hydroxide:
CH2 NCH2COOM and CH2COOM
-I H fH2 - I
HO - CH HO CH. CH
~. .' ' I 12 1~ CH2 - N
CE~2--NC~2COOM : CH2COOM, O where M is as defined in Procedure 13.: :

Thls procedure illustra~es a method which can be used to prepare : CH2CN
: CH -~ ~ N

CH2 l H2 ~ CH2 - -- N

~ by.the reaction represented by the equation ' '' ' ~7~

rN N-CH + 4CH O + 8HCN --~ CH2C~
~ 2 2 C N + 4H2O

(HYPDAN) wherein ~ ~ -CH2~ , a tetramer of 1,3-propanediamine and formaldehyde is used as startlng amine:

98.0 g (0.24 mole) of said tetramer of 1,3-pro-pane-diamine and CH~O 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 50-55C
for 30~minutes until most of the amine dissolves. A premix of 68.2 g (1.0 mole) of 44% CH20 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 minu~es of the end of the feed. The slurry can be stirred for 2 hours at 50-55C
then cooled to 25C, filtered, washed with water, and dried at 50C~ About 138 g (85% yield) of HYPDAN will be obtained.

H~ ~ H
H2 ~C~ C ~ fH

'~ H2Cl-- ~C~----lCH2 1~0~ ~ ~ C~
C /CH2 ~ ~ C OH

H2 C1 H2 ¦ 2 H2 ~H 1' ~--CH2 2 ~ ~ H2 which elsewhere in this specification, is referred to as - 32 ~

7~

L ~;

can be prepared by the genera]. procedure of Krassig (Makromol. Chem., 1956, 17, 77-130 (at 87-88)) wherein said general procedure is modified by replacin~ the 1,3-propanediamine of Krassig with ar equal molar amount of 1,3-diamino-2-propanol.
P~OCEDURE 18 The general method of Procedure 16 can be used to prepared HYPDANOL wherein said general method is modified by replacing the [~N-C~: 2 ]

of Procedure 16 with : ~ _ ¦N ~-CH~ ¦

,.
H :4 which can be prepared a~cording to the method of Procedure 17.
As used herein, the term "ml" means milliliter or milliliters.
-30 As used herein~ the term "g" means qram or grams.
As used herein, the term "mole" has its generally accepted me~ning, a mole being that quantity-~of a substance which contains the same number of molecules of the s~bstances - 33 -"

as there ar~ atoms in 12 g of pure l2C.
As used herein, the term "percent (~)" means pzrts per hundred, and the term "parts" means parts by weight un-less otherwise defined whexe used.
As used herein, the term "water solu~le alcohol"
means an alcohol (including a diol or a polyol) whïch is misci~le or substantially miscible with water in all proportio or in substantially all proportions.
i As used herein, the ~erm "equivalent" as applied to ¦ 10 alkali metal or alkaline earth metal hydroxide means that ¦ quantity o~ hydroxide which will provide 17.007g of hydroxide ions.
¦ As used herein, the term "equivalent" as applied to ¦ an acidic ion exchange resin means that amount o the ion exchange resin which will provide 1.008 g of hydrogen ions.
¦ A st4ichiome~ric amount of sodium (or potassium) hydrogen carbonate based on PDDA dihydrochloride or HYDROXY-1 PDDA dihydrochloride is 2 moles of the sodium (o~ potassium) i hydroge~ carbonate per mole o~ such dihydrochloride.
A lower alkyl group is an alkyl group having about 1-7 carbon atoms, and a hydroxy lower alkyl group is~ a lower alkyl sroup in which one of the hydrogens has been replaced by a hydroxy (-OH) group.
As u~ed herein:
"PDDA" means N,~'-dicarboxymethyl-1,3-propanediamine diacetic acid.
"HYDROXY-PDDA" means N,N'-dicarboxymethyl-2-hydroxy-1,3-propanediaminediacetic ac1d.
"HYPDANa2" means disodium hexahydropyrimidine-1,3-diacetate.
"HYDROXY-HYPDANa2" and "HYPDA-OLNa2" means disodiu~
5-hydroxyhexahydropyrimidine-1,3-diacetate.

~C37~

"HYPDAN" means hexahydropyrimidine-1,3-diacetonitrile.
"HYPDANOL" means 5-hydroxyhexahydropyrimidine-1,3-dlacetonitrile.
"HYPDA-OLNa2" means disodium 5-hydroxyhexahydropyr-imidine-1,3-diacetate.

Claims (6)

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

1. A nitrile having the formula or

2. A process for forming a nitrile having the formula or comprising admixing formaldehyde and a member selected from a first group consisting of ECN and glycolonitrile with a member selected from a second group consisting of 1,3-propanediamine, 1,3-dramino -2- propanol, , , and and maintaining the resulting admixture at a temperature effective for forming the nitrile for a time effective for forming the nitrile, the formaldehyde and the first and second group members being admixed in amounts effective for forming said nitrile.

3. The process of Claim 2 in which the second group member is 1,3-diaminopropane.

4. The process of Claim 2 in which the resulting admixture is formed by admixing the formaldehyde and the first and second group members at 45-70°C and is maintained at said temperature to form the nitrile.

5. A process for forming a nitrile having the formula or comprising admixing formaldehyde and a member selected from a first group consisting of HCN and glycolonitrile with a member selected from a second group consisting of and and maintaining the resulting admixture at a temperature effective for forming the nitrile for a time effective for forming the nitrile, formaldehyde and the first and second group members being admixed in amounts effective for forming said nitrile.

6. A process for forming a nitrile having the formula or comprising admixing formaldehyde, a member selected from a first group consisting of HCN and glycolonitrile, and a member selected from a second group consisting of and and maintaining the resulting admixture at a temperature effective for forming the nitrile for a time effective for forming the nitrile, the formaldehyde and the first and second group members being admixed in amounts effective for forming the nitrile.