Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
A~,,r~ .3~.3
A~kylam~nes having alkyl group~ of about 8 to 18
carbon atoms are well known in the literature as antimlcrobial
compound~O However, they posse~ detrimental dermatological
and toxicological properties ~Jhich prevent their practical
use on a large scale. On the other hand, they are o~ great
interest bec~u~e o~ their acces~ Lty and low pric0. Hence,
a~tempt~ were no~ lack~ng to f'ind simple deri~ative~ which
not only combine the ~ood antimicrobial ef~lcacy ~i~h good
der~al tolerance and ~avorable to~icological properties, but ~ .
can be also prepared economically. ~ .
A~ ob~ect o~ the pre~ent invention is the develop- :
ment of ~-aminocarboxylic acid amld~ which are the reaction
product o~ aliphatic amines h~ing a m~dium-long chain ~ ~
length with aminocarbo~yllc acids or their lactams, as well ~ ~ :
as their preparat~on, and thelr use as antimicrobial ~ub
~tance~.
I A further ob~ect of the present l~vention is the
j development o~ an ~-a~lnocarboxylic acid amide selected
; from the group consi~ting o~ compound~ o~ the ~ormula
R
R-- NH - CO - ~CH23m - N
_ _ j n R2 '
~'1
whereln R i5 an al~phatic hydrocarbon r~sidue having ~rom 10
to 14 carbon atoms sel~c~ed ~rom the group con~isting of alkyl
~, and alke~yl~ Rl and R2 are member~ ~elected ~rom th~ group
- co~si~ting of hydrogen, m~thyl~ ~CH2-CH20H~ -CH2~CHOH-CH3
.~
and ~CH~-CHOH-CH~OHy and m and ~ are integeræ from 1 to 10
~ and their tox~colog~cally-unob~ectable acld addi~ion ~alt~.
.~
,~ ,
~,~p',~1~"il,3~
Another ob~ect of the present invention i~ the
development o~ a proce~ for the production of the abo~e
w-aminocarboxylic acid amides.
A yet further ob~ect of t,he ~vention is the develop
ment of a proces3 for the prevention o~ growth and the des~ruc-
tion of mlcroorgani~m~ ~uch a~ gram-posl~ive bacteria, gram-
negative bacteria, ~ungi and algae by contacting the mi~ro~
organism~ with the abo~e ~ ~aminocRrboxylic acid amlde~.
A still further ob~ect o~ the ln~entlon i~ the
developmenk of antimicrobial compo~ition~ comprising the
above ~-a~inocarboxylie acid ami~e and phosphonate 3eque~ter-
ing agsnt~.
The~e ~nd other ob~ect~ o~ the inv0ntion will -~
become more apparent a3 th@ descrlption thereof proceeds.
It has ~o~ been fou~d that the above ob~cts hav~ -
been achleved by ~-amlnocarbo~yllc acld amide~ havi~g the
~ general formula
,,, ~ 1 /
~H - CO ~ ~CH2~ml ~ N ~
n ~2
in which R de~ignates a strai~ht-chain or bra~ch*d, saturated
or u~atur~ted aliphatic hydrocarbon re~idue hav~ng 10 to 14 ~- -
: carbon atom~, Rl ~nd/or R2 desi~nate hydrog~n, me~hyl,
CH2-CH20H~ -C~2 C~OH~CH33 or -CH2-CHOH-CH20~ and m ~d n ~:~
de~ignate integer~ from 1 to 10
More partlcularly, th~ ention relates to a~
-aminocarbox~lic a~d amlde ~ect~d ~rom the group con-
isting o~ compound~ of th~ for.mula ::
.
. ~ , . . . ..
.,.
;~ - 2 - ~
_ - / R
R - ~ - CO - (CH2)m N
~ _ n P~2
.,
wherein R i~ arl aliphatic hydrocarbon re~idue having ~rom 10
to 14 carbo~ atom~ ~elected ~rom the group con31~tlng of allcyl
a~d alke~yl, Rl ~nd R2 are members selected from the group
co~8i~3tine 5f hydro~erl, mekhyl9 -CH2-CH20H, -CH2-~HOH~cH3
~, and -C~?WCHOH-C~20H, and ~ and n are ixlteg~r~ ~rom 1 to 10
~,nd their toxicologically-wnobJectable acid addition ~al~s.
~ .
:~ The ~aminocarboxylic acid amides can be pr~
pared accordi~æ to the method~ o~ peptide chemistry kno~ ~::
10 ln the literature, as foP ex~mple:
.. ~ethod X
,
( CH2 ) m - COOH ~ Cbû-N~I- ( C~2 ~ COOH
.~ O t~ n~time~
.~ 1) C2EI~OCOCl . .,
, ~ , 2 ) NH~- (CEI2)m-COOH
CbO- ~ ~I ( CH2 ) m~ CC~ -OH .
to ~n+l )
:.
1) C~H~;OCOCl
2 ) R~
: .
.
~H2- L( ~N2 ~ C-~] ~ bO- [~H ~H~ ) m-CO] ~
~, ~ to (n~l) -
.. ~ ,. I
* CbO~l Y C~H5CH20COCl (benzyl chloro~ormate)
. :
: - 3 -
.-~ , -
The compounds according to the invention c~ also
be prepared starting with amines and lactonea or ~-chloro-
carboxylic acid chloride s .
Method II
~~C=O
R-NH2 + (CH2)m 1~ R~ CO-~C~I~)m-OH
~ SOC12
L + cl ~cH2)m-so~l - > R ~ ~o (cH2)m-cl ~ ~
NHRlR2
~ , ,;,,
R~ wC~- ( CH2 ) m~NRlR2 ~ICl
~ the above methode, R, ~1~ R2, n a~d m have the
above asi~gned values. The amine employed ln th~ abo~Te
reaction~ is an an~ne of the ~ormula
H2
wherei~ R ha~ the above~as~igned ~alues. ,Among such amine~
are dccylamine, u~decylami~e, dodec~lamine, tetradecylaDline,
~, undecenylamine ~ isotridecylamine . dodecex~ylamine ., the mi~ced
li amines derived ~r~m the natur~lly occurring ~atty acid~ of
.~ the 10 to-14 cs~,rboll range~ etc.
Special i~portance :is to be attrlbuted to the
: w-arnin~carboxyli~ aGid arnides ha~ing the general ~ormula
(CH ~1 ;1~ R
] ~n whlch Rg Rl3 R2 and n have the abo~e assigned 1~1ealllrlg3,
~ince one can prep~re the~e amides in a simple ma~er by . .
hsatlng the respectlve amlnes wlth -caprolactam.
.j .
'
''
, .
4~ _
~,
, ~ ~, ,, . .. ., , . -
, ,: ,. , , , ~
To prepare the reaction products of the amlnes with
~caprolactam, a melted mixture o~ ~-caprolactam and amine
o~ respective amounts def~ned by the magnitude of n are
heated together at a temperature o~ 230 to 250C under
nitrogen for reaction tlmes of 3 to 20 hours. A~ unreacted
amlne i~ distilled o~ under vacuum. The reaction product~
are obtained as water-clear meltæ ~hich upon cooling, solldi~y
to form solid pulverizable masses~ The~e powder~ can be
directl~ u~ed as an antimicro~ial agent.
E~ually good result~ are obtainable when the ~ree
minocarboxylic acid~ are replaced by thelr ~alt~ with
toxicologically unob~ectionable inor~an~c acid~ or organic
acids.' Acids ~uitable ~or forming ~uch 8alt6 are, ~or
example, hydrochloric acid, sulfuric acid, pho~phoric acid,
~ormic acld, acetic acid~ ~.actic acid, tartaric acld,
citrlc acid, tetrachlorophthalic acid~ tetrabromophthalic
acid, etc. Where the products according to th~ invention
are prepared by ~he reaction of respective am~ne~ with ~-
caprolactam, the c~lculated quantity o~ the above-named acids
or other ~uitable aci~s is stirred l~to the melt of th~
reactlo~ producks~ the melt ls allo~ed to solldi~y and then ~ -
pulYerized; or the de~lred quantity of wat~r is imm~dlately
stirr~d into the melt together with the acid~ ~d,thus9
the aqueous sol~tion o~ the resulting salt is obtaine~
`. dlrectly.
When the terminal-free ami~o group o~ th~ compounds
~`: ~hich have been prepared as de~cribed abova and haYe the
. general ~ormula
~` 3~ R - L~H ~ C0 - (~H2)m] n ~I2
.
:,
''
.... ~ , ; ;............ . . . . .
l3~
i8 caused to react with methylating reagent~ e~hylene oxide,
propylene oxlde and/or glycldol, khen, the product~ which are
obtained are compri~ed ln the general formula ln which R
and R2 bave the additional de~ignations mentioned above.
Thiæ variation in the compositio~ o~ the products m~ke3 it
pos~lble to strongly in~luence 30me propertie~, ~uch a~
~el~ng point~ solubllity~ di~peralbility, without cau~ing
an eæsentla7 change in the ant1microbial e~ficacy. The abov~
named reaction productæ o~ ~ caprolactam wlth the re~pecti~e
: 10 amlne~ are cau3ed to react with ethylene oxide, propylene
oxide, or glycidol in a m~nner kno~n per ~e in a mol ra~io o~ ~-
lol~l to 2.2 where elevated temperatures of 50C to 150C
are uæed. For the economical pr~paration o~ the ~ubstances
accordi~g to the lnventio~, it ha~ proven to be advantageouæ
- to e~fect the addition r~action immediately ~ollowing the
preparatio~ o~ the reaction product~ of ~-caprolactam with
I the amines without carrying out an lntermediate purification.
I Aæ to the a~inea which æerve aæ starting materiale for the
preparat~on of the ~-~minocarboxy~ic acid amldes accordlng to
1 20 ~he in~e~tion~ especially ~or the preparatlon of the reactlon
...... :.. -
produ~tis with -caprolactam~ these a~ines are products known --
, .~
the llterature. Bxamples of such ami~s are those d~
. cussed above, ~uch as decylamine, u~d~cylamine, undecylenyl-
-. amlne, dodecylamine~ tridecylamine, tetradecylamin~, as
well as ~g~tur~s ~hich have been prepared from acid ~i~ur~3
of corresponding chain length~ such as occur in ~atural oils.
The ~-i~minocarboxylic acid amides used as ~uch as
well a5 in the form of their alts show Yery good microbio-
static and microbiocidal activ:Lty with respect to gram-posi-
tlvs and gram-nsgatiYe bacteri~ and fungi as well as a
: ':
- ''' ~'
- .: . . ~
: .. . . . ... . .
. .
~ 3t~;;
good inhibltory ef~ect upon ~lgae. Because of their good
dermatological tolerance and low toxicity, these compounds
are excellently suitable ~or solvin~ variou~ technical pro-
blems of disinfection and preservation. Examples of such
potential appli~ations are, for ~xample, the use as disinfec~
tants in household claaners, ln industrial c~eaners ~or
food~tuff factories, ~airies, breweries, in disin:fectants for
hospital area~; the use for ~l~infection ~n cuatomary ~aundry
processes ~d in dry-cleaning; the use as a pre3ervative
for cosmetic~ and adhesives ba~d on cellulose, starch and
ani~al protein; the use as preservatlve for dispersion
dye~tuffs and ~e~al~working oil~; and in th~ treatmant of ~ -
process ~a~er for man~ di~ferent p~rpose~a ~uch as, for
example, in coolant circuits, swi~ming pools~ scrubbers for
air conditioning installations; as well ae th~ use a~ a
~eodorant ln deodorant ~oap~.
~i For use a-~ antimicrobial sub~tance~, the addition
products accordlng to the i~vention can be incorporated~ nto
liquid~ past~ or solid preparationæ. For this application,
; 20 qu~ltitie~ of these products amounting to Ool~ to 5% by
weight, preferably 0.5% to 3~ by weight, based on the total
weight ar~used. For application in the preservation or tr~at -~
ment o~ proc~ water, a ~uantity i~ used such thak 0.~ to
50 ~gm, preferably 1 to 10 mgm, o~ an ~-a~lnocarboxylic acid
amide according to the in~ention i charged per liter of the
industrial or proces~ water to be tre~ted. When the ~ub-
stance~ accordi~g to the ~vention are to be packa~e~ for
the varlou~ appllcation~, they c~n be com~ned with o~her ~:
, ,
a~ditive~, such as surface-active agent~g water ~oftener~,
ru~t preventatives, complex-for!ning compounds, thicke2~ers,
ba~e~ acids, perfumes~ foam inhibitors, solvent~, e~
.`i .
,;
- 7 -
~ .
The addition products according to the invention
~or the preservation o~ treatment of ~ndustrial and process
water arf advantageously applled in combination with p}lOS~
phonic acidæ or their water-~oluble salts serYing as complex-
form~ng or sequestering ag~ts.
Preferrea are e~pecially phosphonic acid3 wh~ch
form complexe~ with divalent metals ha~lng the following
formulae:
"
. O R3 0
11 1
p _ ~ - ~(OH)2 (I)
l3~I '''''"'''
in which R3 is phenyl or alkyl hav~ng 1 to 5 carbon atoms;
.~ .
~ l_,~ P(OH)2 (II)
! / - P(0~)2 ~
R5 11 :; .
~'. .....
in which R4 and R5 each are hydrog~n or an alkyl having
1 to 4 carbon atomsS and R6 i3 hydro~en or an alkyl with
1 to 4 carbon f~toms or phe~yl;
- . ~,
R~ - CXY O . :
N - CXY P~0~)2(III)
.!( ~ ~ 211 CXY
~'~, ' .': .
::.~ . . .; -
~ in which X ~nd Y e~chf~ar0 hydrogen or an alkyl haYing 1 ~o 4 ~.
:., . .. :
,carbon atom~ ~nd ~ i~ a ~ :
i 1 1 . . .
: - P(OH~2
~group or a group having the ~ormula~
.'
.~ -
',
~. .. , - , : :. - ~ , . . . .
:- , . .. :, .
;~ . . . ~ .
o
- CH2 - N ~ CXY - P(H)2
~ CXY ~ 11 (~)
or
O
Il
~ CXY ~ P(~)H)2 11
- CE2 - ~ ~ CXY - P(oH)2
CXY - CH2 ~n N
CXY - II (OH)2
. , ' ,
and
ll l8
(HO)2P ~ C COO~ ~IV)
H2C - COOH
in whlch R8 i5 hydro~n, methyl or a -CH2-CH -COOH.
, Suitable phosphonic aclds are, for example:
1 l-hydroxyetha~e-l,l-diph~phon~c acid
l-hydroxypropane-l~l~diphosphonic acid
l-hydroxybutane-l,l-diphosphonlc acid
~ 1-hydroxypentane-l,l~dipho~phonic acid
" l-hydrox~hexane~ diphosphonlc acid
Y , .
:~ l-hyd~oxy-l-phenylmethan2~ diphosphonic acid -- -
., , , ~ , .
l-amInoethan~ dipho~phonic acid ~ -
1 amino-l-phe~ylm2t,han~ iphosphonic acid
dlm~thylami~oethane~ dipho~phonic acid
, ., . ~.
I l-(dim~thylamino)butane~ diphosphonic acid
-: diekhyla~rlomethane~ dipho~phonic acid
.-,, .~
propylaml~omethane~ d~phosphoinc acid
butylamino~t~ane~ diphospho;~ic acid
'' :~' '
_ g _
. .
,-. . , . . j, . ~ -,, . ~: : :.
- - .
~6*~
am~ notrimethylenephosphonic acid
ethylenediam~ netetrame~hylenepho~phonic acid
die thylenetriaminepentame thylenephosphonic acid
amino-(2-propylene-2-phosphonic acid)
phosphonosuccinic acid
l-phosphono-l-methyl succinic acid, and
2-phoæphonobutane-1, 2,4~tricarbo:xylic acld .
The water-soïuble ~alts of the above-named phos-
phonic aclds are ~specially the alkali met~l ~alt~, tne
ammonium ~aïts, the lower alkylammonium ~alts and the lower
a~lo3amma~ alt~, such as sodium, pota s~um, ammonlum or
alkanol~mine 3alts. One can either u~e the individual ph~-
phonic acids or their mixtures. E~pecially ad~antageoua i8
a mixture of l~hydro~yethane~ d~ pho~phoni c acid ar~d amlno-
trimethylenepho~phonic acid in a weight ratio o~ 4:1 to 1:~.
The packaged preservatives ~or i~dustrial and
process water contain such amoun~s o~ the phosphonic acid~ :
or their water-soluble salt~ that per liter of the water to
I be treated, these quantities am~unt to from 0.2 mgm to 1 1~2
; 20 -time~ the ~uantity which ~s requlred to totally complex the
:~ .
hardne~ ~orming ions in the sys~em. The weighk ratio of ~.
the phosphoIlic acid component to the biocide component can
v~ry bet~een 1:10 to 10:1. Pre~erably, a weighlt ratio o~
3:1 to 1~3 is u~ed~ The water tre~Lted with the subst~ce6
according to the invention ~hould have a bioeide content ~ ~ .
`1 of bet~e¢n 0 . 5 and 50 gm per cubic meter and a cvntent of
pho~phonic acid o~ between 0.2 and 20 gm per cublc meter. ~ ~
.. When the addition products accordlng t;o the in~en- ~:
tion ar~ u~ed ~or water treatm~rlt, they can also be comb~ned ~;
30 w1 th corrosion-prev@ntln~ agent;s (inhibitors ) ~ Water-soluble
''/ '
.. .
, lLO _
. . . , . ~ .
. ~ :
... , ~, .... . .
.D
orthophosphates, such as monog di or trialkali metal phos~
phates are su~table :~or ~his purpose. Furthermore, water-
soluble zine salts, such as zinc sulfate as well as zinc
nitrate~ can be added ~nstead of the orthophosp~ates. HoweYer,
it ~ preferable to use the water sol.uble zlnc salts together
with the orthophosphates. Other i~hibitors which can be
used, lf so desired, are alkali metal nitrite~, such ~s
potassium nitrit~ or especially sodium n~trite. An addition
o~ alkali metal silicates, such as pota~sium 3~1icate or
sodium sllicate, can likewise be us2d a~ an inhibitor~ T~e
quantities of inhibitors added are 0.5 to 200 mgm per liter,
preferably 1 to 50 mgm/liter, The ind~vidual admixed ~ater-
lals can be worked up to form ~olid mixtures. However~
solutions can also be prepared from these mixtures by the
addit~on of the quantities desired ln each cas~ ~o the water.
There is no difficulty in adJusting thes~ products either by
the addition of an alkali metal hydroxide or car~onate or
by the ~holce of a ~uitable mo~o, di or triorthophosphate
so that at tbe sam~ time,.a certain pH regulation o~ the
treated water is accompli~hed3 in case thls ls desired
or required. ~ :
The combination o~ the addltion products ~ccording : -
to the i~vent~on with th~ phosphonic acid compone~ts has
variou~ adyantages. Amo~g th~m is an lncreased synergi~tic ~ :
a~ack o~ the biocide dir0cted a~ainst khe biological material.
This re~ults ln very ~ast degradation of the proll~erated
organlæm~. Conver~elyg the bioclde favoræ the di~persive
ef~ect o~ the pho~phonic acid compo~en~ as we l as the corro
:~ sion-preventing e~ect. The very lo~ do~ages of the phos-
phonic acid comp~nent as ~ell ~.8 of the biocide component
-- 11
' `,
-
3~ :
re~ult in a minimal load on the ~ewage mains. Through the
adsorptive bind~ng of the biocide component to the biological
material, a ~urther reductlo~ of the harmful material in the .. ~.
sewage main~ occurs, In add~tion, the bivcide component i3
biodeg~adable when diluted corre~pondingly.
The followlng example~ explain the i~vention in
more detall wlthout limiting th~ ~cope of the invent~on in
any respect.
~ X A M P L ~ S
For the tests o~ ~ntlmicrobial and algicidal
efficaey, a serles of pro~uet~ according to the invention
were prepared by the follo~J~ng proce~æ:
~XAUPr~ 1
Product A C1~25~ C-C~2~N~2 ~Cl~ ~ glycyl-dodecyl
amine hydrochloride. ~ -
Thls compound ~as prepared according to the proce~s
whlch wa~ deæignated above as Method II. In a~ autocla~e,
6.5 gm (0.025 mol) o~ N-dodecyl~chloroacetamlae were cau~ed
to react with 100 gm o~ liquid ammonia ~t room temperatur2 - :
1 20 ~or ~ive days. The colorle~ powder that remained after
: the exce~ ammonia had been distilled ofi~ waæ bolled wlth
ether and crystallized from ethano~. 3.1 gm o~ a colorl~s
I powder ha~lng a melting point o~ 98C to 112C was o~tained~
The yi~ld amo~nt~d to 45~ o~ the theory.
EXAMP~ES 2 AND 3
:
;. ~he ~ollowing additio~al cnmpounds were prepared :
eccordi~g to ths procese of Method II a~ deecribed ebove.
.
L
Product ~ Cl0~21~ CO- (CH2)2~ HCl, 3-am$s~oproplonic
ac~d-de cylamide .
Colorless powder, melt$ng point -- 1~5C to 15~C.
~oduct C: C12H25~ CO-(CH2)5-M(CH3)2, 6-(N~N-dimethyl-
am~o ) capronic acid-dode cylamide .
Colorless pCh~ der, melting point 48C to 50C.
EXAMPLE 4
}roduct D: C12~ CO-(CH2~5-NH2, 6 am~capronic
acid-dodecylam~de .
?O Thi~ compound was prepared ac~ordi~g to the process ~ .
.; . .
designated above as Method I. ~5 gm of benzyloxy~arbonyl- -
am:Lnocapronic acid-dodecylam:Lde in 300 ml o~ methanol were
hydxogenated in the presence of 5 gm o~ a 5~ PdiC catalys~
at a ~empera~,ure of 50C and a hyarogen pressure of 55 atm. - .
gauge for a period of 12 hours. After the catalyst had bee~
~iltered of~ the solution was concentrated under vacuum~
. a~d the residue was twice crystallized from benæene. B.3 gm --
o~ a colorless powder having a meltin~; poi~t of 70C to 85C
wa~ obtained. The yield amounts to 48~ of the theory.
ZO ~Y~2~ES 5 AND 6
., .
Th~ fOllOWi~lg additional compounds wer~ prep?red
acc:ord:lng ~o the process of Met~nod 3: a~ deseri~ed abo~
r ~ C12H25 - tNH-Co~(CX~35~ - ~2
Golorless powderg meltlng po~nt = 138C to 14~G. -
A~ i2~ermedlate product produced during the preparation, ;-
_ .- . ''. .
` ~ C~s-cH2-occ1-~H (cH2)~-co~NH 2 ~C12H25 , had a s~
~o~n~; .o~ 146~C ~o 151C.,
, ' ` ' .
,, ' ,
` - ~L3 - :
', - ~ ~ , 1
, , ." . ..
Product F - C14H2g~ C0- ( CH~ ) s-NH2
Colorle~f3 powder, m.p. = 95C to 120C. An inter~
- mediate product produced during the preparation,
C6H~-CH2-OCO~ (CH~)s-C0-NH-ClL~H2g, had a melting point
of 107 C to 110 C .
EXAMPLES 7 T0 15
The products of the general formula
L ~ n 2 ~ ~.
wherein m i~ 5, are o~ speclal interest ~lnce they can be ~,
10 prepared economically. For the preparation of these products,
1 mol of the re~pective amine and n mol~ o~ caprolactam ;
were heated under a 3l,1trogen atmosphere to 230 to 250C
for 20 hours while stlrring vigorou~ly. Sub~eq.uently, the ~:
, , .
unconverted amine was di~3tilled o~f under vacuum. The com-
poullds which were thu~ prepared and are liæted ln the follow-
., in~ Table I are color~ess to light-belg~ solid~ m~lting
, .,
over a wide ra~ge. I~ the ~ormulae, the lndices out~ide the
bracket~ (n) lndicate the mol~ o~ caprolac~am used per mol ~:
o~ a~ne. H~wever, ln the ease o~ the reaction products which
'`.! 20 are mixtures o~ oligosners ~ these indlces can assume the
.~ .
~r~lu~s 1 to 10.
, .
. I . .
:!
.
:~'
`~
~ - ~.4
: (
. ~ 1, , " , ~ , , "" , .",, , , : ' : ' '
. - .. . ... .. . .
, ~, .j . , . ~, ..... . . .
, , :,
T A B L ~3 I
,
Melting
P r o d u c t Ntltr. Point C
.. _ __ ......... . .. .. __ _ ..... . .
G ~lOM21-NH C0- ( CH2 ) 5-NH2 1~ 6~ to 75
H ClOH~ C0-~CH2)5] 2-NH2 3 4 75 to 125
I ClOE~21- [NH-~0-(~I2)5] 3-NH2 2.93 llû to 125
3 C12H2s~ 0-(C~2)5-NH2 1~.17 60 to 80
K C:L2~25~ [~H-CO-(CH~)5]2_N~2 3.30 75 to 85
L Cl2H2s- LN~I_CO (~2)5~ ~-~2 2.67 80 to 110
M C14H25 ~I-CO (CH2)5-1~H2 3 39 75 to 9
N C14H24~ C0-~cH2)5~ 2-~H2 3.16 80 to 130
C14E25'' LNH-CO~ ( CH2 ) 5] -NH2 2 . 55140 to 170
~ , ':" .':
.' '' . .
EXAMPIES 16 T0 19
., . . .~ .
`, For the preparation of prod~icts in which the
re~idues Rl and/Or R2 ~ the above ~en~ral formula can
designate -CH2-CH(0~-CH20H, the reaction product3 of
dodecylamine with ~-~aprol~ctam were caused to r~act with
glyeidol . For thi~ purpose g 1 mol of a react 1 on product of
-caProla¢tam and dodecylamin~ (the average molecula;r weight
20 of ~hi~h wa~ calculated from N~ r ) was melted. "p" mols of
glycidol were added to th~s melt at 80 to 140C and the
mixture wa~ stirred for an addi tional tT~o hours. Further
detail~s a~ to the reaction pro,îucts thus prep~red can be :- .
- found in the ~ollow:lng ~abîP I~
., .
:, .. . ~
3~
T A B L E I I
Starting Appearance .:
Product Product p ~ti tr . Of the Product . .
., ~ , . .. ~ .
P J 1. ~ 3 . 21 Bright, t~cky
wax
: Q J 2 . 2 2 . 76 Yellow, ten-
~clou~ s
R K 1.1 2.68 Col~rle~, :::
solid ma
S K 2. 2 2 .39 Y~llow,
" ~ "~ '
. ,
:: .
: . ,
EXAMPIæ 20
~ .. .
In order to mea~ure the a~tlmicrob~al efficacy of
. .
the above-named ~-amlnocarboxylic a~cid arn~des, their inhibi-
tcry e~ect upon the u~seq7len~ly listed bacteria an~ *ungi, -~
a~ well as upon the germ~ ~n contamiIlated procea~ water was
de~.e~mined.
,
~1) Staphylococcus aureus 5 x 107 organl~ms/ml
2) ~scherlchia coli 4 x 107
. 20 3) P~sudomonas aerugino~a 4 x 107
4) Candida albicans 2 x 10
5) A~pergillus niger 9 x 105
~) Mixtul7e O:e cox~ta~ninated water ,:
. ~roa~ 3 coollng tower~ -
~:. 7) Mixture s~ cotltablinated water
from 3 æcru~bsr~ o~ air c~
:~, ditiorling in3tallatlon~
.
. .
_ ii.6 ~ ~ ~
. ~
::.
.~ . , .. , ... - . - . . .
- . ~ - - -, . ~ . .
~he ~inimum i~hibltory concentrations of the pro-
ducts to be tested were determined by means of the dilution
test according to the ~tandards ~or the examlnation of chemi-
cal di~infectants which had been published ln 1959 by the
Deutsche Gesellschaft ~ur Hygiene und Mikrobiologie (German
As~ociatlon ~or Hygiene and M~cro~iology)~ The tests were
carried out ln test tubes which were ~illed with St~ndard-I-
Broth (~erck) or with ~eer wort ~8 Be) and diluted 1:5 ~rith
tap water, A~ter ~he addition of the active sub~tanees~ the
volume o~ the nutrient 501ution in the te~t tu~a~ was ad~ueted
to 10 ml. Mext, the test tubes were inoculated with 0.1 ml
test organlsm suspension~ In the case of bacteria, the in-
ocula-ted test tubes were incubated in the lncubator for 3 d~ys
at 37C and in the case of fungl, they lncu~ated for 6 days ~t
30C. Subsequently, the concentration o~ the compound added
to the nutrlent medium whlch w~s ~ust able to inhibit com- -
pletely the grc~th o~ th~ germs ~as ~etermined. The value
thus determined was designated as the minimum inhibltory
concentration (m.i.c. ~ . The followin~ concentration intervals
were used ~or the t0sts: 1,000 ppm, 7:~Q ppm, 500 ppm,
~ 250 ppm., 100 ppm, 50 ppm, 2~ ppm, 10 ppm, 7.5 ppm,
;`. 5 ppm, 2. 5 ppm, and 1 ppm.
The inhibitory concentrations of the indiv~ dual
product~ ~or the aboY~-quot~d germæ which ~ere determin~d
ln thla dllutlon test are llsted ln the followin~s Tsblo III.
` :
., .
- 17 -
1 . , . ,. ~ .
: ,.. , ... ~, - , . , :
~_ ~J L6~
:'
T A B L E
. . . . ~
::
Minimum Inhibitory Concentrat~ons
o~ the Product~ A to S in ppm
Used Test Germ or Te~t Product
~ . . ~ ,
., S~'.3.
~tance 1 2 3 4 5 6 7
. ~ .
100 500 50 100 25 25
B 50 50 100 100100 Za5 25 ::
.1 ~ 25 25 1000 100250 10 10 :~ ~
~ D 5 5 100 50 50 5 5 :
.~ 10 ~5 50 50 250 250250 25 25
.~ F 5 5 250 50 100 7 . 57 . 5
:' G 5 5 250 100100 ~-5 25
.~ }I 50 50 100 1~0250 25 25
I 100 100 250 250250 50 5
1' ~ 10 10 50 50 50 7 . ~7 . 5
¦ K 10 10 100 10 50 10 10
L 25 25 ~50 5 100 10 10
M 10 10 1000 50 lOû 10 10
. ~ N 10 ~ 0 500 50 50 7 57 5
. 20 0 50 10 1000 50 100 25 25
. ~ P 10 10 250 50 50 10 10 :
` Q 50 50 1000 ~0 lûO 25 25 ~:
5~ 50 5~00 100 ~ 25 25
S 50 .~liO01~00 50 50 2~ 25 ;
,1 ~
,j ,:
:~:
.,.
, ,~ . , ,
.
r~
.. . .
., I ~ ` , . , !
Table III consFincingly shows the strong inhibitory
ef:Eect exerted on the bacteria and fungl by the products
according to the inverlti~.
EXAMPI.T~ 21
The microb$cid~1 ef~ect o~ ~ome product~ nam0d
above was detern~ned by mear~s o~ the suspenslon ~st. The
methodology o~ th:i~ testing procedure has been taken ~rom the
standards ~or the te~ting of che~cal dlsln~ectants, publishQd
in ïg59 by th~ ~ern~n Association for Hyglene ar~d ~icrob~ology.
In eo~ormit:y with the~e ~tandard~, 0.1 ml of a test organ$~m
: ~uspension of the followlng enumerated bacterla or fungi wa~
pi petted into te~t tube~ at 18C to 2J JC.
1) Staphyloeoccu~ aureus 5 x 107 organi~ms/ml
2 ) ~sr.he~ichi~ coli 4 x 107
3) Pseu~omonas aeruginosa 4 x 1~7
,' The produets of the invention to be tested were
dissol~ed in tap water o~ 16d~ (German degrees of' hardness~
Then, 10 ~1 of the re~pective dilution ~uantity of the product
to be tested were add~d to e~ch teæt tube. The concentrations
o~ the product~ according to the i~Yention were 100 ppm~ 250 :
ppm and 500 ppm in each ca~e. After a duratlo~ of action
amou~t~g to 1~ 2.~ 5, 10, 20~ 30 and 60 minutes, a loop of ~ .
m~terial was taken from each test tubs and inoculated ln 10 ml
of nutrient ~olutlon ~hlch contain~d 3% T~e~n ~n~ 0.3~ Iecithin
; as de-iDhlbitors. Th~ nutrient solution~ inoculated with bac-
;:~ terla w~re incubated ~t 37C where~ the nutrient solutions --
inoculated with ~ungi were incubated At 30C. A~ter 6 days3 : ~-
~ ; ... ..
~, the gr~wth of the culture~ wa~ macroæcopically e~aluated.
. Thu~ the de~truction periods or ~.~erilizat~on time~ ~ere deter- ~
mined and are summ3rized in the following Table IV. ~ -
. . ~ '
, .
- ~1.9 - :
;,
~: , . : ~ . , .
. ~, . ,. - .. ; ,. , .
~ 3~
T A B L E I V
~ .
Tlme Periods in which the Products According to the Invention
Destroyed the Various Test Organism Su~pensions in Minutes
Concentration of the Products
in Tap Water
lOO ppm 250 ppm 500 Ppm
~ ,.
Substance Germ Sterilization Time in Minutes
~ . ~__
A 1 10 .5 5
~ 20 10 10
3 60 20 10
B 1 5 5 5
2 10 10 ~0
3 30 10 10
C 1 5 2.5 ~-5
2 ~0 5 5
3 30 10 5
J 1 5 2.5 2.5
2 ~ 5 2.5
. 3 40 10 2.5
K 1 60 30 5 10
3 60 ~0 3
P 1 2.5 2.5 2.5
2 ~ 2.5 2.5
3 10 5 ~5
Q 1 5 5 5
2 10 10 1
3 40 10 10
-
. .
The above Table IV clearly shows the very good
efficacy of the products of the invention in de~troying
1 both gram-positive and gram negative bacteria.
,~ : 30 EXAMPIE 22
:~ ~The efficacy in lnhibiting growth of algae was
determincd in cy~indrical vessels under int~nsi~ aeration.
I~to the vessels, there were introduced 100 ml of a nutrient
soluti~n to whlch increasin~ quantities o~ active substances
_ 20 -
,
, ~ , ~ . ,
.
, ~ .
,. ~ . .
had been addell as well as 4 ml of a mixed ~uspension of
Scenedesmus obliquus and Chlorella vulgari~.
The nutrltion solu~ion had the ~ollowing com-
poeition:
Gram~
Ammonium ~hloride 0,1
~; Sodium nitrate 1.0
Dipota~si~un hydro~s;en pho~phate 0.25
Magnesium ~ulf`at~., Cl'y8t; . O . 5
~i 10 Calcium ehloride 0.1
Iron- ( III ) chloride 0 . 003
:. .
These compo~ds were di~solved in 1000 ml of
distilled water. The p~I ~Tallle of the nutrlent ~olution was
,::
. 7.2. The tests were carriad out with the ~ollowi~ng concen~
, . , - . ,
tration interval~ o~ the active su~6tance: 10 ppm, 5 ppm, ~ :
. .
2.5 ppm, 2 ppm, 105 ppm, 1 ppm, 0.75 ppm, o.5 ppm,
a~d 0.25 ppm. The m~nimum i~hibitory concentration deter~
mined a~ter 7 days are summarized in the ~ollowing Table V~ ~ ~
:.1 T A B L ~ V ~ :
'~
`~!
~n~ ory
Sub~tance Conce~tration in ppm ¦
. ~ .: ':'
`: B 1 :
-75 :.
~, K 1
.. ....
P 1 .: .,;
2 . 5
`.`. ' - . - .
' : ~,-'
.. . . .
As the above Table V shows, the produc ts according
to the invelltion also ha~e an ex~ellent inhibltory effect on
algae .
EXAMPLE 23
~nibitioxl of the Growth f Su~a~
The minimum lnhibitory conceIltrations were determined
in 50 ml ~crew-top bottles. The bottles were charged wlth an
~ptimum nutrient ~oluti~n f`or the growth of sul~ate-re~ucing
bacteria ~3~i.,the ~ollowing composi tion:
~! 10 Grams
Sodium lactate 4.o
~east ex~ract 1.0 .
:, Ascorbic ac~d 0.1 .
Magne æium sulfate cr~st . o . 5
Dipotassium hydrogen phosphate 0.2 ~'
Ammonium ferric alum 0.1
Sodium chloride 2.0
which compound~ were dissolved in 1000 ml of distllled ~ater.
The pH value o~ the rlutrierlt solution was 7.4.
After va~ious concentratio~s of the product~ to be
`, te~ted had be~n addsd, 1 ml o~ a pure culture o~
;i De~ulfovibrio d~sulfuricans 6 x 105 organ~ s~
wa~ u~ed ~or ~noculation, follow~d by incubation at 37C ~or
4 weeks. The ~oll~ing concerltration interval~ were used
~: ~or the t~ts: 100 ppm, 50 ppm, 40 ppm, 30 ppm, 20 ppm, -
~, 10 ~pm, 5 ppm, 2 . 5 ppm, and 1 ppm.
~, In tbi~ test, the min:Lmum lnhibltory coD~centratiorls
listed ln the following Table VI ~ere d~termlned for the
~, individu0.1 products.
: .
~' .
.:,
- 22 -
,' i
- . . .
, ~
.~ .; ~, . , , : , ,
T A B L E V I
l:nhl bltion of the Growth of
De~ulfovibrlo De3ul~uricans
.; Inh~;bitory
Concentrati on
~ ,
B 5
C 2 . 5
J 5
K 5
p 10 -: ',
;
e _
~ , ~
Thi~ experiment al~o re~lects the excellent
efficacy o:E the su~tances accordin~ to ~he lr~vention.
~,. ., ,. ~. .
}~ 5E[E 24
The coolant circu~t of a ~team power station having
a volume o~ 6,000 m3 and an hourly f~ed supply oi 150 m3 as
w~311 as a turnover circulation of 119000 m3/h at about a 3-iold
~, conc2~tration was treated ~or 6 months w~th a mlxture of
:1l 20 l-hydroxy~harle~ diphospho~c acid an~ amirlotrimethylene- ~
pho~ph~lc a-~-id (in a ratio b~ w~ight of 1:1~. The qa~tity ~ -
'!` O ~ a~lti~ amounted to 4 mg/m3. Although good effcct~ as to
:1 ,
proteotio~ again~t cor~o~io~ and boiler scale were observ~dg
.j ~ di~turbances o~curred aeain and again caus~d by the growth
~ ~ o~ the conde~ssr with ~ orD~n~ bacteria. . ::
f .
~o~se~uently, an addition&l do~age o~ 5 mg/m3 o~ .:
.l
-~ the ~ollowing product waæ introduced./ This prodllct was ::
obtained by the addit~on o~ 1 mol glycidol to a product
~.. ....... .
' ,
. -- 23 ;-
4 ~ ~3~ ~
prepared by the reactlon o~ dodecylamine with ~-caprolact~m
in a molar ratio of 1:1 (Product P)0 When thls product accord-
lng to the invention and ph~sphonic acid~ were added~ the
di~ficulties in the coolant circuit were eomp~etely removed
by this combined addltion~ The degree of hardnes~ of the
coolant water did not increase, and growth of microorganism~
in the coollng water d-Ld not take place.
EXAMPIE 25
-~ The ~roduct J havirlg very favorable micrQ~istakic
: 10 a~ well as microbicidal properties wa~ ~e~ected to ~ho~ the
phy~iological tolerance of the products according to the ~ -
invention. For this~ urpoæe, th~ *ollowing details o~ the
.~ te~ts conducted are reported:
1) The lethal dose (LD5~) was determaned~
2~ The dermal tolerance of the hairless mou~ W~5 .,
determined by treatment with 1~ aqueous preparation~
a~minl~t~red topically to each mouse tw~ce on five
eonsecutiYe days (10 animals).
~: 3) The mucoeutaneous tolerance o~ the eye of the rabbit
wa~ determined by treatment with 1~ aqueous prepara-
tion~.
These te~t~ gave the following results:
1) LD50 = 3.30 gm/mg in the mouseO
~; 2) No ~i~dlngs for any a~imal.
~, 3) Sllght coniunctiv~l reaction which a~ter 48 hours
: ~otally sub~ided; no irrita~ion o~ cornea and
-` irls.
Some further examples a~ to potential applications
o~ the products according to the inventio~ are given
below.
:;
~'` ,
; - 2~ _
~: ,
EXAMPL~ 26
.
prewashing agent having antimlcrobial activity
wa~ prepared ~rom the following recipe by known procesurei~.
Part~
~,
Ole~insulfonate (the sodium ~alt) a .o
Soap 4 0
Foam i~hibitor o,3
lo Na4P2o7 36.:o
~aOH 7-5
' ~a2S4 10.2 -
; Product J 4.0
EXAMPLE 27 :-
., . ~ . ~-- ,
A~ antimicrobial detergen~ ~or laundries was
prepared fro~ the ~oll~wing recipe by known procedures. - .
Parts ~-
b ~ ~ :
Fatty alcohol ~ulfate 25.0
5P30~0 35.0 : -
2C3 7.0 . :.
Na2S04 ~5.0
Na20 ~ 3-3 5i2
.1 . . .
` Carboxymethyl cellulose 1.0 :-:
~` P~u~t P 2,0
I Pentasodium amino~rim~thylene- :~
i~ phospho}~ate 10 . 0 "'`,",
' .
,
.
,'' .
-
.
EXAMPLE 28
An antimicrobial acidie detergent for the beverage
- industry was prepared ~rom the ~ollowing recipe by known
procedure~0
Parts
by Weight
Phoæphor~c acid (80~) 50.0
Nsnylphenol ~ 9 mols ethylene o~ide 4.0
l~Hyd~yethane~ diphoæphonlc acid 5.0
Product B 1.0 :
Water 40 0
,
EXAMP~E 29
- A~timicrobial ~i~ht Duty Deter~ent :-~
, -,
An antimlcrobial light duty detergent wa~ prepared
~rom the ~ollowing recipe by known procedures.
parts
by Weight
Dodecylbenzenesulfonate ~sodium salt) 30.0
Toluenesul~onate (~odium ~alt)2.0
Sodium cocofatty alcohol ~ulfate 8.0
Sodium su}fate 30.0
Sodium carboxymeth~l cell~lose1.0 ; -
Product Q 4.o
Water 25.0
The products accordi~g to the in~ention can be
: also used as antl~lcroblal substances in dr~-cleaning mix-
tures based on organic sol~rents having a small content of
water. For the addition to the cleaning mlxture s of the
,, .
, 30 substances A to S, a concentration of 1 tc 10 gm/liter are used.
;,,
:.,
w 26 - .
~ , , ,... .;. , ,,- . , . : .
, . . . " , . ; .
,,, , . , , . : , ~ . ,
~y/~
Customarily, the activator~ for the cleaning ~olvents based
on anionic or non~ionic surfactants are added ln the form o~
concentrates which, in addition to the surfactant~, contain
solvent~ ~uch as chlorinated hydrocarbons or mineral oil and,
if ~ece~sary, dissolving intermediates, such as for example,
: isopropanol and water. The addltion products of the in~ention
can be incorporated into these concentrate~ and proportioned
~ogether with the activator for the cleaning ac~ion. ~h dry-
cleanin~, ~o much water i8 added to the cleaning mixtures
tha~ durlng ~he c~eaning proces~, the relati~e hum~dity in
the ~team space over the ~.xture amounk~ to at lea~t 70~. .
The produçt~ o~ the invention can be no~ only ~-
u~ed in detergent~ to obtain antimicrobial efficacy of the
; productsg but can ~e also utilized as preservati~e~ of cos- -
meti~s, starch pa~tes, glues~ disperslon dyestu~s~ cutting
~nd borin~ oilæ and the like.
For this purpo~e, an addition o~ 0.1% to 2~ by
wei~ht9 based on the product to be preserved, is generally
~ufficient.
`Z 20 ~X~UP$~ 30
An important field of application for the product~
according to the invention ls the con~ervation of indu~trial
and proces~ water. An additLve suitable for this purpo~e
ha~ the following compo~itionO :
Parts
by We~
Product P 100.0
Sodlum salt o~ the aminotrl-
methylenetripho phonlc acid 15.0
Sodium salt o~ the aminotrimethylene-
triphosphonic acid 15.0
De-ioniz~d water to1000
' ''
:''' ' '" ;
.. , ~, . .. . . . .
lOO cm3 o~ this solution is employed per m3 of the
indus~rial water to be pre~erved, as for instance, the cooling
water for cooling towers.
The preceding specific embodiments are ~ llustrative
of the practice of the invéntlon~ It is to be understood,
however, that other expedients l~no~n to those skilled in the
artg or dlscloæed herein, may be ~mployed wlthout depart,i;ng
from the spirit of the invention or the 8COp~3 of the app~ded
cla~ s-
',~
:
.
-. ~; '
,' ' .
_ 28 ~
-.. - - i. , .. - .. ..
. . .
