Note: Descriptions are shown in the official language in which they were submitted.
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6-12780/MA 1766/~
4-Halo~eno-oxetan-2-ones and process for their production
.
The present invention relates eo ~e~ 4-halogeno-oxetan-2-ones, a pro-
cess for their production, as well as antifoulant composieions~contain-
ing said 4-halogeno-oxatan-2-ones as active ingredients.
~ccorting co the pr2sent invention, ehere are provided compounds
having the formula I
Y C~2 i f (I)
wherein X is a chlorine, bromine or iodine atom and Y is a residue
having the formula RlR2R3C-, wherein Rl and R2 are the same or differ-
ent and each is a fluorine, chlorine or bromine atom and R3 i9 a
hydrogen, fluorine, chlorine or bromine atom, a group -CR4R5R6, a cyano
group,a group -COR or -PO~R )2 ~hereLn R , R , R ,independently, are
F, Cl or ~r, R7 and R ar~ the jame or different and each is a chlorine
atom or a group -oR9 wherein R9 is a Cl-C4 straight chain or branched
alkyl group ~ith the proviso that when X is a chlorine atom, none
of Rl, R2, R , R4, R5 ant R6 can be a bromine atom.
When R is a Cl-C4 alkyl group, it may be a methyl, ethyl, n-propyl,
isopropyl, n-butyl, sec.butyl or t-butyl group. X preferably repre-
sents a chlorine or bromine atom. Rl, R and R3 preferably are each a
fluorine, chlorine or bromine atom. Specific Examples of compounds
of formula I include:
~k
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4-Chloro-4-(2,2,2-trichloroethyl)oxetan-2-one, 4-bromo-4-(2-chloro-
2,2-difluoroechyl)oxetan-2-one, 4-bromo-4-(2-bromo-2,2-difluoroethyl)-
oxetane-2-one, 4-bromo-4-(2,2~2-trichloroethyl)oxetan-2-one, 4-bromo-
4-(2-bromo-2,2-dichloroethyl)oxetan-2-one, 4-bromo-4-(2,2,2-~ribromo-
echyl)oxeean-2-one, 4-chloro-4-(2-chlorocarbony1-2,2-dichloroethyl)-
oxetan-2-one, 4-chloro-4-(2,2-dichloro-2-methoxycarbonylethyl)oxetan-
2-one, 4-chloro-4-(2,2-dichloro-2-ethoxycarbonylethyl)oxetan-2-one,
4-chloro-4-(2,2-dichloro-2-n-butoxycarbonylethyl~oxetan-2-one,
4-chloro-4-(2,2-tichloro-2-dichlorophosphonylethyl)oxetan-2-one,
4-chlorQ-4-(2,2-dichloro-2-tiethylphosphonoethyl)oxetan-2-one,
4-chlor.o-4-(2,2~dichloro-2-cyanoethyl)oxetan-2-one, 4-bromo-4-(2,2-
dihromo-2-methoxycarbonylethyl)oxetan-2-one, 4-bromo-4-(2,2-dibromo-
2-cyanoethyl)oxetan-2-one, 4-chloro-4-(2,2,3,3,3-pentachloropropyl)-
oxetan-2-one, 4-bro -4-(2-bromo-2 r 3,3,3-tetrachloropropyl)oxetan-
2-one, 4-bromo-4-(2-bromo-2-chloro-3,3,3-trifluoropropyl)oxetan-2-one,
and 4-iodo-4-(2,2,2-trifluoroethyl)oxetan-2-one.
Preferred compo.unds of formula I incIude: 4-Chloro-4-(2,2,2-trichloro-ethyl)oxetan-2-one, 4-bromo-4-(2,2,2-trichloroethyl)oxetan-2-one,
4-bromo-4-(2,2,2-tribromoethyl)oxetan-2-one, 4-chloro-4-(2,2-dichloro-
2-ethoxycarbonyl-ethyl)oxetan-2-one, and 4-bromo-4-(2-chloro-2-bromo-
3,3,3-trifluoropropyl)oxetan-2-one.
The present invention al90 provides a process for the production of
compounds of formula I comprising reacting diketene with a compound
XY in.the presence of an agent capable of forming free radicals.
Examples of compounds XY are tetrahalomethanes such as carbontetra-
chloride, carbontetrabromide or bromotricbloromethane; trihalomethyl
compounds such as ethyltrichloroacetate, trichloromethylphosphonyldi-
chloride, trichloroacetonitrile, l-chloro-l,l-dibromotrifluoroethane
or hexachloroethane.
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Agents forming free radicals i~clude for cxample:
i~ Ionising radiation;
ii) Ultraviolet radiation;
iii) Organic peroxides e.g. t-butylperacetate, t-butylperbenzoate,
acetylperoxide, benzoylperoxide, di-isopropylperdicarbonate, bis-(t-
butylcyclohexyl)-perdicarbonate, di-t-butylperoxide, and t-butyl-
hydroperoxide;
iv) Inorganic peroxy compounds e.g. hydrogen peroxide and~a = nium
persulphate;
v~ Orgsnic azo compounds e.g. azobisisobutyronitrile, and azobis-
isopropane;
vi) Combination of iii) or v) with ultraviolet radiation;
vii) Combination of iii) or iv), with a metal ion catalyst, e.g. Cu,
Ti, V, Fe to give a radical producing redox-system e.g.
H22 + Fe
NH + O S-O-O-SO NH4 ~ Cu
t-Butylhydroperoxide + Ti
Preferred agents forming ree raticals are organic peroxides, organic
azo compounds, and combinations of organic peroxides or organic azo
compounds with ultraviolet ratiation.
The radical forming substances [iii), iv), v)] may be used advantage-
ously in catalytic amounts-of 0.1-10 mol~, preferably 1-5 mol%, based
on diketene. The preferred molar ratio of compound XY to diketene
i9 from 1:1 to 20:1. In the above process, the reactant XX may act
as the solvent but, if desired, the reaction may optionally be carriet
out in the presence of a solvent inert under the reaction conditions
e.g. petroleum ether in low temperature reactions; benzene, toluene
or carbon tetrachloride in moderate temperature reactions; or chloro-
benzene in high temperature reactions. The reaction may be effected
under conditions well-known per se e.g. in the temperature range -20C
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to 1;0C, according to ehe radical producing ~ethod employed, pre-
fsrably be~ween 0C to 100C; and, if the compound XY is a gas,
optionally in an inert gas atmosphere and optionally under pressure.
The reactions can be carried out batchwise, or, preferably, in a con-
tinuous manner, for example in a cascade reactor.
Compounds of formula I show broad spectrum biocidal activity in the
range of 1000 ~g/ml and lower against a range of organisms. In parti-
cular the compounts of formula I control the growth of bacteria,
fungi and aIgae, at low concentration. The compounds of formula I are
also useful as intermediate~ for a wide variety of chemirals.
Accordingly, the present invention also provides antifoulant composi-
tions comprising, as active ingredient, a compound of formula I,
optionallg in admixture with suitable carriers.
They are particularly effective in~controlling the growth of bacteria,
fungi and algae in still or circulating water systems, for example in
industrial cooling towers, swimming pools etc., in other aqueous-
based or oil-based systems e.g. cutting fluids and secondary oil re-
covery processes; in industrial processing waters e.g. processing
waters in woot, pulp, paper~ te~tiles and leather processing; and in
surface disinfection e.g. in hospitals, dairies etc.
The compounds of formula I can be applied as biocides in pure form or
as concentrated or dilute solutions or emulsions, which may be option-
ally stabilised with alkali- or alkaline earth metal carbonates. It is
also possible to apply them in admixture with solit carriers. The
compounds can also be applied as suspensions in liquid compositions,
in which case wetting agents or emulsifiers may be used to assist
the distribution of the active ingredient to form homogeneous disper-
sions. If desired, the compounds may be used together with other
biocides.
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One field of appLication is the treatment of cooling wa~er. For pro-
tection against the growth of microorganisms, the active compounds
can advantageously be added direct to the cooling water.
When using the compounds for treating water, it is possible to add
simultaneously other additives, for example, corrosion inhibitors,
antiincrustants, water softeners, complexing agents and low foaming
surfactants or penetrants, for example, polymeric phosphites, phos-
phates 9 amides of phsophoric acids, polymeric carboxylic acids or
anhydrides, for example polyacrylic acids or polymaleic acids, or
salts thereof and other additives.
Organisms whose growth is controlled include for example:
Class/type Examples Problems caused
Algae
Green Chlorella vulgaris . General matting
Chlorella pyrenoitosa
Scenedesmus spec. and fouling
Vlothrix subtilissima
usually by
Blue-green Oscillatoria geminata
Nostoc spec. blocking of pipes
Phormidium foveolarum
Anacystis nidulans pumps, filters, etc.
Brown Tribonema aequale
Bacteria
Gram positive Bacillus cereus var. mycoides
Bacillus subtilis Bacterlal slimes
Streptomyces griseus
Streptomyces aureofasciculu5 produced which
Staphylococcus aureus
cause reduced
Gram negative Pseudomonas aeruginosa
Aerobacter aerogenes plant efflciency
Serratia marcescens
Alcaligenes denitrificans and mcreased
Escherichia coli
Proteus vulgaris corroslon.
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_lass/type Examples Problems caused
~aerobic Desulphovibrio desulphuricans H2S produced
Sulphate w~th resultant
retucing severe corrosion.
Fung Aspergillus niger Surface rot,
Aspergillus phoenicus
Penicillium funiculosum d~scolouratlon,
Alternaria alternata slime production
Cladosporium cladosporioides
Candita albicans and internal
Endomyces geotrichum wood decay.
Aureobasidium pullulans
The foLlowing Examples, in which parts and percentages are by weight,
further illustrate the present invention.
Example l: A mixture of 25.2 parts of diketene, 62.7 parts of bromo-
trichloromethane and 1.5 parts of azobisisobutyronitrile dissolved
in 978 parts of carbon tetrachloride was irradiated by W light at
room ~emperature (20-25C) for 5 hours. The mixture was evaporated
at the water pump and the product, 4-bromo-4-(2,2,2-trichloroethyl)-
oxetan-2-one, was obtained as a yellow oil which crystallised on
cooling. Recrystallis~ation of this material three times from light
petroleu~ ether (b.p. 40-60C) gave white needles m.p. 55-56C.
CalcuLated for C5H4BrC1302: C 21.27; H 1.43
Found C 21.09; H 1.53.
: 2.0 parts of benzoyl peroxide (containing 252 of water)
were dissolved in 163 parts of carbon tetrachloride and dried over
magnesium sulphate. To the filtered dry solution were added 42 parts
of diketene ant the resulting solution was added dropwise over 5 hours
to 815 parts of refluxing carbon tetrachloride. After completion of
the addition the mixture was heated for a further 1 hour, then evapo-
rated to dryness on the water pump. Extraction of the product into
hot petroleum ether gave 4-chloro-4-(2,2,2-trichloroethyl)oxetan-2-
one, shown to be 95% pure by GLC (ground level concentration).
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Distillation of a portion of the extracted material gave an analytical-ly pure sample, b.p. 70-75C at 0.0133 mb(millibar).
Calculated for C5H4C1402 C 25.25; H 1-69; Cl 59-61
Found C 25.47; H 1.87; Cl 59.62.
Example 3: 210 psrts of freshly distilled diketene and 30 part~ of bis-(t-butylcyclohexyl~perdicarbonate were dissolved in 795 parts of car-
bon tetrachloride. This solution was added dropwise over l~hour, with
stirring, to 3180 parts of carbon tetrachloride held at reflux tempe-
rature in an atmosphere of dry nitro~en. When the addition was comp-
lete, stirring at reflux temperature was continued for 1 hour and
the solution was then allowed to cool. The excess carbon ~etrachloride
was distilled off on a rotary evaporator under water pump vacuum at a
bath temperature of 30-40C. The crude product was purified by distil-
lation on a wiped-wall still giving 398 parts of pure 4-chloro-4-
(2,2,2-trichloroethyl)oxetan-2-one.
Example 4: A carbon tetrachloride solution containing 26.35 parts di-
ketene and 3.76 parts of bi~-(t-butylcyclohexyl)-perdicarbonate per
1592 parts of carbon tetrachloride was pumped through a two vèssel
csscade at such a rate as to give residence time of 60 ~inutes (resi-
dence time - vessel volume~vo-lume pumped per minute). The vessels
were stirred vigorously ant heated at carbon tetrachloride reflux tem-
perature. The product stream contained 2.5 parts unreacted diketene
and 67 parts of 4-chloro-4-(2,2,2-trichloroethyl)oxetan-2-one per
1592 parts carbon tetrachloride.
Bxample 5: A mixture of 8.4 parts of diketene, 33.1 parts of carbon
tetrabromide, 0.5 part3 of bis-(t-butylcyclohexyl)perdicarbonate and
326 parts of carbon tetrachloride was heated at 60~C for 2 hours,
then evaporated at the water pump. The residue was recrystalliset
twice from light petroleum ether (b.p. 40-60C) and the product,
4-bromo-4-(2,2,2-tribromoethyl)oxetan-2-one, obtained as white need-
lesrm.p. 71-73~C.
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Calculated for C5H4Br402 C 14-4S; H 0.97; Br 76-89
Found C 14.75; H 0.97; Br 76.20.
Example 6: A mixture of 8.4 parts of diketene, 19.2 parts of ethyl
trichloroacetate and 1.3 parts of bis-(t-butylcyclohexyl)perdicarbonate
was added dropwise over 3 hours to 96 parts of ethyl trichloroacetate
stirred at 85C in a nitrogen at sphere. After the addition, the mix-
~ure was stirred at 85C for a further L~2 hour, then the ùnreacted
starting materials were removed-on a wiped wall still at 90C/0.27 mb.
The residue was distilled twice in a Kugelrohr at 100C~0.33 mb. IR
and NMR on the distillate showed the major component to be 4-chloro-
4-(2,2-dichloro-2-ethoxycarbonyl-ethyl)oxetan-2-one.
Example 7: 1.68 parts of diketene and 0.4 parts of bis-(t-butylcyclo-
hexyl)perdicarbonate were dissolved in 25 parts n-hexane and added
over 1 hour to a stirred ~olution of 5.53 parts of l-chloro-l,l-di-
bromotrifLuoroethane in 25 parts n-hexane at 60C. The mixture was
stirred a further l.S hours at 60C,then cooled to room temperature.
The solution was decanted from an insoluble oil,then evaporated cold
in vacuo~to give 3.8 parts of 4-bromo-4-(2-chloro-2-bromo-3,3,3-tri-
fluoropropyl~oxetan-2-one as a mobile yellow oil, with a characteristic
I.R. carbonyl frequency of 1860 cm 1.
Example 8: A mixet culture of slime-forming bacteria including Pseu-
domonas aeruginosa, Enterobacter aerogenes, Escherichia coli, Proteus
w lgaris, Bacillus mycoides and Staphylococcus aureus in saline
containing 107 organisms~ml was treated with 30 ppm of the product
of Example 2. After one hour, the number of organisms had been re-
duced to 102 organisms~ml and within 24 hours all the bacteria had
been killed, thereby temonstrating the high bacteriocidal activity
of the product of Example 2.
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Example 9: Test demonstrating algistat~
The organisms against which the compounds are to be tested are grown
in an Erlenmeyer flask in a nutrient medium under sterile conditions
oll a shaking ~ater bath at 18C with exposure (14 hours in light alter-
nating with 10 hours in the dark).
Tests are carried out against three algae, namely the blue algae
a~ Phormidium foveolarum (A) which lives in polluted water or moist
earth and forms trichomes;
the green algae
b) the simple filament-forming Ulothrix subtilissima (B) generally
found at colder times of the year in rapidly flowing water;
and the algae with brown chromatophors
c) the widespread, unbranched filament-forming Tribonema aequale (C)
occurring in bodies of water especially in the spring at low tempera-
ture or in the autumn, even in mild winters.
The composition of the medium is as follows (according to Algae broth,
Difco Laboratories):
1.0 g o NaN03,
0 05 g of CaC12,
0.058 g of CaC12,
0.5 g of MgSa4 7 H20,
0.25 g of K2HP04,
0.003 g of FeC13,
dissolved in 1 litre o distilled water. The nutrient medium treated
with the biocide is innoculated with the respective algae suspension
such that a final dilution of V100 (algae divided with a stirrer) is
attained. Evaluation is made after a 3 week incubation in the Erlen-
meyer flask on a shaking water bath. The activity is reported as the
minimum inhibitory concentration (MIC in mg/l) which indicates that
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algicide concentration at which the growth of the algae is ~till
inhibited. The results are summarised in Table 1.
Table 1
_
Compound of formula Minimum inhibitory Concentration, MIC mg/l
Pbor~idium Ulothrix Tribonema
foveolarum subtilissima aequale
_
Product of Example 2
2 2 ¦ f .~ 30 30
