BE520434A - - Google Patents

Description

       

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  IMPROVEMENTS TO ORGANIC COMPOUNDS AND THEIR PREPARATION.



   The present invention relates to certain N- (substituted benzyl) -N- (hydroxyalkyl) -dihaloacetamides and to their preparation.



   The substituted dihaloacetamides according to the invention have the following general formula:
 EMI1.1
 in which Ar is a phenyl radical substituted by a halogen or an alkyl, alkoxy radical. alkylmercapto, alkylsulfonyl or nitro and Y is an alpha, beta-lower alkylene radical or an alpha, gamma-alkylene radical.



  These substituted dihaloacetamides possess valuable chemotherapeutic properties, for example anti-amoebic activity.



   In the formula given above, the substituted phenyl radical, designated by Ar. Includes phenyl radicals substituted., Preferably, by one to three substituents chosen from the class comprising halogens and lower alkoxy radicals, lower alkyl, alkyl mercapto lower, lower alkylsulfonyl and nitro. Moreover, these substituents can be in any of the free positions of the phenyl ring and, in the case where these substituents are more than one in number, they can be the same or different and can occupy the various positions. - possible relative positions. The halogen substituents can be chlorine, bromine, iodine and fluorine.

   As to the Lower alkoxy, lower alkyl, lower alkylmercapto and Lower alkylsulfonyl radicals, they preferably contain one to six carbon atoms. Among these radi-

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 caux substituents the following may be mentioned: methoxy, ethoxy, methylene-dioxy, ethylenedioxy, n-propoxy, isopropoxy, isobutoxy, n-amoxy n-hexoxy and the like, as alkoxy radicals; methyl ethyl, n-propyl. isopropyl.
 EMI2.1
 n-butyl, isobutyl ,. 2-butyl, n-amyl, n-hexyl and the like as lower alkyl radicals; methylmercapto, ethylmercapto, n-propylnercapto, isobutylmercapto, n-hexylmercapto and the like, as lower alkylmercapto radicals;

   and methylsulfonyl, ethylsulfonyl, n-propylsultonyl, isobntylsulionyl, n-hexylsulfonyl and the like as lower alkylsulfonyl radicals.
 EMI2.2
 When Y is an alpha, beta-lower alkylene radical, this radical preferably contains two to six carbon atoms and has its two free-valent bonds on neighboring carbon atoms.
 EMI2.3
 



  As examples of such radicals, there may be mentioned the following: -C-U.0-H.-P -GH (H3) CH? - .. -GHZCHCH3. -G (CH.3) ZCHZ-. -G (CH3): pHCH.3 "-CHIHCHCH I-CHpdUCHp GHZCH.3" - -CHZCHCCHZCCH.3 "and the like. When denoting an alpha, gamma-lower alkylene radical., The symbol Y refers to a such radical preferably comprising three to six carbon atoms and has its two free valent bonds on carbon atoms separated by a third carbon atom. As examples of such radicals, it is possible
 EMI2.4
 cite the following: -GH2CHZCHZ- "-GCHZCHCH.3. -GHZCII2CHCH2GCH3" -GH (GH3) GHGH-, -GH2C (CH3) ZCH2-. -11-1H (CH3) CH (OH3) CH2-, and the like.



  The halogen atoms of the dihaloacetyl radical of the compounds, designated in the formula by -GOOH (halogen) Zs can be chlorine, bromine, iodine or fluorine atoms. Among these radicals, mention may be made of dichloraacetyl radicals. dibromoacetyl ,. diiodoacetyl, difluoroacetyl, bromochloroacetyl and the like.



   The compounds according to the invention are prepared by treatment.
 EMI2.5
 ment of a benzylaminoal1!: a.nol substituted, of formula 1) Ar-GH2-1H Y-flH with a dihaloacetylation agent chosen from the class comprising the
 EMI2.6
 lower alkyl dihaloacetate and the dihaloacetyl halides, Ar and Y having the meanings given above. When using a lower alkyl dihaloacetate, the methyl esters are preferred because of the ease of preparation of these esters and the ease with which they can be obtained. However, other lower alkyl esters, such as the n-propyl, isobutyl, 2-amyl and n-hexyl ethyl esters are also satisfactory.

   When a dihaloacetyl halide is employed, the halogen of the halide, i.e. the halogen linked to the carbonyl function, is preferably chlorine.



  However, other halogens can also be used, such as bromine, iodine or fluorine. As illustrations of the process according to the invention we
 EMI2.7
 may cite: the preparation of N- (2.4-dichlorobenzyl) -N- (2-hydroxy "thyl) dichloroacetamide by treatment of 2- (2 4-dichlorobenzy18mino) ethanol with methyl dichloroacetate; the preparation of N- (3 .g5-tr? Ethoxybenzy.) T- (2-hydxoxypropyl) -dibromoaaetamide by treatment of 1-3,1,., 5-triethoxy'benzylamino) -2-propanol with dibromoacetyl bromide; the preparation of N- (4-nitrobenzylj-T- (2 ydroxyéthy3) -d.if3.uoroacétami.de, by treatment of 2- (4-nitrobenzyl-amino) -ethanol with methyl diffluoroacetate.



  When a lower alkyl dihaloacetate is used, the reaction is facilitated by heating the reactants in a steam bath. When a dihaloacetyl halide is employed, the reaction is carried out. preferably at a temperature below room temperature, cooling if necessary.,
 EMI2.8
 The intermediate substituted benzylaminoa.l.lanols of formula indicated above are prepared by treatment of a substituted benzaldehyde of formula

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 ArCHO with an alkanolamine of formula HZN-Y-OH, Anil, ArCH = N-Y-OH. which probably forms, is then reduced directly, without prior isolation.
 EMI3.1
 ble, in the presence of a catalyst, so that the substituted aminoal1r.anol, ARCH2NH-Y-OH, is obtained.

   Substituted aminoalkanola Intermediates can also be prepared by treating a substituted benzyl halide, AxCHZ-halogen, with an alkanolamine. H2N Y-OH. As illustrations of the preparation of the intermediate substituted benzylaminoalkanols, mention may be made of the preparation of Z- (3,1,5-tribromobenzylamino) -ethanol., By treating 3,1,5-trromobenzaldehyde with ethanolamine. , so as to form anil * which is then catalytically reduced, and the formation of 1- (4-n-butoxybenzylemmo) -2-propanol by treatment of 4-n-butoxybenzyl chloride with 2 -hydroxypropylamine.



   The following examples will illustrate particular embodiments of the invention.



   EXAMPLE 1
 EMI3.2
 A. Ben, substituted zrla.noalkanols.



   As indicated above, these intermediates are prepared by either of the following methods; benzaldehyde reaction
 EMI3.3
 substituted with an alkanolamine and the resulting catalytic reduction of the anil and reaction of a substituted benzyl halide with an alkanolamine. Illustrations of these processes are given below.
 EMI3.4
 ? ,,,! - iso $ ropylbenzyLa3.noi-ethanol.



   A mixture of 44.3 g of 4-isopropylbenzaldehyde and 18.3 g of ethanolamine is heated in a steam bath, under vacuum. for 1 hour. The mixture is dissolved in 125 cc of hot ethanol and catalytically reduced with 0.5 g of palladium chloride and 3.5 g of charcoal, under about two atmospheres of hydrogen. When the reduction is complete, the catalyst is separated by filtration and the alcohol is distilled off under reduced pressure. The residue, which solidifies, is successively recrystallized from n-heptane
 EMI3.5
 (.3). In ether. 2- (4-isopropyl-benzylamino) -ethanol is obtained, melting at 80.9 - 83 3 C (corrected).



  Analysis - calculated for C1H19N 0: 0-74 to 55%; Ho found: C = 74.53; H10, 16, 2- (4-isopropylbenzylamino) -ethanol da7.athydzate melts at 129.4 - 132.2 C, (corrected), after recrystallization from an ethanol-ether mixture.



  Analysis - calculated for CH19NO.HC2: 0 = 62.7 H = $, 77 ;; Cl = 4 ± $ Found: 0-63-100; H = g., 99; Cl = 15.62% 2- (Z-methpxybenzylamino) -ethanol
This compound is prepared by the process described for the preparation of 2- (4-isopropylbenzylamino) -ethanol, except that 41 g of 4-methoxybenzaldehyde and 18 g of ethanolamine are used. After separation of the catalyst and elimination of ethanol, the residue is subjected to fractional distillation.
 EMI3.6
 born at 139cc under 0.6mm pressure, n2 = 1.5431. The material is converted to its hydrochloride and then converted back to the base. The product obtained, namely
 EMI3.7
 2- (4-methoxybenzylamino) -ethanol. is in the form of irradiated oil at 38-39 C (corrected), after recrystallization from n-hexane.



  Analysis - calculated for C10H25N 02: cl H = S..28% found: C = 66.66%: H = 8.7L $ 2- (4-methoxybenzylamino) -ethanol hydrochloride melts at 112.2 - 113.6 C (corrected) , after recrystallization from a mixture

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 EMI4.1
 isopropanol-ether.



  Analysis - calculated for G10-¯i.5N02eHCls 0 = 55J115%; H = 7.4J $; Cl = 16 29% Found G = 55.45sA = 7.61; C1 = 16, lf%
 EMI4.2
 Other substituted henzylaminoalkanols prepared by the process described above are given below. These basic compounds are recrystallized from n-heptane or ether and their hydrochlorides are usually recrystallized from ethanol-ether or isopropanol-ether mixtures. in isopropanol or in acetone.
 EMI4.3
 



  2-14-isopropoxybenzylamino) -ethanol m.p. 75.0-76, 6 C (corrected). Analysis - calculated for C.'j, QNO: C = 68 86 $; H = 9.153 Found: G-C79 .- / 9 '/ ". 2- (4-isopro- hydrochloride)
 EMI4.4
 poxybenzylamino) -ethanol, M.P .:
 EMI4.5
 134f9-.35f4 G (corrected) Analysis - calculated for cgE 9 N0.xcii 0 = 58e65%; H = 8..2:01 = 14.43%. Found: C = 5 $ '63 H = 7 <95%! Gl - 14.35 = 2- (4 ethoxybenzy2ami.no) -ethanol, m.p. 63 o - 63.60G (corrected).



  Analysis - calculated for ClIH1 "W2: c = 67 .SI67J,.; H = 87. Found: s 7.906,; S = 909. 2- (4-ethoxybenzylamino) ethanol hydrochloride PF 103-104 6 0. ( corrected) is calculated for C il17 NO 2HC1: 0 = 57.0% H = 7.83 CI = 15.30% "Found: 0 = 57.00%, Hs7.01 = 15.07%.



  2- (4 n-propoxybenzylamino) -ethanol, m.p. 67 - 68.2 G (cooriginated) Analysis - calculated for 1ZHI9NOZ: G = 68.56 ;; H, 9.15. Found: G = 68.753 A 9W. 2- (4-n-Propo-xybenzylanine) -ethanol hydrochloride m.p. 134..2 - 138.2 G (corrected) Analysis - calculated for C12IS.9NOZ .HCl: 0 = 5865% H = 8.21%: 01143%. Found: C = SD6'7 H = $ 8.31; 01 = 1.



  2- (4.-n-amoxybenzylamino) -ethanol m.p. 51.9 - 55 C. (corrected) Analysis - calculated for GH23NOZ: G = 70.86; H = 9.7'7i Found: s C = 70.14; 13 - g, 72. 2- (4-n-emo-xybenzylamino) ethanol hydrochloride, m.p. 11, - 145a5 G. (corrected) Analysis - calculated for O 2 HOI C = 61.40%; H, 8.83%; Gl = 12.95%. Found: G = 61 43 #; H = 8.71% Cl = 128.



  2- (3, 4hyZned.oxybenzylamino) -ethanol.



  M.p. 62.6 - 64 4 c (corrected) Analysis - calculated for 10H13NO3: c = 61.53%; H-6.72 Found: c = 6160E; Ho Z- (3J14-methylenedioXJ! Benzy1amIID) ethanol hydrochloride P.F. 152. -.152J16 c "(Analysis corrected - calculated for ClOH13N03.HC1: G = 51.85%; H = 609% N = 153C%.



  Found'- Ei "-5.4.607 H C?, 0 I"! N = $ 15 13.



  2- (4-n-Butoxybenzylamino) -ethanol hydrochloride, m.p. 1.46.6-I4.7.5 G (corrected) Analysis - calculated for C ,,H ,112.HC1: c = 60.11; H = 8.47; ci * 13 65% 1 11.ve:G'C711.w1!'"'9r"r "! ci = 13 61%.



  The following substituted benzylaminoal # -anols were prepared
 EMI4.6
 by reacting a substituted benzyl halide with an alkanolamine.
 EMI4.7
 



  2-t2.-dâchlorobenzlno) -ethanol.



  78.2 g of 2, .- dichlorobenzy.e chloride are added, dropwise and with stirring. to 80 gr of ethanolamine. After standing at temperature
 EMI4.8
 room overnight, the mixture is made alkaline using a solution

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 20% sodium hydroxide and extracted with ether. After removing the ether and recrystallizing the residue with n-heptane, 56 g of 2- (2.4-dichlorobenzylamino) -ethanol are obtained. melting at 62 - 62.8 C. (corrected) Analysis - Calculated for C9H11Cl2NO: Cl = 32 22%.



   Found: C1 = 32.43%
This product can also be obtained directly. in solid form by pouring the reaction mixture into a large volume of water and stirring.
 EMI5.1
 



  2- (2 4-Dichlorobenzylammo) -ethanol hydrochloride melts at 184s7 - 186.117 0. (corrected) analysis - calculated for CH11C1zN0.HC: C = 42.12%; ü-4.70 ,; Cl = 138C% Found: C = !. 'a30; H = 4.66.01 = 13.78%.



  Other substituted benzylaminoalkanols prepared by the process illustrated above for the preparation of 2- (2A, -dichlorobenzylammo) -ethanola are indicated in the following paragraphs.



  2- (34 ± dichlorobenzylamino) hydrochloride - ethanol, m.p. 145.9 - 148J11 C (corrected) Analysis - calculated for CHIIClN0o13C1: C = 4.3.3 ,; H # 4.71.,; 01 = 13.82% Found: C = 42926; H = 4.54; C1 = 13.93%.



  2- (2-Chlorobenzylamino) -ethanol hydrochloride. Mp z, 2-13699 C (corrected) Analysis - calculated for CxCl10, xcl: 0 = 48.68%, H5.90; 01 = 15.97%.



  Found: C = 4856%; H = 6.07%; Cl = 15.76%.



   2- (4-Chlorobenzylamino) -ethanol. distills. 126-131 C at 0.7
 EMI5.2
 mm; 5.1D5470. 2- (4-Chlorbbenzylamino) -ethanol hydrochloride .. m.p. 172.7 - 173ag C. (corrected) Analysis - calculated for C9FiC1N0.HC1 .: N = 6 30%; 01 = 31.93% Found: N = 6.3; Cl = 31.96%.



  3- (2p44-dichlorobenzylamino) -propanol is prepared as described above. adding, drop by drop and stirring, over 1 hour 30 gr. 2,4-dichlorobenzyl chloride at 35 gr. of 3-hydroxypropylamine. Stirring is continued for 2 hours and the resulting mixture is made strongly alkaline with a 56% aqueous solution of potassium hydroxide, after which the mixture is extracted with water. ethylene dichloride medium. The solvent is removed after drying and the residue is distilled at 150
 EMI5.3
 - 155 C, under 0.5 mm; n25J1 15600. Yield: 23 gr.



   D Analysis - calculated for C10H13Cl2NO: N = 5.98% Found: N = 6.00%
 EMI5.4
 3-to 4-dichlorabenzylanino) -propanol is prepared according to the procedure given in the previous paragraph, but using 60 gr. of 3.4-dichlorobenzyl chloride and 70 g of 3-hydroxypropylamine. 5 This intermediate product distills at 165 - 17 C, at 0.6 - 0.8 mm. n 1.5590. Yield: 64 gr.



  Anâlyae - calculated for C10H13C. NO: N = 5.98% found: N = 5.96%
When operating in the manner described for the preparation of
 EMI5.5
 3- (2 4-diahlorobenzylanino) -propanol but using 2-hydroxypropylamine instead of 3-hydroxypropylamine. 1- (2, -d3.ah2orobenzylamino) -2-propanol is obtained. This product as its hydrochloride, melts at 152.4 - 154.2 C. (corrected).

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 EMI6.1
 



  Analysis - calculated for COG12NO.HCl: C-46.1; H = 5.66% CI = 12SJ46% Found: C-46.14%;
 EMI6.2
 H = 5 9T% Gl = 12144%
Other substituted benzylaminoethanols can be prepared by the procedures given above, using the appropriate substituted benzaldehyde or substituted benzyl halide and the appropriate alkanolamine;
 EMI6.3
 among these compounds, the following may be mentioned: 2- (2. ± -dibronobenzylaaàno) -etlanol. - (3,4 düdabenzylamino) -ethanol, Z- (4-ffuarobenzylamino) -ethanol. 2- (3.4.



  5-trichlorobenzylam3.no) -ethanol, 2- (4 bromo--chlorobsnzyl.no} -ethanol, - (2, .1, -d3..uorobenzylami, no) -ethanol, 2- (4-n-hexoxybenzylamino) -ethanol. 2- (4-isobutoxybenzylamino) -ethanol, 2- (3, h, 5 rianethoxybenzylamino) -ethanol, 2- (4-isobutylbenzylamino) -ethanol, 2- (4-n-amylbenzylamino) -ethanol. 2- (4-n-hexybenzylamino) -ethanol, 2- (4-nitrobenzylmmo) -ethanol, 1- (4-nitrobenzylamino) -2-propanol, 3 (l nitrobenzylaano} propanol, - (4 butylmercaptobenzylamino) -. Ethanol, 2- (4-n-isobutylsulfonylbgnzylamino) -ethanol, 1- (4-n-butylbenzyl-amino) -2-propanol, 1- (3'-dichlorobenzylamino} -2 butanolg 3- (4-isopropylbenzylamino) propanol, and the like.



  B .ii- -diehlorobenz -3- h dro é h di oroacétide.



   A solution of 4 g of dichloroacetyl chloride in 30 cc of ethylene bichloride is added dropwise, with stirring and cooling.
 EMI6.4
 dissante has a solution of 12 g of 2- (3.e4-dichlorobenzylamino) -ethaaol in 100 cc of ethylene bichloride. The temperature is maintained between 0 and -5 ° C. by cooling using an ice-salt bath. When the addition is complete. the reaction mixture is allowed to return to the temperature am-
 EMI6.5
 biante9 while being restless. ^ - (3, .- dichiarcbenzy3.em3na) - ethanol hydrochloride. which separates is removed by filtration and the filtrate is washed successively with 1N hydrochloric acid and with water and then dried over anhydrous calcium sulfate.

   After distillation of ethylene dichloride under reduced pressure, the residue is triturated with ether. We thus obtain 5.5 g of
 EMI6.6
 N- (3 ± -diehlorobenzyl) -N- (2-hyd = oxyethyl) dichloroacetmide M.P .: 99.4-101.5 C (corrected). after recrystallization from a benzene-n-pentane mixture.
 EMI6.7
 Analysis - calculated for CllH11C14NOZ: Cl =, l, f4jC = 3Ri! H = 3.35%
 EMI6.8
 found: 01 = 42., 680 = 39.70% H = 3.65% It was found that N- (3.4-dichlorobenzyl) -N- (2-hydroxyethyl) - dichloroacetamide possesses anti-amoebic activity. This product is indeed effective against amebiasis (Endamoeba criceti). Hamsters.



   When following the process described above but using diiodoacetyl chloride ,. difluoroacetyl fluoride or chloride
 EMI6.9
 bromochloroacetyl. instead of dichloroacetyl chloride, the following compounds are obtained respectively: N- (3f1-dichlorobenzyl} lü- (hydroxyethyl) d.iodoacétsm.de, N- (34-dichlorobenzyl) -N- (2-hydroxyethyl) d1f 'luoroacetamide or N- (35) 4-dichlorobenzyl) -oN - (2-hydroxyethyl) bromochloroacetamide- ..



  EXAMPLE 2 N- Z -d.ichlorobenz 1 - 2 h dro eth d, i aro ce de.

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   A solution of 7.3 g of dichloroacetyl chloride in 30 cc of ethylene dichloride is added. drip and stirring ,, to
 EMI7.1
 22 gr of 2- (2 4-diahlorobenzylamino) -ethanol in 300 cc of ethylene dichloride. The temperature is kept below 24 C by external cooling. Stirring is continued for one hour and the hydrochloride of the starting amine, which separates, is collected by filtration.



  13.5 g of this hydrochloride are obtained. The filtrate is washed with dilute hydrochloric acid and then with water, and dried. Removal of the solvent gives an oil which solidifies when triturated with ether. After recrystallization from benzene and then from ethylene dichloride, one obtains
 EMI7.2
 N - ('p, -di.ch3.orobenzyl) ï- (2-hydroxyethyl) d, chloroacetar.i.de, melting at 112.4 - u3 4 ca (corrected).



  Analysis - calculated for CZ1H11C1NO: E1 = 1.2.5,; O = 39, g9; H, 3.35%.
 EMI7.3
 found c = 42.95%; c = $ 40.20 3 i 7J'o N- (2,1-dichlorobenzyl) -T- (hydrox3rethyl) - dichloroacetamide has been found to have anti-amoebic activity and is effective against
 EMI7.4
 amoebiasis (Enqoeba criceti) in hamsters.



  Other N- (halobenzyl) -N- (2-hydroxyethyl) -diahloroacetamides can be prepared by the method described above, using other 2- (halobenzylamino) -ethanols instead of - (2 ,. -dichlorobenzylamino) -. âthanoi.



  Thus by using 2- (2, ± -dibromobenzylanbxo) -ethanol, 2- (3 <4-diiodobenzylamino) 9ethanolD 2- (4- ± luorobencylamîno) -ethanol, 2-3 4,5-triahloro - benzylamino) -ethanol. 2- (4 ... bromo-Z ", chlorobenzylamino) -ethanol or zo d3.luorobenzylam3.no) -ethanol, N- (2.4-dibromobenzyl) -N- (2-hydroxyethyl) dichloroacetamide is obtained, N- (3 <4-diiodobenzyl) -N- (2-hydroxyethyl) dichloroacetamide T- (4-fluorobenzyl) -N- (2-hydroxyethyl) dichloroacetamide, N- (3,4D5-trichlorobenzy3) -N- (2-hydroxyethyl) dichloroacetamia, N- (4-broma-2-chlorobenzyL) - (-. Rydroxyethyl) dickz7.oroacetam.de or N- (2 4- difluorobenzyl) -N- (2 -hydroxy "thyl) dichloroac'etamide.



  Other N- (substituted benzylamino) -N- (2-hydroxyethyl) -dichloroacetamides can be prepared by the method described above, using other 2- (substituted benzylamino) -ethanols instead of 2-. (2 4-dichlorobenzy1a-mino) -ethanol. Thus, by employing 2- (ln buty2mercaptobenzy7.am3.no) -ethanol or 2 - {.- n-isobutylsulfonylbenzylamino) -ethanol, N - (- n butylmercaptobenzyl) -T- is obtained respectively. (-hydrccyethyl) d3.chloroacetamide or N- {I n-isobutyLsulfonylbenzyl) - (2 hydroxyethyl) dichloroacetam.de.



    EXAMPLE. 3
 EMI7.5
 -e orobenz -h dro ê 1 d chloro et ide
When the procedure described in Example 2 is applied, but using 27 gr of 2- (4-chlorobenzylamino) -ethanol in 500 cc of ethylene bichloride and 10.7 gr of approximately dichloroacetyl chloride.
 EMI7.6
 10 G9 13 g of N- (4-chlorobenzyl) -N- (2-hydroxyethyl) dichloroacetamine are obtained. After recrystallization from an ether-n-pentane mixture, the product melts at 94.4-97.2 C. (corrected).
 EMI7.7
 



  Analysis - Calculations for G11H12C13N0: C1w35, $? 3 0 = 44.54%; 3H = 4, α7 Found: C1 = 35.82%;
 EMI7.8
 M = 44, F3%? H = 430%.



  It has been found that N- (4-chlorobenzyl) -N- (2-hydroxyethyl) -dichlo-
 EMI7.9
 roacetamide has anti-amoebic activity, this compound being effective against

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 amoebiasis (Endamoeba criceti) in hamsters.
 EMI8.1
 



  Other N-halobenzyl) -N- (2-hydroxyethyl) -dichloroacetamides can be prepared by the method given above, using other 2- (halobenzylamino) -ethanols instead of 2- (4-chlorobenzylamino) -etha - nol. So,. using 2- (1.-Bromo benzyl-aa, ï.no) ethanol, 2- (4-io- - dobenzylamino) -ethanol, 2- (4-fluoro-benzylamino) -ethanol or 2 - (3-chlo- robenzylarnino) -ethanol, N- (4-bromobenzyl) - n- (2-hydroxy.ethyl) -diehloroaeetanide, N- (4-iodobenzyl) -N- (2 -hydroxyethyl) dichloroacetamidej, N- (l.-fiuorobanzyl) -1 - (- hydroxyethyl) dichloroacetamide or N- (3-chlorobenzyl) -I- (z hydroxythy.) d, ciloreactamide.



  Example 4 N- -etho benz 1 -h dro eth I dichloroa st id
A mixture of 7 g of 2- (4-ethoxybenzylamino) -ethanol and 5.7 g of methyl dichloroacetate is heated at 60-70 C for 5 hours, then poured, with stirring, into 100 cc of acid. hydrochloric IN. The product, which solidifies. is collected by filtration and dried in air, after recrystallizations successively in a mixture of benzene and n-pentane and in a mixture of ether and n-pentane. N- (4-ethoxybenzyl) -N- (2-hydroxy-
 EMI8.2
 ethylid1chloroacetamide melts at zo3 - '79, L G. (corrected) Analysis - Calculate for GIHi7C1N03: Cl = 23 16%; 0 = 50.99%. H, 5.60%.



  Found: CI = 23.18%;
 EMI8.3
 G = 51,, 26%; '. 5, s'7 N- (4-ethoxybenzyl) -N- (2-hydroxyethyl) -aichloroacetmide possesses anti-amoebic activity and is effective against amebiasis (Endamoeba. Criceti) in hamsters.



   By following the procedure described above, but using methyl diiodoacetate, ethyl dibromoacetate or n-butyl difluoroacetate, instead of methyl dichloroacetate, respectively, one obtains
 EMI8.4
 the following products: N- (4-ethoxybenzyl) -8- (2-hydroxyethyl) -aiidoacetide.



  N- (4-ethoxybenzyl) -N- (2-hydroxyethyl) dibromoacetamide or N- (4-ethoxybenzyl) -N- (2-hydroxyeth; 1) atlfluoroacetmide.



  Example 5 (2-hvdroxyethvl) -1- so r benz l d.ehloroact ida.



  To a solution of 43 g of 2- (4-isopropyl-benzylaono) -ethanol in 850 cc of ethylene bichloride, is added at 0 C and with stirring a solution of 16.3 g of dichloroacetyl chloride in 40 that of ethylene bichloride ..; After the addition, stirring is continued for one hour and the mixture is left to stand overnight at room temperature, after which it is washed successively with water and acid. dilute hydrochloric acid and again with water. After drying, the solvent is removed by distillation and
 EMI8.5
 16 g of N- (2 - hydroxyethyl) I- (I isoprapyibenzyl) -diahloroacetamine are obtained. After recrystallizations successively from a mixture of ether and n-pentane and from n-heptane, the product melts at * 2ga5- $ 5z5 c (corrected).



  Analysis - Calculate for G .1 Gl z NO: z 01 = 23.32%; G, 55.27%; E = 6.30Ea Found: C1 = 23.07%;
 EMI8.6
 C, 55.17%; H = 6..49%.

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 EMI9.1
 It has been found that N- (hydroxyethyl-1- (t-.soprapylberizyl) - dichloroacetamide has anti-amoebic activity., This compound being ef-
 EMI9.2
 effective against amebiasis (Endamoeba criceti) in hamsters.



  Other N- (alkylated benzyl) -N- (2-hydroxyethyl) -dichloroacetamides can be prepared by the method described above, using other 2- (alkyl-benzyl-amino) -ethanols. instead of 2- (4-isopropylbenzyl-smmo) - ethanol. So. by using 2- (2-ethyl-benzylamino) -ethanol, 2- (3-n = butylbenzylwdno) -ethanol, Z- (t-3.sobutylbenzylam3no) -ethanol, 2- (4-n- hexyl- benzylamino) -éthanoljt 2-3.4-diethylbenzylanmo) -ethanol or Z - (,, 1,5-trimethylbenzylamino) - ethanol, we obtain respectively N- (2-ethyl-benzyl) -N- (2 -hydroxyethyl) dichloroacetamide, N- (3-n-butylbenzyl) -N- (2. hydroxyethyl) dichloroacetamide, N- (2-hydroxyethyl) -N- (± -isobutylb'enzyl) dichloroacetamide, N- (4-n-hexylbenzyl) -N- (2-hydroxyethyl) dlchloroaoéta- m3.de, N- (3,, 4-diethylbenzyl) -N- (2-hydroxyethyl) dichloroacët =:

  Lde. or N- (-hydroxyethyl) -T- (3, 1, 5tr3snethylbenzyl) dichloroacetanaide.



  EXAMPLE 6 N- (2-hydroxvethyl) -N- (3.α-methvlenedioxvbenzvl) dichloroacetamide. z a solution of 46 gr. of 2-3 4-mô% hylene-dioxybenzylamino) - ethanol in 800 cc of ethylene bichloride. 17.6 g of dichloroacetyl chloride are added in 40 cc of ethylene bichloride. After the addition. stirring is continued for 1 hour and the mixture is left to stand overnight at room temperature. The mixture is then washed successively with water, dilute hydrochloric acid and with water.



  After drying, the solvent is removed by distillation.
 EMI9.3
 



  14 g of N- (2-hydroxyethyl) -N- (3 <4'-methylenedioxybenzyl) - dichloroacetamide are thus obtained. After recrystallizations successively from a mixture of ether and n-pentane and from ether, the product melts at 101.9 - 103.4 C.



  (corrected).
 EMI9.4
 



  Analysis - Calculated for cr3c1zN0: 01 = 2317 C = 47.08% H = 4.28%.
 EMI9.5
 



  Found: Gl * $ 22.89; G = 47.09 #; H = 4 ... 39%.



  N- (2 & nydroxyethyl) -N- (3 4-methylenedioxybenzyl) -diehloroacetamide has been found to have anti-amoebic activity and is effective against amebiasis (Endamoeba criceti) in hamsters.



   EXAMPLE 7 @
 EMI9.6
 N- (2-hydroxvethvl-N- (4-nitrobenzvl) -dichloroacetamide,
16 g of 2- (4-nitrobenzylamino) -ethanol are dissolved in 150 cc of ethylene dichloride, heating to 35 C. The solution is cooled while stirring to 25 C. and added, dropwise, 6 g of Dichloroacetyl chloride in 20 cc of etylene dichloride. The temperature rises to 35 ° C and a solid begins to separate. The mixture is stirred for 90 minutes and filtered. The solid material is stirred in water. 5 g of an insoluble material are obtained, melting at 127 - 131 C. After recrystallization.
 EMI9.7
 When dissolved in ethanol, the product, α, namely N- (2-hydroxyethyl) -N- (4-nitro-benzyl) -dichloroacetamide, melts at 132.2 - 133 6 GB (corrected).

   Analysis - Calculated for CliHlCl2N, 04:01 = 23.09%; 0 = 43.02%;
H, 3.94%.



  Found: C1 = 23.01%;
 EMI9.8
 C = 43 22 # j 3 H = s J-5

 <Desc / Clms Page number 10>

 
 EMI10.1
 It was found that N- (2-hydr iyethyl) -N- (4-nitrobenzyl) -dichlorô-acetamide has anti-amoebic activity and is effective against amebiasis
 EMI10.2
 (Endamoeba criceti) hamsters. - Following the same procedure but using 1- (4-ni-trobenzylamino) -Z-propanol, 3- (4-nitrobenzylaàmo) µropanol, 1- (2.4-di-chlorobenzy3arniio} -2-propanol; 1- (4-n-butylbenzylmmo) -2-propanol, 1- (3 4-aichlorobenzylmino) -2-butanol 1- (2.4-dichlorobenzylardno) -2-hexa: '"- nol and 3 = (4 -isopropyibenzylarino) propanol, instead of-Z- (4-nitrobenzylamino) - ethanol, the following products are respectively obtained: N- (2-hydroxypropyl) - N- (l n3trobenzy7.) d3.chloroacttam.de, N- ( 3-hydroxypropyl) -N- (4-nitrobenzyl) dichloroacetamide.

   N- (2 4-dichlorobenzyl) -N- (2-hydroxypropyl) dichloroacetmide N- (4- n butyZbenzyl) T- (2 hydroopyi ;,) dichloroacetamide, N- (3 4 <iahlorobenzyl) -N- (2-hydroxybutyl ) dichloroacetamide. N- (2g1-d3.chlorobenzyl) .ti- (hydroheI) dichloraacetamide and N- (3 ydroxypropyl) = t- (4 isogropylbenzyl) dichloroacetamide.



   Following the procedure of Example 7, but employing
 EMI10.3
 dibromoacetyl bromide. diiodoacetyl iodide ,. difluoroacetyl fluoride or bromochloroacetyl chloride, instead of dichloroacetyl chloride, the following respective compounds are obtained: N- (2-hydroxy-
 EMI10.4
 ethyl) -i (.- nitrobenzyl} dibromoaceta: nide9 N- (2-hydraxyethyl) -N- (4-nitrobenzyl) di10doacéÚlmiâè- N- (2 hydroxyethyl) 1- (h nitrobenzyl) difltsr: acért3.d "ti" ' N - (- hyd = 'tax3 = êthy.)' -'I {, hitrca'.I},. ¯ ## "#,. Bromochloroacét8l'lide.



  EXAMPLE 8 N - (- n-butoxvbenzyl) -N- (2-hvdroxvethvl) dichloroacetAmide.-
A solution of 4.63 g of diacetyl chloride in 20 cc of ethylene bichloride is added dropwise, with stirring and cooling.
 EMI10.5
 sant (0-500), to a solution of 14 g of 2- (4-butoxybensylamino) -ethanol in 100 cc of ethylene bichloride.



  When the addition is complete, the reaction mixture is left to stand overnight at room temperature and ether is added. We thus obtain
 EMI10.6
 8 g of 2 = (4 n butaxybenzylaxio) -ethanol hydrochloride. The solid material is separated by filtration and the filtrate is washed successively with IN hydrochloric acid and with water. After drying over calcium sulphate, the solvents are removed by distillation. The residue is dissolved in ether, fil-
 EMI10.7
 Treated with carbon dioxide and added with n-pentane until cloudiness forms. We obtain 5 g of a product melting at 81 - 85 C.

   After recrystallization from a mixture of ether and n-pentane, N- (4-n-butoxy-
 EMI10.8
 benzyl) -N- (2-hydroxyethyl $ -diahloroaaetauid m.p. 88 ':;' C'8'S.9C (corrected).



  AnalYse- - Calculated for C15H21C12NG3: e1 = 2., $; C = 53.9 H = 6.33 Found: G1 = zls. ', E-3, H = 6.44%
N- (4-n-butoxybenzyl) -N- (2-hydroxyethyl) - dichloroacetamide has been found to have anti-amoebic activity, this compound being ef-
 EMI10.9
 effective against amebiasis (Endamoeba criceti) in hamsters.



  Following the procedure described above, but using 2- (4-ethoxybenzylamino) -ethanol. 2- (4-n-propoxybenzylamino) -etha-no1. 2- (4-isopropoxybenzylamino) -ethanol, 2- (4-isobutoxybenzylamino) - ethanol. 2- (4-n-amoxybenzylamIno) -ethanol, 2- (4-n-hexoxy ± nzylamino) - ethanol or 2- (345-'é'ol instead of 2- (4-n-butoxybenzy- lamino) ) -ethanol, the following products are obtained: N- (4-ethoxybenzyl) -N- (Z hydroxyethyl) dichloroz3e, NJ2-hydroxyethyl) -N- (4-n-propoxybenzyl)

 <Desc / Clms Page number 11>

 
 EMI11.1
 dichloroacetamidej, N- (ahydroxyethyl) -Tl isopropoxybenzyl) d3ek.oroacetamide, N (-hyâroxyeth, y.) - ty4-isobutoxybenzyl) dichloroacetarnide, N- (4-n-amoxybenzyl) - N (-hydroxyethoacetamide) , N- (4-n-hexoxybenzyl) -N-2-hydroxyeth $ 1) dichloroacetamide or N- (3, l, 5-trimethoxybenzyl) - (2-hydroxyethyl) dichloroacet3d.



  EXAMPLE 9 N - (2 -dichlorobenzyl) -N - (2-hvdroxvéthvl) dibromoacetamide A mixture of 5a5 gr of 2- (2 4-diehloTobenzyl-amino) -ethanol and 7 gr of ethyl dibromoacetate is heated to 60 ° C. , during 3 hours. The mixture, which has undergone thickening, is stirred in dilute hydrochloric acid and the product is extracted with chloroform. The chloroform solution is washed with water and dried. After removal of the chloroform by distillation, the residue is recrystallized from ethylene dichloride and a
 EMI11.2
 small amount of n-hexane. 3.5 g of N- (4-dich.orobenzyL) N- (2-hydroxyethyl) -dibromoacetamide are thus obtained, melting at 115.0-117 2 C. (corrected).



  Analysis - calculated for cHciBrNo: Br = 38.07 $; 0 = 31.46%; H = 2.64% Found: Br = 37.75%;
 EMI11.3
 Cs3-a 1H = 2..85% N- (2 4-diehlorobenzyl) -N- (2-hydroxyethyl) - dibromoacetamide has been found to have anti-amoebic activity and is effective against amebiasis (Endamoeba criceti) hamsters.



   EXAMPLE 10
 EMI11.4
 - -di h orobenz 1 - 'h drox ra. -d ro ce amid.



  A mixture of 17 g of 1- (2 I-dichlorobenzylaraino) -2-propa-. nol and 11.5 g of methyl dichloroacetate is heated, with stirring, at 10-70 ° C. for 4 hours. After stirring the resulting mixture with 1N hydrochloric acid, the product was collected and washed with water. The yield reached 18 g.



  After two recrystallizations from ethylene bichloride, the product consisting of N- (2.4-dichlorobenzyl) -N- (2-hydroxypropyl) dichloroaceta-
 EMI11.5
 mid ,,, bottom at 135 1 - 13800. (corrected).



  Analysis - Calculated for CHZClNOC'iy = I1, IO; C = t, .a7'T; H = 3 JI Sc,.



  Found: Cl =, 4, b6; C = l.,., 5b ;; li = 3.97%.



  It was found that N- (2.4 "eohlorobenzyl) -N- (2-hydroxypropyl) -dichloroacetamide possesses anti-amoebic activity, this compound being effective against the amoebiasis (Eda, oeba jack, ti.) Of hamsters.



  EXAMPLE 11, N-) 4dich1orobenzvl) -N - (- hvdroxyoroDyl) dchloroacetide.



  A mixture of 17.5 g of 1- (3 4-diahlorobenzyl & dno) -2-propanol and 11.9 g of methyl dichloroacetate is heated at 60 ° C. for 4 hours. After stirring the resulting mixture with 1N hydrochloric acid, the product is collected and washed with water.



  The yield reaches 8 gr. After two recrystallizations. In bichloru-
 EMI11.6
 re of ethyleneSl the product obtained â, namely N- (3.4-dichlorobenzyl) -N- (2-

 <Desc / Clms Page number 12>

 
 EMI12.1
 hydroxypropyi) -diahloroaaétmide melts at 120 0 - 7.198 G. (corrected).



  Analysis - Calculated for GHl3GlNOZsC = Ifla7?,; H = 3p80 ,; C1KOH = 20.55%
 EMI12.2
 Found aC = L900;: H - 3, g6; C1xOH = 20 52% C1KOH = chlorine of the dichloroacetyl radical
 EMI12.3
 N- (3 4-diehlorobenzyl) -N- (2-hydroxypropyl) - dichloroacetamide has been found to have anti-amoebic activity and is effective against amebiasis (Endamoeba criceti) in hamsters.



   EXAMPLE 12
 EMI12.4
 N- {2-chlorobenz: vl) -N- (2-h: vdroxth: vl) dichloroacetamide.



   A mixture of 15 g of N- (2-chlorobenzylamino) -ethanolamine, 80 cc of IN sodium hydroxide and 100 cc of ethylene bichloride is cooled, with stirring, to less than 0 C. A solution of 12 gr. of dichloroacetyl chloride in 30 cc of ethylene bichloride is added dropwise, over the course of one hour, keeping the temperature below 0 C. After stirring for an additional 2 hours at room temperature, the layers are separated and the ethylene dichloride layer is washed successively with IN sodium hydroxide, with water, with IN hydrochloric acid and with water. The solvent is dried and removed.



  After two recrystallizations from a mixture of n-pentane and benzene and a third recrystallization from a mixture of ether and n-pentane. the
 EMI12.5
 product namely N- (2-ehlorobenzyl) -N- (2-hydroxyethyl) dichloroacetamide, melts at 76 6 - 79.3 ca (corrected); Yield 11n0 gf Analysis - Calculated for l "123'2 '" "" "' G-IÒH 3 $ 8 Found ô C ll., tE1; H = 4.32; COH = 23, D96%.



  N - (2-Chloro benzyl) 41 - (2-hydroxyethyl) -dichloroacetamide has been found to have anti-amiblen activity, this compound being effective against amoebiasis (Endamoeba criceti) in hamsters.



   EXAMPLE 13
 EMI12.6
 N- (3s4md.ichlorobenwl) 1-i3-hvdroxydronyl) -dichloroacemide. A mixture of 9.4 g of 3- (3 <4 "dichlorobenzylsmino) -propanol and 6.4 g of methyl dichloroacetate is heated at 60-70 C for 6 hours. After stirring the resulting mixture with hydrochloric acid In, the product is collected yield: 12.5 g After two recrystallizations from a mixture of benzene and n-pentane and after two recrystallizations from a mixture of ethylene bichloride and n-pentane, the product, namely the NOT-
 EMI12.7
 t34 dichlorobnayl) 3- (3-hydroxygropyl) dichloraacetamide, melts at 91.9 - 97.5 C (corrected); yield: 7 5 gr.



  Analysis - calculated for GH13C1NO2: C = .2.6; H = 3.793 C1 = 41.10%.

 <Desc / Clms Page number 13>

 
 EMI13.1
 



  Found: C = 17., 70 ;; Ha3, $ 9; 0 1-41. N- (3 4-Diohlorobenzyl) -à- (3-hydroxypropyl) - dichloroacetamide has been found to have anti-amoebic activity. this compound being effective against amebiasis (Endamoeba criceti) in hamsters.



   EXAMPLE 14.
 EMI13.2
 



  N- (2L-diehlorobenzvl) -N- (3-hvdroxvDroDvl) -diehloroa, aétµ $ de. A mixture of 9 to 4 g of 3- (2t4 '* dichlorobenzylamino) -propanol and 6.4 g of methyl dichloroacetate is heated at 60 ° C. for four hours. After stirring the resulting mixture with 1N hydrochloric acid, the insoluble material is taken up in chloroform. dried and freed from solvent; yield: 8 gr. After three recrystallizations in a medium
 EMI13.3
 mixture of benzene-n-pentane, the product. namely N- (2,4-dichlorobenzyl) - N- (3-hydroxypropyl) -dichloroacetamide, melts at 83 7 - 86 70C (corrected).



  Analysis - calculated for C12HCOINO: C = 1., 'F; H = 3, '79: Cl = .la., 1 (found: C = 4., 60; R - 3.88%; C1 = 41 < 23% N- (2 4-diahlorobenzyl) -N-3-hydroxypropyi) - dichloroacetamide has been found to have anti-8mibial activity, this amide being effective against amebiasis (Endamoeba criceti) in hamsters.



   EXAMPLE 15
 EMI13.4
 N- (3.Z, -dichlorobezyl) -N- (2-hydrpxyethyl) -dibrQmoacetamide.



  A mixture of 11.0 g of 2- (3 4-diahlorobenzylamàno) -ethanol and 14 g of ethyl dibrouaoacetate is heated to 60PO. during 3 hours.



  After stirring the resulting mixture with IN hydrochloric acid the insoluble material is taken up in chloroform. washed with water and dried.
 EMI13.5
 



  When removing the solvent. the residue solidifies. After two recrystallizations from a mixture of ethylene bichloride-n-pentane, the N- (3,4 dichlorobenzyl) -N- (2-hydroxyethyl) -dibromoacetamide melts at 115.5-128.8 C.



  (corrected).
 EMI13.6
 



  Analysis - Calculated for C1lHBrC.NOZ: G = 3L ,, 6; H = 2 <64%; Br = 38.07% Found: 0-31 54%; H = 2a 4; Ux "$ 3 39.



  N- (3,4-Diahlorobenzyl) -N- (2-hydroxyethyl) -dibromoacetsmide possesses. as has been observed, anti-amoebic activity, this amide being effective against amebiasis (Endamoeba criceti) in hamsters.



   EXAMPLE 16
 EMI13.7
 N-'3D4-dethoXYbenzYl) -N- (2-hYdroéh1) -dch1oroacetid.



  A mixture of 10.5 gr of 2- (34-d1methoxybenzylamino) -ethanol

 <Desc / Clms Page number 14>

 and 8 g of methyl dichloroacetate is heated at 60 ° C. for 3 hours. After stirring the reaction mixture with IN hydrochloric acid, the insoluble material is taken up in ethylene bichloride. The acid layer is then extracted with ethylene dichloride. The ethylene bichloride extracts are combined, washed with water, dried and treated with charcoal. After two recrystallizations of the solid material in a mixture of
 EMI14.1
 Ethylene bichloride and n-pentane, N- (3 4-dinethoxybenzyl) -N- (2-hydro-xyethyl) -dichloroacetamide obtained melts at z, 6 - U7.70r, (corrected).



  Analysis - calculated for Cl, Cil, NOe ['r-l, g, + SH 5s3.R C1KOH = 22.01%
 EMI14.2
 found * 0 = 48.54%; H - 5-16%; ClxOH = $ 22.11.



  N- (3 4-dàmethoxybenzyl) -N- (2-hydroxyethyl) - dichloroacetamide has been found to have anti-amoebic activity, being effective against 1 '
 EMI14.3
 amoebiasis (ikdamoeba cricsti) of hamsters.



  CLAIMS.



  1. Process for the preparation of an N- (substituted benzyl) -N- (lower hydroxyalkyl) -dihaloaaetamide having the formula I given above, in which a (substituted benzylamino) -a3.anoi of formula II is reacted. given above with a dihaloacetylating agent consisting of a lower alkyl dihaloacetate or a dihaloethyl halide.


    

Claims (1)

2. A process: according to claim 1, wherein a beta-(halogenated benzylamino) -lower alkanel is reacted with a dihaloacetylating agent. 3. Process according to claim 2, in which a EMI14.4 lower beta (dihalobenzylami.no) -a3.laa.o1, such as 2- (dihalobenzylamino) - ethanol. 4. A process according to claim 3 wherein a 2- (dihalo-benzylamino) -ethanol is reacted with a lower alkyl dibromoacetate. 5. Method according to claim 4, in which EMI14.5 react 2- (Z, 4-dich2oro benzylamina) - ethanol with ethyl dibromoacetate. 6. A method according to claim 4, in which EMI14.6 react 2-3 4-diahloro-benzylammo) -ethanol with ethyl dibromoacetate. 7. A process according to claim 3, wherein a 2- (dihalobenzylamino) -ethanol is reacted with dichloroacetyl chloride. 8. The method of claim 7. wherein is carried out EMI14.7 gir du - (2, .- dichlorobenzylamol) -ethanol with dichloroacetyl chloride. 9. The method of claim 7. wherein one makes EMI14.8 react a - (3s4-dichlorabenzylamino) = ethanol with dichloroacetyl chloride. 10. The method of claim 1, wherein one makes EMI14.9 reacting a beta-(benzylamino alkoxyléj-allanol with a dihaloacetyl halide. 11. The method of claim 10, wherein one employs EMI14.10 a beta- (monoalkoxybenzyl) -. lower alkancl., for example a 2- (monoalkoxy-ben- <Desc / Clms Page number 15> zylamino) -ethanol. 12. The method of claim 11, wherein a 2- (monoalkoxybenzylamino) -ethanol is reacted with dichloroacetyl chloride. 13. The method of claim 4, wherein one makes EMI15.1 reacting Z- (1-n buto7cybenzylamin.o) -ethanol with dichloroacetyla chloride. 14. N- (substituted benzyl) -N- (lower hydroxyalaoyl) -dihaloa- ketamide of formula I given above, for example N- (halogenated benzyl) -N- (beta-hydroxyalkyl .nower) -d3.haloacetamides and N - (benzyl alcohol) -N- (beta-hydroxy lower alkyl) -dibaloacetamides. 15. N- (dihalobenzyl) -N- (beta.-hydroxy lower alkyl) -d3haloacetamides. for example N- (2 4-dichlorobenzyl) -N- (2-hydroxyethyl) -diahloroacé- tamidep 1Q- (3D / dichlorobenzy.) 1- (2-hydraxyâth3 .-) - diehloroacetam.de, N- (2, " 4- d3.chlorabenzyl) .i- (hydxoxyethyl) -dibromoaoetamide "N- (3 4 + diahlorobenzyl) - N- (2 hydroxyethyl) -d, .bromoacetamide. 16. N - (monoalkoxybenzyl) -N - (indoor beta-hydroxyalkyl) - dihaloacstamideSt eg N- (4-n-butoxybenzyl) -N- (2-hydroxyethyl) -dichlo-roacetamide.