METHOD FOR ENHANCING THE GROWTH RATE OF MEAT-PRODUCING ANIMALS AND FOR IMPROVING THE LEAN MEAT TO FAT RATIO THEREOF

Abstract: There is provided a method for enhancing the growth rate of meat-producing animals, improving the efficiency of feed utilization thereby, and or improving the lean meat to fat ratio thereof, which involves, orally or parenterally, administering to said animals a growth-enhancing amount of a phenylethane compound or the acid addition salt thereof.

Description: PHENYLETHANE DERIVATIVES AND ACID ADDITION SALT THEREOF FOR ENHANCING IT GROMTH RATE OF MEAT-PRODUCING ANIMALS, DMPROVBVE THE EFFICIENCY OF FEED UTILIZATION THEREBY AND/OR IMPROVING THE LEAN MEAT To FAT RATIO THEREOF SUMMARY OF THE INVENTION Substitution products of l-(amino-dihalophenyl) -2-aminoethanes, and the acid addition salts thereof, are disclosed in United States Patent 3,536,712, issued October 27, 1970. Specifically, methods for the synthesis of said compounds are discolsed as useful for enhancing the blood circulation, and as bronchodilators, analgesics, sedatives, antipyretics, antiphlogistics and antitussives in warm-blooded animals. However, only the analgesic utility is examplified. The preparation of other related 1-(amino-dihyalophenyl)-2-aminoethanols and their deriva tives are disclosed in Japanese Itokai 77 83,619(Chemical Abstracts, 87,201061r), German Offenlegungsschrift 2,804,625 (1979), Gcrman Offenlegungsschrift 2,157,040 (1973), German Offenlegungsshrift 2,261,914 (1974), Europen Patent Application 8,715 (1980), Xetherlands Patent Application 7,303,612 (1973). These applications disclose uses selected from analgesics, broncholytic, antiinflanmatory, uterine spasmolytic, ss-blocking activities, antispaemolytic activity on cross-striped muscle structure, for tocology, reducing blood pressure by peripheral vasodilation and mobilizing body fat, and for treating allergies. There is no indication or suggestion in any of these disclosures that said compounds are effective as growth-promoting agents for meat-producing animals, such as poultry, tattle, sheep or the like; nor is there any suggestion that said compounds improve the efficiency of feed utilization by said meat-producing animals. In accordance with the process of the invention, it has been found that the growth rate of meat-producing animals such as chickens, turkeys, rabbits, sheep, swine, goats and cattle, including calves, can be increased, the efficiency of feed utilization thereby measurably improved, and the lean meat to fat ratio improved by the oral or parenteral administratin to said ard of an effective amount of a confound, selected from the group consisting of: : EMI2.1 EMI3.1 wherein, X is hydrogen, halogen or -CN; Y is hydrogen, 2 is hydrogen, halogen, OH, CN, CF3, COOR1, CONH2, C1-C4 alkyl, C1-C4 alkoxy, NO2, C1-C4-dialkylaminomethyl or hydroxymethyl; R1 is hydrogen or C1-C4 alkyl; R2 is hydrogen, C1-C2 alkyl, C. 1-C4 alkenyl, C2-C5 alkanoyl or EMI3.2 is hydrogen C1-C6 alkyl, C3-6 cycloalkyl, methoxypropyl, C3-C alkenyl, phenyl, 2-hydroxyethyl, &alpha;,&alpha;- dimethylphenethyl, benzyl, 3-phenylpropyl or 3-(4carbomethoxyphenyl)propyl; and when R2 and R3 are taken together with the nitrogen to which they are attached, they represent morpholino or N'-C1-C4 alkylpiperazino;/ RI is hydrogen, OH, OR6 or SR11; R5 is hydrogen, C1-C4 alkyl, C1-C4 alkoxy, EMI3.3 R6 is C1-C6 alkyl, C2-C5 alkanoyl, EMI4.1 C3-C4 alkenyl; is hydrogen, C1-4 alkyl or phenyl; R8 is hydrogen, C1-C4 alkyl or C3-C4 alkenyl; is hydrogen, C1-C6 alkyl, C4-C6 cycloalkyl, C3-C4 alkenyl, or benzyl; and when R8 and R9 are taken together with the nitrogen to which they are attached, they represent pyrrolidino; R10 is chloro, dichloro, methyl, dimethyl, methoxy, methoxy or nitro; R11 is C1-C6 alkyl, phenyl or benzyl; with the provisos that when R3 is phenyl, 2-hydroxyethyl, &alpha;,&alpha;-dimethylphenethyl, C3-C6 cycloalkyl, benzyl, methoxypropyl, 3-phenylpropyl, or 3-(4-carbomethoxyphenyl)propyl, R2 is hydrogen; and when R3 is hydroxyethyl, R4 is hydroxyl and the compound is (I)t and when R6 is alkanoyl or EMI4.2 and R3 are substituents other than hydrogen, except when R3 is an alkyl or substituted alkyl group which contains a tertiary carbon attached to nitrogen; and when Y is hydrogen, I and Z are halogen, and R2 is hydrogen, C3-C5 alkanoyl or EMI4.3 R3 is isopropyl, 2-butyl, or t-butyl, and when is C-C4 alkyl or C3-C alkenyl, R9 is hydrogen, C1-C4 alkyl or C3-C4 alkenyl; and when Z is OH, X and Y are hydrogen; and that at least one of X, Y, and Z represents a substituted other than hydrogen; and when X is -CN, Z is -CH; and when Z is hydroxymethyl, R4 is OH; and when Z is a group other than halogen, Y is NR8R9 or NHCOR5; and when Rg is N(R1)2, , RI is OH; and further provided that when X is hydrogen or halogen, and Y is hydrogen, NH2 or NHCOR5, and Z is hydrogen, hal- ogen or OH, then R4 cannot be hydrogen, OH or OR6 where R6 is C1-C6 alkyl; racemix mixtures of the above - identified compounds and the optically active iscmers, and non-toxic, pharmacologically acceptable acid addition salts thereof. A preferred group of compounds for use in the method of this invention have the above formula I structure wherein X is hydrogen or halogen; Y is hydrogen, NR8R9 or NHCOR5; Z is halogen, OH, CN, CF3, COOR1, CONH2, methyl, methoxy, NO2, C1-C4 dialkylaminomethyl, or hydroxy methyl; and the remaining groups are as hereinbefore defined; or a non-toxic, pharmacologically acceptable acid addition salt thereof. Another preferred group of compounds for use in the method of this invention have the above formula I structure wherein X is hydrogen, chlorine, or bromine; T is hydrogen or NR8R9, Z is chlorine, bromins, CN, CF3; R1 is hydrogen or methyl; R4 is OH, OR6, SR11, R6 is C1-C6 alkyl, benzyl, C2-C5 alkanoyl, or henzoyl; or a non-toxic, pharmacologically acceptable acid addition salt thereof. The most preferred compounds for use in this invention are: 4-amino-N-tert-butyl-3,5-dichloro- ss-methoxyphenethylamine; N-tert-butyl 3,5-dichkloro-ss-methoxy-4-methylamine; &alpha;-[(tert- butylamino)methyl3-3,5dichloro-a-isopropylaminGbenzyl alcohol 5-[2-(tert-buytylamino)-1-hydroxyethyl)-3-chlorocanthranilonitril 5-C 2-(tert-butylamFno )-l-hydroxyethyl anthranilonitrile; methyl -5-[2-(tert-buytylamino)-1-hydroxyethyl]-3-chlorocanthronilate; 4Ú-[2-(tert-buytylamino)-1-hydroxyethyl]-2Ú,6Ú-dichlorovaleranilide; benzyl-4-[2-(tert-buytylamino)-1-hydroxyethyl]-2,6-dichlorocarbon ilate; 5-acethylanthranilonitrile; 4-amino-N-tert-buyl-3,5-dichlore -ss-(methylthio)phenylamine; N-tert-butyl-3,5-dichloro-ss-methoxy phenethylamine; &alpha;-[(tert-butylamino)-methyl]-3,5-dichloro-4-methy- laminobenzyl alcohol; &alpha;-[(tert-butylamino)methyl-3,5-dichloro-4- dimethylaminobenzyl alcobol:f 4-amino-3,5-dichloro-&alpha;-([3-phenyl- propyl)amino]methyl]benzyl alcobol; 4-amino-3,5-dichloro-&alpha;{[&alpha;,&alpha;- dimethylphenethyl)amino]methyl}benzyl alcohol; 4-amino-N-tert butyl-3,5-dichloro-ss-ethyoxyphenythylamine; methyl-p-{3-[(4 amino-3,5-dichloro-ss-hydroxyphenethyl)amino]propyl]benzoate; methyl-4-[2-(tert-butylamino)-1-hydroxyethyl]-2,6-dichlorocarbanilate; 4Ú-[2-(tert-butylamino)-1-hydroxyethyl]-2Ú,6Ú-dichkloroacetanilide; 5-[2(tert-butylamino)-1-hydroxyethyl]-3-choroanthranilontrile; 4 amino-ss-(benzyloxy)-N-tert-butyl-3,5-dichlorophenethylamine and the non-toxic, pharmaceuticnlly acceptable acid addition salts thereof. Although it is evident from the above discussion that certain compounds represented by formula I above are described in the literature, many compounds represented by formula I are new and unobvious. The novel and unobvious compounds of the present invention are represented by the structure of formula I. wherein X is hydrogen, halogen or -CN; Y is hydrogen, NR8Rg or NECOR5; Z is halogen, -CN, CF3, COOR1, CONE2, C1-C4 alkyl, C1-C4 alkoxy, NO2 or C1-C4 dialkylaminomethyl; R1 is hydrogen or C1-C4 alkyl; R2 is hydrogen, C1-C4 alkyl, C3-C6 cycloalkyl, C34 alkenyl, C2-C5 alkanoyl or EMI7.1 R3 is hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl, C34 alkenyl, phenyl or benzyl; R4 is OH, OR6 or SR11; R5 is hydrogen, C1-C4 alkyl, C1-C4 alkoxy, EMI7.2 R6 is C1-C6 alkyl, C2-C5 alkanoyl, EMI7.3 R6 is hydrogen, C1-C4 alkyl or C3-C4 alkenyl; R9 is hydrogen, C1-C6 alkyl, C4-C6 cycloalkyl, C3-C4 alkenyl, or benzyl; R10 is hydrogen, chloro, dichloro, methyl, dimethyl, methoxy, dimethoxy or nitro; R11 is C1-C6 alkyl, phenyl, benzyl; with the provisos taht when Y is NH2 , NHCH3, NHC2H5 or NHCOR5, R1 is OR2 or SR11; and when Y is hydrogen, X and Y are halogen, R2 is hydrogen, C2-C5 alkanoyl or EMI7.4 and R3 is isopropyl, 2-butyl or t-butyl; and when X is -CN, Z is -CN; and when R6 is alkanoyl or EMI8.1 2 and R3 are substituents other than hydrogen, except when R3 is an alkyl or a substituted alkyl group which contains a tertiary carbon attached to nitrogen; and when R8 is C1-C4 alkyl, or C3-C4 alkenyl, R9 is hydrogen, C1-C4 alkyl or C3-C4 alkenyl; and further provided that when X and Z are halogen and Y is hydrogen or NH2, then R4 cannot be hydrogen, OH or OR6 where R6 is C1-C6 alkyl. Racemic mixtures of the above identified compounds and the optically active isomers, and nontoxic pharmacologically acceptable acid addition salts thereof. A preferred group of the novel compounds of this invention have the above structure wherein X = hydrogen or halogen; Y is hydrogen, NR8R9, or NH-COR5; Z is halogen, CH, CF3, COOR, CONH2, methyl, methoxy, N02, C1-C4 dialkylaminometyl; RI is hydrogen, or methyl, R2 is hydrogen, C1-C4 alkyl, C3-C4 alkenyl, C2-4 alkanoyl or benzoyl; R3 is hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C4 alkenyl, with the above provisos, and further provided that when X and Z are halogen and Y is hydrogen or NH2, then cannot be hydrogen, OH or benzyl; when R6 is C16 alkyl. A most preferred group of novel compounds of this invention have the above structure wherein X = hydrogen, chlorine, bromine; Z is chlorine, bromine, CN, CF3, COOH, COOCH3, COOC2H5, CONH2; R1 is hydrogen; R2 is hydrogen, C1-C4 alkyl; R3 is hydrogen, C1-C4 alkyl; with the above provisos, and further provided that when X and Z are halogen and Y is hydrogen or NH2, then R4 cannot be hydrogen, OH or OR6 where R6 is C1-C6 alkyl. It is found, that formula (I) compounds below (wherein Y is hydrogen) can be prepared by the condensation of an appropriately substituted styrene oxide with the appropriately substituted amine in the presence of an inert solvent, such as a lower alcohol at or near the boiling point of same, as shown below: EMI9.1 wherein X and 2 are halogen, R2 and R3 are as hereinabove defined and Y is bydrogen. Thus, 3,5-dichlorostyrene oxide can be reacted with an equimolar or molar excess of t-butylamine in ethanol at reflux from about one to about eight hours, or until the reaction is essentially complete and the desired @-[(t-butylamino)methyl]-3,5- dichlorobenzyl alcohol is obtained as illustrated below: EMI9.2 The thus obtained product can be purified by known procedures, such as chromatography or recrystallization of salts thereof. The above styrene oxide is made by reducing the corresponding phenacyl bromide with NaBH4 at or below 5 C in the presence of an anhydrous lower alcohol, such as ethanol. The phenacyl bromide intermediate is prepared by brominating the appropriately substituted acetophenone with CuBr2 in the presence of chloroform and ethyl acetate. The above sequence may be graphically illustrated as follows: EMI10.1 Alternatively, a formula (I) compound wherein r 1s hydrogen may be prepared from the corresponding formula (X) compound wherein Y is amino, via a deamination reaction, by dissolving the amine in 50-521 aqueous hypophosphorous acid (H3P02). The solution is chilled below 10 0C, and an equimolar or excess amount of sodium nitrite is added to an aqueous solution with stirring over a period of time. On completion of the addition, the reaction mixture is warmed to room temperature and stirred for an additional period of time. The product is then recovered from the reaction mixture by standard laboratory procedures and purified if so desired. The preparation of 4-substituted aminoacetophenones required for the preparation of 4-substituted phenylethane derivatives which are now found to be useful for raising meat-producing animals, is exemplified as follows: EMI11.1 The fluorine displacement is carried out with excess amine in the presence or absence of a solvent; and if a solvent is required, water appears to be the most useful. With volatile amines, the reaction is conducted in a sealed vessel and generally temperatures of 50 - 1000C are sufficient to complete the reaction. Chlorination and bromination of these aminoacetophenones may be conducted with N-chlorosuccinimide and N-bromosuccinimide in toluene, chlorobenzene or dichlorobenzene at 90 - 1000C, Iodination may be conducted with Na/N,N-dichlorobenzenesulfonamide or iodine monochloride in acetic acid. By reacting these acetophenones with bromine in chloroform or methylene chloride, the corresponding phenacyl bromides are prepared. These phenacyl bromides are then reacted with R2R3N amines and the aminoketones are reduced with NABS4 or NaCNBH3 by conventional techniques described in references cited hereinbefore. Naturally, compounds which contain groups reactive to halogen, such as when R8 is alkenyl, require other approaches that are discussed below. EMI12.1 wherein X and Z are hydrogen, chlorine, or bromine and R2 and R3 are hydrogen, C1-C4 alkyl, or C2-C3 alkenyl groups. The compounds of formula I, wherein R8 and R9 are groups other than both being hydrogen are also prepared by the following general scheme: EMI13.1 The methods utilized in the above scheme are either reported in references cited hereinbefore or by conventional methods. Oxidation of the alcohol may be conducted with chromic acid (Jones Reagent), MnO2, pyridinium chlorochromate, or other oxidizing agents. Where X or Z are the BH3-reducible groups, CN, COOR, or CONE2, the appropriate acetophenones are prepared by displacement of X or Z represented by bromine with CuCN/DMF at 100 - 1600C by the conventional method, after reduction of the acylated aminoacetophenones in the first step followed by re-oxidation in the second step of the above procedure. The cyano substituted-amino-acetophenones are then converted to their corresponding ethanolamines, which are then converted to the desired esters, acids, and amides EMI14.1 <tb> by <SEP> conventional <SEP> methods, <SEP> such <SEP> as <SEP> R1OH/acidesters, <SEP> <tb> hydrolyses <SEP> # <SEP> acids <SEP> <SEP> and <SEP> partial <SEP> hydrolyses <SEP> # <SEP> amides. <tb> Furthermore, compounds of the following structure are prepared by allowing the corresponding etbanolamines to react with an equivalent or slight excess of the acid anhydrides with or without organize bases such as tertiary amines or pyridine. The reactions are conducted in inert solvents EMI14.2 such as chlorinated hydrocarbons, or aromatic solvents at 0 - 250C. Reaction of the anhydride at the hydroxyl group proceeds well provided R2 and R3 are groups other than hydrogen and when R2 is hydrogen, R3 is a substituent containing a tertiary carbon attached to nitrogen. compounds of the following structure which contain alkanoyl or aroyl groups on ethanolamine moiety are readily prepared by using two equivalents or more of the acid anhydrides in the presence of a tertiary amine, such as triethylamine, or pyridine in an inert solvent (CH2Cl2, CHC13, toluene, etc.) at 50 - 1000C. EMI15.1 Additionally, Formula I compounds, wherein and h are selected from hydrogen and C3-C4 alkenyl, are prepared by alkenylation of 4-amino-3,5-disubstituted phenacyl bromide in dimethylformamide (DMF) in the presence of an acid acceptor, such as triethylamine or sodium carbonate, at 70 - 1000C to afford monoand dialkenylated products which are separated and converted to I by conventional methods. The following scheme illustrates above-described general method: EMI16.1 Formula (I) compounds wherein R4 is OR6 and SR11, wherein R6 and R11 are as hereinabove defined, may be prepared by converting the alcohol (R4-OH) with thionyl chloride under an inert blanket of gas such as nitrogen at a temperature range of from about 0 to 10 C and preferably at 0 to 50C for a reaction period sufficient to essentially complete the reaction. The thus obtained halo compound is isolated by conventional methods and is then reacted with the appropriate alcohol or mercaptan, under an inert blanket of gas, such as nitrogen at a temperature range of from about 0 to 50 C The formula (I) product thus obtained is then isolated by standard laboratory methods and purified, if so desired. The above reaction sequence may be graphically illustrated as follows: EMI17.1 wherein X, Y, Z, R2, R3, R6 and R11 are as hereinabove defined. These displacement reactions may also be performed by using an excess of alkoxide tR6 ) or mercaptide (RliS ) in an inert solvent such as tetrahydrofuran to afford the above ethers and thioethers in a similar manner. Alternatively, a formula (I) compound wherein is OR6 may be prepared by dissloving the corrresponding formula (Z) compound wherein R4 is OH in the corresponding R6OH alcohol and saturating the thus obtained solution with dry HCl gas. The reaction mixture is then stirred at room temperature for a period of time sufficient to essentially complete the reaction and the product is then isolated by standard laboratory procedures and purified, if so desired. This reaction sequence may be illustrated as follows: EMI18.1 wherein X, Y, Z, R2, R3 and R6 are as hereinabove defined. In the present specification and claims, the term a, &alpha;-dimethylphenethyl means a structure having the following configuration: EMI18.2 Animal feed supplements can be prepared by admixing about 10% to 75% by weight of the phenylethane derivative of acid addition salt thereof, with about 909 to 25 by weight of a suitable carrier or diluent. Carriers suit- able for use to make up the feed supplement compositions include the following: alfalfa meal, soybean meal, cotton- seed oil meal, linseed oil meal sodium chloride, corhmeal, can molasses, urea, bone meal, corncob meal and the like. The carrier promotes a uniform distribution of the active ingredient in the finished feed into, which the supplement is blended. It thus performs an important function by ensuring proper distribution of the active ingredient throughout the feed. If the supplement is used as a top dressing for feed, it likewise helps to ensure uniformity of distribution of the active material across the top of the dressed feed. For parenteral administration, the phenylethane derivative may be prepared in the form of a paste or pellet and administered as an implant, usually under the skin of the head or ear of the animal in which enhanced growth rate and/or improved efficiency of feed utilltation is sought. In practice, parenteral administration generally involves injection of a sufficient amount of the above said phenylethane derivative to provide the animal with from 0.001 to 50 mg/kg of body weight of the active ingredient. The preferred dosage level for cattle 1w the range of from 0.001 to 25 mg/kg of body weight of the active phenylethane derivative. The preferred dose level of said phenylethane derivative for poultry is about 0.001 to 35 mg/kg of animal body weight and the preferred dose level of said phenylethane derivative for sheep and goats is 0.001 to 40 mg/kg of animal body weight. The preferred dose level for rabbits ii 0.001 to 35 mg/kg of animal body weight. When orally administered in the feed, generally about 0.01 to 300 grams per ton of feed of the aboveidentified phenylethane derivative or acid addition salt thereof, is effective for enhancing the growth rate and improving the efficiency of feed utilization by the above-mentioned meat-producing animals. Since the effective and preferred dietary levels of the active ingredient vary somewhat from species to species in the above-mentioned animals, said levels for each animal species are listed in Table I below on a gram per ton of feed basis: TABLE I Effective Preferred Feed Level Level Compound g/Ton q/Ton Animal Formula (1) 0.1-200 1-100 Sheep, Goats 0.01-50 0.1-10 Chickens, Rabbits 0.01-50 0.1-10 Turkeys 0.1-300 1-100 Cattle & Swine Animal feed compositions which will provide the desired growth promotion and feed efficiency in the abovementioned animals can be prepared by admiring the phenylethane derivative or acid addition salt thereof, or an animal feed supplement containing said compound, with a sufficient quantity of an appropriate animal feed to provide the desired level of active compound in said feed. Paste formulations can be prepared by dispersing the active phenylethane derivative in a pharmaceutically acceptable oil such as peanut oil, sesame oil, corn oil or the like. Pellets containing an effective level of the phenylethane derivative can be prepared by admixing the above-said active ingredient with a diluent such as carbowax, biodegradable polymers, carnauba wax, or the like. A lubricant, such as magnesium stearate or calcium stearate may be added to improve the pelleing process if desired. It is, of course, recognized that more than one pellet may be administered to an animal to achieve the desired dose level which will provide the increased growth rate and/or improve efficiency of feed utilization by said animal. Moreover, it has been found that additional implants may also be introducted periodically during the treatment period in order to maintain the proper drug release rate in the animal's body. In addition to enhanced growth promotion and improved efficiency of feed utilization by meatproducing animals, the compounds of the present invention have the added advantage that, at selected levels of administration, they increase the deposition of lean meat (i.e., muscle or protein) in said animals and improve the carcass quality thereof by increasing the ratio of lean meat to fat in the animals receiving them. This biological response has substantial advantage to poultrymen, cattlemen, and swine, sheep and goat producers since administration ot said compounds at selected levels yields leaner animals which command premium prices from the meat industry. These and other advantages of the present invention will become apparent from the examples set forth below. Such examples are provided only by way of exemplification and are not intended to be expressions of limitations on the invention. EXAMPLE 1 Evaluation of Test Compounds as Animal Growth Promoters CFI female mice from Carworth Farms are received when they are six weeks old. They are housed ten to a cage in air-conditioned rooms (72 F to 760F) with automatically controlled lights, 14 hours on and 10 hours off. The basal diet used in these studies is Purina Laboratory Chow (see description below), which is supplied ad libitum. Water is allowed ad libitum. Thirteen days after arrival, the mice are weighed in groups of ten and assigned at random to the different treatments. The concentration of the different compounds in the diet is indicated in the following tables. Twelve days later the mice are weighed again, and the experiment terminated. Test data are provided in Table II below wherein data are reported as percentage gain over controls. Different control animals are used for each test. The following is description of the diet to which the growth-promoting compounds were added. DIET Guaranteed Analysis Crude protein not less than 23.01 Crude fat not less than- .5% Crude fiber not more than 6.01 Asb not not than 9.01 ingredients Meat and bone meal, dried skimmed milk, wheat germ meal, fish meal, animal liver meal, dried beet pulp, ground extruded corn, ground oat groats, soybean meal, dehydrated alfalfa meal, cane molasses, animal fat preserved with BRA, vitamin B12 supplement, calcium pantothenate, choline chloride, folic acid, riboflavin supplement, brewer's dried yeast, thiamin, niacin, vitamin A supplement, D-activated plant sterol, vitamin E supplement, calcium carbonate, dicalcium phosphate, iodized salt, ferric ammonium citrate, iron oxide, manganous oxide, cobalt carbonate, copper oxide, zinc oxide. TABLE II Evaluation of Test Compounds as Animal Growth Promoters Dosage Gain % Gain Over Compound (ppm) (grams) Controls 4'-[2-(tert-butylamino)-1-hydroxyethyl]-2'-chloro- 200 16.8 +107.9 acetanilide 100 18.4 +127.7 4-Amino-&alpha;-[(tert-butylamino)methyl]-3,5-diiodobenzyl 200 21.1 +27.1 alcohol hydrochloride 100 20.0 +20.5 4-Amino-N-tert-butyl-3,5-dichlorophenethylamine 50 12.3 7.9 hydrochloride &alpha;-(Aminomethyl)-m-chlorobenzyl alcohol hydrochloride 200 15.8 +4.6 @4-Amino-&alpha;-[(tert-butylamino)methyl]-3,5-diiodobenzyl 200 21.1 +27.1 alcohol hydrochloride 100 20.0 +20.5 TABLE II (continued) Evaluation of Test Compounds as Animal Growth Promoters Dosage Gain % Gain Over Compound (ppm) (grams) Controls &alpha; ;-[(Tert-butylamino)methyl]-3,5-dichloro 200 16.0 0 -4-dimethylaminobenzyl alcohol 50 21.9 +36.9 4-Amino-3,5-dichloro-&alpha;-{[(3-phenyl- 200 16.9 + 5.6 propyl)amino]methyl}benzyl alcohol 50 18.9 +18.1 &alpha;-[(Tert-butylamino)methyl]-3,5-dichloro 200 19.4 +21.3 -4-methylaminobenzyl alcohol 50 24.4 +52.5 4-Amino-N-tert-butyl-3,5-dichloro-ss- 200 14.8 - 7.5 isopropoxyphenethylamine 50 20.9 +30.6 4-Amino-N-tert-butyl-3,5-dichloro-ss- 200 15.9 +30.3 ethoxyphenethylamine hydrochloride 50 22.8 +86.9 Methyl-p-{3-[(4-amino-3,5-dichloro- 200 24.3 +22.6 hydroxyphenethyl)amino]propyl}benzoate 50 19.0 - 4.1 TABLE II (continued) Evaluation of Test Compounds as Animal Growth Promoters Dosage Gain % Gain Over Compound (ppm) (grams) Controls Methyl-4-[2-(tert-butylamino)-1-hydroxy- 50 27.9 +40.8 ethyl]-2,6-dichlorocarbanilate 4'-[2-(Tert-butylamino)-1-hydroxyethyl] 200 21.8 +37.1 -2',6'-dichloroacetanilide hydrochloride 50 23.4 +47.2 5-[2-(Tert-butylamino)-1-hydroxyethyl] 200 27.3 +90.9 -3-chloroanthranilonitrile 50 26.2 +83.2 4-Amino-ss-(benzyloxy)-N-tert-butyl-3,5- 200 22.6 +58.0 dichlorophenethylamine hydrochloride 50 22.4 +56.6 &alpha;-[(Tert-butylamino)methyl]-3,5-dichloro- 200 24.6 +72.0 4-isopropylaminobenzyl alcohol 50 24.3 +69.9 12 28.0 +95.8 3 27.3 +90.8 TABLE II (continued) Evaluation of Test Compounds as Animal Growth Promoters Dosage Gain % Gain Over Compound (ppm) (grams) Controls 5-[2-(Tert-butylamino)-1-hydroxyethyl]- 200 29.6 +79.4 anthranilonitrile 50 29.9 +81.2 Methyl-5-[2-(tert-butylamino)-1-hydroxy- 200 24.4 +47.9 ethyl]-3-chloroanthranilate hydrochloride 50 20.1 +21.8 4'-[2-Tert-butylamino)-1-hydroxyethyl] 200 26.1 +58.2 -2',6'-dichlorovaleranilide 50 26.4 +60.0 Benzyl-4-[2-(tert-butylamino)-1-hydroxy- 50 25.1 +52.1 ethyl]-2,6-dichlorocarbanilate 4-Amino-N-tert-butylamino-3,5-dichloro 200 25.4 +55.8 -ss-(methylthio)phenethylamine hydrochloride 50 25.3 +55.2 N-Tert-butyl-3,5-dichloro-ss-methoxy- 200 21.5 +50.3 phenyethylamine hydrochloride 50 25.8 +80.4 TABLE II (continued) Evaluation of Test Compounds as Animal Growth Promoters Dosage Gain % Gain Over Compound (ppm) (grams) Controls 3-Bromo-5-[2-(tert-butylamino)-1-hydroxyethyl]- 200 16.1 +50.5 anthranilonitrile 50 24.2 +126.2 4-Amino-&alpha;-[(tert-butylamino)methyl]-3-methyl- 100 20.8 +94.5 benzyl alcohol 4-(Butylamino)-&alpha;-[(tert-butylamino)methyl]-3,5- 200 19.3 +80.4 dichlorobenzyl alcohol 50 19.4 +81.3 2-Amino-3-bromo-5-[2-(tert-butylamino)-1- 200 17.4 +62.6 hydroxyethyl]benzamide 50 19.8 +85.0 4-Amino-&alpha; ;-[(tert-butylamino)methyl]-3,5-dichloro- 200 14.6 +36.4 benzyl alcohol acetate (ester) 50 19.1 +78.5 TABLE II (continued) Evaluation of Test Compounds as Animal Growth Promoters Dosage Gain % Gain Over Compound (ppm) (grams) Controls 3-Bromo-5-[2-tert-butylamino)-1-hydroxyethyl]- 200 18.2 +70.1 anthranilic acid 50 13.6 +27.1 N-tert-butyl-3,5-dichloro-ss-methoxy-4-methyl- 200 18.0 +68.2 aminophenethylamine hydrochloride 50 23.1 +115.9 &alpha;-[(tert-butylamino)methyl]-3,5-dichloro-4- 200 19.6 +83.2 (bexylamino)benzyl alcohol 50 20.7 +93.5 4-Amino-&alpha;-[(tert-butylamino)methyl]-3,5-dichloro- 200 14.4 +34.6 benzyl alcohol acetate (ester), acetate 50 18.7 +74.8 4-Benzylamino-&alpha; ;-[(tert-butylamino)methyl]-3,5- 200 15.7 +46.7 dichlorobenzyl alcohol 50 16.4 +53.3 TABLE II (continued) Evaluation of Test Compounds as Animal Growth Promoters Dosage Gain % Gain Over Compound (ppm) (grams) Controls ss-(allyloxy)-4-amino-N-tert-butyl-3,5-dichloro- 200 21.5 +100.9 phenethylamine 50 19.6 +83.2 4'-[2-(tert-butylamino)-1-hydroxyethyl]-2',6'- 200 18.3 +71.0 dichlorobenzanilide 50 13.9 +29.9 4-(allylamino)-&alpha; ;-[(tert-butylamino)methyl]-3,5 200 20.2 +88.8 dichlorobenzyl alcohol 50 21.9 +104.7 4'-[3-(tert-butylamino)-1-hydroxyethyl]-2',6'- 200 25.8 +141.1 dichloroacetanilide acetate (ester), hydrochloride 50 16.2 +51.4 N-(4-amino-3,5-dichloro-ss-hydroxyphenethyl)-N- 200 18.7 +74.8 tert-butylacetamide acetate (ester) 50 15.0 +40.2 TABLE II (continued) Evaluation of Test Compounds as Animal Growth Promoters Dosage Gain % Gain Over Compound (ppm) (grams) Controls &alpha;-[(tert-Butylamino)methyl]-3,5-dichloro-4- 100 23.0 +115.0 cyclohexylaminobenzyl alcohol &alpha; ;-[(tert-Butylamino)methyl]-4-amino-3-chloro-5- 200 16.5 +54.2 methylbenzyl alcohol, hydrochloride 50 19.7 +84.1 EXAMPLE 2 Antilipogenic Evaluation of Test Compounds - Mouse Study CFI female mice, 55 days old, are weighed in groups of 10 and allotted to cages to minimize weight variation among cages. Treatments are randomly assigned to cages. Each of the treatments are tested in 3 replicates, i.e., in 3 cages of 10 mice each. There are 10 cages of 10 control mice each. Drugs are mixed in the diet at the dosage level indicated. Feed and water are offered ad libitum for 12-day test period. Feed spilled ls collected during the test period. At the end of the test period, the collected feed is weighed and the mean feed ccmsu?- tion per cage of ten mice is determined for each treatment. The mice are weighed as a group of 10 and the weight gain determined. The mice are sacrificed by cervical dislocation. The right uterine fat pad of each mouse is removed. The fat pads for each cage of 10 mice are weighed as a unit. Data obtained are reported in Table "1. Data are reported as percent reduction in fat pad weight. Reduction in fat pad weights of animals is generally indicative of reduction of total body fat of the treated animals. TABLE III ANTILIPOGENIC EVALUATION OF TEST COMPOUNDS - MOUSE STUDY DOSAGE % REDUCTION IN FAT COMPOUND (PPM) PAD WEIGHT VS CONTROLS &alpha;-[(Tert-butylamino)methyl]-3,5-dichloro-4-dimethylamino 200 -46.1 benzyl alcohol 50 -14.8 4-Amino-3,5-dichloro-&alpha;-{[(3-phenyl-propyl)amino]methyl} 200 -41.1 benzyl alcohol 50 -36.2 4-Amino-3,5-dichloro-&alpha;-{[(&alpha;,&alpha;-dimethylphenethyl)amino] 200 -13.1 methyl)benzyl alco ol hydrochloride 50 -13.9 &alpha; ;-[(Tert-butylamino)methyl]-3,5-dichloro-4-methylamino- 200 -51.0 benzyl alcohol 50 -41.9 4-Amino-N-tert-butyl-3,5-dichloro-ss-isoproxyphenethylamine 200 -57.0 50 -17.0 4-Amino-N-tert-butyl-3,5-dichloro-ss-ethoxyphenethylamine 200 -33.7 hydrochloride 50 -15.3 TABLE III (Continued) ANTILIPOGENIC EVALUATION OF TEST COMPOUNDS - MOUSE STUDY DOSAGE % REDUCTION IN FAT COMPOUND (PPM) PAD WEIGHT VS CONTROLS Methyl-4-{3-[(4-amino-3,5-dichloro-ss-hydroxyphenethyl) 200 -27.7 amino]propyl]benzoate 50 -14.6 Methyl-4-[2-(tert-butylamino)-1-hydroxyethyl]-2,6dichlorocarbonilate 50 -23.5 4Ú-[2-(Tert-butylamino)-1-hydroxyethyl]-2,6-dichloro- 200 -27.1 acetanilide hydrochloride 50 - 8.8 5-[2-Tert-butylamino-1-hydroxyethyl]-3-chloroanthranilonitrile 200 -45.9 50 -10.4 4-Amino-ss-(benzyloxy)-N-tert-butyl-3,5-dichloro- 200 -24.2 phenethylamine hydrochloride 50 -18.4 &alpha; ;-[(Tert-butylamino)methyl]-3,5-dichloro-4-isopropylaminobenzyl 200 -52.5 alcohol 50 -22.6 12 - 6.3 3 -25.5 TABLE III (Continued) ANTILIPOGENIC EVALUATION OF TEST COMPOUNDS - MOUSE STUDY DOSAGE % REDUCTION IN FAT COMPOUND (PPM) PAD WEIGHT VS CONTROLS 4Ú-[2-(Tert-butylamino)-1-hydroxyethyl]-2Ú,6Ú- 200 -33.2 dichlorovaleranilide 50 -16.1 Benzyl-4-[2-(tert-butylamino)-1-hydroxyethyl]2,6-dichlorocarbanilate 50 -19.6 Methyl-5-[2-(tert-butylamino)-1-hydroxyethyl]- 200 - 5.9 3-chloroanthranilate hydrochloride 50 - 5.8 5-[2-(Tert-butylamino)-1-hydroxyethyl]anthranilo- 200 -41.5 nitrile 50 -10.3 4-[Amino-N-tert-butyl-3,5-dichloro-ss-(methylthio) 200 -28.9 phenethylamine hydrochloride 50 -16.2 N-tert-butyl-3,5-dichloro-ss-methoxyphenethylamine 200 -22.5 hydrochloride 50 -10.4 Example 3 N-tert-butyl-3,5-dichloro-ss-methoxy-4-methylamino phenethylamine hydrochloride A 7 9 sample of &alpha;-[(tert-butylamino)methyl] -3,5-dichloro-4-methylaminobenzyl alcohol is added to 70 ml of thionyl chloride under N2 atmosphere and the mixture is stirred for two hours. Excess thionyl chloride is removed in vacuo, and the glassy residue is dissolved in SO ml of methanol. The solution is stirred for 1.5 hours and evaporated to dryness. The residue is dissolved in 100 ml of H2O and extracted with 2 x SO ml of CH2C12. The aqueous layer is neutralized with solid NaHCO3 and extracted with CE2CL2. The extract is dried (MgSO4) and evaporated to dryness in vacuo to give 4.1 g of semi-solid, which after trituration with ethyl ether affords 1.07 9 of the title compound, mp 220 - 2210C. Similarly, the following ethers are prepared: EMI36.1 Alcohol R ethanol C2H5 1-propanol 1-C3H7 2-propanol 2 c3B7 l-butanol 1-C4E9 2-butanol 2-C4H9 l-hexanol n-c6S13 benzyl alcohol benzyl allyl alcohol allyl 4-methoxybenzyl alcohol 4-methoxybenzyl 4-chlorobenzyl alcohol 4-chlorobenzyl 4-nitrobenzyl alcohol 4-nitrobenzyl 4-methylbenzyl alcohol 4-methylbenzyl 3 ,4-dimethylbenzyl alcohol 3,4-dimethylbenzyl 3, 4-dimethoxybenzyl alcohol 3, 4-dimethoxybenzyl 3 ,4-dichlorobenzyl alcohol 3, 4-dichlorobenzyl 2-chlorobenzyl alcohol 2-chlorobenzyl 2-methylbenzyl alcohol 2-methylbenzyl Example 4 In the manner described in Example 3, the following ethers are prepared by substituting the corresponding alcohols for methanol. EMI37.1 R mp C benzyl 190-193 allyl 57- 59 4-methoxybenzyl 4-chlorobenzyl 4-ni trobenzyl 4-methylbenzyl 3, 4-d imethylbenzyl 3, 4-dimethoxybenzyl 3,4-dichlorobenzyl phenyl oil 4-chlorophenyl 4-me thoxyphenyl 4-methyiphenyl 2-chlorophenyl 4-nitrophenyl Example 5 N-tert-Butyl-3-chloro-5-cyano-B-methoxy-4-aminophenethylamine hydrochloride In the manner described in Example 3, a- t (tert-butylamino) methyli -4-amino-3-chloro-5-cyano- benzyl alcohol is converted into the title compound; and, similarly, the following are also prepared: EMI38.1 Ar 4-amino-3 ,5-dicyanophenyl t-butyl 4-amino-3-chloro-5-trifluor methylphenyl t-butyl 4-amino-3-chloro-5-tr ifluoro- methylphenyl i-propyl 4-acetamido-3,5-dichlorophenyl t-butyl 4-acetamidophenyl t-butyl 4-amino-3-chloro-5-E12N-CO- phenyl 4-amino-3-chloro-5-HO-CO phenyl t-butyl 4-amino-3-chloro-5-methyl phenyl t-butyl 4-amino-3-chloro-5-methoxy- phenyl t-butyl 4-amino-3-chloro-5-nitro phenyl t-butyl 4-amino-3-chloro-5-CH2O-CO phenyl 4-amino-3-chloro-5-dimethyl aminomethylphenyl t-butyl 4-amino-3-cyano-phenyl t-butyl Example 6 5-(4-amino-3,5-dichlorophenyl)-3-tert-butyl-2-oxazdlidinone In 10 ml of CH2CL2, 0.5 g of 4-amino- a [(tert-butylamino)methyl]-3,5-dichlorobenzyl alcohol is Stirred with 1 ml of Et3N at -5 C and 2 ml of 12.51 COC12 in benzene/5 ml of CH2CL2 is added over 15 minutes. The resulting suspension is stirred 20 minutes at 10C and allowed to warm to room temperature with stirring for 1.5 hours. The mixture is evaporated to dryness, and the residue is chromatographed on silica gel with 1:1 hexane/CE2CL2 to afford 0.1 9 of oil which crystallizes to give the title compound, mp 97 - 103 C. In the same manner, &alpha;-[(allylamino)methyl] -(-amfno-3,5-dichlorobenzyl alcohol is allowed to react with phosgene to afford 5-(4-amino-3,5-dichlorophenyl)-3-allyl-z-oxazolidinone. Likewise, the following compounds are prepared by this manner: EMI40.1 Ar R3 3,S-dichlorophenyl t-butyl 3,5-dichloropheny i-propyl 4-acetamidophenyl t-butyl I-Mlino-3-chloro-5-cyanophenyl t-butyl 4-amino-3-chloro-5-trifluoromethylphenyl t-butyl 3-chloro-4-acetamidophenyl t-butyl 3, 5-dichloro-4-methylamino- phenyl t-butyl 3,5-dichloro-4-ethylaminophenyl t-butyl 3,5-dichloro-4-i-propylaminophenyl t-butyl 3 ,5-dichloro-4-acetamido- phenyl F t-butyl 3,5-dichloro-4-methoxyl carhonylaminophenyl t-butyl 3,5-dichloro-4-benzyloxycarbonylaminophenyl t-butyl Ar R3 3 ,5-dichloro-4-methyl- carbamoylaminophenyl t-butyl 4-amino-3-chloro-5 me thylphenyl t-butyl 4-amino-3-cyanophenyl t-butyl 4-amino-3-trifluoromethyl phenyl t-butyl 4-amino-3-chloro-5-NE2CO- phenyl 4-amino-3-chloro-5-HOOC- phenyl t-butyl 4-amino-3-chlÏro-5- CH300C-phenyl t-butyl 4-amino-3-chloro-5 (CH3) 2NCH2-phenyl t-butyl 4-amino-3,5-dicyanophenyl t-butyl Example 7 4-Amino-&alpha;-[(tert-butylamino)methyl]-3,5-dichlorobenzyl alcohol acetate A mixture containing 1 g of 4-amino-o-[(tert- butylamino)methyl]-3,5-dichlorobenzyl alcohol in 35 ml of CE2C12 at 10 - 150C is stirred, and 0.37 g of Ac2O and 0.5 ml of Et3N are added dropwise. The reaction mixture is then allowed to warm to room temperature, and the reaction is followed by thinlayer chromatography to completion. The mixture is evaporated to dryness in vacuo, and the yellow viscous liquid (1.5 g) is stirred with 50 ml of ethyl ether to afford a yellow solid (0.84 g), mp 128 - 131 C. This material is shown by nuclear magnetic resonance spectroscopy and by neutralization with alkali to be the acetic acid salt. On treating 100 mg of this salt in 30 ml of CH2Cl with 30 ml of 10% aqueous NaOH, the salt is neutralized. The CH2Cl2 solution is dried (MgSO4) and evaporated to dryness in vacuo to afford the viscous title compound. Analysis: Calcd for C14H20O2N2Cl: C, 52.67; H, 6.32; N, 8.78; Found: C, 52.38; H, 6.51; N, 8.88. In the same manner, propionic anhydride, butyric anhydride, pivalic anhydride, and benzoic anhydride are allowed to react with 4-amino-&alpha;-[(tert- butylamino)methyl]-3,5-dichlorobenzyl alcohol (A) and -[(tert-butylamino)methyl]-3,5-dichloro-4-methylamino- benzyl alcohol (B) respectively, to afford the propionate, butyrate, pivalate and benzoates of A and B. Example 8 The following esters are prepared by the method of Example 7 by using the appropriate acid anhydride. EMI42.1 R8 R9 R6 H CH3 CH3 H C2H5 CH3 H n-C3H7 CH3 H 2-C3H7 CH3 H benzyl CH3 H allyl CH3 CH3 CH3 CH3 H CH3 C2H5 H CH3O-CO- CH3 H CH3NH-CO CH3 H CH3 n-C4H9 C2H5 C2H5 CH3 n-C4H9 n-C4H9 CH3 EMI43.1 Ar R6 3,5-dichlorophenyl 2-C3H7 4-amino-3-chloro-5-cyanophenyl CH3 4-amino-3-chloro-5-tr if luoro- methylphenyl CH3 4-amino-3-chloro-5-H2NCO-phenyl CH3 4-amino-3-chloro-5-HOOC-phenyl CH3 4-amino-3-chloro-5-methylphenyl CH3 4-amino-3-bromo-5-cyanophenyl CH3 4-amino-3-chloro-5-CH3OCO phenyl CH3 4-amino-3-chloro-5-(CH3)2 NCH2-phenyl CH3 4-amino-3,5-dicyanophenyl CH3 4-amino-3-cyanophenyl t-C4H9 Example 9 N-(4-amino-3,5-dichloro-ss-hydroxyphenethyl)-N-tert -butylacetamide acetate A mixture containing 2.5 g of 4-amino-&alpha; ;-[(tert-butyl- amino)methyl]-3,5-dichlorobenzyl alcohol, 25 ml of pyridine and 10 ml of acetic anhydride is stirred for three hours and evaporated to dryness in vacuo with heating up to 70 C. The residue is treated with ice, 100 ml of CR2C12 and 50 ml of 10t NaOH solution. The CH@Cl@ phase is separated, and the aqueous portion is further extracted with CE2CL2 (2 x 50 ml). The combined CH2CL2 solutions are dried (Na2SO4) and evaporated to dryness to afford a solid after scratching. The solid is washed with hexane and collected to afford 2.61 g of the title compound, mp 126 - 136 C. Similarly, by substituting the appropriate acid anhydrides, the following compounds are prepared. EMI45.1 R8 R9 R6 H CH3 CH3 H C2H5 CH3 H 2-C3H7 CH3 H n-C4H9 CH3 CH3 CH3 CH3 H CH3O-CO CH3 H CH3NH-CO CH3 H CH3CO CH3 H CH3 C2H5 C2H5 C2H5 n-C4H9 EMI46.1 Ar R6 4-amino-3,5-dicyanopheny C2H5 4-amino-3-chloro-t-dimethyl amino methylphenyl CH3 4-amino-3-chloro-5-CH3OOC-phenyl C2H5 4-amino-3-chloro-5-methylphenyl CE3 3, 5-dichlorophenyl CE3 4-amino-3-chloro-5-cyanophenyl CE3 4-amino-3-chloro-5-tr ifluoro- methylphenyl CH3 4-amino-3-chloro-5-H2NCO-phenyl CH3 Example 10 4-Acetamido-a- I Xte -butylamino) methyll -3 ,5-dichloro- benzyl alcohol acetate . In 15 ml of CE2CL2, 1.57 g of 4-acetamido -ss-[(tert-butylamino)methyl]-3,5-dichlorobenzyl alcobol ii suspended and stirred while 1.2 9 of triethylamine in 30 ml of 30 ml of CH2Cl2 is added, followed by 0.7 g of acetic anhydride in 15 ml of CH2CL2. The mixture is stirred for 20 hours and then is washed with 100 ml of 101 NaOH solution. The organic phase is separated, dried (Na2SO4) and evaporated to dryness in vacuo. The residue is dissloved in 30 ml of ethanol and a trace of S20 is added, followed by 10% HCl to acidify. The mixture is evaporated to dryness in vacuo and the residue is crystallized from acetone/ hcxane (30 11/5 ml). This affords 1.35 9, mp. 254 2570C dec., of the title compound. Similarly, by replacing acetic anhydride with propionic anhydride, butyric anhydride, pivalic anhydride, and benzoic anhydride, the corresponding propionate, butyrate, pivalate, and benzoate esters are prepared. Example 11 &alpha;-[(tert-Butylamino)methyl]-m-hydroxybenzyl alcohol acetate In the manner described in Example 10 m-(benzyloxy)-z-l(tert-butyltmino)methyl3benzyl alcohol us converted to m-(benzyloxy)-&alpha;-[(tert-butylamino)- methyllbenzyl alcohol acetate. This material is then deben:ylated to give &alpha;-[(tert-butylamino)methyl]-m-hydroxybenzyl alcohol acetate. Example 12 5-(p-Aminophenyl)-3-tert-butyl-2-oxazolidinone In 270 ml of CH2Cl2, 12.97 g of a-[(tert- butylamino)merthyl]-p-nitrobenzyl alcohol is dissolved. The solution is cooled to -5 C and 54 ml of 12.5% phosgene in benzene is added slowly. After the addition is completed, the mixture is stirred for 3.5 hours and poured on ice. The organic phase is separated, - and the aqueous layer is extracted with C12C12 (2 X 100 a1). The combined organic layers are washed with saturated NaHCO3 solution (2 X 250 ml), 100 ml of E20 and dried over MgSO4. The solution is evaporated to dryness to give 16.3 g, which is recrystallized from MeOH twice to afford 12.58 g of 3-tert-butyl-5-(p-nitro- phenyl)-2-oxazolidinone, mp 123 - 1250C. This product (10 g ) is dissolved in 200 ml of MeOR and hydrogenated over 6 g of Raney nicke at 51 p.a.i.g at 400C to give, after filtration and evaporation, 8.21 g of aminophenyl) -3-tert-butyl-2-oxazolidinone, mp 125 - 129 0C. Example 13 &alpha;-[(tert-butylamino)-methyl]3,5-dichloro-4-dimethyl- aminobenzvl alcohol A mixture containing 50 g of p-fluoroaceto- phenone and 150 ml of 40% aqueous dimethylamine is warmed in a pressure bottle at 90 - 1000C. After two hours, a pale yellow oil is formed. The mixture is cooled, and the oil solidifies. The solid is collected and washed well with H20 to give 54.93 of p-dimethylaminoacetophenone, mp 101 - 103 C, after heptane recrystallization. A 72 g sample of this acetophenone is heated with 129 g of N-chlorosuccinimide in 700 ml of toluene to reflux temperature and maintained at this temperature for 35 minutes. The mixture is cooled and filtered. The filter cake is washed with 200 ml of toluene, and the filtrate and wash solution are evaporated to dryness in vacuo to afford 66 g of oil. This oil is chromatographed on SiO2# with 41% bexane/CH2Cl2 to give 38.9 g of 3.5-dichloro 4-dimethylaminoacetophenone as a yellow oil. A 5.22 g sample of this oil is added portionwise to 2.75 g of SeO2 in 20 ml of dioxane and 0.7 ml of H2O at 55 - 60 C. This mixture in is beated at reflux temperature for 4.5 hours, cooled and filtered through siliceous earth. The filter cake is washed with 20 ml of dioxane. The dioxane solutions are cooled to 15 0C and 2.77 9 of t-butylamine is added dropwise to afford a tan precipitate. After stirring 15 minutes at room temperature, the mixture is diluted with 200 ml of ethanol, cooled to 50C and 7 g of NaBE4 is added portionwise. After 15 hours, the mixture is treated with 300 - 400 g of ice and 200 ml of H2O at below 100C. The mixture is stirred to dissolve all solids and extracted with 300 ml of CE2C12. The CH2C12 layer is washed with 100 ml of H2O, dried (MgSO4) and evaporated to dryness in vacuo to give 5.6 g of orange oil. This oil is dissolved in ethyl ether, decolorized with activated carbon and concentrated to 15 ml. On cooling, crystals are obtained. The title product is collected as white crystals, mp 96 - 990C. EXAMPLE 14 5-(4-amino-3,5-dibromphenyl)-3-tert-butyloxazolidine A mixture containing 2 g of 4-amino-3,5 debromo-&alpha;-[(tert-butylamino)methyl]benzyl alcohol and 5 ml of 37% formalin solution in 20 ml of toluene containing a few crystals of p-toluene sulfonic acid is heated at reflux to azeotrope water. After three hours, the mixture is cooled, diluted to 75 ml with CH2Cl2 and washed with 10% aqueous NaOB solution (2x20 ml). The aqueous portion is further extracted with 10 ml of CE2C12 and the combined organic extracts are dried (MgSO4) and evaporated to dryness in vacuo to afford 1.6 g of clear brown oil. A chemical ionization mass spectrographic analysis gives a Mass + B+ of 377, which is correct for the title compound. The nuclear magnetic resonance proton spectrum reveals a singlet at 64.53 in CDC13 indicative of the O-CH2-N group in the title compound. In the same manner, the following oxazolidines are prepared by substituting the corresponding arylethanolamines for 4-amino-3,5-dibromo-&alpha;-[tert- butylamino)methyl]benzyl alcohol. EMI50.1 Ar 4-amino-3,5-dichlorophenyl 4-methylamino-3,5-dichlorophenyl 4-amino-3-chloro-5-cyanophenyl 4-amino-3-chloro-5-trifluromethylphenyl 4-amino-3-chloro-5-methylphenyl 4-amino-3-bromo-5-NH2-CO-phenyl 4-amino-3-bromd-5-BOOC-phenyl 4-acetamido-3,5-dichlorophenyl 3,5-dichloro-4-methoxycarbonylaminophenyl 3,5-dichloro-4-methylcarbamoylaminophenyl 4-amino-3-cyanophenyl 4-amino-3-trifluoromethylphenyl 4-amino-3,5-dicyanophenyl EXAMPLE 15 4-Benxylamino-&alpha;-[tert-butylamino)methyl]-3,5-dichloro- benzyl alcohol In the manner described in Example 13 the title compound is prepared to give mp 86-89 c. EXAMPLE 16 4'-[2-(tert-butylamino)-1-hydroxyethyl]-2',6'-dichlorobenzanilide A mixture containing 2.04 g of 4-amino-3,5dichloroacetophenone and 0.25 ml of triethylamine in 10 ml of benzoyl chloride is stirred and heated at 130-135 for two hours. The mixture is cooled, filtered and the product is washed with ether. This amide is further oxidized with SeO2 in the manner described in Example t3 to eventually afford the title compound, mp 177-1820C. EXAMPLE 17 v- [tert-butylamino)methyl] -3, 5-dichloro-4-methylamino¯ benzyl alcohol p-Methylaminoacetophenone is prepared and chlorinated by method described in Example 29 to give 3,5-dichloro-4-methylaminoacetophenone. This ketone (18 g) in 200 ml of CHCl3 is stirred and 4.65 ml of Br2 in 50 ml of CHCl3 is added dropwise. After the addition is completed, the mixture is stirred an additional 20 minutes and warmed to reflux temperature for 25 minutes. The mixture is cooled, 100 ml of H20 is added and saturated Na2CO3 solution is added carefully until the mixture is neutral. The CHC13 layer is separated and the aqueous layer is further extracted with 100 ml of CE2Cl2. The combined extracts are dried (MgSO4) and evaporated to dryness to afford 16.3 g of the phenacyl bromide. This material (16 g) in 80 ml of EtOH is stirred at 12-15 C and 40 ml of t-butylamine is added dropwise. After the addition is completed the mixture is stirred for 10 minutes at 12-150C and then cooled to 50 and 4 g of NaBH4 is carefully added. After stirring for 0.5 hours, the mixture is allowed to warm to room temperature and stirring is continued for 0.75 hours. The mixture is poured on 300 ml of ice with stirring and the resulting mixture is extracted with 300 ml of CE2Cl2. The CE2C12 extract is dried (MgSO4) and evaporated to dryness in vacuo to give a yellow oil. Trituration of this residue with ethyl ether affords 7.45 g of the title compound, which melts at 98-1010C after recrystallization from ethyl ether. EXAMPLE 18 5-[2-(tert-butylamino)-1-hydroxyethyl]anthranilonitrile A mixture containing 48.86 g of o-amino- acetophenone in 490 ml of toluene is stirred while 64.5 g of N-bromosuccinimide is added in portions over 0.5 hours at below 400 c. After 15 minutes, the mixture is washed with H20 (4x100 ml). The solution is dried (MgSO4) and evaporated to dryness to afford 70.53 g of 4-amino-3-bromoacetophenone, mp 59-620C. A 35 g sample of this material in 180 ml of dry dimethylformamide is stirred and heated at reflux with 17.57 g of Cu2(CN)2 for 6 hours under N2 atmosphere. Subsequently, 180 ml of FeCl3/HCl solution (40 g FeCl3. 6H2O/10 ml concentrated HC1/60 ml H2) is added and the mixture is heated for 20 minutes at 60-700C and poured into 350 ml of H20. The aqueous mixture is extracted with CH2Cl2 and the extracts are washed with H2O, saturated NaECO3 solution and H20, respectively. The CH2C12 solution is evaporated to dryness in vacuo and the residue is recrystallized from 95% EtOH to afford 14.25 g, mp 155-159 C, of 4-amino-3-cyanoacetophenone. A 4.8 g sample of this product in 100 ml of EtOAc and 100 ml of CHCl3 containing 13.32 g of CuBr2 is heated at reflux temperature for 20 minutes. The mixture is further heated after 20 ml of EtOH is added and then filtered while still hot. The filter cake is washed with 50 ml of hot 20% MeOH/CH2Cl2 and the combined organic solutions are evaporated to dryness in vacuo. The residue is stirred in 25 ml of CH2Cl2 and the solid is collected and washed with CB2C12 to give 8.08 g of the phenacyl bromide. This material is added to 50 ml of t-BuNH2 in 100 ml of EtOH at 50 under N2 atmosphere. After 10 minutes of stirring, the mixture is allowed to warm to 300C to give a solution. This solutionis cooled to 10 and 4 g of NaBH4 is added in portions. After 45 minutes, the mixture is allowed to warm (42 0C) and kept at 20 0C until the exotherm subsides. The mixture is then evaporated to dryness and the residue is washed with H20. The residue is dried and treated with 200 ml of boiling MeOB and the hot MeOH solution is filtered. The filter cake is further washed with hot MeOH and the combined filtrates are concentrated to afford crystals. This solid is recrystallized from MeOH/2-PrOH to afford 2.08 g, mp 184-1860C, of the title compound. In a similar manner, the following related compounds are prepared starting with the appropriate acetophenone: EMI54.1 R8 R9 R3 X H H 2-C3H7 H H CH3 t-butyl H CH3 CH3 t-butyl H H C2H5 t-butyl H H n-C3H7 t-butyl H H 2-C3H7 t-butyl H H n-C4H9 t-butyl H H CE3 2-C3H7 H H benzyl t-butyl H C2H5 C2H5 t-butyl Cl n-C3H7 n-C3H7 t-butyl Cl n-C4H9 n-C4Hg t-butyl Cl EXAMPLE 19 3-chloro-5-[2-(tert-butylamino)-1-hydroxyethyl]anthranilonitrile In 100 ml of toluene, 5 g of 4-amino-3cyanoacetophenone is heated at reflux temperature for 20 minutes with 4.2 g of N-chlorosuccinimide. The mixture is cooled and filtered. The filtrate is further heated at reflux temperature for 2 hours. The precipitate is collected and washed with H20. The remaining solid is treated with 0.75 ml of Br2/14 ml of CHCl3 added to 75 ml of CHCl3 and 4.9 ml of EtOH. The mixture is evaporated to dryness and the residue is slurried with CH2Cl2. collected and washed with CE2C12 to afford 2.84 g of the phenacyl bromide. This material is allowed to react with t-BuNH2 and reduced with NaBE4 by the procedure of Example 18 to afford the title compound, mp 128-1380C. In a similar manner, the following compounds are prepared: EMI56.1 R8 R9 R3 H H 2-propyl H CH3 t-butyl CH3 CH3 t-butyl H C2H5 t-butyl H 2-propyl t-butyl H n-butyl t-butyl H benzyl t-butyl EXAMPLE 20 5-[2-(tert-butylamino)-1-hydroxyethyl]-3-chloroanthranilic acid, methyl ester, hydrochloride A mixture containing 1.36 g of 5-[2-(tert- butylamino)-1-hydroxyethyl]-3-chloroanthranilonitrile in 21 ml of 50t aqueous NaOH and 21 ml of EtOR is stirred under N2 for 0.5 hours. The mixture is @@ evaporated to remove EtOH and acidified to pE 3 and further evaporated to dryness in vacuo. The residue treated several times with Meon and evaporated to dryness. The solid is then treated with a solution which is prepared from 40 ml of MeOH and 2 ml of acetyl chloride. After allowing to stand overnight, the mixture is filtered and the filtrate is evaporated to dryness. The filter cake is àlso washed with HeOB and added to preceding filtrate. The residue is dissolved in acetone, filtered, and evaporated to dryness. The solid is triturated with Et2O and filtered to give 1.49 g, mp 95-1150C, of the title compound. In a similar manner, the following related esters are prepared: EMI57.1 R8 R9 R3 H H 2-propyl H CE3 t-butyl CE3 CH3 t-butyl H C2H5 t-butyl H n-propyl t-butyl H n-butyl t-butyl H benzyl t-butyl H allyl t-butyl C2H5 C2H5 t-butyl n-C4H9 n-C4H9 t-butyl n-C3H7 n-C3H7 t-butyl EXAMPLE 21 2-Amino-3-bromo-5-[2-(tert-butylamino)-1-hydroxyethyl]benzamide A mixture containing 1.02 g of 3-bromo-5 12-(tert-butylamino)-l-hydroxyethyllanthranilonitrile in 25 ml of H2O, 5 ml of 50% NaOH and 30 ml of EtOH is stirred and heated at 55-650C under N2 atmosphere for 1.25 hours. The mixture is evaporated to remove EtOH and extracted with CHCl3. The CHCl3 extract is washed with 25 ml of 2% NaOH, dried (MgSO4) and evaporated to dryness to afford 0.74 g. This solid is stirred with pentane and filtered to afford 0.6 g, mp 135-1450C, of the title compound. Similarly, the following compounds are EMI58.1 R8 R9 X H CH3 Cl H H Cl H C2H5 Cl CH3 CH3 Cl H 2-C3H7 Cl H n-C4H9 Cl H CH3 Br H benzyl Cl C2H5 C2H5 Cl n-C3H7 n-C3H7 Cl n-C4H9 n-C4H9 Cl EXAMPLE 22 3-bromo-5- 12- (tert-butylamino) -l-hydroxyethyllanthranilic acid A mixture containing 2 g of 3-bromo-5- [2-(tert-butylamino)-1-hydroxyethyl]anthranilonitrile in 10 ml of 50% NaOH, 50 ml of H2O and 6l ml of EtOH is stirred and heated to reflux temperature under N2 for an hour. The EtOH is evaporated and the aqueous mixture mixed vith 50 ml of 120 and 50 ml of CHCl3 The CHCl3 layer is removed and the interfacial brown oil is collected, added to 10 ml of MeOH, 5 ml of 820 and this mixture is acidified ton 5. After stirring for an hour, the off-white solid is collected, washed with H20 and dried to give 0.8 g, mp 221.5 C dec., of the title compound. Similarly, the following compounds are prepared: EMI59.1 R8 R9 X H H Cl H CH3 Cl CH3 CH3 Cl B CH3 Br H 2-C3H7 Cl H n-C4H9 Cl H benzyl Cl C2H5 C2H7 Cl n-C3H7 n-C3H7 Cl n-C4H9 n-C4H9 Cl EXAMPLE 23 5-(3-hydroxyphenyl)-3-tert-butyl-2-oxazolidinone In the manner described in Example 8, @ m-benzyloxy) -&alpha;- (tert-butylamino)methyl] benzyl alcohol is coverted to the oxazolidinone compound by treatment with phosgene. Subsequently debenzylation is completed to give the title compound. EXAMPLE 24 5- (3-hydroxyphenyl) - 3-tert-butyloxazolidine In the manner described in Example 12, m- (benzyloxy)-&alpha;- t (tert-butylamino)methyl]benzyl alcohol is reacted with formaldehyde to afford the oxazolidine derivative, which is debenzylated by the procedure of Example 10 to give the title compound. EXAMPLE 25 4-amino-N-tert-butyl-3,5-dichlor-ss-(methylthio)phenethylamine hydrochloride In the manner described in Example 3, N-tert-butyl-3,5-dichloro-ss-chloro-4-aminophenethylamine hydrochloride is prepared. An 11 g sample of this product is portionwise added to 5 ml of methyl mercaptan in 100 ml of dry ethylenedichloride at -100C to OOC. The mixture is stirred and allowed to rise gradually to room temperature over a four day period. The mixture is filtered, the filter cake is washed with ethylenedichloride (2x500 ml). The solid is dispersed in 200 ml of H20, cooled to 50C and basified with 6N NaOH solution to give a white oil, which is extracted with CH2C12 (3x100 ml). The CE2C12 extract is dried (MgS04) and evaporated to dryness to give 6.41 g of dark green oil. This oil is stirred in SCl/isopropanol and the mixture is evaporated to dryness. The residue is stirred in 35 ml of ethyl ether for 16 hours and filtered to give 3.63 g, ip 178-1810C dec. This solid is heated in refluxing ethyl acetate and filtered to give 2.07 g, mp 188-193 C. Recrystallization from 75 ml of ethylenedichloride affords 1.45 g of the title compound, mp 191-196 C. The title compound is also obtained by adding 5-10 fold excess of sodium mercaptlde in tetrahydrofuran at 0-100C and by following the above workup. EXAMPLE 26 In the same manner as described in Example 25, the following, thioethers are prepared by substituting methyl mercaptan with the corresponding mercaptans: EMI61.1 R R3 methyl 2-propyl ethyl t-butyl 2-propyl t-butyl n-butyl t-butyl t-butyl t-butyl n-hexyl t-butyl phenyl t-butyl benzyl 2-propyl EXAMPLE 27 In the manner described in Example 25, substitution of the corresponding chloro compound for N-tert-butyl-3,5-dichloro-ss-chloro-4-aminophenethylamine hydrochloride and adding the appropriate mercaptans afford the following thioethers: : EMI61.2 Ar R R3 4-amino-3-cyanophenyl . methyl 2-propyl 4-methylamino-3,5-dichlorophenyl methyl t-butyl 4-amino-3-chloro-5-trifluromethyl methyl t-butyl 4-amino-3-chloro-5-cyanophenyl methyl t-butyl 4-amino-3-chloro-5-cyanophenyl ethyl t-butyl 4-acetamido-3,5-dichlorophenyl methyl t-butyl 4-amino-3-chloro-5-H2NCO-phenyl methyl t-butyl 4-amino-3-chloro-5-HDCO-phenyl methyl t-butyl 4 -amino- 3-chloro- 5 -methylphenyl ethyl t-butyl 4-amino- 3-chloro-5-methoxyphenyl n-butyl t-butyl 4 -amino- 3-chloro- 5-nitrophenyl methyl t-butyl 4-amino-3-chloro-5-CH3O-CO-phenyl methyl t-butyl EXAMPLE 28 3,5-dichloro-4-(N,N-diethylamino)acetophenone A sample (2.5 g) of 4-amino-3,5-dichloro- acetophenone in 10 ml of acetic anhydride and 25 ml of pyridine is stirred and heated at reflux temperature for 20 hours. The mixture is evaporated to dryness, and the residue is treated with ice and 10t NaOB solution and extracted with CE2C12 (3x50-ml). The extracts are dried (Na2SO4) and evaporated to dryness to give 2.42 g of semisolid, which is purified by chromatography over SiO2 using CH2Cl2 as cluent to afford 1.06 g of 4-(N,N-diacetyamino)- 3,5-dichloroacetophenone as an oil. This material is dissolved in 10 ml of tetrahydrofuran (THF0 under N2 atmosphere and 18 ml of 1M BE3.THF is added dropwise. The mixture is stirred until the reaction is complete and H20 is added cautiously. The mixture is evaporated to remove THF and 20 ml of H20 and 10 ml of 108 NaOH are added. This aqueous mixture is extracted with CH2Cl2 (3x25 ml) and the extracts are dried (Na2SO4) and evaporated to dryness to yield 0.68 g the desired alcohol. This product (0.3 g) in 2 ml of CH2C12 is added to 0.32 g of pyridinium chlorochromate (PCC) in 2 ml of CH2Cl2. After 1.25 hours, an additional 0.3 g of PCC is added and after another 0.5 hours, the solution is decanted and the residue is washed with 10 ml of CH2Cl2. The combined CH2Cl2 solutions are diluted with 50 ml of CE2C12 and washed with 10 ml of saturated Na2CO3 solution and 10 ml of B20 and dried (Na2S04). The solution is evaporated to dryness to afford a residue which is chromatographed on SiO2 with CE2C12 as eluent to yield 0.04 g of the title compound as an oil (NMR in CDC13: 81.0 (6E, triplet), 2.5 (3H, singlet), 3.25 (4H, quartet), 7.83 (2E, singlet). The monoethylaminoacetophenone is also obtained as a solid (0.12 g) as the second component. This 3, 5-dichloro-ethylaminoacetophenone is further reacted with propionic anhydride, reduced and reoxidized in the above manner to afford 3.5- dichloro-N-ethyl-N-propylaminoacetophenone. In a similar manner the following 4- (N,N- dialkylamino-acetophenones which are required for preparing 4-(N,N-disubstituted amino) compounds of formula I are prepared: EMI63.1 R8 R9 X Y n-C3H7 n-C3H7 Cl Cl n-C4H9 n-C4H9 Cl Cl C2H5 n-C3H7 Cl Cl C2H5 C2H5 Cl CH3 C2H5 C2H5 Cl CF3 C2H5 C2H5 Cl NO2 C2H5 C2H5 Cl Br C2H5 C2H5 Cl OCH3 EXAMPLE 29 c-1ltert-butylamino)methyll-3,5-dichloro-4-diethyl- aminobenzyl alcohol In the manner described in Example 13, 3,5-dichloro-4-diethylaminoacetophenone is oxidized with SeO2 and reductively alkylated with t-BuNH2/NaBH4 to afford the title compound, mp 93-960C. Similarly, &alpha;-[tert-butylamino)methyl]-3,5- dichloro-4-(n-dipropyl)aminobenzyl alcohol and &alpha;-[(tert-butylamino)methyl]-3,5-dichloro-4-(n-dibutyl)- aminobenzyl alcohol are prepared EXAMPLE 30 2-bromo-3 ', 5 ' -dichloro-4 ' -diallylaminoacetophenone and 4'-(allylamino)-2-bromo-3',5'-dichloroacetophenone EMI64.1 Triethylamine (17.0 g, 0.168 mol) is added in one portion to allyl bromide (105.9 g, 0.875 mol) under a nitrogen atmosphere. The resulting white emulsion gives an exotherm to 70 0C and becomes a thick white solid mass within S minutes. The solution formed with the addition of ¯100 ml of DMF is stirred for 1 hour at 70-95 C. A solution of 4'-amino-2-bromo-3',5'-dichloroacethophenone (25.0 g, 0.088 mol) in 50 ml of DMF is added in one portion and the resulting brown reaction mixture is maintained at 80-900C for 2 hours. The progress of the reaction is frequently checked by thin layer chromatography(SiO2/CH2Cl2/hexanes (1/1)) since prolonged heating results in the decomposition of both starting material and products. The reaction mixture is poured into 1.51 of H20 and is stirred for 0.5 hours. After a second aqueous trituration, the residual brown semi-solids are stirred with ¯150 ml 'of CC14 for 0.5 hours to form a suspension. The yellowish-brown solids are collected by filtration and are air dried to give 14.9 g (59.6t) of recovered phenacyl bromide starting material. The CCl4 filtrate is stirred with MgS04, filtered and concentrated to yield 9.42 g of a brown syrup. Gradient elution (hexanes/CE2C12 (10/0 - B/2 flash chromatography on a 9"x2" column of Silica Gel 60 gives two major fractions: (A) 1.82 g (5.74) of a faster moving amber syrup, identified as 2-bromo-3' ,5'-dichloro-4 'diallylaminoacetophenone by IR (neat) 1680 NMR (CDC13) ±7.93 (s, 2, AR-H), G.25-5.55 (complex m, 2, CH-), 5.40-4.95 (complex m, 4, CH2-), 4.40 (s, 2, CH2Br and 3.87 (m resembling d, 4, J-6Hz, CH2N); chemicla ioniazation mass spectrum (M + H) + = 3.62; and (B) 3.49 g (]2.2%) of a slower moving brown syrup, ideitified as 4'-(allyamino)-2-bromo- 3' ,5'-dichloroacetophenone by IR(neat) 3330, 1670cm-Ú; NMR(CDCl3) 67.83 (s, 2, AR-H), 6.35-5.65 (complex m, 1, CH-), 5.50-5.00 (complex m, 2, CH2=), 4.84 (br t, 1, NH), 4.37 s, 2, CH2Br) and 4.20 (br m, 2, CH2N); chemical ionization mass spectrum (M + H) = 322. EXAMPLE 31 4-(Allyamino)-&alpha;-[(tert-butylamino)methyl]-3,5- dichlorobenzyl alcohol EMI66.1 A solution of 4'-(allylamino)-2-bromo3',5'-dichloroacetophenone (2.88 g, 8.92 mmol) in 10 ml is added dropwise over 1 hour to a stirred solution of t-butylamine (1.34 g, 18.3 mmol) in 20 ml of THF. The reaction temperature is maintained at -240-130C by cooling in a dry ice CCl4 bath. The resulting amber suspension is warmed to room temperature over 30 minutes and is stirred at 21-22 C for 1.5 hours. sodium cyanoborohydride (2.80 g, 44.6 mmol) is added in two portions over 5 minutes to give a thick tan suspension with an exotherm from 22-250C. Glacial acetic acid (¯10 ml) is added dropwise to gradually form a yellow solution which is stirred at room temperature for 3 days. The reaction mixture is poured into a solution of 100 ml of B2 and 100 ml of saturated aqueous NaCl which is then adjusted to pH7 with 10% Na2CO3 and extracted three times with Et2O. The combined extracts are shaken with two portions of diluted aqueous RC1 which are combined, neutralized with 108 Na2CO3 to pE8 and extracted three times with Et2O. After stirring the combined extracts with anh. K2CO3, the pale yellow-green solution is filtered and concentrated to yield 2.04 g (72.1%) of a pale yellow syrup, identified as 4-(allylamino) a- 1 (tert-butylamino)methyl] -3, S-dichlorobenzyl alcohol by IR(neat) 3400 = 1; NMR(CDCl3) 67.32 (s, 2, Ar-H), 6.35-5.60 (complex m, 1, CH-) 5.45-4.95 (complex m, 2, CH2-). 4.52 (d of d, 1, Ar-CH). 3.97 (overlapping m, 3, Ar-NECH2), 3.03 (br 5, 2, NH and OH), 2.68 (m, 2, CH2N) and 1.13 (s.g. C(CH3)3; chemicla ioniazation mass spectrum (M + M)+ = 317. The CE2Cl2/CH3OE/conc. NH4OH (80/19/1)) shows one major spot (Rf - 0.6) with nine trace impurities. The syrup gradually crystallizes to a tan solid on standing. EXAMPLE 32 N-tert-butyl-m-hydroxy-ss-methylthiophenethylamine hydrochloride By using the procedure of Example 3 and substituting methyl mercaptan for methanol as in Example 25 the title compound is prepared. EXAMPLE 33 The following compounds are prepared by the method of Example 13: EMI67.1 R8 R9 mp C H l-C4Hg oil H 1-C6H13 62-64 H C2H5 209 (HCl salt) H benzyl 85-89 H cyclopentyl oil H cyclohexyl 194-198 (HCl salt) -CH2-CH2-CH2-CH2 EXEMPLE 34 &alpha;-[(tert-butylamino)methyl]-3,5-dichloro-4- diall ylaminobenzyl alcohol EMI68.1 The title compound is prepared using the procedure described for the preparation of 4-(allylamino)-&alpha;-[(tert-butylamino)methyl]-3,5- dichlorobenzyl alcohol (Example31) ) . The pale yellow syrup, which gradually crystallizes on standing, is identified by IR (neat) 3300 and 1630 cm-Ú; NMR(CDCl3) 67.26 (s, 2, AR-a), 6.23-5.54 (complex m, 2. CH-), 5,32-4,87 (complex m, 4, CH2-), 4.48 (m, 1, Ar-CH), 3.78 (m resembling d, 4, J-6Hz, Ar-NCH2), 3.4-2.0 (br z. 2, NH and OH), 2.62 (m, 2, CH2N) and 1.13 (s, 9, C(CE3)3); chemical ionization mass apectrum (M + H) + = 357, corresponding to that expected of the title compound.

Claims: CLAIM 1. An animal feed composition comprising a balanced diet and from 0.01 to 400 grams per ton of feed of a compound having a formula selected from the group consisting of: EMI69.1 wherein, X is hydrogen, halogen or -CN; Y is hydrogen, NR8Rg or NHCOR5; Z is hydrogen, halogen, OH, CN, CF3, COOR1, CONH2, C1-C4 alkyl or C1-C4 alkoxy; R1 is hydrogen, C1-C4 alkyl; R2 is hydrogen, C1-C6 alkyl, C3-C4 alkenyl, C2-C5 alkanoyl or EMI69.2 R3 is hydrogen, C1-C6 alkyl, C3-C6 cycloallkyl, methoxypropyl, C3-C4 alkenyl, penyl, 2-hydroxyethyl, &alpha;,&alpha;-dimethylphenethl, benzyl, 3-phenylpropyl or 3 (4-carbcmethoxypl)propyl; and when R2 and R3 are taken together with the nitrogen to which they are attached, they represent morpholino or NÚ-C1-C4 allkypiperazino; R4 is hydrogen, OH, OR6 or SR11; R6 is hydrogen, C1-C4 alkyl, C1 alkoxy, EMI69.3 or R6 is C1-C6 alkyl, C2-C5 alkanoyl, EMI69.4 C3-C4alkenyl; R7 is hydrogen, C1-C4 alkyl or phenyl; R8 is hydrogen, C1-C4 alkyl or C3-C4 alkenyl; R9 is hydrogen, C1-C6 alkyl, C-C6 cycloalkyl, C3-C4 alkenyl, or benzyl; and yen R8 and R9 are taken together with the nitrogen to which they are attached, they represent pyrrolidino; R10 is chloro, dichloro, methyl, dimethyl, methoxy, dimethoxy or nitro; R11 is C1-C6 alkyl, phenyl or benzyl; with the provisos that when R3 is phenyl, 2-hydroxyethyl, a, &alpha;-dimethyl- phenethyl, C3-C6 cycloalkyl, benzyl, methoxypropyl, 3-phenylpropyl, or 3-(4-carbonethoxyphenyl)propyl, Rz is hydrogen; and when R3 is hydroxyethyl, R4 is hydroxyl and the compound is (I); and when R6 is alkanoyl or EMI70.1 R2 and R3 are substituents other than hydrogen, except when R3 is an alkyl or a substituted alkyl group which contains a tertiary carbon attached to nitrogen; and when Y is hydrogen, X and Z are halogen, and R2 is hydrogen, C2-Cs alkanoyl ar EMI70.2 R3 is isopropyl, 2-butyl, and t-butyl; and when R8 is is C1{74 alkyl or C3-C4 alkenyl, Rg is C1-C4 alkyl or C2-C4 alkenyl; and when Z is OH, X and Y are hydrogen; and that at least one of X, Y and Z represents a substituent other than hydrogen; and when X is -CN, Z is -CN; and when Z is hydroxyethyl, R4 is OH; and when Z is a group other than halogen, Y is NR8R9 or NHCOR5; and when R5 is N(RI)2, R4 is E; and frrther provided that when X is hydrogen or halgen, and Y is hydrogehn, NH2 or NHCOR5. and Z is hydrogen halogen or OH, then R4 cannot be hydrogen, OH ar.OR6 where R6 is C1-C6 alkyl; acetic mixtures of the above - identified canpounds and the optically active isaners, and non-toxic, pharmacolgically acceptable acid addition salts thereof. 2. A method for the preparation of an animal feed cappos- ition copsing admixing an al feed with from 0.01 to 400 grams per ton of feed of a canpound having a structure selected from the group consisting of: EMI70.3 EMI71.1 wherein X, Y, Z, R1, R2, R3, R4 and R7, are as defined in claim 1 above. 3. A composition according to claim 1 wherein said compound is selected from the group consisting of: N-tert-butyl 3,5-dichloro-ss-methyoxy-4-methylaminophenethylemine; &alpha;-[(tert- butylamino)methyl]-3,5-dichloro-4-isopropylaminoenzyl alcohol; 5-[2-tert-butylamino)-1-hydroxythyl]-3-chlorocarthranilontirile; 5-[2-tert-butylamino)-1-hydroxythyl]anthranilonitrile; methyl -5-[2-tert-butylamino)-1-hydroxythyl]-3-chloroanthr nilate; 4'-[2-tert-butylamino)-1-hydroxythyl]-2',6'idchlorvaleranilide; benzyl-4-[2-tert-butylamino)-1-hydroxythyl]-2,6-dichlorocarbenilate; 5-acetylanthranilonitrile; 4-amino-N-tert-butyl-3,5-dichloro -ss-(methylthio)phenethylamine; N-tert-butyl-3,5-dichloro-ss-methoxyphenethylamine; &alpha;-([(tert-butylamino)-methyl]-3,5-dichloro-4-methy- laminobenzyl alcobol; &alpha;-[(tert-butylamino)methyl-3,5-dichloro-4- dimethylaminobenzyl alcohol; 4-amino-3,5-dichloro-&alpha;-{[(3-phenyl- propyl)amino]methylbenzyl alcohol; 4-amino-3,5-dichloro-&alpha;-{[&alpha;,&alpha;- dímethylphenethyl)amino]methyl}benzyl alcolbol; 4-amino-N-tertbutyl-3,5-dichloro-ss-ethoxyphenethylamine; methyl-p[3-[(4 amino-3, 5-dichloro-ss-hydroxphenethyl) amino] propyl ) benzoat ; methyl-4-[2-(tert-butylamino)-1-hydroxyethyl]-2,6-dichlorocarbanilate; 4Ú-[2-(tert-butylamino)-1-hydroxyethyl]-2Ú,6Ú-dichloroacetanilide; S-F 2 (tert-butylamirn )-1-hydroxyethyl]-3-chloroanthranilonitrile; 4- amino-ss-(benzyloxy)-N-tert-butyl-3,5-dchlorophenethylamine and the non-toxic, pharmaceutically acceptable acid addition salts thereof. 4. An anmal feed supplement useful for enhancing the growth rate and lean meat deposition in warm-blooded animals canprising fran about 75% to 95% by weight of a compound having formula selected fran the group consisting of: EMI72.1 wherein X, X, Y, Y, Z, E, R2, R3, R4 and R7, are as defined in claim 1 above and from about 5% to 25s by weight of a suitable carrier or diluent. 5. An injectable composition useful for enhancing the growth rate and lean meat deposition in warm-blooded animals com- prising as an active ingredient a compound having a formula selected fmn the group consisting of: EMI72.2 EMI73.1 wherein X, Y, Z, R1, R2, R3, R4 and , are as defined in claim 1 above, and a pharmaceutically acceptable carrier. 6. A composition according to claim 5 wherein the active ingredient is administered to warm-blooded animals in an amount sufficient to provide said animals with fran 0.001 to 100 mg/kg/ day of body weight of the active ingredient having the formula; EMI73.2 wherein X, Y, Z, R1, R2, R3, and R4, are as defined in claim 1 above. 7. An implant useful for increasing the dressed carcass weight of meat-producing anittals and enhancing the lean meat to fat ratio thereof comrising as the active ingredient a compound having the structure: EMI73.3 wheerein X,Y,Z R1, R2, R3 and R4 are as desorbed in claim 1 above, and a parmeceutically acceptable carrier. 8. A compound of the formula: EMI73.4 wherein X is hydrogen, halogen or -CN; Y is hydrogen, NH8R9 or NHCOR5; Z is halogen, -CN, CF3, COOR, CONH2, C1-C4 alkyl, C1-C4 alkoxy, NO2 or C1-C4 dialkylaminomethyl; R1 is hydrogen or C1-C4 alkyl; R2 is hydrogen, C1-C4 alkyl, C3-C6 cycloalkyl, C3-4 alkenyl, C2-C5 alkanolyl or EMI74.1 R3 is hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl, C3-C4 alkenyl, phenyl or benzyl; R4 is OH, OR6, or OR11; R5 is hydrogen, C1-C4 alkyl, C1-C4 alkoxy, EMI74.2 R6 is C1-C6 alkyl, C2-C5 alknoyl, EMI74.3 R8 is hydrogen, C1-C4 alkyl or C3-C4 alkenyl; R9 is hydrogen, C1-C6 alkyl, C4-C6 cycloalkyl, C3-C4 alkenyl or benzyl; R10 is hydrogen, chloro, dichloro, methyl, dimethyl, methoxy, dimethoxy or nitro; Ril is C1-C6 alkyl, phenyl, benzyl; with the provisos that when Y is NH2, NHCH3, NHC2H6, R4 is OR6 or SR11; and ten Y is hydrogen, X and Z are halogen, is hydrogenm, C5-C5 alkanoyl or EMI74.4 and R3 is isopropyl, 2-buty or t-butyl; and when X is -CN, Z is -CN; and when R6 is alkanoyl or EMI74.5 and R3 are substituents other than hydrogen, except when R3 is an alkyl or a substituted alkyl group which contains a tertiary carton attached to nitrogen; and when R8 is C1-C4 alkyl or C3-C4 aikenyl, R9 is C1-C4 alkyl or C3-C4 alkenyl; and further provided that when X and Z are halogen and Y is hydrogen or NH2 then R4 cannot be hydrogen, OH or OR6 where E is C1-C6 alkyl; racemic mixtures of the above - identified compounds end the optically active isomers, and non-toxic phanmacologically acceptable acid addition salts thereof. 9. A compound according to claim 8 wherein said compound is: N-tert-butyl-3,5-dichloro-ss-methoxy-4-methylaminophenethylamine; &alpha;-[(tert-butylamino)methyl]-3,5-dichloro-4-isopropylaminobenzyl alcohol; 5-acetylanthranilonitrile; 4-amino-N-tert-butyl-3,5dichloro-ss-(methylthio)phenethylamine; &alpha;-[(tert-butylamino)methyl]- 3,5-dichloro-4-dimethylaminobenzyl alcohol; 4-amino-ss-(benzyloxy) N-tert-butyl-3 , 5-dichlorophenethylamine; 4-( allylamino ) - -F (tert- butylamino )methyl-3 ,i-dichlorobenzyl alcohol, and the non-toxic, pharmaceutically acceptable acid addition salts thereof.

Inventors: BAKER, PAMELA KOENIG, KIERNAN, JANE ANN
Applicants: AMERICAN CYANAMID COMPANY
Application year: 1981
Main classification: A23K1
IPC codes: A23K1, C07D263