July 1965
HYDROXYLAMINE CHEXISTRY.T:
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HYDROXYLAMINE CHEMISTRY.V
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a t room temperature. Solid was removed by filtration and recrystallized from ethanol-isopropyl alcohol for analysis had washed with CH2Clz. The filtrate was evaporated t o dryness m.p. 225-226". Anal. Calcd. for C14Hl$02,HCl: C, 63.27; H, 6.07; X, under reduced pressure and the residue was extracted with ether. The ethereal extracts were acidified with HCl in isopropyl 5.27. Found: C, 63.23; H, 6.06; N, 5.59. alcohol affording 38.2 g. of crude aralkoxyamine hydrochloride, 2-Phenoxyethoxyguanidine. A.12-To a stirred suspension of m.p. 199-201' dec. Recrystallization (methanol-ethyl acetate) 20 g. (0.105 mole) of 2-phenoxyethoxyamine hydrochloride in afforded 27.2 g. of analytically pure material, m.p. 206" dec. 150 ml. of toluene n-as added 4.44 g. (0.105 mole) of cyanamide,13 Anal. Calcd. for CiHiClJVO.HC1: C, 36.79; H, 3.53; and the mixture was refluxed under nitrogen for 2 hr.I4 During C1, 46.55; N, 6.13. Found: C, 37.21; H, 3.51; C1, 46.50; N, this time the solid present liquified to a n insoluble oil. The toluene was evaporated under reduced pressure, and the oily 6.31. N-(4-Phenylbenzyloxy)phthalimide.-4-Biphenylniethanol~~ residue was suspended in water with stirring and basified with (16.5 g., 0.09 mole) was converted into 4-phenylbenzyl chloride aqueous NaOH. The resulting suspension was chilled and stirred with thionyl chloride and the crude halide was stirred and briefly, and the solid was collected, washed with water, and dried warmed on the steam bath wvit,h 14.7 g. of N-hydroxyphthalimide, affording 17.45 g. ( 8 5 5 ) , m.p. 120-122". Recrystallization 28 nil. of triethylamine, and 100 nil. of DLIF for 1 hr. The solufrom isopropyl alcohol afforded analvticallv material, - pure tion was cooled and diluted with water (500 nil.). The solid m.p. 122-124'. was collected, washed with water and methanol, and dried 3-Phenylpropoxyguanidine Nitrate. B.I2-The free base, preaffording 23.6 g. of the product, m.p. 191-193". A sample repared from 18.8 E. (0.1 mole) of 3-phenvloro~1oxyaminehvdrocrystallized from benzene-ethanol for anall-sis had m.p. 192-194". chloride by treatment with alkali, ;,as dissofved in 100 i i l . of Anal. Calcd. for C ? l H I B S O ~C, : 76.58; H, 4.59. Found: 50% aqueous methanol. To this solution 13.9 g. (0.1 mole) of C, 76.04; H, 4.55. 2-met,hyl-2-thiopseudourea sulfate was added, and the mixture 4-Phenylbenzyloxyamine Hydrochloride.-A methylene chlowas heated under reflux for 6 hr., then evaporated to dryness ride suspension of ?i-(4-phenylbenzyloxy)phthalimide (23 g., under reduced pressure. The residue was dissolved in 500 ml. 0.07 mole) was stirred with 3.6 g. of hydrazine hydrate and 10 of 507, aqueous methanol and the solution was saturated with ml. of methanol for 16 hr. The solid n-as removed by filtration ammonium nitrate. Methanol was evaporated on the steam and washed with C H L L The filtrate was evaporated, and the bath under a n air stream, and the remaining aqueous solution residue extracted with warm ether. The extracts were washed Tvas refrigerated. The solid that precipitated was separated with water, diluted with methanol, and concentrated on a steam by filtration and recrystallized twice from a mixture of met.hy1 bath to remove t,he ether. Dilution with water afforded 12.4 ethyl ketone and ethyl acet,ate to give 13 g. (51% yield) of prodg., m.p. 61-63", of the free base. Recrystallization from isouct as white needles which decomposed sharply a t 111'. propyl alcohol afforded 9.3 g. of the aralkoxyamine having m.p. 1 -Benzyloxy-3,3-dimethylguanidine Cyclohexanesulfamate. C. l 2 65-64", which was dissolved in isopropyl alcaohol and treated -Benzyloxyamine hydrochloride (16 g., 0.1 mole) and dimethyl with HC1. The crude solid was collected and recrystallized from cgananiideI6 (7 g.) were stirred under nitrogen and heated in a n %yoethanol afording 8.0 g. of the hydrochloride, m.p. 2.55-266' oil bath a t 150-160' for 1.5 hr. The resulting gum was suspended dec. in water and basified; the oil which separated was ext'racted with .Anal. Cakd. for C13H,,J0.HC1: C , 66.24; H, 5.99; K, ether, and the extracts washed with water, dried, and evaporated 5.94. Found: C, 66.46; H , 5.92: 3, 3.74. to dryness under reduced pressure leaving 15.5 g. of mobile oil. 2-(4-Biphenylyloxy)ethyl Chloride.-To a chilled suspension This oil T V ~ Sdissolved in 155 nil. of ethyl acetate and treated in 200 nil. of of 26 g. (0.12 niole) of ~-(4-hiplienylyloxy)ethaiiol~~ with a solution of 14.4 g. of cyclohesylsulfaniic acid in acetone benzene containing 9.75 1111. of p;\-ridine was slowly added 9.0 nil. (150 ml.) affording 24.2 g. of the hexamate salt, n1.p. 120-123". of SOCl? with vigorous stirring. The mixture was stirred briefly l-Benzyloxy-2,3-diisopropylguanidineHydrochloride. D.l2iLt room temperat,ure, refluxed for 3 hr., washed with water and Benzyloxyaniine (12.3 g., 0.10 mole), diisopropylcarbodiimidelo then brine, and dried (NgSO?). The solution was concentrated (6.3 g., 0.05 mole), and 10 ml. of t-butyl alcohol were heated on and the benzene was displaced with methanol. On cooling, a steam bath for 14.5 hr. Volatile materials were removed by 22.85 g., 11i.p. 101-103O, of the chloro compound was obtained. heating under reduced pressure (100' a t 10 mm.) leaving a Recrystallization from methanol afforded a n analytical sample, blue oil. The oil was dissolved in acetone, briefly refluxed, and m.p. 102-104". evaporated to dryness leaving 10.8 g. of pale green oil. This Anal. Calcd. for C,rH&lO: C, '72.26; H, 5.63; C1, 15.24. was redissolved in acetone and treated with a solution of 8.95 g. Found: C, i2.60; H, 5.42; C1, 14.87. of cyclohexylsulfamic acid in acet'one. On chilling overnight N-[2-(4-Biphenylyloxy)ethoxy]phthalimide.--A solution of only a trace of insoluble material separated and was removed by 28.2 g. (0.12 mole) of 2-(4-biphenylyloxy)ethyl chloride, 19.8 g. filtration. The filtrate was evaporated to dryness leaving an of X-hydroxyphthaliniide, and 37 ml. of triethylamine in 185 ml. oil which was distributed between ether and n-ater. The aqueous of D l I F was stirred and heated on the steam bath for 28 hr. layer was separated, basified, and extracted with ether. This (after 1 hr. on the steam bath 90c0 of the biphenylyloxyethyl extract was dried (K?C03and LlgSOr) and evaporated to dryness chloride was still present). The solution was cooled and diluted leaving 5.95 g. of a yellow oil. Dissolution in ethyl acetatewit,h 250 ml. of water with stirring. The solid was collected, ether and acidification with 2-propanolic HC1 afforded 5.80 g. washed with water, taken up in CHgClz, and dried (SasSOr). of crude aralkoxyguanidine hydrochloride, m.p. 113-122 ". The methylene chloride was displaced with ethanol, and the soluRecrystallization from isopropyl alcohol-ethyl acetate afforded tion was allowed t'o cool affording 11.1 g. of crude aralkoxy4.10 g. of the pure material, m.p. 125.5-126.5". phthaliniide, m.p. 169-171". A sample recrystallized from methylene chloride-ethanol for analysis had m.p. 171-172". Acknowledgment.-The authors are grateful to Anal. Calcd. for CZZHIiN04: C, 73.53; H. 4.77. Found: B. Hooker for technical assistance iii the preparaD. C, 73.73: H , 5.10. tion of some of these compouiids, t'o A. P. Tazelaar, 2-(4-Bi~henvlvloxv~ethoxvamineHvdroch1oride.-A stirred solution ;f ~ - ~ ~ - ( ~ b i p h e n ~ ~ l y l o x y ) e t h ; s ~ - ] p h t h(9.1 alim g.,i d e R. R. Russell, and H. J. Triezenberg for technical 0.025 mole) in 200 ml. of CH?Cl? \Vas treated with 1.27 g. of assistance in the biological eraluation of these comhydrazine hydrate in 5 ml. of methanol. After 5 hr. the precipipounds, to Drs. R. T'. Heinzelnian and J. J. Urspruiig tate was renioved by filtration and washed with methylene chlofor helpful discussions, and to the staff of our Physical ride. The filtrate was evaporated t o dryness under reduced pressure. The residue was extracted with ethyl acetate and the and Analytical Chemistry Department for analytical extracts were washed with water, dried (K2C03 and l l g S 0 4 ) , and spectral data. and acidified with isopropanolic HCl, affording 5.60 g., m.p. 227' dec., of product. The salt was converted into its free base, (12) Procedures &D are listed i n Table 11. m.p. 129-130.5' after recrystallization, and the purified base (13) Practical grade cyanamide from Eastman Kodak Co., Rochester, N. Y.. v a s employed. T h e material used was almost completely soluble in was reconverted into the hydrochloride, m.p. 225-227'. A sample ether. (14) I n other runs, reflux periods of 1-6
(11) C . C. Vernon, E. F. Struss, AI. A. O'Nell. and RI. -1.Ford, Chem. Sac., 6'7, 527 (1935).
J . Am.
111. a e r e employed. (15) Practical grade from XIatheson Coleman and Bell, East Rutherford. N. J.
