Experimental Section;
9-fl-i~-Ribofuranosyl-6-hydroxylaminopurine (I1 ).--O-~-I)1~i1~of~rr:iiiosyl-6-chloropurine6 (I, 23:: g., 10 mnioles) was clissolved i n an ethanol solution of Iiyctrosylariiine 1350 nil., prcpared as indicated in ref. 2 ) , heated a t 50" for 6 hr., and then kept a t 25" overnight. The crystalline product which deposited WLS rollected and washed with a little cold water and then with ethanol to yield 2.58 g. (go?), m.p. 210-213'. T'pon recrystal: 21s'. [ e ] ?aii lization from methanol, colorless thin i i o t ~ i l ~ >1n.p. -57" (c 0.5, water), were obtained. :Incd. Calcd. for CloHlaNjOL:C', 42.40; H, 4.59: S , 24.73. Foruid: C', 12.10; 13, 4.86; ?;, 24.54. The product (TI) gave positive FeC,ls aiid p1iouplioniolyl)d:tle tests, both indicative of the hydrosylaniino functioii. I1 \\-a$ recovered iinchanged after 3 hr. boiling in water (10 nnd after heating the same soliltion at 125' iii an aut hr. The solubility of I1 was 6.9 g./l. of water a t 25 =t1 Ultraviolet Spectral Properties.-Compound I1 exhibited a t p l l 1.4, A,,,,x 265 m p ( E 17.7 X l o 3 ) ; a t pH 6.7 (phosphate buffer), A,, 265 nip ( e 14.3 X l o 3 ) ; a t pH 12.2, Xmar 252 mp,i shoulder a t 310 nip; a t pH 1.4, A,,,!, 232 nip ( B 3.31 X l o 3 ) ; a t pH 6.7, X,,i,, 230 l l l p 4.65 x 1 0 3 ) ; R I I :It ~ p~ 12.2, xmi,, 230 IIW; PK,, = :%.li 0.1, pK,,= 9.7 t 0 . 1 . x Hydrogenation of II.--!)-fl-~-r~il~oEiiraiiosyl-G-h~dro piiriiie (11, 40.0 nig., 0.14 mmole) XIS dissolved in 95' ethanol ( I t ) nil.), 5' platinum-ori-charcoal catalyst was added, and the suspension was hydrogenated at 1 atni. at 25". .ifter iiptalie of the theoretical volmne of Ht, the suspeiisioir was filtered, the catalyst was washed with a little ethanol, and tho combined filtrate3 were evaporated t o dryness under rediiced pressure. The residue was wished with 1 ml. of ethanol talline prodnct waq obtained (34.2 mg., WC,,), n1.p. 23223.1". The product, which no longer gave the Feel3 arid phosphoniolybdate tests, was identifie iosine (111)by its inisture nieltiiigpoiiit, ultraviolet hpectra at tfitfereiit pH valiies, : ~ i i d from ltf vdiies iti several .solvent
'.
(.>) Ultraviolet absorption spectra \rere determined with a Cary recordinc npectrolhotometer, ,\lode1 11. Paper chromatograms \\-ere run by I I I P ascending metlioil on Schleicher and S c h ~ i e l lXu. 1 paper in the follo\ring solvent s p t e m s : n n t e r saturated u itli I-butanol; 1-butanol saturated 7vitIi \rater (n ith or u i t h o u t 10:; ammonia) ; 1-butanol-formic acid\ratf'r ( i i :IO: 13. v.,'v.). .\Ielt,ing points \rere taken in a Thomas-€1007-er TTnimelt apparatus and were corrected. The microanalysis \vas carried (lilt by Spang .\Iicroanalytical Laboratory, Ann Arbor, ,\lich. (6) G. 1%. Brown and V, S. Keliky, .I. B i d . C h e m . , '204, l0lY ( 1 hupplied by Cj-clo Chemical Corp., Los . 1 2 .
IIId
N-Substituted Ureidobis(1-aziridiny1)phosphine Oxides
Although some K-wb3titutecl ureidobis(l-aziridiii~1)phosphine oxidevas obtained by Pesticides Research Grniiii, E. TI. Rquibir Co., Division of the Olin llathieson Chemical Corri. .'I c i m i i r e heneive publication covering these data will appear separately. (4) 11. RLtz and C . Grundmann, U. S. Patent 2,858,ROB (Oct. 28, 195X): R. Ratz, E. Koher, c'. Griindmann, and C , . Ottmann. I n o r y . Clism., 3, 7'57 t1064). ( 5 ) .\. T, I\irsanu\- a n d (1961
>.
SI. S, ,\larmt.t*, .I. Gcn, C h m . f . S S I : , 31, I 4 ! X
145
XOTES
January 1966
TABLE I N-ARTLUREIDOPHOSPHORYL DICHLORIDES (11) ClsPOSHCONHR
____
One-step prepn.----M.p., Yield, %"
--
Two-step prepn.---
7ob M.P., OC. 122-1 23 121-122 63.9 91 .o a CGHS b 2-C&C1 49.9 121-122 39.8 118-120 147-148 C '&C&Cl 83.5 156-157 43.4 84.7 163-164 64.4 163-16.5 d 3,4CsHaCl,c 76.5 157-158 43.0 157-158 e 2,4-CsH,C1, 77.2 1.56 56.0 157-160 f 2,4,6-CsH,Cl$ 90.1 170 63.9 163 g '&C&CN h ~-C~H,SO, 79.5 154-155 62.0 143-1 45 88.1 163 53.4 161 i 4-CsH,IC'Oz 75.7 158-1 60 41.6 152-156 j ~-C~-~-NOZC& 77.4 134 58.7 125 k 1-CioH7 Yield calculat'ed on the basis of 66.37, yield of distilled ClvPONCO and the respective yield a Yield based on amount of PClj used. in diethyl ether. c Infrared absorptions of I I d appeared a t 2.98 ( N H adjacent to aromatic ring), 3.24 (NH adjacent to P=O and C=O), 5.9 (C=O stretch), 6.53 (urea absorption), 8.1 (P=O), 6.3, 6.8, 7.27, 7.7, 8.2, 9.5, 11.3, 11.5, 12.15, and 14.5 (aromatic) ,L. R
Compd.
acetone extraction of the crude material. The acetone, however, does not dissolve a small amount of byproduct, CllHl,Cl2N4O4P,m.p. 245". From a large volume of dioxane, IIId can be successfully recrystallized, leaving this contaminant undissolved. Since the infrared spectruni of this dioxane-insoluble residue is very similar to that of pure IIId, it cannot be detected by infrared spectroscopy in admixture with large amounts of the latter. After its isolation, however, the compound shows hydroxyl absorptions at 3.05 and 9.5 p. The absence of bands at 7.9 and 12.0 p indicates disappearance of the aziridine ring with formation of P-hydroxyethylamino groups. Attempted ethylenimine-group titration revealed complete absence of this three-membered ring. Compounds of the general structure 111 are insoluble in water. Dilute aqueous alkali, however, dissolves them completely. Their acidic character made it possible to follow effectively the course of their purification. The acid determination was done potentiometrically using aniline as solvent with tetrabutylammonium hydroxide as titrant. The potentiometric inflection obtained with IIId was strong (-300 mv.) and the end point occurred a t -+650 mv. Aziridine-group titration of IIId was possible with potassium thiocyanate in dimethyl sulfoxide-methanol solution6leading to ring cleavage and formation of IV, the latter being isolated as a crystalline substance. IIId
+ 2SCN-
HL
Attempted purification of compounds of the general structure 111by neutralization of their aqueous alkaline solution either by dilute mineral or acetic acid was unsuccessful, since the aziridine compounds did not separate unchanged from such solution. I n contrast, N-4cyanophenylureidobis(dimethy1amino)phosphine oxide (V), structurally related to IIIg, was readily purified by addition of acetic acid to its dilute sodium hydroxide solution. (6) R. C. Schlitt, Anal. Chem., 85, 1063 (1963).
oc.
Yield,
Experimental Section7 One-Step Reaction Leading to N-Substituted Ureidophosphoryl Dichlorides (II).-One example of the preparation of a compound of the general formula 11, representative of those given in Table I is described. N-3,4-Dichlorophenylureidophosphoryl Dichloride (IId).-A slurry of 208.3 g. (1.0 mole) of PCli and 60 ml. of ethylene dichloride was placed in a 1-1. three-necked flask equipped with a stirrer, dropping funnel, thermometer, an an Allihn condenser. I n the dropping funnel there was placed 89.1 g. (1.0 mole) of ethyl carbamate which was heated by a hot-air stream until molten. The flask was immersed in a mineral oil bath heated to 103'. Addition of molten carbamate was begun and continued at such a rate that the reaction temperature remained between 73 and 81', while the temperature of the oil bath was kept between 95 and 103'. When the addition of the carbamate was complete, the internal temperature was allowed t o rise t o 86' and kept there for 10-15 min. The oil bath was removed and the flask contents were allowed t o cool t o room temperature. An additional portion of 100 ml. of ethylene dichloride was added to the reaction mixture, and a stream of dry nitrogen was bubbled through for 50 min. to ensure the complete removal of the HC1. Then a solution of 162 g. (1.0 mole) of 3,4-dichloroaniline in 350 ml. of ethylene dichloride was added during a period of 15 min. with stirring and external cooling to maintain the internal temperature between 10 and 15". Fine white solid separated from the solution almost immediately. It was separated by filtration shortly after the amine addition was complete. White powder, 284 g., m.p. 183-184', was obtained. The yield based on PCls used was 887c.8 Anal. Calcd. for C7HsChNzOzP: N, 8.70; P, 9.62. Found: h',8.62; P, 9.16. N-Substituted Ureidobis(1-aziridiny1)phosphine Oxides (111) from N-Substituted Ureidophosphoryl Dichlorides (11) and Aziridines.-The preparation of only one representative of the aziridine compounds listed in Table I1 is given in detail. N-3,4-Dichlorophenylureidobis(I-aziridiny1)phosphine Oxide (IIId). Method A. Anhydrous Medium.-In a 500-ml. threenecked flask 9.7 g. (0.037 mole) of the dichloride I I d was suspended in 100 ml. of anhydrous ethyl ether. The flask was immersed in an ice bath, and a solution of 3.0 g. (0.070 mole) of ethylenimine and 6.0 g. (0.0595 mole) of triethylamine in 60 ml. of ether was added dropwise with stirring. The separation of a white solid began immediately. The addition required 65 min., and a t its completion, the reaction mixture was stirred for an additional 10 min. and finally allowed to stand for 1hr. The solid was then collected on a Buchner funnel t o give 15.0 g. of a mixture of product and triethylamine hydrochloride. This mixture was extracted with two 75-ml. portions of cold water. The re(7) All melting points were determined on t h e plate of a Fisher-Johns block. I n t h e case of compounds 111, the sample was placed on a preheated plate a t approximately 5' below t h e melting temperature. Otherwise, because of polymerization, no melting point of these compounds can be determined. (8) On the basis of the maximum yields for the individual reactions, the best over-all yield obtained in the two-step preparation was 64.4%.
146
