obtained 24.2 g of 23,bitartrate, inp 209-210"; liberated base, [ a I z a 5 i 6 0' (1 dm, c 2.96). This material was dissolved in refluxiiig hIeOH-H20 (1: 1, 400 nil) and then allowed to stand for i h r at rooin temperature. The resultarit solid was filtered oif and the filtrate was concentrated in m " o to about 100 nil. The solid was filtered OH' to give 9.; g o f ( - j-23.bitartratme,Inp 21 I - 213'; liberated base, [cyIz4546 -11.6" ( 1 dm, cY.Ol), in11 198-200", And. (CI~~H~~SO C,I )13, : K, 0. Filtrate A f r o m above was coiicent.riited in t~ctcii,o t,o aboiit one-fourth the original volume and the resultant solid was filtered off to give 19.8 g of 23.bit,artrate, nip 216-218": liberated base. i o l 1 2 h i-2.0 (1 dni. c 2.9.:). The solid was dissolved i ~ i refluxing I
.
stand about l b hr a t room teriipe~atuic. Filt I: of 23 bitartrate, nip 213-215'. liberated base, [ L Y ] ~ ~ , ~t-l G 7" I I clm, c 2 . 8 3 ) This i n a t e i d wab then recrvstallized t \ v i w f i o n r AIeOll fllC) ( 1 1, 2 nil) tn givr '17 g of i$-J-23 bitaitr:it(>, mp 209-212" irhe1
_
The Alkylation and Acylation of B10H9NH3-
The reactioii of 2-HloI19Kl13- with ethylene oxide prodtired 113SB,olI;(CII,CII,01-Ih --,heveral .zalti : i i i d derivatives of which were prepared. Treatmelit of 2-BloHp?JH3-wit,h Sa11 followed by the, :idditioii of et hyl a-chloroacetate produced BloR,NH(Cf12COOC2Ha)?-, which was subseqriently reduced to HloTI,?;IT(CfI K f l r OB),-. Benzoylatiori of 2-BloH,?iH,- was found to give the K-substituted in preferelice tlJ the B-srihstitritcd dei,ivative. Prelimiri biological resiilta reveal that. whereas the 5-p-hydroxycthyl derivative is iiot i i i c ~ i i . porated iiito brain, m e, or t r x " tissues the B-8-hydroxyethyl derivative and its pho>phatce.ter :il)peai' t o be stxongly bound to tumor tissues and give very favorable tumor-blood boron raf ius.
choice of BI0H9SH,- :i\ :i 3t:irtirig poitit \v:i> motivated The lo\v toxicity of polyhedral borane3 arid their not only by the fart th,it it off'er3 :L cnhoicac>of t\vo ro' tlerivatir-e-* has stimulated a renewed ititereit in the BO neutron capture therapy of brain tumors.5 The d i ~ :ictive uiteh, the nitrogen arid the ciigc, but t h a t it. chemistry has riot tleeii even superficially explorcd. cowry that these boranes can be rcadily subitituted Allq-latioii and acylatioii reavtion.: were the firit 1o he n i t h a riuniber of organic groups6 opened up :i search examined since they w n provide the >tarting pointh 111 for convenient "handles" for the incorporation of thew the .yiithe.eh of derivative. having t he bor:inca :itboron-rich ions into tumor 203-!2:i4, is readily heiizoy1:itcd rveii without :t Priedel-Crnft;.: ( 6 ) \V. I I . I,\ISO arid hot HzO. .lnal. Calcd for TlB,,IrYNH(CII,C~I,OH),.H,O: C, 10.8; H, 4.94; N, 3.14; B, 24.2; TI, 45.9. Fomd: C, 10.7; H, 4.96; N, 3.53; B, 24.6; T1, 4,5.8. The T1+ salt was dissolved iii a large volume of HzO arid passed through a cation-exchange reah i n the N a + form. The solutioii was evaporated t o drylieas aiid disholved in 1hO; pmr spectrum of the x a + salt, two triplets ( J = 5 cps) of equal area at 7 5.62 aiid 6.32, respectively; equiv wt of the salt, 250 (calcd for KaBloHyNH(CHzCHzOH ) 2 , 245). Benzoylation of BIOHYNH;~-.-Asolution of [ (CH3)4N]B10HyXH3 (3.5 g, 17 mmoles) and C6H;COCl (18 g, 128 mmoles) in 200 ml of lOYc NaOH was stirred for 24 hr at room temperature. The
ACYLATIOS 01, Bl,H,SH3-
37
reaction mixturc! was coricentrated to 100 nil under rediiced pressure, treated with 3 1. of Me,CO to precipitate CsHjCOZYa, and filtered. The filtrate was concentrated under reduced preaxure to iiear dryness and treated with 100 ml of H,O. The resiiltiiig suspeiisiori was cleared by extracting the suspended sclid with five 50-ml aliquots of EtzO. Acidification of the clear aqueous solution with HC1 to p H 2 precipitated a solid which waq redibrolved in J I e C S . Addition of Et20 to the JIeCN solution yielded a mixture of brown and white rolids. The brown solid was washed out with a small amoiuit of cold I I e C S , and the remaining white solid dissolved iii JIezCO. Sddition of EtYO t o the Me,CO solution yielded [(CH,)&] B,oHgNH,COC6H,,mp 218-219'. The yield after i'e tallizatioii from E t d - h I e C S was 0.9 g (177;); ir Fpectnini, baiids attributable to the pheiiyl ring, the cation, aiid the boron cage, aiid a very- strong amidic cahoiiyl peak at 1640 cm-l. A n d . Calcd for [(CHa\,S]BloHlrjyH,COC6H,:C, 42.3; FI) 9.0; ?;, 8.9; B 34.6. Fouiid C, 41.9; H, 8.6: N, 9.2; B, 33.2. Reagents, Apparatus, and Techniques.-Except for BlaH,SHI-, - hydroxylamiiiekvhich was made by the reaction of B l ~ H l o 2with 0-sulfoiiic acid, 8 commercially available reageiit grade chemicals were iwed thimiighorit this woyk. 111 the case of diglyme (Jill?. the fraction boiling at 161-162" at 740 mm was collected after S hr of reflux over LiAlH,. l>.\IFwaz distilled over CaH2, whsreac NeCK wan distilled over PgOi. The ir spectra were recorded iii KBr pellets or Nujol miills o n a Perkiii-Elmer JIodel 337 spectrometer, the pmr spectra on a Variaii 1)A-60 spectrometer a t 60 Ale (TMS). Molecular weights of salt? which had 110additional ionizable H were obtained by exchaiigiiig the cation iii a weighed >ample of a salt for H 3 0 + aiid titrating the resiiltiiig acid with KOH. The titration was monitored with a Leeds and Sorthriip p H meter. Elemental analyses were performed at commercial lab:llat(JlieS.
Acknowledgment.-The authors \\-ish to thank Dr. William H. Sweet, Professor of Surgery at. t'he Harvard :\ledical School aiid Chief of the Seurosurgical Service of the l\Iassachusetts General Hospital, for his interest and Professor Paul R. Shafer, of Dartmouth College, for his many useful suggestions at8several stages of the synthet,ic work. Invaluable technical assistance of N r s . ,Janette R. :\lesser arid her collaborat.ors, and that of l l r . Douglas B. Woodruff and A h . Robert Rix are gratefully acknonledged.
