September 1967 SCHEME I
X
X = HOOC-
X = HZN-
HzNCN
NH
I
16
soc12
X
-COCl 11
X =HzNCNH-
II
12
/ 2
X = ONC-
X OzNNHCNH-
II
14
NH
Y
X = (CICH2CHz)zNCO-
X = (ClCH&Hz),NCONH-
13
15
X = HZNHNSNHI1
NH 17
The preparation of coumarin-6-carboiiyl chloride (11) from the acid (12) by refluxing with IT15 in 1'oCl3 has been reported by Dey and Dalal.I6 They describe it as a substance which began t o shrink at 175" and melted completely at 182". In our hands this procedure resulted only in recovery of 12. However, when 12 was refluxed with SOC12it was smoothly converted to the acid chloride (11) which melted at 131.5-132.5'. On reaction with N,S-bis(2-chloroethy1)amine 11 gave S,S-bis(2-chloroethyl) coumarin6-carboxamide (13). KO rearrangement of 13 was observed during recrystallization and the amide structure is supported by the infrared spectrum. Coumaryl &isocyanate (14) has been prepared in :ibtrut 22yo yield by the action of phosgene on 2 as the free base." By substituting the hydrochloride of 2 for the free amine we have increased the jield of 14 t o 907,. Condensation of 14 with K,S-bis(%chloroethyl) amine readi I y gave S, K-bi s(2-chloroet hyl j -S'(A-coumary1)urea (15). In view of the 1 . 1 1 0 ~ ~ 1 1trvpaiio(*idalaction of a number of' gri:iiiicliiicb dt~riv:iti v e ~ i't ~N:L\ o f ititerrst t o itiveiti(16) 13 13 Dei and H Ilalal J Chrnr hoc 123, J384 (1Q23) (1;) H 13 dIld .ieslladii .I I r L d l r L r i CirrWl & o r 8 , 2 g 3 (1'331) (18) C 11 Lourie and \\ l o r k e Ann T r o p M e r i l'ura~ztol , 31, 435 ( l Y J i ) , H Kinv E AI Lorine, and I\ Y'orhe Liincet, 233, 136 ( i Y d 7 j ,
'r
b
R Sahr
C:
hriiiiner L AI I3rancone, and 1 bribbaron J O r y C h c m ,
13, 924 (1948) z r t l a r ulzu
gate the efl'ect of incorporatioii of a guariidine function into the coumarin molecule. (j-Coumarylguitiiidillc (16) was prepared by reaction of 2 with 30% aqueous cyanamide in ethanol. Inasmuch as aminoguanidirie appears to be less toxiv than g ~ a n i d i n e , 'the ~ preparation of S1-(6-coumaryl)S3-aminoguanidine (17) was attempted. Although S1-(6-coumaryl)-S3-nitroguanidine (18) mas obtained from 2 and S '-methyl-S l-nitroso-S 3-nitroguanidine by the general method of I\IcI t i i , l i r s \\err carrieil o r i t h y the p r o c e d i i r r of fi:agle and l;oley?J a s modified by the Cancer Cliemotheralty National Service Center.25 (24) 11. Eagle and G. E. 1:oley. Cunccr /
