2442
EDWARD C. TAYLOR, 0. VOGLAND C. C. CHENG
formed were distilled and seemed to consist of 1,Z-dibromopropane, b.p. 139-143" (743 mm.) and 2,3-dibromobutane, b.p. 153-158" along with t h e tetrabromide from butadiene, m.p. 118-121'. Tetrahydrofurfuryl Benzoate .-The ester (1.4 moles) was pyrolyzed a t a rate of Od18 mole/hr. with nitrogen carrier at 0.24 mole/hr. a t 563 . The contact time was 56 sec. T h e yield of methyl propenyl ketone was 13.3y0and no unchanged ester was recovered. Tetrahydrofurfuryl Formate.-The ester (0.54 mole) was pyrolyzed at 0.31 mole/hr. at 535' with a contact time of 79 sec. The yield was 3170 of ketone. Tetrahydrofurfuryl Oxalate.-The ester (0.22 mole) was introduced at a rate of 0.04 mole/hr. a t 532" with nitrogen carrier (0.21 mole/hr.) corresponding with a contact time of 98 sec. T h e yield of ketone based on consumed ester was 10.5%. Pyrolysis of4,5-Dihydro-2-methylfuran .-The furan (6.3 g;) was passed through a semi-micro pyrolysis furnace at 540 . The product gave a dinitrophenylhydrazone, m.p. 148E 4 0 1 depressed by admixture with the derivative from cyclopropyl methyl ketone b u t not depressed by mixing with methyl propenyl ketone derivative. Pyrolysis of Cyclopropyl Methyl Ketone .-The ketone (89.5 g.) was pyrolyzed at 500" with a contact time of 47 sec. The product contained methyl propenyl ketone (30.5 g.) corresponding with a 35y0 yield based on consumed material. X viscous residue (15 g.) remained in the flask. Like the residue obtained in the pyrolysis of tetrahydrofurfury1 esters, i t was insoluble in sodium bisulfite solution and gave no dinitrophenylhydrazone.
Vol. 81
Dehydration of Tetrahydrofurfuryl Alcohol by Boric acid." -Tetrahydrofurfury1 alcohol ( 1 mole) and boric acid (1 mole) were placed in a 250-m1. flask fitted with a 40 X 1.3 cm. column packed with glass helices and fitted with a partial take-off head. Heat was applied and the water was removed continuously. After 1 mole of water had been removed, water and 2,3-dihydropyran distilled together. Toward the end of the distillation, tetrahydrofurfuryl alcohol also distilled. Carried along with this was a high boiling, water-insoluble, pale green liquid. Redistillation of the pyrolysate gave 14.7 g. of 2,3-dihydropyran, a 227, yield based upon alcohol consumed. T h e 2,4-dinitrophenylhydrazone from i t had m.p. 113.5-115' and did not depress the melting point of a derivative from authentic 2,3dihydropyran. T h e pale green, high boiling, water-insoluble material mentioned above was combined with the same material from other runs and vacuum distilled. X large fraction, b.p. 158-164' (2 mm.) was obtained. This substance was an ester of boric acid; i t gave white crystals of boric acid when placed on a watch glass and allowed to stand overnight. A sample, b.p. 159' ( 2 m m . ) , was shown to be tetrahydrofurfuryl borate. Anal. Calcd. for (C6H~02)aB:C , 57.4; H , 8.0. Found: C , 57.5; H , 8.5. Pyrolysis of Tristetrahydrofurfuryl Borate.-This ester (60 g . ) was pyrolyzed a t 500'. 2,3-Dihydropyran (6.5 g . ) was obtained, along with unchanged ester (41.1 g.). This is a 4370 conversion t o 2,3-dihydropyran based upon the ester consumed. ~YOTREDAME,IND
[ COXTRIBUTION FROM THE FRICK CHEXICAL LABORATORY, PRINCETON UNIVERSITY]
Studies in Purine Chemistry. 11. A Facile Synthesis of 2-Substituted Adenines1,' BY EDWARD C. TAYLOR, 0. YOGLAND C. C. CHEXC RECEIVED AUGCST15, 1958 The reaction of the silver salt of isonitrosomalononitrile with ainidine hydrohalides j-ields amidine salts of isonitrusoinalononitrile ( I ) ,which are quantitatively isomerized by heating in appropriate solvents to 2-substituted i,B-diamino-j-nitrosopyrimidines ( 1 1 ) . Heating the latter with formamide, formic acid and sodium dithionite yields 2-substituted adenines (111) in high yield. Direct conversion of I to I11 is realized in a mixture of formamide, formic acid and sodium dithionite, and provides what is essentially a one-step synthesis of a variety of hithertofore unavailable adenine derivatives from simple aliphatic precursors. Modifications of these procedures lead t o new syntheses of adenine and isoguanine and to the preparatioii of a novel purine type, illustrated by CY, &bis-(2-adenyl)-butane (171,n = 4). The direct conversion of a n amidine to :i purine is realized in the reaction of guanidine carbonate, the potassium salt of isonitrosomalononitrile, formamide, formic acid and sodium dithionate, to give 2,B-diaminopurine in 7lY0 yield.
The conventional synthetic route to adenines appropriate stage of the synthesis.6-10 Alternate involves the condensation of guanidine or thiourea routes to adenines include aminolysis of G-merwith malononitrile to give a 2-substituted 4,6- capto-, l1 6-methylmercapto-, 12--?l B-carboxymethdiaminopyrimidine, which is then nitrosated, (6) W . Traube, A i z t i . , 331, 6 4 (190-4). reduced, acylated and subsequently ring-closed (7) hf. Hoffer, "Jubilee Volume Dedicated to ISiuil C . Barell,' under dehydrating conditions3 The requisite Bade, 1946, p. 428. 4,5,6-triaminopyrimidine intermediates may al( 8 ) A. Bendich, J . 17. Tinker and G. B. Brown, THISJ O U K N A L , 7 0 , ternately be prepared by reduction of j-arylazo 3109 (1948). (9) G. A. Howard, B Lytligoe and -4. R . Todd, J . C h e m . SOL.,55G derivatives, formed either by coupling of a 4,6- (1945). diamin~pyrimidine~ or directly by condensation ( I O ) G. W. Kcnner, B. I.ythgoe, A. R Todd and A. Topham, Ibid., of arylazomalononitriles with amidines. 4,5 ildenine 574 (1943). (11) G. B. Elion in "The Chemistry and Biology of Purines," ed. b y itself may be prepared by desulfurization of a 2E . W. Wolstenholme and C. Lf. O'Connor, J. and A. Churchill L t d . , mercapto or 2-methylmercapto substituent a t an G. London, 1957, p . 39. (1) This investigation was supported by a research grant (C-2551 P E T ) from t h e National Cancer Institute of the National Institutes of Health, Public Health Service. ( 2 ) Presented in p a r t before t h e Division of Medicinal Chemistry at t h e 131st National A.C.S. Meeting in Miami, Fla., April 7-12, 1957. (3) A. Bendich in "The Nucleic Acids, Chemistry and Biology," ed. by E. Chargaff a n d J. N. Davidson, Vol. 1, Academic Press, Inc., K e a York, N.Y . , 1955, p . 81. (4) B. Lythgoe, A . R . Todd and A. Topham, J . C h e n . SOL.,315 (194.1).
( 5 ) J Baddiley, 13. Lk-thgoe and A. R . Todd, ibid., 386 (1943).
(12) G. B. Elion, E . Burgi and G. H. Hitchings, THISJOURNAL, 74,, 411 (1952). (13) A. Albert and D. J. Brown, J . Chem. SOL.,2060 (1954). (14) C. G. Skinner and W. Shive, THISJOURNAL, 7 7 , 6692 (1955). (15) R. G. H a m , R. E. Eakin, C. G . Skinner and W. Shive, ibid., 7 8 , 2648 (1956). (16) C. G. Skinner, W . Shi\.e, R. G. Ham, D. C . Fitzgerald, Jr., and R. E. Eakin, i b i d . , 7 8 , 5097 (1956). (17) C. G. Skinner, P . D. Gardner and W. Shive, i b i d . , 79, 2813 (1957). (18) C. 0. hIiller, F. Skoog, F.S. Okumura, RI. H. von Saltza a n d F. M. Strong, ibid.,7 8 , 1373 (19561.
2443
PURINE CHEMISTRY:A FACILE SYNTHESIS
May 20, 1959
TABLE I NHz R-k=NHZ+
129-130 141-142 93 125 104' 151-152 194-195 176-177 15'7-158 152-154 106-107 144-145 1'71 179-180
95 100 96 100 93 92 92 83 100 95 100
34.5 39.2 43.0 32.5 57.6 55.8 54.0 46.1 31.2 50.0
3.6 4.6 5.4 3.8 4.9 4.2 4.5 3.1 3.9 3.7
88
37.4 44.0 43.4
3.5 3.7 4.9
100 94
This compound melted without decomposition.
C
C
* Salt
a
l cd- .
I*ield,
%
P
-
oN=C(CN)~
11 p d r c , OC.
H
Analyses, % -F o u n d ------N C
50.3 45.7 42.9
32.5 28.6 32.3 54.5 38.9 37.0 48.2 44.0 42.1
H
N
34.1 39.4 43.1 32.8 57.8 55.7 54.0 45.5 31.3 49.8
3.2 4.4 5.3 4.1 4.9 4.0 4.6 3.0 3.9 4.0
50.0
37.2 44.3 43.4
3.7 4.0 5.0
45.4 43.1
32.6 28.5 32.6 55.0 39.4 37.2 48.3 43.9 41.9
of 2-aminopyridine and isonitrosomalononitrile.
-
CH:C
