4'722
COMMUNICATIONS TO THE EDITOR 0
0
cH3
CH3
1
I
Vol. Mi
H, 5.13; N , 20.43. Found: C, 36.97; H, 5.09; N, 2 0 . 2 3 ) in approximately equal amounts. The former compound must arise by initial reduction of 1 with forfollowed by mic acid to 1,3-dimethy1-4,5-diaminouracil, condensation with phenylglyoxal (thus giving the i phenyl isomer excldsively) , 7 - - 9 while the latter compound apparently arises by initial condensation of the +amino group of 1 with phenylglyoxal followed by reduction of the nitroso group to the hydroxylamino stage, cyclization, dehydration, and deformylation. During the course of this work it was noted t h a t 1 behaved anomalously on heating. The compound decomposes a t its melting point with copious evolution of brown fumes and the loss of its characteristic lavender color, but as the temperature is raised above the melting point the melt resolidifies to an orange solid which does not melt below 360'. LL7e have identified the latter compound as the pyrimidopteridine 7 and suggest that it arises by a reverse-nitrosation reaction (which apparently can be either thermally or acid induced) to give 1,3-dimethyl-4-aminouracil, which then condenses with unchanged 1 to give 7.1° The many complex reactions undergone by the 4amino-5-nitrosopyrimidine 1 under apparently straightforward conditions call attention to the possibility that similar complications may arise with other 4amino-5-nitrosopyrimidines,which are ubiquitous intermediates for the synthesis of purines, pteridines, and other fused pyrimidine heterocycles.
2l
( 7 ) A . A l b e r t , Q u w t R m . ( L o n d o n ) , 6, 227 (1952). (8) W R B o o n , J . Chem Soc., 2146 ( 1 9 5 7 ) . (9) R B. A n g i e r , J . O i g . Chem., 28, 1398 (1963). (10) M Ridi, C P e l l e r a n o , a n d E Masi, A n n . C h i m ( R o m e ) , 63, 1717 (1963), C h e m A b s t v , 60, 10,681b (1964)
II
CH3
DEPARTMEST O F CHEMISTRY PRINCETOS UNIVERSITP PRISCETON, NEIV JERSEY
EDWARD C. TAYLOR EDWARD E. GARCIA
RECEIVED AVGVST6, 1964
A Nuclear Magnetic Resonance Study of a Carbonium 3-carboxaldehyde, 1-naphthaldehyde, p-nitrobenzaldeIon Exchange Reaction hyde, and anisaldehyde gave the corresponding 8Sir: substituted theophyllines : 8-(3'-Indolyl) theophylline \Te wish to report t h a t halide exchange occurs bemelted >360°. Anal. Calcd. for C15H13N503: C, 61.01; tween covalent trityl halides and trityl cations and H , 4.44; N,23.72. Found: C, 61.01; H , 4.44; N , that the n.rr1.r. method readily provides data on the 23.86. 8-(1'-Naphthy1)theophylline melted a t 328rates and mechanism of this exchange process. 329'. Anal. Calcd. for C I ~ H M N ~ O :C, : 66.65; H, The n.m.r. spectrum' of a methylene chloride solu4.61; N , 18.29. Found: C, 66.70; H , 4.54; N , 18.36. tion of tris(p-toly1)methyl chloride (I) exhibits sharp 8-(p-Xitropheny1)theophylline melted >360'. Anal. lines a t -424.5 and -139.5 C.P.S. for phenyl and Calcd. for C13HllN604: C, 51.83; H , 3.68; N , methyl protons while the carbonium ion tris(p-tolyl)23.25, Found: C, 51.61; H, 3.69; N , 23.19. ri-(pmethyl hexachloroantimonate (11) displays an AzB2 51ethoxyphenyl)theophylline melted >360'. Anal. quartet centered a t -437.5 c.p.s. (phenyl) and a Calcd. for C14H&\~403: C , 38.73; H , 4.93; N , 19.37. singlet a t - 102 c.p.s. (methyl). The individual Found: C, 58.55; H , 4.97; N , 19.74. spectra are essentially independent of temperature By analogy with the preceding results, condensation and solvent, in contrast to a mixture of the two comof 1 with phenylglyoxal should have given ri-benzoylponents. theophylline. or perhaps the secondary alcohol formed Time-averaged, temperature-dependent methyl proby reduction of the carbonyl group with formic acid. ton resonances of an equimolar mixture of I and I1 However, the reaction took a completely unexpected in methylene chloride are shown in Fig. 1 , At 37' the course and gave 1,3-dimethyl-i-phenyl-2,4( 1 H,3H)pteridinedione (S)6 and 1,3-dimethyl-4-amino-5-benz-sharp singlet is a t precisely the chemical shift ( - 151 c.P.s.) expected for exchange averaging of the methyl amidouracil (9) (n1.p. 287-289' ; v,":' 3400, 3355, and protons of I and I1 and varies directly with the mole 3200 cm.-'. Anal. Calcd. for Cl3H1aN40e: C , 56.%3; fraction of the constituents. Xs the temperature is k
(6) C, P C, I l i c k . H C S Wood. a n d W R I m g a n . J 19.56)
r h r r n .So(
,
2131 ( 1 ) Val ian A 60 s p e c t r < , m e t e r . intei nal T S I S .
4723
COMMUNICATIONS TO THE EDITOR
Nov. 5 , 1964 151 C . D . S .
I
370
IC) =II
Fig 1 -Temperature dependance of methyl protons for equimolar mixture of I and I1 in CHyClasolution.
lowered, the line broadens and splits symmetrically into two components An analogous process occurs with the phenyl protons ,4n Xrrhenius plot of the data2 gives Ea = 7 kcal /mole from the methyl protons and 8 kcal /mole from the phenyl protons, the agreement falling within experimental error T h e exchange reaction (eq 1) suggests a bimolecular mechanism and second-order kinetics Equally pos-
-
2.0
Fig. 2.-Concentration dependance of line broadening of methyl protons of (p-CH3C6H4)3CfSbC16-(11) and (p-CH3C6H4)aCCI (I) in CH2C12 solution a t -56". The Concentration of I is: ( A ) 0.167 M , ( B ) 0 125 M , ( C j 0.084 ,M.
r = concentration of species/rate of disappearance
of species Assuming bimolecular process (l), eq. 5 is derived TI
=
1 [Ar3CC1] - _ _ _ k , [Ar3CC1][Ar3C+Y-] kx[Ar3C+Y-l
kx
.Ir3CCl
I
+ -Ir3C+Y- e .irJC'E7- + Ar2CC1
Ar3C +Y=
711
SbCls
sible is the Sivl-type process (eq 2) which requires ki
Lir,CCl
e AraC"C1kr
(2)
Ia kxt
.Ir3C+Cl-
+ XrXC +E-- e - i r p C + Y - + .IraC+C1-
first-order kinetics (kf rate determining) From differential line-broadening data we may distinguish between these alternatives Figure 2 illustrates this differential broadening for solutions containing different proportions of I to I1 a t -56' From the line half-widths (&) one may calculate the lifetimes ( 7) of both species using6
~
(5)
(1)
I1 Ar = p-CHxCsH4, Y
(4)
=
-
k , [Ar3C+Y-][Ar3CC1]
1 k,[Ar3CC1]
Lack of agreement between the line-broadening data and the concentration dependence requirements of ( 5 ) effectively eliminates this mechanism. For the s N 1 mechanism (a), only kf is involved in disappearance of I , yielding T~ =
[Ar3CCl]/(kr[Ar3CC1])= l / k t
(6)
A simplified derivation of T A ~ ~ Cis+ obtained from (4) if we assume that k,r[A4r3C+C1-] [Ar3C+Y-] >> kr [Ar3C+C1-] and [Ar3C+Y-] >> [Ar3C+C1-].' The only process now responsible for carbonium ion disappearance is that whose rate is k, [Ar3C+C1-],yielding rII =
[Ar3C+Y-]/:(kr[Ar3C+C1-])= [Ard2+Y-]j(kr[Ar3CCl]) (7)
where &, is the half-width in the absence of exchange averaging. T o discriminate between (1) and (a), expressions are derived for r1 and r I I using the general definitionfi ( 2 ) H. S G u t o w s k y a n d C . H. H o l m , J . Chem. P h y s . , 2 6 , 1228 (1956). ( 3 ) B o t h Swain4 a n d Hughes6 h a v e d e m o n s t r a t e d t h a t e x c h a n g e of t e t r a a l k y l a m m o n i u m radiohalide w i t h t r i t y l chloride in benzene follows firstorder kinetics w i t h r a t e i n d e p e n d e n t of a d d e d radiohalide. T h e bimolecular m e c h a n i s m ( 1 ) c a n n o t , however, be excluded o n t h i s basis i n a s m u c h a s t h e a c i d i t y of c a r b o n i u m z's. a m m o n i u m ion m a k e s t h e bimolecular exchange reasonable for t h e former. O u r a s s u m p t i o n t h a t in o u r low dielectric s o l v e n t (CHgClri we a r e dealing p r i m a r i l y with s o l v a t e d ion p a i r \ , r a t h e r t h a n free inns. followed t h e similar conclusion of Swain.4 (-1) C G . Swain a n d R.I. SI K r e e v o y , J . A m Chrm .SOL., 7 7 , 1 1 2 2 (1955) ( 5 ) I.; D H u g h e s . pi a i . . J C h e m S O L .1220 , (1957). 16) J E Leffler a n d E G r u n w a l d . " K a t e s a n d E q u i l i b r i a [ i f O r g a n i c R e a c t i o n s . " J o h n \Viley a n d Sons. I n c . . S e w \'ork. N Y . . 1!463 p p 88.80
T h e requirements of the lifetime expressions are clear: (6) states that T I be concentration invariant, and ( 7 ) dictates that T~~ vary directly with the ratio of 1 I : I . The experimental results (Fig. 2 a n d Table I) are in accord with these conclusions. Variation in concentration of I or I1 does not affect the chloride line whose half-width remains a t 7.0 0.5 c.P.s., and application of (3) and (6) yields an average value T h e calof l / r I = kf of 8.9 f 0 . 2 set.-' a t -56'. culated r I I (column 4,Table I ) exhibits the concentration dependance predicted by (T) and yields (column 5 , Table I ) an average value for kf of 7.8 0.4 set.-', in good agreement with the previous value.
*
*
( 7 ) T h e first a s s u m p t i o n follows f r o m t h e work of S w a i n , i a n d t h e secund is justified b y t h e small e q u i l i b r i u m c o n s t a n t for t h e ionization of I ( s e e below)
4724
COMRIUKICATIONS TO T I I E EI)ITOR TABLE
\+ARIATION O F D I F F E R E S T I A L
COSCENTRATIOS A T -56';
"
I LISE BROADESISCIYITH DETERMIXATIOS OF k f
I
TI
=
kf.
aec
-1
[ r i . .ti
[ I I I , .ti'
0.125 0.167 0 084 0 063 0 083
0 125 0 084 0.167 0 . 063 0 042
From eq. 3.
From eq 7 .
9 9 8 8
L'ol. hli
1 1 8 8
8 %
1 'I
711.
sec.
i;f .ec.
-1
8.1 14.7 3 7 8 1 16 1
8 7 7 8 8
1
t'
1 4 4 1 2
Knowledge of the equilibrium constant (K,,, = kf l k r ) now makes k , accessible. Ultraviolet data,' using similar solutions of I as for the n.ni.r. experiments. = 2.S X a t -,j(io.$J Ysing yielded a value of K,,, an average value of k f = S.4 set.-', then 8 , = :3 X 1 0 4 set.-'. The conclusion t h a t exchange between I and I I occurs via an Sx1 process agrees with our preliniiriary observation t h a t factors which affect the exchange rates are those which modify kf. &Iccordingly, rate enhancements are observed with : (a) increasing solvent polarity, (b) increasing halogen polarizability, and (c) cation-stabilizing ring substituents. \Vork is continuing. Acknowledgment.-The authors thank Professors G . IVhiteside, C. G. Swain, and H . llorawetz for helpful discussions.
bands were fornied owing to the phenylation of the complexes under the last conditions. b u t no bands owing to free pyridine. \Then the decornpositiun of any complex was evidenced by either a decrease i n the intensity of the ligand infrared bands, or a color change. or the i!)rniation of a precipitate (silver metal by a n oxidation- reduction reaction with the silver complex) over a 3-clay period t h a t complex was discarded. The phenyl source used was N-nitroso-synz-diphenylurea which was completely decornposetl a t 23' over a :$day period under the reaction cuntlitions. This phenyl ( 8 ) \Ye t h a n k Dr I< W a a c k a n d 5 1 i s b SI D o r a n for t h e l i i w - t e m p e r a t u r e ultravi,,let d a t a . source was prepared by the known method4 ant1 also i Y ) T h i s c i i m p a r e s t o K , , = 2.1 X I O - ' for I in ClaCCHCIg a t 20' [ A G. bl- the reaction of diphenylurea with riitrosylsuliuric E v a n s A Price, a n d J. H. T h o m a * , 7 ' 7 a n s . F a r a d o 4 Soc., 62, X i 2 ( l < l X ) 1 . acid generated in sitir by the action o f water up(m THE Do\\- CHEMICAL COMPAXY 13. 1.1. FREEDMAS nitrosylsulfuric anhydride. EASTERSRESEARCH LABORATORY r\. E. V O L ~ S C The pure isomeric phenylpyridines were prepared b y FRAMINGHAM, M A S S A C H U S E T T S 1.. R . SASDEL the phenylation of pyridine by- a standard method: RECEIVED .*UCUST 5, 1964 and separation of the three phenylpyridines by preparative thin layer chromatography. The picrates of the separated samples agreed with those reported previously.A llixtures oi the isomers, both prepare(1 and The Phenylation of Pyridine-Metal Complexes from the reactions, could be separated and their relative amounts measured by gas chromatography using Sir : specially prepared columns. The reliability of the The chemical reactions of coordinated ligands have method for isomer determination was checked and the been an area of recent interest to others,' and also results are : known mixture, : 3 9 I : :39.9: 2 1 . ( I : gas to us in terms of their iree-radical chemistry.2 T o chromatographic integration values, 11.5: :W.2 : 2 2 . 2 : further this inquiry, a set of experiments was designed column factor. 0.94: 1 . IO:0.95: and calculated values. whereby phenyl radicals were caused t o react with 3 S . 6 : :HO: Z3.2. I t was shown that the isolation propyridine dissolved in S.N-dirnethylioritiaiiiide and in cedures were sufficiently efficient to begin with 0.4s g . separate experiments with a group of pyridine -metal of products in a 70.9: 1S.9: 1 0 . 1 ratio anti obtained coniplexes dissolved in the same solvent. 0.47g. in a 7 1. ( I : 19.6: 9.*5ratio. LVhcn these niethotls AIlarge number of complexes of pyridine were prewere applied to phenylation reaction mixtures involving pared, and the ones indicated in Table I were found to coniplrxes. the data in Table I were obtained. be completely stable t o the reaction conditions (all .Itypical reaction involved dissolving I(;,; E. ( I ) . ( I ~ ! ) analyses were satisiactory) , This stability was ascermolej of tli~~~-ricliiiezinc~I I ) thiocyanate in SO ml. of tained by using the pyridine ligand bands in the intli~nethylfor~iia~iii~le, followed by the rapid additicin frared." The stable coriiplexes showed no change in of :
