JUSE,1964
CHLORINATION OF ALKYLS-TRIAZINES
homolysis of the 0-0 bond in t-butyl perbenzoates and benzoyl peroxides in a manner formally identical with that already postulated for neighboring sulfur and iodine. The 2,2-diphenylvinyl group is a better neighboring group than iodide (see Table 111) but not so effective as the phenylthio group in anchimeric acceleration of perester 0-0 bond homolysis. Substituent effects are compatible with the postulated dipolar transition state involving a five-membered ring with a concentration of positive charge on the neighboring
1527
group involved in the displacement on oxygen and a negative charge on the oxygen leaving group (see structures X I V or XIX). Acknowledgment.-We are indebted to the Rohrn and F a a s Company for a fellowship to T. W. K., 1960-1961. We thank the Alfred E. Sloan Foundation for a fellowship for J. C. M., 1962-1964. This research was supported in part by a grant from the U. S. 8 r m y Research Office, Durham, North Carolina.
Chlorination and Bromination of Alkyl s-Triazines FREDC. SCHAEFER AND JOSEPH H. Ross Exploratory Research Department, Central Research Division, American Cyanamid Company, Stamford, Connecticut Received J u l y 15, 1963 Liquid-phase chlorination or bromination of alkyl s-triazines produced exclusively a-substitution by an acidcatalyzed process regardless of the halogenation reagent used. Nuclear halogenation of mono- and dialkyl striazines does not compete. Special emphasis has been given to the development of synthetic procedures using elementary chlorine and bromine for the preparation of mono- and polyhalogenation products from triniethyland triethyl-s-triazine. The chemistry of the wide variety of products has been explored to provide a n insight into their potentialities as reactive intermediates
Perhaps the most promising opportunities for exploitation of the newly available alkyl s-tria~inesl-~ lie in the study of their halogenation products. The work reported here was undertaken to explore the range of compounds which could be obtained in preparatively useful processes. Principal attention has been given to the particularly practical use of 2,4,6-triniethyl-striazine (I) and 2,4,6-triethyl-s-triazine (11) as substrates for chlorination or bromination, and a surprising number of different types of products has been obtained in good yield. Soiiiewhat less work has been done with 2-alkyl s-triazines where unsubstituted nuclear positions are available and might have been competitive sites for halogenation. An exploratory study of the chemistry of t>hehalogenation products was also carried out. h substantial amount of work on the synthesis of chloro- and bromoalkyl s-triazines has been reported, but the bulk of t'his deals with compounds prepared by synthesis of the s-triazine system from reagents containing the halogenated alkyl group. Only a very small number of references report the direct halogenation of an alkyl s-triazine group.4 The work of Reinhardt and Schiefer, who prepared monoand dibroniinated and -chlorinated derivatives from 2ethyl-4,6-diphenyl-s-triazine by direct halogenation is particularly pertinent to the present s t ~ d y . Also ~ significant is the reaction of 2,4-dichloro-6-methyl-striazine with elemental chlorine under rather strenuous conditions to give 2-trichloroniethyl-4,6-dichloro-striazine.6 The halogenation of alkyl groups attached to electronwithdrawing substituents has received a great deal of
attention in recent ~ e a r s . 7 , ~The experimental work in this field provides an excellent basis for the selection of reaction procedures. The literature did riot permit prediction of the reactivity of alkyl s-triazines, but combined with the present findings gives a satisfactory basis for interpretation of the results. Monochlorination and Bromination.-N-Chloro- and N-bromosuccinimide (NBS) were used as halogenating agents in the initial experiments because of their wide applicability for the monosubstitution of methyl aromatic^.^^^^^^ Reactions under coiiventional conditions were sluggish, but 2-chloromethyl-4,6-dimethyls-triazine (111), 2- (1-chloroet hyl) -4,6-dieth yl-s-t riazirie (IV), and 2-(l-bronioethyl)-4,6-diethyl-s-triazine( 5 ' ) were obtained in moderate yield. Bromination of I with S B S was impractically slow. Small amounts of
( I ) F . C. Schaefer and G . A . Peters, J. O r g . Chem., 26, 2778 (1901). ( 2 ) F. C. Schaefer, ztzd., 27, 3362 (1962). (3) F. C. Ychaefer, t h i d . , 27, 3008 (1962). i l j Reaction of N-brornosucrinirnide with 2-methyl-4.0-bisphenylamino8-triazine is reported to give the bromomethyl derivative [ H . K. Reimschriessel and N . T. AIcDevitt, J . A m . Chem. Sbc.., 82, 3756 (1960)). HOWever. i t i s clear from the published infrared spectrum t h a t the product is in i n e . refact 2 - f p - b r o m o p h e n y l a m i n o ! - 4 - m e t h y l - T i - p h e n . ~ l a m i n o - ~ - t ~ i ~ ~See lated work b y C. G . Orerbereer and s. L. Rhspiro, tbid.,76, 93, IO61 (1954). ( 5 ) H. Heinhardt a n d E Schiefer. Chem. B e r . , 90, 2643 (19.57). ( 6 ) E. Kober a n d C. Grundniann. J . A m . Chem. S o c . , 81, 3769 (1959).
(7) See C. Walling. "Free Radicals in Solution,'' John \T'iley and hons, 1957. Chapter 8. Inc.. New York, li. Y., ( 8 ) (a) J3. R . B r o w n , D. I,. Hammick, and n 11. Thewlis, .1.Chum. S o ? .. 1145 (19.51): (b) B. R. I j r o a n . D. L. H a m m i c k . .'J I I . Thewlis. ani! I ) . .J. Wnlbridge. i b l d . . 1309 (1933): (c) G . .\I. I3ennPtt and G 11. \r-~llis,7 h d . , 1960 (1928). (9) (a) C. Djerassi, Chem. Rev.. 43, 271 ( 1 9 4 8 ~ :( b ) R. H.Walker. J . Oro. Chern., 26, 10-17 (19fiO): ( c ) €1. G r s l i o n , K. Ilittmer. and R . Bratin. i b i d . , 26, 1874 ( 1 9 G I j . ( I O ) (a) 5 . P. Buu-Hoi, A n n . , 666, I 11944); (b) .\. Hirschberp and P. E . Spoerri. J . Org. C h e m . , 26, 23.50 (19R1).
CHzCO,
I
NX
CH2CO'
CCl, + 4040% * RCH7 ~ ;Ny~~z~
N y N CHzR
I,R 11, R
= =
H CHs
111, X = C1; I(= H IV, X = C1; R = CH, V, X = Br; I1 = CH,
dihalogenation products were also obtained in these reactions, but it is cleai u a t loss of the desired conlpounds through side reactions n-as the major obstacle to higher yields. I t was found that 111 itself is surprisingly stable to N-chlorosuccinimide (NCS) .
SCHAEFERAND Ross
1528
Although these experiments were moderately successful, various considerations suggested that the reactions might be following predominantly an acidcatalyzed path. If such were the case, no apparent advantage could be gained with the elegant selective halogenating reagents. We therefore concentrated on the use of elemental chlorine and br0mine.l' Direct chlorination and bromination of several alkyl s-triazines has proven to be an easy process. Reactions are rapid at moderate temperatures and yields of monohalogenated products have been at least equal to those obtained with S-halosuccinimides. A particular improvement was the synthesis of 2-bromomethyl-4,6-dimethyl-s-triazine (VI) in 50% yield. Acetic acid is an excellent medium, but successful reactions have also been carried out in chloroform or carbon tetrachloride. Chlorination of I with an equimolar amount of chlorine in acetic acid at 55" gave mono- and dichlorinated products in approximately a 1 : 1 ratio. It was both interesting and useful to find that the presence of an equimolar amount of sodium acetate jn the reaction mixture shifted this product ratio to 1.7:1.0 with consequent greater conversion of I. In this case the yield of I11 was 54% based on unrecovered I.I2 Monobromination, however, was not appreciably influenced by the presence of sodium acetate. Chlorination of 2-methyl-s-triazine (VII) with S C S was sluggish but gave 2-chloromethyl-s-triazine (VIII) in low yield. 2-Ethyl-s-triazine and 2-isopropyl-striazine reacted with chlorine in hot carbon tetrachloride to give the a-chloroalkyl derivatives. In none of these cases was nuclear chlorination detectable. l a
XVIII
VI1
VI11
The halogenation of an ethyl substituent could not safely be assumed to occur exclusively at the a-carbon although this has been found to be the case. Successful reactions with I demonstrated that a-substitution was possible, but the published work on alkane nitriles and similar compounds suggested that p-attack would be probable if a free-radical mechanism were involved.' Reinhardt and Schiefer had reported the preparabut tion of 2-(l-haloethy1)-4,6-diphenyl-s-tria~ines,~ (11) NCS probably is equivalent to free chlorine in any case [P.9. Goldfinger, P. A. Gosselain, a n d R . €1. Martin, Nnlz~re.168, 30 (1951): K. B. Wiberg and L . H. Slaugh, J . A m . Chem. Soc.. 80, 3033 (1958)). (12) Puch experiments which make evident the effects of variables on the relative rates of t h e successive reactions, should n o t be taken a8 optimized synthetic procedures. T h e relative and absolute yields of these products depend upon the extent to which conversion of I is carried. For the preparation of 111, most practical results might he obtained b y running the reaction a t the most selective conditions t o relatively low conversion and recycling unconverted I. 113) Suclear halogenation of the s-triazine ring, a highly "deactivated" system toward electrophilic reagents," would be expected t o be difficult if observable at all. Xevertheless. Grundmann and Kreutzberger's have demonstrated the formation of polyhalogenation products from s-triazine itself. T h e remarkahly easy nuclear chlorination o i 2-methyl- a n d 2,5dimethylpyranne reported recently1at 1 6 further illustrates our inahility to predict with confidence the course of such reactions. Perhalidea m a y well ncriir as intermediates with unforeseeable consequences.'3,'7 ( 1 4 ) I,. Paoloni. G'azz. chim. ital.. 84, 729 (1954). (15) C. J. Grundrnann a n d A . Kreutzberger, J . Am. Chem. Soc., 77, 44 (19.55); U. S. P a t e n t 2,777,847 (1957). (10) H. Gainer, M. Kokoruda, and W. K. Langdon. J . Ore. Chem., 36, 23fi0 (1961). (17) fa) R . D. Brow-n and R . D. Haroourt. J . Chem. Soc., 3451 (1959); f b l J . Eisch. Chem.. I n d . ( L o n d o n ) ,1449 (1959).
VOL. 29 CHART 1 POLYHALOGENATION PRODUCTS FROM 2,4,6-TRIMETHYL-S-TRIAZlNE
C CL
CH 3 - ( N y
+CI*,HOAc
I
B h NaOAc, HOAc
cc13
89%
IX
50%
Ai
CBr3
CBr3
pH;*(,
XI11
BIZ,HOAC
JhCH-7;
.?rNV NyN
CH3
NyN
N
~y CHBrz
N+N
I
CHBrz
X
Br& - f N x Y C B r a Br2, HOAc, NaOAc L 73 %
HBr
c-
N-N
I 0Br3
x IV
these authors believed that dihalogenation gave the l12-dihaloethyl compounds. In the present work we have used n.ni.r. spectroscopy and independent syntheses to obtain unequivocal proof of exclusive CYsubstitution in all cases, regardless of the degree of halogenation, and incidentally have found Reinhardt and Schiefer's products to be the 2-( 1,l-dihaloethy1)4,6-diphenyl-s-triazines. Polychlorination and Bromination.-The end products of the reactions of alkyl s-triazines with excess chlorine or bromine are strongly dependent on the reaction system used. A wide variety of products may be obtained in excellent yield. I t appears that glacial acetic acid is a particularly useful reaction medium, probably acting as an acid catalyst, and substantially different results can be obtained in many cases through the inclusion of sodium acetate in the reaction mixture. Reactions are much the same in chloroform or carbon tetrachloride but are much slower. The principal products derivable by polyhalogenation of I are indicated in Chart I. Also useful was the formation of 2-dichloromethyl4,6-dimethyl-s-triazine (XIX) and 2,4-dimethyl-6-trichloromethyl-s-triazine (XXII) as the major products when I reacted with about 1.7 moles of chlorine in acetic acid. By recycling by-product 111 and unchanged I, compounds XIX and X X I I could be prepared as a mixture in high yield. By recycling XIX also, compound X X I I could be obtained quite practically. It is striking that 2-methyl-4,6-bis(tribromomethyl)s-triazine (XITI) is the major product of bromination in the presence of sodium acetate, although a small amount of 2,4,F-tris(tribromoniethy1)-.s-triazine (XIV) was also isolated. It was not possible to brominate XI11 further under these conditions. On the other hand, X was easily further brominated to XIV in the presence of sodium acetate. Several additional halogenation products of I were isolated in the course of the work and are described in the Experimental section. Bromination of I1 in hot acetic acid gave a nearly quantitative yield of 2,4,6-tris(l,l-dibromoethyl)-s-
CHLORINATION OF ALKYLS-TRIAZINES
JUSE, 1964
1529
triazine (XV). The course of this reaction is indicated by the fact that reaction of I1 with an equimolar amount of bromine in chloroform gave in addition to V isolable amounts of 2,4-bis(l-bromoethyl)ethyl-s-triazine (XVI) and 2,4,6-tris(l-bronioethyl)-s-triazine(XVII), but that no 1,l-dibromoethyl derivative was detectable. Brz, HOAc
I1
95 %
I
CH3CBrz
-(N\v CBrzCHs NYN xv
I
CHBrC&
XVI
CHBrCH3 XVII
The expected product, 2-trichloroniethyl-s-triazine (XVIII), was obtained from VI1 under conditions for exhaustive chlorination. Similarly the 2-(l,l-dihaloethyl)-s-triazines were obtained in our early work by bromination or chlorination of 2-ethyl-s-triazine. The yields were low in these cases, but probably can be substantially improved. The use of n.ni.r. spectroscopy was of invaluable assistance in establishing the structures of several products, The niost significant features of the spectra for this purpose were the chemical shifts established as characteristic of the protons of the CH3-, CHZX-, and CHXz groups which have T-values in the ranges 7.027.52, 4.15-4.56, and 3.4,5-3.57, respectively, measured using 10% solutions of the compounds in carbon tetrachloride. The Mechanism of the Halogenation Reactions.Several observations support the conclusion that freeradical processes take little part in these halogenatioii reactions. The reactions are essentially unaffected by ultraviolet illumination or radical catalysis but are strongly responsive to hydrohalide concentration or the presence of a base. Moreover, easy substitution a t the position CY to the strongly electronegative s-triazine ring to*the exclusion of @-substitutionis contrary to the observed orientation in established free-radical halogenations of other polar niolecules.7 .4n ionic mechanism such as these observations seem to deniand and which is consistent with numerous other aspects of the reactions can be formulated along lines closely related to ketone halogenation and to the work of Brown and Hammick on quinaldine and the picolines.8 Regardless of the reaction conditions, the predominant halogenation process is believed to proceed by acid catalysis, perhaps following an induction period in which a slow radical reaction generates the acid. The alkyl s-triazine, I for example, is presumably converted to an enol analog which reacts with a halogen molecule to give the halomethyl-s-triazine hydrohalide, a process conveniently represented as analogous with the model for acid-catalyzed ketone bromination proposed by Sewman.I8 As a consequence of the greater acidity of the chloromethyl group, the predominant dichlorination product is 2-dichloromethyl-4,6-dimethyl-s-triazine (XIX) (181 M
N e u m a n I Am Chem Soc I S , 4993 (1951)
L
CH3
CBrzCH3
Br2, CHCl8
under all conditions tried. Hoivever, broniination differs in that conditions of relatively high hydrogen h o mide concentration tend to cause 2,4-bis(bronioniet hy1)6-methyl-s--triazine (XX) to be the major, if riot exclusive, product. This is the result of the reversibility of the dihroinoniethyl-s-triazine formation in the prcsence of hydrogen bromide which causes thermodynaniic rather than kinetic control of the product distribution. l 9 If sodium acetate is present during the reactioii, the hydrogen bromide is removed and the isoiiieric dihroniination products, X X and 2-dibromoiiiethyl-I,(i-dimethyl-s-triazine (XXVI) are produced iii about equal amounts. ISxainination of the product mixtures obtaiiird ill reactions of I with varying amounts of chlorine has made it possible to identify the predominant seclucnce of chlorination steps in the presence of hydrogen chlnride. ~
c1
i
CHzCl XXIII
CH3 XIX
CH3 XXII
1
J,
CHzCl XI1
CHZC1 XLIV
CHClz XXIV
It is very clear from several experiinents t,liat thc dichloro isomer, X I X , is favorcd over 2,4-bis(chloromethyl-s-triazine (XXIII) by a factor of a t least ten. Further chlorination gives principally X X I I , but an appreciable amount of XI1 is also formed despite the much greater acidity of the dichloromethyl group coinpared with an unsubstituted methyl group. This may be taken as evidence of appreciable steric inhibition of the X I X + X X I I step. Coinpound X X I I (19) T h e analogous situabion in acid-catalyzed bromination of ketones has been studied by F. Krohnke, ~t d., ( B e r . , 69, 615,921 (19:W' 86, 1559 (1933Jl. I n contrast, chlorination is substantially i r r e v ~ r s i b l e ( s e e ref. 2 6 ) .
SCHAEFERA N D Ross
1530
shows more resistance to higher chlorination than does XI1 and can be obtained in substantial amount. Further chlorination of IX at 60" in acetic acid saturated with hydrogen chloride proceeded at a barely perceptible rate. Bromination of I has a much stronger tendency to give at each stage the product of least "positive halogen" character. I
+
N\\rCH2Br
C&(I
N
-+
NYN
NYN CHzBr
CH3
xx
/."I
CH3-
I
N \yCHBrz
NYN CH3 XXVI BrzCH-(
C H J Y \\rCHZBr
N\\rCHBrl
NYN CHBrz X
BrCHz--[iN\yCH,Br c
NYx CHzBr
xxv
Reaction stops a t X because tribromomethyl groups are unstable in the presence of hydrogen bromide. Reaction of XIV with hydrogen bromide does, in fact, cause reduction to X.20 Bromination of I1 proceeds similarly. When chlorination of I in acetic acid is carried out in the presence of sodium acetate, the hydrogen chloride is removed as formed. Continued reaction then depends on the relatively weak catalytic effect of acetic acid rather than responding autocatalytically to a developing hydrogen chloride concentration. The reduced reaction rate is not of importlance, however, except at high chlorination stages. A more important and useful consequence is a greater selectivity in the reaction as the weaker acid has less tendency to protonate the weaker s-triazine bases.21 This causes an increase in the rate of chlorination of I with respect to I11 and is responsible for the increase in the molar ratio of monoto dichlorination products which obtains when reaction of I with an equimolar amount of chlorine is carried out in the presence of sodium acetate. The effect is slightly greater when a threefold excess of acetate is used. In those reactions where chloroforni or carbon tetrachloride was used as the medium, the starting s-triazine itself probably played a role analogous to that of sodium acetate in the acetic acid system. Separation of insoluble hydrohalide salts usually occurred, the reactions were sluggish, and the products were those typical of weak acid catalysis. An additional effect of the sodium acetate is found in the ratio of the isomeric dichlorination products, XIXX X I I I , obtained. when it is used. Reaction of I with an equimolar amount, of chlorine in acetic acid in the (20) C. Broche [ . I . p r n k t . Chem., [2]60, 97 (1894)l reported the preparation of XI1 b y trimerisation of tribromoacetonitrile with hydrogen chloride or hydrogen iodide. T h e melting point given was 129O. This compound was undoubtedly X. found in this work t o melt a t 129-131': authentic X I V has m.p. 158-159'. (21) This interpretation has no established precedent in ketone halogenation where the kinetics have been studied with strung acid catalysis and ketone-acid equilibration specifically discounted as a rat,e-determining factor [I,. Zucker a n d L. P. H a m m e t t . J . Am. Chem. Sac.. 61, 2785, 2791 (1939)l.
VOL. 29
absence of sodium acetate gave these by-products in a ratio of greater than 1O:l. When 1 equiv. of sodium acetate was present, this ratio was about 7 : 1, and with 3 equiv. it was strongly reduced to 2 : 1. These results suggest that the acetate ion plays a part in the reaction as a basic cocatalyst, possibly facilitating the enolization step.22 The slightly greater crowding at the chloromethyl group in I11 compared to a methyl group could cause the observed reduction in selectivity. The same argument can be made in connection with the more dramatic effect on the XII-XXII ratio a t the trichlorination stage. When exhaustive bromination of 1 was carried out in acetic acid in the presence of sodium acetate, the reaction led nearly exclusively to XIII, which is quite analogous to the work of Hammick and others,* with niethylpyridines, quinaldines, and 2-niethylquinoxaline. This result, when the reducing activity of hydrogen bromide is eliminated, is evidently equivalent to that obtained jn chlorination. The very sluggish chlorination of I to give IX in an acetic acid-sodium acetate system and the complete failure of an attempt to brominate the residual methyl group in XI11 under similar conditions are reflections of the low catalytic activity of acetic acid with the less basic, highly halogenated compounds. Ready bromination of X to XIV under the same conditions is easily seen to be consistent with the expected much higher proton lability in X. The Reactivity of 1-Haloalkyl s-Triazines.-The strongly electronegative character of the s-triazine ring is responsible for striking differences between the chemistry of the 1-haloalkyl s-triazines and that of the superficially similar benzyl halides. The ability of the nucleus to stabilize an a-anion is apparent in the positive halogen character of the 1-monohaloalkyl compounds, which are readily reduced by an acidic acetone solution of sodium iodide.23 On the other hand, reactions of S N 1 type which require stabilization of a positive charge at the a-position have not been observed.24 Such reactivity would be expected to be inhibited by the highly electrophilic character of the carbon atoms of the s-triazine ring. l 4 Perhaps this inhibition of ionization of an a-halogen atom is responsible for the complete absence of an elimination reaction when V reacted with ethanolic potassium hydroxide. The sole product was 2-(l-ethoxyethyl)-4,6diethyl-s-triazine (XXVII). Suclear magnetic resonance spectroscopy was used to show that the product was not the isomeric 2-(2-ethoxyethyl)-s-triazine which could arise by base-catalyzed addition of ethanol to the expected 2,4-diethyl-6-vinyl-s-tnazine (XXVIII). It seems reasonable to interpret this reaction as the result ( 2 2 ) This is probably particul8rly important in the absence of a stronger acid catalyst. In the bromination of w.w-dibromoquinaldine under similar conditions, sodium acetate has been shown n o t to be involved in a ratedetermining step.14h This difference m a y be ascribed to the greater protonation in acetir acid of the quinaldine derivative compared tu the s-triazines concerned. (23) R. L. Shapiro and C. G . Overberger, J . A m . Chem. Soc., 76, 97 (1954). (24) Attempted ,silver ion-catalyzed hydrolysis of IX and other polyhalogenated compounds in aqueous acetic acid or ethanol were unsuccessful under conditions which are useful with a-halo derivatives of quinaldine,'" a-picoline,sR and 4-methylpyrimidine.*s With silser nitrate incomplete halide elimination took place. b u t destsuction of the product b y the liberated nitric acid ensued. With silver acetate n o reaction W R S obtained. (2.5) H. Bredereck. W. Jentzscb, and G . Morlock. Chwn. B e r . , 93, 2405 (1960).
JUXE, 1964
CHLORINATION OF ALKYLS-TRIAZINES
1.531
the ylid X X X by aqueous sodium carbonate.29 An unexpected result of 1i.ni.r. study of X X X was evidence that the two methyl groups were not equivalent. ;\leasurements a t both 40 and GO ;\IC. showed this was not a case of long range splitting due to the phosphorus atom. This result has led to the suggestion that the unsynimetrical structure X X X a may have considerable stability. Reaction of X X X with p-diniethylaniinn-
Br
XXVIII
XXXa
of inability of the s-triazine substituent to stabilize the transition state for biniolecular elimination.26 This reaction of V with ethanolic hydroxide takes place readily a t rooni temperature and is an example of ~ examples were demnormal Sx2 r e a ~ t i v i t y . ? Other onstrated in the displacenient of bromide ion froni V by acetate ion to give 2-( l-acetoxyethyl)-11,G-diethyl-striazine, the easy reaction of 2-bronioniethyl-4,G-dimethyl-s-triazine with pyridine to give the quaternary salt, and the reaction of 2-chloromethyl-4,G-dimethyls-triazine (111) with triphenylphosphine to give the salt X X I X .
benzaldehyde was extremely sluggish, although the formation of a sinal1 amount of 2,4-diniethyl-G-(pdiniethylaminostyry1)-s-triazine was demonstrated. Reaction of XIX with niorpholine took place readily under the conditions used by Kerfanto with a variety of dihaloniethyl to give 2,i-dimethyl- G-diniorpholinomethyl-s-triazine (XXXI) . Hydrolysis of this product apparently proceeded normally but 4,Gdiniethyl-2-s-triazinecarboxaldehyde(XXXII) was not recovered, probably because of solvation and high solubility in water.31 However, X X X I is a useful generator of the aldehyde and reacted readily with thiosemicarbazide and with 2,4-dinitrophenylhydrazjllr to give the expected aldehyde derivatives.
CH3 XIX
CH3
XXXI
I11
/
The quaternary phosphonium salt X X I X had soniewhat exceptional properties. Its infrared spectrum exhibited a band at 2420 cni. - l , believed t'o be the C-H stretching frequency of the acidic methylene group. This is the lowest frequency that was observed in a large group of triphenylphosphoniuni salts which included acylniethyl derivatives.?* The position of this band can presumably be taken as a measure of the acidity of the methylene group. This indication is confirmed by the great ease of conversion of XXTX to ( 2 G ) C. K. Ingold, "Structure and Mechanism in Organic Chemistry," Cornell University Press, I t h a c a , N. Y., 1953, p . 420. (27) By analogy with a-halonitriles and carbonyl compounds, enhanred Rx2 reactivity u-ould be expected in these s-triazine derivatives over benzyl haliiles because of neighboring group participation in the transition state.
N'
I1
,c-c-
/x \
-
"-
I
,c-cq +
/x
+ y-
4
L Y'J I t seems unnecessary to invoke an a-elimination and carbene mechanism for a n y of these reactions, although the potentiality for such processes in the mono- and dihalomethyl-s-triazines appears to be substantial. (28) Unpublished work of h l r . N. R . Colthup and Mrs. I . Chenzoff.
XXXII
2-Choromethyl-4,G-dimethyl-s-triazine ( I TI) rcnctcd normally with benzaldehyde under the conditions of the Daraens condcnsatio~i~~ to give /1.an9-~--(-1,G-dinlethyl-2s-triazinyl)-3-phcnyloxirane ( X X X I I J ) 3 3 ,
C Ha XXXIII (29) This is comparable to the preparatiun of tl.il,iien3.lpil~lsl~l,i"~t,en~,~slmethylene by I.'. Rarnirez a n d S . 1)ershouitz [ . I . 0 ~ 8 C . h p m . . 22, 4 1 :1937)]. (30) AI. Kerfanto, Camp,. r e n d . , 493 ( l ! l f ; 2 ) , ( 3 1 ) E. ICober and C. (:ritnrlmann, .I. A m . C h e m . Soc., 80, >347 ( 1 0 3 8 ) . 132) (a) 11. S. Newman and 1%. .1. AIagerlein, O r g . Reactions. 6 , 4 1 3 (1949); (b) E. Kleucker, B e , . . 6 6 , IC134 (1922). (33) T h e stereorhemistry of such reactions has recently been disriissed [see H. ICwart and L. G. Kirk. J . 0 1 0 . C h r m . , 22, 116 (1937), and H . Dahn and L . Loewe, Chimin (.iarau), 11, 98 (1437)l.
SCHAEFERAND Ross
1532
Several publications during recent yearsd4 have greatly enlarged much earlier reports of the reactivity of trichlorornethyl-s-triazines. We have now found comparable reactivity in the tribronioniethyl-s-triazines although a more complex situation arises because of easy reduction to the dibroniomethyl conipounds in some circunistances. Reaction of 2,4,6-tris(tribronioniethyl)s-triazine (XIV) with aqueous aninionia to displace one substituent is very fast at room temperature, producing the nionoaniine XXXIJ'. Further reaction was slower and acconipanied by reduction, giving a high yield of 2,4-dianiino-B-dibronioiiiethyl-s-triazine (XXXJr) as the final product. Reaction of XIT.' Lvith 2 equiv. of piperidine in methoxyethanol gave only the nionopiperidino-s-triazine, XXXI7I. Displacement of a single tribronioniethyl group froni XIS' by boiling methanol in +he presence of pyridine gave XXXVII, although pyridine apparently does not catalyze such reactions with 2.1,6-tris(trichloroiiiethyl)-s-tria~ine.~~~
BrzCH-(N\yCHBr2 N y N I
CHBr2
X
VOL. 29
CBr3 XI11
CHBrz XL
I CHBrz
CHBi-2 XLI
X
found in the unexpected reaction of XI11 with diniethylforniamide and 2,4-dianiino-6-niethyl-s-triazine to give X. Compound X also was reduced rapidly in a remarkable fashion hy sodiuni iodide and acetic acid in acetone to give 2,4-bis(dihronioniethyl)-6-niethyl-striazine (XLI). Prolonged treatment with this reagent a t room temperature caused complete reduction to I. Reports of the efficient use of hexachloroacetone for generation of d i c h l o r ~ c a r b e n eled ~ ~ us t o evaluate 2niethyl-d,6-bis(trichloroniethyl)+triazine (IX) for this purpose under siniilar conditions. Sonic dichlorocarbene was obtained by reaction with sodium niethoxide in cyclohexene, but the yield was only about 5Yc, the major product being 2-niethyl-4,A-diniethoxy-s-triazinc B ~ J C ~ ; ~ \ V N H ~ (XLII). Compound XLII was also obtained by methoxideN y N catalyzed inethanolysis of I X The intermediate CBr3 X1,III was obtained by adaptation of the niethod of XXXIV Kober.34c I
80%
1
aq. NHs
CH3-(NvCC13 __t
CHBrz XXXVIII
NHz
OCH, XLIII
CH30H
IX
XLII
xxxv
Xttciiipts to displace a tribronioniethyl group from XIV with the anions of nitromethane or i d o n i t r i l e in the presence of pyridine led instead to the reduced product, i. e . , 2,1,G-tris(dibronioniethyl)-s-triazine(X). Reaction of this coinpound with ammonia in aqueous rthanol gave the nionoaniine XXXVIII in low yield. 2,1,6-Tris(l,l-dibroiiioethyl)-s-triazine was unreactive toward animonia or aniines. The reactions of XI11 wit,h aqueous animonia were comparable to those observed with XIY. Displacenient of one tribron~oiiiethylgroup gave X X X I X and subscqucnt, reduetion gave a sniall aiiiouiit of XT,. The latter \vas obt'ainod in substantial yield by waction of XI11 with animonia in hot di~ncthylforiiiaiiiid~ (DIE). . h i cxtrciiie cxainplc of thv oxidation--reductioii rractions Ivhich can occur with these polybroniidcs is ( 3 4 ) ( a i \ . IireutzhrrPer. .I. A M . Chrm. S o r . , 79, 2 G 2 9 (1927): ( b ) H. 3 c I ~ r u e h r .i h j d , , 81, X;>S ( I % < ) ) : ( r ) k:. Koher. .1. O w Chem., 2.5, 1728 ~9firn.
E~perirnental~~ 2-Chloromethyl-4,6-dimethyl-s-triazine(111). Chlorination of I with N-Ch1orosuccinimide.-A mixture of 5.0 g. (0.040 inole) of I , 5 . 6 g. (0.040 mole) of S C S , 0.72 g. (0.003 mole) of benzoyl peroxide, and 50 inl. of carbon tetrachloride was heated at reflux for 4 hr. Filtration gave a 92c/, yield of succininiide. 1Xstill:ition of the filtrate gave 2.3 g. of recovered I and 3.5 g. of crude 111, h . p . R2-120° (20 nun.), ca. 6OC/L yield based on unrecaovered I . Redistillation gave t i fraction boiling at 97-98" ( 8 0 rnm.), n% 1.5032. This was 94.,5 niole (1; 111 as judged by niass spectrometry. It was esselitially identiral with 111 prepared by hydrocahloride with ethyl acetimirewtion of c.hloroac.et~~niidiIie Chlorination of I with Chlorine in Acetic Acid.-Chlorine ( 6 8 passed into :t solution of 123 g . ( 1 . 0 mole) of I in 500 nil. of gl:wid :wetic. wid :it 50-55' during 1 .O hr. Anhydrous sodiuni :tretate ( 1 .0 niole) then was :tdcieti, and the mix-
g , , O . ! I ~ niole) was
~~
(:35) (a) P. IC. ICadaba unci ,J. 0. l < d n n r d s , i b i d . , 2 6 , 1.131 ( l O l i O > ; (b) I'.,W. (:rant nnri \v, 13. Cnssie, t h l d , , 26, 14:j:3 (19tjoJ. (:I(;) hlelting points are uncorrected. AIivroanalyses were carriril uilt ill these laboratvries under tile dirertion of I l r . . I , , \ . I i u c k and I)r. .I. H. 1)eonarine. C:ns-Iiquid rlirornatosraphic sppnrations were carried o!lt c.11 H silicone roliimn. Tlie cooperation of Dr. U. l'rinland and h i s assorintrs was lielpful in this aspect of t h e work.
CHLORINATION OF ALKYLS-TRIAZINES
JUNE,1964
1533
TABLE I COMPOSITION OF PRODUCT MIXTURESFROM CHLORINATION OF I Component of mixture
--Molar 1.0
ratio of chlorine t o 1.3 1.7
I1.5
-Molar 1:l:l
IN
ACETICACID^
ratio of chl7rine t > sodium acetate t o I1:3:1 3:3:1 4.8:9:1
46 8* 3 37 29 I 60 22 29 18 37 43 I11 19 XIX 20 19 29 43 21 18 9 XXIII 1 1 4 3 8 18 XXII 1 11 27 16 1.4 2 9 XI1 1 5 9
