5102
J. Org. Chem. 1981,46, 5102-5109
a [crotyl bromide]/[3-bromo-l-butene] ratio greater than 15 were employed in metal-catalyzed reactions with ethyl diazoacetate. Reactions were performed as previously described for allyl halides. Direct analyses of the crotyl bromide content of product mixtures was performed following complete reaction, usually 24 h. At temperatures at or below 25 OC reactant isomerization was not observed, but at 50 OC isomerization to the equilibrium mixture of [crotyl bromide]/ [3-bromo-l-butene] equal to 4.5 occurred during the course of the catalytic reaction. Product isolation and analyses were performed as previously described. GC analyses were performed by using 4-m 5 % ethylene glycol adipate columns. The averaged results from duplicate and triplicate experiments are reported in Tables IV and V. Ethyl 2-brom&-methyl-4-pentenoate (9): 'H N M R (CDCld of major isomer from RhZ(OAc),-catalyzedreactions at or below 25 "C 6 5.72 (ddd, Jbm = 17.0 Hz, Jci,= 9.7 Hz, J ~ =c7.5 Hz, CH=), 5.11 (dd, Jtr, = 17.0 Hz, JBrm = 0.9 Hz, 1 H), 5.09 (dd, Jci. = 9.7 Hz, Jm = 0.9 Hz, 1 H), 4.20 (9, J = 7.1 Hz, CHZO), 4.07 (d, J = 8.6 Hz, CHBr), 3.04-2.55 (sextet m, CHCH3), 1.28 (t,J = 7.1 HZ,CH,CHtO), 1.21 (d, J = 6.7 HZ,CH3CH); 'H NMR (CDClJ for minor isomer 6 5.80 (ddd, J- = 17.0 Hz, J h = 9.6 Hz, J* = 7.5 Hz, CH=), 5.14 (dd, Jkm = 17.0 Hz, JBm= 0.9 Hz, 1H), 5.13 (dd, J k = 9.6 Hz, J = 0.9 Hz, 1H), 4.24 (9,J = 7.1 Hz, CHZO), 4.11 (d, J = 8.4%z, CHBr), 3.04-2.55 (sextet m, CHCHB),1.29 (t, J = 7.1 Hz, CH3CH20), 1.24 (d, J = 6.8 Hz, CH3CH). Anal. Calcd for Ca13BrO2: C, 43.45; H, 5.94. Found C, 43.62; H, 6.11. Ethyl trans-2-bromo-4-hexenoate (10): 'H NMR (CDC13) 6 5.84-5.14 (m, 2 H), 4.22 (9, J = 7.1 Hz, CH20),4.16 (t, J = 7.4 Hz, CHBr), 3.00-2.40 (m, 2 H), 1.65 (ddt, J = 5.8, 2.2, 1.2 Hz, CH&H=), 1.29 (t,J = 7.1 Hz, CHBCH20). Anal. Calcd for C&I13Br02: C, 43.45; H, 5.94. Found C, 43.58; H, 6.17. Ethyl 2-(bromomethyl)-3-methylcyclopropanecarboxylate (trans-11):'H NMR (CDC13)6 4.16 (q, J = 7.1 Hz, CHzO), (63) Winstein, S.; Young, W. G . J. Am. Chem. SOC.1936, 58, 104.
3.91-3.43 (m, CHzBr), 1.86-1.23 (m, 3 H), 1.28 (t, J = 7.1 Hz, CH3CH20), 1.14 (d, J = 5.0 Hz, CHSCH). Anal. Calcd for C&I&r02: C, 43.45; H, 5.94; Br, 36.14. Found: C, 43.63; H, 6.01; Br, 36.32. Ethyl 2 4 bromomethyl)-j-methylcyclopropanecarboxylate (cjs-11): 'H NMR (CDClJ 6 4.15 (q, J = 7.1 Hz, CH20),3.35 (d, J = 7.2 Hz, CH2Br), 1.95-1.60 (m, 2 H), 1.50-1.28 (m, 1 H), 1.26 (t, J = 7.1 Hz, CH3CHz0),1.23 (m, CH3CH). Ethyl 2 4 1-bromoethy1)cyclopropanecarboxylatewas isolated from the reaction mixture obtained by treatment of combination of crotyl bromide and 3-bromel-butene (molar ratio 1.63) with ethyl diazoacetate and a catalytic amount of Rhz(OAc),. Geometrical isomers were not separable by GC analyses: 'H NMR (CDCl3) 6 4.15 and 4.13 (9, J = 7.1 Hz, CHzO), 3.87-3.43 (quintet, CHBr), 1.78 and 1.76 (d, J = 6.7 Hz, CHCHa), 1.81-0.60 (m, 4 H), 1.26 and 1.25 (t, J = 7.1 Hz, CH3CHz0). The isomer ratio of the isolated product was 1.2.
Acknowledgment. The support of the National Science Foundation for this research is gratefully acknowledged. We thank D. van Leusen for his synthesis of allylamines and W. J. Hoekstra for his preliminary investigations of reactions with allyl halides. Registry No. 4a, 10152-76-8;4b, 2155-94-4; 412, 2588-79-6;(E)-4d, 51752-08-0; (E)-4e,42817-44-7; 5a, 71031-93-1; 5b, 66917-63-3; 5c, 66917-65-5;5d (isomer l),79373-05-0;5d (isomer 2), 79373-06-1;5e. (isomer l),79357-14-5;5e (isomer 2), 79357-15-6; 5 (X = I), 7935716-7;5 (X = Br), 39149-86-5;5 (X = Cl), 29119-70-8;cis-6 (X = Br), 79357-17-8;tram-6 (X = Br), 38506-15-9;cis-6 (X = Cl), 79357-18-9; trans-6 (X = Cl), 79357-19-0;7 (X = Br), 78331-59-6;8 (X = Br), 79357-20-3;8 (X = Cl), 79357-21-4;9 (isomer 11, 79357-22-5;9 (isomer 2), 79357-23-6;(E)-10,79357-24-7;tram-11, 79357-25-8;cis-11, 79390-68-4;ethyl diazoacetate,623-73-4;allyl iodide, 556-56-9;allyl bromide, 106-95-6;allyl chloride, 107-05-1;diethyl diazomalonate, 5256-74-6; (E)-crotylbromide, 29576-14-5;ethyl 2-(l-bromoethyl)cyclopropanecarboxylate, 79357-26-9;3-bromo-l-butene,22037-73-6; Rh,(Co)16, 28407-51-4; Rh,(OAc)d, 15956-28-2; CUC~.P(O-~-P~)~, 78955-42-7;Cu(aca&, 13395-16-9.
Occurrence of the SN(ANRORC) Mechanism in the Hydrazination of 1,2,4,5-Tetra~ines'-~ Anda Counotte-Potman, Henk C. van der Plas,* Beb van Veldhuizen, and Cees A. Landheer Laboratory of Organic Chemistry, Agricultural University, De Dreijen 5, 6703 BC Wageningen, The Netherlands
Received August 21, 1981
3-Alkyl(aryl)-1,2,4,5-tetrazines(7) when treated with hydrazine hydrate were found to undergo a Chichibabin hydrazination into 3-alkyl(aryl)-6-hydrazino-1,2,4,5-tetrazines (8) according to an SN(ANR0RC) mechanism. 'H and NMR measurements indicate that the fmt step in this reaction sequence is the formation of a homoaromatic u adduct anion, due to attack at C6, and that the second step is the formation of an open-chain intermediate. With lSN-labeledhydrazine, part of the label is found in the 1,2,4,5-tetrazinering of the 6-hydrazino compounds 8*. NMR evidence is obtained which shows that the hydrazino compounds with the lSN-labelin the ring (8*II) and with the 15N-labelin the hydrazino group @*I) are formed according to the SN(ANR0RC) mechanism. with hydrazine leads to introduction of a hydrazino group Treatment of 6-amino- or 6-halogeno-l,2,4,5-tetrazines at position 6. During this hydrazino deamination and hydrazino dehalogenation part of the molecules were found to react according to the SN(ANR0RC) mechanism, the other part followed the SN(AE) pathway.
In a preceding paper' we obtained firm evidence that the anion of 6-amino-l,6-dihydro-3-phenyl-1,2,4,5-tetrazine (2), formed upon addition of ammonia t o 3-phenyl1,2,4,5-tetrazine (1, Scheme I), is homoaromatic. This u
Scheme I
~~
(1) Part 5 on 1,2,4,5-tetrazineand ita derivatives. For part 4 see: Counotte-Potman,A.; van der Plas, H. C.; van Veldhuizen, A. J. Org.
Chem., in press. (2) Part 30 on NMR investigations of u adducts of heterocyclic systems with nucleophiles. For part 29 see: van den Haak, H.J. W.; van der Plas, H. C.; van Veldhuizen, A. accepted for publication in J. H e t erocycl. Chem. (3) Part 28 on the SN(ANRORC)mechanism. For part 27 see: Kos, N. J.; van der Plas, H.C. J . Org. Chem. 1980, 45, 2942.
C6H5
kH5
1
2
C6h 3
adduct is in the homotetrazole conformation, containing 6 ?r electrons in t h e tetrazole ring and holding t h e amino group in t h e exo position a n d t h e hydrogen at t h e sp3
0022-3263/81/1946-5102$01.25/00 1981 American Chemical Society
J. Org. Chem., Vol. 46, No. 25,1981 5103
Hydrazination of 1,2,4,5-Tetrazines
Scheme I11
Scheme I1
,CHI
i
c H3 k
5
9
k
R
6'
7
R 10
carbon atom above the ring. This hydrogen is located in the shielding region, resulting in a chemical shift at high field (6 1.51). In the literature it is described4 that addition of am, bond in 1-methylpyrimidinium iodide monia to the C& (4, Scheme 11) is accompanied by an upfield shift of H6 (A6 = 4.91 ~ p m ) ~ . Addition of hydrazine hydrate gave about the same upfield shift (A6 = 4.5-5 ppm),6 from which it was concluded that hydrazine gave an analogous u ad(6). duct, i.e., 6-hydrazino-l-methyl-l,6-dihydropyrimidine From the u adduct 2 was obtained 6-amino-3-phenyl1,2,4,5-tetrazine (3) upon oxidation with potassium permanganate;6 the reaction of 1-3 can be considered as a Chichibabin amination.' It has been published that the Chichibabin amination of 4-phenylp~rimidine~ and phenyl-1,3,5-triazines occurs according to the SN(ANR0RC) mechanism,'O describing a reaction sequence involving Addition of the Nucleophile to the heterocycle, Ring Opening, and Ring Closure. In an extension of our studies on the amination of 1,2,4,5-tetrazinesby liquid ammonia, we became interested whether 1,2,4,5-tetrazinesare also appropriate systems for Chichibabin hydrazination by hydrazine hydrate. The use of sodium hydrazide in the Chichibabin hydrazination of some azaaromatic systems has been rep0rted.l' We were particularly interested whether the hydrazination, if it occurs, is accompanied by the intermediate formation of a 1:l u adduct having homoaromatic (and anionic) properties and whether the hydrazination would occur according to the SN(ANRORC)process. In a previous paper12 we already presented some evidence that in the hydrazinolysis of 6-amino- and 6bromo-3-methyl-l,2,4,5-tetrazine an SN(ANR0RC) mechanism is operative. In this paper we present an extension of these hydrazino deamination and hydrazino dehalogenation reactions and especially the results of our study with lSN-labeledhydrazine and the NMR spectroscopy of (4) Oostveen, E. A; van der Plas, H. C.; Jongejan, H. Red. Trau. Chim. Pays-Bas 1974,93, 114. (5) Brouwer, M. S.; van der Plas,H. C.; van Veldhuizen,A. Red. Trau. Chim. Pays-Bas 1978,97, 110. (6) Counotte-Potman, A.; van der Plas, H. C. J. Heterocycl. Chem.
1981, 18, 123. (7) Pozhorskii, A. F.; Simonov., A. M.; Doron'kin, V. N. USP. Khim. 1978,47, 1933. (8) Breuker, J.; van der Plae, H. C. J. Org. Chem. 1979, 44,4677. (9) Simig. -. G.; . van der Plas. H. C. Recl. Trau. Chim. Paw-Bas 1976. 95,'125. (10) Van der Plae, H. C. Acc. Chem. Res. 1978,11, 462. (11) Kaufman, T., Angeur. Chem. 1964, 76,206. (12) Counotte-Potman,A. D.; van der Plas, H. C. J. Heterocycl. Chem. 1978, 15, 445.
Table I. I5N Excess in Acetone-Hydrazones 9* and in the 6-Bromo Compounds % 15N % av of R 9* 10* ANRORCb ANRORC 26.2, 23.0 24.6 CH, 6.5, 24.6 1.70, 5.7 28.5 1.60, 1.82 28.0, 28.9 C,H, 5.7, 6.3 t-C,H, 0, 0 0 8.0, 20.7 0, 0 0.44, 0.27 4.2, 2.9 3.5 C,H, 10.6, 9.3 ~
SDaVC 0.4
~
0.15
2.6
2.6
a The percentage of 15Nlabel in 9* is a measure for the 15Nenrichment in the I5N doubly labeled hydrazine used for the reaction. This label is incorporated either on the 1,2-position of the 1,2,4,5-tetrazine ring or in the exocyclic hydrazine group, depending on the position of addition of the hydrazine. The percentage of 15Nlabel in 10* is a measure for the molecules in which the label is only present in the 1,2,4,5-tetrazine ring. The percentage ANRORC refers t o the percentage of molecules 8* which have been formed by route I1 (Scheme IV). The standard deviations (SDs) were determined as follows. The ratio of peak heights of the M + 2 and M peaks were determined at high resolving power. The average and standard deviation were determined from 6-10 values. If the value of the SD was
