J . Org. Chem., Vol. 42, No. 23, 1977 3709
Reaction of Di- and Trisubstituted Chloroiminium Chlorides
Reaction of Di- and Trisubstituted Chloroiminium Chlorides with Azide Ion. A New "Curtius Type" Rearrangement1 Rene Imhof, David W. Ladner, and Joseph M. Muchowski* Research Laboratories, Syntex, S. A,, Apartado Postal 10-820,Mexico 10, D. F. Received March 22,1977
It is shown that disubstituted chloroformiminium chlorides 2 (R3= H)react with tetrabutylammonium azide (as well as other azide ion sources) to give the corresponding disubstituted cyanamides 5 presumably via the "Curtius like" rearrangement of an intermediate azidoformiminium salt 3. Certain trisubstituted chloroiminium chlorides 9 undergo a related reaction with azide ion to give 1-substituted 5-disubstituted aminotetrazoles (13) via a trapable carbodiimidinium species 11. Whereas the disubstituted cyanamide synthesis is a general one, the tetrazole synthesis is limited to those trisubstituted chloroiminium salts (e.g., 9) where one of the nitrogen atom substituents and the migrating group are both aryl moieties.
The chemistry of organic molecules containing the azido moeity is rich in rearrangement reactions which stem from the propensity of these substances to lose molecular nitrogen2 The rearrangement of acyl azides to isocyanates (Curtius reaction3) and the reaction of hydrazoic acid with carbonyl compounds (Schmidt reaction4) are well known representatives of this general class of transpositions, while the formation of tetrazoles5 or cyanamides6 by the pyrolysis of geminal diazides are less frequently encountered members of this group of rearrangements. One rarely observed reaction is the rearrangement of imidoyl azides to ~arbodiimides.~ This is because those reactions which are expected to yield the former substances provide tetrazoles instead. In fact, the reaction of imidoyl chlorides with azide ion constitutes one of the most general routes to 1,5-disubstituted tetrazoles and is known as the von Braun-Rudolf synthesis.8 It occurred to us that one possible method of blocking tetrazole formation, and hence promoting rearrangement in the above instance, would be to utilize a substrate in which the nitrogen atom was disubstituted as is found in the azidoiminium salts 3,6, and 10, derived from the corresponding dichlorides (Vilsmeier-Haack reagent@). This publication describes the results of such an investigation. By analogy to the reactions cited above, it was expected that azidoformiminium salts 3 (Scheme I) would rearrange by the Scheme I a ) R1=CgHg RZ=CH3 R 3 = H b ) R1 r R 2 = C 6 H 5 , R 3 = H
R?"
RI,;,R~ CI -
c ) R1_R2:lC3H7,R3=H
R3A0
R3JL
d ) R'=R2=CgH11, R 3 z H o ) R1,RZ=(CH2)5,R3=H
1
-2
I ) R1= C s H g * R 2 = CH3, R3: C g H l , g ) R1: R z = C s H g , R 3 = CH3
6 5
concurrent loss of molecular nitrogen and migration of hydride from carbon to nitrogen to produce, after the loss of a proton from 4, an N,N-disubstituted cyanamide. As a first attempt to effect such a transposition, a solution of N-methylformanilide (la) in dimethoxyethane (DME) was converted into the chloroiminium salt 2a with oxalyl chloride, and then solid sodium azide was added below 30 "C. A vigorous reaction, accompanied by considerable gas evolution, ensued. The product mixture, the composition of which depended on the number of moles of sodium azide utilized (Table I),consisted of the starting material la, N- methylaniline, N-methyl-Nphenylcyanamide (5a), and the tetrazole 7. The cyanamide yield was maximal when 2 mol of sodium azide per mole of the iminium salt 2a was used. Extended reaction periods or higher reaction temperatures favored the formation of the tetrazole at the expense of the cyanamide, a predictable observation in view of the knownlo genesis of tetrazoles from cyanamides and hydrazoic acid. The above reactions were not always reproducible, presumbaly because of the meager solubility of sodium azide in DME, and consequently trimethylsilyl azide," triethylammonium azide,12 and tetrabutylammonium azide13 were examined as more soluble azide ion sources. The cyanamide 5a was produced in each case, but the yield thereof was the highest (Table I) and by-product formation was the lowest with tetrabutylammonium azide.14 The dichlorides 2b-e were then reacted with tetrabutylammonium azide (2 mol) and the cyanamides 5b-e were formed in every instance in preparatively useful yields (Table 11). The reaction clearly is a general one. The successful conversion of disubstituted chloroiminium chlorides into the corresponding disbustituted cyanamides was an added impetus to examine the reaction of azide ion with trisubstituted chloroiminium chlorides such as 9 (Scheme 11). I t was anticipated that the rearrangement of the azidoiminium salts 10 obtained thereby would generate 1aryl-5-(N-alkylanilino)tetrazoles(13) via the highly electrophilic alkylcarbodimidinium species15 11. Indeed, the reaction of tetrabutylammonium azide (2.5 equiv) with N-methylN-phenylchlorobenziminium chlorode (9a) (1equiv), in DME solution at 50-60 "C, gave l-phenyl-5-(N-methylanilino)tetrazole (13a) as the principle (57%) product together with minor amounts of 1,5-diphenyltetrazole (14a) (S%), Nmethylaniline (10-13%), and benzaldehyde (10-13%). The structure of 13a was confirmed by an unambiguous synthesis from the lithium salt of N-methylaniline and l-phenyl-5chlorotetrazole. Other trisubstituted iminium salts 9b-e were also converted into the tetrazoles 13 and 14 and other products, the relative amounts of which (Table 111)depended on the nature of R2. Several aspects of the data recorded in Table I11 are worthv
3710 J. Org. Chem., Vol. 42, No. 23, 1977
Imhof, Ladner, and Muchowski
Table I. Reaction of N-Methyl-N-phenylchloroformiminiumChloride (2a) with Various Azide Ion Sources Azide ion source
Registry no.
Moles azide per mole 2a
NaN3 26628-22-8 NaN3 NaN3 (CH3)3SiN3 4648-54-8 (C~HS)~NHN 30074-14-7 ~ (C4Hd4"3 993-22-6
Cyanamide 5a
Tetrazole 7
4 39
5 5 2
1 2 3 2 2 2
22 27
b
47 75
a
5
Products, % N-Methylaniline N-Methylformanilide (la) 52
9
37 40 59 b 9
11
7 b 5 10
Not detected. Not determined. Table 11. Conversion of Disubstituted Chloroiminium Chlorides into Disubstituted Cyanamides R' \+,R2 R' \ /R N +N
No. a b c
d e
R1
R2
CsH5 CH3 CsH5 CsH5 i-C3H7 i-CsH7 CsHll CsHll -(CH2)5-
Scheme 111 10 -
9
_16_
15 -
Registry no.
% yield
63640-93-7 63640-94-8 54485-04-0 63640-95-9 59611-74-4
75 62 45 44
(59)Q
21
(41)=
Scheme IV
Yield by GLC.
CH3.:,C6H5
17 -
Scheme V of comment. For example, what is the origin of the 1,5-diaryltetrazoles 14a-d, N- methylaniline, the aromatic aldehydes, and the unsymmetrical urea 18? The formation of the 1,5-diphenyltetrazoles 14a-d can be rationalized in terms of a von Braun type of degradationl'j of 9 and/or 10 (Scheme 111).The intermediate imidoyl azide 16 derived directly from 10, or indirectly via the imidoyl chloride 15, would then cyclize to 14 in the expected8 manner. It is probable, however, that the major portion of the 1,s-diaryltetrazole by-product was derived from 15, which had formed prior to the addition of azide ion. This contention is based on the observation that 15a and 15d were formed in 80 and 85% yields (as determined by hydrolysis to the corresponding benzamides) when dimethoxyethane solutions of 9a and 9d Scheme I1
0
rCH3 19 -
were heated at reflux temperature (77 "C in Mexico City!) for 24 and 48 h. (The transformation of 8 into 9 required 4-15 h at 60 "C.) Based on the above mechanism, it is not surprising that no 1,5-diphenyltetrazole was formed in the reaction of 9e with azide ion, since the loss of chlorobenzene from 9e or phenyl azide from 10e would be unlikely. Appreciable amounts of aldehydes and N-methylaniline were formed in the reaction of 9a, 9b, and 9d with azide ion. In the case of 9a, at least," equimolar amounts of benzaldehyde and N-methylaniline were produced, and this was suggestive of a common intermediate for these substances. Hydrolysis of the iminium salt 17 (Scheme IV) which, in principle, could be derived by hydride transfer from the solvent to 10, is one plausible18 source of the above products. Reduction at the chloroiminium salt stage 9 by the solvent is ruled out, because heating 9a and 9d in DME gave the corresponding imidoyl chlorides 15a and 15d in high yield (see above), and little if any (
