Zwitterions as Intermediates in 1,3-Dipolar Cycloadditions of Electrophilic Azides to...

FULL PAPER

Zwitterions as Intermediates in 1,3-Dipolar Cycloadditions of Electrophilic Azides to 2-Alkylidenetetrahydroimidazoles and 2-Alkylidenedihydrobenzimidazoles~1~* Helmut Quast*a, Manfred Ach", Svetlana Ivanovaa, Eva-Maria Peters', Karl Peters', Hans Georg von Schneringb

Institut fur Organische Chemie der Universitat Wiirzburga, Am Hubland, D-97074 Wurzburg, Germany

Max-Planck-Institut fur Festkorperforschungb, Heisenbergstralje 1, D-70506 Stuttgart, Germany

Received May 3 1, 1996

Key Words: Ketene N,N-acetals, cyclic / Imidazole, derivatives of / Benzimidazole, derivatives of / Azides, electrophilic / Cycloaddition, 1,3-dipolar, nonconcerted / Zwitterions

Cyclic ketene N,N-acetals derived from imidazolidine (4a, c) and 2,3-dihydrobenzimidazole (6a-c) add methanesul- phony1 azide (2a) or picryl azide (2f) to afford the zwitterions 5 and 7, respectively. The structure of 7d is elucidated by X-ray crystallography. Reversibility of formation and thermal stability of the N-sulphonyl zwitterions depend on the substi- tution pattern at the carbon atom to which the triazenide moiety is attached: In the case of a pair of geminal methyl groups (5a, ?a) formation is irreversible and decomposition

by cyclisation and subsequent reactions occurs above -2O"C, while in presence of a single alkyl group (7c, d) these processes require heating to 80°C and are accompanied by partial reversion to 2a and ketene N,N-acetals (6b, c). Cycli- sation of the zwitterions yields intermediate spirocyclic [3 + 21 cycloadducts, which may undergo [3 + 21 cycloreversion into N-sulphonylimine 13 and diazo compound 14 or extrude molecular nitrogen to furnish ring-expanded 2-(sulphonyl- imino)piperazine derivatives (9, 11).

According to experimental criteria, the vast majority of 1,3-dipolar cycloaddition reactions proceed by a concerted

Ten years ago, the first limiting case of a non- concerted 1,3-dipolar cycloaddition has been realised by Huisgen and coworkers when they treated (strongly nucleo- philic) thiocarbonyl ylides with strongly electrophilic di- polarophiles. The resulting zwitterions were demonstrated to be true intermediates in [3 + 21 cycloaddition reac- tions"]. More recently, we have disclosed first examples of the second case, which limits the scale of orbital interac- tions at the opposite side, when electrophilic dipoles, viz. sulphonyl azides 2a-c and nitroaryl azides 2d-f, were al- lowed to react with strongly nucleophilic dipolarophiles, i.e. alkylidenedihydrotetrazoles (1). Zwitterions 3 arose as pri- mary products, and their thermal stability varied over a wide range[4-61. Conclusive evidence has been adduced for the role of the zwitterions 3a and c as intermediates in two- step 1,3-dipolar cycloaddition~[~]. We now report that other cyclic ketene NN-acetals, namely alkylidenetetrahydroimid- azoles 4 and alkylidenedihydrobenzimidazoles 6, also react with electrophilic azides (2a, f) to afford zwitterions 5, 7 which closely resemble those obtained from alkylidenedihy- drotetrazoles 1.

Cyclic ketene NN-acetals whose nitrogen atoms are con- nected by a bridge, like alkylidenedihydvotetrazoles 1, -imi- dazole~[~I, and -benzimidazoles 6 as well as alkylidenete- trahydroimidazoles 4, possess extremely electron-rich nucleophilic terminal carbon atoms which may be regarded as anionic part of ylidic systems. This property is reflected

Me I

- la

l b

- 2a

2b

2c

2d

2e

2f

not

\ 2 Me

1

R1 R2

Me Me 3a l4.51

tBu H 3b 161

3

R1 R2 R3

Me

Me

Me

tBu

tBu

tBu

fBu

tBu

Me

Me

Me

H

H

H

H

H

nly by a very high reactivity toward electrophiles[*l but also by photoelectron spectra and unusual high-field shifts in carbon-13

When the cyclic ketene NN-acetals 4 and 6 are allowed to react with methanesulphonyl azide (2a) or picryl azide (20 at low temperatures, colourless 1:l adducts are ob- tained from 2a and orange-red ones from 2f. If nonpolar

Liebigs Ann. 1996,1551-1558 0 VCH Verlagsgesellschaft mbH, D-6945 1 Weinheim, 1996 0947-3440/96/1010-1551$15.00+.25/0 1551

FULL PAPER H. Quast et al.

solvents are employed, the products precipitate from the re- action mixtures (Table 1) . The adducts 5a, 7a of the isopro- pylidenc compounds 4a, 6a with methanesulphonyl azide decompose above -20°C (see below) and hence have been characterised only by NMR spectroscopy (Tables 3 and 4). All other adducts are much more stable and form crystals that melt with decomposition well above 100°C (Table 1).

P R3-N,

4 5

Y R3-N,

Me

6

5a, 7a

5b, l b

7c

5d, 7d

5e, 7e

7

R' R2 R3

Me Me Me-Sq

Me Me 2,4,6-(Nq)3C6H2 Me H Me-Sq

tBu H Me-Sq

tBU H 2,4,6-(Nq)&jHz

Table I . Yields of zwitterions, melting points (decomposition), IR data and solvents used for recrystallisation

Cod. Yield M. D. fdec.) IR Icm-11 (KBr) . . . ,

[Yo] FC] ' C=N,C=C SO., NO, 5b 73 137-138 1601 1530

(CH2C12Et20) 5d 70-79 143-144

(iPrOH) 5e 84 157- 159

(CH,CI2/Et,O) l b 92 156- 158

(MeOH) l c 88 144 ~ 145

7d 84-90 146-147 (MeOHEt20)

7e 82 144 - 146 (CH2CIZIEt70)

1568 1605

1604 1568 1600 1556 1615 1575 1613 1518 1605 1565

1318 1273 1073

1528 1318 1513 1308

1255 1100 1217 1078

1520 1315

The zwitterionic structures 5, 7 are assigned to the 1:l adducts on the basis of NMR spectroscopic evidence (Tables 3 and 4). The presence of a cationic heterocyclic system IS evident from the chemical shifts of the ring carbon atom C-2 which closely resemble those of 2-alkyldihydro- imidazolium ionsIX] and 2-alkylbenzimidazolium ions[']. In particular, this feature disproves isomeric spirocyclic struc- tures of type 8. According to their proton and carbon-I3 spectra, the zwitterions that are derived from the 2-ethylid- enebenzimidazole 6b (+7c) and the 2-isopropylidene com-

pounds 4a (+5a, b), and 6a (+7a, b) exhibit C, symmetry with the mirror plane being orthogonal to the ring plane and bisecting the CC bond of the heterocyclic system. While 5a, b and 7a, b possess a real plane of symmetry in the conformation shown in the Scheme, the observed sym- metry of 7c, whose a-carbon atom is a stereogenic center, must be the consequence of rapid rotation around the (C- 2)-(a-C) bond. Rotation around this bond in the sym- metrical zwitterions 5a and b can be probed with the help of the NMR signals of the four ring protons. At room tem- perature, rotation is rapid on the proton NMR time scale for the zwitterion 5b as indicated by the somewhat broad- ened singlet resulting from the four ring protons. In striking contrast, at - 15 "C those of 5a give rise to an AA'BB' spec- trum, which resembles the spectra of the spirocyclic com- pounds 8b and c[I0l. Obviously, rotation around the (C- 2)-(a-C) bond of 5a is slow under these conditions.

R3

H H & - - ! H

Me % Me M e

5a, b 8b (R3 = Me), 8c (R3 = Ph)

5d, e 7C

Unlike zwitterion 7c, the zwitterions 5d, e and 7d, e, which stem from the neopentylidene compounds 4c and 6c, respectively, do not exhibit apparent symmetry due to rapid rotation around the (C-2)-(a-C) bond. Their proton and carbon-13 spectra differ from those discussed above in as much as they are indicative of rigid (unsymmetrical) struc- tures. Both halves of the heterocyclic rings are diastereo- topic, and the four ring protons of 5d and e yield complex multiplets. Clearly, the tert-butyl groups preclude rapid ro- tation around the (C-2)-(a-C) bond. The conformation in which steric repulsion has been minimized is drawn for 5d and e in the Scheme.

The structure of zwitterion 7d in the solid state has been established by an X-ray diffraction analysis (Figure 1). Many features of 7d closely resemble those found for the corresponding tetrazole zwitterion 3dr41. For example, both adopt a conformation with the tert-butyl group perpendicu- lar above (or below) the ring plane. The azo groups of both triazenide moieties exist in the Z configuration, while neu- tral triazenes prefer the E configuration["]. On the other hand, the NN distances in neutral triazenes["l and the zwit- terions 3d and 7d are very similar (Table 2). This is indica- tive of a considerable localisation of the negative charge at

1552 Liebigs Ann. 1996, 1551-1558

Zwitterions as Intermediates in 1,3-Dipolar Cycloadditions FULL PAPER Figure 1. Perspective drawing of the zwitterion 7d showing the

numbering of the atoms

01

c3

C18

L) C16

the nitrogen atom that is bonded to the methylsulphonyl group (N13 in Figure 1). Obviously, Coulomb attraction between the centres of the opposite charges dominates the structure found in the solid state of the zwitterions 3d and 7d. Not only does it enforce the Z configuration of the azo group but also strikingly short distances between C2 and N13 (258.5 ppm in 3dL41, 259.8 ppm in 7d).

Table 2. Atomic distances [pm] and bond angles ["I (standard devi- ation) of the triazenide side chains of the zwitterions 3d and 7d as

determined by X-ray diffraction analyses

tBu 0

Np-N,,-SO, Cpd. C(2MH-Na- I

3d 151.5(4) 149.7(4) 127.1(4) 134.8(3) 162.9(3) 7d 150.3(3) 148.2(3) 127.5(3) 134.8(3) 162.7(2)

tBu tBu I I

C(2wH-Na CH-Na-Np Na-Np-Ny Np-Ny-S02 3d 109.5(2) 115.6(2) 116.5(2) 1 1 1.0(2) 7d 112.1(2) 116.1(2) 116.2(2) 109.6( 1)

Thermal Decomposition of the Zwitterions 5 and 7

The zwitterions 5a and 7a, which are formed from meth- anesulphonyl azide (2a) and the isopropylidene compounds 4c and 6c, decompose in solution above -20°C with evo- lution of molecular nitrogen and ring enlargement to afford the piperazine derivatives 9 and 11, respectively. Formation of 9 is interpreted in terms of a sequence involving cycli- sation of 5a to produce the labile spirocyclic [3 + 21 cyclo- adduct 8a and its subsequent ring opening to yield the zwit- terion 10 which loses nitrogen with concomitant ring ex- pansion via 1,2 nitrogen shift. In a side reaction, the inter- mediate [3 + 21 cycloadduct derived from 7a undergoes

[3 + 21 cycloreversion to furnish the N-sulphonylimine 13 and 2-diazopropane (14a)['*I.

Me +

NS -Me I 0,

5a Me 9

- I 0,T-Me

Me Me Me Me

8a (R3 = MeSOJ

-

10

Surprisingly, heating in boiling [D,]acetonitrile for ex- tended periods of time is required to bring about decompo- sition of the zwitterions 7c and d. Monitoring the conver- sion by proton spectroscopy revealed three different path- ways: (i) ring expansion to afford the expected quinoxaline derivatives l l b and c, respectively, (ii) [3 + 21 cycloreversion of intermediate spirocyclic [3 + 21 cycloadducts to yield the N-sulphonylimine 13 and diazo compounds 14b, c, which decompose further under the reaction conditions, and (iii) formation of the benzimidazolium ions 12b and c, which were identified by comparison of their proton spectra with those recorded for authentic samples. These pathways were followed by 7c in a ratio of 29:27:44 and by 7d in a ratio of 20:55:25. Flash chromatography of the products of pre- parative experiments allowed us to isolate the pure com- pounds (l lb, c, 13) in moderate yields.

While the first two routes could be anticipated on the basis of previous decomposition of the zwitterions 712, d to yield the benzimidazolium ions 12b, cL9] is novel. A straightforward interpretation of this process rests on the assumption that formation of the zwitterions 7c, d is revers- ible in boiling [D3]acetonitrile. Thus, besides methanesul- phony1 azide, the alkylidenedihydrobenzimidazoles 6b and c are generated and subsequently trapped by a proton source. We note that 12b and c did not incorporate deu- terium from the solvent.

Formation of a zwitterion from a 1,3-dipole and a di- polarophile, and, subsequently, of a [3 + 21 cycloadduct does not a priori constitute evidence for a nonconcerted (two-step) 1,3-dipolar cycloaddition because the zwitterion may end in a side-track and revert to the reactants which yield the cycloadduct by the conventional concerted mech- anismL2I. In fact, reversibility of formation was invoked for the thermally rather stable zwitterions 7c and d in the fore- going paragraph. On the other hand, reversibility could be disproved for the labile zwitterion 7a as follows. Addition of deuterated methanesulphonyl azide ([D3]2a) to the iso-

Liebigs Ann. 1996, 155 1 - 1558 1553

FULL PAPER H. Quast et al.

l lb, lZb,14b

l lc , 12c. 14c

propylidene compound 6a at low temperatures furnished the deuterated zwitterion [D3]7a. This was isolated at -20 "C and allowed to decompose at higher temperatures in the presence of twenty equivalents of nondeuterated methanesulphonyl azide. The products [D,]lla and [D3]13a (4: 1) were separated and purified by flash chromatography. Careful examination of the proton spectra of [D3]lla in- volving comparison with the downfield I3C satellite of an N-methyl signal and with the signal of the CHD2S02 group showed incorporation of less than 0.1 %, if any, of a methyl- sulphonyl group from the added methanesulphonyl azide (Figure 2). Therefore, we conclude that cyclisation of the zwitterion 7a is much faster than the hypothetical cleavage into its components 2a and 6a and hence 7a is a true inter- mediate of a two-step 1,3-dipolar cycloaddition reaction.

\

13 14

Me H Me -k \ ) c N 2

rBu H R2

Me mHH I

R' \ Me

R2=H Me R'

\ la, c, d

6b'c I H +

11 12b, c

P

Discussion

On the basis of the results of the present and the forego- ing w ~ r k [ ~ ~ ' ~ ~ ' ~ ] , a generalised picture can be drawn regard- ing the formation and reactivity of zwitterions that may re- sult from cyclic ketene N X-acetals and electrophilic azides. Zwitterions are obtained only from those cyclic ketene N X - acetals that range at the top of the scale of nucleophilic- ity['], i.e. ketene NN-acetals. Less nucleophilic ketene N X - acetals, e.g. X = S, 0, do not yield zwitterions observable by NMR spectroscopy at low temperatures, but furnish products that are derived from intermediate [3 + 21 cyclo- a d d u c t ~ [ ' ~ ~ ' ~ ] . The high nucleophilic reactivity of cyclic ke- tene NN-acetals is paralleled by the perfect resonance stabilisation of the cationic moiety of the resulting zwit- terions. Thus, delocalisation of the opposite charges is the predominant reason for the existence of the zwitterions.

Me-S-N, (20 equiv.) / ,": Me

The reactions of the zwitterions 3, 5, and 7 that are ob- tained from sulphonyl azides are quite simple. According to the nature of the substituents R' and R2 at the a-carbon atom (see below) the zwitterions may revert to the compo- nents and/or cyclise to afford highly unstable spirocyclic compounds of type 8 and 15. The latter process is the se- cond step of a nonconcerted 1,3-dipolar cycloaddition reac- tion. The unstable spirocyclic [3 + 21 cycloadducts may un- dergo [3 + 21 cycloreversion into N-sulphonylimines and diazo compounds, e.g. 13 and 14, or ring opening to yield a second type of zwitterions, e.g. 8a -+ 10, which loses mo- lecular nitrogen with simultaneous ring expansion by a 1,2 nitrogen shift (10 + 9).

The nature of the substituents R' and R2 at the a-carbon atom of the zwitterions 3, 5, and 7 determines their thermal stability in the first place. Those with two geminal methyl groups (R' = R2 = Me), namely 3aL4], 5a, and 7a cyclise rapidly below 0 "C and decompose into the components very little (3a: 7%L41) or not at all (7a). On the other hand, a tert-butyl group at the a-carbon atom (R' = tBu) as in 3d, e[4.51, f['], 5d, and 7d dramatically enhances thermal stability. At the high temperature (boiling acetonitrile) re- quired for the still slow cyclisation of these zwitterions, their reversion to the components, azide and ketene NN-acetals, becomes competitive. It is tempting to attribute these effects to the bulk of the tert-butyl groupr41. Surprisingly, however, the zwitterion 7c, which possesses a methyl group (R' = Me) instead of the tert-butyl group in 7d, behaves in the same way as 7d and is only slightly less stable. Therefore, the bulk of the tert-butyl group cannot be the main reason

1554 Liebigs Ann. 1996, 1551-1558

Zwitterions as Intermediates in 1,3-Dipolar Cycloadditions FULL PAPER for the observed thermal stability. On the other hand, the strong propensity for cyclisation of the zwitterions with a pair of geminal methyl groups, 5a and 7a, appears as yet another example of the long-known steric promotion of ring formation[l41.

Figure 2. Proton spectra (200 MHz) recorded for solutions of the iminoquinoxalines [D3]lla (top) and l l a (bottom). The signals of the aromatic protons have been omitted. From the expanded parts, the isotopic purity of the S02CD3 groups may be estimated by comparison of the SOzCHDz signal with the down-field carbon-13 satellite of the N(3)-Me signal. The lower part was obtained from [D,]lla that was prepared by thermolysis of [D3]7a in the presence

of methanesulphonyl azide (2a) (20 equivalents).

H~CSOT NMe 13C satellite

d 13c satellite

J J L . 1

I M e

We thank Mrs. E. Ruckdeschel and Dr. D. Scheutzow for re- cording NMR spectra and Dr. G Lunge and Mr. E Dudrich for measuring the mass spectra. Financial support by the Fonds der Chemischen Zndustrie, Frankfurt am Main, is gratefully acknowl- edged. S. I. thanks particularly the Deutsche Akudemische Aus- tauschdienst (DAAD), for a generous stipend.

Experimental Yields, melting points and IR data: Table 1. - 'H NMR: Table

3. - I3C NMR: Table 4. - Molecular formulae, masses and ele- mental analyses: Table 5. - Melting points: Apparatus from C. Reichert, Vienna, or Biichi, Flawil, Switzerland. - 'H and 13C NMR: Bruker AC 200 and AC 250. - IR: Perkin-Elmer 1420. - MS (70 eV): Finnigan MAT 8200. - TLC: Aluminium sheets with silica gel 60 F254 equipped with a concentrating zone (Merck). - Flash chromatography: (30 X 2.5)cm or (40 X 4)cm glass columns with silica gel 32-63 pm (ICN Biomedicals), UV detector Knauer 87.00 (h = 254 nm), 1.8 bar N1. - HPLC: Waters M-6000A equipped with UV detector 440 (h = 254 nm) and differential re-

fractometer R401, (250 X 4.6) mm steel column with silica gel LiChrosorb Si60, 5 pm (Knauer). - Toluene and acetonitrile were distilled from calcium hydride. [D,]Acetonitrile and [Ds]toluene were dried with calcium hydride. - Experiments with ketene N N - acetals were carried out in dry solvents under argon (99.998%). - The following compounds were prepared as described: 2a[l2l, f1I51, 4a, c, 6a, cL91.

Table 3. Chemical shifts (6 values) in proton spectra of the zwitter- ions 5 and 7. If not stated otherwise, single numbers stem from

singlets

Cgd. Me$ NMe R3 Ring-H(4 H) la' 5a 1.54 3.01 2.79 (Me) 3.49 3.68 [b] A [C]

5b 1.56 2.96 SSO(2H) 3.65 D (broadened s)

7a 1.80 3.87 2.44 (Me) 7.55 7.68 [dl A I4 7b 1.86 4.06 8.25 (2 H) 8.03 7.66 Id] D

M d H

7c 1.88 5.20 4.06 2.87(Me) 7.56 T 3J= 7.5 Hz

tBu--CH

5d 1.20 4.03 2.98 3.08 (Me) 3.6-3.9 T 3.21

3.13

3.08

4.08

4.03

4.04

1.16 4.06 2.91 2.77(Me) 3.4-3.9 A

5e 1.13 4.21 2.82 8.52 (2 H) 3.4-4.0 D

7d 1.24 4.88 3.92 2.84 (Me) 7.4-7.7 T

1.22 4.79 3.85 2.47(Me) 7.5 -7.9 A

7e 1.19 4.98 3.82 8.36(2H) 7.5-8.1 D

[a] Solvents: A = [D3]acetonitrile, D = [D6]dimethyl sulphoxide, T = [D]trichloromethane. - b] Centres of an AA'BB' spectrum. - ['I The spectrum was recorded at - 15 "C. - Id] Centres of an AA'XX' spectrum.

2-Ethyl-1H-benzimiduzole: A mixture of 2-aminoaniline (109.5 g , 1.01 mol), propanoic acid (148.2 g, 2.02 mol), and 3 drops of conc. sulphuric acid was heated for 4 h. The temp. of the mixture was raised gradually from 125 to 200 "C, and water was allowed to dis- till. After cooling, the solid product was washed with a sat. aq. solution of KHC03 and water until the washings were neutral. Recrystallisation of the crude product from ethanol/water (3: 1) gave colourless needles (117.7 g, 8O%), m.p. 176-178°C (m.p.

2-Ethyl-I,3-dimethylbenzimiduzolium Tetrujluoroborute (12b, X = BF4): Dimethyl sulphate (68.6 g , 0.54 mol) was added dropwise to a stirred suspension of NaHCO, (54.8 g , 0.65 mol) and 2-ethyl- 1 H-benzimidazole (3 1.8 g , 0.22 mol) in water (150 ml)[171. The mix- ture was stirred for 14 h and the solid removed by filtration. A sat. aq. solution of NaBF, (100 ml), acidified with 3 drops of aq. HBF4 (50%), was added dropwise to the filtrate to afford colourless crys- tals, 42.4 g (74%). Recrystallisation of crude product from ethanol/ water (1O:l) furnished colourless plates (31.7 g , 56%), m.p.

Et), 3.96 (2 NMe), 7.64, 7.78 (AA'BB', 4 Ar-H). - I3C NMR (CD,CN): 6 = 11.0, 18.3 (Et), 32.5 (NMe), 113.7, 127.4 (ring CH), 132.9 (quat. C), 156.0 (C=N).

2-Ethylidene-2,3-dihydro-l,3-dirnethyl-lH-benzin~idazole (6b): A suspension of powdered 12b, X = BF4 (6.40 g, 24.4 mmol) and sodium hydride (0.84 g , 37.6 mmol) in tetrahydrofuran (25 ml) was

177-178"C"61).

173-175°C. - 'H NMR (CD3CN): 6 = 1.35, 3.22 ( 3 J = 7.7 Hz,

Liebigs Ann. 1996, 155 1 - 1558 1555

FULL PAPER H. Quast et al.

Table 4. Chemical shifts (6 values) in carbon-13 spectra of the zwit- terions 5 and 7

Cpd. Me, C NMe S0,Me Ring carbon atoms la'

CH? CH qMt.C C-2 5a 23.8 60.5 37.6 39.6 52.0 172.2 A [bl 5b 23.7 60.3 35.9 51.0 122.4 131.7 169.0 D

139.7 145.5

7a 24.8 60.4 34.7 38.9 112.6 132.5 158.4 Arb] 126.2

7b 27.0 65.8 34.8 112.9 130.0 155.8 D 122.0 132.0 126.3 139.3

147.7

Me-CH

7c 17.6 50.4 32.5 38.7 112.0 131.5 155.5 T 126.4

Me, C 4 H

5d 27.7 35.8 64.7 36.0 38.4 50.2 169.4 T

5e 27.0 36.9 64.0 34.7 49.74 122.3 132.3 165.2 D 37.2 51.2

36.0 50.01 140.0 145.9

7d 27.9 37.4 64.4 33.0 38.5 111.99 131.9 154.4 T 34.9 112.31

126.41 126.62

7e 27.3 38.1 64.4 33.0 112.78 131.68 151.9 D 34.6 113.19 132.00

122.4 132.8 125.97 140.1 126.20 146.0

[.'I Solvents: A = [D,]acetonitrile, D = [D6]dimethyl sulphoxide, T = [D]trichloromethane. - Ih] The spectrum was recorded at -15°C.

Table 5. Molecular formulae and masses, and elemental analyses ~~

Cpd. Molecular Elemental Analysis

Formula Mass C H N 5b Cl,H18Ns0, 394.3 Calcd. 42.64 4.60 28.42

Found 42.99 4.74 28.24 5d C,iH,3N,0,S 287.4 Calcd. 45.65 8.01 24.20

Found 45.74 8.26 23.91 5e Cl6H,,N8O, 422.4 Calcd. 45.50 5.25 26.53

Found 45.44 5.51 26.60 7b CI8Hl8N8O6 442.4 Calcd. 48.87 4.10 25.33

Found 49.04 4.21 25.63 7c CI,Hl7N,O2S 295.4 Calcd. 48.80 5.80 23.71

Found 49.05 5.77 23.83 7d C,,H,,N,O,S 337.4 Calcd. 53.39 6.87 20.75

Found 53.56 6.97 20.99 7e C,,H,,N8O6 470.4 Calcd. 51.06 4.71 23.82

Found 51.37 4.71 23.59 I l b C,,H,,N30,S 267.4 Calcd. 53.91 6.41 15.72

Found 53.97 6.28 15.73 l l c Cl,H,3N30,S 309.4 Calcd. 58.23 7.49 13.58

Found 58.26 7.58 13.34 12b CIOHi,BF4N2 262.0 Calcd. 50.42 5.77 10.69

(X = BF,) Found 50.55 5.74 10.57

stirred under argon in an 80-1111 centrifuge tube, equipped with a septum, until the gas evolution had ceased (24 h). The solid precipi- tate was removed under argon with the help of a centrifuge and washed with tetrahydrofuran ( 5 ml). The solvent and the crude product were distilled in vacuo to afford a colourless low-melting solid (3.15 g, 74'%,), m.p. 51-53"C, b.p. 95-10OoC/0.15 Torr. - ' H NMR (C6D6): 6 = 1.95 (d, ' J = 7.1 Hz, CHMe), 2.51, 2.91 (2

NMe), 3.19 (q, ,J = 7.1 Hz, CH), 6.2-6.9 (4 Ar-H). - I3C NMR (C6D6): 6 = 11.0 (CHMe), 28.6, 32.7 (NMe), 59.9 (CH), 103.1, 104.2, 118.5, 119.7 (ring CH), 136.7, 137.7 (quat. C), 147.9 (C-2).

[D~]Methanesulphonyl chloride was prepared according to a known procedure[l8I from sodium thiosulphate pentahydrate (16.4 g, 66 mmol), [D3]iodomethane (9.00 g, 62 mmol), and chlorine. Colourless liquid (4.93 g, 68'%), b.p. 59-6OoC/20 Torr (42%[18], b.p. 65.5 "U24.5 - 25.5 T ~ r r [ ' ~ ] ) .

(D3]Methanesulphonyl azide ([D3]2a) was prepared according to the procedure described for 2a[l2] from [D3]methanesulphonyl chloride (5.88 g, 50 mmol) and sodium azide (6.50 g, 100 mmol) in acetonitrile (25 ml). Colourless liquid (5.58 g, 90%), b.p. 37-38"C/0.1 Torr. The isotopic purity was >98% as estimated from the proton spectrum recorded for a solution of [D,]7c, pre- pared from [D,]2a and 6b. - IR (neat liquid): P = 2280, 2270 (CD,), 2150 (N3), 1359 (SO,), 1198, 1166 cm-' (SO,). - 'H NMR (CD3CN): 6 = 3.31 (quint, 2JHD = 2.1 Hz, CHD,).

1-[1-(4,5-Dihydro-1,3-dimethylimidazol-2-ylio j-l-methylethyl]-3- (ineth~~lsulphony1)triuzenide (5a): A solution of 4a (31 mg, 0.22 mmol) in [D,]acetonitrile, contained in an NMR sample tube under NZ, was cooled with liquid N,. A small amount of [D3]acetonitrile was placed on top of the solid followed by 2a (27 mg, 0.22 mmol). The mixture was allowed to warm to -30°C and briefly shaken. The resulting solution contained only 5a at -20°C ('H and I3C NMR), only 9 after warming to room temp.

1-(1- (1,3- Dimethylbenzimidazol-2-ylio) - I -methylethyl]-3- (meth- ylsulphonylltriarenide (7a) was prepared from 6a as described for 5a. The solutions contained only 7a at -20°C ('H and 13C NMR), only l l a and 13 (4:l) after warming to room temp.

Zivitterions 5b, d, e and 7b-e. - General Procedure: 2a (0.62 g, 5.1 mmol) or a solution of 2f (0.83 g, 5.1 mmol) in toluene (5 ml) was added dropwise to stirred solutions of 4 or 6 (5 mmol) in tolu- ene (5 ml) under N2 at - 10°C. The mixture was stirred at 0-5°C for 0.5 h. The precipitates were filtered and washed with pentane.

I- f I-(4,5-Dihydro-1,3-dimethylimidazol-2-ylio)-l-methylethyl]-3- (2,4,6-~rinitrophenyl) triazenide (5b): From 2f and 4a. Red powder (1.44 g, 73%), m.p. 136- 138°C (dec.). Recrystallisation from dichloromethane/ether at -20 "C yielded red scales.

I - f 1 - (4,5-Dihydro-l,3-dimethylimiduzol-2-ylio) -2,2-dimethyl- propyl]-3-(methyl.~ulphonylj triazenide (5d): From 2a and 4c. Colourless powder (1.37 g, 95%), m.p. 140-144°C (dec.). Recrystallisation from 2-propanol yielded colourless needles (1.01 g, 70%).

1 -(I - (4.5- Dihydro-l,3-dimethylimiduzol-2-ylio j -2,2-dimethyl- propyl]-3-(2,4,6-trinitrophenyl) triazenide (5e): From 2f and 4c. Red powder ( I .77 g, 84%), m.p. 157- 159 "C (dec.). Recrystallisation from dichloromethane/ether at -20 "C yielded red scales.

1 - f 1 - (l,3-Dimethylbenzimidazol-2-yEio) -1 -methylethyl]-3-(2,4,6- trinitropheny1)triazenide (7b): From 2f and 6a. Red powder (2.04 g, 92%), m.p. 155- 158 "C (dec.). Recrystallisation from methanol at -20°C yielded red scales.

1-(I - (1,3-Dimethylbenzimidazol-2-ylio j ethyl]-3- (methyl- sulphonyljtriazenide (7c): From 2a and 6b. White powder (1.28 g, 88%), m.p. 144-145°C (dec.).

I -I!- (I ,3-Dimethylbenzimidazol-2-ylio j -2,2-dimethylpropyl1-3- (methylsulphonylj triazenide (7d): From 2a and 6c. Colourless pow- der (1.65 g, 98%), m.p. 140-145 "C (dec.). Recrystallisation from methanollethedpentane (1 :2:3) at -20 "C yielded colourless prisms.

1556 Liebigs Ann. 1996, 155 1 - 1558

Zwitterions as Intermediates in 1 ,S-Dipolar Cycloadditions FULL PAPER I - [ I - (1,3- Dimethylbenzimidazol-2-ylio) -2,2-dimethyIpropylj-3-

(2,4,6-trinitrophenyI) triazenide (7e): From 2f and 6c. Dark, brown powder (1.93 g, 82%), m.p. 119- 121 "C (dec.). Recrystallisation from dichloromethane/ether at -20 "C yielded orange-coloured s c a 1 e s .

Synthesis and Thermolysis of [D3]7a. - a) A solution of [D3]2a (12 mg, 0.1 mmol) in [Dx]toluene (0.3 ml) cooled to -30°C was added to a solution of 6a (19 mg, 0.1 mmol) in [D,]toluene (0.3 ml), contained in an NMR sample tube under argon at -78°C. The mixture was placed into a bath of -30°C for 1 h. The colour- less precipitate ([D3]7a) was collected with the help of a centrifuge at -2O"C, washed with cold [Dx]toluene (0.3 ml, -3O"C), and dis- solved in cold [Dltrichloromethane (0.4 ml, -30°C). A cold solu- tion of 2a (242 mg, 2.0 mmol) in [Dltrichloromethane (0.4 ml, -30°C) was added. The mixture was allowed to warm to 0°C within 12 h to afford [D3]lla and [D3]13 (4:1, 'H NMR). Flash chromatography with petroleum ether (50-7OoC)/ethyl acetate ( I : ] ) gave [D3]lla (16 mg, 55%) as colourless powder, m.p. 129- 132°C. Recrystallisation from ethanol (1 ml) yielded colour- less prisms, m.p. 131-132°C ( l l a : m.p. 131-132"C[121). The iso- topic purity was >98'l/0. A proton signal, which might be attributed to the presence of tiny amounts of l l a , was significantly lower than the down-field I3C satellite of the N(3)-Me signal of [D,]lla (<O. 1 %I, 'H NMR, Figure 2). b) An experiment was performed as described under a) except that 2a was omitted. Recrystallisation of the product, obtained after flash chromatography, from ethanol yielded [D3]11a as colourless prisms (12 mg, 42%), m.p. 131-132°C. The isotopic purity was >98% ('H NMR, Figure 2).

Thermolysis of 7c. - a) A suspension of 7c (0.50 g, 1.7 mmol) in acetonitrile ( 5 ml) was heated under reflux until the evolution of gas had subsided ( 5 h). Flash chromatography of the reaction mix- ture with ethyl acetate gave l l b (0.11 g, 25%) as a gray powder, m.p. 133-137"C, and 13 (0.10 g, 250/), as a white powder, m.p. 204-205 "C. The crude products were recrystallised from ethanol to afford l l b as colourless crystals, m.p. 136-13S°C, and 13 as colourless crystals, m.p. 204-205 "C (m.p. 206-208 oC[12]). l lb , 'H NMR (CDC13): 6 = 1.15 (d, 3J = 6.7 Hz, CHMe), 2.89, 3.47 (2 NMe), 3.11 (SO,Me), 5.18 (q, ,5= 6.7 Hz, CH), 6.6-7.2 (4 Ar-H). - I3C NMR (CDC13): 6 = 10.7 (CHMe), 32.5, 35.5 (NMe), 43.6 (SO,Me), 55.7, 113.1, 115.7, 119.0, 125.4 (ring CH), 128.8, 137.0 (quat. C), 162.1 (C=N). - MS, mlz (YO): 267 (19) [M+], 252 (6) [M+ - Me], 189 (13), 188 (100) [M+ - S02Me], 173 (36), 158 (9), 147 (27), 133 (13). b) A degassed solution of 7c (50 mg, 0.1 5 mmol) in [D3]acetonitrile (0.8 ml) contained in an evacuated, flame-sealed NMR sample tube was heated at 80°C. The conversion was monitored by proton spec- troscopy until 7c had disappeared ( 5 h). Thereupon the proton spectrum indicated the presence of l lb , 12b, and 13 (29:44:27) be- sides small amounts of unidentified products.

Thermolysis of 7d. - a) A solution of 7d (1.5 g, 4.5 mmol) in acetonitrile (10 ml) was heated under reflux for 48 h. Flash chroma- tography of the reaction mixture with ethyl acetate gave l l c (0.19 g, 14%1), m.p. 162-167"C, and 13 (0.20 g, 190/), m.p. 200-205°C. Recrystallisation from ethanol afforded l l c as colourless crystals, m.p. 164-168"C, and 13 as colourless crystals, m.p. 203-205°C (m.p. 206-208 0C[12]). l l c , IH NMR (CD3CN): 6 = 0.84 (tBu), 2.97, 3.51 (2 NMe), 3.14 (S02Me), 5.24 (CH), 6.7-7.2 (4 Ar-H). - I3C NMR (CD,CN): 6 = 28.9, 40.97 (tBu), 33.6, 41.65 (NMe), 44.8 (S02Me), 66.2, 113.6, 117.1, 118.4, 126.1 (ring CH), 131.3, 139.2 (quat. C), 156.8 (C=N). - MS m/z (%I): 309 (11) [M+], 253 (19), 252 (100) [M+ - tBu], 174 (53), 173 (74), 158 (16), 147 (24), 133 (17).

b) A degassed solution of 7d (50 mg, 0.15 mmol) in [D3]acetonitrile (0.8 ml) contained in an evacuated flame-sealed NMR sample tube was heated at 80°C. The conversion was monitored by proton spec- troscopy until 7d had disappeared (48 h). Thereupon the proton spectrum indicated the presence of l l c , 12~1'1, and 13 (20:25:55) besides small amounts of unidentified products.

An X-Ray Dgfruction Analysis of 7d was performed from a transparent, colourless crystal. The cell parameters were deter- mined on the basis of 50 reflections. The number of reflections reported in Table 6 was obtained with Mo-K, radiation and 20,,, = 5 5 (graphite monochromator, Wyckoff scan). Measure- ments were carried out with the system Nicolet R3dV. The pro- gramme SHELXTL-PLUSI2'I was employed. The structure was solved by direct methods and refined anisotropically by the least- squares method. The weighting scheme for R,v is 1/02 (fl . The posi- tions of hydrogen atoms were calculated and included in the refine- ments with isotropic description[2i].

Table 6. Experimentals details and results of the X-ray diffraction analysis of zwitterion 7d

Molecular formula Cl,H23N502S, molecular mass 337.44. - Crystal system: monoclinic, space group P2,ln. - u = 1.1553(2), b = 1.4343(3), c = 1.1260(2) nm, p = 111.88(1)O, V = 1.7317(5) nm3, Z = 4, d(ca1cd.) = 1.294 g cm-3. - Size ofthe crystal: 1.0 x 1.1 x 0.7 mm. - Range: h = 0 - 15, k = 0 - 18,1= -14 - 13. Number of measured reflections: 4353, symmetry-independent reflections: 4002, observed reflections F > 3 4 0 : 3575. - Linear absorption coefficient: 0.19 mm-I. Absorption correction: y-scan. - Ratio FOb,,/parameters = 0.058. - R = 0.048, R, = 0.047. - Maximum and minimum of the remaining electron density in the fmal differential Fourier synthesis: Ap,,, = 0.24, Apmi, = - 0.31 eA-3

Dedicated to Professor Gunter Szeimies on the occasion of his 60th birthday. The results are taken from the dissertation by M. Ach, Univer- sity of Wiirzburg, 1992, and the projected dissertation by S. Ivanova, University of Wiirzburg. R. Huisgen in 1,3-DipoIar Cycloaddition Chemistry (Ed.: A. Padwa), 1st ed., vol. I , Wiley, New York, 1984, p. 1 - 176. R. Huisgen, G. Mloston, E. Langhals, J Am. Chem. SOC. 1986, 108, 6401-6402; J Org. Chem. 1986, 51, 4085-4087; R. Huis- gen, E. Langhals, H. Noth, Tetrahedron Lett. 1986, 27, 5475-5478; G. Mloston, E. Langhals, R. Huisgen, ibid. 1989, 30, 5373-5376; R. Huisgen in Advances in Cycloaddition (Ed.: D. P. Curran), vol. 1, JAI Press, London, 1988, p. 1-31. H. Ouast. D. Rennat. E.-M. Peters. K. Peters. H. G. von Schne- ringYAngew Ch& 1990, 102, 124-7261; Angel$ Chem Int Ed Engl 1990,29, 695-697. D. Reenat. Dissertation. Universitv of Wurzbure. 1990. J. BaltYhasar, Diploma Thesis, UniGersity of WiiGburg, 1990. N. Kuhn, H. Bohnen, J. Kreutzberg, D. Blaser, R. Boese, J Chem. Soc., Chem. Commun. 1993, 1136-1137; N. Kuhn, H. Bohnen, D. Blaser, R. Boese, Chem. Beu. 1994,127, 1405- 1407. H. Gruseck, M. Heuschmann, Chem. Beu. 1987, 120, 2053-2064; Tetrahedron Lett. 1987, 23, 6027-6030. H. Ouast. M. Ach. M. K. Kindermann, P. Rademacher, M. Schindler, Chem. Be% 1993, 126, 503-516.

('"1 M. Ach, Dissertation, University of Wiirzburg, 1992. [ I l l A. J. Randall, C. H. Schwalbe, K. Vaughan, .I Chem. Soc., Per-

kin Trans. 2, 1984, 251-253; S. L. Edwards, J. S. Sherfinski, R. E. Marsh, J Am. Chem. Soc. 1974, 96, 2593-2597.

[ I 2 ] H. Quast, M. Ach, E.-M. Peters, K. Peters, H. G. von Schne- ring, Liebigs Ann. Chem. 1992, 1259-1269.

[I3 ] H. Quast, S. Ivanova, E.-M. Peters, K. Peters, H. G. von Schnering, Liebigs Ann. 1996, 1541 - 1549, preceding paper in this issue.

[I4 ] E. L. Eliel, S. H. Wilen, L. N. Mander, Stereochemlytry of Or- ganic Compounds, 1st ed., Wiley-Interscience, New York, 1994, p. 682-684; P. G. Sammes, D. J. Weller, Synthesis 1995,

[I5 ] E. Schrader, Bec Dtsch. Chem. Ges. 1917, 50, 777-778; K. J. Shea, J.-S. Kim, J Am. Chem. Soc. 1992, 114, 4846-4855.

1205- 1222.

Liebigs Ann. 1996, 1551 - 1558 1557

FULL PAPER H. Quast et al.

[ I 6 ] H. Tiefenthaler, W. Doerscheln, H. Goeth, Helv. Chim. Acta

[I7] H. Quast, E. Schmitt, Chem. Ber. 1968,101,4012-4014. [''I G. Toth, L. Toldy, J. Tamas, G. Zolyomi, Tetrahedron 1972,

[ I 9 ] K. Hanai, T. Okuda, Chem. Pharm. Bull. 1977, 25, 815-816. ['"I G. M. Sheldrick, University of Gottingen, unpublished results.

[*'I Further details of the crystal structure investigation are avail- able on request from the Fachinformationszentrum Karlsruhe, D-76344 Eggenstein-Leopoldshafen, on quoting the depository number CSD-404860, the names of the authors, and the jour-

[96 1481

1967, 50, 2244-2258.

28, 167-173. nal citation.

1558 Liebigs Ann. 1996, 1551-1558