HETEROCYCLES

Paper | Special issue | Vol. 84, No. 2, 2012, pp. 945-961
Received, 2nd July, 2011, Accepted, 17th August, 2011, Published online, 29th August, 2011.
DOI: 10.3987/COM-11-S(P)75

■ Reactivity of N-Alkylthiiranimines toward Simple Nucleophiles and Iso(thio)cyanates

Hildegard Nimmesgern, Ernst Schaumann,* and Gunadi Adiwidjaja

Institute of Organic Chemistry, Clausthal University of Technology, Leibnizstrasse 6, D-38678 Clausthal-Zellerfeld, Germany

Abstract

Hydrolysis of N-(1-dimethylcarbamoyl-1-methylethyl)-thiiranimines occurs with S-C(sp2) ring cleavage while attack of hydrochloric acid results in S-C(sp3) ring opening. The latter mode of ring opening is also observed in [3+2] cycloaddition reactions with iso(thio)cyanates where the heterocumulene reacts via the C-chalcogen bond; only a sterically less hindered isopropyl substituted thiiranimine adds to the C=N bond in isocyanates to yield 4-thiohydantoins. The cycloadducts give a variety of hydrolysis products, in particular imidazo[2,1-b]oxazoles and –thiazoles, oxazolones, and stable thietes. Insertion of a thiocarbonyl into an isopropyl CH bond is observed yielding an annulated cyclopropane unit.

INTRODUCTION
The study of small ring compounds has played an important role in the development of our understanding of reactivity and bonding in organic chemistry.1 In handling these systems, problems resulting from ring strain are less pronounced for sulfur-containing compounds because bonds to carbon are long and smaller angles are tolerated.2 So α-thiolactones can be isolated in contrast to their unstable oxygen congeners3 and, in contrast to the unknown oxiranimines,4 stable N-sulfonyl-thiiranimines (2) can be obtained from arenesulfonyl isothiocyanates (1) and diphenyldiazomethane (Scheme 1).4-6 A thiadiazoline as [3+2] cycloadduct can be assumed as intermediate and a thiadiazoline also allows access to a silyl substituted thiiranimine where the exocyclic nitrogen is part of an azine unit.7 In contrast to these “rational” methods, an unexpected route to thiiranimines 6 employs the reaction of thioketene S-oxides 3 with aminoazirines such as 4.8 The reaction is apparently initiated by a [3+2] cycloaddition of the sulfine unit in 3 to the C=N bond to give oxathiazolidines 5 as intermediates. This reactivity of S-oxides 3 is remarkable as non-cumulated sulfines only rarely react as 1,3-dipoles.9,10
So far, only the reactivity of sulfonyl derivatives 2 was probed. The uniform feature is ring-opening by cleavage of the S-C(sp3) bond.4 This is in line with a polarization as in diheterotrimethylenemethanes11 2A,B where the negative charge is efficiently stabilized by the electron-withdrawing sulfonyl group (Scheme 1). In contrast, in thiiranimines 6 the electronic effect of the carboxamido group is certainly negligent and so the N-substituent is of the alkyl type. This should lead to a different reaction behavior. This consideration marks the starting point of the present study.

RESULTS AND DISCUSSION
In contrast to thiiranimines 2, the bulky C-alkyl substituents in 6 prevent an uncatalyzed reaction with methanol, but hydrolytic ring-opening of 6 is achieved under catalysis by trifluoroacetic acid (Scheme 2). The spectroscopic data allow to assign structure 7 to the water addition product. Thus, ring opening occurs via primary attack of water at the imino carbon and leads to S-C(sp2) ring opening.
Aqueous hydrochloric acid and 6 give only trace amounts of 7, but mainly thiazolinones 9. This means that a nucleophilic attack of chloride on C-3 prevails in spite of the extreme steric screening of this carbon and then sulfur is the best possible leaving group leading to 8 as a result of S-C(sp3) bond cleavage formally as in thiiranimines 2.4 The nucleophilic thiol sulfur in 8 finally displaces the amino group to give recyclization product 9 (Scheme 2). The structure of 9a was unambiguously established by a singe-crystal X-ray study (Figure 1).12

N-Sulfonyl-thiiranimines 2 give [3+2] cycloadducts with enamines, ynamines, and aldehydes, but do not react with iso(thio)cyanates.4 In contrast, thiiranimines 6 proved unreactive toward ynamines, acetylene dicarboxylate, isonitriles, or tetracyanoethylene, but undergo a smooth reaction with isocyanates as well with isothiocyanates. Thus, the symmetrically substituted thiiranimines 6a,b react with sulfonylisocyanates 10a,b at 0 °C and with aryl isocyanates 10c,d on gentle warming to give 1:1 cycloadducts 11 (Scheme 3). This structure is derived from the spectroscopic data and from an X-ray investigation of 11a (Figure 2).13 So the isocyanates 10 show the unusual reaction across their carbonyl group.14 The same reaction behavior is seen for the very reactive sulfonylisocyanates 10e,f. However, here the exocyclic sulfonyl moiety is easily hydrolyzed on chromatographic work-up and so yields are low (starting from 10e) or cycloadducts 11h,i (starting from 10f) are only seen in the crude reaction mixture. Hydrolytic loss of the sulfonyl moiety leads to bicyclic compounds 12; apparently the initial product of hydrolysis is an imino compound (11 with R3 = H) which then attacks the exocyclic amide unit with extrusion of dimethylamine and cyclization (Scheme 3). This reaction pathway is substantiated by independent hydrolysis experiments with 11a,b to give 12a,b. Structure 12 is proven by the X-ray structural investigation of 12a (Figure 3).15 Under the more forcing conditions of half-concentrated hydrochloric acid, also the N-aryl-substituted oxazolin-4-thiones 11d,e can be hydrolyzed. These reaction conditions result in complete displacement of the exocyclic imino group by the oxo unit of 14 and by a transition from the dimethylcarbamoyl to a monosubstituted amide derived from the original isocyanate (Scheme 3). Here, we assume the intermediacy of 13 with a tetrahedral carbon resulting from attack of water on the imino carbon. The high density of heteroatoms again called for a single-crystal X-ray study which proved the structure of 14a (Figure 4).16

The sterically less hindered thiiranimine 6c gives two isomeric 1:1 cycloadducts with isocyanates 10. One and the only one starting from 10c is again a 2-imino-oxazolidine-4-thione 11 (Scheme 4). The second product is the corresponding product 15 of cycloaddition across the C=N bond of the isocyanate as finally confirmed by an X-ray study (Figure 5).17 It appears that due to the smaller substituent on C-5 of the five-membered ring Pitzer tension is reduced and allows the C-5 substituents to be accommodated next to the substituted ring nitrogen N1. However, a relatively long N1-C5 bond of 151.6 pm should be noted.

Acid-catalyzed hydrolysis of cycloadducts 11k,l with R2 = i-Pr should be expected to give again oxazolidinones 14. However, in striking contrast to expectation, the reaction mixture turns immediately orange and work-up leads to an orange-colored oil with a complex 1H-NMR spectrum. From this oil, colorless crystals can be isolated which allowed an X-ray structural investigation to reveal thiete structure 19a (Figure 6).18 Now the color of the oil can be explained by the thione unit in valence tautomer 18 (Scheme 4). We see here an amazing β-elimination involving an alkyl CH bond from 16 to 17 and then an enethione/thiete (18/19) equilibrium. Such equilibria have been seen before,19 but the present case is unusual as it involves the thiocarbonyl of a thioamide moiety other than the usual stabilization of thietes by aryl substituents. In previous studies, this type of thiete has only been invoked as an intermediate.20

The noteworthy generation of a thiete from the vicinal thione/isopropyl units in 11k,l motivated to search for the same effect in related structures such as in 15. But when 15c is treated with aqueous hydrochloric acid just as it had been done for 11k,l, there is no orange color at all. From the complex product mixture, a compound lacking the dimethylamino unit can be isolated. But the 13C NMR spectrum shows three quaternary aliphatic carbons which is not compatible with 18 or other compounds found earlier. The solution is again brought by an X-ray structural investigation (Figure 7).21 We are dealing with a tricyclic compound 21 where the original isopropyl group shows up as annulated cyclopropane (Scheme 5). Our rational is the unusual insertion of the thiocarbonyl group into the isopropyl CH bond to give intermediate 20. This may look like a light-induced process rather than acid-catalyzed,22 but in a control experiment the conversion of 15c into 21 could not be induced photochemically. The thiol in 20 finally attacks the amide unit, displaces the dimethylamino group and leads to formation of a γ-thiolactone.

Isothiocyanates are known to be less reactive than isocyanates,23 but cycloadduct formation with thiiranimines 6 is possible, though for 4-nitrophenyl isothiocyanate (22b) heating to 60 °C is required. After isocyanates 10 show the preference for cycloaddition across the C=O bond, it is no surprise that isothiocyanates also enter into the reaction via their C-chalcogen bond to give [3+2] cycloadducts 23 (Scheme 6). Structure assignment is suggested by the similarity of spectroscopic data, especially 13C NMR shifts, to those of isocyanate cycloadducts 11 (vide supra). In some cases trace amounts of hydrolysis products are detected and hydrolysis can also be induced deliberately. Thus, the action of hydrochloric acid on N-tosyl derivatives 23a-c yields bicycles 24a-c as suggested by the similarity of spectroscopic data with those of 12a,b and also the analogous reaction mechanism is invoked (cf. Scheme 3). Starting from 4-nitrophenyl derivatives 23d,e, products 25 are formed by analogy with hydrolysis products 14 and again an intermediate of type 13 is plausible.

CONCLUSION
Thiiranimines 6 with their alkyl type N-substituent show a widely different reaction pattern from their N-sulfonyl congeners 2 though except for the trifluoroacetic acid-catalyzed hydrolysis of 6 both types of thiiranimines enter into reactions via cleavage of the C(sp3)-S bond which is also the longest bond in the molecular structures.5,8 However, the contrasting reactivity toward iso(thio)cyanates demonstrates that N-sulfonyl-thiiranimines 2 are mainly electrophilic while the thiiranimines 6 of the present study are in the first place nucleophilic. Thus, a wealth of heterocyclic structures is provided by the cycloaddition reactions and the subsequent hydrolysis experiments. A limitation is the need for bulky substituents to make thioketene S-oxides 3 isolable and use them in the synthesis of 6. However, the different bond selectivity of 6a,b vs. 6c toward isocyanates shows that even with the presently possible substitution pattern different steric effects are seen. Moreover, it should not be underestimated that the bulky substituents certainly increase the stability of the products and e. g. may be crucial in the formation and stabilization of thietes 19 or to allow the highly unusual thermal insertion reaction in the formation of 21.

EXPERIMENTAL
Melting points were determined on a Leitz hot-stage microscope and are uncorrected. IR spectra were recorded as KBr pellets or for oils as films between NaCl plates on Perkin-Elmer instruments 257, 299, and 399. 1H- and 13C-NMR spectra were recorded on Bruker spectrometers WH 270 and WM 400 with TMS as internal reference at δ = 0.00 and using CDCl3 as solvent. For 13C-NMR spectra, only the significant shifts with δ > 50 are given for characterization and all are inactive in the DEPT mode (quaternary carbons). MS spectra were obtained with a Varian CH7 with ionization energy 70 eV. X-ray measurements were carried out using a single-crystal CAD 4 (Enraf-Nonius; Cu-Kα radiation) or a Hilger & Watts instrument (Mo-Kα radiation). Preparative TLC (layer ca. 2 mm) was performed using silica PF254 (Merck). Isolated products were recrystallized from dichloromethane/n-hexane or diethyl ether/n-hexane unless noted otherwise. Petroleum ether (PE) had boiling point range 60-70 °C. Thiiranimines 6 were synthesized as reported before.8 Isocyanates 10 were commercially available. Isothiocyanate 22a24 and 22b25 were obtained using literature procedures.

Trifluoroacetic Acid-catalyzed Hydrolysis of Thiiranimines 6a,b.
A suspension of 6 (1 mmol) in CF3COOH (1 mL) and H2O (10 mL) was stirred at rt for 5 h when TLC showed no more 6. The reaction mixture was extracted with CHCl3. The extract was shaken with sat. aq. NaHCO3 and dried (Na2SO4). The filtrate was concentrated in vacuo and the product purified by preparative TLC (PE/EtOAc 1:2 v/v) to give 7a (96%) and 7b (99%).
N,N,2-Trimethyl-2-(2,2,6,6-tetramethyl-1-thio-cyclohexanecarbonyl)aminopropionamide (7a): mp 132 °C; IR 3320, 2560, 1640, 1450, 1005 cm-1; 1H NMR δ 0.93, 1.28 (each s, 6H, ring-CMe2), 1.66 (s, 6H, CMe2), 1.77 (s, 1H, SH), 2.6-1.6 (br, 6H, 3 CH2), 3.06 (s, 6H, NMe2), 9.0 (br, 1H, NH); 13C NMR δ 57.7(C-NH), 70.8 (C-SH), 171.9 (C=O), 173.6 (C=O). Anal. Calcd for C17H32N2O2S; C, 62.14; H, 9.84; N, 8.53; S, 9.76. Found: C, 62.18; H, 9.77; N, 8.36; S, 9.69.
2-(1-tert-Butyl-2,2-dimethyl-1-thio-butyryl)amino-N,N-2-trimethylpropionamide (7b): mp 102 °C; IR 3300, 1630, 1400 - 1500 cm-1; 1H NMR δ 1.27 (s, 18H, t-Bu2), 1.65 (s, 6H, CMe2), 2.00 (s, 1H, SH), 3.06 (s, 6H, NMe2), 8.57 (br,1 H, NH); 13C NMR δ 57.5, 73.6 (C-SH), 171.0 , 173.5. Anal. Calcd for C16H32N2O2S; C, 60.70; H, 10.21; N, 8.85; S, 10.13. Found: C, 60.88; H, 10.01; N, 8.59; S, 9.86.

Hydrochloric Acid-catalyzed Hydrolysis of Thiiranimines 6a-c.
6 (1 mmol) in Et2O (5 mL) and 2 M HCl (2 mL) were mixed at rt. Control by TLC showed immediate reaction. The mixture was washed with sat. aq. NaHCO3 and dried (Na2SO4). After preparative TLC (PE/EtOAc 1:2 v/v) gave 9a (86%), 9b (50%), and 9c (85%).
2-(1-Chloro-2,2,6,6,-tetramethylcyclohexyl)-4,4-dimethyl-2-thiazolin-5-one (9a): mp 98 °C; IR 1700, 1600 cm-1; 1H NMR δ 1.08, 1.32, 1.42 (each s, 6H, CMe2), 2.63 – 1.63 (br, 6H, 3 CH2); 13C NMR δ 86.6, 91.1, 169.6 (C=N), 213.0 (C=O); MS m/z 273 (M+ - CO, 20), 237 (M+ - CO - HCl, 100). Anal. Calcd for C15H24ClNOS; C, 59.67; H, 8.03; N, 4.64; S, 10.64, Cl 11.74. Found: C, 59.43; H, 8.00; N, 4.55; S, 10.68, Cl 11.41.
2-(1-tert-Butyl-1-chloro-2,2-dimethylpropyl)-4,4-dimethyl-2-thiazolin-5-one (9b): mp 66 °C; IR 1700, 1600 cm-1; 1H NMR δ 1.32 (s, 18H, t-Bu2), 1.42 (s, 6H, ring-CMe2). Anal. Calcd for C14H24ClNOS; C, 58.00; H, 8.36; N, 4.83; S, 11.06, Cl 12.24. Found: C, 58.21; H, 8.31; N, 4.58; S, 10.56, Cl 12.12.
2-(1-Chloro-1-isopropyl-2,2-dimethylpropyl)-4,4-dimethyl-2-thiazolin-5-one (9c): oil; IR (film) 1710, 1600 cm-1; 1H NMR δ 1.01, 1.13 ( each d, J = 7 Hz, 6H, i-Pr), 1.20 (s, 9H, t-Bu), 1.38 (s, 6H, CMe2), 2.83 (septet, J = 7 Hz, 1H, i-Pr). Anal. Calcd for C13H22ClNOS; C, 56.60; H, 8.06; N, 5.08; S, 11.62, Cl 12.85. Found: C, 57.05; H, 8.46; N, 4.81; S, 11.40, Cl 12.72.

General Procedure for the Reaction of Thiiranimines 6 with Iso(thio)cyanates 10, 22.
6 (1 mmol) in dry Et2O (5 mL) or dry CHCl3 (5 mL) and 10 or 22 (1.1 mmol) were mixed at 0 °C. Sulfonyl iso(thio)cyanates reacted at this temperature, while aryl derivatives required gentle heating up to 60 °C in CHCl3. The reaction was monitored by TLC. In some cases, yellow crystals separated from the reaction mixture which were nevertheless purified by preparative TLC (PE/EtOAc 1:2 v/v) as were, after evaporation, the crude reaction mixtures. Solid products 11, 15, and 23 were further purified by recrystallization from PE/EtOAc. By chromatography of the N-sulfonyl derivatives of 11a-c, traces of hydrolysis products 12 or 14 were detected (vide infra); starting from chlorosulfonyl isocyanate (10e), considerable hydrolysis to 12a,b occurred and, starting from 10f, only products 12 were isolated. Also the reaction products from isothiocyanate 22a gave considerable hydrolysis to 24.
2-(6,6,10,10-Tetramethyl-4-thioxo-2-tosylimino-1-oxa-3-azaspiro[4,5]decan-3-yl)-N,N-2-trimethyl-propionamide (11a): yield 87% from 6a and 10a; mp 131 °C; IR 1655 (br) cm-1; 1H NMR δ 0.77, 1.22, (each s, 6H, CMe2), 1.52 (br s, 6H, (CH2)3), 1.83 (s, 6H, CMe2), 2.38 (s, 3H, Ar-Me), 2.83 (s, 6H, NMe2), 7.50 (mc, 4H, Ar); 13C NMR δ 67.9, 106.0, 126.9, 129.3, 139.1, 143.2, 156.9 (C=O), 169.7 (C=N), 202.9 (C=S). Anal. Calcd for C25H37N3O4S2; C, 59.14; H, 7.35; N, 8.28; S, 12.63. Found: C, 58.99; H, 7.37; N, 8.15; S, 12.47.
2-(5,5-Di-tert-butyl-4-thioxo-2-tosylimino-oxazolidin-3-yl)-N,N-2-trimethylpropionamide (11b): yield96% from 6b and 10a; mp 152-3 °C; IR 1640 (br) cm-1; 1H NMR δ 1.08 (s, 18 H, t-Bu2), 1.83 (s, 6H, CMe2), 2.35 (s, 3H, Ar-Me), 2.80 (s, 6H, NMe2), 7.43 (mc, 4H, Ar-Me); 13C NMR δ 68.1, 106.6, 126.8, 129.2, 138.9, 143.2, 157.4 (C=O), 169.8 (C=N), 204.6 (C=S). Anal. Calcd for C24H37N3O4S2; C, 58.15; H, 7.52; N, 8.48; S, 12.94. Found: C, 58.02; H, 7.65; N, 8.44; S, 12.66.
2-(2-Mesylimino-6,6,10,10-tetramethyl-4-thioxo-1-oxa-azaspiro[4,5]decan-3-yl)-N,N-2-trimethyl-propionamide (11c): yield 86% from 6a and 10b; mp 144 °C; IR 1640 (br) cm-1; 1H NMR δ 0.95, 1.32 (each s, 6H, CMe2), 1.15 (br, 6H, (CH2)3), 1.87 (s, 6H, CMe2), 2.90 (s, 6H, NMe2), 3.17 (s, 3H, Ms); 13C NMR δ 67.6, 105.9, 157.1 (C=O), 169.7 (C=N), 203 (C=S). Anal. Calcd for C19H33N3O4S2; C, 52.86; H, 7.72; N, 9.74; S 14.85. Found: C, 52.47; H, 8.02; N, 9.87; S, 14.98.
2-(6,6,10,10-Tetramethyl-2-p-nitrophenylimino-4-thioxo-1-oxa-3-azaspiro[4,5]decan-3-yl)-N,N-2-tri-methylpropionamide (11d): yield 98% from 6a and 10c; mp 129-130 °C; IR 1710, 1630, 1600, 1330, 1580 cm-1; 1H NMR δ 0.97, 1.30 (each s, 6H, CMe2), 1.60 (s, br, 6H, (CH2) 3), 2.00 (s, 6H, CMe2), 3.00 (s, 6H, NMe2), 7.70 (mc, 4H, Ar); 13C NMR δ 67.5, 102.00, 123.5, 124.6, 143.8, 150.6, 151.1 (C=O), 170.6 (C=N), 202.4 (C=S). Anal. Calcd for C24H34N4O4S; C, 60.74; H, 7.22; N, 11.80; S, 6.76. Found: C, 60.51; H, 7.64; N, 11.76; S, 6.87.
2-(5,5-Di-tert-butyl-2-phenylimino-4-thioxo-oxazolidin-3-yl)-N,N-2-trimethylpropionamide (11e): yield62% from 6b and 10d; mp 139 °C; IR 1695, 1640, 1580 cm-1; 1H NMR δ 1.22 (s, 18H, t-Bu2), 2.00 (s, 6H, CMe2), 2.90 (s, 6H, NMe2), 7.10 (s, 5H, Ph); 13C NMR δ 67.5, 102.4, 123.4, 123.9, 128.7, 144.2, 148.8 (C=O), 171.2 (C=N), 203.7 (C=S). Anal. Calcd for C23H35N3O2S; C, 66.14; H, 8.36; N, 10.06; S, 7.68. Found: C, 66.13; H, 8.20; N, 9.86; S, 8.08.
2-(3-Chlorosulfonylimino-6,6,10,10-tetramethyl-4-thioxo-1-oxa-3-azaspiro[4,5]-decan-3-yl)-N,N-2- trimethylpropionamide (11f): yield 59% from 6a and 10e; mp 92 °C; IR 1650, 1580, 1450, 1180 cm-1; 1H NMR δ 0.98, 1.32 (each s, 6H, CMe2), 1.70 (br, 6H, (CH2)3), 1.88 (s, 6H, CMe2), 2.91 (s, 6H, NMe2); 13C NMR δ 68.5, 108.7, 161.3 (C=O), 169.0 (C=N), 202.6 (C=S). Anal. Calcd for C18H30ClN3O4S2; C, 47.82; H, 6.70; N, 9.30; S, 14.18; Cl, 8.33. Found: C, 47.68; H, 6.52; N, 9.23; S, 14.05, Cl, 8.33.
2-(5,5-Di-tert-butyl-3-chlorosulfonylimino-4-thioxo-oxazolidin-3-yl)-N,N-2-trimethylpropionamide (11g): yield 16% from 6b and 10e; mp 99 °C; IR 1660, 1640, 1360, 1300 cm-1; 1H NMR δ 1.30 (s, 18H, t-Bu2), 1.95 (s, 6H, CMe2), 2.98 (s, 6H, NMe2). Anal. Calcd for C17H30ClN3O4S2; C, 46.40; H, 6.88; N, 9.55. Found: C, 46.68; H, 6.78; N, 5.57.
2-(5-tert-Butyl-5-isopropyl-2-mesylimino-4-thioxo-oxazolidin-3-yl)-N,N-2-trimethylpropionamide (11j): yield 34% from 6c and 10b; mp 105 °C; IR 1700, 1600 cm-1; 1H NMR δ 0.94, 1.18 (each d, J = 6 Hz, 6H, i-Pr), 1.18 (s, 9H, t-Bu), 1.88 (s, 6H, CMe2), 2.65 (sept, 1H, i-Pr), 2.92 (s, 6H, NMe2), 3.02 (s, 3H, Ms); 13C NMR δ 67.9, 106.07, 157.6 (C=O), 169.7 (C=N), 206.2 (C=S). Anal. Calcd for C17H31N3O4S2; C, 50.35; H, 7.70; N, 10.36; S, 15.81. Found: C, 50.03; H, 7.77; N, 10.27; S, 16.30.
2-(5-tert-Butyl-5-isopropyl-2-p-nitrophenylimino-4-thioxo-oxazolidin-3-yl)-N,N-2-trimethylpropion-amide (11k): yield 79% from 6c and 10c; mp 132 °C; IR 1690, 1650, 1600, 1580, 1330 cm-1; 1H NMR δ 0.93, 1.11 (each d, J = 6 Hz, 6H, i-Pr), 1.18 (s, 9H, t-Bu), 2.00 (s, 6H, CMe2), 2.70 (sept, 1H, i-Pr), 2.98 (s, 6H, NMe2), 7.60 (mc, 4H, Ar); 13C NMR δ 67.5, 103.4, 123.6, 124.5, 143.8, 150.7, 150.8 (C=O), 170.5 (C=N), 205.3 (C=S). Anal. Calcd for C22H32N4O4S; C, 58.89; H, 7.20; N, 12.49; S, 7.15. Found: C, 58.92; H, 7.41; N, 12.32; S, 7.40.
2-(5-tert-Butyl-5-isopropyl-2-phenylimino-4-thioxo-oxazolidin-3-yl)-N,N-2-trimethylpropionamide (11l): yield 59% from 6c and 10d, mp 144-145 °C; IR 1700, 1640, 1580 cm-1; 1H NMR δ 0.91, 1.11 (each d, J = 9 Hz, 6H, i-Pr), 1.17 (s, 9H, t-Bu), 2.00 (s, 6H, CMe2), 2.70 (sept, 1H, i-Pr), 2.95 (s, 6H, NMe2), 7.17 (s, 5H, Ph). Anal. Calcd for C22H33N3O2S; C, 65.47; N, 8.24; N, 10.41; S, 7.94. Found C, 65.66; H, 8.12; N, 10.15; S, 8.06.
2,2,5´,5´,6,6-Hexamethyl-3´-thioxo-3’H-spirocyclohexane-1,2´-(7´H)-imidazo[2,1-b]oxazol-6´(5’H)- one (12a): yield 8% from 6a and 10e, 47% from 6a and 10f; mp 135 °C; IR 1760, 1600, 1580, 1370, 1360 cm-1; 1H NMR δ 0.90, 1.20, 1.57, 1.60 (each s, 6H, CMe2 and Me2C(CH2) 3CMe2), ca. 1.7 (br, 6H, (CH2)3); 13C NMR δ 68.2, 116.0, 176.7, 190.5 (C=O, C=N), 194.8 (C=S); MS m/z 308 (M+, 43), 293 (M+ - Me, 18), 182 (54), 167 (100). Anal. Calcd for C16H24N2O2S; C, 62.29; H, 7.86; N, 9.08; S, 10.39. Found: C, 62.49; H,7.97; N, 9.65; S, 10.59.
2,2-Di-tert-butyl-2,3,5,6-tetrahydro-5,5-dimethyl-3-thioxo-imidazo[2,1-b]oxazol-6-one (12b): yield 44% from 6b and 10e, 25% from 6b and 10f; mp 95 °C; IR 1760, 1600, 1360, 850 cm-1; 1H NMR δ 1.27 (s, 18H, t-Bu2), 1.67 (s, 6H, CMe2); 13C NMR δ 68.3, 116.6, 177.3, 190.8 (C=O, C=N), 196.3 (C=S). Anal. Calcd for C15H24N2O2S; C, 60.77; H, 8.18; N, 9.45; S, 10.81. Found: C, 60.57; H, 8.34; N, 9.33; S, 10.51.
2-(5-tert-Butyl-5-isopropyl-2-oxo-4-thioxo-1-tosyl-imidazolidin-3-yl)-N,N-trimethylpropionamide (15a): yield 85% from 6a and 10a; mp 153-4 °C; IR 1750, 1675, 1600, 1275, 1170 cm-1; 1H NMR δ 1.08, 1.24 (each d, J = 5 Hz, 6H, i-Pr), 1.33 (s, 9H, t-Bu), 1.72, 1.80 (each s, 3H, CMe2), 2.43 (s, 3H, Ts), 2.70 (s, 6H, NMe2), 3.53 (m, 1H, i-Pr), 7.70 (mc, 4H, Ar); 13C NMR δ 66.4, 93.3, 128.9, 129.4, 130.5, 145.3, 154.2 (C=O), 170.6 (C=O), 201.7 (C=S). Anal. Calcd for C23H35N3O4S2; C, 57.35; H, 7.32; N, 8.72; S, 13.31. Found: C, 57.28; H, 7.32; N, 8.62; S, 13.35.
2-(5-tert-Butyl-5-isopropyl-1-mesyl-2-oxo-4-thioxo-imidazolidin-3-yl)-N,N-2-trimethylpropionamide (15b): yield 62% from 6c and 10b; mp 160-1 °C; IR 1740, 1630 cm-1; 1H NMR δ 1.23 (br, d, 6H, i-Pr), 1.87 (s, 6H, CMe2), 2.92 (s, 6H, NMe2), 3.52 (s, 3H, Ms); 13C NMR δ 66.9, 92.8, 155.9 (C=O), 170.5 (C=O), 203.1 (C=S). Anal. Calcd for C17H31N3O4S2; C, 50.35; H, 7.70; N, 10.36; S, 15.81. Found: C, 50.53; H, 8.03; N, 10.21; S, 15.43.
2-(5-tert-Butyl-5-isopropyl-2-oxo-1-phenyl-4-thioxo-imidazolidin-3-yl)-N,N-2-trimethylpropionamide(15c): yield 37% from 6c and 10d; mp 50 °C (decomp); IR 1730, 1650, 1590 cm-1; 1H NMR δ 1.2 (mc, 6H, i-Pr), 2.85, 2.92 (2s, br, 6H, CMe2), 2.95 (s, 6H, NMe2), 7.82 (s, 5H, Ph); 13C NMR δ 65.8, 100.2, 120.3, 124.7, 129.1, 137.2, 155.4 (C=O), 169.0, 208.4 (C=S). Anal. Calcd for C22H33N3O2S; C, 65.47; H, 8.24; N, 10.41; S, 7.94. Found: C, 65.66; H, 8.12; N, 10.15; S, 8.06.
2-(6,6,10,10-Tetramethyl-4-thioxo-2-tosylimino-1-thia-3-azaspiro[4,5]decan-3-yl)-N,N-2-trimethyl- propionamide (23a): yield 96% from 6a and 22a; mp 162 °C; IR 1640, 1550 cm-1; 1H NMR δ 0.9 – 2.0 (br, 12H), 1.25 (s, 6H, CMe2), 1.83 (s, 6H, CMe2), 2.43 (s, 3H, Ts), 2.78 (s, 6H, NMe2), 7.48 (mc, 4H, Ar); 13C NMR δ 71.5, 82.8, 126.9, 129.2, 137.0, 143.6, 169.0, 170.6 (C=O, C=N), 207.8 (C=S). Anal. Calcd for C25H37N3O3S3; C, 57.32; H, 7.14; N, 8.02; S 18.36,. Found: C, 57.38; H, 7.10; N, 7.80; S, 18.55.
2-(5,5-Di-tert-butyl-4-thioxo-2-tosylimino-thiazolidin-3-yl)-N,N-2-trimethylpropionamide (23b): yield94% from 6b and 22a; mp 146 °C; IR 1645, 1590 cm-1; 1H NMR δ 1.27 (s, 18H, t-Bu2), 1.87 (br, 6H, CMe2), 2.43 (s, 3H, Ts), 2.80 (s, 6H, NMe2), 7.53 (mc, 4H, Ar); 13C NMR δ 71.6, 85.0, 127.0, 129.2, 137.3, 143.6, 169.1 (C=O), 170.8 (C=N), 207.7 (C=S). Anal. Calcd for C24H37N3O3S3; C, 56.27; H, 7.30; N, 8.21; S, 18.79. Found: C, 56.19; H, 7.40; N, 8.00; S, 18.68.
2-(5-tert-Butyl-5-isopropyl-4-thioxo-2-tosylimino-thiazolidin-3-yl)-N,N-2-trimethylpropionamide (23c): yield 96% from 6c and 22a; mp 142 °C; IR 1640, 1550, 1600 cm-1; 1H NMR δ ca. 1.2 (br,mc, 6H, i-Pr), 1.22 (s, 9H, t-Bu), 2.42 (s, 3H, Ts), 2.80 (s, 6H, NMe2), 7.50 (mc, 4H, Ar); 13C NMR δ 71.2, 83.0, 127.0, 129.2, 137.0, 143.7, 168.7 (C=O), 170.6 (C=N), 210.9 (C=S). Anal. Calcd for C23H35N3O3S3; C, 55.50; H, 7.10; N, 8.44; S, 19.32. Found: C, 55.50; H, 7.29; N, 8.44; S, 19.54.
2-(6,6,10,10-Tetramethyl-2-p-nitrophenylimino-4-thioxo-1-thia-3-azaspiro[4,5]decan-3-yl)-N,N-2-tri-methylpropionamide (23d): yield 77% from 6a and 22b; mp 190 °C; IR 1640, 1590 cm-1; 1H NMR δ 0.87, 1.03, 1.20, 1.57 (each s, 3H, ring-Me2C), 1.67 (s, 6H, (CH2)3), 2.00 (s, 6H, CMe2), 2.97 (s, 6H, NMe2), 7.57 (mc, 4H, Ar); 13C NMR δ 70.7, 82.9, 121.1, 125.3, 144.4, 154.2, 158.3 (C=O), 171.7 (C=N), 207.0 (C=S). Anal. Calcd for C24H34N4O3S2; C, 58.74; H, 7.00; N, 11.42; S, 13.07. Found: C, 58.64; H, 7.16; N, 11.23; S, 12.80.
2-(5-tert-Butyl-5-isopropyl-2-p-nitrophenylimino-4-thioxo-thiazolidin-3-yl)-N,N-2-trimethylpropion-amide (23e): yield 55% from 6c and 22b; mp 158 °C; IR 1640, 1585 cm-1; 1H NMR δ 0.86, 1.08 (each d, J = 5 Hz, 6H, i-Pr), 1.20 (s, 9H, t-Bu), 2.00 and 2.10 (each s, br, 6H, CMe2), 3.00 (s, 6H, NMe2), 7.67 (mc, 4H, Ar); 13C NMR δ 70.4, 83.3, 121.1, 125.3, 144.4, 154.2, 158.3 (C=O), 171.7 (C=N), 209.6 (C=S). Anal. Calcd for C22H32N4O3S2; C, 56.86; H, 6.96; N, 12.06. Found: C, 56.83; H, 7.17; N, 11.76.

General Procedure for the Hydrochloric Acid-catalyzed Hydrolysis of Cycloadducts 11, 15, 23.
A compound 11, 15, or 23 including crude 11h,i (0.5 mmol) in CHCl3 (10 mL) and half-concentrated (5 M) aq. HCl (concd aq. HCl for 11k,l) were mixed at rt and kept at this temperature for up to 24 h while the progress of the reaction was monitored by TLC. If required, the reaction mixture was refluxed till TLC showed no more starting material. The reaction mixture was washed with sat. aq. NaHCO3, concentrated in vacuo and the crude product purified by preparative TLC (PE/EtOAc 1:2 v/v) to give the following products:
12a: yield 65% from 11a, 36% from 11c, 20% from 11d, 20% from 11f, 48% from 11h. Data see above.
12b: yield 68% from 11b, 60% from 11e, 20% from 11g, 20% from 11i. Data see above.
2-(6,6,10,10-Tetramethyl-2-oxo-4-thioxo-1-oxa-3-azaspiro[4,5]decan-3-yl)-2-methyl-N-(4-nitrophenyl)-propionamide (14a): yield 80% from 11d; mp 170 °C; IR 3400, 1770, 1700, 1600, 1590, 1530, 1500, 1340 cm-1; 1H NMR δ 1.00, 1.20 (each s, 6H, ring-Me2C), 1.60 (s, 6H, (CH2)3), 1.90 (s, 6H, CMe2), 7.73 (mc, 4H, Ar); 13C NMR δ 65.8, 100.0, 119.3, 125.0, 143.2, 143.8, 154.6 (C=O), 169.3 (C=O), 205.4 (C=S); MS m/z 447 (M+, 3), 310 (M+ - Ar-NH, 100), 266 (76). Anal. Calcd for C22H29N3O5S2; C, 59.03; H, 6.54; N, 9.39; S, 7.16. Found: C, 58.78; H, 6.47; N, 9.23; S, 7.20.
2-(5,5-Di-tert-butyl-2-oxo-4-thioxo-oxazolidin-3-yl)-2-methyl-N-phenylpropionamide (14b): yield 60% from 11e; mp 207 °C; IR 3300, 1800, 1640, 1600, 1345, 1290 cm-1; 1H NMR δ 1.20 (s, 18H, t-Bu2), 1.83 (s, 6H, CMe2), 7.13 (m, 5H, Ph); 13C NMR δ 65.7, 100.3, 120.3, 124.7, 129.1, 137.4, 155.4 (C=O), 169.1 (C=O), 206.5 (C=S). Anal. Calcd for C21H30N2O3S; C, 64.57; H, 7.84; N, 7.17; S, 8.21. Found: C, 63.62; H, 7.58; N, 6.94; S, 8.36.
1-(3-tert-Butyl-2,2-dimethyl-2H-thiet-4-yl)-5,5-dimethyl-3-phenyl-imidazolidine-2,4-dione (19a): yield 90% from 11k; mp 103 °C; IR 1770, 1720, 1635, 1600, 1350–1390 cm-1; 1H NMR δ 1.20 (s, 9H, t-Bu), 1.63, 1.84 (each s, 6H, CMe2), 7.40 (s, 5H, Ph); 13C NMR δ 55.0, 63.2, 121.0, 126.0, 128.1, 128.9, 131.6, 151.1, 152.1 (C=O), 174.7 (C=O); MS m/z 358 (M+, 94), 343 (M+ - Me, 68), 301 (M+ - t-Bu, 70), 196 (33), 139 (100). Anal. Calcd for C20H26N2O2S; C, 66.99; H, 7.32; N, 7.82; S, 8.94. Found: C, 67.10; H, 7.47; N, 7.76; S, 8.98.
1-(3-tert-Butyl-2,2-dimethyl-2H-thiet-4-yl)-5,5-dimethyl-3-(4-nitrophenyl)imidazolidine-2,4-dione (19b): yield 90% from 11l; mp 129 °C; IR 1780, 1740, 1640, 1620, 1600, 1520, 1380 cm-1; 1H NMR δ 1.20 (s, 9H, t-Bu), 1.67, 1.87 (each s, 6H, CMe2), 8.08 (mc, 4H, Ar); 13C NMR δ 55.3, 63.3, 120.5, 124.2, 125.8, 137.3, 146.4, 151.2, 151.7 (C=O), 174.1 (C=O); MS m/z 403 (M+, 84), 388 (M+ - Me, 78), 346 (M+ - t-Bu, 48), 196 (41), 139 (100). Anal. Calcd for C20H25N3O4S; C, 59.52; H, 6.26; N, 10.42; S, 7.95. Found: C, 59.52; H, 6.32; N, 10.13; S, 7.52.
6a-tert-Butyl-3,3,7,7-tetramethyl-6-phenyl-cyclopropa[4,5]imidazo[5,1-b]thiazol-2,5(3H,6H)-dione (21): yield 10% from 15c; mp 105 °C; 1H NMR δ 1.08 (s, 9H, t-Bu), 1.25 (s, 3H, Me), 1.50 (s, 6H, CMe2), 2.85 (s, 3H, Me), 7.37 (s, 5H, Ph); 13C NMR δ 55.7, 60.0, 66.0, 125.9, 126.1, 128.1, 138.6, 154.4 (C=O), 205.3 (C=O); MS m/z 358 (M+, 1.8), 301 (100), 273 (48). Anal. Calcd for C20H26N2O2S ; C, 66.99; H, 7.32; N, 7.82; S, 8.94. Found: C, 67.11; H, 7.28; N, 7.86; S, 8.88.
5´,6´-Dihydro-2,2,5´,5´,6,6-hexamethyl-7´-thioxo-spirocyclohexane-1,1´-(7´H)-imidazo[2,1-b]thiazol-4´-one (24a): yield 89% from 23a; mp 146 – 7 °C; IR 1760, 1500, 1360, 1290, 1080 cm-1; 1H NMR δ 1.00, 1.33 (each s, 6H, cyclohexane-CH3), 1.67 (s, 6H, CH2), 2.13, 2.77 (each br s, 3H, Me); 13C NMR δ 68.08, 92.8, 185.2, 191.3 (C=O, C=N), 200.5 (C=S); MS m/z 324 (M+, 82), 242 (73), 200 (59), 167 (64), 91 (56), 41 (100). Anal. Calcd for C16H24N2OS2; C, 59.21; H, 7.47; N, 8.63; S, 19.76. Found: C, 59.14; H, 7.44; N, 8.37; S, 19.52.
2,2-Di-tert-butyl-2,3,5,6-tetrahydro-5,5-dimethyl-3-thioxo-imidazo[2,1-b]thiazol-6-one (24b): yield 40% from 23b; mp 98 – 9 °C; IR 1760, 1600, 1380, 1360, 1295, 1250, 1185, 1080 cm-1; 1H NMR δ 1.33 (s, 18H, t-Bu2), 1.67 (s, 6H, CMe2). Anal. Calcd for C15H24N2OS2; C, 57.64; H, 7.76; N, 8.97; S, 20.52. Found: C, 57.72; H, 7.57; N, 8.91; S, 20.21.
2-tert-Butyl-2-isopropyl-2,3,5,6-tetrahydro-5,5-dimethyl-3-thioxo-imidazo[2,1-b]thiazol-6-one (24c): yield 91% from 23c; mp 117 °C; 1H NMR δ 0.92, 1.55 (each d, J = 5 Hz, 6H, i-Pr), 1.27 (s, 9H, t-Bu), 1.70 (s, 6H, CMe2), 2.90 (sept, J = 5 Hz, 1H, i-Pr); 13C NMR δ 67.7, 92.5, 186.3, 191.4 (C=N, C=O), 202.4 (C=S). Anal. Calcd for C14H22N2OS2; C, 56.33; H, 7.44; N, 9.39; S, 21.48. Found: C, 56.41; H, 7.64; N, 9.32; S, 21.65.
2-(6,6,10,10-Tetramethyl-2-oxo-4-thioxo-1-thia-3-azaspiro[4,5]decan-3-yl)-2-methyl-N-(4-nitrophenyl)-propionamide (25a): yield 83% from 23d; mp 232 °C (decomp); IR 3400, 1700, 1615, 1530, 1500, 1480 cm-1; 1H NMR δ 1.50 – 2.80 (br, 6H, (CH2) 3), 1.00, 1.30, 1.93 (3s, each 6H, CMe2), 7.70 (mc, 4H, Ar); 13C NMR δ 69.4, 81.2, 119.0, 125.1, 143.6, 143.7, 169.9 (C=O), 174.2 (C=O), 207.7 (C=S). Anal. Calcd for C22H29N3O4S2; C, 56.99; H, 6.32; N, 9.06; S, 13.83. Found: C, 56.76; H, 6.27; N, 9.05; S, 13.89.
2-(5,5-Di-tert-butyl-2-oxo-4-thioxo-thiazolidin-3-yl)-2-methyl-N-(4-nitrophenyl)propionamide (25b): yield 96% from 6b and 22b by hydrolysis on work-up; mp 180 °C; IR 3400, 1700, 1620, 1600, 1535, 1500, 1400, 1340, 1300 cm-1; 1H NMR δ 1.33 (s, 18H, t-Bu2), 1.93 (s, 6H, CMe2), 7.07 - 8.10 (mc, 4H, Ar). Anal. Calcd for C21H29N3O4S2; C, 55.84; H, 6.49; N, 9.31; S, 14.20. Found: C, 55.63; H, 6.48; N, 9.31; S, 14.53.

ACKNOWLEDGEMENTS
Financial support by the Fonds der Chemischen Industrie, Frankfurt, is gratefully acknowledged.

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