Synthesen makrocyclischer Lactone durch Ringerweiterung Herstellung von (±)-Phoracantholid I, (±)-Dihydrorecifeiolid und (±)-15-Hexadecanolid

Syntheses of Macrocyclic Lactones by Ring Enlargement Reaction Reaction. Preparation of (±)-Phoracantholide I, (±)-Dihydrorecifeiolide and (±)-15-Hexadecanolide A general procedure for the synthesis of macrocyclic lactones is described. The Michael adducts of 2-nitrocycloalkanones and acrylaldehyde were regiospecifically methylated with CH₃Ti[OCH(CH₃)₂]₃ or (CH₃)₂Ti[OCH(CH₃)₂]₂ at the aldehyde carbonyl group. Treatment of the so-formed alkohols with tetrabutylammonium fluoride gave the lactones enlarged by four ring members. This method was used to synthesize the 10-membered (±)-phoracantolide I ( 11 ), the 12-membered (±)-dihydrorecifeiolide ( 17 ), and (±)-15-hexadecanolide ( 24 ) in 52%, 26.5%, and 58.7% respectively.     

3-(Dimethylamino)-2,2-dimethyl-2H-azirin als α-Aminoisobuttersäure(Aib)-Äquivalent: Cyclische Depsipeptide durch direkte Amid-Cyclisierung

3-(Dimethylamino)-2,2-dimethyl-2H,-azirine as an α-Aminoisobutyric-Acid (Aib) Equivalent: Cyclic Depsipeptides via Direct Amid Cyclization In MeCN at room temperature, 3-(dimethylamino)-2,2-dimethyl-2H-azirine ( 1 ) and α-hydroxycarboxylic acids react to give diamides of type 8 (Scheme 3). Selective cleavage of the terminal N,N-dimethylcarboxamide group in MeCN/H₂O leads to the corresponding carboxylic acids 13 (Scheme 4). In toluene/Ph SH , phenyl thioesters of type 11 are formed (see also Scheme 5). Starting with diamides 8 , the formation of morpholin-2,5- diones 10 has been achieved either by direct amide cyclization via intermediate 1,3-oxazol-5(4H)-ones 9 or via base-catalyzed cyclization of the phenyl thioesters 11 (Scheme 3). Reaction of carboxylic acids with 1 , followed by selective amide hydrolysis, has been used for the construction of peptides from α-hydroxy carboxylic acids and repetitive α-aminoisobutyric-acid (Aib) units (Scheme 4). Cyclization of 14a, 17a , and 20a with HCI in toluene at 100° gave the 9-, 12-, and 15-membered cyclic depsipeptides 15, 18 , and 21 , respectively.     

Reaktionen von 3-(Dimethylamino)-2H-azirinen mit 1,3-Benzoxazol-2(3H)-thion

Reaction of 3-(Dimethylamino)-2H-azirines with 1,3-Benzoxazole-2(3H)-thione The reaction of 3-(dimethylamino)-2H-azirines 2 with 1,3-benzoxazole-2(3H)-thione ( 5 ), which can be considered as NH-acidic heterocycle (pK_aca. 7.3), in MeCN at room temperature, leads to 3-(2-hydroxyphenyl)-2-thiohydantoins 6 and thiourea derivatives of type 7 (Scheme 2). A reaction mechanism for the formation of the products via the crucial zwitterionic intermediate A ′ is suggested. This intermediate was trapped by methylation with Mel and hydrolysis to give 9 (Scheme 4). Under normal reaction conditions, A ′ undergoes a ring opening to B which is hydrolyzed during workup to yield 6 or rearranges to give the thiourea 7. A reasonable intermediate of the latter transformation is the isothiocyanate E (Scheme 3) which also could be trapped by morpholine. In i-PrOH at 55–65° 2a and 5 react to yield a mixture of 6a , 2-(isopropylthio)-1,3-benzoxazole ( 12 ), and the thioamide 13 (Scheme 5). A mechanism for the surprising alkylation of 5 via the intermediate 2-amino-2-alkoxyaziridine F is proposed. Again via an aziridine, e.g. H ( Scheme 6 ), the formation of 13 can be explained.     

1,3-Dipolare Cycloadditionen von 2-(Benzonitrilio)-2-propanid mit 4,4-Dimethyl-2-phenyl-2-thiazolin-5-thion und Schwefelkohlenstoff

1,3-Dipolar Cycloadditions of 2-(Benzonitrilio)-2-propanide with 4,4-Dimethyl-2-phenyl-2-thiazolin-5-thione and Carbon Disulfide Irradiation of 2,2-dimethyl-3-phenyl-2H-azirine ( 11 ) in the presence of 4,4-dimethyl-2-phenyl-2-thiazolin-5-thione ( 7 ) yields a mixture of the three (1:1)-ad-ducts 8 , 12 and 13 (Schemes 3 and 6). The formation of 8 and 12 can be explained by 1,3-dipolar cycloaddition of 2-(benzonitrilio)-2-propanide ( 1b ) to the C, S-double bond of 7. Photochemical isomerization of 12 leads to the third isomer 13 (Schemes 3 and 7). Photolysis of the azirine 11 in the presence of carbon disulfide gives a mixture of two (2:l)-adducts, namely 12 and 13 (Scheme 4). A reaction mechanism via the intermediate formation of the 3-thiazolin-5-thione b is postulated. The structure of the heterocyclic spiro compound 13 has been established by single-crystal X-ray structure determination (cf. Fig. 1 and 2).     

Synthese von optisch aktiven Carotinoiden mit 3,5,6-Trihydroxy-5-6-dihydro-β-Endgruppen

Syntheses of Optically Active Carotenoids with 3,5,6-Trihydroxy-5,6-dihydro β-End Groups For the specification of the relative and absolute configuration in carotenoids with 3,5,6-trihydroxy-5-6-dihydro β-end groups, several ionone derivatives and carotenoids bearing this end group were synthesized. Acid-catalyzed hydrolysis of (3S,5S,6R)– acetoxy-5,6-epoxy-5,6-dihydro-β-ionone ( 7 ) and of its (3S,5R,6S)-isomer ( 13 ) gave the diols 8 and 15 , respectively, with exclusive inversion at c(5) (Scheme 2). Compared to this, mild acid hydrolysis of caroten-5-6-expoxides in the presence of H₂O resulted in the formation of 5,6-diols with either inversion or retention of the configuration at C(6) (Scheme 3). Spectroscopic data allowed us to distinguish the relative configurations (3R*,5S*,6S*) (see A ), (3R*,5R*,6R*) (see B ), (3R*,5S*,6R*) (see C ), and (3R*,5R*,6S*) (see D ), of the 3,5,6-trihydroxy-5-6-dihydro β-end groups. Syntheses of the optically active carotene-hexols 20 and 21 and comparison with published data led to a revision of the structure of mectrazanthin (now formulated as 20 ), heteroxanthin (now formulated as 28 ), and further carotenoids with 3,5,6-trihydroxy end groups.     

Die Oxidation von 3-(1-Nitro-2-oxocycloalkyl)propanal

The Oxidation of 3-(1-Nitro-2-oxocycloalkyl)propanal Oxidation of the title compound 1 with KMnO₄ under neutral conditions led to the corresponding acid 2 , 5-(2,3,4,5-tetrahydro-2-nitro-5-oxo-2-furyl)pentanoic acid ( 4 ), and 4-oxononadioic acid ( 6 ). On the basis of experimental results the mechanism of the formation of 4 is discussed (Scheme 1). Oxidation of 1 with KMnO₄ under basic conditions gave 6 which was transformed to (E)-4,5-dihydro-5(2′-oxocyclopentyliden)furan-2(3H)-one ( 12 ) with benzene/TsOH (Scheme 3). In contrast to this result the corresponding 4-oxoheptandioic acid ( 22 ) yields 1,6-dioxaspiro[4,4]nonan-2,7-dione ( 23 ) only (Scheme 4).     

Kupplung von Peptiden mit C-terminalen α,α-disubstituierten α - Aminosäuren via Oxazol-5(4H)-one

Peptide-Bond Formation with C-Terminal α,α-Disubstituted α - Amino Acids via Intermediate Oxazol-5(4H)-ones The formation of peptide bonds between dipeptides 4 containing a C-terminalα,α-disubstituted α-amino acid and ethyl p-aminobenzoate ( 5 ) using DCC as coupling reagent proceeds via 4,4-disubstituted oxazol-5(4H)-ones 7 as intermediates (Scheme 3). The reaction yielding tripeptides 6 (Table 2) is catalyzed efficiently by camphor-10-sulfonic acid (Table 1). The main problem of this coupling reaction is the epimerization of the nonterminal amino acid in 4 via a mechanism shown in Scheme 1. CSA catalysis at 0° suppresses completely this troublesome side reaction. For the coupling of Z-Val-Aib-OH ( 11 ) and Fmoc-Pro-Aib-OH ( 14 ) with H-Gly-OBu¹ ( 12 ) and H-Ala-Aib-NMe₂ ( 15 ), respectively, the best results have been obtained using DCC in the presence of ZnCl₂ (Table 3).     

Basenkatalysierte Cyclisierungen von 2-(2-Propinyl)oxybenzamiden

Base Catalysed Cyclizations of 2-(2-Propynyl)oxy-benzamide Systems 2-(2-Propynyl)oxy-benzamides were cyclized under base catalysis to 6- or 7-membered ring compounds, depending on the reaction conditions. Treatment of 2-(2-propynyl)oxy-benzamide ( 10 ) with sodium methylsulfinylmethanide (NaMSM) in DMSO gave two isomeric oxazepinons 11 (34%) and 12 (7%), while the transformation with sodium-2-propanolate in 2-propanol afforded the oxazinone 13 (34%) and with lithium cyclohexyl-isopropylamide (Li-CHIP) in N-methylpyrrolidone 11 (48%) exclusively (Scheme 4). N-Methyl-2-(2-propynyl)-oxy-benzamide ( 14 ) behaved similarly. In the reaction of 14 with sodium 2-propanolate in 2-propanol yielding the benzoxazinone 16 , the allenyloxy-benzamide 17 could be isolated as an intermediate (Scheme 5). The N-phenyl-compounds 18 and 22 treated with NaMSM/DMSO were converted to 3-anilino-2-methyl-benzo- and naphtho-pyran-4-ones, respectively (Schemes 6 and 7). The mechanisms for these reactions are discussed (Schemes 8, 9 and 10).     

Asymmetric synthesis of (R)-6-amino-1-methyl-4-(3-methyl-benzyl)hexahydro-1H-1,4-diazepine from L-asparagine

An efficient asymmetric synthesis of (R)-6-amino-1-methyl-4-(3-rnethylbenzyl)hexahydro-1H-1,4-diazepine [(R)-2] which serves as the amine part of (R)-1, a potent and selective 5-HT₃ receptor antagonist, is described. Formation of the hexahydro-1H-1,4-diazepine ring was achieved by the intramolecular ami-dation of the optically active aminocarboxylic acid 18 or reductive cyclization of the optically active aminoaldehyde 25. Compounds 18 and 25 were prepared from L-asparagine via the key aziridine derivatives 15 and 22 , respectively, with retention of the configuration. The intramolecular aziridine ring opening reaction of 29 gave the C₂? N bond cleavage product of the aziridine ring, the piperazin-5-one 30 , as the main product along with the desired 7-membered ring, the hexahydro-1H-1,4-diazepine product 19 .     

Total Synthesis of Racemic and Optically Active Compounds Related to Physostigmine and Ring-C Heteroanalogues from 3-[2′-(dimethylamino)ethyl]2,3-dihydro-5-methoxy-1,3-dimethyl-1H-indo l-2-ol

Oxindole 11 , obtained on 3-[2′-(dimethylamino)ethyl]alkylation of oxindole 12 , yielded, on stereoselective reduction with sodium dihydridobis(2-methoxyethoxy)aluminate, aminoalcohol 8 (Scheme 2). The quaternary methiodide 10 , obtained from 8 with MeI, gave, in nucleophilic displacements concurring with a Hofmann elimination, (±)-esermethole 6 , (±)-5-O-methylphysovenol ( 14 ), (±)-5-O-methyl-1-thiaphysovenol ( 15 ), and (±)-1-benzyl-1-demethylesermethole ( 16 ). Syntheses of (±)-1-benzyl-1-demethylphenserine ( 18 ), (±)-1-demethylphenserine ( 19 ), and (±)-phenserine ( 4 ) from 6 and 16 are described. Optically active 8a and 8b , obtained by chemical resolution, similarly gave the enantiomers 6a and 14a–16a of the (3aS)-series (prepared earlier from physostigmine ( 1a )) and their (3R)-enantiomers. The anticholinesterase activity of (±)- 4 , (±)- 18 , and (±)- 19 was compared with that of their optically active enantiomers.     

Efficient Synthesis of Novel 3-[5-(1H-Benzimidazol-2-Ylmethanesulfonyl)-4-Phenyl-4H-(1,2,4)Triazol-3-Yl]-1H-(1,8)Naphthyridin-4-One Derivatives

Abstract

of 1,4-dihydro-4-oxo-1,8-naphthyridine-3-carbohydrazide (4) with substituted phenyl isothiocyanates (5) in ethanol under reflux for 30 min gave thiosemicarbazide derivatives 6, which on cyclization in 2N NaOH under refluxing conditions for 1 h resulted in 3-(5-mercapto- 4-phenyl-4H-1,2,4-triazol-3-yl)-1,8-naphthyridin-4(1H)-one (7). Alternatively, 7 could also be prepared from following sequence of reactions, i.e., 4 → 8 → 7. In another sequence of reactions, condensation of 7 with chloroacetic acid in dimethylformamide (DMF) and K₂CO₃ as a mild base at 120 °C for 2 h resulted in 2-((5-(1,4-dihydro-4-oxo-1,8-naphthyridin-3-yl)-4-phenyl-4H-1,2,4-triazol-3-yl)sulfanyl)acetic acid (10). The latter, on reaction with substituted o-phenylenediamine (11) in 6N HCl for 4 h yielded 3-(5-((1H-benzo[d]imidazol-2-yl)methylthio)-4-phenyl-4H-1,2,4-triazol-3-yl)-1,8-naphthyridin-4(1H)-one (12). Alternatively, 12 could also be prepared by reacting 7 with 13 in DMF and K₂CO₃ as a mild base at 120 °C for 2 h, followed by oxidation with H₂O₂ resulting in the corresponding sulfonyl derivatives 14.     

Synthese von (Methylthio)penam-Derivaten durch Keten-Addition an 4,5-Dihydro-5-(methylthio)-1,3-thiazole

Synthesis of (Methylthio)penam Derivatives via Keten Addition onto 4,5-Dihydro-5-(methylthio)-1,3-thiazoles The 4,5-dihydro-5-(methylthio)-2-phenyl-1,3-thiazoles 3a and 3b , easily prepared from the corresponding 1,3-thiazol-5(4H)-thiones and MeLi, react with dichloroacetyl chloride ( 5a ) and acidoacetyl chloride ( 5b ) in the presence of Et₃N to give (methylthio)penam derivatives 6 (Table 1). The reaction mechanism is either a [2 + 2] cycloaddition of in situ generated ketene or a two-step reaction (Scheme 2). The structure of 6f has been confirmed by X-ray crystallography (Fig. 2). The relative configuration of 6a-e follow from comparison of their ¹H-NMR spectra with those of 6f (Fig. 1). The 6-azidopenams 6d and 6f have been reduced to aminopenams 8a and 8b , respectively. Acylation of 8a with phenacetyl chloride yields 9 (Scheme 4).     

Umsetzungen von 3-(Dimethylamino)-2,2-dimethyl-2H-azirin mit Barbitursäure-Derivaten

Reactions of 3-(Dimethylamino)-2,2-dimethyl-2H-azirines with Barbituric-Acid Derivatives The reaction of 3-(dimethylamino)-2,2-dimethyl-2H-azirine ( 1 ) and 5,5-disubstituted barbituric acids 5 in i-PrOH at ca. 70° gives 2-[5-(dimethylamino)-4,4-dimethyl-4H-imidazol-2-yl]alkanamides of type 6 in good yields (Scheme 1). The formation of 6 proceeds with loss of CO₂; various reaction mechanisms with a zwitterionic 1:1 adduct B as common intermediate are discussed (Schemes 2 and 5). Thermolysis of product 6 leads to 2-alkyl-5-(dimethylamino)-4,4-dimethyl-4H-imidazoles 8 or the tautomeric 2-alkylidene derivatives 8 ′ via elimination of HNCO (Scheme 3). The latter undergoes trimerization to give 1,3,5-triazine-2,4,6-trione. No reaction is observed with 1,5,5-trisubstituted barbiturates and 1 in refluxing i-PrOH, but an N-alkylation of the barbiturate occurs in the presence of morpholine (Scheme 4). This astonishing reaction is explained by a mechanism via formation of the 2-alkoxy-2-(dimethylamino )aziridinium ion H which undergoes ring opening to give the O-alkylated 2-amino-N¹,N¹-dimethylisobutyramide I as alkylating reagent (Scheme 4).     

Synthesen und Thermolysen von 1-Alkinyl-2-methyl-1,2-epoxy-cycloalkanen. - Versuche zur Ringerweiterung um drei Kohlenstoffatome

Syntheses and Thermolyses of 1-Alkynyl-2-methyl-1,2-epoxy-cycloalkanes. - Attempts at Ring Enlargement by Three Carbon Atoms The 1-alkynyl-2-methyl-1,2-epoxy-alkene 2 and -cycloalkenes 9, 28 and 29 were obtained by epoxidation of the conjugated en-ynes 1, 7, 26 and 27 . The 12-membered ring en-ynes 26 and 27 were synthesized by ethynylation or propynylation of 2-methylcyclododecanone ( 19 ) to the 1-ethynyl- or 1-(1′-propynyl)-cyclododecanols 20 A/B and 21 A/B , respectively, followed by dehydration to give separable mixtures of the regio- and stereoisomeric en-ynes 22, 24, 26 and 23, 25, 27 , respectively. Gas-phase thermolyses of the epoxides 2, 9, 28 and 29 were carried out under reduced pressure through a quartz tube at 550–600°. The formation of 5-hexine-2-one ( 3 ) and 4,5-hexadien-2-one ( 4 ) from 2 can be explained by [1, 5]- and [1, 3]- hydrogen shifts, respectively, and subsequent Claisen-type rearrangements. Thermolysis of the six-membered carbocyclic epoxide 9 induced the expected ring expansion by three carbon atoms to give 14% 4-cyclononynone ( 12 ), along with the ketones 13, 14 and 15 as by-products, which probably arose from surface induced heterolytic C, O-bond fission and Wagner-Meerwein-type rearrangement processes. Preliminary experiments with the thermolysis of the 12-membered carbocyclic ethynyl-epoxide 28 , yielded a mixture, which contained 4-cyclopentadecynone ( 30 ) and afforded, after hydrogenation, cyclopentadecanone ( 31 , exaltone®) in 36% yield as the semicarbazone. Traces of 3-methylcyclopentadecanone ( 32 , rac, -muscone) were identified after thermolysis and hydrogenation of the propynyl-epoxide 29 .     

Bildung von 4-, 5- und 6gliedrigen Heterocyclen durch ambidoselektive Ringschlüsse von Enolat-Ionen

Formation of 4-, 5- and 6-membered heterocycles by ambidoselective cyclization of enolate anions N-Acylmethyl-N-chloracetyl-2,6-dimethylanilines 4 were cyclized with base to 4-, 5- or 6-membered ring compounds, depending on the substituent R² (Scheme 2). All products can be rationalized as derived from the intermediate enolate anions a and b . The enolate anion a reacts by intramolecular alkylation to yield either 1, 4-oxazines 5 or azetidines 6 (Schemes 1, 3 and 7). The regioselectivity observed is expected on the basis of the allopolarization principle. The enolate anion b reacts only with formation of a new C? C bond (Scheme 5). Comparison with the behaviour of the 2, 6-unsubstituted anilines 9, 1a and 12 , shows a strong dependence not only on electronic but also on steric factors (Scheme 4 and 6).     

An Unexpected Isomerization of N-Aryl-3-amino-4-nitroisothiazol-5(2H)-imines to 2-(Benzothiazol-2-yl)-2-nitroethene-l,l-diamines

The syntheses of several N-aryl-3-amino-4-nitroisothiazol-5(2H)-imines 12 from 3, 3-diamino-2-nitro-thioacrylamides 11 are reported (Scheme 3). In polar solvents, a spontaneous isomerization of some of the prepared isothiazol-5(2H)-imines 12 yielded benzothiazoles 13 (Scheme 4). In the case of 2-alkyl-substituted derivatives of type 12 , the isomerization occurred only at higher temperatures. Electronic influences of different substituents on the rate of the isomerization were studied, and a polar reaction mechanism is proposed in Scheme 6. The structures of 12e and 13e were established by X-ray crystallography. Conformational analyses of 3-(methylamino)-2-nitro-N-phenyl-3-(pyrrolidin-1-yl)thioacrylamide (111) by NMR and X-ray methods were performed with the aim of explaining the distinct behavior of this amide towards Br₂ or diethyl azodicarboxylate.     

Regio‐ and Stereoselectivity of the SiO2‐Catalyzed Reaction of Thiocamphor (=1,7,7‐Trimethylbicyclo[2.2.1]heptane‐2‐thione) with Optically Active Monosubstituted Oxiranes

The reactions of the enolizable thioketone (1R,4R)‐thiocamphor (=(1R,4R)‐1,7,7‐trimethylbicyclo[2.2.1]heptane‐2‐thione; 1 ) with (S)‐2‐methyloxirane ( 2 ) in the presence of a Lewis acid such as SnCl₄ or SiO₂ in anhydrous CH₂Cl₂ led to two diastereoisomeric spirocyclic 1,3‐oxathiolanes 3 and 4 with the Me group at C(5′), as well as the isomeric β‐hydroxy thioether 5 (Scheme 2). The analogous reactions of 1 with (RS)‐, (R)‐, and (S)‐2‐phenyloxirane ( 7 ) yielded two isomeric spirocyclic 1,3‐oxathiolanes 8 and 9 with Ph at C(4′), an additional isomer 13 bearing the Ph group at C(5′), and three isomeric β‐hydroxy thioethers 10, 11 , and 12 (Scheme 4). In the presence of HCl, the β‐hydroxy thioethers 5, 10, 11 , and 12 isomerized to the corresponding 1,3‐oxathiolanes 3 and 4 (Scheme 3), and 8, 9 , and 13 , respectively (Scheme 5). Under similar conditions, an epimerization of 3, 8 , and 9 occurred to yield the corresponding diastereoisomers 4, 14 , and 15 , respectively (Schemes 3 and 6). The structures of 9 and 15 were confirmed by X‐ray crystallography (Figs. 1 and 2). These results show that the Lewis acid‐catalyzed addition of oxiranes to enolizable thioketones proceeds with high regio‐ and stereoselectivity via an S_n 2‐type mechanism.     

Synthese von 3-(2-Carboxy-4-Pyridyl)- und 3-(6-Carboxy-3-pyridyl)-DL-alanin

Synthesis of 3-(2-Carboxy-4-pyridyl)-and 3-(6-Carboxy-3-pyridyl)-DL-alanine As starting materials for potential photochemical approaches to betalaines C(R = COOH) and to muscaflavine F(R = COOH), β-(2-carboxy-4-pyridyl)- and β-(6(carboxy-3-pyridyl))-DL-alanine ( A and D with R = COOH or 4 and 11 ), respectively, were prepared (Scheme 1). The synthesis of 4 (= A, R = COOH) started with the 2-[(4-pyridyl)methyl]malonate 1 and proceeded via the N-oxide 2 , cyanation and hydrolysis (Scheme 2). Amino acid 11 was obtained from (3-pyridyl)methyl-bromide ( 6 ) via the malonate 7 by an analogous sequence of reactions (Scheme 3).     

Eine neue Aminoazirin-Reaktion. Bildung von 3,6-Dihydropyrazin-2(1H)-onen

A New Aminoazirine Reaction. Formation of 3,6-Dihydropyrazin-2(1H)-ones The reaction of 3-(dimethylamino)-2H-azirines 1 and 2-(trifluoromethyl)-1,3-oxazol-5(2H)-ones 5 in MeCN or THF at 50–80° leads to 5-(dimethylamino)-3,6-dihydropyrazin-2(1H)-ones 6 (Scheme 3). Reaction mechanisms for the formation of 6 are discussed: either the oxazolones 5 react as CH-acidic heterocycles with 1 (Scheme 4), or the azirines 1 undergo a nucleophilic attack onto the carbonyl group of 5 (Scheme 6). The reaction via intermediate formation of N-(trifluoroacetyl)dipeptide amide 8 (Scheme 5) is excluded.     

Reaktion von 3-(Dimethylamino)-2H-azirinen mit 1,3-Thiazolidin-2-thion

Reaction of 3-(Dimethylamino)-2H-azirines with 1,3-Thiazolidine-2-thione Reaction of 3-(dimethylamino)-2H-azirines 1 and 1,3-thiazolidine-2-thione ( 6 ) in MeCN at room temperature leads to a mixture of perhydroimidazo[4,3-b]thiazole-5-thiones 7 and N-[1-(4,5-dihydro-1,3-thiazol-2-yl)alkyl]-N′,N′-dimethylthioureas 8 (Scheme 2), whereas, in i-PrOH at ca. 60°, 8 is the only product (Scheme 4). It has been shown that, in polar solvents or under Me₂NH catalysis, the primarily formed 7 isomerizes to 8 (Scheme 4). The hydrolysis of 7 and 8 leads to the same 2-thiohydantoine 9 (Scheme 3 and 5). The structure of 7a, 8c , and 9b has been established by X-ray crystallography (Chapt. 4). Reaction mechanisms for the formation and the hydrolysis of 7 and 8 are suggested.