On the behavior of α-brominated dimethyl o-benzenediacetate toward nitrogen nucleophiles . Part I. Reaction of dimethyl α,α'-dibromo o-benzenediacetate with hydrazines

Meso- ( 1a ) and racemic dimethyl α,α'-dibromo o-benzenediacetate ( 1b ) when condensed with hydrazine and methylhydrazine furnished respectively 1,3-dicarbomethoxyisoindole ( 5a ) and its N-methyl derivative ( 5b ). Reaction of phenylhydrazine with 1a led to the N-phenylisoindole ( 5c ) and to the N-anilino isoindoline ( 6 ) as the cis isomer; conversely, 1b was transformed into a mixture of the 2-phenyl-1,2,3,4-tetrahydrophthalazine ( 7 ), the trans isomer of ( 6 ), the N-anilinoisoindole ( 5d ) and dimethyl α-(N'-phenylhydrazino)-o-benzenediacetate ( 8 ). Compounds 1a and 1b were also condensed with acetylhydrazine to give a mixture of the N-acetylaminoisoindoline ( 12 ) and of the 2-acetyl-1,2,3,4-tetrahydrophthalazine ( 13 ).     

Substituted γ-lactones. XXX. Reactions of α-Keto-β-Subtituted-γ-butyrolactones with diamines

The condensation reaction between α-keto-β-aroyl (or acyl) -γ-butyrolactones, 4a-4e and o-phenylenediamine or 2, 3-diaminonaphthalene leads under retrograde aldol condensation involving loss of formaldehyde to formation of 3-substituted-3, 4-dihydro-2 (1H) quinoxalinones or benzo [g] quinoxalinones, 7a-7g , respectively as a new convenient synthesis of this type of heterocyclic systems. The reaction of type 4 compound with 4, 5-diaminopyromidine, 8 , was found to proceed differently. 2-[(4-Amino-5-pyrimidinyl)amine]-4-oxo-3-(hydroxymethyl)-4-phenyl-2-butenoic acid 9 was the only product formed when the reaction between 4a and 8 was run in ethanol. The same reaction in glacial acetic acid proceeds with loss of formaldehyde, to afford 7-phenacylidene-7,8-dihydro-6 (1H)-pteridione 10 . The reaction between type 4 compounds and ethylenediamine or 1, 4-phenylenediamine leads to the formation of the bis-condensation products 13–15 , respectively.     

Novel Heterospirocyclic 3-Amino-2H-azirines as Synthons for Heterocyclic α-Amino Acids

The heterospirocyclic N-methyl-N-phenyl-2H-azirin-3-amines (3-(N-methyl-N-phenylamino)-2H-azirines) 1a - d with a tetrahydro-2H-thiopyran, tetrahydro-2H-thiopyran, and a N-protected piperidine ring, respectively, were synthesized from the corresponding heterocyclic 4-carboxamides 2 by consecutive treatment with lithium diisopropylamide (LDA), diphenyl phosphorochloridate (DPPCI), and sodium azide (Scheme 4). The reaction of these aminoazirines with thiobenzoic acid in CH₂Cl₂ at room temperature gave the thiocarbamoyl-substituted benzamides 13a - d in high yield. The azirines 1a-d were used as synthons for heterocyclic α-amino acids in the preparation of tripeptides of the type Z-Aib-Xaa-Aib-N(Ph)Me ( 18 ) by following the protocol of the ‘azirine/oxazolone method’: treatment of Z-Aib with 1 to give the dipeptide amide 15 , followed by selective hydrolysis to the corresponding acid 16 and coupling with the 2,2-dimethyl-2H-azirin-3-amine 17 gave 18 , again in high yield (Scheme 5). With some selected examples of 18 , the selective deprotection of the amino and the carboxy group, respectively, was demonstrated (Scheme 6). The solid-state conformations of the protected tripeptides 18a - d , as well as that of the corresponding carbocyclic analogue 18e , were determined by X-ray crystallography (Figs. 1-3 and Tables 1-3). All five tripeptides adopt a β-turn conformation of type III or III′. The solvent dependence of the chemical shifts of the NH resonances (Fig. 6) suggests that there is an intramolecular H-bond between H-N(4) and O(11) in all cases, which is an indication that a relatively rigid β-turn structure also persists in solution. Surprisingly, the tripeptide acid 20a shows no intramolecular H-bond in the crystalline state (Fig. 7); O(11) is involved in an intermolecular H-bond with the OH group of the carboxy function.     

Brominations of Cyclic Acetals from α-Amino Acids and α- or β-Hydroxy Acids with N-Bromosucinimide

The preparation of novel electrophilic building blocks for the synthesis of enantiomerically pure compounds (EPC) is described. Thus, the 2-(tert-butyl)dioxolanones, -oxazolidinones, -imidazolidinones, and -dioxanones obtained by acetalization of pivalaldehyde with 2-hydroxy-, 3-hydroxy-, or 2-amino-carboxylic acids are treated with N-bromosuccinimide under typical radical-chain reaction conditions (azoisobuytyronitril/CCl₄/reflux). Products of bromination in the α-position of the carbonyl group of the five-membered-ring acetals are isolated or identified ( 2, 5 , and 8 ; Scheme 1). The dioxanones are converted to 2H, 4H-dioxinones under these conditions ( 12 , 14 , 15 , 21 , and 22 ; Schemes 2 and 3). The products can be converted to chiral derivatives of pyruvic acid (methylidene derivatives 3 and 6 ) or of 3-oxo-butanoic and -pentanoic acid ( 16 and 23 ). The mechanism of the brominations is interpreted. The conversion of serine to enactiomcrically pure dioxanones 26–28 (Scheme 4) is also discussed.     

α-Methylidene- and α-Alkylidene-β-lactams from Nonproteinogenic Amino Acids

Treatment of methyl 2-(1-hydroxyalkyl)prop-2-enoates 1 with conc. HBr solution afforded methyl (Z)-2-(bromomethyl)alk-2-enoates 2 , which were transformed regioselectively into N-substituted methyl (E)-2- (aminomethyl)alk-2-enoates 3 (S_N2 reaction) and into N-substituted methyl 2-(1-aminoalkyl)prop-2-enoates 4 (S_N2′ reaction). Regiocontrol of nucleophilic attack by amine was accomplished simply by choice of solvent, the S_N2 reaction occurring in MeCN and the S_N2′ reaction in petroleum ether. Hydrolysis and lactamization afforded β-lactams 7 and 8 , containing an exocyciic alkylidene and methylidene group at C(3), respectively.     

Cyclization of ylidenemalononitriles. X. Synthesis of benzazapropellane derivatives from α-Cyano-β-chloroalkylcinnamonitriles

The reaction of nucleophilic and non-nucleophilic bases wtih 2-carbamoyl-3-(γ-chloropropyl)-1-indenone ( 5 ) have been investigated. Condensation of γ-chlorobutyrophenone with malono-nitrile afforded α-cyano-β-(3-ehloropropyl)cinnamonitrile which was cyclized in concentrated sulfurie acid to produce 5 . Two other products obtained from the cyclization reaction were 2-carbamoyl-3-(γ-ehloropropylidene)-1-indanone ( 4 ) and α-carbamoyl-β-(3-chloropropyl)cinnam-amide. Treatment of a solution of 4 in ethyl acetate with piperidine resulted in cyclization of the γ-chloropropyl side chain to give 2-carbamoyl-3-cycIopropyl-1-indanone. The same compound was obtained in improved yield by the treatment of 4 or 5 with sodium hydroxide solution. The reaction of dirnethylamine with 5 in benzene gave initial Michael addition of the amine followed by internal alkylation of the carbanion so formed to yield 3a-dimethylamino-2,3,3a,8-tetrahydro-8-oxoeyclopent[a]indene-8a(lH)earboxamide ( 7a ). Similarly addition of ammonia, pyrrolidine, piperidine, benzenethiol, p-toluenethiol, 2-naphthalenethiol and nitromethane to the indenone I gave respective analogs of type 7 . Treatment of 5 with sodium cyanide in aqueous t-butyl alcohol resulted in a similar Michael addition followed by internal alkylation. In addition, cyclization between the nitrile and the carbamoyl functions occurred in the same step to give 2-oxo-4-imino-7,8-benzo-3-aza[3.3.3]-propellan-6-one ( 13a ). Hydrolysis of the iminopyrrolido ring in 13a to the corresponding suecin-irnide gave 2,4-dioxo-7,8-benzo-3-aza[3.3.3]propellan-6-one ( 13b ). Reactión of 13b with methyl iodide, allyl bromide, benzyl bromide, and diethyluminoethyl chloride afforded the corresponding N-alkylated products. A similar sequence starling with δ-ehlorovalerophenone led to 5,6-fused ring systems, including a [4.3.3]propellane. 2,9-Dioxo-4-methyl-7,8-benzo-3-aza[4.3.3]propell-4-ene was obtained by the reaction of 5 with acetone in dilute alkali.     

Synthesis and thermolysis of N-heteroarylacetylazides and α-oximino-α-(N-heteroaryl)acetylazides

Treatment of N-heteroarylacethydrazides with an equimolar amount of nitrous acid afforded N-heteroaryacetylazides and subsequent thermolysis of these azides gave the analogues of 2,3-dihydroimidazo[1,5-a]pyridin-3-one. When some of these cyclized compounds were treated with nitrous acid, the ring opening reaction occurred and recyclized 3-(N-heteroaryl)-1,2,4-oxadiazolin-5-ones were obtained. Treatment of N-heteroarylacethydrazides with two equivalent moles of nitrous acid afforded α-oximino-α-(N-heteroaryl)acetylazides. Thermolysis of these azides gave mixtures of 3-(N-heteroaryl)-1,2,4-oxadiazolin-5-one and 3-hydroxy-4-(N-heteroaryl)furazan. On the basis of the effects of heterocyclic rings and solvents upon the relative yield of two types of the products, one plausible mechanistic explanation for the decomposition of such azides was proposed. α-Oximino-α-(H-heteroaryl)acetylazides were converted into cyano N-heterocycles by the action of alkali in good yields.     

Selektive Amidspaltung bei Peptiden mit α,α-disubstituierten α-Aminosäuren

Selective Amide Cleavage in Peptides Containing α,α-Disubstituted α-Amino Acids A new synthesis of dipeptides with terminal α,α-disubstituted α-amino acids, using 2,2-disubtituted 3-amino-2H-azirines 1 as amino-acid equivalents, is demonstrated. The reaction of 1 with N-protected amino acids leads to the corresponding dipeptide amides in excellent yield. It is shown that the previously described selective hydrolysis (HCl, toluene, 80°, or HCl, MeCN/H₂O, 80°) of the terminal amide group results in an extensive epimerization of the second last amino acid. An acid-catalyzed enolization in the intermediate oxazole-5(4H)-ones is responsible for this loss of configurational integrity. In the present paper, a selective hydrolysis of the terminal amide group under very mild conditions is described: In 3_N HCl (THF/H₂O 1:1), the dipeptide N,N-dimethylamides or N-methytlanilides are hydrolized at 25–35° to the optically pure dipeptides in very good yield.     

Reaction of ketenes with N,N-disubstituted α-aminomethyleneketones. XII. Synthesis of N,N-disubstituted 4-amino-3-chloro-6-(2-methyl-l-propenyl) (2-phenylethenyl)-2H-pyran-2-ones

Cycloaddition of dichloroketene to N,N-disubstituted (E)-amino-5-methyl-1,4-hexadien-3-ones IV and (E,E)-1-amino-5-phenyl-1,4-pentadien-3-ones V occurred in moderate to good yield only in the case of aromatic N-substitution to give N,N-disubstituted 4-amino-3,3-dichloro-3,4-dihydro-6-(2-methyl-l-propenyl) (2-phenylethenyl)-2H-pyran-2-ones, which were dehydrochlorinated with DBN to afford in good yield N,N-disubstituted 4-amino-3-chloro-6-(2-methyl-propenyl)(2-phenylethenyl)-2H-pyran-2-ones. In the case of aliphatic N,N-disubstitution (dimethylamino group) of enaminones IV and V, the Cycloaddition led directly in low yield to 3-chloro-4-dimethylamino-6-(2-methyl-l-propenyl)(2-phenylethenyl)-2H-pyran-2-ones.     

The synthesis of β-heteroarylamino-α,β-dehydro-α-amino acid derivatives via thiazolones

2-Alkoxy-4-heteroarylaminomethylene-5(4H)-thiazolones 4 were converted with various nucleophiles into β-heteroarylamino-α,β-dehydro-α-amino acid derivatives 11, 14, 15, 16, 17, 18 , and 19 . Reduction of 4 with sodium borohydride in ethanol saturated with gaseous ammonia afforded the corresponding β-heteroaryl-amino substituted alanyl amides 20 . Thiazoledione derivative 7a was transformed with sodium methoxide in methanol into 1-(4,6-dimethylpyrimidinyl-2)-4-mercaptocarbonylimidazol-2(3H)-one ( 8a ).     

An efficient and convenient transformation of α-haloketones to α-hydroxyketones using cesium formate

A new safe and convenient transformation has been developed. In the presence of cesium formate in dry MeOH solution, α-haloketones underwent direct conversion reaction to afford α-hydroxyketone in excellent yields. Furthermore, this methodology can be extended and applied in 2-chloro-N-(1,3-diphenyl-1H-pyrazol-5-yl)acetamide, 2-chloro-N-(2,6-dimethylphen-yl)acetamide, 1-(bromomethylsulfonyl)benzene, and N-(bromomethyl)phthalimide to give the corresponding products in moderate to excellent yields.     

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.     

Solid‐state conformations of linear depsipeptide amides with an alternating sequence of α,α‐disubstituted α‐amino acid and α‐hydroxy acid

Depsipeptides and cyclodepsipeptides are analogues of the corresponding peptides in which one or more amide groups are replaced by ester functions. Reports of crystal structures of linear depsipeptides are rare. The crystal structures and conformational analyses of four depsipeptides with an alternating sequence of an α,α‐disubstituted α‐amino acid and an α‐hydroxy acid are reported. The molecules in the linear hexadepsipeptide amide in (S)‐Pms‐Acp‐(S)‐Pms‐Acp‐(S)‐Pms‐Acp‐NMe₂ acetonitrile solvate, C₄₇H₅₈N₄O₉·C₂H₃N, ( 3b ), as well as in the related linear tetradepsipeptide amide (S)‐Pms‐Aib‐(S)‐Pms‐Aib‐NMe₂, C₂₈H₃₇N₃O₆, ( 5a ), the diastereoisomeric mixture (S,R)‐Pms‐Acp‐(R,S)‐Pms‐Acp‐NMe₂/(R,S)‐Pms‐Acp‐(R,S)‐Pms‐Acp‐NMe₂ (1:1), C₃₂H₄₁N₃O₆, ( 5b ), and (R,S)‐Mns‐Acp‐(S,R)‐Mns‐Acp‐NMe₂, C₃₀H₃₇N₃O₆, ( 5c ) (Pms is phenyllactic acid, Acp is 1‐aminocyclopentanecarboxylic acid and Mns is mandelic acid), generally adopt a β‐turn conformation in the solid state, which is stabilized by intramolecular N—H…O hydrogen bonds. Whereas β‐turns of type I (or I′) are formed in the cases of ( 3b ), ( 5a ) and ( 5b ), which contain phenyllactic acid, the torsion angles for ( 5c ), which incorporates mandelic acid, indicate a β‐turn in between type I and type III. Intermolecular N—H…O and O—H…O hydrogen bonds link the molecules of ( 3a ) and ( 5b ) into extended chains, and those of ( 5a ) and ( 5c ) into two‐dimensional networks.     

9-deazapurine nucleosides. The synthesis of certain N-5-2′-deoxy-β-D-erythropentofuranosyl and N-5-β-D-arabinofuranosylpyrrolo[3,2-d]pyrimidines

A number of 2,4-disubstituted pyrrolo[3,2-d]pyrimidine N-5 nucleosides were prepared by the direct glycosylation of the sodium salt of 2,4-dichloro-5H-pyrrolo[3,2-d]pyrimidine (3) using 1-chloro-2-deoxy-3,5-di-O-(p-toluoyl)-α-D -erythropentofuranose (1) and 1-chloro-2,3,5-tri-O-benzyl-α-D-arabinofuranose (11) . The resulting N-5 glycosides, 2,4-dichloro-5-(2-deoxy-3,5-di-O-(p-toluoyl) -β-D-erythropentofuranosyl)-5H-pyrrolo-[3,2-d]pyrimidine (4) and 2,4-dichloro-5-(2,3,5-tri-O-benzyl-β-D-arabinofuranosyl-5H -pyrrolo [3,2-d)pyrimidine (12) , served as versatile key intermediates from which the N-7 glycosyl analogs of the naturally occurring purine nucleosides adenosine, inosine and guanosine were synthesized. Thus, treatment of 4 with methanolic ammonia followed by dehalogenation provided the adenosine analog, 4-amino-5-(2-deoxyerythropentofuranosyl) -5H-pyrrolo[3,2-d]pyrimidine (6) . Reaction of 4 with sodium hydroxide followed by dehalogenation afforded the inosine analog, 5-(2-deoxy-β-D-erythropentofuranosyl) -5H-pyrrolo[3,2-d]pyrimidin-4(3H)-one (9) . Treatment of 4 with sodium hydroxide followed by methanolic ammonia gave the guanosine analog, 2-amino-5-(2-deoxy-β-D-erythropentofuranosyl) -5H-pyrrolo[3,2-d]pyrimidin-4(3H)-one (10) . The preparation of the same analogs in the β-D-arabinonucleoside series was achieved by the same general procedures as those employed for the corresponding 2′-deoxy-β-D-ribonucleoside analogs except that, in all but one case, debenzylation of the sugar protecting groups was accomplished with cyclohexene-palladium hydroxide on carbon, providing 4-amino-5-β-D-arabinofuranosyl-5H-pyrrolo [3,2-d]pyrimidin-4(3H)-one (18) . Structural characterization of the 2′-deoxyribonucleoside analogs was based on uv and proton nmr while that of the arabinonucleosides was confirmed by single-crystal X-ray analysis of 15a . The stereospecific attachment of the 2-deoxy-β-D-ribofuranosyl and β-D-arabinofuranosyl moieties appears to be due to a Walden inversion at the C₁ carbon by the anionic heterocyclic nitrogen (S_N2 mechanism).     

Photochemical reactivity of α,β-unsaturated δ-lactams: Synthesis of seco-steroids. Photochemical reactions. XIII [1]

The UV. irradiation of 17 β-hydroxy-2-aza-4-androsten-3-one (1) , N-methyl-17 β-hydroxy-2-aza-4-androsten-3-one (3) , 17 β-hydroxy-4-aza-5 β-androst-1-en-3-one (2) and N-methyl-17 β-hydroxy-4-aza-5 β-androst-1-en-3-one (4) , gives rise to 1,10-seco (from 1 and 3 ) and 5, 10-seco (from 2 and 4 ) steroids.     

Substituted γ-Lactones. 35 . Reduction of 4-aroyl-3-hydroxy-2(5H)-furanones

The reduction of 4-aroyl-3-hydroxy-2(5H)-furanons 1a-c was investigated using different reducing agents. Sodium borohydride reacts with type 1 compounds by loss of water to yield 4-(arylmethylene)-2,3(4H,5H)-furandiones 2a-c . Platinum or charcoal supported by pallodium chloride transforms 1a to 4-benzyl-3-hydroxy-2(5H)-furanone ( 3). Compounds 2a and 2b react with o-phenylenediamine to give 3-(E-(1′-hydroxymethyl-2′-aryl)ethenyl]-2-quinoxalinones 4a and 4b . The lactone 3 under the same conditions splits out formaldehyde and forms 3-(2′-phenylethyl)-2-quinoxalinone ( 6 ). The structure assignments of the novel compounds are based on elemental analysis and nmr as well as ir spectroscopic data.     

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).     

Synthesis of novel 5H‐Pyrimido[5,4‐b]mdole‐(1H,3H)2,4‐diones as potential ligands for the cloned α1‐adrenoceptor subtypes

A new series of 3‐[ω‐[4‐(4‐substituted phenyl)piperazin‐1‐yl]alkyl]‐5H‐pyrimido[5,4‐b]indole‐(1H,3H)‐2,4‐diones ( 3–10 and 12–13 ) were synthesized from the N‐(2‐chloroethyl)‐N'‐[3‐(2‐ethoxycarbonyl)indolyl] urea ( 1 ) or the N‐(3‐chloropropyl)‐N'‐[3‐(2‐ethoxycarbonyl)indolyl] urea ( 2 ) and a number of 1‐(4‐substi‐tuted‐phenyl)piperazines. 3‐[2‐[4‐(4‐Aminophenyl)piperazin‐1‐yl]ethyl]‐5H‐pyrimido[5,4‐b]indole‐(1H,3H)2,4‐dione ( 14 ) was obtained by reduction of the parent nitro compound 8 . The obtained 5H‐pyrimido[5,4‐b]indole‐(1H,3H)2,4‐dione derivatives were tested towards cloned α_1A, α_1B and α_1D adrenergic receptors subtypes in binding assays. Some compounds showed good affinity and selectivity for the α_1D‐adrenoceptor subtype.     

Synthesis of α-(aminomethylene)-9H-purine-6-acetic acid derivatives

α-(Aminornethylene)-9H-purine-6-acetamide ( 3a ) and the corresponding ethyl acetate 9 have been synthesized by catalytic hydrogenation of 6-cyanomethylenepurine derivatives 2 and 7 which were obtained by the substitution of 6-chloropurine derivatives with α-cyanoacetamide and ethyl cyanoacetate, respectively. Substitution of α-(aminomethylene)-9-(tetrahydrofuran)-9H-purine-6-acetamide ( 3b ) with amines gave the corresponding N-alkyl- and N-arylamines 5 , which were treated with acid to give N-substituted α-(aminomethylene)-9H-purine-6-acetamides 6 . Substitution of 9 with amines gave the corresponding N-alkyl- and N-aryl substituted amines 10 .     

Reaction of ketenes with N,N-disubstituted α-aminomethyleneketones VII. Synthesis of 2H,5H-[1]benzothiopyrano[4,3-b]pyran and 2H,5H-thiopyrano[4,3-b]pyran derivatives

The dipolar 1,4-cycloaddition of dichloroketerie to N,N-disubslituled 3-aminomethylene-2,3-dihydro-4-thiochromanones and 3-aminomethylenetelrahydro-4-thiopyranones gave N,N-disubstituted 4-amino-3,3-diehloro-3,4-dihydro-2H,5H-[1]benzolhiopyrano[4,3-b]pyran-2-ones and 4-amino-3,3-dichloro-3,4,7,8-tetrahydro-2H,5H-thiopyrano[4,3-b]pyran-2-ones, respectively, only in the ease of aromatic or strong hindering aliphatic N-substitution. The adducts gave N,N′-disubstituted 4-amino-3-chloro-2H,5H-[1]benzothiopyrano[4,3-b]pyran-2-ones and 4-amino-3-chloro-7,8-dihydro-2H,5H-thiopyrano[4,3-b]pyran-2-ones, respectively, by dehydro-chlorination with DBN. By chromatography on neutral alumina, 3-(2,2-dichloroethylidene)-2,3-dihydro-4-thiochromanone was isolated as an unstable liquid from the reaction between dichloroketerie and 3-diethylaminornethylene-2,3-dihydro-4-thiochromanone.