Additionsreaktion von 3-Dimethylamino-2,2-dimethyl-2H-azirin mit Phenylisothiocyanat

Reaction of 3-Dimethylamino-2,2-dimethyl-2H-azirine with Phenyl Isothiocyanate In contrast to the reactions of 3-dimethylamino-2,2-dimethyl-2H-azirine ( 1a ) with various isothiocyanates, leading to thiazoline derivatives, the reaction of 1a with phenyl isothiocyanate at room temperature gives 5,5-dimethyl-3-phenyl-Δ¹-imidazolin-4-dimethyliminium-2-thiolate ( 9 , Scheme 2). The structure of 9 is deduced from spectral data and reactions of this zwitterionic compound (Schemes 2 and 4).     

Herstellung und Reaktionen der valenzpolaromeren Verbindung (4,4-Dimethyl-2-thiazolin-5-dimethyliminium)-2-thiolat ⇌ (1-Dimethylthiocarbamoyl-1-methyl-äthyl)-isothiocyanat aus 3-Dimethyl-amino-2,2-dimethyl-2H-azirin und Schwefelkohlenstoff

Synthesis and reactions of the valence polaromeric compound (4,4-dimethyl-2-thiazoline-5-dimethyliminium)-2-thiolate ? 1-dimethylthiocarbamoyl-1-methyl-ethyl isothiocyanate from 3-dimethylamino-2,2-dimethyl-2H-azirine and carbon disulfide. 3-Dimethylamino-2,2-dimethyl-2H-azirine ( 1 ) reacts with carbon disulfide to give crystals which have the dipolar structure 3a [(4,4-dimethyl-2-thiazoline-5-dimethyliminium)-2-thiolate, Scheme 1]. In solution, the non-dipolar (charge-free) isomeric form 3b (1-Dimethyl-thiocarbamoyl-1-methyl-ethyl isothiocyanate) is almost exclusively populated. Reaction products are derived from both forms: Derivatives of 3a are the hydrolysis product 6 , the sodium borohydride reduction product 7 and the methylation products 9 and 10 , respectively (Scheme 2). The isothiocyanate form 3b is responsible for the various reaction products with amines (Scheme 3). One of the reaction products with ammonia, namely 20 , is also obtained by the reaction of 1 with thiocyanic acid. Thermolysis of the azirine/carbon disulfide adduct 3 leads to 2-dimethylamino-4,4-dimethyl-2-thiazoline-5-thione ( 17 ) in high yield. A possible mechanism is outlined in Scheme 4. The same compound is also formed by rearrangement of 3 under the catalytic influence of dimethylamine. Its structure has been established by X-ray crystallography (section 4). Again a rearrangement is involved in the reductive (NaBH₄) conversion of 17 to 7 , the direct reduction product of the dipolar species 3a (Scheme 5). The isothiocyanate form 3b is able to react with a second molecule of 3-dimethylamino-2,2-dimethyl-2H-azirine ( 1 ) to yield compound 25 , which in the crystalline or dissolved state appears to be almost entirely populated by the carbodiimide form with structure 25b (Scheme 7), though all reaction products of 25 (reduction with sodium borohydride, addition of water or hydrogen sulfide, Schemes 7 and 8) are derived from the dipolar form 25a , not detectable as such; here again therefore there is a dynamic equilibrium 25a ? 25b . The two forms of adduct 3 , namely 3a and 3b , are obviously very easily interconverted at room temperature and therefore can be considered as valence polaromeric forms (section 5). A classification of the dipolar (zwitterionic) form is given, which allows a comparison of various dipolar species and gives as indication of charge stabilization by delocalization. The versatile reactivity of the 3-dimethylamino-2,2-dimethyl-2H-azirine/carbon disulfide adduct is demonstrated by the fact that with simple reagents approximately 25 derivatives have been obtained, most of them being new heterocyclic compounds.     

Reaktion von 3-Dimethylamino-2,2-dimethyl-2H-azirin mit 6-Methyluracil; Kristallstruktur der Reaktionsprodukte

Reaction of 3-Dimethylamino-2,2-dimethyl-2H-azirine with 6-Methyluracil; Crystal Structure of the Products The reaction of 3-dimethylamino-2,2-dimethyl-2H-azirine ( 1 ) with 6-methyl-uracil ( 4 ) in 2-propanol at 80° yields the 4H-imidazoje derivative 5 as the main product. This reaction is similar to the previously reported ones with heterocyclic compounds containing the sequence NH? CO? NH? CO. In the presence of water, 5 is easily hydrolyzed to 6 . The structures of 5 and 6 have been established by X-ray crystallography.     

Die Struktur des Adduktes aus 3-Dimethylamino-2,2-dimethyl-2H-azirin und 3-Methyl-2,4-diphenyl-1,3-oxazolium-5-olat. Vorläufige Mitteilung

Structure of the adduct from 3-dimethylamino-2,2-dimethyl-2H-azirine and 3-methyl-2,4-diphenyl-1,3-oxazolium-5-olate 3-Dimethylamino-2,2-dimethyl-2H-azirine ( 1 ) reacts with 3-methyl-2,4-diphenyl-1,3-oxazolium-5-olate ( 5a ) to give a 1:1 adduct ( 7 ) in a 88% yield. Its crystal structure has been determined by X-ray analysis (direct methods) and refined with 1056 structure amplitudes to R = 0,032. The crystal system is monoclinic, space group P2₁/c, with unit cell dimensions a = 10.663, b = 9,828, c = 18,592 Å, and β = 90,63°. It is obvious that 4-dimethylamino-5,5-dimethyl-2-[α-(N-methyl-benzamido)benzyliden]-Δ³-1,3-oxazoline ( 7 ) arises from an addition of 1 to the valence-polaromeric ketene form 5b of the mesoionic oxazolone 5a (Scheme 3).     

Die Struktur einer stabilen dipolaren Verbindung aus 2,2-Dimethyl-3-dimethylamino-2H-azirin und Benzoylisothiocyanat. Vorläufige Mitteilung

Structure of a Stable Dipolar Compound from 2,2-Dimethyl-3-dimethylamino-2H-azirine and Benzoylisothiocyanate. Benzoylisothiocyanate and 2,2-dimethyl-3-dimethylamino-2H-azirine ( 1 ) react to given the dipolar compound 4,4-dimethyl-2-thiazolin-5-dimethylimminium-2-benzcarboxamidate ( 2 ), whose structure has been proved by X-ray analysis. Compound 2 , upon addition of water, yields the thiourea derivative 3 , whereas by acid catalyzed hydrolysis the thiazolinone derivative 4 is formed. The dipolar structure 2 is also existent in organic solvents like dimethylsulfoxide or chloroform.     

Reaktionen von 3-Dimethylamino-2,2-dimethyl-2H-azirin mit. NH-aciden Heterocyclen; Synthese von 4H-imidazolen

Reactions of 3-Dimethylamino-2,2-dimethyl-2H-azirine with NH-Acidic Heterocycles; Synthesis of 4H-Imidazoles In this paper, reactions of 3-dimethylamino-2,2-dimethyl-2H-azirine ( 1 ) with heterocyclic compounds containing the structure unit CO? NH? CO? NH are described. 5,5-Diethylbarbituric acid ( 5 ) reacts with 1 in refluxing 2-propanol to give the 4H-imidazole derivative 6 (Scheme 2) in 80% yield. The structure of 6 has been established by X-ray crystallography. Under similar conditions 1 and isopropyl uracil-6-carboxylate ( 7 ) yield the 4H-imidazole 8 (Scheme 3), the structure of which is deduced from spectral data and the degradation reactions shown in Scheme 3. Hydrolysis of 8 with 3N HCl at room temperature leads to the α-ketoester derivative 9 , which in refluxing methanol gives dimethyl oxalate and 5-dimethyl-amino-2,4,4-trimethyl-4H-imidazole ( 10 ). On hydrolysis the latter is converted to the known 2,4,4-trimethyl-2-imidazolin-5-one ( 11 ) [6]. Quinazolin-2,4 (1H, 3H)-dione ( 12 ) and imidazolidinetrione (parabanic acid, 14 ) undergo with 1 a similar reaction to give the 4H-imidazoles 13 and 15 , respectively (Schemes 4 and 5). In Scheme 6 two possible mechanisms for the formation of 4H-imidazoles from 1 and heterocycles of type 16 are formulated. The zwitterionic intermediate f corresponds to b in Scheme 1. Instead of dehydration as in the case of the reaction of 1 with phthalohydrazide [3], or ring expansion as with saccharin and cyclic imides [1] [2], f , undergoes ring opening (way A or B). Decarboxylation then leads to the 4H-imidazoles 17 .     

Reaktion von 3-Dimethylamino-2,2-dimethyl-2H-azirin mit Barbitursäure

Reaction of 3-Dimethylamino-2,2-dimethyl-2H-azirine with Barbituric Acid The reaction of 3-dimethylamino-2,2-dimethyl-2H-azirine (1) with barbituric acid (4) in dimethyl formamide at room temperature yields a mixture of several compounds. The two main products 5 and 6 have been isolated in 40 and 10% yield, respectively, and their structures established by X-ray analysis. In Schemes 4–6 reaction mechanisms for the formation of 5 and 6 are postulated, the first step beeing either a C- or an N-alkylation of barbituric acid. Reduction of 5 and 6 with NaBH₄ in ethanol at room temperature yields 6,6-dimethyl-1,5,6,7-tetrahydro-pyrrolo[2,3-d]pyrimidin-2,4(3H)-dione (7) and 3,3-dimethyl-2,3-dihydro-imidazo[1,2-c]pyrimidin-5,7(1H, 6H)-dione (8) in 38 and 48% yield, respectively. Treatment of 6 with 3N aqueous NaOH at room temperature gives 3,3-dimethyl-imidazo[1,2-c]pyrimidin-2,5,7 (1H, 3H, 6H)-trione (9) in 51% yield (Scheme 3).     

Synthese von 3,3-Dimethylperhydro-1,4-diazepin-2,5,7-trionen aus 3-Dimethylamino-2,2-dimethyl-2H-azirin und Malonsäuremonoamiden

Synthesis of 3,3-Dimethylperhydro-1,4-diazepin-2,5,7-triones from 3-Dimethylamino-2,2-dimethyl-2H-azirine and Malonic Acid Monoamides Reaction of the aminoazirine 1 and malonic acid monoamides 5 in CH₃CN yielded triamides of type 6 (Scheme 2), which were transformed to the corresponding phenylthioates 9 by treatment of a solution of 6 and thiophenol in CH₃CN with HCl (Scheme 4). Cyclization of 9 to give the 1,4-diazepin-2,5,7-trione of type 10 was achieved with NaH in toluene at about 90°. It has been shown that 2-oxazolin-5-ones are intermediates in the selective cleavage of the therminal amide function of 6 (Scheme 3).     

Additionsreaktionen von 3-Dimethylamino-2,2-dimethyl-2H-azirin an Phenylisocyanat und Diphenylketen

Addition Reaction of 3-Dimethylamino-2,2-dimethyl-2H-azirine with Phenylisocyanate and Diphenylketene 3-Dimethylamino-2,2-dimethyl-2H-azirine ( 1a ) reacts with carbon disulfide and isothiocyanates with splitting of the azirine N(1), C(3)-double bond to give dipolar, fivemembered heterocyclic 1:1 adducts. In some cases, these products can undergo secondary reactions to yield 1:2 and 1:3 adducts. In this paper it is shown that the reaction of 1a with phenylisocyanate also takes place by cleavage of the N(1), C(3)-bond, whereas with diphenylketene N(1), C(2)-splitting is observed. The reaction of 1a and phenylisocyanate in hexane at room temperature yields the 1:3 adduct 2 in addition to the trimeric isocyanate 3 (Scheme 1). A mechanism for the formation of 2 is given in Scheme 5. Hydrolysis experiments with the 1:3 adduct 2 , yielding the hydantoins 4–6 and the ureas 7 and 8 (Schemes 3 and 5), show that the formation of this adduct via the intermediates d , e and f is a reversible reaction. The aminoazirines 1a and 1b undergo an addition reaction with diphenylketene to give the 3-oxazolines 14 (Scheme 8), the structure of which has been established by spectral data and oxidative degradation of 14a to the 3-oxazolin-2-one 15 (R¹ ? R² ? CH₃, Scheme 9).     

Reaktionsprodukte aus 3-Dimethylamino-2, 2-dimethyl-2H-azirin und Phthalohydrazid bzw. Maleohydrazid

Reaction Products from 3-Dimethylamino-2,2-dimethyl-2H-azirine and Phthalohydrazide or Maleohydrazide 3-Dimethylamino-2, 2-dimethyl-2H-azirine (1) reacts in dimethylformamide at room temperature with the six-membered cyclic hydrazides 2, 3-dihydrophthalazin-1, 4-dione (2) and 1, 2-dihydropyridazin-3, 6-dione (15) to give the zwitterionic compounds 3 and 16 , respectively (Scheme 1 and 7). The mechanism of these reactions is outlined in Scheme 1 for compound 3 (cf. also Scheme 8). The first steps are thought to be similar to the known reactions of 1 with the NH-acidic compounds saccharin and phthalimide (cf. [1]). Instead of ring expansion to the nine-membered heterocycle i (X=CONH, Scheme 8), a proton transfer followed by the loss of water gives 3 (Scheme 1). The structure of the zwitterionic compounds 3 and 16 is deduced from spectral data and the reactions of these compounds (see Schemes 2, 3, 4, 6 and 7). Methylation of 3 yields the iodide 4 , which is hydrolysed easily to the 2-imidazolin-5-one derivative 5 (Scheme 2). Hydrolysis of 3 under basic conditions leads to the amide 6 , which undergoes cyclization to 7 at 220–230° (Scheme 3). The analogous cyclization has been realized under acidic conditions in the case of 17 (Scheme 7). Catalytic reduction of 3 yields the tertiary amine 14 (Scheme 6), whereas the reduction with sodium borohydride leads to a mixture of 14 and the 2-imidazoline derivative 13 . The alcohol 11 , corresponding to the amine 14 , is obtained by sodium borohydride reduction of the 2-imidazolin-5-one 7 or of the amide 6 (Scheme 3). This remarkably easy reaction of 7 shows the unusual electrophilicity of the lactamcarbonyl group in this compound. The reduction of 6 to 11 is understandable only by neighbouring group participation of N (2′) in the dihydrophthalazine residue.     

15N-Markiertes 3-(Dimethylamino)-2,2-dimethyl-2H-azirin zur mechanistischen Untersuchung von Reaktionen mit NH-aciden Heterocyclen

₁₅N-Labelled 3-(Dimethylamino)-2,2-dimethyl-2H-azirine for Mechanistic Studies of Reactions with NH-Acidic Heterocycles The synthesis of 3-(dimethylamino)-2,2-dimethyl(1-¹⁵N)-2H-azirine ( 1 *) was accomplished via reaction of 1-chloro-N,N,2-trimethyl-1-propenylamine ( 9 ) and sodium (1-¹⁵N) azide (Scheme 3). The earlier reported reactions of 1 with saccharin ( 10 , Scheme 4), phthalimide ( 12 , Scheme 5), and 2H-1,3-benzoxazin-2,4(3H)-dione ( 16 , Scheme 6) were repeated with 1 *, and the position of the ¹⁵N-label in the products was determined by ¹⁵N-NMR spectroscopy. Whereas the postulated reaction mechanisms for 10 and 12 were confirmed by these experiments, the mechanism for the reaction of 16 had to be revised. With respect to the position of ¹⁵N in the products 17 and 18 , a new mechanism is formulated in Scheme 7. Treatment of 5,5-dimethyl-1,3-oxazolidine-2,4-dione ( 19 ) with 1 * led to 3,4-dihydro-2H-imidazol-2-on 20 in which only N(3) was labelled. The mechanism of a ring expansion and transannular ring contraction as shown in Scheme 8 is in agreement with this finding.     

1, 5, 6, 7-Tetrahydro-2H-[1,4]diazepin-5,7-dione aus Malonimiden und 3-Dimethylamino-2,2-dimethyl-2H-azirin

1, 5, 6, 7-Tetrahydro-2H-[1, 4]diazepin-5, 7-diones from Malonimides and 3-Dimethylamino-2, 2-dimethyl-2H-azirine Reaction of the aminoazirine 1 with malonimides of type 7 in 2-propanol at room temperature leads to the 1,4-diazepine derivatives of type 9 (Scheme 3). The structure of 6, 6-diethyl-3-dimethylamino-2,2-dimethyl-1,5,6, 7-tetrahydro-2H- [1,4] diazepin-5, 7-dione ( 9a ) has been proved by single crystal X-ray analysis (Chapter 4). Reduction of the 7-membered heterocycle 9a with sodium borohydride yields the perhydro-[1,4]diazepin-5, 7-dione 10 , while 9a in ethanol at 60° undergoes a ring contraction to the 4 H-imidazole derivative 11a (Scheme 4): Mechanisms of these two reactions are discussed in comparison with previously reported reactions (Chapter 5).     

Synthese von 1, 3, 4-Oxadiazolen und 4, 5-Dihydro-1, 2, 4-triazinen aus 3-Dimethylamino-2, 2-dimethyl-2 H-azirin und Carbohydraziden

Synthesis of 1,3,4-Oxadiazoles and 4,5-Dihydro-l,2,4-triazines from 3-Dimethylamino-2,2-dimethyl-2 Hazirine and Carbohydrazides 3-Dimethylamino-2, 2-dimethyl-2 H-azirine ( 1 ) reacts with aromatic carbohydrazides to give 2-(1-amino-1-methylethyl)-5-aryl-1, 3, 4-oxadiazoles ( 7 , 10 , 11 ). With ethyl carbazate the azirine 1 forms the aminoester 15 , which is easily cyclized to the 4, 5-dihydro-1, 2, 4-triazin-3 (2H)-one 16 . From the reaction of 1 with oxamohydrazide ( 17 ) and oxalodihydrazide 19 the 4, 5-dihydro-1, 2, 4-triazin-3-carboxamide 18 and the symmetric compound 20 , respectively, have been isolated. Reactions supporting the structures of the new compounds are described.     

Heterocyclole als Zwischenprodukte einer neuen, überraschenden Umlagerung bei der Reaktion von 3-(Dimethylamino)-2,2-dimethyl-2H-azirin mit monosubstituierten Parabansäuren. Vorläufige Mitteilung

Cyclols as Intermediates in the Reaction of 3-(Dimethylamino)-2,2-dimethyl-2H-azirine with Monosubstituted Parabanic Acids; a New and Unexpected Rearrangement The reaction of 3-(dimethylamino)-2,2-dimethyl-2H-azirine ( 1 ) with N-methylparabanic acid ( 4 ) in 2-propanol at room temperature gives the cyclol 5 in 97% yield. In acetonitrile solution 5 rearranges to the imidazoline derivative 6 (Scheme 2). The structures of the unexpected products 5 and 6 have been established by X-ray crystallography.     

Photochemische Cycloadditionen von 3-Phenyl-2H-azirinen an Carbonsäurechloride. 35. Mitteilung über Photoreaktionen

Irradiation of 2, 3-diphenyl-2H-azirine ( 1a ) and 1-azido-1-phenyl-propene, the precursor of 2-methyl-3-phenyl-2H-azirine ( 1b ), in benzene, with a high pressure mercury lamp (pyrex filter) in the presence of acid chlorides yields the oxazoles 5a–d (Scheme 2). Photolysis of 2, 2-dimethyl-3-phenyl-2H-azirine ( 1c ) under the same conditions gives after methanolysis the 5-methoxy-2, 2-dimethyl-4-phenyl-3-oxazolines 7a, b, d , while hydrolysis of the reaction mixture leads to the formation of the 1, 2-diketones 8a, c, d (Scheme 4). The suggested reaction path for all these reactions is a 1, 3-dipolar cycloaddition of the photochemically generated benzonitrilemethylides 2 to the carbonyl double bond of the acid chlorides to give the intermediates 4 , followed by either elimination of hydrogen chloride or solvolysis (Schemes 2 and 4). Irradiation of 1c in the presence of acetic acid anhydride leads via the intermediate 9 to the 5-hydroxy-3-oxazoline 10 and the 5-methylidene-3-oxazoline 11 (Scheme 5).     

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).     

Photochemische Cycloadditionen von 3-Phenyl-2H-azirinen mit Benzoyl-, Äthoxycarbonyl- und Vinylphosphonaten 34. Mitteilung über Photoreaktionen

The irradiation of the 3-phenyl-2H-azirines 1a–c in the presence of diethyl benzoylphosphonate ( 8 ) in cyclonexane solution, using a mercury high pressure lamp (pyrex filter), yields the diethyl (4, 5-diphenyl-3-oxazolin-5-yl)-phosphonates 9a–c (Scheme 3). In the case of 1b a mixture of two diastereomeric 3-oxazolines, resulting from a regiospecific but non-stereospecific cycloaddition of the benzonitrile-benzylide dipole 2b to the carbonyl group of the phosphonate 8 , was isolated. Benzonitrile-isopropylide ( 2a ), generated from 2,2-dimethyl-3-phenyl-2H-azirine ( 1a ), undergoes a cycloaddition reaction to the ester-carbonyl group of diethyl ethoxycarbonylphosphonate ( 15 ) with the same regiospecificity to give the 3-oxazoline derivative 16 (Scheme 5). The azirines 1a–c , on irradiation in benzene in the presence of diethyl vinylphosphonate ( 17 ) give non-regiospecifically the Δ¹-pyrrolines 13a–c and 14a–c (Scheme 6).     

Additionen von 2,2-Dimethyl-3-dimethylamino-2H-azirin an 2-Formyl-cycloalkanone und Sulfinsäuren

2,2-Dimethyl-3-dimethylamino-2H-azirine ( 1 ) reacts with the formyl-cycloalkanones 4 – 8 in boiling benzene to give the 1:1 adducts 13 – 17 in 60–99% yield (Table). These adducts are N′-[(2-oxo-cycloalkylidene)-methyl] derivatives of 2-amino-N, N-dimethylisobutyramide. The reaction mechanism (Scheme 6) is analogous to the mechanism of the reaction of 1 with carboxylic acids and cyclic enolisable 1,3-diketones [1]. Sulfinic acids and 1 undergo a similar reaction at ?15° to yield 2-sulfinamido-N, N-dimethylisobutyramides (Schemes 4 and 7), while sulfonic acids and the azirine 1 lead to a dimeric salt of type 20 , which with sodium hydroxide gives the dihydropyrazine 21 (Scheme 5).     

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-2,2-dimethyl-2H-azirin mit Phenolen und Halogenaromaten

Reactions of 3-dimethylamino-2,2-dimethyl-2H-azirine with phenols and aryl halides The reactions of 3-dimethylamino-2,2-dimethyl-2H-azirine ( 1 ) with phenols are described in chap. 1. The azirine 1 reacts with the 2-formyl- and 2-acetylphenols 5 – 8 to yield the N′-methylidene derivatives of 2-amino-N,N-dimethyl-isobutyramide 9 - 12 (Scheme 2, tautomeric form b ). These products are in equilibrium with the tautomeric quinoide forms 9a-12a . Under similar conditions 4-hydroxybenzaldehyde did not react with 1 . Reaction of 1 with 4-hydroxycoumarine ( 13 ) gives the 4-amino-coumarine 14 (Scheme 2). The mechanism of these reactions is analogous to the previously reported one for the reaction of 1 with cyclic enolisable 1,3-diketones [2] [3]. Activated phenols with pK_a-values < 8, e.g. 2- and 4-nitrophenol, 2,4-dinitrophenol and pentachlorophenol, undergo addition reactions with 1 in boiling benzene solution to give the aniline derivatives 15 - 18 (Scheme 3). A reaction mechanism is given in Scheme 3: after protonation of the azirine 1 followed by attack of the phenolate ion at the amidinium-C-atom, the intermediate of type e undergoes a rearrangement to the spiro-Meisenheimer complexes of type f . Ring opening leads to 15 – 18 . A similar reaction is observed for 2,4-dinitro-thiophenol and 1 , giving 2-(N′-(2,4-dinitrophenyl)amino)-N,N-dimethyl-isobutyrothioamide ( 19 ). The azirine 1 reacts with the more acidic 2,4,6-trinitrophenol (picric acid) to yield 3,3,6,6-tetramethylpiperazine-2,5-bis(N,N-dimethyliminium) dipicrate ( 21 , Scheme 4). The methacrylamidinium salt 22 is the only product (97% yield) in the reaction of 8-hydroxy-5,7-dinitroquinoline and 1 in acetonitrile solution. The reaction of 1 with picric acid can be explained in a similar way as the previously reported one with strong acids (cf. Scheme 1, [1] [3] [5]). An alternative mechanism without formation of the 1-aza-allylcation c is postulated in Scheme 5, together with a mechanism which could explain the exclusive formation of 22 in the reaction of 1 with 8-hydroxy-5,7-dinitroquinoline. In chap. 2 a few reactions of the azirine 1 with aryl halides are reported. In the reaction with 2,4-dinitrofluorobenzene it is shown by UV. and NMR., that m , n and o are intermediates (Scheme 6). Working up the reaction mixture with water, hydrogen sulfide or benzylamine leads to the aniline derivatives 17 , 19 and 26 , respectively. With picryl chloride and 8-hydroxy-5,7-dinitroquinoline the azirine 1 undergoes a nucleophilic aromatic substitution to afford the intermediates p and q , which via deprotonation and ring opening give acrylamidine derivatives ( 27 and 29 , Scheme 7 and 8). The steric hindrance in p and q between the aziridine ring and the two groups in o-position could be the reason for the different behaviour of the intermediates n and p or q (cf. Schemes 6 and 8).