Ynamine

The imonium salt (199), obtained from ynamines and phosgeneimonium chloVide, underwent ready reaction with monosubstituted hydrazines to give the 3,5-bis(dimethyl-amino)pyrazole (200) (68T4217, 69T3453). Similarly, the adduct (201), resulting from the addition of phosgene to ynamines, likewise reacted with sym-disubstituted hydrazines to give pyrazoles (202). With hydroxylamine derivatives the isoxazolinone (203) was obtained. 

Diazoalkanes and ynamines react with the electrophilic C(4)—C(5) double bond of pyrazolenine (359) to afford the cycloadducts (360) and (361), respectively, whereas diphenylketene yields the bicyclic diazetidinone (362) by reaction with the c/s-azo system of (359) (79CC568). 

The azine (583) of hexafluoroacetone adds the ynamine (584) to give the azetine (585). On heating (585) in the presence of triethylamine it is converted into the pyrazole (586) as indicated in Scheme 48 (75ZN(B)622). 

Since 1,3-dipolar cycloadditions of diazomethane are HOMO (diazomethane)-LUMO (dipolarophile) controlled, enamines and ynamines with their high LUMO energies do not react (79JA3647). However, introduction of carbonyl functions into diazomethane makes the reaction feasible in these cases. Thus methyl diazoacetate and 1-diethylaminopropyne furnished the aminopyrazole (620) in high yield. 

Diazoalkanes add to the carbon-carbon double bonds of 2,3-diphenylthiirene 1-oxide and 1,1-dioxide. The adducts lose SO or SO2 to give pyrazoles and related compounds (Scheme 103) (80CB1632). Mesoionic oxazolones (75CLH53), 4-methyl-5-phenyl-l,2-dithiolene-3-thione (80JOU395) and pyrylium betaines (72JOC3838) react similarly via intermediate adducts (Scheme 104). Enamines (Scheme 96) and ynamines add to the double bond of 2,3-diarylthiirene 1,1-dioxides to give acyclic and cyclic sulfones by a thermal. 

Thiirane is more bactericidal than oxirane, and derivatives of 2-mei captomethylthiirane inhibit tuberculosis. The following pharmacological uses have been reported for compounds derived from thiirane derivatives gold complexes of the adducts of diethylphosphine and thiirane (antiarthritic), adducts of thiiranes and malononitrile (antibacterial, blood vessel dilators, muscle relaxants, sedatives), thermolysis products of thiirane 1-oxides and adducts of thiirane 1-oxides with sulfenyl chlorides (antibacterial), adducts of 2,3-diarylthiirene 1,1-dioxides with ynamines (antibacterial, parasiticidal), adducts of 2,3-diarylthiirene 1,1-dioxides with enamines (antifertility), adducts of p-aminophenylacetic esters with thiirane (immunosuppressants), adducts of amines and thiiranes (radioprotective drugs). 

Tungsten, tricarbonyleyelopentadienylhydrido-reaction with ynamines, 1, 666 Turpin reaction, 3, 1033 Tylophorine occurrence, 4, 478 synthesis, 4, 472, 475 Tylosin... 

The following compounds have been obtained from thiete 1,1-dioxide Substituted cycloheptatrienes, benzyl o-toluenethiosulfinate, pyrazoles, - naphthothiete 1,1-dioxides, and 3-subst1tuted thietane 1,1-dioxides.It is a dienophile in Diels-Alder reactions and undergoes cycloadditions with enamines, dienamines, and ynamines. Thiete 1,1-dioxide is a source of the novel intermediate, vinylsulfene (CH2=CHCH=SQ2). which undergoes cyclo-additions to strained olefinic double bonds, reacts with phenol to give allyl sulfonate derivatives or cyclizes unimolecularly to give an unsaturated sultene. - Platinum and iron complexes of thiete 1,1-dioxide have been reported. 

The use of ynamines, ketenimines and mercuric acetate as electrophiles in DMSO oxidations has also been reported but, as yet, appear to offer no advantages over the reagents described above. 

Ynamines also react with many fluorinated alkenes by an ionic mechanism to give fluorocyclobutenes, accompanied by varying amounts of diene depending on the fluoroalkene [107, 108] (equation 41). 

Bis(trifluoromethyl)-substituted pyrimidines are also available fromtrifluoro-acetonitrde on reaction with enamines and ynamines [d ] With dimethylami-nocrotonates, a cyclocondensation takes place to give 2-pyridones. 5-Cyano-6-trifluoromethyluracil is available via a similar route [95] (equation 18)... 

Recently a-chloro-)3-chlorocarbonyl enamines have been obtained from ynamines and phosgene (121a). 

Aminocyclopropanes were prepared from enamines by the addition of Simmons-Smith reagent (688) or best through the cuprous-chloride-promoted decomposition of diazomethane (689). The reaction of an enamine with chloroform and base and opening of the resultant aminocyclopropane to an ynamine was reported (690). 

Analysis of the NMR chemical shifts of the triple bond carbon atoms of the substituted ynamines and comparison of these data with the corresponding values for compounds of the ethylene series suggest the presence of counterpolarization... 

The aminobutynones 342 contain a push-pull system with a strongly electron-withdrawing carbonyl group therefore, they show electrophilic properties. Cyclizations with their participation proceed differently from those with ynamines (91UK103 00UK642) and acetylenic ketones (73UK511). 

In these reactions, the formation of imidazoline and oxazoline rings corresponds to the reagent orientation previously observed for ynamines (84ZOR1648) and alkenylynamines (83ZOR926), as well as in their reactions with mononucleophiles such as amines (79ZOR1824 81ZOR1807) and alcohols (80ZOR1141). 

Thus, ynaminoketones with 1,2-diaminobenzene form benzodiazepines with retention of the dialkylamino group. The reaction occurs as a nucleophilic addition in the absence of catalysts. With Q, /3-acetylenic ketones 1,2-diaminobenzene reacts in the same manner, but under proton-catalyzed conditions (72LA24). At the same time, ynamines and enynamines furnish with 1,2-diaminobenzene substituted benzimidazoles as aresultof double attack at the acetylene bond(83ZOR926 84ZOR1648). 

Analogously to ynamines and o, /3-acetylenic ketones, 4-aminobut-3-yn-2-ones react with 1,3-dipoles (68HCA443 73HCA2427 92KGS867). The reaction of 4-dimethylaminobut-3-yn-2-one with diphenylketene follows a route of [2-1-21-cycloaddition (30°C, THF, 1 h) to give 2-acetyl-3-dimethylamino-4,4-diphenyl-cyclobut-2-en-l-one (377) in 15% yield. With ethyl azidoformate (30°C, THF, 3 h), the tiiazole 378 is formed in 82% yield, whereas with phenyl isocyanate, the quinoline 379 is the product (by a [2- -4] scheme) in 70% yield (68HCA443). 

In reactions of this type, the character of cyclization is determined by the ynamine moiety. The features of the heterocyclization of diverse ynaminocarbonyl compounds are generalized by the formation of the compounds 348,384, and 385 (92KGS867 00UK642). 

The ynaminoketones (X = Me) obtained from diacetylene react with 1,2-diaminoethane as simple ynamines by double attack at the triple bond to form imidazoline derivatives 348. 

The hetero Diels-Alder [4+2] cycloaddition (HDA reaction) is a very efficient methodology to perform pyrimidine-to-pyridine transformations. Normal (NHDA) and Inverse (IHDA) cycloaddition reactions, intramolecular as well as intermolecular, are reported, although the IHDA cycloadditions are more frequently observed. The NHDA reactions require an electron-rich heterocycle, which reacts with an electron-poor dienophile, while in the IHDA cycloadditions a n-electron-deficient heterocycle reacts with electron-rich dienophiles, such as 0,0- and 0,S-ketene acetals, S,S-ketene thioacetals, N,N-ketene acetals, enamines, enol ethers, ynamines, etc. 

Similarly, the monothione 24 reacts with acetylhydrazine to give the [l,2,4]triazolo[4,3-a][l,5]benzodiazepinone 25 with prop-2-ynamine the imidazo[1,2- ][1,5]benzodiazepinone 26 is produced and bromoacetaldehyde diethyl acetal provides the thiazolo[3,2-a][l, 5]ben-zodiazepinonc 27.282... 

The reaction of several substituted imidazo[4,5-c/]-, pyrazolo[3,4-r/]- and triazolo[4,5-zf]pyrid-azines 3 with ynamines, in competition with [4 + 2] cycloaddition, leads to [2 + 2] derivatives 4, which rearrange to l,2-diazocines5.7 8 The reaction seems to be sensitive to the substituents, as replacement of the electron-withdrawing group R on the pyridazine ring of the pyrazolo compound (A = N, B = CH) by chlorine completely inhibits both the [4 + 2] and [2 + 2] cycloaddition reactions. The X-ray structure of the imidazo derivative 5 (R = Ms, A = CH, B = N) reveals a tub conformation of the eight-membered ring. 

A solution of 1-phenyl-1//-pyrazolo[3,4-rf]pyridazinc-7-carbonitrilc (150 mg. 0.68 mmol) and A,A-diethyl-prop-l-ynamine(151 mg, 1.36 mmol) in l,4-dioxane(2 mL) was refluxed for 5 h. After cooling, the reaction mixture was poured onto excess ice, and extracted with CHC13. The extract was washed with H20, dried (Na2S04) and concentrated under reduced pressure. Purification by chromatography (silica gel, benzene then bcnzene/EtOAc 20 1) gave, from the benzene eluate, 6-diethylamino-1 -phenyl-1 //-indazole-7-carbo-nitrile [yield 81 mg (39 %) mp 104-105 C (benzene/petroleum ether)] as slightly yellow prisms and, from the second eluate, the diazocine 5 as yellow needles yield 90 mg (40 %) mp 121-122 C (benzene/ petroleum ether). 

An important method for the synthesis of 1,3-diazocines consists of the reaction of pyrimidines 1 with ynamines to give [2 + 2] cycloadducts, which rearrange to the eight-membered-ring compounds 2 by valence tautomerization.2-3... 

The reaction is hindered by substitution in the 7-position, as revealed in the formation of 2e. Ynamine attack at the other imino moiety in the pyrimidine ring is even possible, which leads to 1,5-diazocines in an analogous reaction mechanism (cf. Section 1.5.). 

Some annulated pyrimidines react with ynamines via [2 + 2] cycloadducts to give 1,5-diazocine systems. The reaction strongly depends on the substitution pattern of the starting material and may also lead to 1,4-diazocine systems (see Section 1.3.1.2.).46,47... 

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