Ynamines reaction with

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). 

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

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)... 

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). 

Both 3-diazO 1,2,4-triazoles and 4-diazo-l,2,3-triazoles easily give cycloaddition reactions with ynamine leading to 4-aminotriazolo-triazine 284 and the yields are generally higher than in the pyrazole and imidazole series (77S556) (Scheme 85). 

Thiete sulfones show an irregular behavior pattern when involved in cycloaddition reactions. With 1,3-dienes, dienamines, enamines, ynamines, diazoalkenes, cyclopropadiene, and its substitution products, furan, and anthracene, the addition proceeds in the normal fashion. With certain Diels-Alder reagents such as tetraphenylcyclopentadienone (tetracycloneX however, the cyclic sulfones react anomalously. The Diels-Alder adducts undergo decomposition with SO 2 and CO extrusion to a seven-membered ring, the tetraphenylcycloheptatriene 223. Bicyclic octadienone is produced as well (Eq. 62). The mechanism of this unusual reaction is proposed by... 

Unlike ynamines, ethyl vinyl ether requires the more electron-deficient 4-nitro-2-phenyl-5-oxazolecarboxylic acid methyl ester 271b for reaction to occur. The initial [4 + 2] cycloadduct 279 undergoes further reaction with ethyl vinyl ether to give the tricyclic oxazoline 280 in 76% yield (Scheme 8.79). 

Upon reaction with ynamines 2-methyl-7-tosylfuro[2,3-4]pyridazine 21 undergoes [2-1-2] cycloaddition-ring-expan-sion reactions to afford 22 (Equation 7) <1996H(43)199> as one of three products isolated. 

Some examples dealing with the [4 + 2] cycloaddition of ketenimines have been recorded (Scheme 58). Thus, thioketones and ynamines reacted with N-aryl ketenimines 257 through the carbon—nitrogen and the conjugated aromatic carbon—carbon double bonds to yield benzothiazine derivatives 258 (80JOC3766 82JOC3998) and substituted quinolines 259 (73JA5417), respectively. Simple ketenimines 261 were formed by reaction... 

Ynamines 119 and 120 give pyrazines 121 and 122 directly upon reaction with DISN (Scheme 41). 

Triazines are reactive electron-deficient dienes in Diels-Alder reactions with inverse electron demand. They react with alkenes, strained double bonds, electron-rich and electron-deficient alkynes and C=N double bonds. In most cases it is found that the dienophile addition occurs across the 3- and 6-positions of the triazine ring, but ynamines can also add across the 2- and 5-positions. The reactions are still under active theoretical and practical investigation. 

Another well-studied cycloaddition of 1,2,4-triazines is the reaction with ynamines (423). In this the dienophile often attacks the 1,2,4-triazines across the 2- and 5- rather than the 3- and 6-positions. This can perhaps be due to the transition state of the cycloaddition with ynamines being more polar than that in the cycloaddition with alkenes, and a partial negative charge in the 1,2,4-triazine ring is better stabilized at a nitrogen (N-2) than at a carbon (C-6). The products isolated from these reactions are pyrimidines (424). It was shown by using lsN-labelled 3-methyl-l,2,4-triazine that the reaction is in fact a [4 + 2] cycloaddition to N-2 and C-5 and not a [2 + 2] cycloaddition to the N(4)—C(5) bond (72LA(758)125). 

Neunhoeffer and Lehmann have shown that it is possible to reverse the diene character of the 1,2,4-triazine ring by introducing alkoxy or dialkylamino groups into the ring. Alkoxy-, dialkoxy- and dialkylamino-1,2,4-triazines are therefore less reactive toward ynamines but they still react with these dienophiles. Bis(dialkylamino)-, trialkoxy- and tris(dialkylamino)-l,2,4-triazines (425) behave as electron-rich dienes and give cycloaddition reactions with acetylenedicarboxylate (426) but not with ynamines. Compounds (425) and (426) afford the 2,4-bis(dialkylamino)pyrimidine-5,6-dicarboxylates (427) (77LA1413). 

A few cases of [4 + 2] cycloaddition reactions of 1,2,4-triazines with C=N double bonds have been reported. Reaction of 1,2,4-triazines (441) with benzamidine (442) in boiling toluene led to the isolation of the 1,3,5-triazines (443). It may be supposed that here the dienophile adds to the 2- and 5-positions of the 1,2,4-triazine, as in the reaction with ynamines, then a nitrile (R6CN) is eliminated and aromatization follows by loss of ammonia. In one case, the initially formed 1,3,5-triazine (443) reacted with a second molecule of benzamidine by [4 + 2] cycloaddition and elimination of R3CN and ammonia, resulting finally in triphenyl-1,3,5-triazine (444). This is a known reaction in the 1,3,5-triazine series (see Chapter 2.20) (81TL1393). 

The reaction between thioacylformamidines and ketenes leads to thiazine-6-ones (29) (Scheme 16) (75T3055). 4-Amino-4//-thiazines (30) are obtained by condensation of thioacylformamidines with acetylenic compounds (Scheme 17) (85JOC1545). Thiobenzoyl-1 and )V,A/-diethylami-nothiocarbonyl isocyanates and isothiocyanates have been reacted with enaminoketones and ynamines. Enaminoketones and ynamines reacted with thiobenzoyl isocyanate give thiazine-4-ones 31 and 32, respectively (Scheme 18) (76BCJ2828 85ZC324). 

In the following example (Eq. 7) P—QH means styrene polymer where a di-ethylaminoethynyl moiety is built up via a formylation, Wittig reaction with dichloro-methylene phosphorane and elimination-substitution steps. This polymer-bound ynamine is till now unique 18). 

Reactions with tertiary amines proceed via ethynylammonium salts which in many cases can be isolated 23 26 Their degradation to ynamines can be brought about thermally. This process becomes more easy in the presence of an excess of tertiary amine upon which an alkyl group is transfered (9, 10) 24 25>. 

A small amount (up to one equivalent) of HMPT is necessary in order to accelerate the alkylation step. Sec.-butyl bromide gives 38 % of the expected ynamine together with 25 % butene and 22 % of diethylaminoacetylene. Expectedly, t-butyl bromide undergoes only elimination and it serves as a convenient proton source to liberate N-ethynyl-methylaniline 106 Primary substrates react smoothly, however, even in complex cases and with this in mind, the scope of this reaction is almost unlimited. One more example illustrates this technique (83),35). 

Acetylenes can be prepared by intramolecular Wittig reaction but at least one of the groups R, R must be an electron-withdrawing group-aryl, ketone or ester function (152)171). Thus understably this approach could not be applied to the synthesis of ynamines starting with 101 (153). 

It was soon realized that the far more readily available 1-chloro and bromo acetylenes could be used too and in fact phenylchloroacetylene gives with lithium dimethylamide in ether, 87 % of the corresponding ynamine Similarly, N-lithium pyrroline affords 67 % of the corresponding ynamine In the following example (Eq. 7) P—CgH4 means styrene polymer where a di-ethylaminoethynyl moiety is built up via a formylation, Wittig reaction with dichloro-methylene phosphorane and elimination-substitution steps. This polymer-bound ynamine is till now unique... 

Reactions with tertiary amines proceed via ethynylammonium salts which in many cases can be isolated Their degradation to ynamines can be brought about... 

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