Diacetylene, reaction

Vinylacetylenes or -diacetylenes, reactions with binucleophiles leading to N-heterocycles 81 UK 1252. 

The synthetic method utilizes the three dimensional periodicity of a crystalline monomer phase as a template to determine the molecular and crystallographic structures of a polymer(4-12). In the ideal case, solid state reaction (initiated either thermally, mechanically, or by exposure to actinic radiation) transforms a monomer single crystal to a polymer single crystal with nearly the same dimensions and similar structural perfection. G. Wegner first demonstrated that certain diacetylene reactions closely approximate this ideal case(4) ... 

Phase separation occurs during certain diacetylene reactions, despite the fact that a continuous monomer-to-polymer single crystal transformation is not forbidden by symmetry considerations. For example, the diacetylene with substituent groups -CH2OH can be pol)nnerized to a limiting conversion of about 70% as a one-phase reaction. Annealing this partially pol3nnerized phase results in phase separation to produce a non crystalline polymer phase and the initial monomer phase(6). 

Photopolymerization reactions of monolayers have become of interest (note Chapter XV). Lando and co-workers have studied the UV polymerization of 16-heptadecenoic acid [311] and vinyl stearate [312] monolayers. Particularly interesting is the UV polymerization of long-chain diacetylenes. As illustrated in Fig. IV-30, a zipperlike process can occur if the molecular orientation in the film is just right (e.g., polymerization does not occur readily in the neat liquid) (see Refs. 313-315). 

A solution of the monosodium salt of diacetylene in 300 ml of liquid ammonia is prepared from 13.8 g (0.6 g-atoms) sodium and 24.6 g (0.2 moles) l,4-dichlorobut-2-yne. To this mixture is added a suspension of 5 g (17.6 mmoles) 3-methoxyestra-l,3,5(10)-trien-17-one in anhydrous tetrahydrofuran at —40° and the reaction mixture is stirred and maintained at this temperature for 2 hr. Ammonium chloride is then added and the ammonia is allowed to evaporate overnight. The residual solids are extracted with methylene dichloride and the extracts washed with water, dried over magnesium sulfate, and evaporated at 70°. The resultant dark gum is... 

The first representative of the acetylenic derivatives, 3(5)-ethynylpyrazole, was obtained by condensation of diacetylene with diazomethane by Kuhn and Henkel (41LA279) and later by other authors (69IZV2546), and by reaction of acetylene with diazopropyne (62AG252 68LA113) (Scheme 2). 

The standard technique for obtaining alkynylpyrazoles consists of mixing up the ether solutions of diazoalkane and diacetylene or its derivatives (or diazopropyne and acetylene) and keeping the reaction mixture either for several hours or for three weeks within a narrow temperature range (0-20°C) (Tables II and III). 

Thus, the reaction of diazoalkanes andnitrilimines with diacetylenic derivatives can be used as a method for synthesizing acetylenylpyrazoles. 

It is known that diacetylenes (in Favorsky s reaction, for example) are 1000-fold more active than monoacetylenes. It is of interest to consider how the accumulation of triple bonds will affect the compound acidity. However, in the literature there are no data on the CH acidity of diacetylenic compounds. We were the first to estimate the p/ifa of a monosubstituted diacetylene, 4-butadiynyl-l,3,5-trimethylpyrazole, to be about 24-26 log units. Unfortunately, the authors (83IZV466) have failed to determine the acidity of the diyne more accurately owing to the side processes of remetallization that complicate control over reaction. 

First we consider diacetylene transformations leading to fundamental heterocycles (pyrroles, thiophene, selenophene, tellurophenes, pyrazoles, isoxazoles, pyridines, pyrimidines). Then cyclization reactions involving 1-heterobut-l-en-3-ynes, 4-heterobut-3-en-2-ones, and 4-heterobut-3-yn-2-ones (91UK103 92KGS867 00UK642) as diacetylene equivalents are discussed. 

If the reaction of diacetylene and its substituted derivatives with ammonia or primary amines is carried out in the presence of a copper(I) salt, the main reaction product formed in an autoclave after brief heating to 150°C turns out to be pyrrole or pyrrole derivatives 1 (65CB98 71MI1). 

Because diacetylene is unstable, a stable diacetylene derivative, 1-methoxybut-l-en-3-yne (65CB98), is often employed in the synthesis of pyrroles. The reaction with ammonia proceeds under conditions of heterogeneous catalysis (a mixture of reagent vapors is passed through a catalyst-containing reactor heated to 150°C), approaching a yield of 50-70% but with primary aromatic amines, the yield drops to 20%. 

The synthesis can be conducted both in solution and without solvents. The reaction in solvent (e.g., methanol, ethanol, dioxane, dimethylformamide) is recommended for volatile 1,3-diynes and amines in this case the pyrroles are purer and the yield is higher. With disubstituted diacetylenes, ammonia and primary alkyl- and arylamines produce 1,2,3-trisubstituted pyrroles under the same conditions (65CB98 71MI1). Since disubstituted diacetylenes are readily obtained by oxidative coupling of acetylenes (98MI2), this reaction provides a preparative route to a wide range of pyrroles. 

A process for the preparation of functionalized pyridines from diacetylene and the ethyl ester of /3-aminocrotonic acid and acetylacetonimine (72ZOR1328 75DIS) has been described. Owing to the lower nucleophilicity of nitrogen in the initial enamine esters and enamine ketone, the reaction with diacetylene occurs in the presence of sodium metal (80°C, dioxane, 3 h, yield of up to 20%). 

In 1967 Matsoyan discovered the reaction of diacetylene with hydrazine hydrate leading to 3(5)-methylpyrazoles (13) (68AKZ998 70AKZ640 71AKZ743 72MI1). 

In the reactions of nucleophilic addition to diacetylene, monoalkylhydrazines behave in two ways (71AKZ743). In an anhydrous medium at 40-50°C, the reaction with methyl- and ethylhydrazines proceeds in such a way that a more nucleophilic disubstituted nitrogen atom attacks the terminal carbon atom of diacetylene to form l-alkyl-3-methylpyrazoles (17), the content of isomeric 1-alkyl-5-methylpyrazoles being 15% according to GLC (71AKZ743 73DIS 77AKZ332). 

At the same time, the reaction of diacetylene with anhydrous 2-hydroxyethyl-hydrazine leads to l-(2-hydroxyethyl)-5-methylpyrazole (19) only (71AKZ743). 

The reaction direction remains the same for methyldiacetylene and diphenyl-diacetylene (120°C, 20 h, yield 85.8%) (71AKZ743), the cyclization products being 1,3,5-trisubstituted pyrazoles 20 and 21. 

The reaction of disubstituted diacetylenes with hydrazine hydrate was reported by Darbinyan et al. (70AKZ640). In the first stage the addition of hydrazine to the terminal carbon atom of the diacetylene system is analogous to that of primary amines to diacetylene (69ZC108 69ZC110). With monosubstituted diacetylenes (R = H), hydrazine adds to the terminal triple bond. This leads to the formation of vinylacetylenic hydrazine 22 which cyclizes to dihydropyrazole 23 subjected to further isomerization to the pyrazole 25. It is possible that hydrazine 22 undergoes hydration to the ketone 24 which can easily be cyclized to the pyrazole 25... 

The reaction of diacetylene and its asymmetric homologs (penta-l,3-diyne, hexa-1,3-diyne) with semicarbazide (72ZOR2605) affords the amides of 3-methyl-pyrazole- 1-carboxylic acid (27) (80°C, EtONa, EtOH, 40 h). Amide 26 undergoes irreversible rearrangement to amide 27 at 80°C (EtONa, EtOH). 

The reaction of diacetylene or its monosubstituted homologs with guanidine in the presence of an equimolar amount of sodium ethylate (80°C, EtOH, 14 h) leads to 2-amino-4-alkylpyrimidines (33) (70ZOR1347 71ZOR14). Their structures were proved by comparison of their properties (as well as those of their picrates) with those of authentic samples obtained by independent synthesis. 

The reaction of diacetylene with propane-1,3-diol gives 2-(prop-2-ynyl)-l,3-dioxane (39), 2-(propa-l,2-dienyl)-l,3-dioxane (40), and 2-(prop-l-ynyl)-l,3-dioxane (41) (74ZOR953). 

As in the reaction of diacetylene with alcohols (00UK642), the addition of glycols seems to start with attack at the terminal carbon atom of diacetylene, but no intermediate hydroxyl-containing enyne ether was isolated. 

Depending on the conditions, the reaction of diacetylene with sulfide ions leads either to di(2-ethynylvinyl)sulfide (46) (79ZOR1554) or thiophene (76DIS 80GEP2818580 81KGS1694), the product of cyclization of ethynylvinylthio anion or of the corresponding thiol. 

Benzylmercaptan reacts with diacetylenes 57 under base-catalyzed conditions in aregio- and stereoselective fashion to form diadducts Z,Z-l,4-di(benzylthio)buta-1,3-dienes (59). In this case, monoadducts 58 can be isolated (96T12677). The reaction with r-butylmercaptans gives good results for diacetylenes with aromatic substituents. 

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