Phenylacetylene amination

These authors observed that in 80% aqueous ethanol, the rates were pseudo first order in bromostyrene, except for the P-NO2-isomer, which did not react even at 190° C. The products of reaction in the cases where X = NH2, CH3CONH, and CH3O were exclusively the corresponding acetophenones and, for X = H, 74% acetophenone and 22% phenylacetylene. Reaction rates were found to increase with solvent polarity as well as addition of silver ion, but they were independent of added triethylamine (except in the very unreactive p-nitro isomers, where in the presence of added amine, a second-order reaction ensued that resulted exclusively in p-nitrophenylacetylene as product). 

Tu found that when aniline was used instead of the secondary amine under otherwise identical conditions 2,4-diphenyl-substituted quinoline was formed in 56% yield. Phenylacetylene and aniline were initially used as model substrates for exploring the aldehyde scope. With aromatic aldehydes the reactions proceeded smoothly to give the corresponding quinolines in moderate to good yields. A heteroaromatic aldehyde is also compatible with this transformation and the expected product was afforded in 83% yield. However, when ahphatic aldehydes were subjected to the reaction, the desired product was obtained in low yield (Scheme 19) [34]. 

PhNHj react in the presence of HgClj (5%) to produce the same anils as those obtained with the HgO/BFj.OEtj system (Eq. 4.63), but at room temperature and with a higher TOF (12 h ) [259]. Phenylacetylene and secondary aromatic amines afford enamines Hke those of Eq. (4.64), but ahphatic terminal alkynes and secondary aromatic amines give rise to a mixture of enamines (Eq. 4.65) [259]. 

The hydroamination of alkynes with primary and secondary ahphatic amines necessitates the use of higher amounts of catalyst (17%) and higher temperatures, and TOFs are low (<1 h ) [260]. With ahphatic and aromatic terminal alkynes and a 5-fold excess of primary aliphahc amines, the products are the corresponding imines (40-78% yield, TOF up to 0.3 h ). In contrast to the CujClj-catalyzed reaction of phenylacetylene and secondary ahphatic amines (Scheme 4-12), the HgClj-catalyzed reachon is fully regioselechve for the Markovnikov hydroamination products which do not evolve under the reachon condihons (Eq. 4.66) [260]. 

The hydroamination of phenylacetylene with primary or secondary aromahc amines is also catalyzed by Tl(OAc)3 to give imines or enamines, respectively, in low to good yields (10-89%) with TOF up to 6 h [261]. 

A combination of Co-mediated amino-carbonylation and a Pauson-Khand reaction was described by Pericas and colleagues [286], with the formation of five new bonds in a single operation. Reaction of l-chloro-2-phenylacetylene 6/4-34 and dicobalt octacarbonyl gave the two cobalt complexes 6/4-36 and 6/4-37 via 6/4-35, which were treated with an amine 6/4-38. The final products of this domino process are azadi- and azatriquinanes 6/4-40 with 6/4-39 as an intermediate, which can also be isolated and separately transformed into 6/4-40 (Scheme 6/4.11). 

The amine adduct Et2Mg(tmeda) (R = Me, Et) reacts with phenylacetylene to produce [Mg2Et(phenylethynyl)3-(tmeda)]2 benzene 46 (Figure 22).170 Related to that of alkali metal alkynyl magnesates, the structure of 46 is... 

Free-radical additions of trichlorosilane to acetylenes initiated by benzoyl peroxide were stereospecific trans additions, giving only cis adducts. The same workers observed that tri-n -butyl amine also catalyzed addition of trichlorosilane to phenylacetylene but gave a mixture of cis- and trans -l-phenyl-2-trichlorosilylethene, 1,1-phenyltrichlorosilylethene, and 1-phenyl-l,2-bistrichlorosilylethane (54). No stereospecificity was observable with the amine as catalyst. 

The Sonogashira reaction is of considerable value in heterocyclic synthesis. It has been conducted on the pyrazine ring of quinoxaline and the resulting alkynyl- and dialkynyl-quinoxalines were subsequently utilized to synthesize condensed quinoxalines [52-55], Ames et al. prepared unsymmetrical diynes from 2,3-dichloroquinoxalines. Thus, condensation of 2-chloroquinoxaline (93) with an excess of phenylacetylene furnished 2-phenylethynylquinoxaline (94). Displacement of the chloride with the amine also occurred when the condensation was carried out in the presence of diethylamine. Treatment of 94 with a large excess of aqueous dimethylamine led to ketone 95 that exists predominantly in the intramolecularly hydrogen-bonded enol form 96. 

A-Propargylpiperidines 218 (Ar = Ph, 4-MeOCgH4 or 2-thienyl) are produced from the aminals 217 and phenylacetylene under the influence of copper chloride215. 

Unlike W and Mo catalysts, Rh catalysts are not suited to oriho-swhstxtutcd phenylacetylenes because Rh catalysts are rather sensitive to the steric effect. Instead, Rh catalysts are suitable to various phenylacetylenes having polar groups (e.g., ether, ester, amine, carbazole, imine, nitrile, azobenzene, nitro groups) at ra-position, resulting in the formation of high MW poly(phenylacetylenes). Many such examples are found in Table 3. 

The air oxidation of phenylacetylene and secondary amines in the presence of cupric acetate in benzene solution yields ynamines [22], This reaction requires only catalytic amounts of cupric salts and gives high conversions in less than 30 min when the Cu+2/phenylacetylene ratio is only 0.02. Only 1,4-diphenylbutadiyne is produced if the stoichiometric amount of cupric ion is used in the absence of oxygen. The yield of ynamine can be increased from 45 to 90 % if the stoichiometric amounts of a reducing agent such as hydrazine are continuously added during the course of the reaction. The use of primary amines under similar conditions yields the acetamide derivative. 

Catalytic amination of phenylacetylene and its derivatives may be performed by using [Ru3(CO)i2] catalyst to afford the corresponding enamines in high yields 595... 

Bis-amine disulfides can serve as sulfur sources in a radical condensation with two equivalents of an alkyne. When a mixture of a bis-amine disulfide and phenylacetylene was heated in a Paar bomb for three hours at 140 °C, an 82% yield of a mixture of 2,5-diphenylthiophene (278 R1 = Ph, R2 = H) and 2,4-diphenylthiophene (279) was obtained. 2,4-Diphenylthiophene was the major product, constituting 85% of the mixture. When methyl propiolate was so treated, the only product was (278 R1 = C02Me, R2 = H) in about 48% yield. Similarly, methyl phenylpropiolate gave only (278 R1 = C02Me, R2 = Ph) in 67% yield. Thus there is a degree of regiospecificity to the reaction, and a radical mechanism which ultimately involves a polar [3 + 2] mechanism, as shown in Scheme 23, was proposed (77TL3413). 

Since the substitution reaction succeeded so well with olefins, the obvious extension to acetylenes was tried. Of course, only terminal acetylenes could be used if an acetylenic product was to be formed. This reaction has been found to occur but probably not by a mechanism analogous to the reaction of olefins (43,44). It was found that the more acidic acetylene phenylacetylene reacted with bromobenzene in the presence of triethylamine and a bisphos-phine-palladium complex to form diphenylacetylene, while the less acidic acetylene, 1-hexyne did not react appreciably under the same conditions. The reaction did occur when the more basic amine piperidine was used instead of triethylamine, however (43). Both reactions occur with sodium methoxide as the base (44). It therefore appears that the acetylide anion is reacting with the catalyst and that a reductive elimination of the disubstituted acetylene is... 

Although, at that time, the term supramolecular chemistry had not yet been coined, the practical potential for inclusion complexation for acetylene alcohol guests 1 and 2 was recognized back in 1968 [12], Spectroscopic studies showed that 1 and 2 formed molecular complexes with numerous hydrogen-bond donors and acceptors, i.e. ketones, aldehydes, esters, ethers, amides, amines nitriles, sulfoxides and sulfides. Additionally, 1 formed 1 1 complexes with several n-donors, such as derivatives of cyclohexene, phenylacetylene, benzene, toluene, etc. The complexation process investigated by IR spectrometry revealed the presence of OH absorption bands at lower frequencies than those for uncomplexed 1 and 2 [12], These data, followed by X-ray studies, confirmed that the formation of intermolecular hydrogen bonds is the driving force for the creation of complexes [13],... 

Zn(OTf)2) and amine base (e.g. triethylamine, Hiinig s base) could be readily monitored by observation of the disappearance of the stretch corresponding to the terminal C-H bond of phenylacetylene. Consistent with a reversible metalation, reappearance of the terminal C-H stretch could be observed on stepwise addition of triflic acid. During treatment of phenylacetylene with either amine base or Zn(OTf)2 alone, no evidence of deprotonation was detected. 

Table 1 Results of oxidative coupling reaction of phenylacetylene using different amine-CuCl complexes ...

The macromolecular helicity induced in poly(phenylacetylene)s 28-30 (Fig. 14) upon complexation with chiral amines is dynamic in nature, and therefore, the ICD due to the helical chirality immediately disappears when exposed to a stronger acid such as trifluoroacetic acid. However, during the intensive exploration of the helicity induction and chirality amplification mechanism of the poly(phenylacetylene)s, such an induced helical chirality of 28-30 by an optically active amine such as (R)-39 has been found to be maintained, namely memorized , when the chiral amine is completely removed and replaced by various achiral amines, for example, 71 and 72 for 28 and diamines such as ethylenediamine for 29 and 30 in... 

The noncovalent helicity induction and chiral memory concept is versatile enough to produce and maintain either a right- or left-handed helix because the helix-sense is predetermined by the chirality of the enantiomeric amines used. Consequently, the opposite enantiomeric helicity induction and the memory requires the opposite enantiomeric amine, followed by replacement with achiral amines. However, both mirror-image enantiomeric helices can be produced with a high efficiency from a helical poly(phenylacetylene) induced by a single enantiomer (Fig. 26) [129]. This dual memory of enantiomeric... 

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