RU2515241C1 - Method of producing 1-phenyl propargyl alcohol - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: reaction is carried out at atmospheric pressure and temperature of 0-10°C in the presence of a catalyst system of sodium hydroxide/aliphatic alcohol/DMSO, with molar ratio benzaldehyde:NaOH:aliphatic alcohol of 1:0.5-1.8:0.6-2, and benzaldehyde concentration of 0.86-1.72 mol/l. The end product is separated by vacuum distillation of the reaction mixture after neutralisation thereof with ammonium chloride and separating solid products by filtering.

EFFECT: method enables to obtain a 1-phenyl propargyl alcohol with high output.

3 cl, 9 ex

Description

The invention relates to methods for producing secondary acetylene alcohols, in particular 1-phenylpropargyl alcohol.

Secondary acetylene alcohols are universal building blocks for the synthesis of a number of organic compounds (unsaturated ketones, acetylenes, indoles, pyrroles, oxazoles). Especially valuable of these is 1-phenylpropargyl alcohol (FPS). It is widely used in fine organic synthesis, for example, to obtain acetylene and other unsaturated ketones (US patent 4418079, 1983). FPS is used as a crosslinking agent (patent RU 2171264, 2001), as an intermediate in the synthesis of antiplatelet agents of blood platelets (patent US 4418079, 1983), inhibitors of calcium uptake by leukocytes and platelets (patent US 5223518, 1993), adenosine A3 receptors (R. Volpini, S. Costanzi, C. Lambertucci, S. Taffi, S. Vittori, K.-N. Klotz, G. Cristalli, J. Med. Chem. 2002, v. 45, 3271-3279).

FPS is obtained in several ways. The most common of them is based on nucleophilic addition of metallized acetylenes to benzaldehyde. As the latter, lithium is used (MMMidland, J. Org. Chem. 1975, v.40, 2250-2252) or dilithium acetylinide (J. Mortier, M.Vaultier, F. Carreaux, J.-M. Douin, J. Org. Chem. 1998, v. 63, 3515-3516), sodium acetylenide (KN Campbell, W. K. Campbell, LT Eby, J. Am. Chem. Soc. 1938, v. 60, 2882-2884; ERHJones , JTMc Combie, J. Chem. Soc. 1942, 733-735; MWLeeds, M.Hill, HLKomarowski, Pat US 325457465, 1966), Zinc acetylenide (H. Sasaki, D. Boyall, EM Carreira, Helv. Chim Acta 2001, v. 84, 964-971), ethynyl magnesium halides (reagent Yotsitsa, A. Kojima, T. Irie, S. Harada, Y. Kameno, J. Katsube, H. Yamamoto, Pat US 4418079, 1983; U .Kazmaier, S. Lucas, M. Klein, J. Org. Chem., 2006, v. 71, 2429-2433; J.-J. Liu, F. Konzelmann, K.-C. Luk, Tetrahedron Lett. 2003 , v. 44, 3901-3904), sodium trimethylethynylaluminate (MJJoung, JHAhn, NMYoon, J. Org. Chem. 19 96, v. 61, 4472-4475).

Thus, the reaction of benzaldehyde with lithium monoacetylenide in dry tetrahydrofuran (THF) leads to FPS with a yield of 93% (MMMidland, /. Org. Chem. 1975, v.40, 2250-2252) or 81% (T.E. Nielsen, S. Le Quement, D. Tanner, Synthesis 2004, 1381-1390).

To a solution of lithium monoacetylenide obtained from acetylene and n-butyl lithium in THF (-78 ° C), a solution of benzaldehyde in THF is added, the mixture is stirred for 20 minutes and allowed to warm to room temperature. FPS is isolated from the reaction mixture (after dilution with water and neutralization with K ₂ CO ₃ ) by extraction with diethyl ether and subsequent vacuum distillation (MM Midland, J. Org. Chem. 1975 v.40, 2250-2252) or column chromatography (i.e. Nielsen, S. Le Quement, D. Tanner, Synthesis 2004, 1381-1390).

This method of producing FPS is implemented at -78 ° C; at a higher temperature, a more stable dilithium acetylenide is formed, which leads to a decrease in the yield of the target alcohol.

It was later shown (J. Mortier, M. Vaultier, F. Carreaux, J.-M. Douin, J. Org. Chem. 1998, v. 63, 3515-3516; Mortier, M. Vaultier, J.-M. Douin, W09929644, 1999) that at 0 ° C, the disproportionation of lithium monoacetylenide to dilithium acetylenide and acetylene is reversible, and when aldehyde is added, PPS is formed in 90% yield.

FPS with a yield of 76% is synthesized from benzaldehyde and lithium bis (diisopropylamino) boracetylide obtained from chloro-

bis (disopropylamino) borane and lithium acetylenide followed by treatment with n-butyllithium (THF, 0 ° C) (C. Blanchard, M. Vaultier, J. Mortier, Tetrahedron Lett. 1997, v. 38, 8863-8866).

The reaction of benzaldehyde with lithium trimethylsilylacetylenide in the presence of a chiral ligand - (28,2′S) -2-hydroxymethyl-1 - [(1-methylpyrrolidin-2-yl) methyl] pyrrolidine - leads to FPS in 87% yield (T. Mukaiyama , K. Suzuki, K. Soai, T. Sato, Chem. Lett. 1979, 447-448; T. Mukaiyama, Tetrahedron 1981, v. 37, 4111-4119).

The synthesis is carried out as follows: to a solution of 2-hydroxymethyl-1 - [(1-methylpyrrolidin-2-yl) methyl] pyrrolidine in diethyl ether (-35 ° C) trimethylsilylacetylene in dimethoxyethane (DME) and n-butyllithium in hexane are added sequentially. After 30 minutes of stirring at this temperature, the suspension was cooled to -123 ° C and a solution of benzaldehyde in DME was added dropwise, the mixture was stirred for 1 hour. After treatment with 2N hydrochloric acid, extraction with diethyl ether, drying over Na ₂ SO ₄ and removal of the solvent by thin layer chromatography (SiO ₂ ) allocate FPS.

FPS (73-86% yield) was obtained by reacting benzaldehyde with sodium acetylenide in dioxane (36-39 ° C), pyridine (39-41 ° C) or diethylene glycol dibutyl ether (30-33 ° C) (MWLeeds, M. Hill H. L. Komarowski, Pat US 325746565.1966). Sodium acetylide is obtained by the reaction of sodium metal with acetylene at 65-70 ° C for 2 hours in a solvent (dioxane, pyridine, diethylene glycol dibutyl ether), transfer it to the reaction flask and add benzaldehyde at a temperature of 30-41 ° C for 1-2 h, the mixture is stirred for another 3-4 hours. After cooling to 10 ° C, the mixture is hydrolyzed with water, the organic layer is separated, which is treated with crushed carbon dioxide and filtered. FPS is isolated by vacuum distillation.

From sodium benzaldehyde and sodium trimethylethynylaluminate (THF-toluene, room temperature), the FPS was synthesized in 93% yield (M.J. Joung, J.N. Ann, N. M. Young, Org. Chem. 1996, v. 61, 4472- 4475). Sodium trimethylethynylaluminate is obtained by adding slurry of sodium acetylenide in xylene to a solution of trimethylaluminum in a mixture of THF-toluene (0 ° C) with vigorous stirring. Then, the resulting solution was added to a solution of benzaldehyde in toluene at room temperature, after 1 h, the mixture was neutralized with a saturated solution of ammonium chloride and extracted with ethyl acetate, the organic layer was dried and concentrated under reduced pressure, the crude product was purified by column chromatography (SiO ₂ , hexane / ethyl acetate 9: 1 )

FPS is also obtained from benzaldehyde and ethynyl magnesium bromide in THF (A. Kojima, T. Irie, S. Harada, Y. Kameno, J. Katsube, H. Yamamoto, Pat US 4418079, 1983; U. Kazmaier, S. Lucas, M Klein, J. Org. Chem. 2006, v. 71, 2429-2433; PCChen, REWharton, PAPatel, AKOyelere, Bioorg. Med. Chem. 2007, v.15, 7288-7300). This synthesis of FPS is described in detail in the patent (A. Kojima, T. Irie, S. Harada, Y. Kameno, J. Katsube, H. Yamamoto, Pat US 4418079, 1983). A solution of ethyl magnesium bromide in dry THF was added to a solution of acetylene in THF (-30 + -20 ° C, 50 min). The reaction mixture is stirred for 50 min at a temperature below 0 ° C, then a solution of benzaldehyde in THF is added to it for 1 h, maintaining the temperature from 0 to 10 ° C, after which the mixture is stirred at room temperature (24 h), diluted with stirring and cooled with water and filtered. The solvent was removed from the filtrate, and the residue was distilled to obtain FPS. The output of FPS is not indicated in the patent. In (U. Kazmaier, S. Lucas, M. Klein, J. Org. Chem. 2006, v. 71, 2429-2433), a reaction scheme of benzaldehyde with ethynyl magnesium bromide (THF, 0 ° C) is given and the yield of PPS 90%), but the specific methodology for its preparation is not described.

With a quantitative yield of FPS in the form of a crude product (brownish oil without distillation), it was obtained by adding a solution of ethynyl magnesium bromide in THF to a solution of benzaldehyde in THF at room temperature (1 h) under argon (PCChen, REWharton, PAPatel, AKOyelere, Bioorg Med. Chem. 2007, v. 15, 7288-7300).

By the reaction of ethynyl magnesium chloride with benzaldehyde (THF, from -65 ° C to room temperature, 1.5 h), FPS was synthesized in 98% yield (J.-J. Liu, F. Konzelmann, K.-C. Luk, Tetrahedron Lett. 2003, v. 44, 3901-3904).

The interaction of zinc benzaldehyde and zinc acetylenide, obtained in situ from zinc triflate and acetylene in the presence of (+) - N-methylephedrine, leads to the high purity (S) -PSP enantiomer (97%) (H. Sasaki, D. Boyall, E. M. Carreira, Helv. Chim. Acta 2001, v. 84, 964-971). The reaction is carried out as follows: (+) - N-methyephedrine, toluene and triethylamine are added to the heated and evacuated zinc triflate in a nitrogen atmosphere. The mixture was kept under nitrogen at room temperature for 2 hours. Benzaldehyde was added to the suspension thus obtained (benzaldehyde: (CF ₃ SO ₃ ) ₂ Zn 1: 1.1 ratio), the mixture was cooled to -40 ° C and saturated with acetylene for 20 minutes passing it through the solution. After that, the reactor was sealed and the mixture was stirred for 14 days at room temperature. Then the reactor was again cooled to -40 ° C, opened and a saturated aqueous solution of ammonium chloride was added dropwise to the reaction mixture, the mixture was stirred while warming to room temperature for 2 hours. The organic layer was separated, washed with saturated NaCl and dried with sodium sulfate. After removal of toluene, the crude product was purified on silica gel (eluent hexane-ethyl acetate). The yield of acetylene alcohol is 35%, the conversion of benzaldehyde is 68%, the yield, taking into account the conversion of 52%. The disadvantages of the described method: the duration of the process (with the incomplete conversion of benzaldehyde and a low yield of the target product), the use of excess expensive zinc triflate and the need for additional cooling to -40 ° C.

The reaction of a bisulfite derivative of benzaldehyde with sodium acetylenide in liquid ammonia leads to FPS with a yield of 48% (J. Cymerman, K. J. Wilks, J. Chem. Soc. 1950, 1208-1209). To a solution of sodium acetylenide obtained from sodium metal and acetylene in liquid ammonia, a fractionally bisulfite derivative of benzaldehyde is added at a low flow of acetylene, and the mixture is stirred for 5.5 hours. Then, ammonium chloride (4.5-fold excess) is added and ammonia is evaporated. After ammonia has evaporated, a solution of dilute sulfuric acid (2N) is added to the residue and extracted with diethyl ether.

Removal of the solvent from the ether extracts after successive washing of the latter with saturated solutions of sodium bicarbonate and sodium bisulfite and drying (Na ₂ SO ₄ ) gives a residue from which PPS is obtained by vacuum distillation. The disadvantages of this method are the need for preliminary production of both sodium acetylenide and a bisulfite derivative of benzaldehyde, as well as the use of liquid ammonia and metallic sodium.

Lithium trimethylsilylacetylene obtained from trimethylsilylacetylene and lithium hexamethyldisilazane reacts with benzaldehyde, resulting in α - [(trimethylsilyl) ethynyl] benzylmethanol, treatment of which (THF, 0 ° C, 1 h) with tetra-butylammonium fluoride gives 81% FPS Dinerstein, JSSabol, K.A. Diekema, Pat US 5223518, 1993). Trimethylsilyl protection is also removed (methanol, room temperature, 3 h, FPS yield 95%) by treatment with potassium carbonate (V. Maraval, C. Duhayon, Y. Coppel, R. Chauvin, Eur. J. Org. Chem. 2008, 5144- 5156), or with silver salts (nitrate or phthalate) in a solvent mixture (acetone-water-methylene chloride, room temperature, 2.5-22 hours), FPS yield 76-86% (A.Orsini, A.Viterrisi, A. Bodlenner, J.-M. Weibel, P. Pale, Tetrahedron Lett. 2005, v. 46, 2259-2262).

The above methods for the preparation of PPS allow obtaining acetylene alcohol in high yields, but they have a number of significant drawbacks, the main of which is the use of metallized acetylenes, which requires a reaction in an inert atmosphere, as well as thorough drying of solvents and reagents. In most cases, cooling to low temperatures (-78, -123 ° C), as well as the use of special equipment, is necessary. In some methods, several solvents are used to carry out the reaction and isolate the desired acetylene alcohol., The target product is most often isolated using fire and explosive diethyl ether. Thus, all of the above methods for the synthesis of PPS are suitable only for its preparation in laboratories.

A three-stage process for the preparation of PPS by epoxidation of 3-phenyl-2-propene-1-ol (8% diisopropyl dihydroxy succinate, 5% tetraisopropyl titanium, 2 equivalents of tert-butyl hydroperoxide, CH ₂ Cl ₂ , -20-0 ° C, 76% yield) is described with subsequent chlorination (triphenylphosphine, 1.2 equiv., CCl ₄ , boiling, 4 h, 87% yield) and treatment with n-butyllithium (THF, -35 ° C, 74% yield), PPS yield, taking into account all stages, 49-52% ( S. Takano, K. Samizu, T. Sugihara, K. Ogasawara, J. Chem. Soc., Chem. Commun. 1989, 1344-1345; JSYadav, K. Premalatha, SJ Harshavardhan, BVSubba Reddy, Tetrahedron Lett. 2008, v .49, 6765-6767).

The multi-stage process, the use of expensive catalysts and organometallic compounds makes this method difficult to implement in industry.

Boiling in toluene (3 h) of hard-to-reach 2-phenyl-N-2- (3-phenyl-2-oxiranyl) ethylidene-1-aziranamine (α, β-epoxy-N-aziridinyl imine) leads to FPS in 95% yield ( Sunggak Kim, Chang Mook Cho, Tetrahedron Lett. 1994, v. 35, 8405-8408).

PPS with a yield of 93% was obtained by decarboxylation of 4-hydroxy-4-phenyl-2-butynoic acid (S. Ceylan, T. Klande, C. Vogt, C. Friese, A. Kirschning, SynLett, 2010, 2009-2013). The reaction is carried out by the flow method (acetonitrile, 3 hours) with induction heating (60 ° C) of a microreactor containing a copper wire, pumping a solution of propargylic acid by a pump through a reactor; at the outlet of the reactor, the reaction mixture is passed through a special cartridge that traps metal particles.

The disadvantage of this method of obtaining FPS is the use of a special reactor equipped with an induction heater, a magnetic field generator and a cartridge for removing metal particles. In addition, the original connection is not readily available. The method is suitable only for laboratory use.

Using multistage synthesis (6 steps), high-enantiomeric PPS (97%) was obtained from α, β-unsaturated esters (J. Chun, H.-S. Byun, R. Bittman, Tetrahedron Lett. 2002, v. 43, 8043 -8045). A preparative yield of FPS is not indicated.

When tetrabutylammonium is treated with fluoride (THF, room temperature, 5 min) or sodium hydride (THF, 0 ° C, 30 min) 1-phenyl-2- (p-tolylsulfinyl) -3- (trimethylsilyl) -2-propen-1- ol is converted into PPS with a yield of 28% and 83%), respectively (S. Nakamura, S. Kusuda, K. Kawamura, T. Toga, J. Org. Chem. 2002, v. 67, 640-647).

The disadvantages of this method are the inaccessibility of the starting compound. It is obtained in three stages using a wide range of reagents and solvents (diisopropylamine, n-butyl lithium, dry THF, phenylselenyl bromide, m-chloroperbenzoic acid, methylene chloride), as well as low temperatures (-78 ° C, -100 ° C), which requires special hardware design.

When treated with lithium diisopropylamide (THF, -78 ° C, 1 h), 2-chloro-1-phenyl-2-propen-1-ol synthesized from benzaldehyde and 1,1,1-trichloroethane in the presence of excess (4 equiv.) CrCl ₂ , FPS was obtained in 89% yield (JRFalck, DK Barma, Tetrahedron Lett. 1999, v. 40, 2091-2094). The disadvantages of this method are the use of a large number of extremely hygroscopic and irritating chromium dichloride and trimethylsilyl chloride, an organometallic compound and low temperatures.

Thus, it is obvious that despite the many and varied methods for producing FPS, none of them is technologically advanced enough to be implemented on an enlarged scale.

The most suitable for practical use are methods based on the reaction of benzaldehyde with lithium or sodium acetylenides, which are based on the nucleophilic addition of an acetylenide anion to a carbonyl group. Due to the increased danger of working with solutions of n-butyllithium in low-boiling solvents (usually n-hexane) and technical inconveniences (low temperatures, inert atmosphere), as well as the high cost of lithium reagents, the method based on the reaction of benzaldehyde with sodium acetylenide in liquid ammonia (KN Campbell, B.K. Campbell, LTEby, J. Am. Chem. Soc. 1938, v. 60, 2882-2884; ERH Jones, JTMcCombie, J. Chem. Soc. 1942, 733-735), which to date is most often used for the enlarged production of FPS. This method can be objectively considered the prototype of the invention. It is also based on the reaction of nucleophilic addition of an acetylenide anion to a carbonyl group. However, the fundamental difference between the present invention and the prototype is that acetylenide anions are generated in a fundamentally different way - not from sodium acetylenide, but by deprotonation of acetylene under the influence of NaOH in DMSO containing aliphatic alcohol.

Few variants of the methods for producing acetylene alcohols from acetylene and only aliphatic aldehydes in the presence of potassium hydroxide in various solvents are known - the Favorsky reaction (I.A. Favorskaya, Z.A. Shevchenko, I.M.Koshkina, ZhORKh 1967, v. 3, 2075 ; O.A. Tarasova, B. A. Trofimov, A. V. Afonin, L. M. Sinegovskaya, N. A. Kalinina, S. V. Amosova, ZhORKh 1991, v. 27, 1172-1180). However, until now it was believed that sodium hydroxide was not at all capable of catalyzing the Tabor reaction.

Thus, the closest in technical essence to the present invention is a method for producing PPS by the reaction of sodium acetylenide with benzaldehyde in liquid ammonia (E.R.H. Jones, J.T. McCombie, J. Chem. Soc. 1942, 733-735). This prototype method is implemented as follows: purified acetylene is quickly passed through liquid ammonia (1000 ml) with stirring and metallic sodium (23 g, 1 mol) is added in small pieces at such a rate that the blue color of the solution lasts no more than a few moments. Then a solution of benzaldehyde (106 g, 1 mol) in diethyl ether (100 ml) was added over 1 h and the mixture was stirred while cooling for another 3 h while continuing to let acetylene pass through. The mixture was left overnight to evaporate ammonia, after which diethyl ether and diluted cold sulfuric acid were added to the residue. Isolation of FPS is carried out in the usual way (extraction with ether, drying of the extracts, removal of solvent, vacuum distillation of the residue), obtaining 110 g (83%) of FPS.

Despite the high FPS yield, this method has significant disadvantages:

1) the use of toxic ammonia in a liquefied state, which involves its thorough drying and additional cooling to maintain the liquid state of the solvent;

2) the use of metallic sodium, which requires special precautions when working with it;

3) preliminary preparation of sodium acetylenide.

Also a significant disadvantage of the prototype method should include the method of isolation of the target product, namely the need for long-term evaporation of ammonia and the use of fire and explosive diethyl ether as an extractant.

These shortcomings impede the practical use of the prototype method for producing FPS in large quantities.

The proposed method for producing FPS, having a significant novelty, is devoid of these disadvantages of the prototype method.

According to the proposed method, the reaction of benzaldehyde with acetylene is carried out in the presence of NaOH (0.5-1.8 mol per 1 mol of benzaldehyde, preferably 1 mol per 1 mol of benzaldehyde) in a medium of dimethyl sulfoxide (DMSO) containing aliphatic alcohol (methanol, ethanol or tert-butanol, preferably ethanol) in an amount of 10-20% (preferably 10% or 1 mol per 1 mol of benzaldehyde) of the volume of DMSO taken at a temperature of 0-10 ° C. The proposed method differs from the prototype also in the allocation scheme of the target product and provides FPS with a yield of 47%.

R = Me, Et, t-Bu

In general terms, the proposed method for producing FPS is as follows. A mixture of DMSO, aliphatic alcohol and sodium hydroxide is heated to 125-130 ° C with stirring, and a soluble equilibrium catalytic system is formed:

R = Me, Et, t-Bu

In such a system, the basicity of the hydroxide anion increases and even more basic alkoxide anions are formed, which contribute to the deprotonation of acetylene. The resulting complex sodium cations with DMSO generate loose (solvate-separated) ion pairs with acetylenide anions in which acetylene carbanions have increased activity due to weakening of the interaction with the sodium cation.

Then, acetylene is passed into the resulting catalytic solution, cooled to 4-10 ° C, and a solution of benzaldehyde in DMSO is slowly added (over 1.5-3 hours), reducing the temperature to 0-1 ° C. After adding a benzaldehyde solution, the mixture is further stirred for 15-20 minutes. 1.2 equiv. (per sodium hydroxide taken) of dry ammonium chloride, stirred for 15-20 minutes, the resulting sodium chloride and polymer products are filtered off, the filtrate is distilled in vacuum, releasing aliphatic alcohol, DMSO, which after azeotropic drying can be used again in the process, and the target 1- phenylpropargyl alcohol.

Despite the fact that the yield of FPS obtained by the proposed method does not exceed the yield that is provided by the prototype method, the obvious technological advantages, the availability of the components of the catalytic system and the safety of the new method make the proposed method attractive for implementation in small tonnage chemistry and for obtaining large batches of product in laboratory conditions on bench installations.

The technological advantages of the proposed method include:

1) carrying out the process at atmospheric pressure;

2) carrying out the reaction at a temperature of 0-10 ° C, easily controlled technically (does not require deep cooling of the reaction mixture, as in the prototype method or analog methods);

3) the use of an inexpensive and affordable base - sodium hydroxide;

4) the use as a solvent of a non-toxic fire, explosion and environmentally friendly solvent (DMSO), which can be further used in the same process;

5) a new, more rational and safe scheme for the isolation of the target product — DMSO distillation from the reaction mixture in vacuum and subsequent vacuum distillation of the residue (the extraction stage using fire and explosive diethyl ether is excluded);

6) the process does not require special conditions for the process such as: inert atmosphere, carefully dried solvents and reagents;

7) the method is simple and convenient in hardware design.

The following non-limiting examples illustrate the invention.

Example 1

In a 3-necked round bottom flask with a capacity of 100 ml, equipped with a magnetic stirrer, reflux condenser and bubbler for feeding acetylene, 50 ml of DMSO, 3.44 g (0.086 mol) of NaOH, 5 ml [10% of the volume of taken DMSO, 4.01 g ( 0.086 mol)] of ethanol, the mixture is heated (125-130 ° C), then acetylene is bubbled with stirring at a speed of 40-45 ml / min, cooling to 4-10 ° C. Upon reaching the indicated temperature, a solution of benzaldehyde is added dropwise to the mixture [9.13 g (0.086 mol); the molar ratio of benzaldehyde: NaOH: alcohol is 1: 1: 1; the concentration of benzaldehyde 1.72 mol / l] in 10 ml of DMSO for 1 h 30 min, gradually reducing the temperature of the reaction mixture to 0-1 ° C. After adding the entire benzaldehyde solution, the reaction mixture was additionally stirred for 15-20 minutes, ammonium chloride (5.52 g, 0.103 mol, 1.2 equivalents per NaOH taken) was added, stirred for 15-20 minutes, sodium chloride was filtered off, washed with DMSO (10 ml × 2) . The filtrate was distilled in vacuo, initially distilling off ethanol and DMSO (57-68 ° C / 8 mm Hg), and then acetylene alcohol.

5.34 g (47%) of FPS are obtained, b.p. 111-112 ° C / 6 mmHg (lit. 135-136 ° C / 13 mmHg). ¹ H NMR (Bruker-400DPX, 400.13 MHz, CDCl ₃ , δ, ppm, internal standard HMDS): 7.62 (2H, m, m-Ph), 7.53 (2H, m, o-Ph), 7.34 ( 1H, m, p-Ph), 5.46 (1H, s, CH), 2.65 (1H, s, ≡CH), 2.23 (1H, br.s, OH).

Example 2

In the conditions of example 1, at the same temperature (0-10 ° C), using the same load, except for the amount of NaOH [6.19 g (0.155 mol) instead of 3.44 g (0.086 mol); the molar ratio of benzaldehyde: NaOH: alcohol 1: 1.8: 1; the concentration of benzaldehyde 1.72 mol / l], after processing, as described in example 1, receive 4.66 g (41%) of FPS.

Example 3

In the conditions of example 2, at the same temperature (0-10 ° C), using the same load, except for the amount of DMSO (100 ml instead of 50 ml) and ethanol [10 ml, 10% of the volume of taken DMSO, 8.02 g (0.174 mol) instead of 5 ml, 4.01 g (0.086 mol); the molar ratio of benzaldehyde: NaOH: alcohol 1: 1.8: 2; the concentration of benzaldehyde 0.86 mol / l], after processing, as described in example 1, get 2.41 g (21%) of FPS.

Example 4

In the conditions of example 1, at the same temperature (0-10 ° C), using the same load, except for the amount of NaOH [1.72 g (0.043 mol) instead of 3.44 g (0.086 mol); the molar ratio of benzaldehyde: NaOH: alcohol is 1: 0.5: 1; the concentration of benzaldehyde 1.72 mol / l], after processing, as described in example 1, receive 4.10 g (36%) of FPS.

Example 5

In the conditions of example 1, at the same temperature (0-10 ° C), using the same load, except for the amount of ethyl alcohol [7.5 ml, 15% of the volume of DMSO taken, 6.01 g (0.130 mol) instead of 5 ml, 10% from the volume of DMSO taken, 4.01 g (0.086 mol); the molar ratio of benzaldehyde: NaOH: alcohol is 1: 1: 1.52; the concentration of benzaldehyde 1.72 mol / l], after processing, as described in example 1, receive 4.79 g (42%) of FPS.

Example 6

In the conditions of example 1, at the same temperature (0-10 ° C), using the same load, except for the amount of ethyl alcohol [10 ml, 20% of the volume of DMSO taken, 8.02 g (0.174 mol) instead of 5 ml, 10% from the volume of DMSO taken, 3.98 g (0.086 mol); the molar ratio of benzaldehyde: NaOH: alcohol is 1: 0.5: 2; the concentration of benzaldehyde 1.72 mol / l], after processing, as described in example 1, receive 4.77 g (42%) of FPS.

Example 7

Under the conditions of Example 2, at the same temperature (0-10 ° C), using the same load, methyl alcohol was taken instead of ethyl alcohol [5 ml, 10% of the volume of DMSO taken, 3.96 g (0.124 mol); the molar ratio of benzaldehyde: NaOH: alcohol 1: 1.8: 1.44; the concentration of benzaldehyde 1.72 mol / l], after processing, as described in example 1, get 4.09 g (36%) of FPS.

Example 8

In the conditions of example 2, at the same temperature (0-10 ° C), using the same load, tert-butyl alcohol [5 ml, 10% of the volume of DMSO taken, 4.05 g (0.055 mol) was taken instead of ethyl alcohol; the molar ratio of benzaldehyde: NaOH: alcohol 1: 1.8: 0.6; the concentration of benzaldehyde 1.72 mol / l)], after processing, as described in example 1, 3.20 g (28%) of FPS are obtained.

Example 9

Under the conditions of example 3, at a temperature (0-10 ° C), using the same load, but the benzaldehyde solution is added over 3 hours instead of 1 hour 30 minutes and after processing, as described in example 1, 3.98 g (35%) are obtained FPS.

Claims (3)

1. The method of producing 1-phenylpropargyl alcohol by the interaction of benzaldehyde with acetylene in the presence of a basic catalyst, characterized in that the reaction is carried out at atmospheric pressure and a temperature of 0-10 ° C in the presence of a sodium hydroxide / aliphatic alcohol / DMSO catalyst system with a benzaldehyde: NaOH molar ratio : aliphatic alcohol, equal to 1: 0.5-1.8: 0.6-2, and a concentration of benzaldehyde 0.86-1.72 mol / l. 2. The method according to claim 1, characterized in that the catalyst system is obtained by preheating sodium hydroxide / aliphatic alcohol in DMSO at a temperature of 125-130 ° C for 20-30 minutes 3. The method according to claim 1, characterized in that 1-phenylpropargyl alcohol is isolated by vacuum distillation of the reaction mixture after neutralizing it with ammonium chloride and separating the solid products by filtration.