Acryloyl chloride synthesis

The scheme used to prepare the direct 8-aza-analogue 21 of estrone bears at least formal similarity to the Torgov-Smith steroid total synthesis sequence. Acylation of the phenethylamine 9 with acryloyl chloride gives amide 16. Michael addition of dimethylamine followed by Bischler-Napieralski cyclodehydration gives the dihydroisoquinoline, 17. 

Finally, another related study from the Sun laboratory concerned the synthesis of hydantoins utilizing acryloyl chloride to prepare a suitable polymer support [87]. All steps were carried out under reflux conditions in a dedicated microwave instrument utilizing 50-mL round-bottomed flasks. Identical reactions under classical thermal heating did not proceed in the same time period. 

As shown by the two examples represented in Scheme 99, chiral enaminoesters are good candidates for the synthesis of saturated or partially saturated oxazolo[3,2- ]pyridine derivatives (Scheme 99) acylation of 374 with acryloyl chloride or conjugate addition of 376 to 377 afford in both cases substrates that readily undergo cyclization, respectively to 375 <2002TL2521> and 378 <1996JOC1890>. 

The preparation of fluorinated alcohols was carried out in multistep routes according to the reported procedures.1012 The synthesis of acrylic and methacrylic esters as shown in Table 11.1 was carried out in a fluorocarbon solvent such as Freon 113 by the reaction of the respective fluorinated alcohol with acryloyl chloride or methacryloyl chloride and an amine acid acceptor such as triethyla-mine with examples shown in Scheme 1. Other attempts to esterify the fluoroalcohols directly with acrylic acid or acrylic anhydride were not successful.11 Product purification by distillation was not feasible because of the temperature required, but purification by percolation of fluorocarbon solutions through neutral alumina resulted in products of good purity identified by TLC, FTIR, and H-, 13C-, and 19F- FTNMRs. 

COPOLYMERIZATION WITH PARTICIPATION OF MULTIMONOMERS Synthesis of various multimonomers and their copolymerization with styrene, acrylonitrile or acrylic acid was described in a set of papers. Most of the early work on the copolymerization of multimonomers with vinyl monomers employed p-cresyl formaldehyde resins, esterified by methacryloyl chloride or acryloyl chloride, as one of the comonomers, and a simple vinyl monomer such as styrene or acrylonitrile as the other monomer. 

This product is then treated with acryloyl chloride. The initial step in this case probably involves the acylation of nitrogen on the enamine conjugate addition then completes the formation of the lactam ring (23-5). Treatment of that product with triethyl silane then reduces the ring unsaturation and cleaves the benzylic nitrogen bond on the auxiliary to yield (23-6) as the optically pure tmns isomer. Displacement of bromine with the mercapto benzthiazole (23-7) completes the synthesis of izonsteride (23-8) [25]. 

Kevin J. Quinn of the College of the Holy Cross chose (Organic Lett. 2005, 7, 1243) a complementary approach in his synthesis of rollicosin. The symmetrical diol 4 is also available from carbohydrate precursors. Monosilylation followed by esterification with acryloyl chloride gave 5. Exposure of 5 to the Grubbs catalyst in the presence of 6 led, by ring-closing metathesis and cross metathesis, to the y-lactonc 7. Note that 5-lactone formation did not compete ... 

A number of methods of 2-imino-TA synthesis are based on the cycliza-tion of acylthioureas containing an a,/ -unsaturated acid fragment. In the case of reactions of acryloyl chloride with thiourea (72MI1) or with N-substituted thioureas (73MI2), no A-acryloylthioureas were isolated and hydrochlorides of 3-substituted 5,6-dihydro-TAs 128 were obtained (Scheme 42). 

When the derivatives are required to convert to the parent 5-FU in vivo, appropriate substituents were introduced across the carbonyl groups in the chemical modification [20-25]. Though the first synthesis of acryloyl derivatives of 5-FU, which is the simplest polymerizable derivative, was done by Gebelein, the monomer has not been purified and collected [23]. In the present case, as shown in Scheme 2, silylated 5-FU was used instead of just 5-FU so as to give selectivity to the 1 TV-acylation similar to that of the acryloyl derivatives of thymine [9]. For the preparation of acryloyl-5-FU (AFU), methacryloyl-5-FU (MAFU) and / -vinylbenzoyl-5FU (VBFU), trimethylsilylated 5-FU (1) was allowed to react with acryloyl chloride, methacryloyl chloride and vinyl-benzoyl-chloride, respectively. The reaction was carried out in water-free acetonitrile solution after the addition of acid chloride at room temperature the solution was stirred for 30 min. This procedure afforded AFU in 16%, MAFU in 56%, and VBFU in 63% yield. 

A complementary approach, developed by Paquette, - uses substituted acryloyl chlorides as addends in reaction with structii ly embellished vinylsilanes. A general route to the vinylsilanes (87) was found in the silylation of vinyllithiums generated by the Shapiro reaction.The acylation with acryloyl chlorides takes place readily with aluminum trichloride to afford the divinyl ketones which are subsequently cyclized with tin tetrachloride. The Nazarov cyclization products were formed as a mixture of double tend isomers (equation 47). The best results were obtained with p,p-dimethylacryloyl chloride. Crotonyl chloride could be employed, but acryloyl chloride proved impractical. This metl owes much of its utility to the regiocontroUed synthesis of Ae vinylsilmes, thereby clearly establishing the loci of cyclopentannulation. 

Blasser, J. Synthesis and uses of pure chloromethyl chloroformate and an economical new route to trichloro-acryloyl chloride Ph. D. Thesis, The Pennsylvania State University, 1993... 

A third approach to brefeldin A by Greene dealt with a version of the second synthesis designed to provide optically active 161, as shown in Scheme 1.39. Enantiomerically pure alcohol (S)-( -i- )-240, obtained via resolution of the derived phthalate mono ester with brucine, was acylated with acryloyl chloride to afford 241. Lewis acid promoted Diels-Alder reaction of 241 and cyclopentadiene then led to a 75% yield of diastereomers 242a (endo) and 242b (exo) in a 97 3 ratio. 

Another original macromonomer, based on VAc, afforded interesting properties however the functionalization of such a monomer remains difficult [252,268-270]. The group of Sato [269,271-275] suggested the synthesis of VAc macromonomer by functionalization onto VAc telomers, obtained with 2-mercaptoethanol. The functionalization can be realized with acryloyl chloride, giving macromonomers with different molar masses (Table 24). 

Additive aldol reaction. An anri-selective synthesis of 5-phenylthio esters of 3-hydroxy-2-phenylthiomethylalkanethiolates from a mixture of acryloyl chloride, PhSLi and aldehydes is mediated by MgBr2 OEt2. 

Aza-annulation of 104 with a variety of acrylate reagents has been utilized in the synthesis of indoloquinoiizidine alkaloid skeletons (eq. 25). Aza-annulation of 104 was affected with acrylic acid (91%), acrylic acid/DPPA (95%), acryloyl chloride/DMAP (64, 63%), and methyl acrylate (37, 52%) to generate the pentacyclic eburnane skeleton 105.42 Carbonyl reduction gave Wenkert s enamine (106), which was carried on in the synthesis of ( )-apovincamine (107) and the clinically active synthetic analog ( )-Cavinton (108).42... 

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