Facile reaction

Most aromatic acid chlorides impart a strongly acid reaction when shaken with water (compare Section 111,88). All are completely hydrolysed by boiling with solutions of caustic alkalis and yield no product volatile from the alkaline solution (compare Eaters, Sections 111,106 and IV, 183). They may be distinguished from acids by their facile reactions with alcohols (compare Section 111,27), phenols (compare Section IV,114), and amines (compare Sections 111,123 and IV.lOO). 

Facile reaction of a carbon nucleophile with an olefinic bond of COD is the first example of carbon-carbon bond formation by means of Pd. COD forms a stable complex with PdCl2. When this complex 192 is treated with malonate or acetoacetate in ether under heterogeneous conditions at room temperature in the presence of Na2C03, a facile carbopalladation takes place to give the new complex 193, formed by the introduction of malonate to COD. The complex has TT-olefin and cr-Pd bonds. By the treatment of the new complex 193 with a base, the malonate carbanion attacks the cr-Pd—C bond, affording the bicy-clo[6.1,0]-nonane 194. The complex also reacts with another molecule of malonate which attacks the rr-olefin bond to give the bicyclo[3.3.0]octane 195 by a transannulation reaction[l2.191]. The formation of 194 involves the novel cyclopropanation reaction of alkenes by nucleophilic attack of two carbanions. 

Aminopalladation and subsequent carbonylation are also facile reactions. The carbonylation of substituted 3-hydroxy-4-pentenylamine as a carbamate (254) proceeds smoothly via the aminopalladation product 255 in AcOH to give 256[228). The protection of the amino group of the carbamate as tosyl amide is important in the carbonylation of 257 to give 258[229],... 

A trialkylsilyl group can be introduced into aryl or alkenyl groups using hexaalkyidisilanes. The Si—Si bond is cleaved with a Pd catalyst, and trans-metallation and reductive elimination afford the silylated products. In this way, 1,2-bis-silylethylene 761 is prepared from 1,2-dichloroethylene (760)[625,626], The facile reaction of (Me3Si)2 to give 762 proceeds at room temperature in the presence of fluoride anion[627]. Alkenyl- and arylsilanes are prepared by the reaction of (Me3Si)3Al (763)[628],... 

The most common catalysts are sodium hydroxide and calcium hydroxide, generally used at a modest excess over the nominal stoichiometric amount to avoid formaldehyde-only addition reactions. Calcium hydroxide is cheaper than NaOH, but the latter yields a more facile reaction and separation of the product does not require initial precipitation and filtration of the metal formate (57). 

Nucleophilic Reactions. The strong electronegativity of fluorine results in the facile reaction of perfluoroepoxides with nucleophiles. These reactions comprise the majority of the reported reactions of this class of compounds. Nucleophilic attack on the epoxide ring takes place at the more highly substituted carbon atom to give ring-opened products. Fluorinated alkoxides are intermediates in these reactions and are in equiUbrium with fluoride ion and a perfluorocarbonyl compound. The process is illustrated by the reaction of methanol and HFPO to form methyl 2,3,3,3-tetrafluoro-2-methoxypropanoate (eq. 4). 

The facile reaction of metallic tin in the presence of hydrogen chloride with acryUc esters to give high yields of bis( P-alkoxycarbonyleth5l)tin dichlorides is reported in References 115 and 116. This reaction proceeds at atmospheric pressure and room temperature and has been practiced commercially. Halogenostaimanes have been postulated as intermediates (105). 

This facile reaction involves a modest change in the absorption of visible light, largely because of the visible absorption band of <7 -azobenzene [1080-16-6] having a larger extinction coefficient than azobenzene [17082-12-1]. Several studies have examined the physical property changes that occur upon photolysis of polymeric systems in which the azobenzene stmcture is part of the polymer backbone (17). 

In accordance with observations in halodinitrobenzene derivatives, fluoropyrazines are by far the most reactive of the halopyrazines. Fluoropyrazine undergoes facile reaction with sodium azide to give azidopyrazine (27), which exists in dynamic equilibrium with tetrazolo[l,5-a]pyrazine (28) (66JHC435). 

Recently it has been shown that certain unsaturated ketones and alcohols are dehydrogenated extremely easily by DDQ. While the rapid dehydrogenation of the A ° -dien-3-one (73) is predictable (c/. A -3-ketones), the equally facile reaction of the 3-alcohol (75) is surprising. Presumably (73) is an intermediate in the conversion of (75), although oxidation of nonallylic alcohols normally requires higher temperatures. A -3-Ketones, A ° -3-ketones and A ( o) 3(x aicohols do not react at room temperature. ... 

The high reactivity of monoperfluoroalkyl-substituted alkenes was demonstrated prior to 1972 via the facile reaction of diazomethane with 3,3,3-tnfluoro-propene [9] More recently, such dipolarophiles were found to be similarly reactive... 

Steroidal a,j8-unsaturated ketones such as /l -3-ketones undergo a facile reaction with pyrrolidine to give the corresponding, d - -dienamines (111) (40,53). The reaction is much slower with morpholine and piperidine, which is undoubtedly due to the generation of the double bond exocyclic to the six-membered hetero rings in the step involving the dehydration of the intermediate carbinolamine (112) to the corresponding iminium ion (113). 

As the equilibrium concentration of N2O2 decreases rapidly with increase in temperature the decrease in rate is explained. However alternative mechanisms have also been suggested. ° l Nitric oxide reacts with the halogens to give XNO (p. 441). Some other facile reactions are listed below ... 

Similar syntheses carried out with sodium dithioformate 21 instead of dithiophenylacetate gave 5-amino-4-carbethoxythiazole 22 in a facile reaction, where 22 is identical with the product obtained by heating the analogous 2-mercaptothiazole with Raney nickel. ... 

The reactivity of 1-methyl groups is further exemplified by their facile reaction with aromatic aldehydes to... 

Factor b above is discussed in Sections II, B, 1 II, B, 4 and II, C. A hydrogen-bonded structure such as 221 can account for the facile reaction of 5-bromouracil or for the unique, so-called hydrolyzability of carboxymethylthio-azines (237). The latter may also react via the intramolecular mechanism indicated in 136. The hydrogen-bonded transition state 238 seems a reasonable explanation of the fact that 3,4,6- and 3,4,5-trichloropyridazines react with glacial acetic acid selectively to give 3-pyridazinones while other nucleophiles (alkoxides, hydrazine, ammonia, or sulfanilamide anion) react at the 4- and 5-positions. In this connection, 4-amino-3,5-dichloro-pyridazine in liquid hydrazine gives (95°, 3hr, 60%yield)the isomer-... 

Isopropoxycarbonyloxy radicals undergo facile reaction with aromatic substrates (e.g. toluene) by reversible aromatic substitution. 94 Isopropoxycarbonyloxy radicals react with S to give ring substitution (ca 1%) as well as the expected double bond addition.40 ... 

Traditionally thiols or mercaptans are perhaps the most commonly used transfer agents in radical polymerization. They undergo facile reaction with propagating (and other) radicals with transfer of a hydrogen atom and form a saturated chain end and a thiyl radical (Scheme 6.6). Some typical transfer constants are presented in Table 6.2. The values of the transfer constants depend markedly on the particular monomer and can depend on reaction conditions.4"1 44... 

Polymers with primary or secondary amine functionality cannot be prepared directly by RAFT polymerization these groups undergo facile reaction with thiocarbonylthio compounds. Such polymers can be prepared indirectly using RAFT agents with latent amine functionality, such as the phthalimido group in... 

This category is represented in the facile reaction of o-phenylenediamine (408) with 4-benzoyl-5-phenyl-2,3-dihydro-2,3-thiophenedione (409) (in toluene at 20°C for 30 min) to afford 3-(a-benzoyl-p-mercaptostyryl)-2(l//)-qumoxalinone (410) in 98% yield " also in the complicated reaction of 3-methyl-2,2,4-trinitro-2,5-dihydrothiophene 1,1-dioxide (411) with 2 equiv of ethyl 4-aminobenzoate (412) (in acetonitrile but no further details) to give ethyl 2-(p-ethoxycarbonylphenyl)-3-(l-methyl-2-nitrovinyl)-6-quinoxalinecarboxylate (413) in 51% yield.Several... 

Strictly analogous, but more facile reaction occurs when L = P(OCH2)3CEt. No insertion in MeCo(CO)[P(OCH2)3CEt]3 could be effected with the phosphite at 100°C. 

These are examples of structure Insensitive (facile) (Reactions 1-4) and structure sensitive (demanding) reactions (Reactions 3-7). 

Phenols are important antioxidants, with vitamin E being the most important endogenous phenolic membrane-bound antioxidant. Membrane levels of vitamin E are maintained through recycling of the vitamin E radical with ascorbate and thiol reductants. Vitamin E is a mixture of four lipid-soluble tocopherols, a-tocopherol being the most efiective radical quencher. The reaction of a-tocopherol with alkyl and alkylperoxyl radicals of methyl linoleate was recently reported. These are facile reactions that result in mixed dimer adducts (Yamauchi etal., 1993). 

Scheme 11.2 shows some representative halogenation reactions. Entries 1 and 2 involve Lewis acid-catalyzed chlorination. Entry 3 is an acid-catalyzed chlorination using NCS as the reagent. Entry 4 shows a high-yield chlorination of acetanilide by i-butyl hypochlorite. This seems to be an especially facile reaction, since anisole is not chlorinated under these conditions, and may involve the A-chloroamide as an intermediate. Entry 5 describes a large-scale chlorination done with NCS. The product was used for the synthesis of sulamserod, a drug candidate. 

That carbon monoxide could be oxidised in a facile reaction at cryogenic temperature (100 K) was first established in 1987 by XPS at an aluminium surface.21 The participation of reactive oxygen transients O 1 (s) was central to the mechanism proposed, whereas the chemisorbed oxide O2 state present at 295 K was unreactive. This provided a further impetus for the transient concept that was suggested for the mechanism of the oxidation of ammonia at a magnesium surface (see Chapter 2). Of particular relevance, and of crucial significance, was Ertl s observation by STM in 1992 that oxygen chemisorption at Al(lll) resulted in kinetically hot adatoms (Figures 4.1 and 4.7). 

In 1972 Wynberg and Heldersl> reported a facile reaction between tetramethyl-thiophene (80) and dicyanoacetylene at room temperature in the presence of aluminum chloride. On the basis of spectroscopic data of the reaction product as well as its sulfone, 3,4-dicyano-2,5,6,7-tetramethylthiepin structure (81) was assigned. The product was pyrolyzed at 140 and 300 °C to 83 and 84, respectively. Un-... 

According to the data in Table I this process is exothermic by 9 kcal/mol. Reaction 4 is one of the few processes in which methane is known to undergo a facile reaction at a transition metal center. Interestingly, the analogous reaction with FeH+ is not observed, even though it is exothermic by 10 kcal/mol (31). 

So far, no systematic work has been done on the use of recyclable, solid-phase catalysts in cross-coupling reactions. Most of the examples have been obtained for cross-couplings with either arylboronic acids or terminal acetylenes. It should be noted, however, that due care should be exercised when interpreting results on the cross-coupling of arylboronic acids with aryl iodides, as this extremely facile reaction can be catalyzed by practically any palladium-containing material, including trivial Pd black,481 e.g., as a sediment on the reaction vessel. Therefore, this reaction cannot serve as a reliable test for comparison between different catalytic systems. 

The useful chemoselective feature of the reaction is apparent from the reduction of trans-cinnamaldehyde (cinnamaldehyde/NaBH4-alumina, 1 1 mol equivalent) olefmic moiety remains intact and only the aldehyde functionality is reduced in a facile reaction. 

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