Reaction neat reagent

Solvendess organic reactions, neat reagents (solid-solid or solid-liquid) react together in the absence of a solvent and have been well reviewed as a fast developing technology [14a, 15] the postulated model by Scott et al. for such solventless reactions was proposed for better understanding the mechanism [16], Some selected representative reactions under solvent-free conditions are discussed below with emphasis on product separation. 

The first report appeared in 1999 when Banks described the basic reaction of 2,5-hexanedione and aniline, which was successfully carried out mixing the neat reagents and irradiating for 30 s in a domestic microwave oven. Several 2,5 dimethypyrroles 9 were prepared starting from the same 1,4 diketone [30] (Scheme 3). 

MW heated reactions in homogeneous media, using either neat reagents or in the presence of solvents, may also be performed at atmospheric pressure. This approach has been used particularly by Bose et al. [17]. (MORE Chemistry), who reported, for example, the rapid synthesis of heterocycles [18] in open vessels. Another approach, which avoids hazards due to the flammability of solvents, is to perform the reactions under reflux in a MW oven, which is modified to allow the reaction vessel to be attached to a reflux condenser outside the MW oven [7, 19]. It should be pointed out, however, that most of the available evidence shows that rate enhancements of MW heated reactions in homogeneous media at atmospheric pressure are small or nonexistent [19], This will be discussed in more detail later in this review (see also Chapt. 5 of this book). 

When the reactions are performed by adsorption of the reagents on to Ki0 mon-tmorillonite clay the aminoester is formed but when the reaction is performed by mixing the neat reagents with KF and 18-crown-6 and irradiation in a closed vessel /(-lactams were isolated in moderate to good yields [67]. 

Methyl hypofluorite (McOF) and tert-butyl hypofluorite (f-BuOF) have been prepared by the reaction of elemental fluorine with methanol and tert-butyl alcohol, respectively, in acetonitrile or propionitrile at — 78 °C. Methyl hypofluorite can be removed from the reaction mixture in a stream of nitrogen and purified by fractional distillation the liquid compound has a freezing point of — 142 C, is moderately long-lived, but explodes upon rapid warming.is tert-Butyl hypofluorite melts around — 94 °C and has an extrapolated boiling point of about 40 C the neat reagent must be regarded as a substance the hazards of which have not been fully defined.16... 

A mixture of methanesulfonic acid and P2Os used either neat or diluted with sulfolane or CH2C12 is a strongly acidic system. It has been used to control the rcgiosclcctivity in cyclization of unsymmetrical ketones. Use of the neat reagent favours reaction into the less substituted branch whereas diluted solutions favour the more substituted branch[3]. 

Reaction with neat reagent proceeds mainly with inversion. A marked solvent effect is observed in the reaction of 1 with DAST. 

Reduction of a,p-ynones. a,/J-Acetylenic ketones are reduced by 1 to (S> propargyl alcohols in 86-96% enantioselective purity. It is thus comparable to B-3-pinanyl-9-BBN in enantiomeric yields, although the reductions require 1-2 days and an excess of neat reagent for complete reaction. 

Phase-transfer catalytic (PTC) conditions, which are specific for anionic reactions (and anionic activation) are perfectly well tailored for microwave activation, because after ion exchange between a substrate and catalyst, the resulting nucleophilic ion pair is a highly polar species especially prone to interaction with microwaves [32]. Eventually, the mixture of neat reagents in an open vessel can lead to a reaction under microwave conditions provided that one of the reagents is liquid or a low melting solid that couples well with microwaves. On the other hand, even a small amount of a good microwave absorber (e.g,. H20, DMF for example, see Table 1.3) added to reaction mixtures that consist of substrates that do not absorb microwaves in the solid state can initiate an increase of reaction mixture temperature and then chemical reaction. 

Tris[(trimethylsilyl)methyl]aluminum, [(CH3)3SiCH2]3Al (1). This reagent is generated in situ by reaction of A1C13 with [(CH3)3SiCH2]Li. The neat reagent is pyrophoric. 

An important and extensively studied case involves reactions carried out in heterogeneous media between a solid and a liquid as neat reagents. The reaction can occur as an interfacial procedure allowed by either a partial solubilization of the solid in the liquid or by adsorption of the liquid on the surface of the solid, essentially owing to its high specific area [34,55]. 

The reactions of 4-alkoxyphenyl 4-dimethylaminophenyl tellurium dichlorides with hydrobromic acid were carried out with the neat reagents. The reaction mixtures were diluted with water and partially neutralized with dilute aqueous ammonium hydroxide to precipitate the tellurium dibromide6. 

Solvent-free reactions without support or catalyst (neat reagents)... 

The final conditions which we found consistently to give a quantitative analysis for carboxylic acids are shown in the Figure 10. Neat thallium ethoxide is a clear, not very viscous or volatile liquid at room temperature and pressure. Simple immersion of the polymer in this tetramer causes rapid penetration and reaction. Excess reagent can be washed out easily with ethanol to leave the thallium label behind. To remove excess ethanol, the sample was left in the vacuum prechamber for 30 minutes before measurement. Some excess oxygen is still seen. The samples are stable and have been found to keep the same thallium level even after being in the spectrometer under X-rays for more than an hour. Much less time is needed for analysis since the cross section is about 12 times that of C(ls). Carboxylic acid salts of thallium are known to be very stable to air, moisture and light (14). Preliminary experiments on an analogous mixed acid/ester system show that the ester functionality is not labeled, while the acid is. 

Dialkyl, diaryl, unsymmetrical dialkyl, alkyl aryl, and unsymmetrical diaryl telluriums served as the tellurium-containing starting materials (Vol. IX, p. 1075). The reactions with methyl iodide and low molecular mass organic bromides proceed at 20° in organic solvents such as chloroform and methanol or in mixtures of the neat reagents.With aryl telluriums several days are required for completion of the reaction. Diaryl telluriums with ortho-substituents react only with difficulty. Bis[2,4,6-trimethylpheny 1] tellurium did not combine with methyl iodide. The reactions with ethyl iodide and a-bromocarboxylic acids are accelerated by gentle heating. 

Indeed the reaction occurred explosively if the neat reagents were allowed to warm to room temperature. An ene reaction also occurred between methyl 2-methylcycloprop-2-ene-l-... 

Conversion of 1-oxoalkylphosphonates into 1,1 -di 11 uoroalkylphosphonates by reaction with (dieth-ylamino)sulfur trifluoride (DAST) has been explored using a variety of solvents and temperatures. The most satisfactory results are obtained by running the reaction neat at room tempera-ture, - but the reagent is also used in large excess in CH2CI2 solution (Scheme 7.79). 

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