MCRs processes

Figure 1-6. The MCR process for liquefying natural gas (1) coolers, (2) heat exchangers, (3,4) two stage compressors, (5) liquid-vapor phase separator.

MCR also tolerates the aliphatic isocyanide functionality [150], thus allowing the union with various IMCRs. Finally, we developed the first example of a triple MCR process (SCR toward 83) based on our 2//-2-imidazoline (65) and W-(cyano-methyl)amide (32) MCRs united with the Ugi-4CR (Fig. 25). 

The longest known and most widely used MCRs involve amines and carbonyls as two of the key components (Scheme 7.1). These processes benefit from the ability of amines 1 to react with aldehydes and ketones 2 in a reversible manner initially to form aminols, which can lead to various condensation adducts including imi-nium salts 4, depending on the substrates and reaction conditions. Reaction of 4 with a nucleophile 5 can lead to a new product 6, while if 5 can co-exist or be generated in the presence of 1 and 2, it would be possible to have an MCR process among 1, 2 and 5. If the reaction between 5 and 4 is reversible such an MCR would be of Type I, while an irreversible reaction will constitute a Type II MCR. Indeed, several well-established MCRs are based on the combination of an amine, a carbonyl and a third nucleophilic component. 

A major advantage of this MCR is that organoboronic acids are readily available in a large variety of structural configurations and they can be formed in isomeri-cally pure forms. As a result of their widespread utility in Suzuki-Miyaura coupling [27, 28] and other reactions [29, 30], a variety of aryl and heteroaryl [31] boronic adds are now commercially available and can be employed in this MCR process. Most of these compounds are also air and water stable as well as non-toxic and environmentally friendly. They also tolerate many functional groups, thereby... 

Multicomponent reactions (MCRs) are one-pot processes combining three or more substrates simultaneously [1], MCR processes are of great interest, not only because of their atom economy but also for their application in diversity-oriented synthesis and in preparing libraries for the screening of functional molecules. Catalytic asymmetric multicomponent processes are particularly valuable but demanding and only a few examples have been realized so far. Here we provide an overview of this exciting and rapidly growing area. 

The use of multicomponent reactions (MCRs) constitutes an attractive synthetic strategy for rapid and efficient library generation because diverse products are formed in a single step. Usually, MCR transformations do not involve the simultaneous reaction of all components. Instead, they are undertaken in a sequence of steps that are determined by the synthetic design. A drawback of many MCR processes is that they can be slow and inefficient, but microwave heating can be used as a tool to overcome these problems, as illustrated here with selected examples. 

The MCr process is based on the use of microporous hydrophobic membranes to concentrate feed solutions above their saturation limit through the evaporative mass transfer of volatile solvents. The partial evaporation of... 

As a mechanism of this MCR process, it is proposed that the Au-catalyst effects (1) a three-component coupling of pyridine-2-aldehyde, amine, and alkyne to give the (2-propargyl)pyridine 33 and (2) enhancement of the triple-bond activity by Au-coordination in favor of the cyclization 33 34 finally the Au-heterocycle 34 should undergo deprotonation ( 35) and demetalation to give the products 32. 

The Hantzsch synthesis can be conducted directly to the pyridines 167 in one-pot procedures (i) by combining the MCR process with oxidative aromatization by Pd-C/montmorillonite K-10 [123] and (ii) by using [NH4]C103 as a source of NH3 [124]. (b) In a three-component domino process, a,p-unsaturated aldehydes (mainly cinnamaldehydes), aromatic primary amines, and P-ketoesters catalyzed by CAN [125] or L-proline [126] are cyclocondensed to give N-arylsubstituted-5,6-unsubstituted 1,4-dihydropyridines 173 ... 

Aminobenzothiazole, benzaldehyde, and ethyl q anoacetate were reacted in aqueous medium with microwave irradiation (600 W) for 7-8 min at 2S°C. As result of this MCR process, a product A was isolated in 89% yield. 

In a three-component MCR process, cylopentan-l-on-2-(N-phenyl)carboxamide, 1,2-diamino-ethane, and 4-fluorobenzaldehyde (neat) were heated to 120 °C for 4h. 

When pyrrole-2-aldehyde is reacted with phenacyl bromide and diethyl acetylenedi-carboxylate (three-component MCR process) in DMF in the presence of K2CO3 at 50 °C, a product A is obtained in 85% yield. 

DeMoliner F, Hulme C (2012a) Straightforward assembly of phenylimidazoquinoxalines via a one-pot two-step MCR process. Org Lett 14(5) 1354—1357. doi 10.1021/oB003282... 

They envisioned that assembly of three different components which is, for instance, 2-siloxydiene and two different dienophilic unsaturated ketones [33]. They believed it is important that discrimination between the reactivity of two a,(3-unsaturated carbonyl substrates in the initial Diels-Alder reaction is essential for the success of three-component MCR processes. In this respect, they envisioned that more dienophilic unsaturated ketones would undergo Diels-Alder... 

Refiners use sweetening processes to remove mcr-captans that give a vei y unpleasant odor to gasolines and middle distillates (the skunk uses mercaptans to protect itself). This is done by washing the hydrocarbon stream with a caustic solution followed by a wash with water to remove die caustic. 

Typically, electric boiler designs are limited to under 600 kWh (2,000 lb/hr) output. However, in some countries where electricity is of particularly low cost (say, where where supplied by hydroelectric generation) electric boiler designs of up to 12,000 to 24,000 kWh (40,000-80,000 lb/hr) or more are commonly used in large-process industry. The maximum continuous rated (MCR) output is about 175,000 lb/hr. 

A number of new MCRs, that are either facilitated or accelerated by microwave irradiation, have been reported recently for the synthesis of simple N-, 0- and S-containing heterocycles. These one-pot domino processes offer... 

Fewer procedures have been explored recently for the synthesis of simple six-membered heterocycles by microwave-assisted MCRs. Libraries of 3,5,6-trisubstituted 2-pyridones have been prepared by the rapid solution phase three-component condensation of CH-acidic carbonyl compounds 44, NJ -dimethylformamide dimethyl acetal 45 and methylene active nitriles 47 imder microwave irradiation [77]. In this one-pot, two-step process for the synthesis of simple pyridones, initial condensation between 44 and 45 under solvent-free conditions was facilitated in 5 -10 min at either ambient temperature or 100 ° C by microwave irradiation, depending upon the CH-acidic carbonyl compound 44 used, to give enamine intermediate 46 (Scheme 19). Addition of the nitrile 47 and catalytic piperidine, and irradiation at 100 °C for 5 min, gave a library of 2-pyridones 48 in reasonable overall yield and high individual purities. 

The diversity of the Ugi-MCR mainly arises from the large number of available acids and amines, which can be used in this transformation. A special case is the reaction of an aldehyde 9-26 and an isocyanide 9-28 with an a-amino acid 9-25 in a nucleophilic solvent HX 9-30 (Scheme 9.5). Again, initially an iminium ion 9-27 is formed, which leads to the a-adduct 9-29. This does not undergo a rearrangement as usual, but the solvent HX 9-30 attacks the lactone moiety. Such a process can be used for the synthesis of aminodicarboxylic acid derivatives such as 9-31 [3, 30],... 

Other variations such as a combination of an Ugi-5C-4CR with an Ugi-4CR, creating an Ugi-9C-7CR, or a combination of an Ugi-4CR and a Passerini-3CR to form a 7C-6CR process, are also known [3, 36]. However, the limitations of these approaches are clear, as in higher MCRs competing reactions can occur more often such that the formation of unwanted side products is preprogrammed. In some cases the addition of a catalyst, which would accelerate single transformations in these domino processes, can be helpful [3]. 

Beside the Ugi-MCRs, several other novel multicomponent processes using isocyanides as central substrates are known. Kaime and coworkers have described a MCR between nitro compounds, isocyanides and an acylating agent such as acetic acid anhydride [54]. The a-oximinoamides of type 9-75 obtained are probably formed via the intermediates 9-72 to 9-74 (Scheme 9.14). 

Table 1. The critical mass and energy released in the conversion process of an HS into a QS for several values of the Bag constant and the surface tension. Column labeled MQs,max denotes the maximum gravitational mass of the final QS sequence. The value of the critical gravitational mass of the initial HS is reported on column labeled Mcr whereas those of the mass of the final QS and the energy released in the stellar conversion process are shown on columns labeled Mfi and Econv respectively. BH denotes those cases in which the baryonic mass of the critical mass configuration is larger than the maximum baryonic mass of the QS sequence (M r > MQS>max). In these cases the stellar conversion process leads to the formation of a black hole. Units of B and a are MeV/fm3 and MeV/fm2 respectively. All masses are given in solar mass units and the energy released is given in units of 10B1 erg. The hadronic phase is described with the GM1 model, ms and as are always taken equal to 150 MeV and 0 respectively. The GM1 model predicts a maximum mass for the pure HS of 1.807 M .

Figure 3. Mass-radius relation for a pure HS described within the GM1 model and that of the HyS or SS configurations for several values of the Bag constant and ms = 150 MeV and as = 0. The configuration marked with an asterisk represents in all cases the HS for which the central pressure is equal to I The conversion process of the HS, with a gravitational mass equal to Mcr, into a final HyS or SS is denoted by the full circles connected by an arrow. In all the panels a is taken equal to 30 MeV/fm2. The dashed lines show the gravitational red shift deduced for the X-ray compact sources EXO 0748-676 (z = 0.35) and IE 1207.4-5209 (z = 0.12-0.23).

BIU < B < l>11. In this case, the critical mass for the pure hadronic star sequence is less than the maximum mass for the same stellar sequence, i.e., Mcr < Mus,max- Nevertheless (for the present EOS model), the baryonic mass Mb(Mcr) of the hadronic star with the critical mass is larger than the maximum baryonic mass MqS max of the hybrid star sequence. In this case, the formation of a critical size droplet of deconfined matter in the core of the hadronic star with the critical mass, will trigger off a stellar conversion process which will produce, at the end, a black hole (see cases marked as BH in Tab. 1 and Tab. 2). As in the previous case, it is extremely unlikely to populate the hybrid star branch. The compact star predicted by these EOS models are pure HS. Hadronic stars with a gravitational mass in the range Mhs(MqS rnax) < Mhs < Mcr (where MqS max is the baryonic mass of the maximum mass configuration for the hybrid star sequence) are metastable with respect to a conversion to a black hole. 

Besides the usual chemistry, an increasing number of chemical compounds can be prepared by MCRs just by mixing more than two educts. Such processes do not proceed simultaneously, but they correspond to collections of subreactions, whose hnal steps form the products. Any product that can be prepared by an MCR whose last step is practically irreversible requires considerably less work and is obtained in a much higher yield than by any conventional multistep synthesis. 

In PAT applications, MCR methods have been found to be particularly useful for scouting studies of new products and new processes, where little is known about the chemistry and process dynamics, and reliable reference analytical methods have not yet been developed. 

Ring-closing metathesis seems particularly well suited to be combined with Passerini and Ugi reactions, due to the low reactivity of the needed additional olefin functions, which avoid any interference with the MCR reaction. However, some limitations are present. First of all, it is not easy to embed diversity into the two olefinic components, because this leads in most cases to chiral substrates whose obtainment in enantiomerically pure form may not be trivial. Second, some unsaturated substrates, such as enamines, acrolein and p,y-unsaturated aldehydes cannot be used as component for the IMCR, whereas a,p-unsaturated amides are not ideal for RCM processes. Finally, the introduction of the double bond into the isocyanide component is possible only if 9-membered or larger rings are to be synthesized (see below). The smallest ring that has been synthesized to date is the 6-membered one represented by dihydropyridones 167, obtained starting with allylamine and bute-noic acid [133] (Fig. 33). Note that, for the reasons explained earlier, compounds... 

---