Initial studies

Initial investigations showed that the direct hydrogenation of pyrazine carboxylic acid derivatives 14—16 was possible [15] (Fig. 13). This is one of the few examples known today for a homogeneous heteroarene hydrogenation [16]. With [Rh(NBD)Cl]2 and a variety of standard ligands, for example Chiraphos, Norphos, Duphos, Deguphos, PPm, BDPP, BINAP, BPPFOAc no reaction was observed. Similarly no reaction could be observed with Ir catalysts. The positive results are given in Tab. 6. 

The impracticality of the conditions, particularly the high S/C ratio necessary to achieve a reasonable conversion, aligned with the difficulty in enrichment of the desired enantiomer by crystallization led to the abandon of this variant. 

The second approach, hydrogenation of tetrahydropyrazine derivatives was much more fruitful, as the substrate reactivity could be tuned by modification of the substituents on N-l and N-4 [17]. Initially the esters were synthesized by partial hydrogenation of the corresponding pyrazine derivatives followed by mono-functionalization at N-l (see Fig. 14). The corresponding amides could only be prepared through trapping the intermediate tetrahydropyrazine as the less reactive 

N-l acetyl derivative. A much more powerful synthesis of the tert-butylamides was the Ritter reaction of the corresponding nitrile, which allowed direct production of N-l-acylated tetrahydropyrazines [18]. These in turn could be selectively further functionalized at N-4 so that selective protective group removal was possible, giving access to the final N-4 Boc substitution pattern [2], Some examples of the results obtained in the original screening are given in Tab. 7. 

The positive effect of acyl substituents in the N-l and N-4 positions is striking, both for the ester experiments above and also for the corresponding experiments with the amides 14. The ruthenium BINAP system performed similarly to the rhodium (R)-(S)-PPF-P( Bu)2 system, but as the (R)-(S)-PPF-P( Bu)2 ligand had 

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The biosynthesis of the fortimicins has received some initial study (220—222) and a significant amount of semisynthetic modification has been carried out in this series. 3-0-Demethylfortimicin A (223,224) was found to be significantly more potent than the parent fortmicin A, especially against P aeruginosa 3-0-Demethyl-2-epi-, 2,3-di-epi-, and 3-0-demethyl-2,3-di-epi-fortimicin A are somewhat less active than fortimicin A, but the... 

The eight fl ials in this design have included evety combination of the variables, with each variable at one of the two levels in each trial, there being four trials with each variable at one of the two levels. Needless to say, the results of the analysis will be improved if each trial is repeated (replicated) but for an initial study this is usually not necessary. 

The initial studies on nickel-aluminide synthesis defined a number of important issues in shock-induced solid state synthesis. This work was extended to the influence of powder particle morphology in recent work of Thadhani and... 

Initial studies on the Jacobsen-Katsuki epoxidation reaction identified conjugated eyelie and acyelic cw-disubstituted olefins as the class of olefins best suited for the epoxidation reaetion. " Indeed a large variety of c/s-disubstituted olefins have been found to undergo epoxidation with a high degree of enantioselectivity. 2,2"-Dimethylehromene derivatives are especially good substrates for the epoxidation reaetion. Table 1.4.1 lists a variety of examples with their corresponding reference. 

An initial study of the infrared spectrum of oxindole purported to show the presence both of the hydroxy (78) and of the oxo forms (79), and, indeed, chemical evidence led to the same conclusion. On the basis of later infrared work, however, oxindole and its derivatives were considered to exist more or less completely in the oxo form, and this conclusion is supported by ultraviolet spectroscopic data, i.e., by comparison of the spectrum of the parent compound with those of its methyl derivatives. " The infrared spectrum of... 

By the early 1980 s the federal labeling requirements had taken effect and all residential appliances were labeled with yellow Energy Guide stickers. Initial studies, however, suggested that theses stickers were not particularly effective in specific purchase decisions. More recent analysis has found that despite high levels of awareness of the label, significant comprehension problems exist with it. 

Our initial studies were directed towards the synthesis and characterization of phenylboronate esters derived from methyl 6-deoxy-/ -D-allopyranoside, methyl a-L-rhamnopyranoside, methyl -L-fucopyranoside, and methyl 6-deoxy-/ -D-glucopyranoside. Previous work (14) in this laboratory indicated that the reaction of triphenylboroxole and methyl... 

Subsequent to the announcement (47) of this reaction, a similar transformation of 4,6-O-benzylidene acetals was reported (35) in which a free radical initiator was used. Under these conditions a blocked derivative such as 93 (R = Bz) was transformed in 76% yield into the corresponding 94. Selective formation of the 6-bromo derivative was observed as in the initial studies (47). 

The synthesis of 3//-azepines by the photolysis of aryl azides in nucleophilic media is a much more efficient and versatile route than the thermolytic process. Initial studies involved photolysis of the aryl azides in an excess of a secondary aliphatic amine, and moderate yields of A, V-dialkyl-3//-azepin-2-amines 38 were obtained.35-1 72... 

Polymorphisms have been described for all (3-adrenergic receptors while initial studies, notably of the (3i-subtype, suggested that these might be predictors of diseases as well as of therapeutic responses, these results have more recently been questioned. Alterations in responsiveness may be limited to certain compounds and a causative role in diseases has not been or remains to be substantiated in larger trials. 

Lu, Vyn, Sandus and Slagg (Ref 17) conducted ignition delay time and initiation studies on solid fuel powder-air mixts in an attempt to determine the feasibility of solid-air detonations. The materials investigated included Al, Mg, Mg-Al alloy, C and PETN. Ignition delay time was used as a method of screening the candidate fuels for further work in initiation studies which determined detonation wave speed, detonation pressure, detonation limits, initiation requirements, and the effect of particle size and confinement. The testing showed the importance of large surface area per unit mass, since the most... 

Kochi (1956a, 1956b) and Dickerman et al. (1958, 1959) studied the kinetics of the Meerwein reaction of arenediazonium salts with acrylonitrile, styrene, and other alkenes, based on initial studies on the Sandmeyer reaction. The reactions were found to be first-order in diazonium ion and in cuprous ion. The relative rates of the addition to four alkenes (acrylonitrile, styrene, methyl acrylate, and methyl methacrylate) vary by a factor of only 1.55 (Dickerman et al., 1959). This result indicates that the aryl radical has a low selectivity. The kinetic data are consistent with the mechanism of Schemes 10-52 to 10-56, 10-58 and 10-59. This mechanism was strongly corroborated by Galli s work on the Sandmeyer reaction more than twenty years later (1981-89). 

The initial study by Berliner369 used R = Me, R = H, and R" variable, the reaction being carried out in a refluxing mixture of acetic acid (10 ml), hydro-bromic acid (4 mole, 48 %) and water (1 ml). The rate coefficients (the reaction was first-order in aromatic) are given in Table 95 and it appeared that the reaction... 

Peroxodiphosphoric acid (PDPA) may also be used to convert sulphoxides to sulphones in good yields. An initial study of this reaction80 concluded that the mechanism was a free radical process, involving the reaction of a hydroxyl radical with the sulphoxide as shown in equation (26). This was later claimed to be incorrect the reaction actually occurs by the initial decomposition of PDPA to PMPA which then reacts as described above81. 

The search for the racemic form of 15, prepared by allylic cyclopropanation of farnesyl diazoacetate 14, prompted the use of Rh2(OAc)4 for this process. But, instead of 15, addition occurred to the terminal double bond exclusively and in high yield (Eq. 6) [65]. This example initiated studies that have demonstrated the generality of the process [66-68] and its suitability for asymmetric cyclopropanation [69]. Since carbon-hydrogen insertion is in competition with addition, only the most reactive carboxamidate-ligated catalysts effect macrocyclic cyclopropanation [70] (Eq. 7), and CuPF6/bis-oxazoline 28 generally produces the highest level of enantiocontrol. 

Erdal, B.R. Aguilar, R.D. Bayhurst, B.P. Daniels, W.R. Duffy, C.J. Lawrence, F.O. Maestas, S. Oliver, P.Q. Wolfsberg, K. "Sorption-Desorption Studies on Granite. I. Initial Studies of Strontium, Technetium, Cesium, Barium, Cerium, Europium, Uranium, Plutonium, and Americium", in "Proceedings of the Task 4 Waste Isolation Safety Assessment Program Second Contractor Information Meeting", Vol. II, Report PNL-SA-7352, Battelle Pacific Northwest Laboratory, 1978, pp. 7-67. 

The initial studies of LSDAs were carried out with oleochemicals because of their structural similarity to soap. However, since the molecular structure of an efficient LSDA is characterized by a bulky hydrophilic polar head attached to a long hydrophobic tail, it is also possible to prepare LSDAs from petrochemicals. Sulfated sulfonamide derivatives of alkylbenzenes, such as commercially available detergent alkylates, were synthesized as follows [17] ... 

As already noted the strength of chemisorptive bonds can be varied in situ via electrochemical promotion. This is the essence of the NEMCA effect. Following initial studies of oxygen chemisorption on Ag at atmospheric pressure, using isothermal titration, which showed that negative potentials causes up to a six-fold decrease in the rate of 02 desorption,11 temperature programmed desorption (TPD) was first used to investigate NEMCA.29... 

For the solid-phase experiments [115], the commercially available Wang and HMPB-AM resins were chosen due their stability under the applied reaction conditions and an easy cleavage with TFA/DCM mixtures. Moreover, a novel, tailor-made and readily available linker, derived from inexpensive syringaldehyde was designed and proven to be superior to both standard Wang and HMPB-AM resins. For an initial study, as a proof of concept , the Wang linker was mimicked with a 4-methoxybenzyl group at N-1 position of a pyrazinone, and the sequence was evaluated in solution (Scheme 41). 

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