The Three-step Procedure

Ferrocene Monomers. Although the isopropenylferrocene monomer has been reported previously by several groups of investigators,34-37 we were able to develop a more facile, dependable, high yield synthesis for this compound, utilizing the three-step procedure shown below ... 

Because both enantiomers, (+) and (-)-camphoric add, are available by oxidation either from natural (+)-D-camphor or from natural (-)-L-borneol, both enantiomers of camphanoyl chloride can be prepared conveniently.3 5 The corresponding enantiomers of camphanic acid were described for the first time by Wreden6and Aschan.7 The three-step procedure, described above is an adaptation of procedures described by Aschan,8 Zelinsky et al.,9 Meyer et al.,10 and Gerlach.3... 

The first demonstration of fluorous synthesis was in the preparation of small (8-12 members) isoxazo-line and isoxazole libraries by the three-step procedure outlined in Figure 8.1461 All reactions were purified by three-phase liquid-liquid extraction. The starting substrates were simple allylic alcohols which were tagged with the fluorous silyl halide 5 to make substrates 6 for an ensuing dipolar cycloaddition. This was conducted by the Mukaiyama method with a large excess of nitro compound and... 

The three-step procedure described for the preparation of the illustrated crotylsilanes is initiated with the hydrosilation of rac-3-butyn-2-ol. This procedure is significantly improved with respect to the positional selectivity of the hydrosilation resulting in exclusive formation of the racemic (E)-vinylsilane, and as a result the present procedure is much more amenable to scale-up than those previously described in the literature.8 The enzymatic resolution of the racemic secondary allylic alcohol (vinylsilane) has also been reported using commercially available lipase extracts. The use of a Johnson ortho ester Claisen rearrangement affords the (E)-crotylsilanes 4 in nearly enantiomerically pure form. 

Selective monoalkylation of methyl aryl-acetates by alkylhalides is difficult with conventional bases. It may be achieved by application of the three-step procedure outlined above adding (33) to the methyl arylacetates at a low temperature... 

Strategy We use the three-step procedure above, but write the actual calculation as a single step. Convert each mass in another mass unit to a mass in grams. 

The three-step procedure described here illustrates a convenient, general route to di-tert-alkylamines. Extensive purification or isolation of intermediates is not required. The reactions are easily monitored. Only in the final step is the exclusion of air and moisture necessary. It should be noted that tert-butyl-tert-octylamine is considerably more hindered than 2,2,6,6-tetramethylpiperidine. tert-Butyl-tert-octylamine is inert to methyl iodide, while 2,2,6,6-tetramethylpiperidine gives a white precipitate of the pentamethylammonium iodide within minutes upon treatment with methyl iodide at room temperature. The extreme hindrance of this amine has been exploited in the selective deprotonation of carbon adds and in other reactions.10... 

The three-step procedure described here, using inexpensive, commercially available starting materials and the chiral auxiliary SAMP, Illustrates the synthetic utility of the "SAMP-/RAMP-hydrazone method".18 It is remarkable that the classical electrophilic substitution of a conformationally flexible, acyclic ketone 1 (S)-4 occurs with virtually complete asymmetric... 

Such base-free hydrocarbyls can be easily isolated by recrystallization from hydrocarbon solvents. The last step, i.e. the hydrogenolysis reaction, proceeds under very mild conditions at one atmosphere of hydrogen and ambient temperature. The facile conversion of organolanthanide hydrocarbyls into hydrides in the presence of molecular hydrogen appears to be generally applicable. The three-step procedure outlined above has been successfully carried out with other lanthanide elements. 

The three-step procedure described here illustrates a convenient, general route to di-tert-alkylamines. Extensive purification or isolation of... 

Chiral bicyclic lactams are excellent precursors to a wide variety of chiral, non-racemic carbocycles including cyclopentenones, cyclohexenones, cyclopropanes, indanones, naphthalenones, and asymmetric keto acids.3 Recently they have been applied to the synthesis of chiral, non-racemic pyrrolidines and pyrroiidinones,4 that are medicinally and synthetically important molecules.5 The three-step procedure described here provides an efficient route (overall yield 46%) to (S)-5-heptyl-2-pyrrolidinone of high enantiomeric purity. The scheme below illustrates this reaction. 

The yields of Wittig olefination products are generally higher when 1 is prepared by the three-step procedure formulated. 

Titanium-containing pure-silica ZSM-48 (e.g., [71, 72]), a unidimensional medium pore zeolite, and titano-aluminosilicates with the structure of zeolite Beta [72-74] are materials which are currently scrutinized in catalytic oxidation reactions [75]. In the latter case, however, residual acidity created by framework aluminum leads to undesired side reactions. Since, so far, the direct synthesis of Al-free pure titaniumsilicate Beta was not successful, van Bekkum et al. [76] developed a special post-synthesis modification technique. The three-step procedure... 

The three-step procedure above illustrates the usefulness of a 1-amino-3-siloxy diene for the synthesis of functionalized cyclohexenones and is representative of the general usefulness of the dienes. The first step in the sequence, the Diels-Alder reaction between the parent aminosiloxy diene nd methyl acrylate, cleanly produces the cycloadduct as a mixture of endo and exo diastereomers. This diene also reacts with many other dienophiles and the results are summarized in Table I.3 The cycloadducts are generally obtained as mixtures of endo-exo diastereomers, except for the reactions with N-phenylmaleimide and methacrolein, which proceed with high endo selectivity, and with dimethyl maleate, which gives predominantly the exo adduct. 

These tests are also relatively fast, omitting the final immunoglobulin reagent, and are at least as sensitive as the three step procedures. In these assays a universal blocking solution may be required as some of the antibodies used for detection may be from multiple species. In some cases, a blocking step may not be... 

As a variation of the three step procedure described above, tbe patent also relates that if tobacco is first moistened, solely nicotine can be extracted with supercritical CO2. For example, CO2 at 70 °C and 300 atm passed through moistened tobacco reduced the nicotine content from 1.36 to 0.08% (dry basis) while leaving the aromas untouched. One of the authors (VJK) has not been able to reproduce this finding in tests with moistened tobacco from commercial cigarettes. Aromas were found to be exu acted along with the nicodne. Another example in the patent contains some other curious information. It is related that 5 wt% ammonia is added to supercritical CO2 at 70 °C and 250 aun and the mixture used to extract nicotine. One of the authors (VJK) has tested this mixture and finds that CO2 and ammonia react to form a compound, probably ammonium carbamate, which is insoluble in supercridcal CO2 at 70 °C and 250 atm. 

In the next phase of the three-step procedure, the health-based recommended exposure limit is assessed for technical and economic feasibility by the MAC-Value Sub-Committee of the Social and Economics Affairs Council. Based on the results of this study, the Council either advises the Minister and State Secretary for Social Affairs and Employment to adopt the health-based recommended exposure limit or it recommends a different value. 

We can now use the three-step procedure to calculate the equilibrium concentrations. 

When the nitroalkene 125 was subjected to the three-step procedure of Michael addition of propargyl alcohol, Henry reaction, and intramolecular radical cyclization, the Incyclic structure 126 was obtained,... 

B.1.3.1 Explosives shall be classified as unstable explosives or shall be assigned to one of the six divisions identified in B.1.2 in accordance with the three step procedure in Part I of the UN ST/SG/AC.10 (incorporated by reference See 1910.6). The first step is to ascertain whether the substance or mixture has explosive effects (Test Series 1). The second step is the acceptance procedure (Test Series 2 to 4) and the third step is the assignment to a hazard division (Test Series 5 to 7). The assessment whether a candidate for ammonium nitrate emulsion or suspension or gel, intermediate for blasting explosives (ANE) is insensitive enough for inclusion as an oxidizing liquid (See B.13) or an oxidizing solid (See B.14) is determined by Test Series 8 tests. 

Polyimides can be synthesized via a three-step procedure, the synthesis of a polyamic acid, conversion of the polycunic acid to a polyisoimide (a pol)dmide isomer), and conversion of the polyiso-imide to the polyimide (Eq. 4) [33, 34]. The polyisoimide solution is obtained by addition of a dehydrating agent, for example, N,N dicyclohexylcarbodiimide, to the polyamic acid solution, emd the conversion of the polyisoimide to the polyimide is performed at a lower temperature (about 200°C) than that used for conversion of polyamic acid to polyimide. As no water is formed in the conversion to the polyimide, the production is smooth. The thermosetting polyimide oligomer "Thermid PI-600" (Figure 7.4) [33] is prepared by the three-step procedure. 

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