Intermediates, isolation

When the sodium derivative, which is used in ethanol it solution without intermediate isolation, is boiled with an alkyl halide, e.g., methyl iodide,... 

From the nitrile. By refluxing a mixture of the nitrile with alcohol and concentrated sulphuric acid the intermediate isolation of the acid is unnecessary. The net result may be represented by, for example ... 

This heating prior to distillation obviates the necessity of intermediate isolation of the carbinol. The dehydration is evidenced by small explosions when the water drops on the hot reaction mixture. 

In many cases, it is also helpful to have the path repel itself so that the transition pathway is self-avoiding. An acmal dynamic trajectory may oscillate about a minimum energy configuration prior to an activated transition. In the computed restrained, selfavoiding path, there will be no clusters of intermediates isolated in potential energy minima and no loops or redundant segments. The self-avoidance restraint reduces the wasted effort in the search for a characteristic reaction pathway. The constraints and restraints are essential components of the computational protocol. 

Despite its apparent simplicity, the PK pyrrole synthesis has retained its mystique since being discovered. Several investigations into the PK mechanism have been reported, including a gas phase study. Current evidence (intermediate isolation, kinetics, isotope effects) suggests the following (abbreviated) mechanism for the formation of pyrrole 13. However, the specific PK mechanism is often dependent on pH, solvent, and amine and dicarbonyl structure, especially with regard to the ringclosing step. 

However even arenediazonium ions generally are stable only at temperatures below 5°C usually they are prepared prior to the desired transformation, and used as reactants without intermediate isolation. They can be stabilized more effectively through complexation by crown ethers." ... 

Hastings, J. W., Balny, C., Le Peuch, C., and Douzou, P. (1973). Spectral properties of an oxygenated luciferase-flavin intermediate isolated by low-temperature chromatography. Proc. Natl. Acad. Sci. USA 70 3468-3472. 

Polybenzoxazole and Polybenzothiazole 5.4.4.1 Formation without Intermediate Isolation... 

Heating pyridine-2,3-dicarboxylic acid anhydride with l-ethyl-2-methylindole has been claimed to yield solely the pyridine-2-carboxylic acid, albeit in low yield. This then clearly reacts with Af,A/-diethyl-3-toluidine in acetic anhydride to give the 7-azaphthalide. This is surprising in view of a later report70 in which a one-pot process has been described. Heating pyridine-2,3-dicarboxylic anhydride, prepared in situ, with the indole and subsequent reaction with 3-/V,/V-diethylamino-phenetol under identical conditions to those used in Scheme 8 (but without intermediate isolations) produced a 20 1 mixture of the 4- and 7-azaisomers 16 and 17. It appears that in the previous report the major intermediate isomer, the pyridine-3-carboxylic acid, has not been isolated. 

The treatment of choice until susceptibility of the organism is known as the combination of vancomycin plus ceftriaxone. Penicillin may be used for drug-susceptible isolates with minimum inhibitory concentrations of 0.06 mcg/mL or less, but for intermediate isolates ceftriaxone is used, and for highly drug-resistant isolates a combination of ceftriaxone and vancomycin should be used. A high percent of S. pneumoniae is either intermediately or highly resistant to penicillin. 

It is important to note that the Ru-catalyzed RCM and the Zr-catalyzed resolution can be carried out in a single vessel, without recourse to intermediate isolation. The unsaturated medium-ring amides 5 and 8 can be subjected to 10 mol% of the chiral Zr catalyst and EtMgCl, in the same flask, to afford unsaturated 6 and 9 in 81% and 54% isolated yield, respectively. As depicted in Eq. 1, a similar tandem diene metathesis/ethylmagnesation can be carried out on ether 10, leading to the formation of unsaturated chiral alcohol 11 in 73% yield and >99% ee. 

There are a number of factors that determine the release rate and initial geometry of a hydrocarbon gas release. The most significant is whether the gas is under pressure or released at atmospheric conditions. Depending on the release source the escaping gas can last from several minutes or days, until the supply is isolated, depleted or fully depressured. Common long duration sources are underground reservoirs (e.g., blowouts), or long pipelines without intermediate isolation capabilities. 

Compound 108 may be prepared directly from 104 without intermediate isolation of 104 by treating the dicarboxylic acid 107 with monohydrate or with concentrated sulfuric acid at 35°C, followed by bromination in the presence of iodine as a catalyst. 

Route B of this process may be substantially improved in terms of yield and product quality (purity) of the resulting triarylaminoarylcarbonium pigment. To this end, the solution of the free dye base is treated with an excess of aqueous sulfuric acid (20 to 40% ) in a solvent such as chlorobenzene or an aromatic amine. This method produces the sulfate of the basic dye, which is insoluble in this medium, together with the soluble sulfates of the primary aromatic amines, which can therefore easily be separated. The isolated sulfate of the basic dye is then washed and in dry or wet condition monosulfonated with 85 to 100% sulfuric acid. Based on the dye base sulfate, this step affords 96 to 98% yield, compared to only 83 to 89% achieved by the previously described method. The entire synthesis, including the intermediate isolation of the triarylaminoarylmethane sulfate, may also be performed by continuous process [3]. 

Opportunity to combine two or more chemical steps with no intermediate isolation (telescoping to increase throughput). 

As these reagent systems are anchored on a solid, they also allow the simultaneous use of multiple reagents to achieve one-pot transformations where, because of incompatibility of the reagents, no solution-phase equivalent exists or would require intermediate isolation. Many examples of this are illustrated in the following sections where it can be seen that these concepts add a new dimension to how one can think about organic synthesis and will certainly have important ramifications on the design and implementation of new chemical reactions and processes in the future. 

All process development starts with chemistry. The selection criteria for the most suitable chemistry for a continuous process do not suffer from the same constraints as those for a large-scale batch process. For example, highly exothermic reactions are not only possible in a flow reactor, but are in fact preferred [47]. As operator exposure will be low and so will stock levels, different safety considerations come into play that may allow utilisation of otherwise intolerably toxic reagents. Process telescoping is a necessity to minimise the number of intermediate isolations. Examination of all these factors is facilitated by online analysis because of its speed and maintenance of experimental integrity (i.e. no requirement for sampling). 

Analogously to the previous work, a significant improvement was achieved using much shorter reaction times (seconds instead of hours) and less stringent conditions in comparison to the previously reported batch procedures a temperature of 0°C was sufficient to perform the reaction successfully, while in batch a temperature of —78°C was necessary to avoid the formation of numerous side products. Also, the batch reaction demanded the intermediate isolation of the monosubstituted derivative before the second reaction with the aryllithium, as the main reaction product was the monosubstituted derivative, while under... 

The route is, however, important as it shows the possibility of passing from multistep sequences in batch that usually require intermediate isolation and purification in between steps to a continuous sequence using flow chemistry that produces the desired molecules requiring a minimum purification at the end and providing important savings in time and resources. 

For the five-membered heterocycles (Fig. 1), it is important that the term meso-ionic is reserved for members of the general types 19 and 20. This point needs to be emphasized because recently several structures have been described as meso-ionic although they were in fact ylides 17 and 18. Petersen and Heitzer" have referred to Ae intermediate isolated... 

Figure 3. UV spectra of the photolysis of X ( 7 X 10 M) in EtOH-MeOH (9 1) mixture at —150° with 405 nm narrow band light. The spectra were monitored with a Cary 14 spectrophotometer (A) before the irradiation (B) after 28 min irradiation (C) UV absorption curve of the intermediate isolated from spectrum B with a Du Pont 310 Curve resolver.

Despite aU of betulinic add pharmacological potential, it is obtained by extrachon of barks or core of some plant species or by synthetic processes, e.g. using the betulin (alcohol triterpene) as a S)Tithetic intermediate isolated from the bark of Betula alba and Betula pendula [Galgon., et al. 1999]. Therefore, research is necessary to identify new natural sources, which produce large... 

The step 3 was reacted with IV-chlorosuccinimide and the heterocyclic intermediate isolated in 82% yield. 

An exhaustive study has been made on the 3,4-dinitrothiophene system <78JCS(Pl)li40>. This gives rise to a plethora of interesting products, depending on the 2,5-substituents and on the nucleophile used. In the reaction of 3,4-dinitrothiophene with thiophenoxide in methanol, the major compound isolated was the cine substituted product (421) based on the intermediates isolated, the mechanism shown in Scheme 138 has been put forward. 

A concerted elimination-cyclization mechansim, involving a sulfenyl halide in a 1,3-butadiene-1-thio system, is the most probable mechanism for the formation of benzo[6 Jthiophenes from cinnamic acids or 4-aryl-2-butanones by treatment with thionyl chloride. The reactions shown in Scheme 5 have been carefully worked out, and the intermediates isolated (75JOC3037). The unique aspect of this synthesis is the reduction of the sulfinyl chloride (a) by thionyl chloride to form the sulfenyl chloride (b). The intermediate (b) was isolated and converted in pyridine to the 3-chlorobenzo[6]thiophene-2-carbonyl chloride in 36% yield (73TL125). The reaction is probably initiated by a sulfenyl ion attack on the aromatic ring, since it is promoted by electron-releasing groups para to the site of ring closure. For example, when X in (36) was N02, a 23% yield of (37), a mixture of 5-and 7-nitro derivatives, was obtained, but when X in (36) was OMe, a 54% yield of (37) was obtained, contaminated with some 3,4-dichloro-5-methoxybenzo[6]thiophene-2-carboxylic acid. 

The evidence above shows quite clearly that irradiation of substituted benzenes under a variety of conditions will lead to the formation of intermediate, isolable nonaromatic isomers, most of which return thermally to the ground state of the present molecule. 

The crude distillate can be used directly without intermediate isolation of l-(2-carbethoxyethyl)azetidine to furnish a 50% yield of azetidine, assuming that all of the crude material was l-(2-carbethoxyethyl)azetidine and running the reaction as described for the pure material. 

Small specimens of all products, including reaction intermediates isolated from reaction sequences, and particularly samples of fractions isolated as the result of lengthy chromatographic or other purification procedures, should invariably be retained for reference purposes. The commercially available straightsided specimen tubes with polyethylene plug seals, which are available in a range of sizes, are suitable in the case of solid samples. It is usually advantageous to label them with the name and a code reference to enable physical data (elemen-... 

A further extension to the trisazo dyes on the principle of series coupling D—>Mr M2— M3— K offers no advantages, because the intermediate isolation that is frequently necessary leads to yield losses, and a chain extension is therefore ruled out on economic grounds. This is also reflected in the number of poly-azo dyes listed in the Colour Index [5], Although 78 tetrakisazo dyes with eleven different synthesis principles are listed, only 14 dyes with five and more azo groups are mentioned, two of which are specified with eight azo groups. 

In the manufacture of trisazo dyes, good yield and purity during final coupling are often obtained only in the presence of pyridine or other bases as coupling accelerators [10], Intermediate isolation and separation of impurities prior to continuation of coupling are also frequently necessary. 

The relative trans stereochemistry of the substituents in the tetrasubstituted 3,4-dihydro-27/-thiopyran 85, an intermediate isolated from the [4+2] cycloaddition between an enaminothione and a nitroalkene, has been established by H NMR spectroscopy <1994JPR434>. The methylene units of 5-(diethylphosphono)-3,4-dihydro-277-thiopyran 86 appear as multiplets in the range 2.0-2.8 ppm and the vinyl proton (H-6) displays coupling to the P atom with V= 21.6Hz <20050BC924>. 

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