Yield during isolation

Protonation of the a-carbanion (50), which is formed both in the reduction of enones and ketol acetates, probably first affords the neutral enol and is followed by its ketonization. Zimmerman has discussed the stereochemistry of the ketonization of enols and has shown that in eertain cases steric factors may lead to kinetically controlled formation of the thermodynamically less stable ketone isomer. Steroidal unsaturated ketones and ketol acetates that could form epimeric products at the a-carbon atom appear to yield the thermodynamically stable isomers. In most of the cases reported, however, equilibration might have occurred during isolation of the products so that definitive conclusions are not possible. 

Yield of the crude product according to the NMR spectra. In parentheses yield of the isolated pure hydrazine. Hydrazines arc known to be prone to air oxidation and unstable upon storage or handling on silica gel. This might be the reason for the considerable loss of yield during purification. 

In the preparation from lead(II) chloride and vinylmagnesium bromide in THF-hexane, violent explosions occurred during isolation of the product by distillation of solvent. This could be avoided by a procedure involving steam distillation of the tetravinyllead, no significant loss of yield by hydrolysis being noted. It is likely to be considerably more endothermic than tetraethyllead. 

A similar acetylation reaction is known25 for various primary and secondary phosphine oxides. Besides 23 and its diastereoisomers, a complex product resulting from phosphorus-phosphorus dimerization of 15 was isolated, in 25% yield, during the aforementioned acetylation this appears to be analogous to the formation of tetraphenyldiphosphine monoxide [Ph2P - P(=O) Ph2] from diphenylphosphine oxide in the presence of acetic anhydride and pyridine at room temperature.26... 

Treatment of 107 with 75 in the presence of 0.15-0.45 mol. equivalent of p-toluenesulfonic acid for 40 - 50 h at room temperature gave60 the (5RS)-5-[(RS)-dimethoxyphosphinyl]-5-(p-tolylsulfonylhydrazino)hexo-furanoses 108 (70% yield). Likewise, compound 107 and methyl phenyl-phosphinate gave an 100% yield of the 5-[(methoxy)phenylphos-phinyl] compound 109, whereas hydrazone 106 afforded four products, namely, two isomers of the xylofuranoses 110 (15%) and two isomers of the 5-C-[(RS)-(0,P-anhydro)phenylphosphinyl] derivatives 111 (51 and 26%). Compound 111 was considered to be produced from 110 during isolation employing sodium hydrogencarbonate, because 110 readily afforded 111 by treatment with sodium methoxide. 

The lability of peptides and proteins to acidic conditions was first reported in 1920 by Dakin,12031 who found that acid hydrolysis of peptides or proteins that contain consecutive N-alkyl amino acids leads to the formation of piperazine-2,5-diones (DKP) this side reaction lowered their yield during amino acid analysis. For example, the piperazine-2,5-dione c[-Hyp-Pro-] was isolated from the hydrolyzate of gelatine. 

Furthermore, FD-factors and CHARM values are not corrected for losses during the isolation steps, caused by the volatility of the odorants during isolation and concentration procedures or by their chemical stability. As shown in Table 7, significant differences in the yields of odorants have been observed [59]. 

The preparation of azulene (Expt 6.16) provides an interesting series of rearrangements.9 The key step in the synthesis is the intramolecular insertion reaction, carried out under conditions of high dilution, of the ketocarbene (22) into the 1,2-position of the benzene ring. The unstable norcaradiene (23) which is formed then ring-opens to the bicyclic trienone (24), which isomerises to the more stable cross-conjugated trienone (25) during isolation. Dehydration of the trienone with a mixture of phosphorus pentoxide and methanesulphonic acid yields azulene. 

Sildenafil (Viagra,13.73) is the prototype of a drug class that treats erectile dysfunction. The original med chem route for sildenafil is shown in Scheme 13.12. From pyrazole 13.67, the synthesis occurs in 7.5% yield. Sulfonyl chloride 13.72 was identified as the major problem in the sequence. Compound 13.72 reacts slowly with water, and loss of product to hydrolysis is unavoidable during isolation. Also, sulfonyl chloride 13.72 is toxic. In the conversion of 13.72 to 13.73, unreacted 13.72 contaminates the final product. Complete removal of 13.72 from sildenafil requires multiple recrystallizations, which further decrease the overall yield. 

This plant yielded gentioflavine, gentianaine, and oliveramine whose structure, based on spectral study, was given as 100. It was not indicated whether or not these bases are artifacts generated during isolation (75). 

The first 1-ADPM rearrangement of an acyclic derivative, reported five years later, was observed in studies of the sensitized irradiation of the (3,y-unsaturated imine 8 that yielded the corresponding cyclopropylimine 9 exclusively (Sch. 5) [11]. This photoproduct undergoes hydrolysis during isolation to generate the corresponding cyclopropane carbaldehyde 10. 

Nitro-3,5-diarylisoxazoles were isolated with low yields during the nitration of 1,2-diarylcyclopropanes with copper nitrate [531-533] (Scheme 89). 

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