Yield, in synthesis

The photolysis of liquid O2 with production of O3 has been known almost since the first availability of liquid O2. Photolysis of liquid O2—F2 solutions (which are miscible in all proportions) results in the formation of O2F2 and O3F2. Cryogenic photolysis is attractive since one may break a particular bond and thereby produce the particular desired reactant species directly in the cold environment. Photolysis is, however, unattractive from the point of view of quantity yield in synthesis unless a chain mechanism is involved. 

Extremely dry (or super-dry ) ethyl alcohol. The yields in several organic preparations e.g., malonic ester syntheses, reduction with sodium and ethyl alcohol, veronal synthesis) are considerably improved by the use of alcohol of 99-8 per cent, purity or higher. This very high grade ethyl alcohol may be prepared in several ways from commercial absolute alcohol or from the product of dehydration of rectified spirit with quicklime (see under 4). 

By the time j ou get to a ten step synthesis, the arithmetic demon ensures that the yield is down to a miserly 35%. And this with 90% yield in eaeh step So clearly a short synthesis is a good one. But we ean cheat the arithmetic demon by making our five steps convergent rather than linear. The convergent version is this ... 

A second scheme uses a database of known chemical reactions. This more often results in synthesis routes that will work. However, this occurs at the expense of not being able to suggest any new chemistry. This method can also give many possible synthesis routes, not all of which will give acceptable yield or be easily carried out. The quality of results will depend on the database of known reactions and the means for determining which possible routes are best. These are often retro synthetic algorithms, which start with the desired product and let the researcher choose from a list of possible precursors. 

The recent discovery that propadiene can be converted into a lithio compound, which is stable enough at low temperature to allow functionalization, has made it an important starting compound for the synthesis of derivatives. A fortunate circumstance is that allene can be obtained in > 30% yield in an extremely simple... 

Di- and trinucleotides may be used as units instead of the monomers. This convergent synthetic strategy simplifies the purification of products, since they are differentiated by a much higher jump in molecular mass and functionality from the educls than in monomer additions, and it raises the yield. We can illustrate the latter effect with an imaginary sequence of seven synthetic steps, c.g. nucleotide condensations, where the yield is 80% in each step. In a converging seven-step synthesis an octanucleotide would be obtained in 0.8 x 100 = 51% yield, compared with a 0.8 x 100 = 21% yield in a linear synthesis. 

The cyclized products 393 can be prepared by the intramolecular coupling of diphenyl ether or diphenylamine(333,334]. The reaction has been applied to the synthesis of an alkaloid 394[335]. The intramolecular coupling of benzoyl-A-methylindole affords 5-methyl-5,10-dihydroindenol[l,2-b]indol-10-one (395) in 60% yield in AcOH[336]. Staurosporine aglycone (396) was prepared by the intramolecular coupling of an indole ring[337]. 

Desulfonylation of equally substituted allylic sulfones with NaBH4 and LiBHEt3 usually yields a mixture of regioisomeric alkenes[406,407]. However, the regioselective attack of the less substituted side of the unsymme-trically substituted allylic system with LiEtjBH has been utilized for the removal of the allylic sulfone group in synthesis of the polyprenoid 658[408],... 

The conversion of esters to hydrazides and of hydrazides to the sulfonyl derivatives occurs in good yield in the McFadyen-Stevens synthesis, but the decomposition of sulfonyl derivatives gives low yields of the desired products, for example, thiazole hydrazide (28) with 10% excess of PhSOjCl in pyridine gave a 75% yield of l-phenylsulfonyl-2-(4-methyl-5-thiazo ecarbonyl)hydrazine (29) (66). The Newman-Caflish modification of the McFadyen-Stevens synthesis gave 37% 4-methyl-5-thiazole-carboxaldehyde (30) (Scheme 27). 

Chloroacetate esters are usually made by removing water from a mixture of chloroacetic acid and the corresponding alcohol. Reaction of alcohol with chloroacetyl chloride is an anhydrous process which Hberates HCl. Chloroacetic acid will react with olefins in the presence of a catalyst to yield chloroacetate esters. Dichloroacetic and trichloroacetic acid esters are also known. These esters are usehil in synthesis. They are more reactive than the parent acids. Ethyl chloroacetate can be converted to sodium fluoroacetate by reaction with potassium fluoride (see Fluorine compounds, organic). Both methyl and ethyl chloroacetate are used as agricultural and pharmaceutical intermediates, specialty solvents, flavors, and fragrances. Methyl chloroacetate and P ionone undergo a Dar2ens reaction to form an intermediate in the synthesis of Vitamin A. Reaction of methyl chloroacetate with ammonia produces chloroacetamide [79-07-2] C2H ClNO (53). 

However, BASF developed a two-step process (25). After methyl formate [107-31-3] became available in satisfactory yields at high pressure and low temperatures, its conversion to formamide by reaction with ammonia gave a product of improved quaUty and yield in comparison with the earlier direct synthesis. 

An important consideration for all radiopharmaceuticals and especially radiolabeled biologically active molecules is specific activity. There are two types of specific activity radionucHdic and biological. RadionucHdic specific activity refers to the ratio of the number of atoms of a particular radioisotope to the total number of atoms of the element. For Tc, the radionuchdic specific activity is the number of Tc atoms to the total number of Tc and Tc atoms. Because all isotopes of an element ate chemically identical, a low specific activity may lead to a low yield in the synthesis of a radiopharmaceutical if a significant proportion of the reagents is consumed by the undesited isotopes. 

Protection of carboxyflc acids and sulfenic acids requires efficient sdyl donors, eg, BSA, MTSA, and bis(ttimeth5isdyl)urea [18297-63-7] (BSU). BSU is often prepared in situ from hexamethyldisda2ane and urea to yield over 90% of the sdylated derivative in synthesis of cephalosporins (5). 

Since syntheses of three-membered rings with two heteroatoms almost always proceed under mild conditions with good yields and from simple starting materials, they are useful intermediates in synthesis. The easy formation of N—O and N—N bonds offers synthetic potentialities. Furthermore, the three-membered ring may serve as a protecting group during additional operations of substitution. 

NaN02, 1 N HCl, CH3OH, H2O, 0°, 3 h, 76% yield. In the last step of a synthesis of erythronolide A, acid-catalyzed hydrolysis of an acetonide failed because the carbonyl-containing precursor was unstable to acidic hydrolysis (3% MeOH, HCl, 0°, 30 min, conditions developed for the synthesis of erythronolide B). Consequently the carbonyl group was protected... 

Quite recently, Ciampolini and coworkers have reported the synthesis of two isomeric mked oxygen-phosphorus macrocycles and the crystal structures of their cobalt complexes. Synthesis of macrocycle 27 was accomplished by condensation of 1,2-bis-(phenylphosphino)ethane dianion with 2,2 -dichlorodiethyl ether in THE. The two isomers of 27 were isolated in 1.5% and 2% yield. The synthesis is formulated in Eq. (6.17), below. 

The dl-pukateine methyl ether obtained in small yield in the analogous synthesis was isolated as the hydriodide and resolved by the successive use of d- and 1-tartaric acids into the 1-base, m.p. 136°, [a]ff° — 252° (EtOH), identical with the methyl ether of pukateine, and the d-base, m.p. 136°, [a] " -f 256-4° (EtOH). 

This reaction is commonly achieved by diazotization of the amine in fluoro-boric acid, followed by decomposition of the diazonium salt (Schiemann reaction).Thus, l-amino-4-methylestra-l,3,5(10)-trien-17-one (50) is converted to the fluoro derivative (51) in 29% yield. The synthesis of 3-fluoroestra-l,3,5(10)-triene-17-one (55) from estrone proceeds via (52) and (53)... 

The [SaN]" cation was first obtained in low yield in 1978 by the oxidation of S7NH with SbCls. The reaction of in situ generated [SN]" salts with sulfur (Scheme 5.3) or the reduction of the [ClSNSCl] cation with anhydrous tin(II) chloride in SO2 or CH2CI2 can be used to prepare [S2N] salts. The best large scale synthesis involves the reaction of AsFs with a mixture of S4N4 and sulfur in the presence of a trace amount of bromine (as a catalyst) (Eq. 5.10). ... 

It IS by a similar process that alizaiin has been synthesised w ith the oliject of ascertaining its constitution (see Notes on Prep. 110, p. 316), When two molecules of phenol and one molecule of phthalic anhydride are heated together with cone, sulphuric acid, then phenolphthalein is formed (Baeyei). Its constitution has been determined by its synthesis from phthalyl chloride and benzene by means of the Friedel-Crafts leaction (see Notes on Piep. 100, p. 309). Phthalyl chloride and benzene yield in presence of AlCl., phthalophenone. 

Bis(phe nylthiomethyl)dihydropyran, CSA, CHCI3, 54-93% yield. This dihydropyran can be used for the resolution of racemic diols or for regio-selective protection, which is directed by the chirality of the dihyropyran. Other 2,2 -substituted bisdihydropyrans that can be cleaved by a variety of methods are available, and their use in synthesis has been reviewed. ... 

N02)2C6H3NHNH2 H2S04, EtOH, H2O, 25°, 10 min, 80% yield. In a synthesis of sativene a carbonyl group was protected as a 2,4-DNP, while a double bond was hydrated with BH3/H2O2/OH . Attempted protection of the carbonyl group as a ketal caused migration of the double bond protection as an oxime or oxime acetate was unsatisfactory, since both of these would be reduced with BH3. 

The Madelung indole synthesis has been employed in the preparation of some complex indole systems. Uhle et al. reported the conversion of N-formyl-5,6,7,8-tetrahydronaphthylamine 28 into 1,3,4,5-tetrahydrobenz[c,ti]indole 29 with t-BuOK in 11% yield in regard to synthesis of ergot alkaloids. ... 

The Leuckart synthesis has been applied successfully in the thiophene series, iV,A -Dimethyl thenylamine and A, A -diethyl thenylamine were obtained from 2-thiophenealdehyde and the appropriate for-mamide. Seven -(2-thienyl)- -arylethylamine hydrochlorides have been prepared from the corresponding ketones in about 40-60% yields and, finally, A -methyl-1-(3-thienyl)-2-propylamine was obtained in 48% yield in the Leuckart reaction from 3-thienylace-tone, methylamine, and formic acid. ... 

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