Identity with an Authentic Sample

One of the major advances in organic chemistry in the last decade has been the shift in emphasis from chemical to physical methods for structure determination, made possible by the development of many versatile physical tools. The major advantages of physical methods are ease of application and freedom from the ambiguity due to the possibility of chemical rearrangement. Chemical methods are still of great value, but they are usually not employed until after the readily accessible physical methods have been exhausted, and then only when the physical methods do not give a sufficiently conclusive answer. 

If the unknown has been described in the literature and is well characterized, to establish the structure of the unknown it is necessary only to demonstrate that the two substances have the same structure. If the unknown has not been previously described, its structure determination may well involve showing that one or more of its degradation products are identical with known compounds. Thus, it is valuable to assess the ways of showing that two samples consist of the same substance. 

Infrared, NMR, and mass spectra are usually reliable as fingerprints. Mixed melting point determinations with solid unknowns or with solid derivatives of liquid unknowns rarely give misleading results. Identity should 

With the comparison methods above, it is generally easy to establish the identity of an unknown with a previously described compound, especially if an authentic sample of the known is on hand. The major problem is usually recognizing with which of the millions of compound of known structure to make the comparison this is often not apparent until some of the methods described in the next sections have been used to reveal something of the structure. 

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The Claisen rearrangement of lactonic enolates provides a new route to cycloalkenes. Cyclocitral was converted to the lactone (642) through a multistep sequence, the lactone deprotonated with LDA in THF at -78 °C, and the enolate quenched with f-butyldimethyl-chlorosilane (80JA6889, 6891). The crude ketene acetal (643) was heated at 110 °C for 10 h, and the product treated with fluoride ion to afford a single acid. Replacement of the quaternary carboxyl group by hydroxyl was accomplished through use of the carboxy inversion reaction (Scheme 147). The product (645) of this last reaction was identical with an authentic sample of widdrol in all respects excluding its optical rotation. 

Ketone (67) was reduced to the 2-ethyl derivative (71) identical with an authentic sample prepared by an independent synthesis (Scheme 18) (76AHC(19)123). Ketones (67) and (69) were also produced by the action of acetyl chloride on the corresponding acetoxymercury derivatives. 

Extracted polymer material had an IR spectrum identical with an authentic sample of polyfmethacrylic acid). They also report data on Mw (85.000 in 0.002 M HC1) and tacticity of the polyfmethacrylic acid) obtained. On the basis of Kunitake s fundamental investigation of vesicle forming dialkylammonium salts 14) similar results were reported recently by J. E. Brady u2). 

The trimethyl-D-glucose proved instead to be 2,3,5-trimethyl-D-glucose, which had been synthesized by Smith.14 It was characterized as the crystalline phenylhydrazide of the corresponding trimethyl-D-gluconic acid, the derivative being identical with an authentic sample of 2,3,5-trimethyl-D-gluconic acid phenylhydrazide prepared by Smith.14... 

The reaction was carried out in a glovebox under an atmosphere of dry N. Xep2 (251 mg, 1.48 mmol) was added to a solution of (4-/cr/-butylphenyl)trimethylsilane (153 mg. 0.74 mmol) in hexafluorobenzene (5 inL). The mixture was stirred at rt and its color slowly turned from colorless to pale yellow. After 1 h the reaction was shown to be complete by H NMR spectroscopy and the product composition was analyzed by GC/MS. Purification was carried out using chromatography [silica gel, petroleum ether (bp 60-80 C), followed by petroleum ether (bp 60 80 C)/EtOAc 9 1] to give the title compound yield 96mg (86%), identical with an authentic sample prepared from 4-/e -butylaniline. 

Application of the oxo reaction at 100—110° for 20 minutes to tri-O-acetyl-l,2-anhydro-D-glucopyranose (Brigl s anhydride) (73), followed by acetylation, gave, in over 80% yield, 1,3,4,5,7-penta-O-acetyl-2,6-anhydro-D-gli/cero-D-gttlo-heptitol (74), identical with an authentic sample. Reduction of the minor component [presumed to be the aldehydo precursor of (74)] with sodium borohydride, followed by acetylation, afforded the acetylated heptitol (74). 

Cyanoamino)imidazole-4-carboxamide (lOOmg, 0.66mmol) was dissolved in 6M NaOH (20mL). and the solution was rapidly healed to reflux for 1 h. When the solution was made neutral by addition of coned HCl, guanine precipitated. The crude product was recrystallized (5% HCI) to give 25 mg (20%) of guanine hydrochloride, which was identical with an authentic sample. 

Triphenylmethyl-4-methyl-2,8,9-trioxa-1-phosphaadamantane Tetrafluoroborate from Isomers A and B. To 1.00 g. (5.12 mmoles) of silver tetrafiuoroborate in acetone (10 ml.) was added a solution of 1.43 g. (5.12 mmoles) of triphenylmethyl chloride in acetone (15 ml.). After 5 min., the filtered solution was added to a stirred suspension of 0.90 g. (12 mmoles) of isomer A in acetone (20 ml.). After 4 hrs., a colorless precipitate formed which was filtered off and dried under vacuum at room temperature. The colorless solid (0.52 g., 30% yield), was shown to be identical with an authentic sample of l-triphenylmethyl-4-methyl-2,8,9-trioxa-l-phosphaadamantane tetrafluoroborate (16) by infrared spectroscopy. A similar procedure with isomer B gave the same product in 31% yield. 

However, in a subsequent study with a human subject, who received a single subcutaneous dose of azidomorphine, small quantities of a metabolite characterized as 6-deoxy-6-/S-aminodihydroisomorphine ( aminomor-phine , 73) were identified in the urine by g.l.c-m.s [88]. This metabolite proved identical with an authentic sample prepared by the reduction of azidomorphine with sodium borohydride, and was detected at a urinary concentration approximately 10-fold lower than that of the parent compound and its conjugates. Although only conducted with one subject. 

Saponification of chasmaconitine gave acetic acid, benzoic acid, and bikhaconine (CCLXX), which was characterized as its triacetyl derivative. The latter was identical with an authentic sample of triacetyl-bikhaconine (CCLXXIII). Hence, chasmaconitine should be identical with deoxyindaconitine (CCLXIV) i.e., N-ethyl-N-desmethyldelphi-nine. A comparison of chasmaconitine with an authentic sample of... 

Reduction with excess lithium aluminum hydride gave the diol 449 and the enamine alcohol 450. Reaction of the latter with acetyl chloride and aqueous sodium hydroxide solution gave the 1-acetyl derivative, which was reduced catalytically under pressure to deoxylimapodine (446) in almost quantitative yield. When this compound was heated with mercuric acetate in 5% acetic acid at 65-70°, -acetylaspidoalbidine (445) was isolated in 64% yield (Scheme 20). The product was identical with an authentic sample (212). 

Dendrobium pierardii Roxb. (D. aphyllum Roxb.) (Orchidaceae) (Vol. 1, p. 459) Pierardine (71) has now been synthesized and shown to possess the (S) configuration. Condensation of the lithium salt of phthalaldehydic acid with 3-dimethylaminopropylmagnesium chloride followed by lactonization with acid gave ( )-pierardine, which was resolved by recrystallization of its di-0-benzoyl-L-tartrate. The (— )-enantiomer was shown to be identical with an authentic sample of the alkaloid. The absolute configuration of pierardine as (3S)-(3-dimethylaminopropyl)phthalide (71) was determined by comparison of... 

R = Ac] and milliamine B [74 R = R = H, R = (75)] have been isolated. The structure of milliamine A rests on spectral evidence and hydrolysis with sodium methoxide in methanol to the diterpene (74 R = R = R = H) and the methyl ester corresponding to part structure (75). The structure of the diterpene tetraol, (74 R = R = r3 = H) had been previously determined by X-ray crystallographic analysis the structure of the alkaloidal portion was established by further degradation with hydrochloric acid to methyl anthranilate and compound (76), which was found to be identical with an authentic sample... 

For the completion of the total synthesis from XXI-A it was necessary to preferentially attach the unsaturated acetic acid side chain to C-13 by a Reformatsky-type reaction and to maintain the base-unstable configuration at C-14. Compound XXIV, which has been obtained from XXI-A and from XXII-A through the equilibration of the ketals, was a very important intermediate since it is a monoketone and the methyl group adjacent to the keto function is held in an axial position by the equatorial hydroxy group at C-7. A Reformatsky reaction, followed by oxidation, dehydration, and hydrolysis afforded cassaic acid (XXXIV) identical with an authentic sample (12). Since cassaic acid had been converted to cassaine (XXXV) in 1939 by Faltis and Holzinger (2), this constituted a total synthesis and a final confirmation of structure of the parent alkaloid. 

A mixture of 9-ethynylanthracene (0.02 g, 1.1 mmol), cupric acetate monohydrate (5.0 g, 25 mmol), pyridine (10 mL) and methanol (1 mL) was stirred for 3 h at 50 °C. The insoluble material was collected by filtration and washed with a small amount of methanol, water, and a small amount of ethanol, successively. The orange tiny cubes (0.20 g, 91%, mp 287-291 °C), thus obtained, were dissolved in toluene, and passed through a short column of alumina to give 43 as orange cubes, mp 290-292 °C, which was identical with an authentic sample. 

The H-NMR spectrum of the tetramethyl ester (4b) formed from streptonigrinic acid showed the presence of a primary amino group (2H, 7.84 5, exchangeable with D2O) and treatment of (4b) with nitric acid gave the desaminotetraacid (5) after ester hydrolysis. Thermal decarboxylation of (5) over soda lime produced 5-methyl-2,2 -bipyridyl (6) identical with an authentic sample. 

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