Zimmerman reaction

Colorimetric procedures used In steroid assays are often subject to drug Interference. In the determination of 17-Ketosterolds by the Zimmerman reaction, drugs with the 17-Keto basic structure such as ascorbic acid, morphine and reserplne will cause Increased values. In the determination of 17,21 -dlhydroxysterolds by the Porter-Sllber reaction the dlhydroxy-acetone chain Is the reactive unit. Drugs like meprobamate, chloral hydrate, chloropromazlne and potassium Iodide will Interfere with this reaction and cause elevated values. In the colorimetric determination of vanlllylmandellc acid (VMA) by a dlazo reaction, drugs like methocarbamol and methyl dopa cause... 

Chapter 1, by Armesto et al., summarizes the recent results on di-ir-methane and related rearrangements. Many of the reactions reported in this chapter were discovered by Armesto s group and expand the potential of this versatile reaction often known as the Zimmerman reaction. This chapter complements many of the reactions discussed previously in this series. 

The determination of 17-ketosteroids is most often determined in the clinical laboratory by the Zimmerman reaction, in which the ether-extracted material is allowed to react with m-nitroaniline to yield a colored product. Thus, any compound with the 17-keto basic structure such as reserpine, morphine, ascorbic acid, or their metabolites will interfere. The Porter-Silber reaction used in the determination of 17,21-dihydroxysteroids is also not specific, and the reaction requires a di-hydroxyacetone side chain. Paraldehyde, chloral hydrate, meprobromate, and potassium iodide have been found to interfere, and patients should be maintained free of these drugs for 24-48 hours before the urine collection (Bll). 

The Janovsky reaction became an important analytical test which could be used to detect both reagents di- or trinitro rompounds or ketones and aldehydes. The modification of the reaction consisting in the use of m-dinitrobenz-ene as a test for 17-ketosteroids is sometimes called the Zimmerman reaction [15,56). 

The photochemical production of vinylcyclopropane derivatives from compounds having two 7t-moieties bonded to an sp3-hybridized carbon648 is termed the din-methane rearrangement, also known as the Zimmerman reaction.649 A very broad spectrum of di-7t-systems can lead to photoproducts that are usually not obtainable by alternative routes.632,633 The reaction may be classified formally as a [l,2]-shift but, according to the proposed stepwise biradical mechanism,650 651 1,3- and 1,4-biradical (BR) intermediates and also the second 7t-bond may be involved652 (Scheme 6.29). A concerted (pericyclic) pathway for the di-7t-methane reaction from the excited singlet state is, however, not excluded. Typically, the singlet state reaction occurs upon direct... 

Zak and Epstein (Zl), have automated the Zimmerman reaction for 17-ketosteroids by the development of a novel aqueous reagent using Hyamine-KOH as base. This paper well repays a close study. 

This statement too may cause raised eyebrows but an objective assessment of errors and costs can support it. Thus, De Courcy s trichloroacetic acid reagent (D2) is capable of convenient application to the detection of pregnanetriol in the nonketonic fraction from one-sixteenth of a 24-hour collection from men (100-150 ml) on simple LLC paper chromatograms (a TLC method could no doubt also be devised for this). As she pointed out, the same quantity can be obtained from one-thousandth of a 24-hour collection (1.5-2 ml) of urine from some patients with adrenal hyperplasia. Quantitative estimation by the same reaction after elution from the paper or TLC chromatogram could also be used either by one of the many variations of the micro-17-ketogenic steroid methods or by the same fluorescence reaction (e.g., W7). Further confirmation of identity could be obtained by using a small fraction of the latter after the periodate oxidation for a paper LLC, or TLC, chromatogram and application of the Zimmerman reaction to demonstrate the formation of etiocholanolone (B32). 

If greater precision is required, the zones from paper LLC or TLC, chromatograms can be eluted and measured by the micro-Zimmerman reaction (e.g., W7). There is no objective evidence that the precisions to be obtained are any worse than those by the more sophisticated modem methods for comparable degrees of care and attention to detail. 

K5. Kellie, A. E., and Smith, E. Characterization of 17-oxosteroids by derivatives formed in the Zimmerman reaction. Nature 178, 323 (1956). 

Darcey and Evenson (D4) have compared GLC and the Zimmerman reaction in the analysis of total 17-ketosteroids in urine. Urinary 17-keto-steroid GLC patterns have been studied by Cawley et al. (C5), who noted the presence of several peaks with retention times shorter than those of 17-ketosteroids. A comparison of different methods of hydrolysis has been made by Curtius and Muller (C18) in their study of the GLC of 17-ketosteroids and progesterone metabolites of urine. The simultaneous determination by GLC of pregnanediol and pregnanolone in urinary extracts has been reported by Guarnieri and Barry (G8). GLC was found to be the method of choice in a study by Barry et al. (B2) of four methods for the quantitative analysis of pregnanediol in urine. 

J. Beger, R. Sass, and G. Zimmerman, Reactions of alkenes in the presence of tungsten- and molybdenum-containing Ziegler-Natta catalysts. J. Prakt. Chem., 1978, 320, 283. 

Electi ocyclic reactions are examples of cases where ic-electiDn bonds transform to sigma ones [32,49,55]. A prototype is the cyclization of butadiene to cyclobutene (Fig. 8, lower panel). In this four electron system, phase inversion occurs if no new nodes are fomred along the reaction coordinate. Therefore, when the ring closure is disrotatory, the system is Hiickel type, and the reaction a phase-inverting one. If, however, the motion is conrotatory, a new node is formed along the reaction coordinate just as in the HCl + H system. The reaction is now Mdbius type, and phase preserving. This result, which is in line with the Woodward-Hoffmann rules and with Zimmerman s Mdbius-Huckel model [20], was obtained without consideration of nuclear symmetry. This conclusion was previously reached by Goddard [22,39]. 

Barrelene was obtained via a double Diels-Alder reaction from a-pyrone with methyl acrylate (H.E. Zimmerman, I969A). The primarily forming bicyclic lactone decarboxylates in the heat, and the resulting cyclohexadiene rapidly undergoes another Diels-Alder cyclization. Standard reactions have then been used to eliminate the methoxycarbonyl groups and to introduce C—C double bonds. Irradiation of barrelene produces semibullvalene and cyclooctatetraene (H.E. Zimmerman. 1969B). 

The ratio of products 15 and 16 is dependent on the structures, base, and the solvent. The kinetics of the reaction is likewise dependant on the structures and conditions of the reaction. Thus addition or cyclization can be the rate-determining step. In a particularly noteworthy study by Zimmerman and Ahramjian, it was reported that when both diastereomers of 20 were treated individually with potassium r-butoxide only as-epoxy propionate 21 was isolated. It is postulated that the cyclization is the rate-limiting step. Thus, for these substrates, the retro-aldolization/aldolization step reversible. ... 

The di- r-methane rearrangement is a fairly recent reaction. One of the first examples has been reported in 1966 by Zimmerman and Grunewald with the isomerization of barrelene 8 to semibullvalene 9. This rearrangement reaction occurs in the presence of acetone as photosensitizer, and proceeds from the Ti-state. ... 

The diastereoselectivity observed on carbonyl addition of ( )-alkenyltitanium derivatives is in accordance with the reaction proceeding via a chair-like six-membered Zimmerman Traxler transition state. The following facts are diagnostic ... 

The most widely accepted transition state hypothesis for aldol reactions is the Zimmerman Traxler model29 which involves a six-membered chair-like assembly of the rcaetants. This... 

Although the chiral propanoates I and 5 are similar and the reaction conditions are almost identical, the stereochemical outcomes arc explained by completely different transition state models. Predominant attack of the ketene acetal 2 to the Ai-face of 2-methylpropanal is interpreted by assuming a Zimmerman-Traxler like model, which minimizes steric hindrance in a plausible way65. 

Schuel H, Goldstein E, Mechoulam R, Zimmerman AM, Zimmerman S. Anandamide (arachidonylethanlamide), a brain cannabinoid receptor agonist, reduces sperm fertilizing capacity in sea urchins by inhibiting the acro-some reaction. Proc Natl Acad Sci USA, 1994 91 9460-9464. 

The photochemical interconversion of cis- and tra/w-5,6-diphenyl-bicyclo[3.1.0]hexanones has been extensively studied by Zimmerman, Hancock, and Licke.<77) Using isotope dilution analysis, these workers obtained very accurate quantum yields for the various photochemical processes involved in this reaction ... 

Zimmerman and co-workers were also able to obtain some information regarding the multiplicities of the excited states responsible for the initial /9-cleavage through quenching and sensitization studies. It was found that both trans-to-cis and cis-to-trans isomerizations could be sensitized by chlorobenzene under conditions where the latter absorbed over 95% of the light. The same product ratio was obtained under these conditions as in the direct irradiation of the ketones. With 1,3-cyclohexadiene or 2,5-dimethyl-2,4-hexadiene as quenchers nearly 90% of the reaction of the trans isomer could be quenched. Again the ratio of the quenched reaction products was the same as in the unquenched reaction. The reaction of the cis isomer, on the other hand, could not be quenched by 1,3-cyclohexadiene or 2,5-dimethyl-2,4-... 

It is interesting to note that the reactivity of the excited states of (25), (26), (27), and (28) in Table 8.4 increases in this order as stabilizing terminal substitution is increased. Zimmerman suggests that vinyl-vinyl bridging (the start of bond formation between 2 and 4) controls the reaction rate. 

The alternate approach of Dewar and Zimmerman can be illustrated by an examination of the 1,3,5-hexatriene system.<81,92> The disrotatory closure has no sign discontinuity (Hiickel system) and has 4n + 2 (where n = 1) ir electrons, so that the transition state for the thermal reaction is aromatic and the reaction is thermally allowed. For the conrotatory closure there is one sign discontinuity (Mobius system) and there are 4u + 2 (n = 1) ir electrons, so that the transition state for the thermal reaction is antiaromatic and forbidden but the transition state for the photochemical reaction is aromatic or allowed (see Chapter 8 and Table 9.8). If we reexamine the butadiene... 

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