Addition of diazomethane

A good example of a surface-modified lens is the Sola/Bames-Hind Hydrocurve Flite lens, introduced in 1986. The material for the commercial Hydrocurve lens, bufilcon A [56030-52-5] contains methacrylic acid and has a high affinity for protein and subsequent deposition. The surface of the Flite lens was chemically modified with the addition of diazomethane (190) to reduce the surface charge. In vitro testing demonstrated a decrease in protein adsorption (191). 

The addition of diazomethane to unsaturated esters (1), as ethyl acrylate, methyl crotonate and ethyl cinnamate, was investigated by Auwers who showed that the primary addition product is a A -pyrazoline (2) which rearranges spontaneously to the conjugated A -pyrazoline (3). 

Stereospecific addition of diazomethane is observed with dimethyl di-methylmaleate (7) and dimethyl dimethylfumarate (10). ... 

The addition of diazomethane to a,/l-unsaturated ketones, e.g., benzalace-tone and benzalacetophenone, results in A -pyrazolines (16) which decompose thermally to the conjugated ketones (17). Cyclopropane formation is not observed in this instance. 

The first addition of diazomethane in the steroid series was carried out with the A -20-keto system (1) leading to a [17a,16a-c]-A -pyrazoline (2). ... 

The addition of diazomethane to 17j -hydroxy-5a-androst-l-en-3-one (7) gives the A -pyrazoline (8) in which the C=N bond is conjugated with the 3-keto group. °°... 

Addition of diazomethane to the A -17-ketone (20) proceeds from the -face of the molecule to give (22) in high yield after cleavage of the intermediate pyrazoline (21). ° ... 

An unusual seven-membered ring-forming rearrangement was observed m the addition of diazomethane to a perfluorinated cyclobutene [5] (equation 3)... 

Bis(lrifluoromethyl)oximes also are highly reactive dipolarophiles, as evidenced by the facile regiospecific addition of diazomethane [32] (equation 28)... 

Dipolar additions of diazomethane to acetylenes under mild conditions are restricted to monosubstituted acetylenes thus the formation of pyrazole derivatives 1 (1,3-dipolar addition, C=C isomerization, then methylation) confirms the existence of a terminal acetylene in caryoynencins (87TL3981) (Scheme 5). 

Addition of diazomethane to cyanoallene took place at the internal C=C bond of the cyanoallene to give 4-methylenepyrazoline 85. The following isomerization via 1,3-hydrogen shifts afforded 4-methyl-5-cyanopyrazole 86 [83], a-Diazo carbonyl compounds reacted in an analogous way [84]. 

Figure 4.5 The four possible isomers from single addition of diazomethane to Qo-...

A second and related consequence in aliphatic nitro compounds is the acidification of the directly bonded CH unit through the attendant stabilization of the derived conjugate bases (5,6). As with all delocalized anions, reprotonation gives rise to tautomers, the original C-nitro compound (I) and the oci-nitro or isonitro form (II), Eq. 2.1. The aci-nitro tautomers are typically present in very minor concentrations, with equilibrium constants (A eq) between 10 and 10 (7). Alkylation of the delocalized anion leads to both a-substituted nitro compounds and the regioisomeric nitronic esters (nitronates). Nitronates were described as early as 1894 (8), however, the first isolated nitronic ester was obtained several years later upon the addition of diazomethane to phenylazonitromethane (1), Eq. 2.2 (9). 

Attempts to generate thiocamphor (5)-methylide (44) by the addition of diazomethane to thiocamphor and subsequent N2-elimination from the [3-1-21-cycloadduct 43 led to enethiol ether 45 via a 1,4-H shift (Scheme 5.17). The formation of an unstable intermediate 43 was proposed on the basis of the proton nuclear magnetic resonance ( H NMR) spectrum of the crude mixture. The postulated intermediate 44 could not be intercepted by dipolarophiles or methanol, and did not undergo electrocyclization to give the corresponding thirrane (41). 

The addition of diazomethane to cyclobutanones results in a convenient expansion to cyclopen-tanones. With few exceptions, the rearrangement of the intermediate nitrogen ylide is highly regioselcctive, only one product is generally isolated, particularly in cases where both substituted cyclobutanones and substituted diazomethanes are used. Typical examples are shown in Tabic 6 further examples can be found in refs 57, 59. 61 -63 and 65-68. 

Birch reduction, followed by acid treatment and addition of diazomethane leads to the A9(11)-enone 159 in 41% yield. Then, the double bond is hydrogenated and, by using PhSeCl and hydrogen hydroperoxide, the double bond A13 is formed. Treatment of the enone with lithium disopropylcuprate-dimethyl sulfide complex gives an intermediate enolate that is trapped again using PhSeCl. Enone 160 is obtained via oxidative elimination (62%). 

Esters of racemic pyrazolidine-3-carboxylic acid (5-azaproline, 16) are obtained by a two-step reaction via addition of diazomethane to acrylic acid esters to form the corresponding dihydropyrazoline derivatives, which are converted into the desired pyrazolidine-3-carb-oxylic acid derivative by hydrogenation over palladium on charcoal,11621 or by reduction with sodium cyanoborohydride,[164l or with zinc in acetic acid. Details are given in Table 6J1651... 

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