Ammonia, reaction with cyclopropanes

Haloalkyl phenyl sulfides produce cycloalkyl phenyl sulfides on treatment with base. The synthesis of cyclopropyl phenyl sulfides has attracted particular interest since these compounds can be metal-lated - - by Bu"Li in THF and the resulting 1-phenylthiocyclopropyllithium has been used for spiro-annelation of various cycloalkanones. - Thus, 3-chloro-l-phenylthiopropane leads to phenylthiocyclopropane on reaction with potassium amide in liquid ammonia (Scheme 7, entry a), but attempts to prepare 2-methylcyclopropyl phenyl sulfide from 3-chloro-l-phenylthiobutane by an analogous route failed in the cyclization step. Neither 3-mesyloxy- and 3-tosyloxy-l-phenylthiododecanes " nor 3-tosyloxy-l-phenylthiobutane produce cyclopropane derivatives either on reaction with LDA in THF (Scheme 7, entry b). Failure in these ring closure reactions has been attributed to inadequate car-... 

Metallic bronze fh(N 11, ), can, furthermore, be prepared from calcium-ammonia solution by evaporation of the ammonia. A bronze sohd is obtained, which in TH F at -30 °C behaves as a sohd surface in its reaction with alkyl hahdes (Scheme 4.17) [39]. Its apphcation in the reduction of 61 b produces a mixture of cyclopropane derivative 62 (81%) and straight-chain diphenylbutane 64 (8%). The process involves the formation of a tight anion radical-cation radical as an intermediate. Carbon-halogen bond cleavage occurs on the surface of the metalhc cluster. 

The bisammine complexes are prepared by condensing dry ammonia at low temperatures onto I Oxygen ligands such as 1,4-dioxane, THF or DMF can be used as well. Simple alkylated cyclopropanes can be converted to the corresponding tetrameric platinacyclobutanes on reaction with chloroplatinic acid in ethyl acetate , rather than in acetic anhydride ... 

Reaction of cyclopropane with sodium or potassium amides in liquid ammonia results in the loss of a vinylic proton rather than a methylene proton [198,199] similarly methyl cyclopropene-1--carboxylate exchanges its vinylic but not its methylene proton in base [200]. The structure of the cyclopropenide anion is clearly shown by its H-n.m.r. spectrum. In the case of the sodium salt this is as follows 56.73 (t,lH), -0.45 (d,2H), J = 1.94 Hz [199]. These compounds dimerise on steuiding with alkyl halides they give mono- and di-alkyl cyclopropenes [199] ... 

The hydrogenolyaia of cyclopropane rings (C—C bond cleavage) has been described on p, 105. In syntheses of complex molecules reductive cleavage of alcohols, epoxides, and enol ethers of 5-keto esters are the most important examples, and some selectivity rules will be given. Primary alcohols are converted into tosylates much faster than secondary alcohols. The tosylate group is substituted by hydrogen upon treatment with LiAlH (W. Zorbach, 1961). Epoxides are also easily opened by LiAlH. The hydride ion attacks the less hindered carbon atom of the epoxide (H.B. Henhest, 1956). The reduction of sterically hindered enol ethers of 9-keto esters with lithium in ammonia leads to the a,/S-unsaturated ester and subsequently to the saturated ester in reasonable yields (R.M. Coates, 1970). Tributyltin hydride reduces halides to hydrocarbons stereoselectively in a free-radical chain reaction (L.W. Menapace, 1964) and reacts only slowly with C 0 and C—C double bonds (W.T. Brady, 1970 H.G. Kuivila, 1968). 

Although many recent improvements in the preparation of the Simmons Smith reagent might be helpful23 24, the authors of this chapter would recommend one to consider an alternative two-step cyclopropanation procedure, which includes cycloaddition of dichloro- or dibromocarbene to methylenecycloalkane25 followed by reductive dehalo-genation (equation l)26. The first reaction is usually carried under phase transfer conditions and presents a very simple and efficient procedure. Reduction of gem-dihalocyclopropanes with lithium in tert-butanol or with sodium in liquid ammonia usually proceeds without complications and with high yield. 

Reductive opening with zinc only occurs with vicinal diactivated cyclopropanes whereas lithium in liquid ammonia also works with compounds having one activating substituent. In this case the bond overlapping most effectively with a C=0 group is broken The degree of stereoselectivity, however, is largely dependent on the proton source present and on the reaction temperature (equation 35) as well as on the nature of more remote substituents . ... 

Ammonia is also capable to induce ring cleavage of electrophilic cyclopropanes. Reaction of ammonia with the nitrocyclopropane 417 affords the alkylidenemalonate... 

The first report on the reduction of a carbonyl substituted cyclopropane was published in 1949. Reactions of methyl cyclopropyl ketone (131) with sodium in liquid ammonia in the presence of ammonium sulfate yielded instead of the expected methyl cyclopropylcarbinol (132) only a mixture of 2-pentanone (133) and 2-pentanol (134). 

Although it seems appropriate to formulate rearrangements of cyclopropanes induced by electron transfer reactions via trimethylene radical anions (see Sect.t 2.3.2) the existence of such species so far had not been proven unambigously. Especially noteworthy in this context is the observation of Walborsky 49) that in the reaction of optically active (+)-(R)-42 with sodium in ammonia the three-membered (+)-(R)-42 is recovered without loss of optical activity. Thus, the formation of the trimethylene radical anions 46 and 47, if it occurs, is irreversible (see page 12 and 13). Therefore, electron transfer reactions of various cyclopropanes with special attention to the question of the formation of radical anion intermediates have been studied by Boche and coworkers 59). 

Various cyclopropanecarboxylic acids and esters have been converted to various amides, TV-alkylated amides, and hydrazides by treatment with ammonia, alkylamines, - and hydrazines, respectively. In many cases the acids have been converted via the corresponding acid chlorides generated in situ. Diethyl esters of a variety of cyclopropane-1,1-dicarboxylic acids also react with urea. Generally, all these reactions proceed smoothly and in fairly good yield and give only very small amounts of byproducts due to opening of the cyclopropane ring. 

There have been numerous reports on the reduction of activated cyclopropanes with alkali metals either dissolved in liquid ammonia or used in suspension. Most of these reactions were carried out with lithium as reducing agent. In an early study, various substituted cyclopropyl ketones were treated with lithium in liquid ammonia. rranj-l-Acetyl-2-methylcyclopropane (1, R = Me = H R = Me) gave 3,4,4-trimethyl-2-pentanone (3) as the result of... 

When diethyl tetracyanocyclopropane-l,l-dicarboxylate (6), a cyclopropane derivative with six electron-withdrawing groups, was treated with ammonia in diethyl ether, the reaction took an unforeseen course cleavage of the tetracyano-substituted bond occurred and one of the ester functions was eliminated to give a stabilized allyl anion 1 ... 

Aryl-substituted cyclopropyl ketones, e.g. 34, are reductively cleaved to acyclic ketones by refluxing in ethanol, or butanol, with zinc metal or a mixture of zinc metal and zinc(II) chloride. The reaction is thought to proceed via radical anion intermediates analogous to those of the lithium/ammonia process. Various substituted derivatives were studied and the aryl substituent in the cyclopropane ring was found to be essential alkyl-substituted analogs were not reductively cleaved with this reagent. 

Treatment of cyclopropane-1,1-diacetic acid (99) with ammonia to give the imide followed by reduction with lithium aluminium hydride gave the spiropiperidine (100). Alkylation with chloroacetonitrile, reduction, and the Rathke reaction gave spirgetine (101) Scheme 5.24.). The product was claimed to have antihypertensive action with a duration twice that of guanethidine [112]. 

Examples of carbonyl insertion reactions involving compounds of Group VIII metals are more common. The reaction of iron pentacarbonyl with the cyclopropylalkene (41) involves both carbonyl insertion and cyclopropane ring opening. Reduction of cobalt(n) to cobalt(o) in aqueous ammonia is thought to involve a carbonyl insertion stage, with... 

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