Three- and four-membered rings

Three and Four-membered Rings.— Thiaziridine-1,1-dioxides (280) have been prepared by the reaction of diazoalkanes with N-sulphonylamines. The compounds are stable at -30 C but lose SO2 to form aldimines on warming. Elimination of halogen from a-halosulphonamides and from A -chlorosul-phonamides failed to give the required products. Only a few three-membered 

Flve-membered Rings.—In a series of papers Cambie and co-workers - have shown that iodoisothiocyanates (285) will react with carbon and other nucleophiles to form a variety of 2-substituted-2-thiazolines (286). The yields are good and the products useful since protons attached to the 2-substituents are acidic, thus offering the opportunity for further modification. Also, thiones 

3-Amino-2-arylazo-2-butenoic acids (289) have been prepared by two pathways from acetoacetic esters. The reaction of these compounds with bligomeric a-mercapto-aldehydes leads to substituted thiazoleacetic esters (290), which appear to be useful intermediates for the synthesis of penicillin analogues. Most syntheses of 2,4-dioxa-l,3-thiazolidines (292), which show an interesting spectrum of biological activity, involve oxidation of thiol precursors. A new method uses readily available dihydropyrimidine thiones in reaction with chloro-acetic acid. The reaction does not proceed if R = H in (291). 

The reaction of thioketens and amino-azirines proceeds by C=N cleavage to give the dipolar species (293) or ketenimines (294), depending upon substitution hydrolysis of the latter leads to 2-thiazolin-5-ones (295). There are few general routes to 1,3,4-thiadiazolines and a new method, discovered accidentally, provides the derivatives (296) which, since they have amidine characteristics, will probably prove to be useful synthons. Thiadiazolidine diones are readily available from metallated iV-(trimethylsilyl) alkylamines. 

The anti-fungal and anti-bacterial properties of l,2-benzisothiazol-3(2ff)-ones has caused much synthetic activity to be focused upon them and two new routes have been published this year, from the O-acylhydroxylamines (297) and the sulphinylbenzamides (298). As one would expect, spirocyclic benzo-thiazolines are readily prepared from o-aminothiophenols and cyclic 

Without doubt the most general method for the synthesis of chiral epoxides to date is that of Sharpless and co-workers such that the stereochemical outcome of the epoxidation of the allylie alcohol (6) holds true almost no matter the nature of to R. However, recent studies have shown that if t-butyl groups are incorporated at either the carbinol carbon or at the P- -position then the e.e.s of the a-hydroxy-epoxides are much reduced. The synthesis of a-keto-epoxides by the Darzens condensation is well known, but this year has seen the first example of chiral, aqueous-catalysed Darzens condensation to give the epoxy-ketones (7) albeit in only moderate optical and chemical yields (2-62% and 5- 3% respectively).  

Several new or modified general syntheses of epoxides have also appeared this year. For example Mosset and Gree have found that trimethylsulphonium methylsulphonate (8) is a highly reactive 

The conversion of a ketonic carbonyl into a functionalized epoxide presents much more of a synthetic challenge, and a useful method for doing just that has been published by Cookson and Crurabie. Thus, addition of allyl Grignard reagents to the ketones (9) affords the homoallylic alcohols (10), which are converted into the epoxides (11) by treatment with NBS followed by cyclization with NaH.  

Kirschenbaum and Sharpless have shown that by altering the conditions of the Payne method for tungstate-catalysed epoxidation of a,e-unsaturated acids the yields are greatly improved and the scope of the reaction is increased. It was also concluded from this 

The system developed by Edwards and Curci to generate dimethyl-dioxirane in situ has been modified by Murray and Jeyaraman to allow the distillation of a number of dioxiranes (12) as solutions, thus allowing spectroscopic characterization and a study of their chemical properties. 

The first two paragraphs of the corresponding chapter in Volume 1 of this Report also relate to this chapter. Several relevant reviews and books have been published on particular topics and compound types. The report of the International Symposium on the Chemistry of Small Rings held at Louvain (Belgium) in 1971 has also appeared.  

Randic and Maksi6 have reviewed the maximum-overlap method of describing the hybridization of bonded atoms, and a number of cyclopropane and cyclobutane derivatives are included. The method has also been applied to benzocyclopropene and benzocyclobutene. One measure of the hybridization of the bonding orbitals of carbon is the magnitude of the and 

3-tetramethylcyclobutane, bicyclobutane, bicyclopentane, and trans-tricyclo [3,1,0,0 ] hexane have been reported and used to calculate the s-character of the carbons bonding orbitals. 

Besides electronic structure and bonding, other molecular features of cyclopropane derivatives, such as conformation, have been theoretically scrutinized. The barrier to rotation about the bond joining methyl to cyclopropyl in methylcyclopropane has been calculated to be 1.82 kcal mol using the INDO approximation. When methyl is replaced by amino- or phosphino-groups, there is more than the single minimum -in the rotation energy profile but, for both compounds, (1) is the most stable conformation. It is calculated 

Internal rotation within vinylcyclopropane and vinylcyclobutane and their 

Since the last Report/ the number of publications relevant to this chapter has increased by 35 %. There have been numerous reviews and articles concerning aspects of the chemistry of three- and four-membered rings/ 

Amongst theoretical calculations for these systems is included a quantum chemical study of the 7c-eIectron delocalization in triphenylphosphonium ylides, leading to an evaluation of the criteria for reactivity and aromaticity in the Wittig reaction. It was predicted that the as yet unknown ylide (1 X = PPhg) will not take part in the Wittig reaction.  

Matlin, in Alicyclic Chemistry , ed. W. Parker, Specialist Periodical Reports, The Chemical Society, London, 1975, Vol. 3, Chapter 1. 

Using graph-theoretical technique, Hearndon and Ellzey have identified, within the Hiickel MO formalism, a new class of n-stnictures containing even numbers of 7t-orbitals of which 2-cyclopropenylallyl is the smallest member. This has a closed shell of electrons according to HMO theory, but is required to have a biradical valence bond structure, and dicationic species should be obtainable.  

From a graphical study of positional isomers containing bivalent sulphur, it was predicted that (2a) should be more stable than (2b). The former has been synthesized, whereas the latter is not a known compound. 

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A. Rosowsky, ia A. Weissberger, ed., Heteroyclic Compounds with Three- and Four-Membered Rings, Part One, Interscience PubHshers, a division of John Wiley Sons, Inc., New York, 1964, pp. 289, 308. 

Onium ions of small and large heterocyclics are usually produced by electrophilic attack on a heteroatom. In three- and four-membered rings nucleophilic attack on an adjacent carbon follows immediately, in most cases, and ring opening stabilizes the molecule. In large rings the onium ion behaves as would its acyclic analog, except where aromaticity or transannular reactions come into play (each with its electronic and steric pre-conditions). A wide diversity of reactions is observed. 

The loss of CO, S, SO or SO2 by thermolysis or photolysis has been used to make three-and four-membered rings. Scheme 26 gives examples. 

Cycloadditions Forming Three- and Four-Membered Rings... 

Tlie present chapter reviews the chemistry of three- and four-membered ring compounds containing an S—S bond in their ring. Dithiiranes 1,2-dithietanes and 1,2-dithietes are the compounds of this type. Although 1,3-dithietanes are four-membered heterocycles which are prepared much more easily and are seemingly more familiar, they have no S-S bond in the ring and hence are not included in this chapter. 

Progress in the chemistry of three- and four-membered rings containing two sulfur atoms has been rapid in the past few years. An updated survey of the chemistry of dithiiranes, 1,2-dithietanes, and 1,2-dithietes is now provided from a major center in this area by Professor J. Nakayama and Dr. A. Ishii (Saitama University, Japan). 

Scheme 1 Little difference in the ring strain between the three- and four-membered ring molecules...

Three- and four-membered ring molecules of nitrogen and phosphorus are investigated (Scheme 32) [80]. The unsaturated four-membered ring molecule, tetracyclo-phosphene 79 is less strained than the saturated molecule, tetracyclophosphane 15... 

There are no exceptions in Tables 1 and 2 [7], For 4N electron systems, the singlet ground states of trimers and tetramers do not assnme three- and four-membered ring structures of and symmetry, respectively. 

The i-orbital array of three and four-membered rings is of the Hiickel conjugation. (Scheme 2). The splitting patterns of the orbital energy levels (Scheme 3) show that the total number of valence electrons for the closed-shell structures is 4Af + 2 for the three- N= 0) and four-membered rings (N= 0, 1). 

The ability to probe specific pathways using these statistical approaches relies completely on the geometric structures determined from the calculated stationary points of the PES. In other words, the knowledge that, for example, two particular stationary points represent a three- and four-member ring intermediate, respectively, allows one to calculate rates, and therefore pathway branching ratios through these channels. 

Difficulties encountered in the preparation of three- and four-membered rings via radical cyclization are due to the strain of these compounds. Thus, ring opening usually proceeds much faster than ring closure. 

The formation of the linear polymer from the cyclic monomer requires a decrease of the free energy. Because usually entropy is lost during polymerization, the main driving force for the ring-opening process is the release of the angular strain upon conversion of the cycles to linear macromolecules. Thus, a majority of three- and four-membered rings can be readily and quantitatively converted into polymers. 

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