Study of the transamidative ring expansion of N--halogenoalkyl--lactams of alkyl chain lengths 2–12 in liquid ammonia and other liquid amines: syntheses of 7-, 8- and 9-membered 1,5-diaza cyclic ketones, including routes to (±)-dihydroperiphylline and (±)-celabenzine

N-(3-Halogenopropyl)-4-phenylazetidin-2-ones undergo amination in liquid ammonia followed by transamidative ring expansion to give the eight-membered 4-phenyl -1,5-diazacyclooctan-2-one in excellent yield. Ring expansion of the amines in liquid ammonia is found to be much more effective than in hydrocarbon solvents. Formation of 7-, 8-, and 9-membered azalactams from the requisite -halogenoalkyl--lactams is an excellent synthetic process, though it is not applicable to 10membered rings. In the cases of rings of 13-, 15- and 17-members, although amination and apparent expansion takes place, the large rings appear not to be stable to ammonia and the final products are acyclic amides. N-[4-Halogenobut-2(Z)-enyl]-4-phenylazetidin-2-one satisfactorily forms a 9-membered (Z)-olefinic azalactam, but the (E)-isomer gives an acyclic amino amide. By using alkyl-substituted -lactam side-chains, C-substituted medium rings can be obtained; the relative instability of N-acyl -lactams to ammonia, however, leads to acylamino amides rather than expanded rings.Employing ethylamine in place of ammonia, it is shown that N-ethylated azalactams are formed satisfactorily, and using allylamine, N-allyl medium rings capable of further elaboration are obtained. The chemistry of these systems is discussed. Using transamidation in liquid ammonia, a short synthesis of the 9-membered spermidine alkaloid (±)-dihydroperiphylline is reported. Synthesis of key intermediates, whose transformation into the 13-membered alkaloids of the celabenzine group has already been effected, has been carried out.X-Ray single-crystal structure determinations for 4-phenyl-1,5-diazacyclononan-2-one, trans-4-phenyl-8-methyl-1,5-diazacyclooctan-2-one and (Z)-4-phenyl-1,5-diazacyclonon-7-en-2-one are reported, and comment is made on certain conformational features.

‘Making Older People Equal: Reforming the Law on Access to Education and Other Services’

Age-based discrimination in the supply of goods and services (including educational services) has only very recently been outlawed in the United Kingdom by the Equality Act 2010, the relevant sections of which have not yet been brought into force. This paper critically considers the Act and its implications, as well as the current proposal for an EU Directive on Goods and Services.The greatest immediate potential of the Equality Act lies in the general prohibition against age discrimination and the scope of the exceptions to it. The paper argues that exceptions permitting service providers to discriminate against older people (i.e. negative exceptions) should be very specifically set out in the reforming legislation.There should be no general defence to a claim of age discrimination based around the concept of ‘reasonableness’, which would not be consistently interpreted by courts and tribunals in a way that steers clear of traditional ageist assumptions and stereotyping.The paper argues that service providers should be permitted to discriminate in favour of older people (i.e. make positive exceptions) if the reason for doing do so satisfi es legislative criteria which are designed, amongst other things, to meet the particular needs of older persons or to promote social inclusion. Under this proposal, preferential treatment such as age-related concessionary fees for adult education courses and programmes would be lawful.

Benzylguanidines and Other Galegine Analogues Inducing Weight Loss in Mice

Dimethylallylguanidine, also known as galegine, isolated from Galega officinalis, has been shown to have weight reducing properties in vivo. Substitution of the guanidine group with an N-cyano group and replacement of guanidine with amidine, pyrimidine, pyridine, or the imidazole moieties removed the weight reducing properties when evaluated in BALB/c mice. However, retention of the guanidine and replacement of the dimethylallyl group by a series of functionalized benzyl substituents was shown to exhibit, and in some cases significantly improve, the weight reducing properties of these molecules in BALB/c, ob/ob, and diet induced obesity (DIO) mice models. The lead compound identified, across all models, was 1-(4-chlorobenzyl)guanidine hemisulfate, which gave an average daily weight difference (% from time-matched controls; +/- SEM) of -19.7 +/- 1.0, -11.0 +/- 0.7, and -7.3 +/- 0.8 in BALB/c, ob/ob, and DIO models, respectively.

Production of ion beams in high-power laser-plasma interactions and their applications

Energetic ion beams are produced during the interaction of ultrahigh-intensity, short laser pulses with plasmas. These laser-produced ion beams have important applications ranging from the fast ignition of thermonuclear targets to proton imaging, deep proton lithography, medical physics, and injectors for conventional accelerators. Although the basic physical mechanisms of ion beam generation in the plasma produced by the laser pulse interaction with the target are common to all these applications, each application requires a specific optimization of the ion beam properties, that is, an appropriate choice of the target design and of the laser pulse intensity, shape, and duration.