A modified version of the Bischler indole synthesis has been developed in which the key step is the N-H insertion reaction of rhodium carbene intermediates derived from α-diazo-β-ketoesters with anilines. Thus N-methylanilines 1 react with diazoketoesters 2 in the presence of dirhodium() acetate to give (N-arylamino)ketones 3, cyclisation of which using boron trifluoride-ethyl acetate or acidic ion exchange resin gives the indoles 4. In order to extend this method to the synthesis of N-unsubstituted indoles, a new protecting group strategy for indoles was developed. In this, anilines are reacted with α,β-unsaturated-esters or -sulfones to give the conjugate addition products 6 and 9, cyclisation of which gives indoles 8 and 11. The N-(2-ethoxycarbonylethyl)-and -(2-sulfonylethyl)-protecting groups are readily removed from indoles 8 and 11 by treatment with base.

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A study has been made of the physical chemistry of the development of colonies on the surface of a minimal agar medium by a standard strain of Aerobacter (Klebsiella) aerogenes and by drug-resistant strains derived from it. Histograms of final colony diameter, constructed from measurements on plates having different numbers of colonies, have one maximum and are approximately symmetrical. Normal Gauss curves have been verified to fit some of the histograms, most of which are of similar form, although occasionally a somewhat wide spread on the side of increasing diameter occurred. When moderate or large numbers of colonies are present the total colony area supportable by the plate is proportional to the total capacity of the plate. The distribution of sizes, however, is shown to depend partly on the variation in the lags of the single cells inoculated and upon the free space left around the different individuals on the plates. A complex interplay of individual with cooperative or competitive factors thus exists. A detailed study has been made of the growth of single colonies. The initial exponential growth of the single cell is soon replaced by a phase in which the radius of the developing colony is linearly related to the time of incubation. In this phase diffusion of nutrients, buffer or waste products is not rate determining and the colonies remain more or less disk-shaped with a fairly regular perimeter. With moderate or large numbers of colonies exhaustion of the plate stops growth at this stage, but in the protracted growth which occurs when a few colonies only are present the ‘radial law’ phase gives way eventually to a slower phase in which the area of the colony increases linearly with time. Diffusion, chiefly affecting pH rather than nutrient supply, now becomes more and more the dominant factor controlling growth and the colony perimeter becomes increasingly irregular. Morphological changes may now appear. This is dealt with briefly as a prelude to a further paper. Kinetic models have been constructed for various aspects of the research and have been tested against the results.

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