Where the work of others has been used, this has been acknowledged in the text. I would like to mrs. Zarina Sayed Alley and Mr. Selwyn Petersen thanks for their assistance with the management of DV spectra.
List of Schemes
List of Tables
Abstract
INTRODUCTION
1:...6- Lactams
Synthetic routes to p-lactams
The first p-Iactam was prepared by Staudinger and his co-workers during their studies of ketenes. A recent publication also uses β-amino acids as precursors for β-Iactamer.17 The amino acids themselves were prepared by a new method whereby N-Alkoxycarbonyl-1-methoxyamines and an ester are added to LDA (lithium diisopropylamide).
LDA/THF
An example of this method is the reaction between benzylidenaniline and phthaloylglycyl chloride in the presence of triethylamine, yielding 1,4-diphenyl-3-phthalimido-2-azetidinone in 50% yield. Treatment of the prepared imines with acetoxyacetyl chloride in the presence of triethylamine yields the desired β-actam.
Unexpected ring opening to afford p-Iactams
- Kinetic and thermodynamic aspects of ring strain
The term 'strain energy' refers to the difference between ~Hfo of the cycloalkane and. Analyzing the data, we find that cyclopropane and cyclobutane are similarly strained (although strain per methylene differs between the two) and are the most unstable of the cycloalkanes.
C COOH OH
COOH +
Radical addition reactions
- Production of free radicals via photolysis
- Radical addition to olefins
The orbitals of concern are the SOMO (singly occupied molecular . orbital) of the radical and the HOMO (highest occupied molecular orbital) and LUMO (lowest unoccupied molecular orbital) of the double bond, i.e. the table below shows that the orientation of addition to an electron-rich and an electron-poor olefin is almost identical, however, the rate of addition differs very significantly, as discussed in the previous sections.
Footnote to Introduction
This makes it possible to distinguish which radical is the attacking radical in the reactions of olefins with terminal methylene groups by observing which product is formed.
Discussion
Formation of ethyl N-2-bromo-alkylcarbamates via photolysis reactions
Ethyl N-bromo-N-methylcarbamate was prepared by stirring ethyl N-methylcarbamate in the presence of bromine in the dark for 48 hours.2 The percent conversion of the starting material was determined by titration against standard O. Sodium thiosulfate solution IOOM.3 This procedure is fully discussed. in the section 'Preface to the trial' (page 60). The energy barrier for rotation about a single bond at room temperature is 15-20 kcallmo1.7 Scanning calculation results showed that the largest energy barrier to be overcome is from the smallest at about to the rotational transition state at about 235 °C. °, is about 7 kcalmol.
Formation of ethyl N-bromo-alkylcarbamates via traditional synthetic routes
For the first portion, the reaction was initially spontaneous but subsided after the addition of the acid was complete. The reaction was carried out by heating a mixture of the aldehyde, nitromethane and ammonium acetate under reflux for 2.5 hours.
1 LAB
Intermolecular additions and intramolecular cyclizations
However, the reaction result was identical to that observed in the first experiment. As in the case of ethyl N-2-bromo-2-phenylethyl-N-methylcarbamate, the steric bulk of the adjacent phenyl group is a factor.
Comments
However, this reaction used a carbamate to diene molar ratio of 2:1, which was not the case for previous photolysis reactions where a molar ratio of 1:2 was used. If this type of reaction were successful, the vinyl group would be an ideal replacement for the phenyl group. Assuming that this change produces the same results as described above, the nature of the group involved would be irrelevant.
In the case of oxazolidinone, this would imply that entropy considerations are the main factor driving the cyclization. A possible approach could be to repeat the pyrolysis of ethyl N-2-bromo-2-phenylethyl-N-methylcarbamate in the absence of triethyl phosphite, lowering the temperature to find the highest temperature at which ox-3-azolid-2-one formation ceases. However, these comments are mere speculation and further investigation is needed to substantiate them.
Preparation of ethyl N-bromocarbamates General procedure 2
Carbamate (25 mmol), III dichloromethane (180 mL) and saturated sodium bicarbonate solution (135 mL) were treated with bromine (25 mmol) and stirred in the dark for 24 h. The mixture is then treated with a further amount of bromine (25 mmol) and stirred for another 24 hours in the dark. The solution is then cooled (0°C), separated and the organic layer is washed with cold saturated sodium bicarbonate solution (2 x 150 ml).
The organic layer was then dried (MgSO 4 ) and concentrated (rotary evaporator temperature <30 °C) to give ethyl N-bromocarbamate. Notes: The IH NMR spectrum is somewhat misleading as the coupling constants for the triplet appear to be different. This is due to the presence of the parent carbamate as an impurity, which has a slightly different chemical shift.
Formation of ethyl N-2-bromo-alkylcarbamates via photolysis
Formation of ethyl N-bromoalkylcarbamates via traditional synthetic methods
- Ethyl N-bromoalkyl-N-alkylcarbamates
The benzene was evaporated, anhydrous ether was added to the residue, and the solution was refrigerated overnight. Notes: The integration of the two groups of methylene protons is distorted due to the presence of impurities. A solution of 3-phenylpropyl bromide in methanol was added dropwise, with stirring, and the mixture was heated at reflux for 48 hours.
As a result, the spectrum contains a number of impurities, but clearly shows that cyanide is the main component of the mixture. The mixture was then extracted with dichloromethane, dried (MgSO 4 ) and concentrated to give a red/orange oil which was purified to give 4-phenylbutylamine as a yellow oil (0.65 g, 4.36 mmol, 14%) . The mixture was then filtered and the inorganic salts were washed with dichloromethane and water.
The mixture was placed in a separatory funnel and the upper ether layer was separated, washed with cold water and extracted with ice-cold 10%. The mixture is then cooled to room temperature and treated very slowly with water (1.5 ml), 15% sodium hydroxide solution (1.5 ml) and water (3 ml).
Intermolecular additions and intramolecular cyclizations
Ethyl N-methyl-N-phenylcarbamate (1.11 g, 6.19 mmol) was added to the solution and heated under reflux for 22 hours. The presence of two resonances between 5.05-5.22 ppm in the 1H NMR spectrum, corresponding to the methine proton next to bromine, indicates this. The mixture was then cooled to room temperature and the water condenser was replaced with a Vigreux column.
Then ethyl-N-methyl-N-phenylcarbamate (1.16g, 6.47mmol) was added dropwise to the solution and the mixture was stirred for a further 30 minutes at -60°C. In the IR spectrum, the absorption corresponding to the p=o stretch can be found at 1255 cm-1.14. Notes: It is clear from the HMBC and COZY spectra that the triplet at ∼1.2 ppm and the multiplet at ∼4.1 ppm do not correlate with any of the resonances attributed to the oxazolidone.
In the NOESY spectrum, a correlation between ~b and Hg, H12 indicates that H4 bond is the phenyl ring relative to the 4-5 bond (Fig. 23). The crude reaction mixture was purified by preparative thin layer chromatography (EhO/Hex) to yield ethyl N-methyl-N-4-phenyl-3-butenylcarbamate as a colorless oil (33.1 mg, 0.14 mmol, 35% ).
5 Miscellaneous reactions
List of Abbreviations
Porifera (The sponges)l
A sponge's body looks like a long vase with a single large opening at the top (the ossulum) and numerous tiny pores, which penetrate the body walls. The body wall is composed of three layers; an outer layer of flat cells, a middle, jelly-like mesenchyme, and an inner layer that lines the central cavity. The figure below (Fig. 1) shows a cross-section of a simple sponge with accompanying detail of a body wall.
In addition to this organic skeleton, the mesenchyme consists of spiky silicon spicules, which give the sponge a cactus-like appearance under a microscope. The inner layer of the body wall consists of flagellated cells, also called collar cells, whose whipping action drives water through the sponge and out of the osculum. This water is replaced by sucking more from the environment through the pores of the body wall.
This creates an extremely fine mesh that catches small particles as the water flows through the sponge. Many sponges have optimized this process by developing complex body walls that are folded to increase the surface area of the neck cells.
Introduction to sterols 1. General Remarks
- Marine Sterols
The figure below (Fig. 7) shows the two sterol cores to which the side chains (R) are attached, labeled A and B. The revised structure of petrosterol is shown above (Fig. 8c).14 The p-bromobenzoate derivative was used in this X-ray diffraction analysis. Three new sterols containing cyclopropane rings from the New Zealand sponge Petrosia hebes were reported in 1987 by Cho et al.16 The major sterol in this case was again petrosterol (Fig. 8c), which made up more than 50% of the sterol mixture, which totaled twenty percent. five sterols.
Also isolated was 23,24-dihydrocalysterol (Fig. 8d), as well as its saturated analogue 23,24-dihydrocalystanol (Fig. 8f), the second new sterol. The isolation of hebesterol provided what was described as "the key 'missing link'" in a proposed biosynthetic sequence leading to 23,24 dihydrocalysterol (Fig. 8d) and petrosterol (Fig. 8c). Nicasterol (Fig. 8i) was isolated as a trace sterol from Calyx nicaensis in 1985 by Proudfoot et al.17 The structure and absolute stereochemistry of nicasterol was determined by partial synthesis.
This showed that the two cyclopropane ring protons were trans to each other across the 23-24 bond, as shown (Fig. 8i). The three sterols shown above (Fig. 9) were reported between 1992 and 1994 by Iguchi et al.18,19 All three compounds were isolated from the same sponge from the.
Biosynthesis of cyclopropane-containing sterols
1 SAM
Structure elucidation of compound 1
All spectra described in the following text can be found in Appendix C, Part 2, of this work. The impurity present, marked with 'x' is ethyl acetate.). First and most noticeable, is the presence of two very high-field resonances at 0.36 and -0.18 ppm. In the NOESY spectrum, a correlation between H24 and one of the terminal methyl groups is observed.
In summary, the downfield resonance at 0.36 ppm is assigned as H2Sp and the upfield resonance at -0.18 ppm is assigned as H2Sa. The methyl group to which H24 and H2SP correlate in the NOESY spectrum is assigned by convention as C27. This was attributed to H3 and was assigned as a due to a correlation with Hs in the NOESY spectrum.
In the IH NMR spectrum of the product it was clear that the signal attributed to H3 had moved upfield, from its position at 3.56 ppm, to 4.66 ppm, because it was now near the electron-withdrawing acetyl group. In the spectrum it was also clear that an additional methyl group was now present at 21.49 ppm, due to the carbon of the methyl group of the acetyl group.
Appendix A
List of spectra (chapter 1)
P38) 4.2 IHNMR spectrum of diethylbenzylphosphonate (P39) 42 31p NMR spectrum of diethylbenzylphosphonate (P40) 4.2 Infrared spectrum of diethylbenzylphosphonate (P41) 4.3 IHNMR spectrum of adduct phosphonate 4.3 IHNMR spectrum of phosphophosphonate 4P4CN (4P4-phosphonate) spectrum (4P4 -phosphonate) to adduct (P43).
Wavelength (nm)
Wavenumbers (cm-1)
Wavenumbers (cm-i)
