2.2.2- Trichloroethyl derivatives

Chloral can also be reacted with urea to give 1-hydroxy-2,2,2-trichloro-ethyl urea [34, 35] and with other ureas (linear and cyclic) as well as sulfamides to give 1-hydroxy-2,2,2-trichloroethyl derivatives as described in references 34, 35. Other references to ureas containing the 2,2,2-trichloroethyl groups or flame retardants for polyurethanes should also be consulted [35,36, 37]. 

Campbell s group synthesized the spiro-p- lactams 123 and 124 (Brem-ner et al., 1976a,b) by treatment of 109 and 111 with 2 equiv of phen-yllithium in THF at -78°C, followed by an excess of phosgene. Spi-roureido adduct 123 was isolated in 19% yield and displayed characteristic infrared (IR) absorptions at 1858 and 1800 cm. Trichloroethyl derivative 124 was prepared in 16% yield and furnished 125 upon deprotection. This acid was inactive against a range of organisms. 

Six protective groups for alcohols, which may be removed successively and selectively, have been listed by E.J. Corey (1972B). A hypothetical hexahydroxy compound with hydroxy groups 1 to 6 protected as (1) acetate, (2) 2,2,2-trichloroethyl carbonate, (3) benzyl ether, (4) dimethyl-t-butylsilyl ether, (5) 2-tetrahydropyranyl ether, and (6) methyl ether may be unmasked in that order by the reagents (1) KjCO, or NH, in CHjOH, (2) Zn in CHjOH or AcOH, (3) over Pd, (4) F", (5) wet acetic acid, and (6) BBrj. The groups may also be exposed to the same reagents in the order A 5, 2, 1, 3, 6. The (4-methoxyphenyl)methyl group (=MPM = p-methoxybenzyl, PMB) can be oxidized to a benzaldehyde derivative and thereby be removed at room temperature under neutral conditions (Y- Oikawa, 1982 R. Johansson, 1984 T. Fukuyama, 1985). 

Among the aldonolactone-based surfactants are aldonolactone-linked fatty esters which have been prepared by selective acylation of unprotected aldono-1,4-lac-tones or aldono-1,5-lactones, One of the first reported examples of this type of surfactant was applied to the enzymatic synthesis of 6-0-aUcanoylgluconolactones [35], Thus, 6-0-decanoyl- and 6-0-dodecanoyl- derivatives (21a and 21b, respectively, Scheme 8) were obtained in 26-27% yield by esterification of glucono-1,5-lactone (1) at C-6 with the corresponding 2,2,2-trichloroethyl carboxylate in the presence of porcine pancreatic lipase (PPL) as catalyst. Compounds 21a,b are soluble in water at 90-96°C but precipitate when cooled to 30-37°C, NMR and GC-MS analysis after dissolution and precipitation indicated the presence in the mixture of compound 21b, the glucono-1,4-lactone-derived ester 22, and the... 

The effect of the side chain bulkiness has been further studied on a series of chloro derivatives of poly(ethyl methacrylate)(PEMA). Though poly(2-chloroethyl methacrylate) exhibits69 a pronounced peak at Ty = 117 K, poly(2,2,2-trichloroethyl methacrylate), poly(2,2,2-trichloro-l-methoxyethyl methacrylate), and poly(2,2,2-trichloro-l-ethoxyethyl methacrylate) do not show (Fig. 6) any low-temperature loss maximum above the liquid nitrogen temperature157. However, these three polymers probably display a relaxation process below 77 K as indicated by the decrease in the loss modulus with rising temperature up to 100 K. Their relaxation behavior seems to be similar to that of PEMA rather than of poly(2-chloroethyl methacrylate) which is difficult to explain. 

The nucleotide derivatives (330, R = H, R = P032- and R = Me, R =P032-) were obtained analogously from (328) (R = H, Me) and the selectively protected nucleotide (331) [166, 167], The trichloroethyl groups were reductively cleaved with Zn-Cu couple, and saponification then gave the desired analogues. 

Methods for the conversion of derivatives of morphine into their N-nor-com-pounds, using vinyl chloroformate,149 trichloroethyl chloroformate,150 and phenyl chloroformate,151 have been patented. Norneopine has been prepared from neopine and diethyl azodicarboxylate and by the hydrolysis of 7V-nitrosonor-neopine.152 The conversion of N-nor-bases into N-alkyl-compounds by the reduction of amides has been covered by a further patent.153... 

Vilceanu et al. [483] performed acetylation of the free hydroxyl group of (1-hydroxy-2,2,2-trichloroethyl)dialkyl esters of phosphoric acid prior to analysis, as unchanged original substances often decompose in the column. They prepared the derivatives by reaction with acetic anhydride in acetonitrile with pyridine as catalyst and performed the analysis on a column packed with Apiezon L (15% on Chromosorb W) on which acetates showed good chromatographic properties. 

Chlorophenoxy acids are chromatographed after esterification. Methyl esters [498] and propyl esters [499] prepared by transesterification from methyl esters by heating for 5 min with n-propanol and sulphuric acid are often used. For a very sensitive analysis, Mierzwa and Witek [500] proposed the following procedure. They esterified acids with 20% of 2,2,2-trichloroethanol in TFA anhydride in the presence of sulphuric acid by heating at 100°C for 15 min (or several hours at room temperature) and analysed the derivatives on a column packed with 15% of QF-1 plus 10% of DC-200 (1 1) at 195°C. Trichloroethyl esters permit down to hundredths of 1 ppb of chlorophenoxy acids to be... 

Carboxylation. Bredereck s reagent has been used in a simple synthesis of L-y-carboxyglutamic acid (S), an unusual natural amino add present in prothrombin and believed to be involved in elotting. The starting material is the lactam 1 derived from L-glutamic acid and available commercially. It is converted by reaction with this reagent into the enamide 2. Reaction with 2,2,2-trichloroethoxycarbonyl chloride transforms 2 into the trichloroethyl ester 3 in moderate yield. The synthesis of 5 is completed by reaction with benzyl alcohol and triethylamine followed by hy drogenolysis. ... 

Later work has shown that a dynamic kinetic asymmetric transformation could be obtained if the acetates were converted into carbonate groups. With the tetra(2,2,2-trichloroethyl) carbonate derivative, reactions with carbon and nitrogen nucleophiles gave exclusively the monosubstituted products in high yield (61-95%) and excellent enantiomeric excesses (95-99%). However, car-boxylate nucleophiles afforded the disubstituted products in high yield and enantiomeric excess (eq 7). This allowed an efficient synthesis of D-myo-inositol-l,4,5-trisphosphate to be devised. 

Due to the relatively high stability of the N-2,2,2-trichloroethoxycarbonyl (Troc) group to acids and its selective removal by zinc reduction even in the presence of Al-benzyloxy-carbonyl derivatives, it can offer interesting possibilities in the syntheses of particular pep-tidic compounds for example, it has been used for N -protection of lysine in the synthesis of The Af -Troc-protected lysine is readily prepared by reaction of the copper(II) complex with 2,2,2-trichloroethyl chloroformate (Troc-Cl)h d or by reaction of Z-Lys-OH (obtained via the benzylidene route, see Section 2.1.2.2.1.3) with 2,2,2-trichloroethyl chlor-oformate.f ... 

Magnusson, G, Noori, G, Dahmen, J, Frejd, T, Lave, T, BFs-Etherate induced formation of 2,2,2-trichloroethyl glycopyranosides. Selective visuahzation of carbohydrate derivatives on TLC plates, Acta Chem. Scand. B, 35, 213-216, 1981. 

Trichloroethoxycarbonyl groups have been installed on primary and secondary hydroxyl groups of carbohydrate derivatives by standard coupling with 2,2,2-trichloroethyl chlorofor-mate. It has been shown that a Troc group in the primary position of a glycosyl donor reduces its reactivity but enhances a-selectivity in glycosylation couplings (O Scheme 46) [276]. 

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