Chloroaldehydes

Various compounds were obtained from the corresponding halomethyT ketones. Yields are generally better than in the case of a-chloroaldehydes... 

Further studies by Bode and co-workers have shown that enolate formation from a-chloroaldehydes and subsequent reaction with 4-oxo-enoates or unsaturated a-ketoesters 232 generates dihydropyranones 233 in excellent diastereo- and enantio-selectivities, and with impressively low catalyst loadings [90], This work has been extended to the generation of enolate equivalents from bisulfite adducts of a-haloaldehydes 234 under aqueous conditions (Scheme 12.50) [91]. 

Under Vilsmeier-Haack conditions 1-substituted 5-hydroxy-l,2,3-triazoles were converted into the chloroaldehydes (75) in 60-90% yields (84JHCI603) (Scheme 27). Phosphorus pentachloride in toluene gave the 5-chloro derivatives from some ethyl 5-hydroxy-1,2,3-triazole-... 

When an a-chloroaldehyde or an a-chloroketone is condensed with a /3-ketoester, in the presence of aqueous base, a furan is produced bearing an ester substituent at the /3-position. It is thought that the reaction is of the aldol type intermediate dihydrofurans (256) have been isolated in certain cases (Scheme 70) (74BSF519). The condensation of ethyl bromopyru-vate and sodium oxaloacetate follows a similar mechanism (54JOC1671). The one-pot synthesis of 2,4,5-trisubstituted furans (257) from ketones and ethyl 3,4-dibromo-2-butenoate is a useful addition to a well known route (80S52). The analogous reaction of cyclic /3-diketones, i.e. cyclohexane-1,3-dione and 5,5-dimethylcyclohexane-l,3-dione, results in the formation of the condensed furans (258) and (259). These reactions are preformed either in ethanol with sodium ethoxide or in DMF with potassium carbonate. 

Phosgene was identified as the principal intermediate during the photooxidation of all five compounds. Chloroaldehyde and chloroacetylchloride were also detected in low concentrations (Bhowmick and Semmens, 1994). The concentrations of these intermediates reached a maximum value but subsequently fell with time as the oxidation process continued. The rates of oxidation of the VOCs tested are proportional to UV irradiation intensity. The addition of ozone to UV irradiation improved the kinetics of TCE and PCE oxidation however, no significant change in the oxidation rates of CHL, TCA, and CTC was observed. 

Alkoxyacetylenes are obtained by alcohol and hydrogen halide elimination from dialkylacetals of a-chloroaldehydes, induced by NaNH, in liquid ammonia (equation 81)108. 4-Pentyn-l-ol is obtained in similar fashion (equation 82) . 

The short and convenient synthesis of novel naphthopyranoquinolines from naphthopyran chloroaldehydes via the Doebner-Miller synthesis was developed in the laboratory of J.K. Ray. The chloroaldehydes were treated with 2.5 equivalents of a substituted aniline in ethanol in the presence of 2N HCI to afford enaminoimine hydrochlorides in good yield. These hydrochloride salts were exposed to heat at a temperature slightly above their melting point, resulting in ring-closure and elimination of one equivalent of arylamine hydrochloride. 

Sami, I., Kar, G., Ray, J. K. Synthesis of polycyclic oxacoumarins, potential antitumor agents and a short and convenient synthesis of naphthopyranoquinolines from naphthopyran chloroaldehydes. Tetrahedron 992, 48, 5199-5208. 

Intermediates that undergo ring closures of type 93 are probably generated in the reactions of 6a-halopenicillanic acids with nucleophiles, and of p-mercaptoethylamines with either a-chloroaldehydes or 1,2-dibromoethenes. 

Another carbonyl group derivative which forms an imidazole ring with a diamine is 5,iS-dimethyl-Af-tosyliminodithiocarbonimidate (76.10), which is useful in the synthesis of 8-aminopurines. In an attempt to prepare a l,S-benzo-diazepine, the chloroaldehyde (76.11) was stirred or warmed with o-phenylene-diamine but the main product was the benzimidazole. 

A chemical synthesis of (2RS, 3R)- and (2RS, 3S)-[3- //i]lysines 257, H = H, and 257, Hg = H, respectively, has been achieved as outlined in Scheme 67 using the, by now familiar, reduction of a [ H]aldehyde with chiral boranes (262, 263). Thus reduction of the chloroaldehyde 255, with chiral boranes gave the alcohols 2 H — H, and 256, Hg = H. The chirality of these compounds was verified by H NMR spectroscopic methods, and mesylation and further elaboration, involving inversion of the labeled center, gave the... 

SYNONYMS chloroacetaldehyde monomer, 2-chloroacetaldehyde, chloroaldehyde, 2-chloroethanal, 2-chloro-l-ethanal, monochloroacetaldehyde. 

The easy condensation of aldehydes with 3-monosubstituted oxindoles has been further exploited by Ban and co-workers, who synthesized several 3-spirooxindole derivatives 48). The approach was used in the stereospecific synthesis of racemic iV-methylrhynchophyllane (Chart X). The Iraws-diethylcyclopentanone CVIIIa was subjected to Baeyer-Villiger oxidation to yield the threo lactone CIX, which was converted to the chloroaldehyde CXI, by successive reaction with phosphorus... 

Vilsmeier reaction to the chloroaldehyde (106), followed by reductive meth-ylation, yielded the aldehyde 107 (Scheme 14) with the precedented stereochemical outcome. Attempted halogenation of the derived neopentyl-type alcohol was unsuccessful under a variety of conditions, so an alternative scheme involving two successive Wittig-type reactions was developed. The aldehyde 107 was converted to the unsaturated aldehyde 108 by the method of Nagata and Hayase. Reduction with triethylsilane and tris (triphenylphosphine) rhodium chloride was followed by condensation with isopropylidene phosphorane to give the desired product 109. 

Thermal degradation of chloromethyl-1,3,5-trioxanes 127 (Scheme 29) in the presence of catalytic amounts of montmorillonite clay generated a-chloroaldehydes which could be treated in situ with thiourea to afford 2-aminothi-azoles 128, or with ethylene glycol to yield the corresponding 2-chloromethyl-l,3-dioxolanes 129 <1994CL2039>. The acidic sites in montmorillonite clays may act as acid catalysts, though the details of the mechanism were not provided. 

Only a sparse amount of material has been published on this topic. Chlorination of 2,4,6-trimethyl-l,3,5-trioxane provided a mixture of chloroaldehydes which could be treated with concentrated sulfuric acid to yield 2,4,6-tri(chloromethyl)-l,3,5-trithiane 168 <1992CL171>. The corresponding dichlorination reaction catalyzed by SbCls at 80 °C (via the previously mentioned chloroaldehyde and hydrolysis to the hydrate) finally yielded the dichloro analog 167 (Scheme 44) <1993SC1289>. Actually, it is chlorination of 1,3,5-trioxane substituents via open-chain reactants that is the process in effect. 

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