Oxalyl chloride products using

The disadvantage of the Swern oxidation is the formation of side products from the Pum-merer rearrangement (see section 1.6.1, Scheme 1.26). To avoid the side reactions in the Swern oxidation, the temperature is kept at -78°C, but when trifluoroacetic anhydride instead of oxalyl chloride is used the reaction can be warmed to -30° C. The use of diisopropylamine as a base stops side reactions. 

A.iv. Reaction with Acid Chlorides. As briefly mentioned in Section 8.4.C.ii, the reaction of a dialkyl cuprate and an acid chloride is a preferred method to synthesize ketones.399,400 -phe reaction with acyl halides usually requires low temperatures to isolate the ketone product.388,387 -p is method is usually preferable to and more general than one that uses dialkylcadmium reagents (sec. 8.4.C.ii). Masamune et al. used this reaction to convert acid 422 to ketone 423 in a synthesis of erythronolide. In this case, oxalyl chloride was used to prepare the requisite acid chloride because of the sensitive nature of the molecule. 

The reaction giving A is chloromethylation, a reliable metliod of adding a CH2OH equivalent to an aromatic ring. You may have been surprised at the use of reagent B to make an acid chloride. B is oxalyl chloride and is often used when pure acid chlorides are wanted - the other products are gases (which ). 

Specialty Isocyanates. Acyl isocyanates, extensively used in synthetic appHcations, caimot be direcdy synthesized from amides and phosgene. Reactions of acid haUdes with cyanates have been suggested. However, the dominant commercial process utilizes the reaction of carboxamides with oxalyl chloride [79-37-8]. CycHc intermediates have been observed in these reactions which generally give a high yield of the desired products (86). 

Reaction of (S)-(+)-2-aminobutyrate hydrochloride with ethyl oxalyl chloride followed by replacing of the ethyl ester with amino alcohol, oxidation with Dess-Martin periodinate and cyclization using TFA/TFAA in acetic acid gave the cyclic product, which was further converted to the bromide. Sub-... 

DMSO or other sulfoxides react with trimethylchlorosilanes (TCS) 14 or trimefhylsilyl bromide 16, via 789, to give the Sila-Pummerer product 1275. Rearrangement of 789 and further reaction with TCS 14 affords, with elimination of HMDSO 7 and via 1276 and 1277, methanesulfenyl chloride 1278, which is also accessible by chlorination of dimethyldisulfide, by treatment of DMSO with Me2SiCl2 48, with formation of silicon oil 56, or by reaction of DMSO with oxalyl chloride, whereupon CO and CO2 is evolved (cf also Section 8.2.2). On heating equimolar amounts of primary or secondary alcohols with DMSO and TCS 14 in benzene, formaldehyde acetals are formed in 76-96% yield [67]. Thus reaction of -butanol with DMSO and TCS 14 gives, via intermediate 1275 and the mixed acetal 1279, formaldehyde di-n-butyl acetal 1280 in 81% yield and methyl mercaptan (Scheme 8.26). Most importantly, use of DMSO-Dg furnishes acetals in which the 0,0 -methylene group is deuter-ated. Benzyl alcohol, however, affords, under these reaction conditions, 93% diben-zyl ether 1817 and no acetal [67]. 

As second example for the scale-up of solid-phase reactions directly on solid support, we chose an arylsulfonamido-substituted hydroxamic acid derivative stemming from the matrix metalloproteinase inhibitor library (MMP) of our research colleagues (Breitenstein et al. 2001). In this case, there was already a solution-phase synthesis available for comparison (see Scheme 4). The synthesis starts with the inline formation of a benzaldehyde 18 with the glycine methyl ester, which is then reduced to the benzylamine 20 using sodium borohydride in methanol/ THF (2 1). The sulfonamide formation is carried out in dioxane/H20 (2 1) with triethylamine as the base and after neutralisation and evaporation the product 21 can be crystallised from tert. butylmethyl ether. After deprotection with LiOH, the acid is activated by treatment with oxalyl chloride and finally converted into the hyroxamic acid 23 in 33.7% yield overall. 

Methods of acylating pyrrole similar to the present one have been reported using oxalyl chloride,5 trifluoroacetic anhydride,6 carbamic acid chloride,7 and trichloroacetyl chloride.8 In the last preparation, it was necessary to separate the product from highly colored by-products by alumina chromatography. Pyrrol-2-yl trichloromethyl ketone has also been prepared by the interaction of pyrrolylmagnesium halide and trichloroacetyl chloride.9... 

Alternatively, the lactone mixture 7 and 8 may be ring opened by hydrolysis, followed by the separation of the corresponding carboxylic acids. The desired atropisomer may be converted into the product alkaloid, whereas the undesired isomer may be recycled by conversion back to the lactone mixture using oxalyl chloride for the acyl activation36. 

The rather different scheme used to prepare the propionic acid side chain in cicloprofen (52-5) leads to the inclusion of this tricyclic compound in the present chapter, which is intended to deal with monocychc compounds. The synthesis starts with the Friedel-Crafts acylation of the hydrocarbon fluoiene (52-1), with the half-ester of oxalyl chloride to give the a-ketoester (52-2) as the product. The required side chain methyl group is then added by reaction of the product with methylmagnesium bromide this apparently proceeds selectively... 

Swern oxidations have been performed using the PEG2000 bound sulfoxide 34 as a dimethylsulfoxide (DMSO) substitute (reaction 13).49-50 Several alcohols were efficiently oxidized to their aldehydes or ketones using this reagent, oxalyl chloride, and triethylamine. Precipitation of the polymer with cold diethyl ether and filtration through a pad of silica afforded the desired oxidized products in very good yields and purities. The reduced sulfide polymer could be reoxidized to sulfoxide 34 with sodium metaperiodate and used again in reactions with no appreciable loss in oxidation capacity. 

Goerdeler and Jonas161 have reported a useful method for the preparation of substituted 2-aminothiazolinc-4,5-diones (65) by reaction of thioureas with oxalyl chloride. Other diketo products in this series were prepared by cyclization of 2-( -carboniethoxyalkyl)-2-thiopseudourea hydrobromides in water to form the thiazolidine-2,4-diones 66 probably via hydrolysis of intermediate 2-iminothiazolidin-4-ones.185... 

Ethyl oxalyl chloride (0.24 mL, 2.1 mmol) was added to a chilled (—30 °C) mixture of the hydrazide 58 (0.407 g, 2.0 mmol) and TEA (0.29 mL, 2.1 mmol) in THF. The soln was gradually allowed to warm to rt and stirred for 3h. The triethylammonium hydrochloride was filtered off, and the filtrate was concentrated. The residue was partitioned between Et20 and H20. The organic layer was extracted with sat. aq NaHC03 and 1M NaHS03, dried (MgS04), filtered, and concentrated. The crude product 59 was used in the next step without further purification. 

A new synthesis of reserpine (Scheme 19)60 makes use of a very neat synthesis of cw-hydroisoquinoline derivatives, e.g. (Ill), by means of a Diels- Alder /Cope rearrangement sequence. Manipulation of (111) by unexceptional methods then gives (112), which possesses the required stereochemistry in ring E. Oxidative cyclization of (112) affords 3-isoreserpinediol (113) but, unfortunately, some inside isomer, originating from the cyclization of C-2 with C-21, is also obtained. The synthesis also loses some elegance in the multi-stage conversion of 3-isoreserpinediol into 3-isoreserpine (114), since, in the Swem oxidation of the C-16 aldehyde cyanhydrin by means of DMSO with oxalyl chloride as activator, the over-oxidized products (115) and (116) were obtained. However, reduction of (115) gave 3-isoreserpine (114), which has previously been converted into reserpine by four different methods. 

The Swern oxidation uses dimethyl sulfoxide (DMSO) as the oxidizing agent to convert alcohols to ketones and aldehydes. DMSO and oxalyl chloride are added to the alcohol at low temperature, followed by a hindered base such as triethylamine. The reactive species (CH3)2SC1, formed in the solution, is thought to act as the oxidant in the Swem oxidation. Secondary alcohols are oxidized to ketones, and primary alcohols are oxidized only as far as the aldehyde. The by-products of this reaction are all volatile and are easily separated from the organic products. 

The best reagents for converting carboxylic acids to acid chlorides are thionyl chloride (S0C12) and oxalyl chloride [(C0C1)2] because they form gaseous by-products that do not contaminate the product. Oxalyl chloride is particularly easy to use because it boils at 62 °C and any excess is easily evaporated from the reaction mixture. 

---