Reaction with Trichloroacetamide

This procedure enables direction of the reaction toward the formation of either the a ox p anomer. Control is achieved during attachment of the trichloroacetimi-date group to the anomeric position of the sugar. If the reaction is performed in the presence of NaH, 96 % of the trichloroacetimidated product (9) is obtained with an aip ratio of 96 4. In the presence of Na2C03, 80 % of the product is obtained with an alp ratio of 25 75. Substitution of the trichloroacetimidate by the alkyl group occurs with inversion of the configuration. 

This process, although stereoselective, involves many steps including neutralization, filtration, and separation that strongly reduce its potential commercial interest. 

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Diethyl succinate, reaction with 3 hy droxycinchomnic acid to yield 3-hydroxyquinoline, 40, 56 N,N-Diethyl-2,2,2-trichloroacetamide, 41, 21... 

O-Allyl imidate esters undergo [3,3]-sigmatropic rearrangements to /V-allyl amides. Trichloromethyl imidates can be made easily from allylic alcohols by reaction with trichloroacetonitrile. The rearrangement then provides trichloroacetamides of IV-allylamines.260... 

Protection of hydroxyl groups Benzyl or allyl ethers of carbohydrates are obtained in satisfactory yield by reaction with 1 or 2 in cyclohexane in the presence of triflic add (20°). Trichloroacetamide precipitates and the desired ethers are obtained from the filtrate after neutralization. 

Phosphorus-containing enamines have been prepared by phosphorylation of N-vinyl substituted tertiary amides, lactams and cyclic imides with phosphorus pentachloride ". Addition of amines to diphosphoryl alkynes has been described. Addition of RR NH [R = H, Ri = Me, cyclohexyl, PhCH2 RR = (CHj) to (Et0)2P(0)C=CP(0K0Et2)2 in CH2CI2 at 25 °C gave 93-100% of (Et0)2P(0)C(NRRi)=CHP(0)(0Et2)2 . Speziale and coworkers have studied the reactions of phosphorus compounds with trichloroacetamides. 

Synthesh of amines by l3,3]sigmatropie rearrangement Trichloroacetimidic esters (2) of allylic alcohols (1) can be prepared in 80-100% yield (crude) by reaction with trichloroacetonitrile catal3rzed by the corresponding sodium or potassium alkoxide (O, ether). Inverse addition is preferred for secondary or tertiary alcohols. These esters undergo Claisen-type rearrangement at 25-140° to give allylic trichloroacetamides (3), in which the rrans-isomcr usually predominates. 

Acetamides have been prepared in moderate to good yield from alcohols by reaction with acetonitrile and sulphuryl chloride. It has been found that the hydrolysis of nitriles to amides can be effected in excellent yield using potassium hydroxide in t-butanol if the amide produced is relatively insoluble in water. Experimental details for the large scale anodic oxidation of iV-formyl derivatives of amines to a-methoxyalkylamides have been recorded, and an interesting synthesis of trichloroacetamides from allylic alcohols via a thermal [Att + 2a] rearrangement has been described (Scheme 50). ... 

Speziale and his co-workers have carried out comprehensive studies of the reactions of phosphorus compounds. It has been shown 108) that the reaction of N,N-dialkyl-a-trichloroacetamides (127) with phosphites and phosphines gives trichlorovinylamines (128). In general the trialkyl-phosphines gave somewhat higher yields (60 to 83%) and purer products... 

In a later paper Speziale and Smith 109) investigated the reaction of trivalent phosphorus compounds with N-monosubstituted a-trichloro-acetamides and a-trichloroacetamide. The products were imidoyl chlorides (129) and dichloroacetonitrile (130), respectively. The intermediacy of enamines (131) was assumed. For the monosubstituted amides the enamine... 

The isolation of 73 was then fully optimized. Upon completion of the etherification reaction, the insoluble trichloroacetamide 68 was filtered, leaving a 17 1 mixture of 18 and 19 as a DCE/heptane solution, together with starting material 10. The solvent was switched to MeOH and the esters were saponified with KOH. The carboxylic acid was isolated after neutralization and the addition of NEt3 which gave the highly crystalline triethylamine solvate 73 as a 40 1 mixture of diastere-omers. Recrystallization from MTBE/heptane gave a 109 1 diastereomeric mixture of 73 in 54% overall yield from 10. This final process was successfully implemented in the pilot plant without incident. 

Alkylation of trifluoro- and trichloroacetamides with a-bromoacetic esters has been utilized for the synthesis of a wide range of a-aminoacetic acids [11-13] (Table 5.13). Hydrolysis of the intermediate a-trihaloacetamidoacetic esters with methanolic potassium hydroxide converts the methyl and ethyl esters directly into the amino carboxylic acids. /-Butyl a-aminoacetates are more stable, but they are hydrolysed under phase-transfer catalytic conditions (see Chapter 9.2). Reaction of the trihaloacetamides with 1,4-dibromobutane and 1,5-dibromopentane and subsequent hydrolysis provides a simple route to pyrrolidine-2-carboxylic acid (75%) and piperidine-2-carboxylic acid (58%) [11, 12],... 

The reduction of the trichloroacetamide derivative 56 with (TMS)3SiH afforded 57 in a 60% yield (Reaction 7.58) [68]. The final product is the result of cyclization and further removal of two chlorine atoms. In fact, 3.5equiv of silane and 1.1 equiv of AIBN are used. 

Reaction of 7V,A-diethyl-2,2,2-trichloroacetamide with trialkyl phosphites or triphenylphosphine to give N, N-diethyl-1,2,2-trichlorovinylamine [152-154],... 

CCI3 CONH2 (aq.). Calvet2 measured the heat of reaction of aqueous trichloroacetamide with aqueous NaOH to be 19.71. 

The reactions of TMSA (14) with aldehydes165 23° gives a-trimethylsiloxy-alkyl azides (246, 413-417) they are highly stable against hydrolysis and higher temperatures (Scheme 62). Thermolysis of the azides 246, 413-417 gives directly N-TMS-butyr- (246), valero- (413), capro- (414)-, isobutyr- (415)-, pival- (416) and trichloroacetamide (417), respectively. 

To a stirred solution of 8.0 g (25 mmol) of JV-(l-benzyloxymethyl-2-propenyl)trichloroacetamide (5) in 100 mL of CHClj are added 6.0 g (27 mmol) of NIS at 20 °C. After 8 h the reaction mixture is diluted with CHC13 and successively washed with 10% aq sodium thiosulfate and II20, then dried over Na2S04 and concentrated to give the crude 4,5-dihydrooxazolcs yield 10.7 g (96%) d.r. (trimsicis) 80 20 (detennined by 13C NMR and GLC analysis). Recrystallization from methanol gives the trans-isomer as a white solid yield 7.8 g (70%) mp 81 -83 C. The m-isomer is obtained from the mother liquors as a yellow oil yield 1.9 g (17%). 

Finally, in order to directly incorporate the nitrogen and sulphur functionalities in a single step with total stereoselectivity, the chiral allylic trichloroacetimidate 16 was treated with methyl sulfenyl triflate to give the corresponding A -sulfenyl imidate 17 in good yield. Further reaction of 17 with methyl sulfenyl triflate gave the 4,5-dihydro-l,3-oxazole 18, together with a minor amount of the trichloroacetamide 19, formed by hydrolysis of 18246. 

Ring Cleavage of 2-Trichloromethyl-s-triazine (IX). An amount of 30 ml. of 5% aqueous ammonia was added to 4.0 grams of IX (0.02 mole) at room temperature. The two immiscible layers soon penetrated each other and became translucent, and white, heavy needles started to crystallize. The reaction seemed complete within 2 hours. The crystalline solids were collected on a Buchner funnel and dried the yield was 2.1 grams or 64.3%. By recrystallization from water, colorless prisms were obtained. Their melting point of 141° C. (corr.) remained unchanged when mixed with authentic trichloroacetamide (XI) (23). 

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