Methyl chloro formate

Reaction of arylhydrazones 216 of piperidin-2-ones with methyl chloro-formate, phosgene, or thiophosgene yielded (80USP4213773) the fused-ring system 217. Reaction of 2,2 -azopyridine (218) with diazoalkanes afforded [66JCS(C)78 73LA2088] the 2-(pyrid-2-yl)-l,2,4-triazolo[4,3-a]-... 

The sodium salt of enamine 8 is formed by deprotonation with NaHMDS followed by selective TV-protection with methyl chloro-formate at -78 °C to give carbamate 9 in 52-60 % yield. 

In a typical example, we developed a new synthetic strategy that does not use MIC for the preparation of the herbicide Methazole. Methazole was classically made through the reaction of MIC with 3,4-dichlorophenyl hydroxylamine followed by treatment with methyl chloro-formate and cyclisation as shown in scheme 150. 

The mixture is cooled while being well stirred, and when the temperature reaches about 65°, 57 g. (0.6 mole) of methyl chloro-formate is added during five to ten minutes. The mixture is then warmed slowly so that the boiling point is reached in about fifteen to twenty minutes. Boiling and stirring are maintained for five hours. 

The resin-bound chiral auxiliary 84 was allowed to react with different vinyllith-ium reagents. The resulting alcohols 85 were treated with n-BuLi, methyl chloro-formate and different cuprate reagents. Finally, the a-alkylated adducts 86 were liberated from the polymer with ozone followed by one of three different workup conditions to provide a primary alcohol, an aldehyde or a carboxylic acid (Scheme 12.32). 

The synthesis of ipalbidine (125), the aglycon of ipalbine, was based on a related approach. The vi-nylogous carbamate (123) was prepared from the V-alkylated thiobutyrolactam (122) via an analogous sulfide-contraction process as described above (Scheme 26). The bicyclic intermediate (124) was generated by selective hydrolysis of the saturated ester followed by immediate treatment with methyl chloro-formate in the presence of catalytic tetrabutylammonium iodide. The bicyclic compound (124) was further elaborate to racemic ipalbidine (125). Parallel applications of this strategy were employed to prepare a series of Elaeocarpus alkaloids (126), (127) and (128) (Scheme 27) as well a benzomorphan analog (129 Scheme 28). °... 

A regioselective synthesis of alkylpyrazines (155) starts with condensation of a-oximino carbonyl compounds with allylamines (Scheme 38). The imine intermediates are isomerized in the presence of potassium r-butoxide to the corresponding 1-hydroxy-1,4-diazahexatrienes. Thermal cyclization-aromatization to pyrazines is best performed after 0-acylation of the oximes with methyl chloro-formate <91JOC2605>. 

Attempts to condense 3,4,5-triamino-2/7-l,2,6-thiadiazine 1,1-dioxide (155) with methyl chloro-formate in dimethylformamide solution gives not the expected 6-oxoimidazo[4,5-c][l,2,6]thiadiazine... 

Arnold U., Ludwig E., Kuhn R. and Moschwitzer U. (1994) Analysis of free amino acids in green coffee beans. Part I. determination of amino acids after precolumn derivatization using 9-fluorenyl methyl chloro formate. Z. Lebensm. Unters. Forsch. 199, 22-5. 

The process of chlorination takes place in a stepwise manner, methyl chloro-formate being formed first and then, successively, the monochloro-, dichloro-, and trichloromethyl chloroformates. Methyl formate reacts readily with chlorine in the dark, giving methyl chloroformate. Further chlorination in the dark without the aid of a catalyst gives some chloromethyl chloroformate, but the reaction is slow and the yield is poor. Complete conversion can only be achieved by photochlorination at near the boiling point of the liquid [51, 70]. 

The herbicide Methazole was traditionally manufactured by the addition of 3,4-dichlorophenyl hydroxylamine to MIC, followed by treatment with methyl chloro-formate or phosgene and cyclization. 

Several reviews and research papers discussing the application and extension of this method have appeared.40 For example, Weber et al.41 reported an interesting result in which cerium acted as a counterion in the modified proline auxiliary (SAMEMP 40) for selective addition of organocerium reagents to hydrazones. The initial adduct was trapped with either methyl or benzyl chloro-formate to afford the stable /V-aminocarbonatc 41 (Scheme 2-24). From this example readers can see that this proline chiral auxiliary can be used not only for a-alkylation but also for nucleophilic addition, which is discussed in detail later. 

This cyclization has also been observed in a variety of substituted azobenzenes,344 and is sometimes accompanied by the expulsion of methyl, chloro, iodo, and carbethoxy substituents from the position of cyclization. In the photocyclization of 2,4,6-trimethylazobenzene (328), a methyl migration is observed leading to the formation of... 

The oxazolidin-2-ones 53 (R = H=CCH=CH2 or COEt) are obtained in a one-pot reaction of amino alcohol carbamates 52 with sodium hydroxide, followed by allyl bromide or propi-onyl chloride (94TL9533). A modified procedure for the preparation of chiral oxazolidin-2-ones 56 from a-amino acids 54, which avoids the hazardous reduction of the acids with borane and the intermediacy of water-soluble amino alcohols, is treatment of the methyl ester of the amino acid with ethyl chloro-formate to give 55, followed by reduction with sodium borohydride and thermal ring-closure of the resulting carbamate f95SC561). The 2-prop-ynylcarbamates 57 (R = Ts, Ac, Bz, Ph or allyl) cyclize to the methyleneoxazolidinones 58 under the influence of silver cyanate or copper(I) chloride/triethylamine (94BCJ2838). 

The hydrazone of a 5-formylpyrimidine (114) when treated with sodium hydride and then heated to 150°C also results in formation of a pyrrolopyrimidine (115) (Equation (36)) <89H(29)1993>. In a related reaction, treatment of 2,4-diamino-6(l//)-oxopyrimidine (116) with methyl chloro-formylacetate gives both the pyrrolopyrimidine (117), and the furopyrimidine (118) (Equation (37)) <89JCS(Pl)2375>. The latter can be converted into pyrrolopyrimidine products. Pyrrolopyrimidines with 5-amino substituents can be prepared from 5-cyanopyrimidines utilizing similar chemistry <88LA633>. 

The proposed transition states have been supported by deuterium isotope studies Evidence such as the decomposition behaviour in solution and the nature of the increases in the rates of decomposition along the series of chloro-formates methyl, ethyl, isopropyl, 2-butyl, /-butyl suggests that the transition states are somewhat polar °> . Lewis and Herndon found 2-methylbut-1-ene and 2-methylbut-2-ene as the olefinic products of the elimination reaction of neopentyl chloroformate, and the kinetic evidence supports a Wagner-Meerwein rearrangement in the gas-phase as in the case of neopentyl chloride pyrolysis (refs. 407, 408, 566). 

Methoxydioxocanadine (283) on pyrolysis affords a 15% yield of the lactone (284), convertible by 4 -methylation and reduction into racemic a and 6-hydrastine (Elango and Shamma, J.org. Chem., 1983, 48, 4879). Treatment of o-acetylophiocarpine with ethyl chloro-formate yields (285, R=C1), hydrolysable to (265, R=0H) and oxidation of this followed by hydrolysis of the acetoxy group yields the hemi-acetal (286, R=H). Conversion of this into the mixed acetal (286, R=Et) allows the N-COOEt group to be reduced to NMe and subsequent hydrolysis gives the aldehyde (287) which can be oxidised to a-hydrastine. A similar reaction sequence starting from epiophiocarpine yields g-hydrastine (Hanaoka, K. Nagami and Imanishi, Chem. Pharm.Bull., 1979, 1947). The reverse conversion of a... 

Compared to the reaction with phosgene, better yields are obtained in this reaction when the R substituents are small alkyl groups, such as methyl or ethyl, although in other cases the reaction was found to be better when phosgene was used. Cyclic carbamic acid derivatives 6 have been similarly prepared using phenyl chloro-formate [24] see also Chapter 6. 

The diazoester of hydroxyacetic add methyl ester 87 was prepared via the chloro-formate 86 using diphosgene as chloroformylating agent [47]. 

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